DEVICES, SYSTEMS AND METHODS FOR SAMPLE COLLECTION

专利摘要:
devices, apparatus, systems, methods and kits for collecting and storing a fluid sample from an individual are described here. a device for collecting fluid sample may include a housing comprising a recess having an opening, a vacuum chamber in the housing and in fluid communication with the recess, and one or more perforating elements that are extendable through the opening to penetrate the skin of the individual. the vacuum chamber can be configured to have a vacuum that positions the skin in the recess. the recess can be configured with a size or shape that allows an increased volume of the fluid sample to accumulate on the skin positioned in the recess.
公开号:BR112019014231A2
申请号:R112019014231-2
申请日:2018-01-10
公开日:2020-03-17
发明作者:Dagmar Beyerlein；Masao Drexel；Brett L. Jordan；Alicia Jackson；Kara Juneau
申请人:Drawbridge Health, Inc.；
IPC主号:

专利说明:

DEVICES, SYSTEMS AND METHODS FOR SAMPLE COLLECTION
CROSS REFERENCE WITH RELATED APPLICATIONS [0001] This application claims the benefit of provisional US patent application number 62 / 444,764, filed on January 10, 2017, and US provisional patent application number 62 / 468,906, filed on March 8, 2017 2017, both of which are incorporated herein as a reference in their entirety.
BACKGROUND [0002] The collection of body fluid, for example the collection of blood samples for carrying out diagnostic tests, can be used to assess and report on the health of individuals. Early detection and reliable diagnosis can play a central role in making effective therapeutic decisions for the treatment of diseases or in the management of certain physiological conditions. Detection may involve the identification of disease-specific biomarkers in human body fluids that may indicate irregularities in cellular regulatory functions, pathological responses or therapeutic drug intervention.
[0003] Many individuals, however, may not appreciate the process of having blood drawn from their bodies, possibly due to the association with pain, cuts, bleeding, sharp objects, blood sight, fear of infections etc. Typically, an individual's venous blood collection is performed at external facilities such as hospitals, specialized nursing facilities and outpatient settings such as a primary care physician (PCP) and specialized hospital clinics, surgical centers, clinics occupational health or medical practices. The blood collection process can be tedious and time-consuming for individuals who need to attend these facilities for blood draws and for healthcare personnel who need to see multiple patients in a single day.
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2/134 [0004] Thus, there is a need for improved devices and methods that allow blood collection to be carried out easily and conveniently by users, and that can reduce the users' dependency on traditional health facilities for blood collection .
SUMMARY [0005] This report addresses at least the above needs. Several achievements in this report are focused on the demand for devices and methods that enable individuals to easily, conveniently and reliably collect and store blood samples outside traditional health facilities, for example, in their own homes, in remote locations, while in travel etc. Individuals who have minimal or no medical training can use the devices and methods described in order to collect and store blood efficiently by themselves or with the help of others, without the need for trained health personnel. The achievements described here can obviate the need for individuals to schedule, or make special or frequent trips to health facilities for the collection of blood samples, which helps in freeing up individuals' time and reducing the burden of patients on medical resources . However, it should be noted that the devices and methods described are also suitable for use by health personnel or non-health personnel in a variety of environments or applications, for example, at personalized health care points (POC), Emergency (EMS), outpatient care, hospitals, clinics, emergency rooms, patient exam rooms, severely ill care rooms, field settings, infirmary offices in educational facilities, occupational health clinics, operating or surgery rooms operation etc.
[0006] Blood samples collected using the devices and methods described here can be analyzed to determine a person's physiological state, to detect diseases and also to monitor the user's health conditions. In some cases,
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3/134 individuals can quickly assess their physiological status since blood samples can be quickly collected using the devices and methods described here, and either (1) analyzed on the spot using, for example, immunological assays or ( 2) sent immediately to a test facility. The reduced time for blood collection, analysis and quantification can be beneficial for many users, especially users with certain physiological conditions / diseases that require constant and frequent blood sample collection / monitoring. Taking diabetes as an example, hemoglobin Ale (HbAlc) can represent up to 60% of all glycohemoglobins and can be used to monitor glycemic control. The amount of HbAlc, as a percentage of total hemoglobin, may reflect the average blood glucose concentration in the blood of a patient in the preceding 120 days. It is generally recommended that diabetic patients test HbAlc levels every three to six months. The glycemic recommendation for non-pregnant adult women with diabetes may be <7.0%, while HbAlc levels> 8% may indicate that medical action may be required to control diabetic complications, including cognitive disability and hypoglycemic vulnerability.
[0007] The various achievements described here are capable of drawing blood at increased flow rates and larger sample volumes beginning at the time of the skin incision, compared to traditional non-venous blood collection devices and methods. The devices and methods described can be used to collect blood samples of predefined volumes, for example, through the use of customized matrices for sample collection, and absorbent pads to hold and measure for holding and excess blood. Additionally, the blood collection devices and methods described here are minimally invasive and allow for lower levels of pain (or perception of pain) in an individual, which helps to improve the overall blood collection experience for the individual.
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4/134 [0008] In some ways, a portable device or method activated by the user described here can be configured or be able to collect at least 150 uL of blood from an individual in less than 3 minutes from the time of incision of a part of the individual's skin.
[0009] In some respects, a device is provided to collect fluid samples from an individual. The device may comprise a recess and a pre-evacuated vacuum chamber located within the device. The recess can be configured to maintain contact with at least 5.0 cm ² of a surface area of the subject's skin under vacuum pressure, before and during the collection of the fluid sample from the subject's skin.
[0010] In some respects, the device for collecting an individual's fluid sample may comprise: a housing comprising a recess having an opening; a vacuum chamber in the housing in fluid communication with the recess; and one or more piercing elements that are extensible through the opening to penetrate the individual's skin. The vacuum chamber can be configured to have a vacuum that positions the skin in the recess, and the recess can be configured with a size or shape that allows an increased volume of the fluid sample to accumulate on the skin positioned in the recess.
[0011] In some respects, a method for collecting a fluid sample from an individual may comprise: the provision of a device featuring a housing, said housing configured to support a vacuum chamber and a drilling module, the housing comprising a recess showing an opening; the placement of the housing recess adjacent to the individual's skin; activation of the vacuum in the vacuum chamber to position the skin in the recess; the accumulation of an increased volume of the fluid sample on the skin positioned in the recess, where the recess is configured with a size or shape that allows the increased volume of the fluid sample to be accumulated; the extension of one or more piercing elements through the opening to penetrate the skin; and maintaining the device adjacent to the skin for a
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5/134 sufficient amount of time to withdraw the fluid sample into the device.
[0012] In some embodiments, the fluid sample may comprise the individual's blood. The recess can act as a suction cavity to position the skin and increase the capillary pressure differential. The increased volume of the fluid sample may depend on a volume and / or a surface area of the skin that is positioned in the recess. In some cases, the volume of skin involved by the recess can vary from about 0.4 cm ³ to about 4.0 cm ³ . The surface area of the skin in contact with the recess can vary from about 3.2 cm ² to about 7.2 cm ² . The increased volume of the fluid sample may depend on a vacuum pressure in the vacuum chamber. The vacuum pressure in the vacuum chamber can vary from about -4 psig to about -15 psig. The increased volume of the fluid sample in the skin positioned in the recess can be at least about 50 pL before penetration of the skin. In some cases, the increased volume of the fluid sample in the skin positioned in the recess, an increased capillary pressure and with the aid of a vacuum, can allow the fluid sample to seal off from the skin and collected at an average flow rate of at least 30 pL / min. In some cases, the fluid sample can be collected at an average flow rate of at least 100 pL / min. In some cases, the fluid sample can be collected at an average flow rate of at least 150 pL / min. In some cases, the average flow rate can be sustained until at least about 150-300 pL of the fluid sample has been collected. The size and / or shape of the recess can be configured to allow the skin to substantially conform to the recess. A gap between the skin and the recess can be negligible when the skin is positioned in the recess. A recess surface can be substantially in contact with the skin positioned in the recess. In some cases, a recess size can be at least twice the size of the opening inside the recess. In some cases, the size of the opening inside the recess can vary from about 1.5 mm to about 6 mm, and the size of the recess in its outermost periphery can vary from about 10 mm to about
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6/134 of 60 mm. A surface area of the recess can be substantially larger than an area of the opening. In some cases, the surface area of the recess can be at least ten times the area of the opening. In some cases, the surface area of the recess can vary from about 75 mm ² to about 2900 mm ² , and the area of the opening can vary from about 1.5 mm ² to about 30 mm ² . In some cases, an area of skin directly under the opening may be at least 1.5 times smaller than a total area of skin positioned in the recess. In some cases, the area of the skin directly under the opening may be at least 5 times smaller than the total area of the skin positioned in the recess.
[0013] In some embodiments, the recess may comprise a concave cavity. In some cases, the concave cavity may have a volume ranging from about 1.0 cm ³ to about 5.0 cm ³ . The recess may be in the form of a spherical hood. In some cases, a base diameter of the spherical hood can vary from about 10 mm to about 60 mm, and a height of the spherical hood can range from about 3 mm to about 30 mm. The spherical hood can be a hemisphere. The opening can be at an apex of the spherical hood recess. In some embodiments, the recess may comprise one or more fillets configured to increase vacuum suction on the skin and reduce vacuum leakage. The one or more fillets may extend continuously along a periphery of the recess. The one or more fillets in the recess can be configured to be in contact with the skin when the skin is positioned in the recess.
[0014] In some embodiments, a vacuum pressure of at least about -1 psig can be provided in order to position the skin and completely fill the recess. In some cases, the skin can be positioned in the recess by vacuum and can completely fill the recess in less than 1 second. In some cases, the skin can be positioned in the recess by vacuum and can completely fill the recess in no more than 5 seconds.
[0015] In some embodiments, (1) the size or shape of the recess or (2) a vacuum pressure can be configured to obtain a minimum capillary pressure in the skin positioned in the recess. In some cases, (1) the size or
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7/134 shape of the recess or (2) a vacuum pressure can be configured to obtain a minimum tension in the skin positioned in the recess. The device can be supported and held in place on the individual's skin with the aid of an adhesive. The device can be supported and held in place on the individual's skin with the aid of a vacuum. The device can be supported and held in place on the subject's skin mainly with the aid of a vacuum. The device can be configured for use on an individual's upper arm. The device can be configured to remain in position on the subject's arm regardless of any movement or changes in the subject's arm orientation.
[0016] In some embodiments, the device may be able to collect 250 μL of fluid sample from the individual in less than 1 minute 45 seconds. In some cases, the device may be able to collect at least 175 μl to 300 μl of the individual's fluid sample in less than 3 minutes. In some cases, the device may be able to collect at least 200 pL of the individual's fluid sample in less than 5 minutes. The device can be configured to collect the fluid sample at a rate that is dependent on the size or shape of the recess and / or the vacuum pressure. The recess can be configured with a size and shape that allows an increased volume of the fluid sample to accumulate on the skin positioned in the recess. The recess can be configured with a size and shape that allows the increased volume of the fluid sample to accumulate. In some cases, (1) the size and shape of the recess and (2) a vacuum pressure can be configured to obtain minimal capillary pressure in the skin positioned in the recess. In some cases, (1) the size and shape of the recess and (2) a vacuum pressure can be configured to obtain minimal stress on the skin positioned in the recess. The device can be configured to collect the fluid sample at a rate that is dependent on the size and shape of the recess.
[0017] In some other aspects, a device is provided to collect a fluid sample from an individual. The device can comprise: a
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8/134 housing comprising a perforation activator configured to activate one or more perforating skin elements, and a vacuum activator separate from the perforation activator and configured to activate an evacuated vacuum chamber prior to activation of one or more perforating elements by the activator drilling.
[0018] In some respects, a method for collecting a fluid sample from an individual may comprise: placing a device packaged with an evacuated vacuum chamber and one or more perforating elements in the individual's skin area; activating the evacuated vacuum chamber to create a vacuum pressure in the skin area; perforation of the skin area after activation of the vacuum; and maintaining the vacuum pressure during and after penetration of the individual's skin area, in order to withdraw the fluid sample from the skin to the device.
[0019] In some embodiments, the drilling activator and the vacuum activator can be two separate components. The vacuum activator can comprise a first entrance interface to the housing, and the drilling activator can comprise a second entrance interface to the housing. In some cases, at least one between the first input interface or the second input interface may comprise a button. In some alternative cases, the vacuum activator may comprise a first inlet interface and the drilling activator may comprise a second inlet interface, and at least one between the first inlet interface or the second inlet interface may be remote to the housing .
[0020] In some embodiments, the perforation activator can be configured to activate the one or more perforating elements after the skin is positioned in the recess. The piercing activator can be configured to activate the one or more piercing elements after the skin is positioned in the recess by the vacuum for a predetermined period of time. In some cases, the predetermined period of time can vary from about 1 second to about 60 seconds. In some embodiments, the housing may comprise the pre-evacuated vacuum chamber, and the vacuum activator may be configured to activate the vacuum in the vacuum chamber
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9/134 pre-evacuated. In some cases, the drilling activator can be configured to activate the one or more piercing elements only after the vacuum has been activated. In some cases, the perforation activator may be blocked and unable to activate the one or more perforating elements before activating the vacuum. The drilling activator may comprise a locking mechanism coupled to the vacuum activator. The locking mechanism can be configured in such a way that the drilling activator is initially in a locked state. The vacuum activator can act as a key to unlock the drilling activator, and the drilling activator can be simultaneously unlocked when the vacuum activator is activated. The vacuum activator can be configured to activate the vacuum by establishing fluid communication with the pre-evacuated vacuum chamber. For example, the vacuum activator can be configured to pierce a foil seal or open a valve in order to establish fluid communication with the pre-evacuated vacuum chamber. [0021] In some embodiments, the vacuum activator can be located in the housing in such a way that the vacuum activator is configured to be pressed in a first direction, and the drilling activator can be located in the housing in such a way that the activator drilling tool is configured to be pressed in a second direction. In some cases, the first direction and the second direction can be substantially the same. Alternatively, the first direction and the second direction can be substantially different. In some cases, the first direction and the second direction can be substantially parallel to each other. In some cases, at least one of the first or second directions does not extend towards the individual's skin. For example, the second direction does not extend towards the individual's skin. In some cases, at least one between the first or the second direction can extend substantially parallel to the individual's skin. In some cases, the first direction and the second direction can both extend substantially parallel to the individual's skin. In some cases, at least one between the first direction or the second direction may extend
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10/134 in a direction of the gravitational force. In some cases, the first direction and the second direction can both extend in the direction of the gravitational force. In some embodiments, the drilling activator and the vacuum activator can be located on the same side of the housing, and can be ergonomically accessible by the individual when the device is mounted on an individual's arm. For example, the drilling activator can be located on a housing cover, and the vacuum activator can be located on a base of the housing where the vacuum chamber is located. Alternatively, the drilling activator and the vacuum activator can be located on different sides of the housing, and can be ergonomically accessible by the individual when the device is mounted on an individual's arm.
[0022] In some additional aspects, a method is provided to collect a fluid sample from an individual. The method may comprise: with the aid of a fluid collection device: the perforation of the individual's skin and placement of the individual's fluid sample in a matrix arranged inside a fluid collection device deposit chamber, where the fluid sample placement is aided or improved by the use (1) of gravitational force, (2) of vacuum force, (3) of a pressure difference between capillary pressure and the internal pressure of the device, and (4) behavior of the fluid sample passing through the matrix.
[0023] In some aspects, a device is provided for collecting a sample of fluid from an individual's skin and transferring it to a deposit chamber, where the flow of fluid from the skin to a matrix in the deposit chamber can be preferably be increased (1) by the gravitational force, (2) by the vacuum force, (3) by a pressure differential between the capillary pressure and the internal pressure of the device, and (4) behavior of the passage of the fluid sample along of the matrix.
[0024] In some embodiments, the device may comprise a container for holding one or more piercing elements, and the container may be in fluid communication with the deposit chamber. The deposit chamber and the
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11/134 container can be initially at ambient pressure, before the activation of a vacuum from a pre-evacuated vacuum chamber located inside the device. In some cases, the deposit chamber, the vacuum chamber and the container can be configured to equalize at an internal pressure that is less than the ambient pressure after the vacuum has been activated. The internal pressure may be greater than the initial evacuated vacuum pressure from the vacuum chamber. In some cases, the internal pressure can be about -5.5 psig, and the sealed vacuum pressure can be about -12 psig. The internal pressure can be configured to position the skin in a recess in the housing. The internal pressure can be configured to draw blood from capillary beds to the skin being positioned in the recess. A pressure differential can be created between capillary pressure and internal pressure when the skin is penetrated by one or more perforating elements of the device. The internal pressure may increase as the fluid sample is drawn from the skin into the deposit chamber and into the container. In some cases, the internal pressure in the container may increase more rapidly compared to an internal collection pressure of the deposit chamber and the vacuum chamber. The internal pressure in the container can increase substantially more than the internal collection pressure of the deposit chamber and the vacuum chamber. The substantially increased internal pressure of the container can inhibit the flow of the fluid sample to the container. The substantially increased internal pressure of the container can result in a preferential flow of the fluid sample towards the deposit chamber instead of towards the container. The substantially increased internal pressure of the container can cause the flow of the fluid sample to the container to be slower or to be interrupted, while the fluid sample can continue to flow towards the deposit chamber under the influence of the pressure differential. In some cases, (1) a volume of the container and (2) a volume of collection from the deposit chamber and the vacuum chamber, can be configured in such a way that minimal amounts of the fluid sample flow towards and from the container. In some cases, a proportion of the volume of the container for the
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12/134 collection volume of the deposit chamber and the vacuum chamber can vary from about 1: 5 to about 1:15. In some cases, the one or more perforating elements can be configured to penetrate the skin in order to generate cuts, and the pressure differential can enable deeper cuts and the cuts to be kept open under tension. The pressure differential can be configured to increase the size of the cuts in order to enable a higher flow rate and a volume of the fluid sample to be collected from the skin.
[0025] In some additional aspects, a device is provided to penetrate an individual's skin. The device may comprise: one or more piercing elements supported by a mobile piercing cable by two or more spring elements; an implantation spring positioned to implant the one or more piercing elements through an opening in the device; and a retraction spring positioned to retract the one or more piercing elements back into the device, where a length of the one or more piercing elements is less than about 20 mm, and the penetration depth of the one or more piercing elements is about 2 mm. In some cases, the length of the one or more piercing elements is about 12.7 mm.
[0026] In some respects, a method for penetrating an individual's skin may comprise the provision of the device mentioned above; positioning the individual's skin in a recess of the device; the activation of the implantation spring and implantation of one or more perforating elements through the opening in the device; penetration of the individual's skin using one or more perforating elements; and using the retraction spring to retract the one or more spring elements back into the device.
[0027] In some embodiments, two or more piercing elements can be supported by a support and a random configuration. In some cases, the two or more perforating elements may have random orientations in relation to each other. The two or more piercing elements may comprise beveled edges that are randomly oriented with respect to each other. The beveled edges of the two or more perforating elements may not be
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13/134 symmetrical to each other. The beveled edges of the two or more piercing elements can be at an acute angle or at an oblique angle to each other. [0028] In some cases, two or more piercing elements can be supported by a support in a predefined configuration. The two or more piercing elements may have predefined orientations in relation to each other. The two or more piercing elements may comprise beveled edges that are oriented in relation to each other in a predefined manner. The beveled edges of the two or more piercing elements can be symmetrical to each other. [0029] In some embodiments, the piercing elements may comprise two or more lancets. Optionally, the piercing elements may comprise needles and / or microneedles. In some cases, two or more lancets may have the same chamfer angle. Alternatively, two or more lancets may have different chamfer angles. In some cases, the chamfer angle (s) can vary from about 10 degrees to about 60 degrees. In some cases, the two or more lancets may comprise chamfered faces having the same chamfer length. Alternatively, the two or more lancets may comprise chamfered faces having different chamfer lengths. In some cases, the chamfer length (s) can vary from about 2 mm to about 10 mm.
[0030] In some embodiments, two or more piercing elements can be configured to generate cuts in the skin that extend in different directions along the skin and that are not parallel to each other.
[0031] In some embodiments, the implantation spring can be configured to displace and cause the perforating elements to penetrate the individual's skin at speeds ranging from about 0.5 m / s to about 2.0 m / s. The implantation spring can be configured to dislodge and cause the piercing elements to penetrate the individual's skin with a force ranging from about 1.3 N to about 24.0 N. A spring force of the retraction spring can be less than a spring force of the implantation spring. In some cases, the implantation spring may have a spring rate of around 2625 N / m, and the
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14/134 retraction can have a spring rate of about 175 N / m. The implantation spring can be configured to cause the one or more perforating elements to penetrate the skin to depths ranging from about 0.5 mm to about 3 mm. The retraction spring can be configured to retract the perforating elements of the individual's skin at speeds ranging from about 0.1 m / s to about 1.0 m / s.
[0032] In some embodiments, the device may additionally comprise a vacuum activator configured to activate a vacuum to position the skin in a recess of the device. In some cases, a drilling activator can be configured to activate the implantation spring only after the vacuum activator is activated.
[0033] In some additional aspects, a device is provided to monitor the collection of fluid samples from an individual. The device may comprise: a housing comprising a cartridge chamber; a cartridge operationally coupled to the cartridge chamber; components to penetrate the individual's skin and remove the fluid sample from the skin into the cartridge; and a flow meter in the housing that allows the individual or user to monitor the progress of fluid sample collection in real time as the fluid sample is collected into the cartridge.
[0034] In some respects, a method for monitoring an individual's fluid sample collection may comprise: providing (1) a housing comprising a cartridge chamber, (2) a cartridge operably coupled to the cartridge chamber, ( 3) components to penetrate the individual's skin and withdraw the fluid sample from the skin into the cartridge, and (4) a flow meter in the housing; and monitoring, with the aid of the flow meter, a progress of fluid sample collection in real time as the fluid sample is collected into the cartridge.
[0035] In some embodiments, the flow meter can be provided in a cover that covers a base of the housing. The flow meter is not obscured by a housing cover. The flow meter can be close to the
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15/134 cartridge chamber. The flow meter can be substantially aligned with a cartridge located inside the cartridge chamber. In some embodiments, the flow meter may comprise a plurality of windows arranged parallel to a longitudinal axis of the cartridge. The plurality of windows can be made of an optically transparent material. The fluid sample can be visible through the windows and sequentially fill each window as the fluid sample is being collected into the cartridge. Each window can be indicative of a known amount of fluid sample that is collected. Fluid sample collection is complete when the fluid sample is visible in all windows. The plurality of windows can comprise three or more windows.
[0036] In some embodiments, the flow meter may comprise a single window arranged parallel to a longitudinal axis of the cartridge. The window can be made of an optically transparent material. The fluid sample can be visible through the window and continuously fill the window as the fluid sample is being collected into the cartridge. The fluid sample collection is complete when the fluid sample is visible through the window.
[0037] In some additional aspects, a cartridge assembly is provided. The cartridge assembly may comprise: a cartridge for holding one or more arrays for storing a fluid sample; a cartridge holder releasably coupled to the cartridge, where the cartridge assembly is releasably coupled to a device used to collect the fluid sample.
[0038] In some embodiments, a device is provided to collect a fluid sample from an individual. The device may comprise: a housing comprising a deposit chamber and a pre-evacuated vacuum chamber, where the deposit chamber is configured to receive and releasably be coupled to the cartridge assembly, and the deposit chamber is in fluid communication with the vacuum chamber.
[0039] In some embodiments, a fluid sample collection kit may comprise the device and cartridge assembly. In some achievements,
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A fluid sample collection assembly may comprise the device and the cartridge assembly releasably coupled to said device. In some embodiments, a cartridge inlet port can be releasably coupled to and in fluid communication with a device channel, and the fluid sample can be collected from the subject's penetrated skin and transported through the channel to the cartridge.
[0040] In some embodiments, a method for collecting a fluid sample from an individual may comprise: the releasably coupling of the cartridge assembly to the device; placing the device adjacent to the individual's skin; activation of vacuum in the vacuum chamber to position the skin in a recess of the housing; the use of one or more piercing elements of the device to penetrate the skin; maintaining the device adjacent to the skin for a sufficient amount of time to draw the fluid sample into the device and collect the fluid sample into the cartridge; and uncoupling the cartridge assembly from the device after a certain amount of fluid sample has been collected in the cartridge.
[0041] In some embodiments, the cartridge holder can be releasably attached to the cartridge via a quick release mechanism. In some cases, the quick release mechanism may comprise one or more spring clips on the cartridge holder. The cartridge assembly may be able to be attached and detached from the deposit chamber without the use of tools. The cartridge assembly may be able to be coupled and detached from the deposit chamber by using no more than two steps of movement. The cartridge assembly can be attached to the deposit chamber before collecting the individual's fluid sample. The cartridge assembly can be detached from the deposit chamber after the individual's fluid sample has been collected into the cartridge.
[0042] In some embodiments, the cartridge may comprise two or more matrices for the collection and storage of the fluid sample. The two or more matrices can be arranged in a configuration that allows the fluid sample to pass between and along two or more matrices. For example, the two or
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17/134 more matrices can be arranged substantially parallel to each other. In some cases, the two or more matrices can be separated by a space of about 0.5 mm. In some cases, at least one of the matrices may be able to collect at least 60 μL of fluid sample. In some cases, each of the two or more arrays may be able to collect at least 60 µL of fluid sample.
[0043] In some embodiments, the cartridge may additionally comprise one or more absorbent pads configured to be in fluid communication with one or more matrices, where the one or more absorbent pads can be used to hold the excess fluid sample. The one or more absorbent pads can assist in ensuring that a predefined volume of the fluid sample can be collected and maintained in one or more arrays, regardless of an inlet volume of fluid sample into the cartridge up to a predefined range. In some cases, the one or more arrays may include two arrays which are each configured to hold up to about 7 µL of fluid sample. Each of the two arrays can be configured to hold about 75 μl of fluid sample according to the volume of fluid sample input to the cartridge increases beyond 150 μl to the predefined range. In some cases, the predefined range can be from about 150 uL to about 300 uL. In other cases, the predefined range can be greater than 300 uL. In some cases, one or more absorbent pads may be able to hold at least 100 µL of excess fluid sample.
[0044] In some embodiments, the cartridge holder may comprise a cartridge flap which is configured to be releasably coupled to a distal end of the deposit chamber. The cartridge tab can be configured in such a way that the individual or a user is able to (1) support the cartridge assembly by holding the cartridge tab, (2) attaching the cartridge assembly to the device by pushing the cartridge tab, and / or (3) uncouple the cartridge assembly from the device by pulling on the cartridge tab.
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18/134 [0045] In some additional aspects, a transport glove is provided. The sleeve may comprise: an opening configured to be coupled to a cartridge flap included with the cartridge; and a dual support-release mechanism inside the sleeve, where the dual support-release mechanism can comprise:
(a) a retaining element configured to be coupled with a corresponding combining characteristic on the cartridge and securing the cartridge inside the sleeve, and (b) a release element configured to cause the spring clips in the cartridge holder to release and in this way, uncouple the cartridge from the cartridge holder. The dual support-release mechanism can allow the cartridge support to be removed from the sleeve opening while the cartridge is fixed to the location inside the sleeve, without exposing the tapes to the environment. In some cases, the carrying glove may additionally comprise a desiccant inside the glove. In some cases, the glove can be sized and formatted to accommodate user or patient identity (ID) labels.
[0046] In some embodiments, a transport assembly may comprise: the transport sleeve, and the cartridge coupled to said transport sleeve. In some cases, the cartridge flap can be configured to tightly seal the opening of the sleeve.
[0047] In some embodiments, the cartridge can be oriented in such a way that the flow of the fluid sample to the cartridge is additionally aided by gravity. In some cases, the cartridge may comprise a luer-type adjustment that can be attached to the device when the cartridge is inserted into the deposit chamber.
[0048] In some embodiments, one or more matrices may comprise absorbent paper. In some cases, one or more of the matrices may comprise stabilizing chemicals. In some cases, a first matrix may comprise a first stabilization chemical and a second matrix may comprise a second stabilization chemical other than the first stabilization chemical. In some cases
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19/134 alternatives, one or more of the matrices do not comprise a stabilizing chemical.
[0049] Systems, medical devices and methods for sample collection and storage are provided here. The systems, devices and methods described here may comprise structural features that facilitate sample collection (for example, blood collection devices), as well as components for collecting blood samples from the substrate for storage and transportation.
[0050] Any of the devices described here can be based on the generation of a vacuum in order to apply negative pressure to deform an individual's skin and apply local suction directly to the sample collection site, thus facilitating the flow and collection of the sample. sample. Any of the devices described here can comprise a concave cavity that can be placed on the surface of the individual's skin, this concave cavity can be configured to apply vacuum (e.g., negative pressure, suction, etc.) to the individual's skin. Any of the devices described here can comprise an opening arranged at the apex of the or other surface of the concave cavity, the internal diameter can be configured to allow a piercing element to pierce the individual's skin; and a piercing element can be configured to pass through the inner diameter. Local suction can be applied to the sample collection site through the internal diameter.
[0051] In some embodiments, a vacuum can be configured to deform the individual's skin using different mechanisms, for example, the vacuum can be configured to position the individual's skin in the concave cavity. A concave cavity can be configured to press the skin surface against all or part of its concave surface, at the point where the piercing element can be configured to pierce the individual's skin. A contiguous opening with a cylinder (for example, a cylinder in fluid contact with a cartridge) can be configured to draw blood from the individual to the
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20/134 device when the vacuum is applied to the individual's skin and after an incision has been made in the individual's skin.
[0052] The vacuum pressure can be generated using an evacuated vacuum chamber configured in such a way that the activation of the device pierces the evacuated vacuum chamber forming a negative pressure that draws the individual's blood through the opening and channels and stops inside a cartridge and on a solid matrix for storing the sample the vacuum pressures can be in the range of 1-20 psi. The vacuum pressure can be about 5 psi. The volume of the vacuum chamber can be within 10% -100% of twice the volume of the combined hollow cavity, opening, channel and cartridge. Any of the devices described here can comprise a vacuum activation trigger configured to activate the vacuum by actuating the vacuum activation trigger. The vacuum activation driver can comprise a button.
[0053] Any of the devices described here can be configured to remove a specific volume (for example, above 20 pL, above 40 pL, above 60 pL, above 80 pL, above 100 pL, above 150 pL , or above 200 pL) of blood (for example, capillary blood) from an individual over a defined period of time (for example, less than 4 minutes), may have specific vacuum and device parameters. The structure of the concave cavity may have an impact on blood collection, for example, the rate of blood sample collection may be dependent on the curvature and size of the concave cavity and the vacuum pressure.
[0054] In order to facilitate blood collection, the surface area that is affected by the vacuum may have specific parameters, for example, the surface area of the skin under vacuum and in contact with the concave cavity may be within a margin within 10 % 500 mm ² and the opening in fluid contact with a cylinder (for example, a cylinder in fluid contact with a cartridge) can have a diameter within a 10% margin of 8 mm ² . Any of the devices, systems and methods here for sampling (for example,
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21/134 blood samples) can be configured with a removable cartridge. The removable cartridge can be kept in fluid communication with the cylinder (for example, the cylinder in contact with the opening in the concave cavity). Any of the devices described here can comprise a visual measurement window configured to allow viewing of the removable cartridge while the removable cartridge is in the device. Any of the devices described here can comprise a piercing module, where the piercing module comprises one or more piercing elements. The piercing elements can be operated with a button. Before and after activation, the piercing element can be removed when the piercing element is in a deactivated state.
[0055] Also described here are cartridges configured to collect sample from the device and transfer it to the solid substrate in such a way that accurate volumes of sample are collected and measured by the absorbance of the solid substrate. For example, the standardized amount of blood that saturates each substrate strip can be within the range of 50-100 uL on a substrate with a surface area within the range of 100-300 square millimeters. A cartridge can comprise a channel disposed between two substrate tapes configured to transfer a blood sample to the two substrate tapes. A cartridge may comprise a spacer disposed between a portion of each of the two substrate tapes. A spacer can be configured to adjust the space between the two substrate tapes depending on one or more conditions. The cartridges can be removable from the device, for example, using methods to secure the cartridge in place. The cartridges may additionally comprise pass-through pigtails. A pass-through can be configured to standardize the amount of saturated blood in the two substrate strips.
[0056] Standardized amounts of blood collection on the specific surface area substrate can be obtained using various methods. Methods for applying blood to at least two solid supports can
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22/134 understand the steps of providing a cartridge comprising at least two solid supports. The cartridge provided may comprise at least two solid supports that are substantially the same size, such that a surface of each of the at least two solid supports facing each other and the surface of at least two solid supports are substantially parallel to each other. The at least two solid supports can be separated by a defined distance (for example, within the 10% 0.4 mm range), and the cartridge can be configured in such a way that a channel is formed between the two solid supports. Blood can be passed through the tunnel between at least two solid supports, where blood is absorbed by each of at least two solid supports as it passes through the tunnel between at least two solid supports. The solid supports used in these methods can have fixed dimensions (for example, a width between 3 mm and 10 mm and a length between 3 mm and 26 mm). The cartridge used in the method may additionally comprise a passageway configured to measure blood flow through the device.
[0057] Additional aspects and advantages of this report will be readily clear to those skilled in the art from the detailed description below, where only illustrative achievements of this report are shown and described. As will be noted, the present report is capable of other and different achievements, and its various details are capable of modifications in several obvious aspects, all without departing from the report. Likewise, the drawings and description should be seen as illustrative and not restrictive.
INCORPORATION BY REFERENCE [0058] All publications, patents and patent applications mentioned in this report are hereby incorporated by reference to the same extent that each publication, patent or patent application was specifically and individually indicated to be incorporated by reference.
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23/134
BRIEF DESCRIPTION OF THE DRAWINGS [0059] The new features of the invention are presented with particularity in the appended claims. A better understanding of the characteristics and advantages of the present invention will be obtained by reference to the detailed description below which presents illustrative embodiments, in which the principles of the invention are used, and in the accompanying drawings in which:
[0060] FIG. AI is a perspective view of a sampling device according to some embodiments;
[0061] FIG. 1B shows a recess in the device for sucking the skin;
[0062] FIG. 1C shows a device flow meter to monitor the progress of the sample collection;
[0063] FIG. 1D shows a removable cartridge assembly for sample collection;
[0064] FIG. 2A shows a perspective view of the mounting of the base of the device housing;
[0065] FIG. 2B shows a perspective view of a housing cover of the device;
[0066] FIG. 2C shows another perspective view of the device;
[0067] FIG. 3A shows a side section view of the device before inserting the cartridge assembly;
[0068] FIG. 3B shows a top view of the device of FIG. 3A;
[0069] FIG. 4A shows a side view of the device after inserting the cartridge assembly;
[0070] FIG. 4B shows a top section view of the device of FIG. 4A;
[0071] FIG. 5A shows a side section view of the device placed on an individual's skin without the activation of a vacuum;
[0072] FIG. 5B shows a schematic block diagram corresponding to the device of FIG. 5A;
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24/134 [0073] FIG. 6A shows the individual's skin being positioned in the recess under vacuum pressure;
[0074] FIG. 6B shows a schematic block diagram corresponding to the device of FIG. 6A;
[0075] FIG. 7A shows a puncture activator for the device in a locked state;
[0076] FIG. 7B shows the device's drilling activator in an unlocked state;
[0077] FIG. 8A shows the individual's skin being penetrated by the perforating elements after the perforating elements have been activated;
[0078] FIG. 8B shows a schematic block diagram corresponding to the device of FIG. 8A;
[0079] FIG. 9A shows the blood being drawn from cuts in the skin after the perforating elements have been retracted;
[0080] FIG. 9B shows a schematic block diagram corresponding to the device of FIG. 9A;
[0081] FIG. 10A shows the preferred and increased blood flow from the cuts towards the cartridge in the deposit chamber of the device;
[0082] FIG. 10B shows a schematic block diagram corresponding to the device of FIG. 10A;
[0083] FIGS. 11A and 11B show schematic block diagrams of a sampling device prior to insertion of a cartridge assembly;
[0084] FIGS. 12A and 12B show schematic block diagrams of the device after inserting the cartridge assembly;
[0085] FIGS. 13A and 13B show the device of FIGs. 12A / 12B being placed on an individual's skin;
[0086] FIGS. 14A and 14B show the equalization of the individual's pressures and skin being positioned in the recess, by perforating the sheet that separates the vacuum chamber and the deposit chamber;
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25/134 [0087] FIGS. 15A and 15B show the individual's skin being completely positioned in the recess by negative pressure;
[0088] FIG. 16A shows the development of the perforating elements and the penetration of the individual's skin into the recess;
[0089] FIG. 16B shows the individual's skin being penetrated and the retraction of the perforating elements;
[0090] FIG. 16C shows the initial blood flow from the cuts in the skin; [0091] FIG. 16D shows the blood being drawn towards the cartridge in the deposit chamber with the aid of vacuum, pressure differentials, and gravitational force;
[0092] FIG. 16E shows the preferential flow of blood towards the deposit chamber, and the passage of blood along the matrices in the cartridge;
[0093] FIG. 16F shows the blood absorbed in the matrices, and completion of blood collection;
[0094] FIGS. 17A, 18A, and 19A show schematic block diagrams of the blood flow along the matrices in the cartridge at different stages of blood collection;
[0095] FIGS. 17B, 18B, and 19B illustrate a flow meter indicating the progress of blood collection according to some achievements;
[0096] FIGS. 17C, 18C, and 19C illustrate a flow meter indicating the progress of blood collection according to some other achievements;
[0097] FIG. 20A shows a top view of a device with the flow meter indicating that blood collection has been completed;
[0098] FIG. 20B is a schematic block diagram corresponding to the device of FIG. 20A before removing the full cartridge assembly;
[0099] FIG. 21A shows a top view of the device with the full cartridge assembly removed;
[00100] FIG. 21B is a schematic block diagram corresponding to the device of FIG. 21A with the full cartridge assembly removed;
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26/134 [00101] FIG. 22A shows a perspective view of a carrying glove;
[00102] FIG. 22B shows a top view of the carrying sleeve and a full cartridge assembly prior to insertion into the sleeve;
[00103] FIG. 22C shows the full cartridge assembly inserted into the carrying sleeve;
[00104] FIG. 23 shows an exploded view of the carrying sleeve and cartridge assembly;
[00105] FIG. 24A shows a side section view of the transport sleeve with the cartridge assembly inserted therein;
[00106] FIG. 24B shows a side section view with the cartridge holder removed, leaving the cartridge inside the transport sleeve;
[00107] FIGS. 25A and 25B show a typical procedure for collecting blood samples from an individual using a sample collection device, and packing the blood sample for dispatch;
[00108] FIG. 26 shows an exploded view of certain components of the sampling device;
[00109] FIG. 27A shows different views of piercing elements;
[00110] FIG. 27B shows the piercing elements being supported by a support;
[00111] FIG. 28A shows different views of an implantation spring;
[00112] FIG. 28B shows different views of a retraction spring;
[00113] FIG. 29 shows different views of two arrays separated by spacers with an absorbent pad at one end;
[00114] FIG. 30 shows examples of different types of recesses that can be used in a sampling device;
[00115] FIG. 31 A, FIG. 31B, FIG. 31C and FIG. 31D illustrate features that can be included in a device for collecting a blood sample;
[00116] FIG. 32A, FIG. 32B, FIG. 32C and FIG. 32D illustrate front, side and rear views of a device that can be used to collect a
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27/134 sample of defined volume and store it in a removable stabilization matrix;
[00117] FIG. 33A, FIG. 33B and FIG. 33C illustrate features of a device that can be used to increase sample collection;
[00118] FIG. 34A, FIG. 34B, FIG. 34C and FIG. 34D illustrate an embodiment of a device for collecting a blood sample from an individual, and means for storing the sample in a removable cartridge;
[00119] FIG. 35 illustrates an internal view of a removable cartridge that can be used with any of the sample collection devices described (for example, the sample collection devices illustrated in FIGS. 31A-31D, FIGS. 32A-32D, FIGS. 33A -33C and Figures 34A-34D);
[00120] FIG. 36A and FIG. 36B illustrate a typical orientation of a device or device configured to use one or more mechanisms (for example, gravity, capillary action, global vacuum and local suction) for collecting and depositing a blood sample in a solid matrix for storage;
[00121] FIG. 37A, FIG. 37B, FIG. 37C and FIG. 37D illustrate a modular design of a device with components configured to generate a vacuum, lance the individual's skin, collect, measure and stabilize an individual's blood sample, and store the collected sample;
[00122] FIG. 38A illustrates external characteristics of a low profile embodiment typical of a device provided here;
[00123] FIG. 38B illustrates the internal work of a device provided here in a typical starting position, when the device is not activated;
[00124] FIG. 38C illustrates the internal work of a device provided here once the button is pressed (1), and the blade holder is released (2);
[00125] FIG. 38D illustrates the internal work of a device provided here at one end of a blade support displacement path, where the collection arm is released by a tongue that contacts the blade support at the end of the displacement path;
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28/134 [00126] FIG. 38E shows a side view of a device provided here, providing a view of a release mechanism for the blood collection arm;
[00127] FIG. 38F illustrates a released blood collection arm creating a seal around the cuts created by the blades shown in FIG. 38E;
[00128] FIG. 39A, FIG. 39B, FIG. 39C, FIG. 39D and FIG. 39E illustrate top, bottom, side and internal views of a low profile blood collection device;
[00129] FIG. 40A, FIG. 40B, FIG. 40C and FIG. 40D illustrate various views of a blood collection device and its components configured to lance for an individual using a vertical cut, and extracting a sample from the individual using a syringe;
[00130] FIG. 41A illustrates a safety mechanism that can be used to prevent inadvertent blade implantation of a blood sample collection device to collect a sample that is based on vertical cutting using a rotating blade;
[00131] FIG. 41B illustrates a mechanism for collecting a sample using a blood collection device that is based on vertical section using a rotating blade;
[00132] FIG. 42A, FIG. 42B and FIG. 42C illustrate a device and mechanism for collecting a sample using a rotating spring-loaded blade to perform vertical cutting;
[00133] FIG. 43A and FIG. 43B illustrate a device for applying global vacuum and local suction to collect an appropriate amount of sample within a desired period of time (for example, at a rate that falls within a desired range);
[00134] FIG. 44A and FIG. 44B illustrate two views of a device for simultaneously lancing and an individual and forming a fence;
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29/134 [00135] FIG. 45A, FIG. 45B and FIG. 45C illustrate a typical vacuum chamber that can be used with any of the devices and methods described here;
[00136] FIG. 46A, FIG. 46B and FIG. 46C illustrate a typical chamber for the collection, measurement, storage and stabilization of a sample and mechanisms for directing the sample through the chamber and for the solid matrices for the storage of the sample;
[00137] FIG. 47 illustrates the components of a system configured to collect a blood sample using a sample collection device and a removable sample storage cartridge;
[00138] FIG. 48 illustrates the steps that an individual or clinician must take to collect and provide a sample for a facility for analysis;
[00139] FIG. 49 illustrates the steps that a laboratory (for example, a CLIA certified laboratory or other facility) must take to prepare a sample for analysis;
[00140] FIG. 50A, FIG. 50B and FIG. 50C illustrate a visual measurement window that allows a user to view the progress of the withdrawal (FIG. 50A illustrates visual tracking by a healthcare provider (HCP) as the stabilization matrix tape is filled. When the final window is filled , withdrawal is complete Fig. 50B illustrates a passage cushion that captures excess blood Fig. 50C illustrates varying levels of blood deposition in the matrix tapes);
[00141] FIG. 51 illustrates the percentage of HbAlc in blood samples of five different volumes (30 pL, 45 pL, 60 pL, 75 pL, 100 pL) taken from two different donors;
[00142] FIG. 52 illustrates a flowchart of a clinical trial to assess the accuracy of blood tests performed using blood drawn with the devices described here in comparison with venipunctures;
[00143] FIG. 53 illustrates the principles of operation and flow of use of a device;
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30/134 [00144] FIG. 54 illustrates HbAlc as a percentage of total hemoglobin (Y-axis) for various experimental conditions (X-axis) (for each condition, the average of replicated measurements is plotted as a black bar and sample measurements are shown as open circles. dashed lines delineate ± 6% relative error around the mean measure of Day 0);
[00145] FIG. 55 illustrates HbAlc as a percentage of total hemoglobin (Y-axis) for various experimental conditions (X-axis) (for individuals, Day 0, liquid whole blood, replicates for each donor are plotted as circles. Two technical replicates for each strand dried blood stain (DBS) are averaged and the resulting DBS tape averages are also plotted as circles. For each experimental condition, the average of all measurements is plotted as a black bar. Dashed lines outline ±% error relative to the specific donor, Day 0, average measurements); and [00146] FIG. 56 illustrates a typical procedure for collecting and storing blood using a device described here.
DETAILED DESCRIPTION [00147] Reference will now be made in detail to typical achievements of the report, examples of which are illustrated in the attached drawings. Whenever possible, the same numerical references will be used in all drawings and reports to refer to the same or similar parts.
I. General [00148] Here, devices, methods and kits are provided for collecting a sample of fluid, for example, from an individual's body. The fluid sample may, for example, be blood drawn from the subject's penetrated skin. The device described here can be portable and user activated and suitable for use outside traditional healthcare facilities, for example, in homes, in remote locations, while an individual is working, etc. The devices can be portable and easy to use, and allow individuals to reliably collect their own blood samples efficiently, without requiring trained healthcare personnel and without requiring that the individual has been there for a long time.
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31/134 any previous training experience in drawing blood. The devices and methods described here can be minimally invasive and allow low levels of pain (or perception of pain) in an individual compared to the use of other devices and methods, which can help to increase the overall blood draw experience for the individual. Kits can be provided with detailed instructions that guide users on how the devices can be used for collecting and storing blood samples. Optionally, in any of the embodiments described here, kits can include transport gloves and bags for shipping / transporting cartridges to test facilities. A cartridge can be configured to support one or more arrays configured to hold at least a predefined volume of blood collected.
[00149] In particular, the sampling devices and methods described here can improve the collection of a fluid sample (e.g., blood) from the individual. The sampling device and the methods described may be able to draw blood at increased flow rates and larger sample volumes starting at the time of skin incision, compared to currently available non-venous blood collection devices and methods. According to various achievements in this report, an average collection flow rate and sample volume collected can be increased with the aid of a number of features, for example, a recess that is configured or optionally designed for skin suction, vacuum , pressure differentials, aid of gravitational force, passing or capillarity effects, as described in greater detail below. Additionally, the achievements described here are advantageous in relation to the currently available non-venous blood collection devices and methods, as the described devices and methods may allow the stabilization of the controlled volumes of blood samples to be deposited on one or more strips of the matrix. Additional advantages of the described achievements may include the ease of
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32/134 removing the sample from a sample collection device, and the sample packaging removed for subsequent transportation to test facilities.
[00150] Samples, for example, blood samples, collected using the device and sampling methods described here can be analyzed to determine a person's physiological state, for disease detection and also to monitor a condition user health. Individuals can quickly assess their physiological status, since samples, for example, blood samples can be quickly collected using the devices and methods described, and samples, for example, blood samples can be or (1) analyzed on site using, for example, immunological assays or (2) promptly shipped to a test facility. The reduced time for blood collection, analysis and quantification can be beneficial for many users, for example, users who have certain physiological conditions / diseases that require constant and frequent blood sample collection / monitoring.
[00151] Various aspects of the devices, methods, and kits described here can be applied to any of the particular applications presented here and to any other types of fluid sample devices, in addition to blood collection devices. The devices, methods and kits can be used in any system that requires a fluid sample to be taken from the individual's body. The devices, methods and kits described here can be applied as a stand-alone device or method, or as part of a medical system in a healthcare setting. It should be understood that different aspects of the devices, methods and kits described here can be enjoyed individually, collectively or in combination with each other.
II. Sampling devices [00152] FIGs. 1A-1D illustrate a sampling device (100) according to some embodiments. A sampling device as described here can refer to any device, device or system that is designed, configured or used for collection, storage and / or
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33/134 stabilization of a fluid sample, for example, a fluid sample taken from an individual. In many ways, the sample is a biological sample. Non-limiting examples of biological samples suitable for use with the reporting devices may include blood, blood serum, blood plasma, and the like.
[00153] The devices here can be used in a variety of environments and applications including the individual's own home, remote locations, on-site or while traveling, personalized health care, personalized health care points (POC), hospitals, clinics, emergency rooms, patient exam rooms, severely ill care rooms, outpatient care, pediatrics, field settings, nursing rooms in educational facilities, occupational health clinics, operating and operating rooms.
[00154] In some of the embodiments described here, a sample collection device is preferably used to collect and store a sample, for example, of blood, taken from an individual. An individual, as described here, can be a person, a user, an end user, a patient, and the like. An individual can be an animal, preferably a primate or a non-primate. An individual can be male or female. An individual may be a pregnant woman, suspected of being pregnant or planning to become pregnant. An individual may be ovulating. An individual may have a condition, for example, cancer, autoimmune disease, or diabetes. A human can be a baby, child, teenager, adult or an elderly person. In certain embodiments, the mammal is 0 to 6 months old, 6 to 12 months old, 1 to 5 years old, 5 to 10 years old, 10 to 15 years old, 15 to 20 years old, 20 to 25 years old, 25 to 30 years old, 30 to 35 years old, 35 to 40 years old, 40 to 45 years old, 45 to 50 years old, 50 to 55 years old, 55 to 60 years old, 60 to 65 years old, 65 to 70 years old, 70 to 75 years old, 75 to 80 years old, 80 to 85 years old, 85 to 90 years old, 90 to 95 years old
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34/134 or 95 to 100, or over 12 years of age, over 16 years of age, over 18 years of age, or over 21 years of age.
[00155] The sampling device described here can be easily and conveniently used by an individual to take a sample, for example, blood sample, without the help or assistance of others. Optionally, in some cases, the device can be used by a third party to collect blood from an individual. A third party may include, for example, a member of the individual's family, trained medical professionals such as doctors and nurses, Emergency Medicine Technicians (EMTs), clinicians, laboratory technicians, untrained medical personnel, etc. Optionally, in any of the achievements described here, a third party can be a non-living entity, for example, a robot.
[00156] The device can be designed in such a way that it is minimally invasive and generates a low level of pain (or reduced perception of pain) in users. For example, the device may include a small number (for example, one or two) of piercing elements, instead of a set of multiple (three, four, five or more) needles or microneedles to penetrate the skin. Optionally, a device does not need to be prepackaged with one or more piercing elements. For example, a variety of piercing elements can be operably and releasably coupled to the device and / or interchangeable in the device, for example, after each use. In some alternative cases, a device can be operated without the use of perforating elements. For example, an individual's skin may have one or more pre-existing cuts, and the device can be placed over the one or more pre-existing cuts to draw blood using vacuum suction skin suction.
[00157] The device can be portable, disposable and designed for use in a single session with the patient. Optionally in any of the embodiments described here, the device can be reusable. For example, a device can be used more than once, for example, two, three, four,
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35/134 five six, seven, eight, nine, ten or more times. Optionally in any of the embodiments described here, a single device can be used in multiple sessions with a patient, with the same individual or with a plurality of different individuals. The device can be shaped and ergonomically designed to facilitate the sample collection process. Sample collection, treatment and storage can be performed in a single device. In some cases, sample collection, treatment and storage can be performed using multiple components or devices (for example, a drilling module and a vacuum module can be provided as separate devices that are operationally connected or coupled together through one or more channels).
[00158] In some embodiments, a sampling device may be configured or capable of collecting at least 150 uL of blood from an individual within a time window starting at the time of incision or penetration of a part of the individual's skin. The time window can be less than 5 minutes, preferably less than 3 minutes. In some embodiments, the time window can be under 2 minutes. Optionally in any of the achievements described here, the time window can be less than a minute. The device is capable of collecting larger blood at higher average flow rates compared to the non-venous collection devices available today. [00159] In some other embodiments, a sample collection device can be configured to collect smaller amounts of blood (for example, less than 150 uL, 140 uL, 130 uL, 120 uL, 110 uL, 100 uL, 90 uL, 80 µl, 70 µl, 60 µl, 50 µl, 40 µl, 30 µl, or 25 µl) of an individual within a time window starting at the time of incision or penetration of a part of the individual's skin. The time window can be less than 5 minutes, preferably less than 3 minutes. In some embodiments, the time window can be under 2 minutes. Optionally in any of the achievements described here, the time window can be less than a minute.
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36/134 [00160] FIGS. 1A, IB, 1C and ID illustrate different views of a typical sampling device (100). Specifically, FIG. IA shows a global perspective view of the device. The device can include a housing (102). The housing may include a housing base (110) and a housing cover (152) operably coupled together. The housing base can comprise a vacuum chamber and a deposit chamber as described hereinafter.
[00161] Optionally, in any of the embodiments described here, a housing can be provided separately from the components of the device, and the housing does not need to be part of or integrated with the components. For example, a vacuum chamber, deposit chamber, cartridge chamber and / or cartridge assembly as described herein can be operationally coupled to a housing provided separately. A recess, such as that described here, can be provided in a part of the housing. A housing can include a compartment, container, shell, box, and the like. A housing may include one or more hollow chambers, cavities or recesses. The housing can be formed with any shape and / or size. The housing can be configured to support one or more components as described here. Additionally or optionally, one or more of the components can serve or function as the housing. The housing can be integrated with one or more of the components here, or one or more of the components can be integrated with or in the housing. The housing can be configured to be mounted on a surface such as, for example, an individual's skin. Optionally, in any of the embodiments described here, a support or brace can be provided that allows the housing to be mounted to a surface.
[00162] The device may include a vacuum activator (114). The vacuum activator may include a button (115) located at the base of the housing base. In some cases, the device does not have a vacuum activator or does not need to have a vacuum activator (for example, the device can be configured to automatically provide a vacuum by detecting contact with a surface
Petition 870190079292, of 08/15/2019, p. 41/211 appropriate, without requiring a user to manually or semi-manually activate a vacuum activator). The device may additionally include a drilling activator (166). The drilling activator may include a button (167) located on the housing cover. In some cases, the device does not have a puncture activator or does not need to have a puncture activator (for example, the device can be used to draw blood from skin that has already been penetrated or pre-cut by other discrete autonomous piercing elements). The drilling activator can preferably be activated after the vacuum activator has been activated. In some cases, the drilling activator can be activated regardless of the vacuum activator or vacuum state of the device. In some embodiments, the drilling activator can be locked before using the device, and the drilling activator can be activated only after the vacuum activator has been activated. In some cases, the vacuum activator is locked before using the device, and the vacuum activator can be activated only after the drilling activator has been activated. The drilling activator (for example, button (115)) and the vacuum activator (for example, button (167)) can be located on the same side or face of the housing. Alternatively, the drilling activator (for example, button (115)) and the vacuum activator (for example, button (167)) can be located on different sides or faces of the housing. The device (100) or any of the devices here can additionally include a cartridge assembly (180). Such a cartridge assembly can be releasably attached to the device and decoupled from the device. As shown in FIG. IA, a cartridge tab (192) of the cartridge assembly may protrude from an edge of the device. Optionally, in any of the embodiments described here, the cartridge tab and the punch activator / vacuum activator (for example, buttons (115/167)) can be located on different sides (for example, opposite ends) of the housing. Additional details about the vacuum activator and the drilling activator are described here.
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38/134 [00163] FIG. IB shows a bottom perspective view of the device, in particular a recess (136) provided at the base of the housing (110). The recess can be a concave cavity. The recess may have a cup-like appearance. Optionally, in any of the embodiments described here, the recess may have a substantially hemispherical shape. The base of the housing can be configured to be placed and releasably attached to a part of an individual's body, for example, on the individual's upper arm. A part of the individual's skin can be positioned in the recess with the aid of vacuum pressure, for example, as described here. The recess can be configured with a shape and / or size that allows an increased volume of a fluid sample (eg, blood) to be collected from an individual. The base of the housing may include a flat part (132) to be placed on the subject's skin. The flat part may surround the periphery of the recess. The flat part of the base of the housing can take any shape. Optionally, in any of the embodiments described here, the flat part may include a ring-like shape. An adhesive (not shown) can be placed on the flat part of the base of the housing in order to promote the adhesion of the device to the individual's skin, and in order to create a hermetically sealed seal to the air after the device has been placed on the skin. Optionally, in any of the embodiments described here, a thread (138) can be provided between the periphery of the recess and the flat part of the base of the housing. The fillet can increase the suction of the vacuum in the skin and reduce leaks. As shown in FIG. 1B, the recess may include an opening (140). The opening can be located anywhere in the recess. For example, the opening can be located in a more internal part of the recess. Optionally, in any of the embodiments described here, a thread (139) can be provided at the periphery of the opening. Additional details about the recess, opening and suction of the skin into the recess are described here.
[00164] The opening (140) can be an opening of a lumen (142). The lumen may include a port (144) leading to a deposit chamber (not
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39/134 shown) located at the base of the housing. Optionally, in any of the embodiments described here, the lumen can include a cutout (145), and the door (144) can be provided inside or close to the cutout. The cutout (145) can assist in reducing or preventing occlusion of the door (144) by an individual's skin when the skin is positioned in the recess at the base of the housing. Maintaining access to the open door (144) (for example, not having the door occluded or blocked by the skin) can assist in ensuring that blood drawn from an individual's skin is able to flow through the door (144) inwards deposit chamber. The lumen may additionally include a door (150) leading to a container for containing one or more piercing elements (not shown). The one or more perforating elements may be configured to extend out of the opening so as to penetrate the individual's skin when (or after) the skin is positioned in the recess by vacuum pressure. The one or more piercing elements can subsequently be retracted back into the housing after penetrating the skin. Additional details about the one or more piercing elements and their activation are described here.
[00165] Blood can be drawn from cuts made on the skin. Blood can flow from the cuts through the port (144) towards a cartridge (not shown) located in a deposit chamber at the base of the housing. The flow rate and volume of blood collection can be improved (for example, increased) with the aid of vacuum, pressure differentials, gravitational force, and passing / capillarity effects, for example, as described in detail here. The cartridge may include one or more matrices for the collection and storage of blood volume. Additional details about the improved fluid collection are described in several parts of the report, for example, in Section II Part G.
[00166] FIG. IC shows a flow meter (170) of the device. The flow meter may include one or more optically transparent windows (172). The flow meter can be substantially aligned with the cartridge (specifically the dies in the cartridge) when the cartridge assembly is inserted into the device. The flow meter can allow the individual or a
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40/134 another user monitors the progress of the sample collection (eg blood) in real time as the sample is being collected for the cartridge. In some embodiments, the flow meter may be provided in a cover on the base of the housing. For example, the flow meter can be formed as part of the cover. The cover can be an intervening layer between the base of the housing and the cover of the housing. The cover can cover the base of the housing, and seal a vacuum chamber at the base of the housing. In some embodiments, the cover can be ultrasonically welded to the housing base. The cover can provide an air tight seal. Additional details about the flow meter are described, for example, in Section II Part F of the report.
[00167] FIG. 1D shows a cartridge assembly (180) that can be releasably attached to the device. The cartridge assembly can be part of the device, and can be detached from the device. The cartridge assembly can be inserted into a deposit chamber (or cartridge chamber) at the base of the housing through an opening (128). The cartridge assembly can include a cartridge (182) and a cartridge holder (190). The cartridge holder is configured to support the cartridge. The cartridge holder can include a cartridge tab (192), a seal / gasket (194) and soft clips (196). An individual or user can manipulate or secure the cartridge assembly using the cartridge tab. For example, the individual can insert the cartridge assembly into the deposit chamber (cartridge chamber) of the device by pushing the cartridge tab. After the sample collection has been completed, the individual can remove the cartridge assembly from the deposit chamber (cartridge chamber) from the device by pulling on the cartridge tab. The individual can also hold the cartridge assembly by the cartridge tab in order to avoid contamination of the cartridge and / or sample. The seal / gasket (194) can hermetically seal the deposit chamber (cartridge chamber) once the cartridge assembly has been properly inserted into the device. The spring clips (196) allow the cartridge to be held in place by the cartridge holder.
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41/134 [00168] The cartridge can be configured to support one or more matrices (186) in which the fluid sample (for example, blood) is collected. In some embodiments, the cartridge can support two or more arrays. The two or more arrays can be separated by one or more spacers. The cartridge can include a cartridge port (184) and a channel (not shown) leading to the arrays. The cartridge can be configured to support one or more absorbent pads (not shown) to hold excess fluid. Absorbent pads help to ensure that a predefined volume of fluid can be collected in each of the matrices. Additional details about cartridge assembly are described, for example, in Section II Part C of the report.
[00169] The base of the housing (110) and the cover of the housing (152) can each be provided separately and coupled together in order to form the housing. For example, FIG. 2A shows a perspective view of the base of the housing (110) with a cover (124) covering / sealing the base of the housing. The base of the housing may include a vacuum chamber (112) and a deposit chamber (126). The vacuum chamber and the deposit chamber can be separated by one or more walls (125). The walls can be substantially impervious to fluids (for example, gases and liquids). The cover (124) can hermetically seal the vacuum chamber and the deposit chamber. The cover can include the flow meter (170). The deposit chamber can also serve as a cartridge chamber, and can be interchangeably referred to as such here. A cartridge assembly (180) is shown inserted in the deposit chamber (or cartridge chamber). The seal / gasket (194) can hermetically seal the deposit chamber once the cartridge assembly is fully inserted in the deposit chamber. FIG. 2B shows a perspective view of the housing cover (152). The housing cover can include a hollow hole (153) through which the button (167) of the drilling activator (166) can be inserted. The housing cover may include wings (155) having a U or V shape to prevent obscuring the flow meter on the housing base cover.
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Likewise, the housing cover can be formatted in a way that allows an individual or another user to view the flow meter and monitor the progress of fluid sample collection. The housing cover can have sufficient vertical clearance (height Z) to allow the placement of a drilling module (154). The piercing module may comprise one or more piercing elements that are configured to extend and retract through the opening in the recess. FIG. 2C shows a perspective view of the assembled device (100), whereby the housing cover and the housing base are coupled together. Typical means of fixing the housing cover to the housing base may include snapfits, ultrasonic welding, nuts and bolts, rivets, screws, nails, latches, tongues, wires, joints, welds, glues and the like. In some alternative embodiments, the housing base and housing coverage can be formed in a monolithic and collective manner as a single component.
[00170] The device housing can be formed showing any shape and / or size. The housing or any components thereof can be formed using any of a number of known techniques such as injection molding, blow molding, three-dimensional (3D) printing, etc. The housing may include materials suitable for healthcare applications (for example, the housing material is compatible with use with biological materials), depending on the particular application. For example, housing components may include or be manufactured from materials such as cellophane, vinyl, acetate, acrylic polyethylene, butyl rubber, ethylene vinyl acetate, natural rubber, a nitrile, silicone rubber, a block copolymer styrene, a vinyl ether or a bonding agent. Optionally, in any of the embodiments described here, the device can include antimicrobial and / or antiseptic materials, for example, sodium bicarbonate; hydrogen peroxide; benzalkonium chloride; chlorhexidine; hexachlorophene; iodine compounds; and combinations of these.
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43/134 [00171] Optionally, in any of the embodiments described here, one or more components of the device may include or may be manufactured from materials such as polyvinyl chloride, polyvinylidene chloride, low density polyethylene, low polyethylene linear density, polyisobutene, poly [ethylene-vinyl acetate] copolymer, low weight aluminum foil and combinations thereof, stainless steel alloys, commercially pure titanium, titanium alloys, silver alloys, alloys and copper, Grade 5 titanium , super elastic titanium alloys, cobalt-chromium alloys, stainless steel alloys, super elastic metal alloys (eg Nitinol, super elastic plastic metals, such as GUM METAL® manufactured by Toyota Material Incorporated in Japan), ceramics and composites of these such as calcium phosphate (eg SKELITE ™ manufactured by Biologix Inc.), thermoplastics such as polyarylketercetone (PAEK) including poly etherotercetone (PEEK), polyethylketonone (PEKK) and polyethercetone (PEK), carbon-PEEK composites, PEEK-BaSO4 polymeric rubbers, polyethylene terephthalate (PET), fabric, silicone, polyurethane, silicone-polyurethane copolymers, polyester rubbers polyolefins, hydrogels, semi-rigid and rigid elastomeric materials, rubbers, thermoplastic elastomers, thermoset elastomers, elastomeric composites, rigid polymers including polyphenylene, polyamide, polyimide, polyetherimide, polyethylene, epoxy, partially absorbable materials, such as metals and, for example, partially absorbable materials housed calcium-based ceramics, PEEK composites and housed calcium-based ceramics, PEEK composites with resorbable polymers, fully resorbable materials, such as, for example, housed calcium-based ceramics such as calcium phosphate, tri phosphate -calcium (TCP), hydroxyapatite (HA) -TCP, calcium sulfate or other resorbable polymers such as polyeaide, polyglycolide, polytyrosine carbonate, polycaroplaetohe and their combinations.
[00172] The device housing may comprise styrene acrylobutadiene (ABS), polypropylene (PP), polystyrene (PS), polycarbonate (PC), polysulfone (PS), polyphenyl sulfone (PPSU), polymethyl methacrylate (acrylic)
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44/134 (PMMA), polyethylene (PE), high molecular weight polyethylene (UHMWPE), lower density polyethylene (LPDE), polyamide (PA), liquid crystal polymer (LCP), polyaryl amide (PARA), sulfide polyphenyl (PPS), polyether etherketone (PEEK), polyvinyl chloride (PVC), polyethylene terephthalate (PET), polyethylene flourethylene (PTFE), polyarethylketone (PAEK), polyphenyl sulfone (PPSU) or a combination of these. In some embodiments, a device described here may comprise polypropylene, polycarbonate, glass-filled polycarbonate, a low permeability copolyester (e.g., Eastman MN211), polyisoprene rubber and / or injection moldable TPE seals.
[00173] Various components of the device may have composite materials, including one or more of the above materials, in order to obtain various desired characteristics such as strength, stiffness, elasticity, acceptance, biomedical performance, durability and / or radiolucency preference. One or more of the components of the device may comprise antimicrobial and / or antiseptic materials. The components of the device, individually or collectively, can also be manufactured from heterogeneous materials such as a combination of two or more of the materials described above. The components of the device can be formed in a monolithic way or connected integrally.
[00174] The device can be designed ergonomically in such a way that an individual or user is able to hold the device comfortably with one hand or both hands. The device may feature a compact form factor that makes it highly portable (for example, easy to carry in a user's bag or pocket). The typical dimensions (for example, length, width and height) of the device can be given as follows. In some embodiments, the length is about 1.5 inches, about 2.0 inches, about 2.5 inches, about 3.0 inches, or about 3.5 inches. The length can be between about 2.0 inches and about 3.0 inches. The length can be between about 1.5 inches and about 3.5 inches. In some embodiments, the width is about 1.25
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45/134 inches, about 1.5 inches, about 1.75 inches, about 2.0 inches, or about 2.25 inches. The width can be between about 1.5 inches and about 2.0 inches. The width can be between about 1.25 inches and about 2.25 inches. In some embodiments, the height is about 1.25 inches, about 1.5 inches, about 1.65 inches, about 2.0 inches, or about 2.25 inches. The height can be between about 1.5 inches and about 2.0 inches. The height can be between about 1.25 inches and about 2.25 inches. The length by width by height can be about 2.5 inches by about 1.75 inches by about 1.65 inches.
[00175] FIG. 3A shows a side section view of the device (100) prior to insertion of the cartridge assembly (180) into the device, and FIG. 3B shows a corresponding top view. FIG. 4A shows a side view of the device with the cartridge assembly inserted, and FIG. 4B shows a corresponding top section view. Various characteristics of the device (100) and the cartridge assembly (180) are described below in detail with reference to the figures above other relevant figures.
A. Skin suction recess [00176] Referring to FIGs. IB and 3A, the base of the housing (102) of the device can include the recess (136). The recess can be provided in a part (for example, bottom surface) of the base of the housing. The recess can be formed as a sunken cavity or trench at the base of the housing. In some cases, the recess may be formed as an extrusion molded at the base of the housing. The recess can be shaped like a cup and configured to provide a “cup” effect on the skin with the aid of vacuum pressure. The recess can be sized and / or shaped to receive a portion of a surface, for example, the individual's skin, and to allow the surface, for example, of the skin to substantially conform to the recess by applying vacuum pressure. A surface of the recess may be substantially in contact with the skin positioned in the recess. A space between the skin and the recess
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46/134 can be neglected when the skin is positioned in the recess. The recess can serve as a suction cavity in order to position the skin inside and to increase the capillary pressure differential. The recess can be configured with a size and / or shape that allows an increased volume of blood to accumulate in the skin positioned in the recess. The increased volume of the fluid sample may depend in part on a volume and / or surface area of the skin that is positioned in the recess.
[00177] In some alternative embodiments, the device can be configured to position other types of objects (for example, objects other than skin or skin surfaces) in the vacuum recess, and to additionally take a fluid sample from these objects. Examples of these other types of objects may include sponges, cloths, fabrics, paper, porous materials, organic products such as fruits or vegetables, or any other solid materials that contain (or are capable of containing) fluid samples. Additional non-limiting examples of biological samples suitable for use with the reporting device may include sweat, tears, urine, saliva, feces, vaginal secretions, semen, interstitial fluid, mucus, sebum, crevicular fluid, aqueous humor, vitreous humor, bile, breast milk, cerebrospinal fluid, cerumen, endolymph, perilymph, gastric juice, peritoneal fluid, vomiting and the like. In some embodiments, a fluid sample can be a solid sample that has been modified with a liquid medium. In some cases, a biological sample can be obtained from an individual in a hospital, laboratory, clinical laboratory or doctor.
[00178] The recess can be configured to maintain contact with a surface area of the individual's skin under vacuum pressure, before and as blood is being collected from the individual's penetrated skin. In some embodiments, the surface area of the individual's skin in contact with the recess may be at least 3 cm ² , 4 cm ² , 5 cm ² , 6 cm ² , 7 cm ² , 8 cm ² , 9 cm ² , or 10 cm ² , or any value between them. In some preferred embodiments, at least 5 cm ² of the individual's surface area of skin may be in full contact with the surface of the recess when the skin is positioned in the recess under pressure of
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47/134 vacuum. In some embodiments, the volume of the skin contained within the recess may be at least about 1.0 cm ³ , 1.1 cm ³ , 1.3 cm ³ , 1.4 cm ³ , 1.4 cm ³ , 1.5 cm ³ , 1.6 cm ³ , 1.7 cm ³ , 1.8 cm ³ , 1.9 cm ³ , 2.0 cm ³ , 2.1 cm ³ , 2.2 cm ³ , 2, 3 cm ³ , 2.4 cm ³ , 2.5 cm ³ , 2.6 cm ³ , 2.8 cm ³ , 2.9 cm ³ , 3.0 cm ³ , or any value between these. In some embodiments, at least 1.8 cm ³ of the individual's skin may be contained within the recess when the skin is positioned in the recess under vacuum pressure. In some embodiments, the volume contained within the recess can be substantially the same as the internal volume of the recess.
[00179] Optionally in any of the embodiments described here, the base of the device housing may have more than one recess, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more recesses. The recesses can be connected together, for example, by one or more channels. Alternatively, the recesses do not need to be connected to each other. The recesses can be in fluid communication with one or more of the vacuum chambers and deposit chambers described here. The plurality of recesses can be configured to allow suction to occur on multiple parts of a surface (e.g., skin surface). In some cases, the plurality of recesses may allow blood to be drawn from different parts of a user's skin (which is positioned in the plurality of recesses).
[00180] The recess can be formed showing any shape, design, depth, surface area and / or size. The recess can have any convenient shape, such as a curved, hemispherical, spherical cap, square, circle, cuboid, trapezoidal shape, disc etc. The recess can be symmetrical, for example, a hemisphere. Alternatively, the recess may be irregularly shaped and does not need to be symmetrical. The recess may have rounded corners or edges. Additional examples of possible shapes or designs include, but are not limited to: mathematical shapes, two-dimensional geometric shapes, multidimensional geometric shapes, curves, polygons, polyhedron, polytopes, minimal surfaces, ruled surfaces, non-orientable surfaces, quadrics, pseudo-spherical surfaces, surfaces algebraic,
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48/134 Riemann surfaces, geometric shapes, and so on. Optionally, in any of the embodiments described here, the recess may have a substantially circular or elliptical shape. The surface of the recess can be smooth. In some embodiments, the recess can be configured to have a shape and / or size that can reduce or eliminate bruises on the skin when the skin is positioned in the recess by vacuum pressure. Optionally, the recess surface can take on a variety of alternative surface configurations. For example, in some cases, the surface of the recess may contain raised or depressed regions.
[00181] With reference to FIG. IB, the recess may comprise a concave cavity. The concave cavity can have an internal volume of at least about 1.0 cm ³ , 1.1 cm ³ , 1.3 cm ³ , 1.4 cm ³ , 1.4 cm ³ , 1.5 cm ³ , 1 , 6 cm ³ , 1.7 cm ³ ,
1.8 cm ³ , 1.9 cm ³ , 2.0 cm ³ , 2.1 cm ³ , 2.2 cm ³ , 2.3 cm ³ , 2.4 cm ³ , 2.5 cm ³ , 2.6 cm ³ ,
2.8 cm ³ , 2.9 cm ³ , 3.0 cm ³ , or any value between them. In some embodiments, the concave cavity may preferably have an internal volume of about 1.85 cm ³ .
[00182] The recess may have a depth ranging from about 2 mm to about 30 mm, or preferably at least deep enough that part of the individual's skin is positioned in and completely fills the recess under vacuum pressure. The depth can be a height of the recess. The depth can be measured in relation to a more internal part of the recess. In some other embodiments, the recess may have a depth that is less than 2 mm or greater than 10 mm.
[00183] The recess may have a rigid surface (for example, a rigid concave surface) that does not deform when an individual's skin is positioned in the recess under vacuum pressure. Alternatively, the recess may have a flexible surface (for example, a flexible concave surface). For example, the bottom of the recess may include an elastic material such as an elastomer. The elastic material can be configured to conform to the skin when the skin is positioned in the recess. The elastic material can be
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49/134 compressed or pressed against the skin when the skin is positioned in the recess. Compression can help to increase the contact area between the skin and the recess. An increased contact area can allow the skin to completely fill the recess with reduced spaces or creases. This can assist in ensuring that the skin is sufficiently tensioned (under tension) before the skin penetrates for blood collection. Keeping the skin taut can allow deeper cuts to be made on the skin. In addition, keeping the skin taut can also keep the cuts more open compared to loose skin.
[00184] As shown in FIGs. IB and 3A, the recess may be in the form of a spherical cap. The spherical hood can be, for example, a hemisphere or part of a hemisphere. In some embodiments, a diameter of the spherical cap at the base of the housing can vary from about 10 mm to about 60 mm, preferably about 25 mm. A spherical cap height can vary from about 2 mm to about 30 mm, preferably about 6 mm. A volume of a hemisphere formed by the concave surface can be equivalent to, or about half, or about a quarter, of a volume of a vacuum chamber in the device.
[00185] With reference to FIGs. IB and 3A, the recess may include the opening (140). The opening can be located in a more internal part of the recess. For example, the opening can be located at the apex of the recess in a spherical shape. The opening can be formed with any shape and / or size. In some embodiments, the opening may have a substantially circular or elliptical shape. In some cases, the recess may have more than one opening, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 25, 50, 100, 1000, or more openings. One or more of the openings may be in fluid communication with a vacuum source and / or a container containing one or more piercing elements. In some cases, one or more openings, for example, connected to a vacuum source, can be found over the entire surface of the recess, or at least 10%, 25%, or 50% of the surface of the recess.
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Optionally, in any of the embodiments described here, a plurality of openings can be distributed over the entire surface of the recess, for example, in a manner similar to a shower. A vacuum can be applied through the plurality of openings in order to position the individual's skin in the recess. In some cases, one or more of the plurality of openings may be additionally configured to allow one or more perforating elements to extend and retract through them, and to perforate the skin that is positioned in the recess.
[00186] The opening (140) can provide access to / from the lumen (142). The device may include one or more piercing elements which are configured to extend through the lumen and to form the opening into the recess, in order to penetrate the skin that is positioned in the recess under vacuum pressure. Skin penetration can allow blood to be drawn from the individual, for example, as described in detail here. The lumen can include two or more ports. For example, the lumen may include a first door (144) leading to the deposit chamber (126) located at the base of the housing and a second door (150) leading to a container (156) located on the housing cover. A piercing module (154) comprising one or more piercing elements (158) can be provided in the container (156).
[00187] The size of the recess (136) can be substantially larger than the size of the opening (140). For example, the size of the recess can be at least twice the size of the opening. In some embodiments, the size (for example, diameter) of the opening can vary from about 1.5 mm to about 6 mm, and the size (for example, diameter or width of the base) of the recess can vary from about 10 mm to about 60 mm. In some preferred embodiments, a diameter of the opening may be about 5 mm, and a diameter of the base of the recess may be about 25 mm.
[00188] In some embodiments, a ratio of the size (e.g., diameter) of the opening to the size (e.g., base diameter) of the recess can be about 1: 2, about 1: 3, about 1 : 4, about 1: 5, about 1: 6,
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51/134 about 1: 7, about 1: 8, about 1: 9, about 1:10, about 1:20, about 1:25, about 1:50, or about 1: 100, or any proportion between them. In some embodiments, a ratio of the size (e.g., diameter) of the opening to the size (e.g., diameter of the base) of the recess can be from about 1: 2 to about 1:10, or about 1: 5 to about 1:50, or about 1:10 to about 1: 100. The ratio mentioned above can also be less than about 1: 2, 1: 3, 1: 4, 1: 5, 1:10, 1:15, 1:20; 1:25; 1:30; 1:50 or 1: 100. In some embodiments, the ratio of the size (e.g., diameter) of the opening to the size (e.g., diameter of the base) of the recess may preferably be at least about 1: 5.
[00189] A surface area of the recess (136) can be substantially larger than an area of the opening (140). The surface area of the recess can be associated with the interior of the recess (excluding the opening), and can be measured in a 3D plane (for example, a concave hemisphere). The aperture area can be measured in a substantially 2D or almost 2D plane defined by the aperture. In some embodiments, the surface area of the recess may be at least five times, six times, seven times, eight times, nine times, ten times or five times the opening area. In some embodiments, the surface area of the recess can vary from about 75 mm ² to about 2900 mm ² , and the area of the opening can vary from about 1.5 mm ² to about 30 mm ² . In some embodiments, the opening area can preferably be about 0.2 cm ² , and the surface area of the recess can preferably be about 5.2 cm ² .
[00190] In some embodiments, an area of skin directly under the opening (140) can be at least 1.5 times smaller than a total area of skin positioned in the recess (136). In some embodiments, the area of the skin directly under the opening may preferably be at least 5 times smaller than the total area of the skin positioned in the recess.
[00191] With reference to FIG. IB, the flat part (132) of the base of the housing can be configured to be placed on the skin (for example, on the upper arm) of the individual. The flat part can be provided around the recess.
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An adhesive (not shown) can be placed on the flat part of the housing base. The adhesive can create an air tight seal on the skin that prevents ambient air from entering the recess after the device has been placed on the individual's skin. The seal can also prevent fluids (for example, blood, gas, etc.) from escaping out of the recess into the environment after the device has been placed on the subject's skin. An appropriate biocompatible adhesive material or gasket can be placed on the flat part at the base of the housing, in order to promote the adhesion of the device on the individual's skin to increase contact. Any suitable adhesive can be used. The adhesive can be a hydrogel, an acrylic, a polyurethane gel, a hydrocolloid or a silicone gel.
[00192] The adhesive can be a hydrogel. Optionally, in any of the embodiments described here, the hydrogel can comprise a synthetic polymer, a natural polymer, a derivative thereof, or a combination of these. Examples of synthetic polymers include, but are not limited to, poly (acrylic acid), poly (vinyl alcohol) (PVA), poly (vinyl pyrrolidone) (PVP), poly (ethylene glycol) (PEG) and polyacrylamide. Examples of natural polymers include, but are not limited to, alginate, cellulose, chitin, chitosan, dextran, hyaluronic acid, pectin, starch, xanthan gum, collagen, silk, keratin, elastin, resiline, gelatin and agar. The hydrogel can comprise a derivatized polyacrylamide polymer.
[00193] In some embodiments, the adhesive may be a 3-layer laminate comprising (1) hydrogel for application next to the skin), (2) Tyvek ™ and (3) a secondary adhesive to attach to the flat part of the base of the device housing.
[00194] In some embodiments, the adhesive can be pre-fixed to the flat part at the base of the device housing (100). The device may comprise a protective film or support covering the adhesive on the flat part. The protective film can be removed before using the device and placing the device on the individual's skin. In another embodiment, an adhesive in the form of a gel, a hydrogel, a paste, or a cream can be applied to the individual's skin or to the flat part on the
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53/134 base of the device housing, before placing the device on the individual's skin. The patch can then be placed in contact with the subject's skin for a predetermined period of time (for example, on the order of several seconds to several minutes) in order to form an adhesive layer between the skin and the device. The adhesive can be a pressure sensitive adhesive or a heat sensitive adhesive. In some embodiments, the adhesive may be hypoallergenic.
[00195] In some embodiments, the adhesive may be a peelable adhesive, and may have a shape and size corresponding to the flat part at the base of the device housing. In the example shown in FIG. IB, the flat part at the base of the housing can be in the shape of a ring, although any shape can be contemplated. Likewise, the peelable adhesive can be provided as a ring corresponding to the flat part at the base of the housing.
[00196] In some embodiments, a fillet (138) can be provided at an interface between the flat part and the recess. For example, the fillet (138) can extend continuously along a periphery of the recess joining the flat part of the base of the housing. The fillet can be configured with a radius or curvature that can help to increase the suction of the vacuum to the skin and reduce vacuum leakage. For example, the fillet of the recess may conform and substantially contact the individual's skin when the skin is positioned in the recess. In some embodiments, a thread (139) can be provided along the periphery of the opening, for example as shown in FIGs. IB and 3A. The use of fillets can also eliminate sharp edges and reduce unwanted cuts or injuries to the skin when the skin is positioned in the recess under vacuum pressure.
[00197] Optionally, in any of the embodiments described here, the recess can be coated or sprayed with copper, silver, titanium, or other metal, coating or any other antimicrobial material, antiviral material, surfactants or agents that are designed to reduce microorganisms illnesses
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54/134 viruses, cells, bacteria, or airborne or surface particles that get stuck on the surface and / or edges of the recess. Optionally, in any of the embodiments described here, one or more walls of the recess can be impregnated with an antimicrobial material. For example, the antimicrobial material can be formed integrally with the housing recess in order to assist in controlling the bacterial level present in or inside the recess.
B. Vacuum Chamber and Deposit Chamber [00198] The device may include a vacuum chamber (112) and a deposit chamber (126), for example, as shown in FIGs. 2A, 2C, 3A and 4B. The vacuum chamber and the deposit chamber can be provided in the housing (for example, integrated into the base of the housing). Optionally, the vacuum chamber and the deposit chamber can be operationally coupled to a housing provided separately. The vacuum chamber can be configured to be in fluid communication with the recess and the deposit chamber. The vacuum chamber and the deposit chamber can be part of the housing base. The vacuum chamber and the deposit chamber can be located in different sections (for example, compartments) of the base of the housing, and provided in various shapes or configurations. For example, in some embodiments, the vacuum chamber can be shaped like a horseshoe surrounding the deposit chamber, as shown in FIGs. 2A and 4B. The vacuum chamber and the deposit chamber can be separated by one or more walls (125). The walls can be substantially impervious to fluids (for example, gases and liquids) and can prevent leaks between chambers. The walls can be made of materials with very low permeability values. For example, polypropylene may have a permeability coefficient of 9x10 ¹¹ (cm ³ cm) / (sec.cm ² .cm.Hg) to oxygen, and 4.5x10 ^-11 (cm ³ cm) / (sec.cm ² .cm.Hg) to air. As an example, PETG may have a permeability coefficient of 1.5 x 10 ^-11 (cm ³ cm) / (sec.cm ^2. Cm.Hg) to oxygen and 7.5 x ^{10 12} (cm ³ cm) / (sec .cm ² .cm.Hg) to air. In some alternative cases, the vacuum chamber and the
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55/134 deposit chamber do not need to be separated, for example, by walls. For example, the vacuum chamber and the deposit chamber may be the same chamber in a device as packaged. The combined vacuum chamber and deposit chamber can be a monolithic chamber. A camera can have more than one function or purpose, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more functions or purposes. For example, in some cases, a vacuum chamber can also serve the function of a deposit chamber. Likewise, in some cases, a deposit chamber can also be used as a vacuum chamber.
[00199] The deposit chamber can be interchangeably called a cartridge chamber, since the deposit chamber can be configured to receive a cartridge assembly (180) inside it. Blood can be collected from the individual, and transported from the recess to the deposit chamber for collection and storage in a cartridge (182). In some cases, the device comprises more than one vacuum chamber, for example 2, 3, 4, 5, 6, 7, 8, 9, 10, or more vacuum chambers (each vacuum chamber can be connected to a different recess or the same recess), and / or more than one deposit chamber, for example 2, 3, 4, 5, 6, 7, 8, 9, 10 or more deposit chambers (each deposit chamber can be connected to the same vacuum chamber or to a different vacuum chamber). Any number of vacuum chambers and / or deposit chambers can be contemplated depending on the design and needs of the applications.
[00200] The base of the housing may include a cover (124) that covers and hermetically seals the vacuum chamber. The cover can serve as a vacuum chamber cover. The lid can also cover the deposit chamber or part of it. The vacuum chamber may be an evacuated chamber, and may be referred to interchangeably as such. With reference to FIG. 4B, the vacuum chamber may include a self-sealing septum (122) through which air can be drawn from the vacuum chamber. A vacuum state can be generated in the vacuum chamber, for example, by inserting a distal end of a syringe through the septum (122) and using the syringe to withdraw from the vacuum chamber.
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The distal end of the syringe can comprise a needle that is inserted through the septum into the vacuum chamber. The septum can be made of any suitable flexible or elastomeric material that does not allow air to pass. In some embodiments, the septum may be made of polyisoprene. The septum can be in a naturally sealed state and can revert to its sealed state when the needle is removed from the septum.
[00201] In some other embodiments, a mechanical device such as a vacuum pump can be used to empty the vacuum chamber (for example, before or after packaging). The mechanical device can include components such as pistons, motors, blowers, pressure regulators, and the like. In some cases, non-mechanical media, such as chemicals or other reagents, can be introduced into the vacuum chamber and can be subjected to reaction in order to reduce the pressure inside the vacuum chamber (for example, creating a vacuum state ).
[00202] The base of the housing may include a separation interface (120) that separates the vacuum chamber from the deposit chamber. The separation interface can be, for example, a sheet. In some embodiments, the separation interface may be a multilayered sheet laminate. The separation interface can include any materials or media that can serve as a fluid barrier between the vacuum chamber and the deposit chamber. The separation interface can be “opened” in order to allow fluid communication between the vacuum chamber and the deposit chamber. Other non-limiting examples of a separation interface include diaphragms, covers, seals, covers, membranes, valves, and the like. The separation interface can be connected to the base of the housing using any fixing means described here. The separation interface can include any suitable polymer or composite material that can be pierced by a sharp object. The separation interface can be impermeable or semi-permeable to gas or liquids. For example, materials suitable for use in the separation interface may include thin polymer films, polyethylene, latex, etc.
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57/134 [00203] The separation interface, for example, sheet, can assist in maintaining the vacuum pressure in the vacuum chamber, and the pressure difference between the vacuum chamber and the deposit chamber. The perforation of the separation interface, for example, sheet, can result in the pressure equalization between the vacuum chamber and the deposit chamber, and create a pressure differential (negative pressure) that (1) positions the skin in the recess and ( 2) additionally draws blood from the individual's skin after the skin has been penetrated. In some embodiments, a vacuum pressure of at least about -1 psig to -2 psig is provided, in order to position the surface, for example, of the skin in the recess and completely fill the recess. In some embodiments, the skin is positioned in the recess by the vacuum and completely fills the recess in less than 2 seconds, preferably less than 1 second. In some embodiments, the skin is positioned in the recess by the vacuum and completely fills the recess in no more than 5 seconds.
[00204] In some cases, the vacuum chamber and the deposit chamber do not need to be separated, that is, the vacuum chamber and the deposit chamber may be the same chamber, or may collectively constitute the same chamber. In these cases, the combined vacuum chamber / deposit chamber can be separated from an opening in the recess by a separation interface, for example, sheet. As an example, the separation interface can be provided at or proximal to the opening of the recess, and can be used to establish fluid communication between the recess and the combined vacuum chamber / deposit chamber.
[00205] As previously described, the recess of the device can be configured presenting a size and / or shape that allows a higher average flow rate, and an increased volume of blood to be accumulated and collected. The collection flow rate may be dependent on the shape and / or size of the recess. For example, the recess shown in FIG. 1B can assist in increasing the rate of blood flow collected from the individual.
[00206] The increased volume and flow rate of blood collection may depend on a starting or starting vacuum pressure from the vacuum chamber. THE
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58/134 starting or initial vacuum pressure may correspond to the vacuum chamber pressure after evacuation. In some embodiments, the initial vacuum pressure of the vacuum chamber can vary from about -4 psig to about -15 psig, preferably about -8 psig to about -12 psig. In some preferred embodiments, the initial vacuum pressure of the vacuum chamber can be about -12 psig. In some other embodiments, the initial vacuum pressure of the vacuum chamber may be less than -15 psig, for example -16 psig, -17 psig, -18 psig, -19 psig, -20 psig, -21 psig, -22 psig, -23 psig, -24 psig or less.
[00207] The vacuum chamber can have a V1 volume ranging from about 3 cm ³ to about 30 cm ³ . The deposit chamber can have a V2 volume ranging from about 1 cm ³ to about 20 cm ³ .
[00208] In some embodiments, the volume VI of the vacuum chamber is preferably about 10 cm ³ and the volume V2 of the deposit chamber is preferably about 6 cm ³ . The volumes of the vacuum chamber and the deposit chamber can be designed in such a way that the pressure in both chambers is equalized to a desired value when the separation interface, for example, sheet, which separates the two chambers is perforated. For example, the vacuum chamber can have an initial vacuum pressure of about -12 psig, and the ratio of VI to V2 can be configured such that the equalized pressure in both chambers is about -4 psig after the sheet has been perforated. Any V1: V2 ratio can be contemplated, for example, 1: 1, 1: 2, 1: 3 and so on.
[00209] In some embodiments, the increased volume of blood in the skin positioned in the recess is at least about 20 pL, 30 pL, 40 pL, 50 pL, 60 pL or 70 pL before the skin penetrates. Higher flow rates and larger blood sample collection volumes can be achieved in part due to the increased volume of blood in the skin positioned in the recess, increased capillary pressure and with the aid of vacuum pressure. In some embodiments, the device is able to draw blood from the penetrated skin and collect blood at a flow rate of at least about 30 pL / min. In some achievements, the
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59/134 device may be able to draw blood from penetrated skin and collect blood at a flow rate of more than 600 pL / min. Generally, the device is able to draw blood from the penetrated skin and collect blood at an average flow rate of at least about 100 pL / min, 125 pL / min, 150 pL / min, or any values or ranges between these. In some embodiments, the device can sustain the average flow rate (s) mentioned above at least until a substantial amount of blood has been collected (for example, ranging from about 150 pL to about 1000 pL of blood, or in some cases more than 1 ml of blood). In some embodiments, the device is able to collect about 250 μL of fluid sample from the individual in less than 1 min 45 seconds. In some cases, the device is able to collect at least 175 μl to 300 μl of the individual's fluid sample in less than 2 mins. In some cases, the device is able to collect at least 200 pL of the individual's fluid sample in less than 4 minutes.
[00210] In some other embodiments, the device (100) can be configured to collect smaller amounts of blood (for example, less than 150 uL, 140 uL, 130 uL, 120 uL, 110 uL, 100 uL, 90 uL, 80 uL, 70 uL, 60 uL, 50 uL, 40 uL, 30 uL or 25 uL) of an individual's blood within a time window starting from the moment of incision or penetration of a part of the individual's skin. The time window can be less than 5 minutes, preferably less than 3 minutes. In some embodiments, the time window can be under 2 minutes. In some embodiments, the time window can be under one minute.
[00211] In some embodiments, (1) the size and / or shape of the recess and / or (2) the vacuum pressure can be configured to obtain a minimum capillary pressure in the skin positioned in the recess. Similarly, (1) the size and / or shape of the recess and / or (2) the vacuum pressure can be configured to obtain minimal stress on the skin positioned in the recess. As an example, the skin tension can be about 0.8 Ibs / force and a vacuum pressure of about -1 psig.
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60/134 [00212] An area of skin under vacuum when the device is applied to the skin can be about 100 to about 1000 mm ² , or about 100, 200, 300, 400, 500, 600, 700, 800 or 900 mm ² . An area of skin under the opening can be about 0.1 mm ² to about 20 mm ² , or about 2, 4, 6, 8, 10, 12, 14, 16, 18, or 20 mm ² . A skin area under vacuum when the device is applied to the skin can be at least 100, 200, 300, 400, 500, 600, 700, 800 or 900 mm ² , or less than 100, 200, 300, 400, 500 , 600, 700, 800 or 900 mm ² , or from about 100 to about 900 mm ² , or from about 200 to 800 mm ² .
[00213] In some embodiments, an area of skin under vacuum is an area of skin encompassed by the area of the concave cavity at the base of the device housing. In some embodiments, a skin area under vacuum is a skin area under the opening. In some embodiments, an area of skin under the opening is at least 5 times smaller than an area of skin under vacuum when the device is applied to the skin. In some embodiments, an area of skin under the opening is about 5, about 10, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about about 90, about 100 teams, about 200, about 300, about 400, about 500, about 600, about 700, about 800, about 900, about 1000, about 2000, about 3000, about 4000, about 5000, about 6000, about 7000, about 8000, about 9000, or about 10,000 times smaller than an area of skin under a vacuum. An area of skin under the opening can be less than 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000 or 10000 times smaller than an area of skin under vacuum.
C. Piercing Module [00214] The device may include a piercing module (154) to penetrate the individual's skin when the skin is positioned in the recess under vacuum pressure. In some alternative cases, the device does not need to comprise a drill module. The drilling module (154) can be provided in a container (156). The container can be located within the housing cover (152). The container can be provided as a separate component
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61/134 which is coupled to the housing cover (see, for example, FIG. 26). The piercing module can include one or more piercing elements (158) supported by a support (160), for example, as shown in FIGs. 27A and 27B. The piercing elements can include lancets, spears, blades, needles, microneedles, surgical knives, sharp objects, rods, and the like. Any number of perforating elements (for example, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more perforating elements) can be contemplated. In some embodiments, the piercing elements may preferably comprise two lancets.
[00215] The piercing elements may comprise tempered steel, high carbon steel or stainless steel. Examples of stainless steel include, but are not limited to, stainless steel 304, stainless steel 316, stainless steel 420 and stainless steel 440. In some embodiments, the piercing elements can be coated with a surface finish. The surface finish can increase lubricity when cutting the skin. The surface finish can also increase the precision or penetrability of the piercing elements. In some embodiments, the surface finish may be a zirconium nitride coating or a titanium nitride coating.
[00216] The piercing elements can be made of a biocompatible plastic or a biocompatible metal. Biocompatible plastic can include a number of suitable types of polymeric materials including, but not limited to, thermostable materials, elastomers or other polymeric materials. In addition, suitable biocompatible metals may include, for example, stainless steel, titanium etc. Additionally or optionally, the piercing elements can be formed from various composite materials. Perforating elements can be manufactured using a number of suitable production processes. For example, piercing elements can be manufactured using known metal processing techniques, such as casting or forging, or, for polymeric materials, any suitable polymer processing system can be used, including,
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62/134 for example, injection molding. A piercing element may have a sharp, pointed end that can be used to pierce a user's skin in order to collect blood.
[00217] The drilling module can additionally comprise one or more driving elements (for example, spring elements) to drive the support and move the piercing elements. Other non-limiting examples of drive elements may include magnets, electromagnets, pneumatic drives, hydraulic drives, motors (eg brushless motors, direct current brush (DC) motors, rotary motors, servo motors, direct drive rotary motors , DC torque motors, solenoid linear stepper motors, ultrasonic motors, gear motors, speed reduction motors or piggyback motor combinations), gears, cams, linear drives, belts, pulleys, conveyors, and the like . Non-limiting examples of spring elements may include a variety of suitable spring types, for example, nested compression springs, buckling columns, conical springs, variable pitch springs, snap-rings, double torsion springs, wire, limited displacement extension springs, braided wire springs, etc. In addition, the drive elements (for example, spring elements) can be made from a number of metals, plastics or composite materials.
[00218] In some embodiments, the spring elements may include an implantation spring (162) positioned to extend the one or more perforating elements through the opening of the recess, in order to penetrate the individual's skin. An example of an implantation spring is shown in FIG. 28A. In some embodiments, the implantation spring can be configured to move and cause the piercing elements to penetrate the skin at speeds ranging from about 0.5 m / s to about 1.5 m / s, preferably about 1 m / s s, and with a force ranging from about 1.3 N to about 18 N. The implantation spring can be configured to make the one or more elements
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63/134 perforators penetrate the skin at depths ranging from about 0.5 mm to about 3 mm.
[00219] The spring elements may additionally include a retraction spring (164) positioned to retract the one or more piercing elements through the opening back to the device, after the subject's skin has been penetrated. An example of a retraction spring is shown in FIG. 28B. The retraction spring can be configured to retract the perforating elements of the individual's skin at a speed of about 0.2 m / s. A spring force of the retraction spring can be less than a spring rate of the implantation spring. In some embodiments, the implantation spring may have a spring rate of about 2625 N / m, and the retraction spring may have a spring force of about 175 N / m.
[00220] A piercing element can have a length of about 1.0 mm to about 40.0 mm, or about 1.0 mm, about 1.5 mm, about 2.0 mm, about 4, 0 mm, about 6.0 mm, about 8.0 mm, about 10.0 mm, about 15.0 mm, about 20.0 mm, about 25.0 mm, about 30.0 mm, about 35.0 mm, about 40.0 mm; the width of about 0.01 mm to about 3.0 mm, or about 0.01 mm, about 0.05 mm, about 0.1 mm, about 0.5 mm, about 1.0 mm , about 1.5 mm, about 2.0 mm, about 2.5 mm, about 3.0 mm. The length of a piercing element can be measured along a longitudinal direction, for example, as shown by length 1 in FIG. 27A.
[00221] Each of the one or more piercing elements can be configured to pierce the individual's skin to a depth of about 1.0 mm to about 25.0 mm, or about 1.0 mm, 1.5 mm, 2.0 mm, 3.0 mm, 4.0 mm, 5.0 mm, about 6.0 mm, about 7.0 mm, about 8.0 mm, about 9.0 mm, about 10 , 0 mm, about 15.0 mm, about 20.0 mm or about 25 mm. In some embodiments, the penetration depth of the one or more piercing elements may preferably be about 2 mm into the subject's skin.
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64/134 [00222] In some embodiments, the piercing elements may include lancets, and a length l of the lancet may preferably be less than about 13 mm. This length can be relatively shorter than the lancets currently available commercially and the shorter length of the lancets in the embodiments described here can assist in reducing the form factor of the device as well as the type of spring and spring forces to drive these lancets. For example, a shorter spring with a lower spring rate is needed to drive a shorter lancet, compared to longer lancets that tend to require longer springs and higher spring rates. Shorter springs and lancets can assist in reducing the size of the drill module, which leads to a corresponding reduction in the size of the housing cover and the overall size of the device.
[00223] In some embodiments, two or more piercing elements can be supported by a support in a random configuration. For example, two or more perforating elements may have random orientations in relation to each other. The two or more piercing elements may comprise beveled edges that are randomly oriented with respect to each other. The beveled edges of the two or more piercing elements can be non-symmetrical to each other. For example, the beveled edges of the two or more piercing elements can be at an acute or oblique angle to each other. Likewise, the two or more perforating elements in the above configuration can be configured to generate cuts in the skin that extend in different directions along the skin and that are not parallel to each other.
[00224] In some alternative embodiments, two or more piercing elements can be supported by the support in a predefined configuration. The two or more perforating elements may have predefined orientations in relation to each other. For example, the two or more piercing elements may comprise beveled edges that are oriented relative to each other in a predefined manner. The beveled edges of the two or more piercing elements can be symmetrical to each other.
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65/134 [00225] In some embodiments, the piercing elements may include two or more lancets. Lancets can have the same chamfer angle or different chamfer angles. An example of a lancet and a chamfer angle is shown in FIG. 27A. The chamfer angle (s) can vary from about 10 degrees to about 60 degrees. In some embodiments, the bevel angle of the lancets may preferably be about 42 degrees. The two or more lancets may have the same chamfer length. Alternatively, the two or more lancets may have different chamfer lengths. The bevel length of a lancet, as described here, can refer to a length of the sharp or angled beveled edge of the lancet, as shown by l 'in FIG. 27A. In some embodiments, the bevel length of a lancet can vary from about 1.6 mm to about 2.2 mm.
[00226] A method for penetrating an individual's skin using the device (100) can be provided as follows. The method may include (1) placing the device on the subject's skin, (2) positioning the skin in the recess of the device by using a vacuum, (3) activating a trigger element (for example, a spring implantation) and the implantation of one or more perforating elements through the opening in the device; (4) penetration of the individual's skin using one or more perforating elements; and (5) the use of another driving element (for example, a retraction spring) to retract the one or more piercing elements back into the device.
D. Vacuum Activator and Drilling Activator [00227] The device may include a vacuum activator (114) configured to activate the vacuum chamber (evacuated), which generates a vacuum pressure that can position the skin in the recess and subsequently facilitate blood collection from penetrated skin. The device may also include a drilling activator (166) configured to activate the implantation spring, to drive the piercing elements. The vacuum activator can be separated from the drilling activator.
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For example, the vacuum activator and the drilling activator can be two separate discrete components of the device. In some alternative embodiments (not shown), the vacuum activator and the drilling activator can be integrated together as a single component that can be used to simultaneously or sequentially activate the vacuum and the piercing elements.
[00228] The vacuum activator can include a first inlet interface, and the drilling activator can include a second inlet interface. The first and second input interfaces can be located in different parts of the housing. Examples of suitable input interfaces may include buttons, knobs, finger triggers, dials, touch screens, keyboards, mice, or joysticks. In some embodiments, at least one between the first input interface or the second input interface may comprise a button. For example, the vacuum activator can include a button (115) located at the base of the housing (110) and the drilling activator can include a button (167) located on the cover of the housing (152). In some embodiments, the vacuum activator and the drilling activator can be located on the same side of the housing and the buttons (115/167) can be ergonomically accessible by the individual when the device is mounted on an individual's arm. The buttons can have different or different shapes and / or sizes and can be ergonomically located for easy use (for example, easy identification by the user and well placed locations for simple activation).
[00229] In some alternative embodiments (not shown), at least one between the first or the second input interfaces can be remote from the device housing. For example, one or both and second input interfaces can be located on a user terminal (for example, a mobile device or remote control) that is connected to the device (100) via one or more wired communication channels or wireless.
[00230] Examples of wireless communication channels may include
Bluetooth®, WiFi, Near Field Communication
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Communication ”- NFC), 3G and / or 4G networks. The signals for activating the vacuum and / or the piercing elements can be transmitted remotely from the user terminal to the device (100) on one or more communication channels.
[00231] In some embodiments, the vacuum activator can be activated first, followed by the drilling activator. In other words, the vacuum pressure can be activated before activating the piercing elements. In certain embodiments, the drilling activator can be activated only after the vacuum activator and the vacuum have been activated. For example, the drilling activator may initially be in a locked state and unable to activate the one or more piercing elements before activating the vacuum. The drilling activator can be unlocked only after the vacuum activator has been activated. The above effect can be achieved by providing a locking mechanism that couples the drilling activator to the vacuum activator. The locking mechanism can be configured in such a way that the drilling activator is initially in the locked state. The vacuum activator can act as a key to unlock the drilling activator, and the drilling activator can be simultaneously unlocked when the vacuum activator is activated. With reference to FIGs. 7A and 7B, the locking mechanism can include a locking pin (169) coupled to the button (115) of the vacuum activator. Before using the device for sample collection, the pin locking pin can be engaged in a slot or hole (174) located on the button (167) of the drilling activator, which prevents the button (167) from being pressed by a user. Likewise, the drill activator is unable to be activated when the button (167) is in the locked position. When the user presses the button (115), the locking pin (169) is retracted in the direction shown in FIG. 7B and is disengaged from the slot (174), thus unlocking the button (167). Pressing the button (115) also pierces the sheet (120) separating the vacuum chamber and the deposit chamber which causes the vacuum to be activated. Specifically, the chambers are equalized to a negative pressure that positions the individual's skin in the recess. O
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68/134 the user can then press down the unlocked button (167) in order to activate the perforating elements (158) to penetrate the skin of the individual who is positioned in the recess.
[00232] In some embodiments, the piercing activator can be configured to activate the one or more piercing elements after the skin is positioned in the recess. The perforation activator can be configured to activate the one or more perforating elements after the skin is positioned in the recess by the vacuum for a predetermined period of time. The predetermined length of time can vary, for example, from about 1 second to about 60 seconds.
[00233] The vacuum activator can be configured to activate the vacuum by perforating the sheet, which establishes fluid communication between the vacuum chamber, the deposit chamber and the recess, and introduces negative pressure in the recess and in the deposit chamber .
[00234] In some embodiments (not shown), the leaf can be replaced by a valve, and the vacuum activator can be configured to open the valve in order to establish fluid communication. A valve can be a flow control valve having an open and closed binary position. Alternatively, a flow control valve can be a proportional valve that can control the flow rate of the air flowing between the vacuum chamber and the deposit chamber. For example, a proportional valve can have a wide open configuration that can allow a higher flow rate than a partially open configuration that can allow a lower flow rate. Optionally, regulating, throttle, gauge or needle valves can be used. Return or non-return valves can be used. A valve can have any number of ports. For example, a two-port valve can be used. Alternatively, a three-port, four-port or other type of valve can be used in alternative configurations. Any description of valves here can apply to any other type of flow control mechanism. Flow control mechanisms can be any type of control mechanism
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69/134 binary flow control (for example, containing only one open position and one closed position) or variable flow control mechanism (for example, which can include degrees of open and closed positions).
[00235] In some embodiments, the vacuum activator can be located in the housing in such a way that the button (115) is configured to be pressed in a first direction when the device is mounted on an individual's arm. The drilling activator can be located in the housing such that the button (167) is configured to be pressed in a second direction when the device is mounted on the subject's arm. In some embodiments, the first direction and the second direction can be substantially the same. The first direction and the second direction can be substantially parallel to each other. In some embodiments, the first direction and the second direction can be substantially different, for example, orthogonal or oblique to each other.
[00236] In some embodiments, at least one between the first direction or the second direction does not extend towards the individual's skin. For example, the second direction may not extend towards the individual's skin. At least one between the first direction or the second direction can extend substantially parallel to the individual's skin. In some embodiments, the first direction and the second direction can both extend substantially parallel to the individual's skin. At least one between the first direction or the second direction can extend in one direction of the gravitational force. In some embodiments, the first direction and the second direction can both extend in the direction of the gravitational force.
[00237] It should be noted that by pressing the button (167) of the perforation activator (which activates the perforating elements) in a direction opposite to the skin, for example, downwards as opposed to against the skin, it can be advantageous in reducing the perception of fear and pain associated with penetrating the skin. By locating the drill trigger and the button (167) in the housing in the settings as shown, the overall user experience with the device can be improved.
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70/134 [00238] In some alternative embodiments (not shown), the vacuum activator can be configured to generate one or more visual, audio, tactile and / or message signals to indicate the state of the vacuum for a user. The signals may indicate to the user, for example, that (1) the vacuum has been activated, (2) the pressure (s) inside the different chamber (s), (3) the vacuum after internal pressure equalization, (4) that the drilling activator is close to being ready for activation, and the like. Visual signals can be generated using visible markers that are visible to the naked eye. A visible marker can include an image, shape, symbol, letter, number, barcode (for example, ID, 2D, or 3D barcode), quick response code (QR) or any other type of visually distinguishable feature . A visible marker can include an array or sequence of lights that can be distinguished from one another. For example, lights of various configurations with flash on or off. Any light source can be used, including, but not limited to, light emitting diodes (LEDs), OLEDs, lasers, plasma, or any other type of light source. The visible markers can be provided in black and white or in different colors. The visible markers can be substantially flat, raised, recessed or have any texture. In some cases, visible markers can emit heat or other radiation in the IR spectrum, UV radiation, radiation along the electromagnetic spectrum.
[00239] Audio signals may include vibrations or sounds of different frequencies, steps, harmonics, tracks, or patterns of sounds that can be detected by the user. For example, sounds can include words or musical tones. Vibrations / sounds can be discernible by the human ear. Vibrations / sounds can be used to indicate the state of the vacuum. For example, a first vibration / sound can be generated when the vacuum is properly activated, and a second vibration / sound different from the first can be generated if the vacuum is improperly activated or below a minimum internal pressure differential.
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71/134 [00240] In some alternative embodiments (not shown), the drill trigger can be configured to generate one or more visual, audio, tactile and / or message signals for a user. Such signals can be useful, for example, in preparing the user's mental state for imminent skin penetration by one or more perforating elements. Such signs can be used to distract the user before, during and after skin cuts are made. For example, lights and / or music emitted by the device can be used to attract the user's attention, which potentially helps in reducing the level of pain (or perception of pain) during and after the cuts are made.
[00241] Optionally, in any of the realizations described here, the activation of the vacuum can be semi-automatic or completely automatic. In some embodiments, the device does not require manual vacuum activation. For example, the device can be configured to automatically apply the vacuum when it feels or detects that the device has been placed on a surface (for example, on an individual's skin), or that the recess of the device is properly placed on the surface. Optionally, in any of the embodiments described here, the activation of the piercing elements can be semi-automatic or completely automatic. For example, the piercing elements can be activated automatically to penetrate the surface (for example, the individual's skin) when feeling or detecting that the surface is positioned in the recess of the device and / or that the surface is close to the opening (for example, (140)) from the recess. Sensation or detection (for vacuum activation and / or perforation activation) can be enabled using any variety of number of sensors. The sensors can be included with the device (for example, inside the device) or remote to the device. Non-limiting examples of sensors that can be used with any of the embodiments here include proximity sensors, tactile sensors, acoustic sensors, motion sensors, pressure sensors, interferometric sensors, inertial sensors, thermal sensors, image sensors, and the like. In some cases, if the activation of the vacuum and / or the activation of the
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72/134 drilling is configured to be semi-automatic or fully automatic, the buttons for the drilling activator and / or drilling activator can be optionally included (or omitted) in the device.
E. Cartridge Assembly [00242] As previously described, the deposit chamber of the device can also function as a cartridge chamber, and these two terms can be used interchangeably here. The cartridge chamber can be configured to receive a cartridge assembly. The cartridge assembly may include a cartridge configured to support one or more arrays for storing a sample of fluid (e.g., blood), and a cartridge holder. The cartridge holder can be releasably attached to the cartridge by using, for example, spring clips. The cartridge assembly can be configured to be releasably attached to the device (100) used to collect blood from the individual. The cartridge holder may include a cartridge tab that is configured to be releasably attached to a distal end of the cartridge chamber. The cartridge tab can be designed in such a way that the individual or a user is able to (1) support the cartridge assembly by holding the cartridge tab, (2) attaching the cartridge assembly to the device by pushing the cartridge tab and / or (3) detach the cartridge assembly from the device by pulling on the cartridge tab.
[00243] With reference to FIG. 3A, the cartridge may include a cartridge port (184) that is configured to be releasably coupled to an outlet port (148) in the deposit chamber (126). Fluid communication can be established between a channel (146) of the device and a channel (185) of the cartridge when the ports (148) and (184) are coupled together. As shown in FIG. 3A, the channel (146) can extend towards the door (144) which is adjacent to the opening (140) of the recess (136). Blood can be drawn from the individual's penetrated skin, and transported through channels (146) and (185) to the cartridge with the aid of vacuum, pressure differentials and gravitational force.
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73/134 [00244] The cartridge chamber may include guides for the cartridge (130) to guide and hold the cartridge inside the cartridge chamber. The cartridge assembly can be releasably attached to the cartridge chamber by means of a quick release mechanism. A quick-release coupling mechanism can allow a user to mechanically and quickly engage (attach) and / or disengage (remove) the cartridge assembly from the cartridge chamber with a short sequence of simple movements (for example, rotating or rotating movements). twisting; sliding movements; pressing a button, switch or plunger etc.). For example, a quick release coupling mechanism may require no more than one, two, three or four movements of the user in order to perform a coupling and / or uncoupling action. In some cases, a quick release coupling mechanism can be attached and / or uncoupled manually by a user without the use of tools. In some embodiments, the quick release coupling mechanism may include a luer-type adjustment that mechanically engages with the cartridge when the cartridge assembly is inserted into the cartridge chamber.
[00245] The cartridge assembly can be attached to the cartridge chamber prior to the individual's blood collection, and detached from the cartridge chamber after the individual's blood has been collected into the cartridge. The cartridge may include one or more matrices for collection, storage and / or stabilization of the collected blood sample. The matrices can be provided in the form of tape. A tape as used here can refer to a solid matrix that is sized to maximize the blood collection volume while still being able to fit into commonly used containers (for example, a 3 ml BD vacuum container, deep well plate or 2 ml Eppendorf tube). A matrix as used herein can be referred to interchangeably as a matrix ribbon, a ribbon, a solid matrix, a solid matrix ribbon, and the like. A solid matrix can be configured to measure, collect and stabilize fixed volumes of blood or plasma (for example, above 25 uL, above 50 uL, above 75 uL, above 100 uL, above 125 uL, above 150
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74/134 µL, above 175 µL, above 200 µL, or above 500 µL of blood or plasma). The cartridge assembly can be configured to support any number of arrays (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more tapes) and in various configurations.
[00246] The matrices may also enable transport tapes / lateral blood flow. Non-limiting examples of matrices may include tapes of absorbent paper or a membrane polymer such as nitrocellulose, polyvinylidene fluoride, nylon, Fusion 5 ™, or polyethersulfone. In some embodiments, the matrices may comprise cellulose-based paper (for example, Whatman ™ 903 or 226 paper), paper treated with chemical products or reagents for sample stabilization, or one or more components of the sample (for example, matrix of stabilization matrix or protein stabilization matrix). In some embodiments, the matrix comprises a cellulose filter paper. Any suitable commercially available filter paper can be used. Examples of commercially available filter paper include, but are not limited to, Whatman® filter paper, such as sample collection cards 903 and rapid transit analysis card (FTA®). In some embodiments, the matrix may comprise a nitrocellulose filter paper. In some embodiments, the matrix does not comprise fiberglass filter paper.
[00247] The collection of the fluid sample can be aided by the natural passage or capillary action associated with the matrix, which can increase and accelerate the absorption or collection of the fluid sample in the matrix. For a matrix showing a surface area within the range of 100-300 square millimeters, a standardized amount of blood saturating the matrix can be within a range of about 50-100 µL. In some embodiments, the amount of blood absorbed by each matrix is about 30 to about 100 pL. In some embodiments, the amount of blood absorbed by each matrix is about 67 to about 82 pL. In some embodiments, the amount of blood absorbed by each matrix is 30 pL. In some embodiments, the amount of blood absorbed by each matrix is about 45 pL. In some achievements, the
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75/134 amount of blood absorbed by each matrix is about 60 pL. In some embodiments, the amount of blood absorbed by each matrix is about 75 pL. In some embodiments, the amount of blood absorbed by each matrix is about 100 pL. In some cases, the dies may be composed of a material comprising a plurality of capillary beds in such a way that, when in contact with a fluid sample, the fluid sample is transported laterally by all the dies. The fluid sample can flow along the flow path from a proximal end to a distal end of the dies, for example, by passage or capillarity.
[00248] In some embodiments, two or more matrices are arranged in a configuration inside the cartridge that allows blood to pass between and flow along the matrices. The two or more arrays can be arranged substantially parallel to each other. The two or more arrays can be separated by spacers. Spacers can be made of an appropriate biocompatible material. Two or more spacers can be placed between two matrices in order to form a channel through which blood can flow through capillary and passage action. In the example of FIGs. 3A and 29, the two arrays (186) can be separated by a pair of spacers (187). Spacers can be positioned at opposite lengths of the dies so as to form a channel (189) through which blood can flow through capillary and passive action. In some embodiments, the two or more dies can be separated by a space of about 0.5 mm (that is, the spacers can have a thickness of about 0.5 mm). Any size of space can be contemplated. Spacers between matrices can be adjustable and removable, depending on other relevant aspects (for example, the needs and applications of the sample being collected, analyte stability, absorption rate requirements, etc.). Spacers can comprise a range of widths and coverings. Typical widths include widths ranging from millimeters to centimeters (for example, above 2 mm, above 4 mm, above 6 mm, above 8 mm, above 10 mm, above 0.2 cm, above
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76/134 of 0.4 cm etc.). In additional embodiments, the spacers may be coated with hydrophobic coating materials, hydrophilic coating, antimicrobial coatings, coatings that bind to one or more components in a sample, coatings for binding or inhibiting enzymes that may degrade or otherwise impact on the quality of one or more analytes in the sample.
[00249] In some embodiments, at least one of the matrices is capable of collecting at least 60 uL of blood. In some cases, each of the two or more matrices is capable of collecting at least 60 uL of blood. The volume of blood collected may depend on the number of matrices in the cartridge. For example, the provision of two matrices each capable of holding 60 μl can yield a total blood sample volume of about 120 μl.
[00250] With reference to FIGs. 3A and 29, the cartridge assembly (180) can include one or more absorbent pads (188) to hold excess fluid sample (e.g., excess blood flow beyond the dies). Absorbent pads can serve as a pass-through worm that can be used to absorb excess sample, and standardize or measure the volume of blood deposited in the saturated matrices. The absorbent pads can be placed at a distal end of the channel (189) opposite the cartridge port (184) and can be placed in contact with extreme parts of the dies (186). The absorbent pads can be supported or held in place by the cartridge holder (190). For example, absorbent pads can be placed in a slot in the cartridge holder. Absorbent pads can be configured to absorb excess sample. Each absorbent pad may be able to hold at least about 10 µL of excess fluid sample. In some cases, each absorbent pad may be able to hold at least about 20 uL, 30 uL, 40 uL, 50 uL, 60 uL, 70 uL, 80 uL, 90 uL, 100 uL, or more than 100 uL excess fluid sample. Absorbent pads can be used to allow controlled matrix measurement. Absorbent pads and their ability to contain blood
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77/134 in addition to the matrix saturation volume may allow consistent blood volumes in the matrices, regardless of the variable volumes entering the device and cartridge. The absorbent pads can be configured (for example, to have the composition adjusted) in such a way that the absorbent pads can be used as a means of controlling the volume of the sample absorbed in the matrices.
[00251] The cartridge assembly may comprise high measurement capacity that can be advantageous for collecting a predefined volume of blood on the matrix strips for each individual, regardless of the volumes of blood flow entering the cartridge for different individuals. Variations in incoming blood volume can occur since capillary pressures and blood flow can often vary from individual to individual (for example, due to age, gender, health, etc.). The design of the cartridge assembly can ensure that the matrix strips consistently contain a target blood volume independent of the volume of blood entering the cartridge (within or even a predefined range). In the example of FIG. 29, the two matrix tapes (for example, (186)) are in contact with one or more absorbent pads (for example, (188)) at opposite ends of the inlet port (for example, (184)) of the cartridge. As blood enters the cartridge through the port (184) during withdrawal, the matrix tapes are gradually saturated and during this time, the volume contained in the tapes may increase (for example, linearly) with the volume of blood entering the cartridge. cartridge. In some embodiments, once the matrix tapes are saturated at ~ 75 µL, excess blood can pass into the absorbent pad (s). By using absorbent pads to absorb excess blood, the blood contained in the two matrix strips can be maintained at approximately 75 μL in each strand, even if (or according to) the inflow volume of the blood flow to the cartridge increases plus 150 uL. The volume of blood in the matrix tapes can be measured / maintained unless or until the absorbent pads saturate with blood. In some embodiments, any volume of blood entering between -150 uL and 300
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78/134 μl for the cartridge may also result in the same volume (~ 75 μl) of blood contained in each of the two matrix tapes, with the aid of the absorbent pad (s). In some embodiments, a range of blood volume collected on the matrix tapes can be increased or reduced, for example, by adding one or more additional absorbent pads, increasing or reducing the size / saturation level of the tape etc.
[00252] The collection of blood in the matrix tapes can occur in phases. For example, during an initial phase, while the volume of blood entering the cartridge is between 0-150 μL, the two strips are filled, but are not yet saturated and the blood volume in each of the two strands gradually increases from 0-75 µL. During a subsequent phase, as the volume of blood entering the cartridge increases beyond 150 µL (for example, 150 µL 300 µL), the tapes are saturated with a constant blood volume of ~ 75 µL per tape, with excess flow of blood going to the absorbent pads. The passive measurement mechanism described above can be advantageous in maintaining a predefined blood volume (for example, 75 µl per strip) with varying inlet blood volumes within a target range.
[00253] It should be noted that the cartridge can include any number of matrix tapes. Matrix tapes can have the same saturation volumes or have different saturation volumes. The cartridge can also include any number of absorbent pads. The number of absorbent pads may or may not be the same as the number of matrix tapes. The saturation volumes for the absorbent pads can be the same or different. The cartridge can be designed in such a way that the matrix tapes and absorbent pads have self-measuring capability as described above. For example, the volumes collected from samples on the matrix tapes may increase until the matrix tapes reach their saturation volumes. After the matrix tapes are saturated, any excess fluid is collected in the absorbent pads. Likewise, well-defined controlled volumes of the sample can be collected on the matrix tapes, even though the volume of
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79/134 input to the cartridge can and often exceeds the total saturation volumes of the matrix tapes.
[00254] The use of matrices with absorbent pads can facilitate accurate and accurate sample collection. Two or more matrices can be stacked or arranged in order to facilitate collection, distribution, precision and reproduction of blood sample volumes or analytes per surface area of each matrix. In some embodiments, the matrices may have different compositions or purposes. For example, a first matrix (s) can be used to separate cells from a cell-free component and collect the cell-free component into a matrix, and a second matrix (s) ) can be used to collect non-separated crude sample. In some embodiments, absorbent pads can be used as or incorporated into an indicator or be visible through a viewing window (from a flow meter) to inform a user that the collection procedure is complete.
[00255] In some embodiments, a method may be provided for collecting a sample of fluid (e.g., blood) from an individual. The method may include: (1) releasably coupling the cartridge assembly to a device (for example, device (100)); (2) placing the device adjacent to the individual's skin; (3) activation of the vacuum in the pre-evacuated vacuum chamber to position the skin in a recess of the housing; (4) the use of one or more piercing elements of the device to penetrate the skin; (5) maintaining the device adjacent to the skin for an amount of time sufficient to withdraw the fluid sample for the device and collect the fluid sample for the cartridge; and (6) uncoupling the cartridge from the device after a certain amount of fluid sample has been collected in the cartridge.
[00256] In some embodiments, one or more of the matrices can be designed and manufactured on a substrate. The substrate can be rigid or flexible.
Examples of suitable substrates may include silicon, glass, printed circuit cards, polyurethane, polycarbonate, polyamide, polyimide, and the like.
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80/134 [00257] The cartridges described here generally show fluid samples stored in solid matrices. However, this should not be taken to limit the devices described here. For example, devices may include cartridges or means for sample collection, treatment, stabilization and storage in both a liquid and a solid state. In some embodiments (not shown), the cartridge may include a vessel for storing liquid sample. The vessel can be used in conjunction with one or more matrices. Alternatively, the vessel can be used in place of the matrices. Any number of vessels for storing liquid samples can be contemplated.
[00258] In some embodiments, the device described here may have multiple vacuum chambers (for example, 2, 3, 4, 5 or more vacuum chambers) and multiple drilling modules (for example, 2, 3, 4, 5 or more drilling modules). The device can be reusable and can be used to collect multiple samples in multiple cartridges. For example, a first vacuum chamber and a first drilling module can be activated to fill a first cartridge, a second vacuum chamber and a second drilling module can be activated to fill a second cartridge, a third vacuum chamber and a third punch module can be activated to fill a third cartridge, and so on. In some embodiments, the same vacuum chamber and the same drilling module can be used to fill a plurality of different cartridges, within the same sample procedure or in multiple procedures performed at different points in time.
F. Flow Meter [00259] In some embodiments, the device may include a flow meter (170) in the housing. The flow meter can be interchangeably referred to here as a measurement window (or measurement windows). The flow meter can enable an individual or a user to monitor progress of fluid sample collection (eg, blood sample collection) in time
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81/134 actual as the fluid sample is collected into the cartridge. For example, the individual or user can rely on the flow meter to determine if the fluid sample collection is complete or close to being complete. In some embodiments, the flow meter may be provided at the base of the housing (110). For example, the flow meter may be a part of, or integrated with, the lid (124) of the housing base. The flow meter can be located near the deposit chamber (126) (or the cartridge chamber). The flow meter can be located directly above the deposit chamber (or the cartridge chamber). The flow meter can be substantially aligned with the cartridge (182) when the cartridge assembly is inserted into the cartridge chamber, for example, as shown in FIGs. 3B, 4B, 20A and 20B. [00260] In some embodiments, the flow meter (170) may include a plurality of windows (172) arranged in parallel to a longitudinal axis of the cartridge chamber. The plurality of windows can include three, four, five or more windows. In the example of FIGs. 17B, 18B, and 19B, the flow meter (170) may include the windows (172-1, 172-2, 172-3, 172-4, 172-5). The windows can line up with the cartridge arrays (186) when the cartridge assembly is inserted into the cartridge chamber. The windows can be made of an optically transparent material that allows the individual or user to view the underlying matrices in the cartridge. The fluid sample that is collected in the matrices can be viewed through the windows. The fluid sample and the cartridge dies may have different colors, preferably highly contrasting colors in order to allow easy visualization of the flow through the dies. The color of the fluid sample (for example, red for blood) can sequentially fill each window as the fluid sample is being collected from the matrices in the cartridge. Each window can be indicative of a known amount of fluid sample that is collected. For example, in FIG. 17B, window 172-1 may have a visible color that indicates to the user that the matrices are about 20% full. In FIG. 18B, the windows (172-1, 172-2, 172-3, 172-4) may have a visible color that
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82/134 indicate to the user that the matrices are about 80% full. In FIG. 19B, all windows (172-1, 172-2, 172-3, 172-4, 172-5) can have a visible color that indicates to the user that the matrices are 100% full. Likewise, the user is able to determine that the sample collection is complete when the color of the fluid sample is visible in all windows.
[00261] FIGS. 17C, 18C, and 19C show a flow meter (175) in accordance with some other embodiments. The flow meter (175) can consist of a single window (176) arranged in parallel to a longitudinal axis of the cartridge chamber. The single window can align with the cartridge matrices (186) when the cartridge assembly is inserted into the cartridge chamber. The single window can be made of an optically transparent material. The fluid sample can be seen through the single window. The color of the fluid sample (for example, red for blood) can continuously fill the window as the fluid sample is being collected in the cartridge. In some embodiments, the window may include one or more markers that indicate a known amount of fluid sample that is being collected. A user may be able to determine if the fluid sample collection is complete when the color of the fluid sample is visible throughout the entire window.
[00262] In some alternative embodiments (not shown), the flow meter may include one or more visible markers. The visible markers can replace the flow meter windows, or can be used in conjunction with the measurement windows. The visible markers can be seen with the naked eye. A visible marker can include an image, a shape, a symbol, a letter, a number, a barcode (for example, arrangement or sequence of lights that can be. For example, lights of various configurations can be used. used, including a barcode in ID, 2D, or 3D), a quick response code (QR), or any other type of visually distinguishable feature. A visible marker can include one distinguishable from another, be turned on or off.
but not limited to, light-emitting diodes (LEDs), OLEDs, lasers, plasma,
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83/134 or any other type of light source. The visible markers can be provided in black and white or in different colors. The visible markers can be substantially flat, raised, lowered or have any texture.
[00263] In some cases, visible markers can emit heat or other radiation in the IR spectrum, UV radiation, radiation along the electromagnetic spectrum. In another example, the device or flow meter may emit vibrations or sounds of different frequencies, steps, harmonics, bands, or patterns of sounds that can be detected by the user. For example, sounds can include words or musical tones. Vibrations / sounds can be discernible by the human ear. Vibrations / sounds can be used to indicate progress in the fluid sampling process. For example, a first vibration / sound can be generated when the fluid sample starts to flow into the matrices, and a second vibration / sound different from the first can be generated when the fluid sample has completely filled the matrices.
[00264] In some embodiments, the flow meter can be used to detect (for example, enable the individual or a user to view) a characteristic, change in color, presentation of a symbol, masking of a symbol or other means of indication progress of fluid sample collection and to indicate that fluid sample collection has been completed.
[00265] In some embodiments, one or more graphical user interfaces (GUIs) can be provided on the device. GUIs can complement the use of the flow meter. In some embodiments, the flow meter function can be incorporated into the GUIs. GUIs can be made into a splash screen on the device. A GUI is a type of interface that allows users to interact with electronic devices using graphic icons and visual indicators such as secondary annotation, as opposed to hosted text-based interfaces, typed command labels or text navigation. Actions in a GUI can be performed through direct manipulation of graphics. In addition to computers, GUIs can be found
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84/134 on portable devices such as MP3 players, portable media players, gaming devices and smaller home, office and industry equipment. GUIs can be provided in software, a software application, etc. GUIs can be provided through a mobile application. GUIs can be rendered through an application (for example, through an application programming interface (API) that runs on the device). GUIs can allow a user to visually monitor the progress of sample collection. In some embodiments, GUIs may allow a user to monitor the levels of analytes of interest in the sample collected.
[00266] In some embodiments, the device may be able to transmit data to a remote server or mobile devices. Data may include, for example, details / information about the user, the date / time / location on which the sample is collected from the individual, the quantity / volume of sample collected, time taken to complete sample collection, flow rates maximum / minimum / averages during sample collection, position of individual's arm during sample collection, if any errors or unexpected events occurred during sample collection, etc. In some cases, data can be transmitted to a mobile device (for example, a cell phone, a tablet), a computer, a cloud application or any combination of these. Data can be transmitted by any means for data transmission, including, but not limited to, downloading the data from the system (for example, USB, RS-232 serial, or other industry standard communication protocol) and wireless transmission (for example, Bluetooth®, ANT +, NFC or other similar industry standard). The information can be shown as a report. The report can be shown on a device or computer screen. The report can be transmitted to a health care provider or caregiver. In some cases, data can be downloaded to an electronic health record. Optionally, the data can comprise or be part of an electronic health record. For example, data can be uploaded to a user's electronic health record of devices and methods
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85/134 described here. In some cases, data can be transmitted to a mobile device and displayed to a user in a mobile application.
G. Sample Collection [00267] Below, typical methods of using the devices here for sample collection are described in detail with reference to the various figures. With reference to FIG. 5A, the device (100) having a cartridge assembly (180) can be placed on the skin of an individual (104) (for example, on the subject's upper arm). The individual's skin may initially be in a free state (105) (that is, the skin is not under tension or positioned in the recess by vacuum pressure). The flat part (132) of the base of the housing (110) can be in contact with the subject's skin, and fixed to the skin with the aid of an adhesive (134) as described here. The device can be configured for use in orientation as shown in FIG. 5A, with channels (146) and (189) and matrices (186) substantially aligned in the direction of gravity in order to assist in the flow of the sample.
[00268] FIG. 5B shows a schematic block diagram corresponding to FIG. 5A, and shows the different chambers and the container. With reference to FIG. 5A, the device (100) may include (1) the deposit chamber (126), (2) the vacuum chamber (112), (3) the container (156) for supporting the drilling module (154) and ( 4) a cavity (107) placed between the skin and the surface of the recess. The vacuum chamber and the deposit chamber can be separated by the sheet (120). The deposit chamber can be in fluid communication with the cavity (107) and the container (156) via the channel (146). Prior to the activation of the vacuum, the pressures inside the deposit chamber (126) (Pdc), the container 156 (Pia), and the channel (146) can be atmospheric pressure (or ambient pressure). The pressure P _vc inside the vacuum chamber (112) can be maintained at its pressure which is below atmospheric while the separation interface (120) is closed (for example, when the sheet is intact). In some embodiments, the pressure P _u can be about -12 psig before the sheet breaks (120). The capillary blood pressure inside the skin (P _cap ) is higher than atmospheric pressure. In
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In some embodiments (not shown), the separation interface (120) can include a valve that can be opened in order to establish fluid communication between the vacuum chamber and the deposit chamber. In some cases, the sheet can be replaced by a valve, or used in conjunction with the valve. [00269] With reference to FIGs. 6A and 6B, the vacuum in the vacuum chamber (112) can be activated by opening the separating interface (120), for example by breaking the leaf (or in some cases, opening the valve). The vacuum activator may comprise a sharp protuberance (116) coupled to the button (115). The vacuum can be activated by pressing the button (115) downwards (FIG. 5A), which causes the protrusion (116) to break the sheet (FIG. 6A). Subsequently, the pressure inside the vacuum chamber, deposit chamber, container and internal channel is equalized to a pressure (Pint) that is lower than atmospheric, but above the initial pressure of the vacuum chamber. In some embodiments, the equalized pressure can be around -4 psig. This negative pressure value can position the skin in the recess (136) and direct blood to that region within the capillary beds. This action can result in an increase in capillary blood pressure within the skin that is under tension inside the recess.
[00270] As previously described, the activation of the vacuum can release the lock on the button (167) of the drilling activator. With reference to FIGs. 8A and 8B, when the button (167) is pressed down, the implantation spring (162) (which may initially be in a compressed state) is released, and extends the piercing elements (158) in the direction of the opening (140) to penetrate the skin at the opening. In some embodiments (not shown), the implantation spring may initially be in an uncompressed state, and compressed by one or more actuating elements in preparation for extending the piercing elements. With reference to FIGs. 9A and 9B, the piercing elements are retracted from the skin by the retraction spring (164) after the skin has been penetrated. The initial blood flow is triggered by the pressure differential between the capillary blood pressure (P _cap ) and the internal pressure of the device (Pint). As
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87/134 mentioned previously, the internal pressure can be about -4 psig, and the capillary blood pressure is higher than atmospheric. Initially, a small amount of blood can be moved towards and into the container (156) while blood can also enter the channel (146) guiding it towards the deposit chamber (126).
[00271] With reference to FIGs. 10A, 10B and 11, the blood flow can quickly reach a "steady state". As blood enters the device, the volume of blood present naturally causes the internal pressure to increase due to the negative value of the internal pressure. The volume Vi _a of the container (156) can be substantially less than the combined volumes Vdc + vc of the deposit chamber (126) and the vacuum chamber (112). In some embodiments, a ratio of Vi _a to Vdc + vc can be about 1:10. The container (156) can have an internal pressure Pi _n t_i _a , and the deposit chamber (126) and the vacuum chamber (112) can collectively have an internal pressure Pint_dc + vc. Due to the substantially smaller internal volume of the container, the internal pressure Pint_i _a inside the container increases with the presence of blood much more quickly than the internal pressure Pint_dc + vc inside the deposit chamber and vacuum chamber which increase in a very large amount little. The increase in internal pressure in the container causes the blood flow to the container to be slower or interrupted, while the blood continues to be drawn into the deposit chamber by the pressure differential between the internal pressures Pint_i _a and Pint_dc + vc and capillary blood pressure (P _cap ). The flow of blood towards the deposit chamber can be further aided by the gravitational force, and by capillary action along the channels (146) of the device and the channel (189) of the cartridge. The blood flow can be further aided by passing through the dies (186) as the blood flows pass through the channel (189) of the cartridge.
[00272] The preferred blood flow in the direction of the deposit chamber (126) allows more blood to be collected in the deposit chamber. A minimal blood flow to the recipient (156) can also assist in reducing the
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88/134 waste of blood, since the blood in the container is not collected and used. Likewise, the device settings described above can assist in increasing the flow rate and the volume of blood collected in the deposit chamber.
[00273] FIGS. 11A to 16F are schematic block diagrams showing the same operating principles as the achievements described in FIGs. from 5A to 10B. Schematic block diagrams are simplified generic views of the device and cartridge assembly, in order to show the change in pressures between chambers and fluid flow. As such, some of the elements can be omitted in the interests of clarity. Similar numerical references refer to similar elements throughout the figures.
[00274] FIG. 11A shows a side section view of the device before inserting the cartridge assembly, and FIG. 11B shows the corresponding front view. The cartridge assembly may include the dies (186) and the cartridge tab (192). The device may include (1) the vacuum chamber (116), (2) the deposit chamber (126), (3) the recess (136), (4) the container (158) for the piercing element (158) and (5) the channel (146) leading to the deposit chamber. The deposit chamber and the vacuum chamber can be separated by a sheet (120). As shown in FIG. 11B, the vacuum chamber can surround the deposit chamber in a U-like shape and the two chambers can be separated by one or more walls (125). The pressures in the vacuum chamber, deposit chamber, and recess can be given by P _v , Pa, and P _r , respectively. Initially, Pa and P _r can be atmospheric pressure (P _a tm). The pressure P _v inside the pre-evacuated vacuum chamber can be a vacuum pressure (Po) that is below atmospheric while the sheet (120) is closed (i.e., the sheet is intact). Initially, Popode may be substantially less than Pa. In some embodiments, Po may be around -12 psig. In some embodiments (not shown), the sheet (120) can be replaced by a valve that can be opened in order to establish fluid communication between the vacuum chamber and the deposit chamber.
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89/134 [00275] FIGS. 12A and 12 B show the cartridge assembly inserted in the deposit chamber. Next, the device can be placed on the subject's skin (104), as shown in FIG. 13A. The skin may initially be in a free state (105) (that is, not under tension due to vacuum suction). A cavity (107) can be placed between the skin (104) and the surface of the recess (136). The initial pressures inside the chambers and the various compartments can remain the same since there is no fluid communication causing any changes in pressure.
[00276] With reference to FIGs. 14A and 14B, the vacuum in the vacuum chamber (112) can be activated by breaking the leaf (120) (or, in some cases, opening a valve). The vacuum activator may comprise a pointed protrusion (116) coupled to the button (115). The vacuum can be activated by pressing the button (115) downwards, which causes the protrusion (116) to break the sheet. Air from the deposit chamber (126), cavity (107), container (156) and channel (146) can be taken to the vacuum chamber in order to equalize the pressures, as shown in FIGs. 14A and 14B. As a result, Pa and P _r will decrease while P _v increases. At the same time, the skin can be positioned in the recess by pressure differentials.
[00277] With reference to FIGs. 15A and 15B, the skin can be completely positioned in the recess. The pressure P _p in the container (156), P _v and Pd, and the pressure in the channel (146) equalize in a pressure Pi, where Po <Pi <Patm. In some embodiments, Pi can be around -4 psig. This negative pressure value can position and maintain the skin in the recess (136), and take blood to the skin region within capillary beds. This can result in an increase in capillary blood pressure P _c within the skin which may now be under tension.
[00278] Next, with reference to FIGs. 16A and 16B, the piercing element (158) can be extended and penetrate the skin into the opening (140) of the recess, and be retracted from the skin as shown in FIG. 16C. The initial blood flow can be triggered by the pressure differential between P _c and Pint, where P _c > P _a tm> Pi.
Initially, a small amount of blood can move towards and
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90/134 to the container (156) while blood also enters the channel (146) that guides it towards the deposit chamber (126), as shown in FIG. 16C.
[00279] The Viado container volume (156) can be substantially smaller than the combined volume Vdc + vc of the deposit chamber (126) and of the vacuum chamber (112). In some embodiments, a ratio of Vi _a to Vdc + vc can be about 1:10. As blood flows into the container and towards the deposit chamber, the pressure P _p of the container increases to P2, and the pressures Pd and P _v of the deposit chamber and the vacuum chamber may increase to P3. However, P2 can be substantially greater than P3 since Via can be substantially less than Vdc + vc. In other words, the pressure in the container (156) increases much more rapidly than the pressure inside the deposit chamber and the vacuum chamber which increases by a very small amount. The growth of the internal pressure in the container causes the blood flow to the container to be slower or to be interrupted, while the blood continues to be drawn into the deposit chamber by the pressure differential between the internal pressures Pintja and Pint_dc + vc e capillary blood pressure P _ca p. Likewise, the blood flow reaches a "steady state" in which blood is drawn only in the direction of the deposit chamber. The flow of blood towards the deposit chamber can be further aided by the gravitational force g, and by the capillary action c along the channels (146) of the device and the channel (189) of the cartridge. The blood flow can be further aided by passing w along the dies (186) as blood flows through the cartridge channel (189).
[00280] As previously described, the preferred blood flow towards the deposit chamber (126) can allow more blood to be collected in the deposit chamber. A minimum blood flow to the container (156) can also help to reduce blood waste, since in some cases the blood in the container is not collected and used. Likewise, the device settings described above can assist in increasing the flow rate and volume of blood collected in the deposit chamber.
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91/134
III. Cartridge Packaging and Transport After Sample Collection [00281] As previously described with reference to FIGs. 17A-19A, 17B-19B and 17C-19C, the use of flow meters on the device by allowing a user to monitor the progress of the sample collection and to know when the sample collection has been completed. FIG. 20A shows a top view of the device with a completely filled cartridge and FIG. 21A shows a top view with the full cartridge removed from the device. The cartridge assembly can be removed from the deposit chamber of the device by pulling on the cartridge tab. The filled cartridge can subsequently be packed and transported to an external facility for further processing. For example, the sample can be treated, stabilized and stored. In any of the achievements described here, the devices can be configured to collect, process and store the sample. The samples taken by the device can be stored in liquid or solid form. The sample can be subjected to an optimal treatment before being stored. Storage can take place on the device, outside the device or in a removable container, vessel, compartment or cartridge inside the device.
[00282] FIG. 22A shows a perspective view of a carrying sleeve (200) that can be used for packaging a full cartridge or samples inside the cartridge. The sleeve may include a hollow interior for storing the full cartridge or samples during shipping / transportation. The sleeve may include an opening for receiving the cartridge. In some embodiments, the glove may include a cover (212) to cover the opening before using the glove. The cover (212) can be, for example, a thin sheet that can be fixed to the opening by means of an adhesive and removed by a user before using the glove. A desiccant (not shown) can be placed inside the glove and used to keep the samples dry. The thin sheet can help to protect the inside of the glove against moisture and contamination before use.
[00283] FIG. 22B shows a top view of the carrying sleeve and a full cartridge assembly prior to insertion into the sleeve. FIG. 22C shows the
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92/134 full cartridge assembly inserted into the carrying sleeve, with the cartridge tab (192) extending from one edge of the sleeve. FIG. 23 shows an exploded view of the carrying sleeve and the cartridge assembly. With reference to the figures above, the glove can include a glove base (202) and a glove cap (208) configured to be operationally coupled together. The base of the sleeve may include an opening (204) for receiving the cartridge assembly. The opening can be configured to be attached to the cartridge holder (for example, proximal to the cartridge tab). The sleeve may include a dual support-release mechanism comprising (a) a retaining element configured to engage with a matching combination feature on the cartridge and holding the cartridge inside the sleeve and (b) a release element configured to make with the spring clips on the cartridge holder release and thus disengage the cartridge from the cartridge holder. In some embodiments, the dual support-release mechanism can be implemented by using a plurality of columns (206) and (207).
[00284] FIG. 24A shows a side section view of the transport sleeve with the cartridge assembly inserted. FIG. 24B shows a side section view with the cartridge holder removed, leaving the cartridge inside the transport sleeve. As shown in the figures above, the cartridge assembly is inserted into the opening (204) of the sleeve (200) by pushing the cartridge tab (192) to a rear of the cartridge holder and the seal / gasket (194) contacts and seal the opening (204). The columns (206) can be configured to engage and release the spring clips (196) on the cartridge holder when the cartridge assembly is properly inserted into the sleeve. Releasing the spring clips decouples the cartridge from the cartridge holder. The columns (207) can serve as stoppers and come in contact with a part of the cartridge adjacent to the cartridge port (184). As shown in FIG. 24B, the cartridge holder can subsequently be removed from the sleeve, leaving the cartridge held in place by the columns (206) and (207) inside the sleeve. As described above, columns (206) and (207) can provide the dual support-release mechanism. O
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93/134 decoupling the cartridge from the cartridge holder via the dual holder-release mechanism can allow the cartridge holder to be removed from the sleeve opening while the cartridge is held in place inside the sleeve without exposing the tapes in half environment.
[00285] In some embodiments, additional treatment and / or stabilization of the sample in the dies (186) may occur inside the transport sleeve after the cartridge is released from the cartridge holder. In some embodiments, a desiccant can be provided inside the glove for drying the sample in the matrices. In some embodiments, the glove can be placed in a carrying bag (220) and sent for further processing (see, for example, steps 13 and 14 of FIG. 25B).
[00286] FIGS. 25A and 25B illustrate typical procedures for collecting and storing blood samples using any of the devices described here (for example, the device (100)). With reference to FIG. 25A, the device can first be removed from its packaging (step 1). An individual or another user (for example, a healthcare professional) can record patient information on a glove label (step 2). An alcohol swab is then used to clean the skin on the patient's upper arm where the device will be applied (step 3). Then, an adhesive coating is removed from the flat part at the base of the device housing in order to reveal a hydrogel adhesive (step 4). Then, the device is placed and adhered to the patient's skin with the hydrogel adhesive (step 5). The button labeled “1” on the device is pressed in order to activate the vacuum to position the patient's skin in the recess (step 6). The button labeled “2” on the device is then pressed to activate one or more perforating elements to penetrate the patient's skin at the opening of the recess (step 7). The blood is absorbed by one or more matrices in the device's cartridge. As the blood is absorbed, the flow meter on the device can indicate the progress of blood collection and indicate when the arrays are full (step 8). Once the arrays are full, the device is removed (step 9). The cartridge is removed from the
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94/134 device (step 10) and inserted into a carrying sleeve (step 11). The device is no longer needed and can be properly disposed of in a sharps container (step 12). The glove can be placed in a bag (step 13) that is used to send the sample to a laboratory for processing (step 14).
IV. Additional Achievements [00287] Here are provided devices, methods and kits for collecting an individual's blood. The devices, methods and kits provided here may allow a vacuum to be applied to an individual's skin, followed by piercing the individual's skin under vacuum (for example, with one or more blades). Applying a vacuum can increase the blood flow to a region of the skin under vacuum and can increase the rate and volume of blood collection in the device. The vacuum can be generated using a bleed action by means of, for example, a rigid concave surface or a flexible concave surface, for example, a concave cavity (see, for example, FIGS. 31A-31D). A volume of a hemisphere formed by the concave surface can be equivalent to, or about half, or about a quarter, of a volume of a vacuum chamber in the device. The concave cavity can comprise an opening with an internal diameter and the concave cavity can comprise a diameter on a base of the device.
[00288] Any of the devices provided here may comprise one or more piercing elements, for example, blades. The one or more perforating elements, for example, blades, can be configured to pass through the opening of the device and pierce an individual's skin. Each of the one or more blades can comprise a length of about 1 mm to about 10 mm, or about 1 mm, 1.5 mm, 2 mm, 4 mm, 6 mm, 8 mm, 10 mm, a width from about 0.01 to about 2 mm, or about 0.01 mm, 0.05 mm, 0.1 mm, 0.5 mm, 1 mm, 2 mm, and a depth of about 1 to about 20 mm, or about 1, 5, 10, 15, or 20 mm. Devices can comprise one or more
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95/134 piercing elements, for example, at least 1, 2, 3, 4, 5, 6, or 7 piercing elements (for example, lancets, needles or blades).
[00289] A method for collecting blood from an individual is provided here, the method comprising applying a vacuum to an individual's skin using a device; after the application of vacuum, perforation of the individual's skin under which the vacuum is applied, where the device is used to perforate the individual's skin, thereby generating an incision in the skin under which the vacuum is applied; and blood collection from the vacuum incision, where the collection takes place on the device. The vacuum can deform the skin, increase perfusion and draw blood from the smaller incision area. The vacuum can be a global vacuum. A local vacuum can also be used, however skin deformation and perfusion can be much less.
[00290] In some embodiments, the individual has diabetes. In some embodiments, an individual's blood collection further comprises the stabilization of a component or analytes of interest to the blood. In some embodiments, the analyte of interest is hemoglobin Ale (HbAlc).
[00291] The device can be configured with user friendly features. FIG. 31 A, FIG. 31B, FIG. 31C and FIG. 31D illustrate features that can be integrated into the devices described in the present application. Such features may include single or multiple triggers or activators (for example, 2, 3, 4, 5) (for example, which may include buttons) for device activation, with positions that can be readily activated by the user given the format of the device and location of the trigger. Triggers or activators can have different shapes, sizes and locations configured (for example, positioned or structured on the device) for easy use (for example, facilitating user identification and well placed locations for simple activation). An example of a device with triggers or activators for performing one or more direct user actions is shown in FIG. 31 A, where two buttons are shown in an easily identifiable format and comfortable to locate the use. The circular button shown in FIG. 31A can be
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96/134 used to activate a vacuum and the rectangular button can activate a piercing element (for example, lancet) to pierce the skin. In some cases, a single actuator or activator can be used to activate a vacuum and a piercing element. The device may comprise a lancet activation trigger configured to activate the lancet by triggering the lancet activation trigger. The lancet trigger can comprise a button.
[00292] The features, for example, user-friendly features, can comprise mechanisms to speed up blood collection by increasing a rate or means for collecting a sample, thus reducing the time required to collect a sample. Such a feature is illustrated in FIG. 31B, which features a device with a vacuum cavity for skin and a lancet to reduce the amount of time required to collect a sample. The vacuum cavity for skin and lancet may comprise a concave cavity in which the subject's skin can be positioned (for example, under negative pressure), and an opening comprising an internal opening through which one or more piercing elements (for example , lancets), for example, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 perforating elements, can come out and pierce the skin in such a way that a blood sample can be taken from the individual. In some embodiments, the device may comprise a vacuum actuator (e.g., button) to actuate the vacuum.
[00293] FIG. 31C shows additional features. For example, a device for collecting a blood sample may comprise a visual measurement window that can allow a user to monitor the sample collection and determine when the sample collection is complete. When the sample collection is complete, a visual measurement window can be used to detect (for example, view) a characteristic, colorimetric change, show a symbol, mask a symbol or other means of indicating that the collection is complete. Additional user-friendly features may comprise a removable cartridge (for example, clip-removable cartridge)
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97/134 for collecting and transporting a blood sample, as shown in FIG. 31D. A removable cartridge (for example, clip-removable cartridge) may comprise a cartridge tab for releasing and removing the cartridge. In some embodiments, a removable cartridge (for example, clip-removable cartridge) may comprise a solid matrix for the collection, storage and / or stabilization of a collected sample and the removable cartridge can facilitate transport (for example, transport at room temperature ) and transport without the need for subsequent sample preparation or stabilization procedures.
[00294] FIG. 50A shows an additional realization of the visual measurement window and illustrates how blood absorption in the matrix tapes can appear. In some embodiments, a passage pad captures excess blood that is unable to be absorbed by the matrix strips (FIG. 50B). The absorption of blood in the matrix strips is illustrated in FIG. 50C.
[00295] FIG. 32A, FIG. 32B, FIG. 32C and FIG. 32D illustrate an integrated device with several of the user characteristics described in FIG. 31 A, FIG. 31B, FIG. 31C and FIG. 31D. FIG. 32A illustrates a front view of a device with a double button configuration. In some embodiments, one button may be responsible for activating a vacuum and a second button may be responsible for activating a perforation mechanism (for example, lancet drilling); for example, the lower round button or the vacuum button can be configured to cause a vacuum (negative pressure value) to be applied to the skin and the upper rectangular button or lancet button can be configured to activate a lancing mechanism in the vertical in order to perforate the skin. Alternative button realizations can be activated using a variety of methods; for example, the buttons can be activated separately, in a specific sequence or order, or the two buttons can be combined into one button in such a way that only a single button is required to activate the collection mechanisms on the device. The buttons can perform different functions and have different shapes, sizes, colors or
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98/134 locations that support the function of each button. FIG. 32B illustrates a side view of the device shown in FIG. 32A. FIG. 32B illustrates a device with a lancet housing, the lancet housing in this embodiment comprises a raised area for housing the lancing mechanism. Also shown is a removable cartridge for storing a solid matrix, with a cartridge tab for removing the removable matrix from the cartridge. FIG. 32C shows an alternative view of the device illustrated in FIG. 32A and 32B. The features illustrated include the rear cartridge closing cap and cartridge flap, as well as a visual measurement window configured to alert the user when removal is complete. FIG. 32D illustrates a side perspective view of the device shown in FIG. 32A, FIG. 32B, and FIG. 32C. [00296] FIG. 33A shows the bottom view of a device for collecting a blood sample, the bottom region shown is the location of the device configured to make contact with the individual's skin. As is known, the bottom of the device can comprise a concave cavity, for example, a concave hemispherical cavity as shown here, although other shapes can also be used. The concave cavity in this embodiment forms a hemispherical bowl arranged inside the bottom of the device. The cup area of the skin can be substantially larger than the lanced area. In some embodiments, the ratio of the cup skin to the lanced area may be greater than 20: 1, greater than 30: 1, greater than 40: 1, greater than 50: 1, greater than 60: 1, greater than 70: 1, greater than 80: 1, greater than 90: 1 or greater than 100: 1. In some embodiments, the cup area may be within 20% of the 500 mm2 margin and the lanced area may be within 20% of the 8 mm ² margin. The lanced area may comprise a hole in the center of the concave cavity from which the lancets can protrude; this area can additionally act as a vacuum channel and as part of the blood path to the deposit cartridge. Lancets or other piercing elements can be maintained in a cylinder shaped lancet driver. The lancet drive can have a diameter of 1-10 mm (for example, 1, 2, 3, 4, 5, 6, 7, 9, 10 mm). The lancet trigger area
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99/134 can be between 5 and 100 mm ² (e.g., 5, 10, 13.2, 15, 20, 40, 60, 80, 100 mm ² ). The lancets or blades maintained by the lancet driver can generate an incision area of between 1 and 20 mm ² (for example, 1, 3, 5, 9, 11, 15, 17, 20 mm ² ).
[00297] Any of the sampling devices here may also be referred to as the "device", the housing, outer housing, upper housing, lower housing or lancet housing of the device may comprise styrene acrylobutadiene (ABS), polypropylene (PP ), polystyrene (PS), polycarbonate (PC), polysulfone (PS), polyphenyl sulfone (PPSU), polymethyl methacrylate (acrylic) (PMMA), polyethylene (PE), ultra high molecular weight polyethylene (UHMWPE), low polyethylene density (LPDE), polyamide (PA), liquid crystal polymer (LCP), polyaryl amide (PARA), polyphenyl sulfide (PPS), polyether etherketone (PEEK), polyvinyl chloride (PVC), polyethylene terephthalate (PET), polytetra flourethylene (PTFE), polyarylethercetone (PAEK), polyphenyl sulfone (PPSU), or a combination of these. In some embodiments, the outer housing comprises polypropylene.
[00298] After the device is placed on the individual's skin and the device is activated, a vacuum or pressure differential can be formed between the surface of the skin, as well as the components disposed inside the device. The skin can be pulled into the cavity by the pressure differential and can be constricted by the cavity walls. At some point after a vacuum has been formed between the device and the skin, a piercing element (for example, a lancet) can be activated to pierce the skin. As such, the “cup” formed by the vacuum can be configured to increase the blood flow to the lanced area and also to suck blood from the opening of the collection site, through the device and into a collection cartridge.
[00299] A side view of the device shown in FIG. 33A is illustrated in
FIG. 33B. In some embodiments, the bottom of the device may comprise a curved base. A slight curvature at the base of the device can allow the device to better conform to the patient's anatomy (eg, arm,
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100/134 (upper arm) and can guide the orientation of the device. In some embodiments, the device described here is used to draw blood from the arm. In some embodiments, the device is not used to draw blood from the fingertip. In some embodiments, the device is not used to draw blood from a newborn.
[00300] The sample collection can comprise steps and components configured to pierce (for example, lancing) the individual's skin and providing and creating a vacuum in order to facilitate the sample extraction. In some cases, a vacuum can be provided before lancing the skin; in other cases, the vacuum can be provided after lancing the individual's skin, and in still other cases, the vacuum can be provided simultaneously with the action of lancing the individual's skin. FIG. 33A and FIG. 33B illustrate features of a device that can facilitate efficient blood collection by applying a vacuum to the individual's skin. The vacuum can operate as a means to deform the skin, and this action coupled with the action of lancing the deformed skin can facilitate sample collection. In additional cases, the device can be configured to perform one or more processing steps (for example, treatment, stabilization and storage of the collected sample).
[00301] FIGS. 33A and 33B illustrate an embodiment of a device for collecting a sample using global vacuum and local suction. Methods for using the device may comprise multiple steps. For example, a device as shown in FIG. 33A and FIG. 33B can be placed on an individual's arm using the orientation illustrated in FIG. 33C. The global vacuum cavity can be placed in contact with the skin, and a seal can be created with an adhesive material or gasket material placed on the base of the device (for example, on the curved surface of the device shown in FIG. 33B). The vacuum can be applied with the push of a button or other mechanism. Subsequently, the lancet can be applied, for example, by using a spring loaded plunger mechanism that causes two (may be more or less) lancets to penetrate the skin and retract. The action
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101/134 lancing can be performed by a single blade or multiple blades (for example, two or more, three or more, four or more, five or more or ten or more blades). The blades can have points with various sizes and shapes (for example, slanted, triangular, circular, pointed, blind, serrated). In cases where more than one slide is present, the slides can be configured or arranged in patterns with different shapes or orientations (for example, ring, star, tic-tac-toe, square, rectangular etc.) [00302] After sample collected, additional processing steps can be performed on the sample. Once blood has been collected using a sample collection device, the sample can be treated, stabilized and stored. In some embodiments, the collection devices, for example, the devices described in this application, can be configured to collect, process and store the sample. The sample taken by the device can be stored in liquid or solid form. The sample can be subjected to an optimal treatment before being stored. Storage can take place on the device, outside the device, or in a removable container, vase, compartment or cartridge inside the device.
[00303] A sampling device can be configured to collect, treat, stabilize and store a collected sample. Further processing (for example, treatment, stabilization and storage) may comprise steps or methods and device components configured to concentrate the sample, adjust or measure the sample flow, expose the sample to one or more reagents and deposit the sample in a solid substrate or matrix. Methods for using a sample collection device may include steps to perform one or more of the following processes: sample collection, treatment, stabilization and storage. Collection, treatment, stabilization and storage can be performed inside a single device. The treatment may comprise filtering the sample to separate the components or analytes of interest. In some embodiments, the collected sample can be collected, processed and stabilized before transfer to a
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102/134 removable cartridge for storage. In other embodiments, one or more steps comprising collection, treatment and stabilization can take place in a removable cartridge.
[00304] In some embodiments, a single action (for example, activation using a button) can activate alternative processing steps including treatment, stabilization and storage of the sample. Additional processing steps can be performed on the device in response to a single action, or in some cases, two or more actions by the user may be required to move the sample through one or more different processes (e.g., collection, treatment, stabilization and storage). User actions may include pressing a single button, pressing multiple buttons, pressing two or more buttons at the same time and pressing two or more buttons in a prescribed sequence (for example, based on a prescribed sequence for performing a set of treatment steps desired by the user).
[00305] The sample collected in a device can be subjected to a treatment step before being deposited on a solid substrate. A cartridge containing the two or more depositing strips can be kept in an orientation close to vertical in order to reduce the deposition speed and increase the consistency of the sample deposition. The vacuum can be released by the user and the device can be removed when a visual measurement mark (or other) is observed. The sample cartridge containing the two or more solid matrix strips can be removed from the device.
[00306] In some embodiments, the solid matrix tapes can be sized to maximize the blood collection volume while being able to be adjusted in the commonly used containers (for example, a 3 ml BD vacutainer, deep well plate or tube Eppendorf 2 ml). The solid matrix can be configured to measure, collect and stabilize fixed blood or plasma volumes (for example, greater than 25 uL, greater than 50 uL, greater than 75 uL, greater than 100 uL, greater than 125 uL, greater than 150 uL, greater than 175
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103/134 µL, greater than 200 µL or greater than 500 µL of blood or plasma). A solid matrix may comprise cellulose-based paper (for example, Whatman ™ 903 or 226 paper), paper treated with chemicals or reagents for sample stabilization or one or more components of the sample (for example, RNA stabilization matrix or Protein Stabilization Matrix). In some embodiments, the solid matrix comprises a cellulose filter paper. In some embodiments, any suitable commercially available filter paper is used. Examples of commercially available filter paper include, but are not limited to, Whatman ® filter paper, such as sample collection cards 903 and rapid transit analysis card (FTA®). In some embodiments, the solid matrix comprises a nitrocellulose filter paper. In some embodiments, the solid matrix does not comprise fiberglass filter paper.
[00307] The sampling devices (for example, the devices shown in FIGS. 31A-D, FIGS. 32A-D and FIGS. 33A-C) may comprise a removable cartridge or container for storing a liquid sample or solid matrix to remove the sample as soon as it is collected. FIG. 34A, FIG. 34B, FIG. 34C and FIG. 34D illustrate steps for removing a removable cartridge from a typical device configured with a removable cartridge (for example, the devices shown in FIGS. 31A-D, FIGS. 32A-D and FIGS. 33 AC). A device may come with a cartridge pre-loaded in the device, as shown in FIG. 34A, or a device may come without the cartridge in such a way that a cartridge can be purchased separately and installed in the device by the user prior to sample collection. The device illustrated in FIG. 34A is shown with a cartridge loaded in the device and with the cartridge tab protruding from the rear of the device. After a withdrawal is complete, the cartridge can be removed as shown. The cartridge may comprise one or more solid matrix tapes, or a vessel for storing the liquid sample. Alternatively, the cartridge may be empty. In some cases, the cartridge may include liquid handling reagents. In some
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104/134 realizations, the cartridge / device interface may contain a seal (for example, gasket or other type) to maintain internal pressure during the withdrawal period.
[00308] FIG. 34B illustrates the partially removed cartridge. Cartridge removal can be performed using the cartridge tab shown in FIG. 34A. In FIG. 34C, the cartridge shown in FIG. 34B has been completely removed and is placed at the rear of the collection device in an orientation by which it was removed. FIG. 34D illustrates the completely removed cartridge placed in parallel with the collection device to illustrate the placement of the cartridge inside the device. Once removed, a cartridge can be placed in a secondary vessel with desiccant to dry the sample. In cases where the cartridge comprises solid matrix tapes for storing the sample, the tapes can be removed with an extraction tool or other mechanism prior to analysis.
[00309] A cartridge, for example, the cartridge illustrated in FIGs. 34A-D, can comprise multiple components to facilitate accurate and accurate sample collection. FIG. 35 illustrates an enlarged cross section of a cartridge embodiment that can be used in any of the devices described here. In some cases, a cartridge may comprise one or more solid matrices for collecting a blood sample. In embodiments in which two or more solid matrices are included in the sample, the matrices can be stacked or arranged so as to facilitate the collection, distribution, precision and reproducibility of volumes of or analytes per surface area of solid substrate. In cases where two or more solid matrices are included, the matrices can have different compositions or purposes; for example, an array can separate cells from a cellless component and collect the cellless component in an array, and a second array or other arrays can collect unseparated raw sample.
[00310] A typical sample storage cartridge is shown in FIG.
35. The cartridge can comprise two parts, a top part and a part
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105/134 lower that can be joined to form integral chambers. The sample can travel through the opening to the device's concave cavity and into the cylinder-shaped sample inlet for tunnel entry before entering a chamber. The chamber may comprise solid matrix tapes to absorb the sample and a spacer (e.g., plastic spacer) to separate the two solid matrix tapes. The spacer (for example, plastic spacer) between the two tapes can be adjustable and removable, depending on other relevant aspects (for example, the needs and application of the sample being collected, analyte stability, absorption rate requirements, etc.) . The spacer (for example, plastic spacer) can comprise a variety of widths and coatings. Typical widths include widths ranging from millimeters to centimeters (for example, over 2 mm, over 4 mm, over 6 mm, over 8 mm, over 10 mm, over 0.2 cm, over 0, 4 cm etc.). In additional embodiments, the spacer (e.g., plastic spacer) can be coated with materials including hydrophobic coatings, hydrophilic coatings, antimicrobial coatings, coatings that bind to one or more of the components of a sample, coatings to be bonded to or for inhibit enzymes that may degrade or otherwise impact the quality of one or more analytes in the sample.
[00311] As shown in FIG. 35, after moving through the sample chamber, the excess sample can be displaced out of the storage cartridge by means of a passage tail. The pass-through tail can be configured to absorb excess sample flow. The pass-through can be configured (e.g., adjusted composition) in such a way that the pass-through can be used as a means to control the sample volume absorbed in the solid matrix tapes. In additional realizations, the pass-through can be used as or incorporated in an indicator or be visible through a viewing window configured to inform a user that the collection procedure is complete. The cartridges illustrated in FIG. 35 show the sample stored in a matrix
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106/134 solid; however, this should not be taken as limiting the devices described here - the devices may comprise cartridges or means for collecting, treating, stabilizing and storing a sample in both a liquid and a solid state.
[00312] FIG. 36A and FIG. 36B illustrate a typical device configured with a sample storage cartridge similar to the cartridge illustrated in FIG. 35. FIG. 36A shows a removable external housing configured to apply a global vacuum to the sample collection site located on an individual's arm. In some embodiments, the global vacuum can be applied through a concave cavity to deform the skin before the lancing procedure. FIG. 36B illustrates typical local suction and blood collection components of the device shown in FIG. 36A and 36B. A depression is apparent in the individual's arm, indicating that a global suction has been applied. Local suction, by means of a suction cup, is provided on the surface of the skin around the place where the individual's skin was lanced. The sample is shown moving from the lancet site to a cartridge comprising a saturated matrix and a passing tail. The pass-through can be used to absorb excess sample and standardize or measure the volume of blood deposited in the saturated matrix.
[00313] In some embodiments, the solid matrices, for example, the solid matrices included in a cartridge, can be sized to maximize the volume of blood collection while still being able to be placed in the commonly used containers (for example, a BD Vacutainer of 3 ml, a deep well plate or 2 ml Eppendorf tube). The cartridge can include a solid matrix, two solid matrices, three solid matrices, four solid matrices, or more than four solid matrices. In some embodiments, the cartridge includes two solid arrays. The solid matrix can be configured to measure, collect and stabilize fixed volumes of blood or plasma (for example, above 50 uL, above 75 uL, above 100 uL, above 125 uL, above 150 uL, above 175 uL, above 200 uL or above 500 uL of blood or plasma). In some
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107/134 realizations, the cartridge comprises two solid matrices, where each solid matrix stabilizes 75 pL of blood for a total of 150 pL of blood. A solid matrix may comprise cellulose-based paper (for example, Whatman ™ 903 paper), paper treated with chemical products or reagents to stabilize the sample, or one or more of the sample components (for example, RNA stabilization matrix or Matrix Protein Stabilization).
[00314] The devices for collecting a blood sample can be modular, with two or more compartments to perform specific actions or functions in the device. A typical modular device is shown in FIG. 37A, FIG. 37B, FIG. 37C and FIG. 37D. FIG. 37A illustrates the top view of a modular sampling device (for example, similar to the device shown in FIGS. 31A-D, FIGS. 32A-D and FIGS. 33A-C and FIGS. 34A-D). Arranged within the upper cover of the device illustrated in FIG. 37A, there is a lancet module and a lancet button to activate the lancet module. FIG. 37B illustrates the vacuum chamber and the cartridge chamber disposed within the bottom or "foot" of the device. This module comprises a perforated vacuum chamber and a cartridge chamber, inside the cartridge chamber there is a cartridge. Projecting out from the rear of the device is a cartridge tab, which can be used to remove the cartridge as illustrated in FIGs. 34A-D. FIG. 37C illustrates a cross section of the device. The cross section shows the top cover and the lancet module is also shown in FIG. 37A, and at the bottom of the device, the vacuum chamber / cartridge chamber shown in FIG. 37B. Also shown in FIG. 37C is a side view of the removable cartridge with the cartridge tabs, the cartridge is removed from the device and positioned on the side of the cartridge chamber where the cartridge can be inserted or where the cartridge can be removed. FIG. 37D illustrates a top view of the device in a top down view showing the components present in FIG. 37B. FIG. 37D shows the vacuum button, with a pointed end to pierce the evacuated chamber, the perforation of the evacuated chamber can form a suction that pulls the sample
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108/134 through the opening of the concave cavity, for the sample entry of the cartridge and for the solid matrix strips in the cartridge.
[00315] FIGS. 38A-38F show various views of a typical embodiment of a device configured for single activation drilling and collecting a blood sample from a patient. As shown in FIG. 38A, the device may comprise a low profile mold with a lancet safety sticker, and a button for single activation of the device. FIG. 38B illustrates the internal work of the device in a typical starting position. In the starting position, a movable blade holder is maintained in a spring loaded state by a hook that releases the blade holder when the button is pressed. The device also comprises a path or trail for the released blade holder to move once the blade holder has been released. And also illustrated in FIG. 38B the sample collection location and the mobile collection arm. FIG. 38C illustrates the internal work of the device once the button has been pressed (1), and the blade holder released (2). When the button is pressed, the movable blade holder is released and moves down the path or trail. At this point in the activation of the device, the mobile collection arm is still in the starting position, disposed above the sample collection location with enough space for the mobile slide holder to move between the mobile slide holder and the sample collection location . FIG. 38D illustrates the internal work of the device. Once released, the button that activated the movable blade holder rotates on the device as it travels along the path or trail. At the end of the path or trail, it activates a tongue, thus releasing the blood collection arm. FIG. 38E shows a side view of the device, illustrating the movable blade holder reaching the end of the path or trail where the removable blade holder reaches a tongue that activates the spring loaded blood collection arm resulting in the release of the spring loaded collection arm (3). The blood collection arm is released at the sample collection site. They are also shown in FIG. 38E the blades and a typical blade depth to a depth by which the blades are configured to
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109/134 protrude through the bottom of the device and onto the individual's skin. The depth of the blades is determined by the shape and height of the trail or path in which the movable blade holder moves. FIG. 38F illustrates the formation of a seal by the blood collection arm released over the sample collection site (4). The typical device illustrated in FIGs. 38A-38F comprises four activation steps; first a single button is pressed causing a blade holder to be released and the blade holder to move down the trail or path. Along the way, the blades held by the blade holder pierce the skin and at the end of the trail or blade holder path, the blade holder activates a tongue that releases a spring loaded collection arm over the sample collection site . The collection arm forms a seal with the sample collection site and the collection arm can draw blood from the individual. In some cases, the device illustrated in FIGs. 38A-38F may comprise an evacuated chamber or internal vacuum for creating suction.
[00316] An alternative embodiment of a low profile sample taking device is shown in FIGs. 39A-39E. A top view (FIG. 39A), bottom view (FIG. 39B) and side view (FIG. 39C) of a typical low-profile sample taking device, together with internal views of the device (FIG. 39D and FIG. 39E ), illustrate the button, blade holder with two blades, collection arm, main spring of the collection arm and release spring, as well as the tongue that releases the collection arm. In this embodiment (FIG. 39D and FIG. 39E), the button can be pressed by the user, causing the blade holder and installed blades to rotate, triggered by the main spring and during rotation to pierce the individual's skin, at the end of the rotation , the blade holder can activate the catch of the collection arm which releases the spring of the collection arm causing the collection arm to be released placing it in contact with the individual's skin. The collection arm can create contact with the skin and can be configured to provide suction or vacuum in order to draw the blood sample.
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110/134 [00317] The devices illustrated in FIGS. 38A-38F and FIGs. 39A-39E, and any devices described in the present application, may comprise a single blade or multiple blades for piercing individuals' hair; for example, one or more, two or more, three or more, four or more, five or more or ten or more blades. The blades can be configured in different shapes or orientations, for example, a ring shape, a star shape, a tic-tac-toe shape, square shapes, rectangular shapes etc.
[00318] The devices illustrated in FIGs. 38A-38F and FIGs. 39A-39E, and any devices described in this application, can be configured to collect, process and store the sample. The sample taken by the device can be stored in liquid or solid form. The sample can be subjected to an optional treatment before being stored. Storage can take place on the device, outside the device or in a removable container, vessel, compartment or cartridge inside the device.
[00319] The devices illustrated in FIGs. 38A-38F and FIGs. 39A-39E, and any devices described in the present application can be configured to collect, store, stabilize and store a collected sample. A device can be configured to perform one or more of the following processes: sample collection, treatment, stabilization and storage. Collection, treatment, stabilization and storage can be performed within a single device. The treatment may comprise filtration of the sample in order to separate components or analytes of interest. The treatment may also comprise buffers or reagents for sample stabilization. In some embodiments, the device can be configured to concentrate one or more of the sample components.
[00320] In some cases, one or more of the processes (for example, collection, treatment, stabilization and storage of the sample) can be performed on the device in response to a single activation of the device by the user. In other cases, two or more actions by the may be necessary to move the sample through one or more different processes (for example,
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111/134 collection, treatment, stabilization and storage). User actions may include pressing a single button, pressing multiple buttons, pressing two or more buttons at the same time, and pressing two or more buttons in a prescribed sequence (for example, based on a sequence prescribed for performing a set of treatment steps desired by the user).
[00321] The collection of the sample can comprise steps and components configured to lance the skin of the individual and provide or create a vacuum to extract the sample. In some cases, a vacuum can be provided before lancing the skin, in other cases, the vacuum can be provided after lancing the skin of the individual, in additional cases, the vacuum can be provided simultaneously with the procedure of lancing the skin of the individual .
[00322] The treatment of the device may comprise the concentration of the sample, adjustment or measurement of the sample flow, exposure of the sample to one or more reagents and deposit of the sample on a solid substrate or solid matrix. Embodiments of the device may comprise a removable cartridge or container for storing a liquid sample or solid matrix for removing the sample once it has been collected. The solid matrix may comprise cellulose-based paper (for example, Whatman ™ 903 paper), paper treated with chemicals or reagents for sample stabilization, or one or more of the sample components (for example, RNA stabilization matrix or Protein Stabilization Matrix).
[00323] The devices for collecting a blood sample from an individual can also be based on a vertically oriented device, as shown in FIGs. 40A-40D, FIGs. 41A-41B and FIGs. 42A42C.
[00324] FIG. 40A illustrates a typical embodiment of a sample taking device with a vertical sectioning mode. The device may comprise a syringe with a syringe plunger, connected to a housing comprising a plunger and a blade. The device can comprise a
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112/134 housing inside which a plunger and a blade are arranged. The housing can be oriented towards the individual's skin with the syringe and syringe plunger oriented away from the individual. FIG. 40B shows the same device positioned on its side to illustrate the cup-shaped protection with slits for the blades. FIG. 40C illustrates a side view of the housing part of the device in the starting position. The view illustrates the presence of a sealed chamber between the housing and a plunger arranged inside the housing. The blade is maintained in a spring-loaded state by a shoulder arranged inside the housing. At the bottom of the device, a cup-shaped protection with slits allows the blades to move through the cup-shaped protection to pierce the individual's skin and, through microchannels, cut through the cup-shaped protection, direct the blood flow to the center of the cup. FIG. 40D is a side view of the device with a view of the housing and the plunger disposed inside. Also visible at the bottom of the device is the cup-shaped shield with the blades protruding through the slits of the cup-shaped shield, showing how the individual's skin is cut.
[00325] Methods for using the device illustrated in FIGs. 40A-40D, are illustrated in FIG. 41A and FIG. 41B. As shown in FIG. 41 A, a lancet safety ring is then removed from the device (1). At this point, the device is still in the locked position with the blade resting on a ledge inside the device (see FIG. 41B). Then a user pushes down the outer ring (2), pressing an inner spring and releasing the blade (3). The blade then rotates (4a-4d) cutting the user's skin and exposing the blood that moves to the cup-shaped protection. Finally, the user pulls the syringe plunger (5) in order to create a negative pressure and withdraw the sample through microchannels and slits at the bottom of the cup-shaped protection and into the syringe.
[00326] FIG. 42A, FIG. 42B and FIG. 42C illustrate a device with a vertical rotary cutter similar to those illustrated in FIGs. 40A-40D and FIGs. 41Application 870190079292, of 15/08/2019, pág. 117/211
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4IB, however, a spring mechanism is used to control a blade holder and thus trigger the rotation of the blade in the device. FIG. 42A illustrates the blade and the spring, with the blade in the locked position - leaning on a feature inside the housing, with the spring loaded. A force is applied to the top of the device to press the spring (la), and the blade is free to rotate (1b). As shown in FIG. 42B, the blade rotates in the path (2a-2d) during which it cuts through the individual's skin, until it reaches an uncharged state. The cut skin of the individual releases the blood sample that moves through the shield which directs the blood flow to the center center, as shown in FIG. 42C (side view). A possible flap “valve” can be included which covers the blade access slots and forms a seal to stop suction. Finally, as shown in FIG. 42C, the syringe can be retracted and the sample can be withdrawn into a sample storage compartment disposed within the device.
[00327] The sampling devices (for example, the devices illustrated in FIGS. 40A-40D, FIGS. 41A-41B and FIGS. 42A-42C), may comprise a single blade or multiple blades for piercing the skin of a individual; for example, one or more, two or more, three or more, four or more, five or more or ten or more blades. The blades can be configured in different formats or orientations, for example, a ring shape, a star shape, a tic-tac-toe shape, square shapes, rectangular shapes etc.
[00328] The sampling devices (for example, the devices illustrated in FIGS. 40A-40D, FIGS. 41A-41B and FIGS. 42A-42C), can be configured to collect, process and store the sample. The sample taken by the device can be stored in liquid or solid form. The sample can be subjected to an optional treatment before being stored. Storage can take place on the device, outside the device or in a removable container, vessel, compartment or cartridge inside the device.
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114/134 [00329] Sampling devices (for example, the devices illustrated in FIGS. 40A-40D, FIGS. 41A-41B and FIGS. 42A-42C) can be configured to collect, treat, stabilize and store a collected sample. A device can be configured to perform one or more of the following processes: sample collection, treatment, stabilization and storage. Collection, treatment, stabilization and storage can be performed inside a single device. The treatment may comprise filtering the sample to separate the components or analytes of interest. In some cases, one or more of the processes (for example, sample collection, treatment, stabilization and storage) can be performed on the device in response to a single activation of the device by the user. In other cases, two or more actions by the user may be necessary to move the sample through one or more different processes (for example, collection, treatment, stabilization and storage). User actions may include pressing a single button, pressing multiple buttons, pressing two or more buttons at the same time, and pressing two or more buttons in a prescribed sequence (for example, based on a sequence prescribed for perform a set of treatment steps desired by the user).
[00330] Sample collection can comprise steps and components configured to lance the individual's skin and provide or create a vacuum or suction to extract the sample. In some cases, a vacuum or suction can be provided before lancing the skin, in other cases, a vacuum or suction can be provided after the procedure of lancing the individual's skin, in additional cases, the vacuum can be provided simultaneously with the lancing the individual's skin.
[00331] The treatment of the device may comprise the concentration of the sample, adjustment or measurement of the sample flow, exposure of the sample to one or more reagents and deposit of the sample on a solid substrate or solid matrix. The achievements of the device may comprise a removable cartridge or
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115/134 container for storing a liquid sample or solid matrix for removing the sample once it has been collected. A solid matrix may comprise cellulose-based paper (for example, Whatman ™ 903 paper), paper treated with chemical products or reagents for sample stabilization, or one or more of the sample components (for example, RNA stabilization matrix or Protein Stabilization Matrix).
[00332] FIG. 43B illustrates a device configured to apply global vacuum and local suction to collect a sample. Lancet blades can be used to pierce an individual's skin before applying the device to collect the sample. Lancets can comprise high flow or low flow. After the lancing procedure, a device is used to apply global vacuum and local suction to the cut site. The device, as shown in FIG. 43B, can comprise two nested components, an external element for the application of global vacuum in order to deform the skin and an internal element to provide local suction. Connected to the internal element is a tube with a luer-type adapter at its end, suction is provided through the adapter, allowing the sample to be taken into the collection tube. The suction provided by the luer adapter is used both to deform the skin and to extract the sample.
[00333] The method and device for collecting a blood sample, as illustrated in FIG. 43B are configured to collect a target volume of blood in less than 5 minutes. Examples of blood volumes and corresponding collection times for seven samples are shown in Table
1. The average volume of blood drawn was 245 µL +/- 12.2 µL over an average time of 1.9 minutes +/- 0.8 minutes. The average rate for blood collection was 127 uL per minute. Blood samples collected by methods and devices comprising global vacuum and local suction can cover a range above 50 µL per minute, above 75 µL per minute, above 100 µL per minute, above 125 µL per minute, above 150 uL per minute, above 175 uL per minute and above 200 uL per minute. Examples of pressure generated by
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116/134 global vacuum can include greater than 5 inHg, greater than 8 inHg, greater than 10 inHg, greater than 12 inHb, and any pressures or pressure ranges sufficient to pull the skin into the outer element chamber and create a vacuum overall skin in the tube.
[00334] Mechanisms that incorporate global vacuum and local suction can increase the sample collection rate in methods that do not have global vacuum and local suction. Table 1 below illustrates withdrawal times for a global vacuum and local suction device illustrated in FIG. 43B. Global vacuum and local suction can comprise any method or device configured to suck or deform skin in a larger cavity under negative pressure and draw blood samples from the sample surface. In mechanisms that are based on global vacuum and local suction there may be two or more contacts; for example the outer element (for example, the bell-shaped cup) and the inner element (for example, local internal suction cup). These nested elements can be configured in such a way that the proportion of the affected surface areas (for example, proportion generated by the surface area of the global vacuum area divided by the local suction area) are present in a particular proportion. The proportion can be configured to deform the skin and then break the site above the incision in order to facilitate sample removal.
Table 1: Time of withdrawal using the Blood Collection Method with Global Vacuum and Local Suction
Global Vacuum with 25 mm Cup and Suction Cup + Measuring Tube (2x | (2X Becton Dickinson (BD) High Flow Lancets) Withdrawal Volumes ofBlood (ul) Times ofWithdrawal(min)
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1 232 2.2 2 236 3.5 3 246 1.7 4 245 1.8 5 262 1.0 6 236 1.5 7 261 1.5 Average 245 1.9 Standard deviation 12.2 0.8 Average Withdrawal Rate 127
[00335] The devices illustrated in FIGs. 43A and 43B, and any sampling device described in the present application, may comprise a single blade or multiple blades for piercing an individual's skin; for example, one or more, two or more, three or more, four or more, five or more or ten or more blades. The blades can be configured in different formats or orientations, for example, a ring shape, a star shape, a tic-tac-toe shape, square shapes, rectangular shapes etc.
[00336] The devices illustrated in FIGs. 43A and 43B, and any sampling devices described in the present application, can be configured to collect, process and store the sample. The sample taken by the device can be stored in liquid or solid form. The sample can be subjected to an optional treatment before being stored. Storage can take place on the device, outside the device, or in a removable container, vase, compartment or cartridge inside the device.
[00337] The devices illustrated in FIGs. 43A and 43B, and any sampling devices described in the present application can be configured to collect, treat, stabilize and store a collected sample.
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A device can be configured to perform one or more of the following processes: sample collection, treatment, stabilization and storage. Collection, treatment, stabilization and storage can be performed inside a single device. The treatment may comprise filtration of the sample in order to separate components or analytes of interest.
[00338] In some cases, one or more of the processes (for example, collection, treatment, stabilization and storage of the sample) can be performed on the device in response to the single activation of the device by the user. In other cases, two or more actions by the user may need to be performed to move the sample through one or more different processes (for example, collection, treatment, stabilization and storage). User actions may include pressing a single button, pressing multiple buttons, pressing two or more buttons at the same time, and pressing two or more buttons in a prescribed sequence (for example, based on a sequence prescribed for performing a set of treatment steps desired by the user).
[00339] The device can be attached to a patient's skin with an adhesive. In some embodiments, any suitable adhesive is used. The adhesive can be a hydrogel, an acrylic, a polyurethane gel, a hydrocolloid or a silicone gel.
[00340] The adhesive can be a hydrogel. In some embodiments, the hydrogel comprises a synthetic polymer, a natural polymer, a derivative thereof or a combination thereof. Examples of synthetic polymers include, but are not limited to, poly (acrylic acid), poly (vinyl alcohol) (PVA), poly (vinyl pyrrolidone) (PVP), poly (ethylene glycol) (PEG), and polyacrylamide. Examples of natural polymers include, but are not limited to, alginate, cellulose, chitin, chitosan, dextran, hyaluronic acid, pectin, starch, xanthan gum, collagen, silk, keratin, elastin, resiline, gelatin and agar. The hydrogel can comprise a derivatized polyacrylamide polymer.
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119/134 [00341] In some embodiments, the sticker is attached to the device. The device may comprise a protective film or a backing covering the adhesive on the base of the device, where before using the film the protector is removed. In another embodiment, an adhesive in the form of a gel, a hydrogel, a paste or a cream is applied to the individual's skin or to the base of the device before in order to adhere the skin to the device. The patch can stay in contact with the patient for less than about 10 minutes. In some embodiments, the adhesive is a pressure sensitive adhesive. In some embodiments, the adhesive is hypoallergenic.
[00342] The collection of the sample can comprise steps and components configured to lance the skin of the individual and provide or create a vacuum to remove the sample. In some cases, a vacuum can be provided before the procedure for lancing the skin, in other cases, the vacuum can be provided after the procedure for lancing the skin of the individual, in additional cases, the vacuum can be provided simultaneously with the procedure for lancing the skin. lancing the individual's skin.
[00343] The treatment of the device may comprise the concentration of the sample, adjustment or measurement of the sample flow, exposure of the sample to one or more reagents and deposit of the sample on a solid substrate or solid matrix. Embodiments of the device may comprise a removable cartridge or container for storing a liquid sample or solid matrix for removing the sample once it has been collected. A solid matrix may comprise cellulose-based paper (for example, Whatman ™ 903 paper), paper treated with chemical products or reagents for sample stabilization, or one or more of the sample components (for example, RNA stabilization matrix or Protein Stabilization Matrix).
[00344] FIGS. 44A and 44B illustrate a device configured for horizontal cutting, with simultaneous sealing formation. The device may comprise a square-shaped external housing. A blade holder can be installed on a track and the blade can be arranged to
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120/134 move on a semicircular trail. When the actuator is pressed, the blade moves along the semicircular track, cutting an elastomeric material (for example, polyurethane) and creating a seal between an adhesive (for example, hydrogel) of material in the shape of a circle or thread arranged from the base of the device. In this realization, the activation of the trigger triggers the blade that cuts the elastomeric material forming a seal, while simultaneously lancing the individual's skin. FIG. 44A shows the blade before being activated and FIG. 44B shows the blade after cutting the elastomeric material and forming a seal with the individual's skin.
[00345] The devices illustrated in FIGs. 44A-44B, and any sampling devices described in the present application, may comprise a single blade or multiple blades for piercing an individual's skin; for example one or more, two or more, three or more, four or more, five or more or ten or more blades. The blades can be configured in different formats or orientations, for example, a ring shape, a star shape, a tic-tac-toe shape, square shapes, rectangular shapes etc.
[00346] The devices illustrated in FIGs. 44A-44B, and any sampling devices described in the present application, can be configured to collect, process and store the sample. The sample taken by the device can be stored in liquid or solid form. The sample can be subjected to an optional treatment before being stored. Storage can take place on the device, outside the device or in a removable container, vessel, compartment or cartridge inside the device.
[00347] The devices illustrated in FIGs. 44A-44B, and any sampling devices described in the present application can be configured to collect, treat, stabilize and store a collected sample. A device can be configured to perform one or more of the following processes: sample collection, treatment, stabilization and storage. Collection, treatment, stabilization and storage can be carried out within a single
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121/134 device. The treatment may include filtering the sample in order to separate components or analytes of interest.
[00348] In some cases, one or more of the processes (for example, collection, treatment, stabilization and storage of the sample) can be performed on the device in response to the single activation of the device by the user. In other cases, two or more actions by the user may be necessary to move the sample through one or more different processes (for example, collection, treatment, stabilization and storage). User actions may include pressing a single button, pressing multiple buttons, pressing two or more buttons at the same time, and pressing two or more buttons in a prescribed sequence (for example, based on a prescribed sequence for performing a set of treatment steps desired by the user).
[00349] Sample collection can comprise steps and components configured to lance the individual's skin and provide or create a vacuum to extract the sample. In some cases, a vacuum can be provided before the procedure for lancing the skin, in other cases, the vacuum can be provided after the procedure for lancing the skin of the individual, in additional cases, the vacuum can be provided simultaneously with the procedure for lancing the skin. lancing the individual's skin.
[00350] The treatment of the device may comprise the concentration of the sample, adjustment or measurement of the sample flow, exposure of the sample to one or more reagents and deposit of the sample on a solid substrate or solid matrix. Embodiments of the device may comprise a removable cartridge or container for storing a liquid sample or solid matrix for removing the sample once it has been collected. A solid matrix can comprise cellulose-based paper (for example, Whatman ™ 903 paper), paper treated with chemical products or reagents for sample stabilization, or one or more of the sample components (for example, RNA or DNA).
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122/134 [00351] Any of the embodiments described in the present application can comprise a vacuum chamber. The vacuum chambers can vary in size, shape, pressure and can have structural variations, as well as a variety of mechanisms for generating a vacuum. A vacuum chamber can be preloaded using an internal evacuated chamber (for example, a chamber installed in the device using a membrane that when penetrated generates negative pressure in the adjoining containers) or generated through a user action through a syringe or other means for generating negative pressure. The vacuum chamber (e.g., evacuated chamber) can seal one end with a sheet or elastomer (e.g., polyisoprene) at the other end, such that the perforation of the sheet or septum allows vacuum to be generated inside the device. The sizes of the vacuum chamber may vary, for example, the vacuum chamber may be larger than 2 ml, greater than 4 ml, greater than 6 ml, greater than 8 ml or greater than 10 ml in volume. An embodiment of a vacuum chamber is illustrated in FIGs. 45A-45C. FIGs. 45A and 45B illustrate a side view of a vacuum chamber that can be used in the described devices. The vacuum chamber may comprise a Polyisoprene septum with a needle connected to a small diameter tube to apply the vacuum. The chamber can also comprise, on the opposite side, a luer-type adapter, such that a syringe can be connected by means of a check valve in order to create a vacuum. The vacuum chamber may comprise an opening, a vacuum chamber cover and one or more threaded holes to hold the cover in place. FIG. 45C shows a side view of a vacuum chamber, as well as an enlarged view of the assemblies that hold the septum in place and illustration of the type of needles that can be used with the vacuum chamber.
[00352] Once the device has lanced the skin of an individual and the blood sample has been drawn into the device, the sample can be optionally treated and then stored in a matrix. Sample storage and treatment methods may comprise treating the sample in such a way that
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123/134 fix the volume, uniformity or concentration of the sample deposited in the sample collection matrix. The methods and devices for collecting and storing sample in the matrix may comprise a cartridge or compartment that can be removed from the device. A typical cartridge or compartment for depositing and storing the collected sample is illustrated in FIGs. 46A-46C.
[00353] FIG. 46A, FIG. 46B and FIG. 46C illustrate a sample collection matrix for sample collection and storage in a stabilization matrix. As shown in FIG. 46A, the sample collection matrix may comprise an inlet through which the blood sample is drawn into a channel inside the device that allows blood to flow along the bottom of the solid matrix. A vacuum withdrawal is present on the other side of the device to withdraw the sample into the solid matrix. The sample collection housing may comprise an upper housing and a lower housing (as shown in FIGS. 46B and 46C) with the matrix and channel displacing the sample within the housing, disposed between the upper and lower housing. A tongue and groove feature can create a seal between the upper and lower housing.
[00354] FIG. 47 illustrates components of a device or kit for collecting a sample from an individual. The kit may comprise a sample collection device, a removable cartridge carrying sleeve with desiccant (with or without a barcode or label), a removable blood storage matrix cartridge, blood storage matrix tapes and a cartridge carrying bag.
[00355] FIG. 48 illustrates methods by which a user can obtain a sample using the kit. The kit can be obtained and the user can insert the cartridge into the device. The steps performed by the user can understand the use of the device to collect a sample, remove the cartridge once the sample collection is complete, place the removable cartridge in the transport sleeve with desiccant and place it in the cartridge transport bag.
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Multiple samples can be taken by the user and then the user can send the sample (s) to a facility for analysis.
[00356] FIG. 49 illustrates steps in a typical method that a laboratory can perform when receiving a shipping container containing the sample (s). The sample bag can be removed from the shipping container, the sample cartridge can be removed from the sample bag and the pull tab can then be removed from the cartridge. Matrix # 1 can be removed from the cartridge and placed in an extraction tube, then matrix # 2 can be removed from the cartridge and placed in an extraction tube. The extraction tube where matrix # 2 is placed may be an extraction tube different from the extraction tube where matrix # 1 is placed. The extraction tube where the matrix # 2 is placed can be the same as the extraction tube of the extraction tube where the matrix # 1 is placed. The extraction tube can be a micro centrifuge tube. From there any number of tests or analyzes can be performed on the sample.
[00357] The devices, systems and methods described here can stabilize the sample in a matrix (for example, blood storage matrix, sample collection matrix, matrix, sample stabilization matrix, stabilization matrix (for example, matrix stabilization matrix, protein stabilization matrix), solid matrix, solid substrate, solid support matrix or solid support). The matrix can be integrated into the device or external to the device. In some embodiments, the matrix can be incorporated into a cartridge for removal (for example, after sampling). In some embodiments, the matrix may comprise a flat dimensional matrix that is at least 176 mm ² . A matrix can be prepared according to the methods of US patent No. 9,040,675, US patent No. 9,040,679, US patent No. 9,044,738 or US patent No. 9,480,966 which are all incorporated herein by reference. in its entirety.
[00358] In some embodiments, a system, method or device may comprise a matrix of high surface area that selectively stabilizes nucleic acids or proteins. In some cases, the matrix can be
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125/134 configured to comprise a flat sheet with a total dimensional area (length multiplied by width) greater than 176 mm ² .
[00359] The matrix can be configured to selectively stabilize sample preparation reagents comprising protein and / or nucleic acids. The matrix that can be configured to stabilize protein and nucleic acids can comprise an oligosaccharide (for example, a trisaccharide) in a substantially dry state. The oligosaccharide or trisaccharide can be selected from the group comprising: melezitosis, raffinose, maltotriulose, isomaltotriose, nigerotriose, maltotriose, ketosis, cyclodextrin, trehalose or combinations thereof. In some embodiments, the matrix may comprise melezitosis. In additional embodiments, the melezitosis may be in a substantially dry state. In some embodiments, melezitosis in a substantially dry state may have less than 2% water content. In the matrix, the concentration of melezitosis can be in the range of about 10% to about 30% by weight by mass (for example, calculated as the mass of the solute divided by the mass of solution comprising both the solute and the solvent together) . The concentration of melezitosis can be 15% by weight by mass. Melezitosis can be impregnated in the matrix. In some embodiments, the concentration of melezitosis impregnated in the matrix results from immersing the matrix in a melezitosis solution comprising between about 10 to about 30%. In some other embodiments, 15% of melezitosis is impregnated in the matrix in a dry state. The matrix can be passively coated or covalently modified with melezitosis. In other embodiments, melezitosis can be applied to the matrix surface (for example, by dipping, spraying, brushing, etc.). In some other embodiments, the matrix can be coated with a 15% melezitosis solution. In some embodiments, the matrix may comprise a flat dimensional matrix with a surface area that is at least 176 mm ² . In some embodiments, melezitosis may be present at more than 0.01 ng / mm ² , more than 0.05 ng / mm ² , more than 0.1 ng / mm ² , more than 0.5 ng / mm ² , more than 1 ng / mm ² , more than 5 ng / mm ² , more than 0.01 pg / mm ² , more than 0.05 pg / mm ² , more than
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0.1 pg / mm ² , more than 1 pg / mm ² , more than 5 pg / mm ² , more than 0.01 mg / mm ² , more than 0.05 mg / mm ² , more than 0.1 mg / mm ² , more than 1 mg / mm ² , more than 5 mg / mm ² , more than 10 mg / mm ² , more than 50 mg / mm ² , more than 1 g / mm ² , more than 5 g / mm ² or more than 10 g / mm ² . The matrix may comprise additional components to stabilize protein and / or nucleic acids, including various stabilizing molecules. A non-limiting example of a stabilizing molecule is validamycin. In some embodiments, the matrix may comprise 31-ETF (for example, cellulose-based matrix) and melezitosis.
[00360] The matrix can comprise a buffer reagent. A buffer reagent can be impregnated in the matrix. Buffers can stabilize sample preparation reagents and / or various sample components. The matrix can additionally include at least one buffer disposed or impregnated within the matrix, where the matrix can be substantially dried with a water content of less than 2%. The buffer can be a metered buffer reagent for acid that generates a pH in the range of about 3 to about 6, or about 2 to about 7. The matrix can contain any of the following: 2-Amino-2- hydroxymethylpropane-1,3-diol (Tris), 2- (N-morpholino) sulfonic acid (MES), 3 (N-morpholino) proponic sulfonic acid (MOPS), citrate buffers, 4- (2hydroxyethyl) -l- acid piperazinoethanesulfonic (HEPES), phosphate buffers or combinations thereof, or Tris-Hydrochloride (TrisHCl). The matrix can be configured to produce a solution by rehydration comprising about 20 to about 70 mM Tris-HCl and about 5 to about 30 mM MgCE. The amount of various dehydrated buffer reagents impregnated in a matrix can be configured to stabilize the sample preparation reagent (s).
[00361] The matrix can comprise a reagent or compound that minimizes nuclease activity, for example, a nuclease inhibitor. Examples of nuclease inhibitors include RNase inhibitors, compounds capable of altering pH such as acids or bases such as HCl, NaOH, HNO3, KOH, H2SO4, or combinations thereof; denaturants including urea, guanidine hydrochloride, guanidinium thiocyanate, a thiocyanate metal salt other than thiocyanate
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127/134 guanidinium (GuSCN), beta-mercaptoethanol, dithiothreitol; inorganic salts including lithium bromide, potassium thiocyanate, sodium iodide or detergents including sodium dodecyl sulfate (SDS).
[00362] The matrix may comprise a reagent or compound that minimizes or inhibits protease activity, for example, a protease inhibitor. A protease inhibitor can be synthetic or naturally occurring (for example, a naturally occurring peptide or protein). Examples of protease inhibitors include aprotinin, bestatin, chemostatin, leupeptin, alpha-2-macroglobulin, pepstatin, phenylmethanesulfonyl fluoride, N-ethylmaleimide, ethylenediaminetetraacetide, antithrombin or combinations thereof. In one example, protease inhibitors increase protein stability by inhibiting proteases or peptidases in a sample.
[00363] The matrix can comprise one or more free radical scavengers. The matrix may comprise a UV protector or a free radical trap. Typical UV protectors include hydroquinone monomethyl ether (MEHQ), hydroquinone (HQ), toluhydroquinone (THQ), and ascorbic acid. In some ways, the free radical trap may be MEHQ. The matrix may also comprise oxygen scavengers, for example, ferrous carbonate and metal halides. Other oxygen scavengers may include ascorbate, sodium hydrogen carbonate and citrus.
[00364] The matrix can comprise a cell lysis reagent. Cell lysis reagents can include guanidinium thiocyanate, guanidinium hydrochloride, sodium thiocyanate, potassium thiocyanate, arginine, sodium dodecyl sulfate (SDS), urea or a combination thereof. Cell lysis reagents can include detergents, where typical detergents can be categorized as ionic detergents, non-ionic detergents or zwitterionic detergents. Ionic detergents can comprise anionic detergent such as sodium dodecyl sulfate (SDS) or cationic detergent such as ethyl trimethyl ammonium bromide. Examples of non-ionic detergent for cell lysis include TritonX-100, NP-40, Brij 35, Tween 20, Octy glycoside, Octy thioglycoside or
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128/134 digitonin. Some zwitterionic detergents may comprise 3 - [(3Colamidopropyl) dimethylammonium] -l-propanesulfonate (CHAPS) and 3 - [(3Colamidopropyl) dimethylammonium] -2-hydroxy-1-propanesulfonate (CHAPSO). The cell lysis reagent can comprise a thiocyanate salt. One or more embodiments of the solid support matrix comprise a thiocyanate salt impregnated in a dry state. Typical thiocyanate salts include, but are not limited to, guanidinium thiocyanate, sodium thiocyanate, potassium thiocyanate or combinations thereof. In some other embodiments, the cell lysis reagent is selected from guanidinium thiocyanate, sodium thiocyanate, sodium dodecyl sulfate (SDS) or combinations thereof.
[00365] A solid support matrix can comprise a reducing agent. Reducing agents can include dithiothreitol (DTT), 2-mercaptoethanol (2-ME), tris (2-carboxyethyl) phosphine (TCEP) and combinations thereof. The reducing agents may additionally comprise oxygen scavengers. Oxygen scavengers or reducing agents may comprise ferrous carbonate and metal halides. A solid support matrix can comprise a chelating agent. Chelating agents can include ethylene diaminetetraacetic acid (EDTA), citric acid, ethylene glycol tetracetic acid (EGTA), or combinations thereof. The solid support matrix can be configured to provide an acidic pH by hydrating and / or preserving nucleic acids in a substantially dry state at room temperature. The solid support matrix can be configured to provide a pH between about 2 and about 7 per hydration. The solid matrix can be configured to provide a pH between about 3 and about 6 per hydration.
[00366] In some embodiments, a sample can be filtered or separated before being deposited in a matrix. The liquid sample can be collected or collected in a collection chamber, after the collection chamber or in place of a collection chamber the sample can optionally be absorbed by means of one or more particles, materials, structures or filters with porosity and capacity absorption points optimized to take the sample to the device. Sampling materials for the devices here can consist of any
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129/134 absorbent or adsorbent surfaces, or materials with modified surfaces; optional materials including, but not limited to, paper-based media, gels, spheres, membranes, matrices including polymer-based matrices, or any combination thereof.
[00367] In some embodiments, the device or cartridge may comprise a sample separation unit comprising one or more substrates, membranes or filters for the separation of the sample components. The sample separation unit can be integrated into the sample stabilization component, or it can be attached to or separated from the sample stabilization component. In some embodiments, sample separation may occur at an intermediate stage between obtaining the sample and transferring the sample to the matrix. In some cases, the sample can be separated and stabilized in one step without the need for intervention by the user. Sample separation can additionally occur sequentially or simultaneously with sample stabilization.
[00368] In some embodiments, obtaining and stabilizing the sample may require action by the user to proceed between one or more phases of the sample collection, optional separation and stabilization process. A device may require action by the user to activate sample acquisition and move the sample between separation, stabilization and storage. Alternatively, user action may be required to start obtaining a sample, as well as one or more additional steps of sample collection, separation or stabilization process. The user's action can include any number of actions, including pressing a button, puncture, agitation, rupture of internal parts, turn or rotate the device components, force the sample through one or more chambers and any number of other mechanisms . Movement through the phases can occur in tandem with sample collection, or it can occur after sample collection. At any time during or before the processing phases the sample as a whole or sample components can be exposed to any number of techniques or
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130/134 treatment strategies for pre-treatment of cells of biological components of the sample; potential treatment includes, but is not limited to, treatment with reagents, detergents, evaporation techniques, mechanical stress or any combination of these.
[00369] In some embodiments, the devices described here are configured to draw capillary blood.
[00370] In some embodiments, the devices described here are designed to be used once and then discarded. Re-sterilization or reuse can compromise the structural integrity of the device or increase the risk of contamination or infection leading to device failure, cross-infection, or patient injury, illness or death.
[00371] FIG. 53 and FIG. 56 illustrate typical blood collection and storage procedures using a device described here.
[00372] In certain embodiments, kits for use with one or more of the methods described here are described here. A kit may include the blood sample collection device described here. The kit may comprise a sample pouch or carrying sleeve, where the pouch or sleeve is used to store a cartridge comprising at least one solid matrix tape. A desiccant can be added to the bag or glove. In some embodiments, the desiccant is a silica gel desiccant. The kit may additionally comprise a sample return envelope, a bandage, an alcohol pad, a gauze pad or a combination thereof.
[00373] A kit can include labels listing the content and / or instructions for use and packaging inserts with instructions for use. A set of instructions can be included.
[00374] In one embodiment, a label is on or is associated with a bag or glove. In one embodiment, a label stays in a bag or glove when letters, numbers or other characters forming the label are attached, molded or engraved on the bag or glove itself; a label can be associated with a bag or glove when it is present inside a receptacle or carrier that also
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131/134 keeps the pouch or glove, for example, as a package insert. The label can indicate directions for the use of the contents, as in the methods described here.
[00375] The devices, methods, systems and kits described here may comprise one or more sample separation units. Sample separation units can be used, for example, to separate blood plasma, cells from an aqueous sample, or cells from cell-free components. The solid matrix can be used to store nucleic acids in circulation or free of cells (for example, DNA or RNA) separated from a sample, for example, a blood sample, after filtration. Circulating DNA can be circulating tumor DNA. For blood samples, one or more components can be used to separate plasma or specific cells from other components of a blood sample. Alternatively, devices, methods and systems can selectively separate any number of sample components including cells, plasma, platelets, specific cell types, DNA, RNA, protein, inorganic materials, drugs or any other components.
[00376] Non-limiting embodiments of the sample stabilization unit may employ sample separation components in order to separate also other non-plasma components. The sample separation components can be connected to the sample taking component, for example, through channels, including microchannels, passage of absorbent materials or other means that allow the sample to flow through the device. The systems and methods for separating the sample are exemplary and not limiting.
[00377] There are many methods to perform the separation, some of which use size, deformation capacity, shape or any combination of these. The separation can take place by means of one or more membranes, chambers, filters, polymers, or other materials. Membranes, substrates, filters and other components of the device can be chemically treated to stabilize
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132/134 selectively components, facilitate sample flow, dry the sample or any combination of these. Alternative separation mechanisms may include liquid-liquid extraction, solid-liquid extraction and selective precipitation of the target or non-target elements, separation by charge, binding affinity or any combination thereof. Phase separation can be comprised of one or more steps, with each step being based on different mechanisms for separating the sample. Such a mechanism can use size, shape or deformation to separate larger components from smaller ones. Cell separation can take place through a classifier that can, for example, be based on one or more filters or other size exclusion methods to separate the sample components. The separation can also be conducted by means of selective bonding where specific components are separated by bonding events while the unbound eluent travels to or through alternating chambers.
[00378] In some devices, systems, methods or kits, a membrane, substrate, or single filter can be used for the separation and collection of one or more sample components from the complete sample. Membrane, substrate or single filter methods may comprise a device where samples can be applied to one end of the membrane, substrate or filter and as the sample flows, a first component of the sample, for example, cells, can be separated from a second component of the sample, for example, plasma, based on the pore size of the membrane, substrate or filter. After operation of the device, the membrane, substrate or filter containing the first component of the sample, cells in this example, can be separated from the part containing the second component of the sample, plasma in this example, requiring an additional step to separate the membranes, substrates or filters. In another method, two separate membranes, substrates or filters can be used for the separation and collection of the sample components; specifically, a first membrane, substrate, or filter for the separation of a component, for example, blood cells and a second membrane, substrate or filter for
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133/134 the collection of other components, for example, plasma. These membranes, substrates or filters can be arranged in such a way that a distal end of the first membrane, substrate or filter contacts a proximal end of the second membrane in order to facilitate the separation of a large component, for example, cells, for example. through the first membrane, substrate or filter and the collection of a second smaller component, for example, plasma, through the second membrane, substrate or filter.
[00379] Generally, a sample may contain or is suspected of containing one or more analytes. The term "analyte" as used here can refer to any substance that can be analyzed using assay devices or immunoassays. As an example, an immunoassay device can be configured to detect the presence of 1,2, 3, 4, 5, 6, 7, 8, 9, 10 or more analytes in a sample. Non-limiting examples of analytes may include proteins, haptens, immunoglobulins, hormones, polynucleotides, steroids, drugs, infectious disease agents (e.g., of bacterial or viral origin), drugs of abuse, environmental agents, biological markers and the like.
[00380] As used in the report and in the claims, the singular forms "one", "one" and "o / a" include references in the plural unless the context clearly indicates otherwise. For example, the term "a cell" includes a plurality of cells, including mixtures of these.
[00381] As used here, the term “about” a number refers to this number more or less 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2 %, 1%, of this number.
[00382] Although the preferred embodiments of the invention have been shown and described here, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes and substitutions will occur to those skilled in the art without departing from the invention. It is to be understood that various alternatives to the embodiments of the invention described herein can be employed in the practice of the invention. The following claims are intended
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134/134 define the scope of the invention and that the methods and structures within the scope of these claims and their equivalents are covered by them.

权利要求:
Claims (189)
[1]
1. A user-activated portable device or device is as in any of the claims here, in which the device or device is configured or capable of collecting at least 150 uL of blood from an individual in less than 3 minutes starting at moment of incision or penetration of a part of the individual's skin.
[2]
2. Device for collecting fluid sample from an individual, in which a recess and a pre-vacuum chamber is evacuated located inside the device, where the recess is configured to maintain contact with at least 5.0 cm ² of a surface area of the individual's skin under vacuum pressure, before and according to the fluid sample being collected from the individual's skin.
[3]
3. Device for collecting fluid sample from an individual in which: a housing comprising a recess with an opening;
a vacuum chamber in the housing in fluid communication with the recess, and one or more perforating elements that are extensible through the opening to penetrate the individual's skin, where the vacuum chamber is configured to present a vacuum that places the skin in the recess, and the recess is configured with a size or shape that allows an increased volume of the fluid sample to accumulate on the skin placed in the recess.
[4]
4. M is all for collecting a fluid sample from an individual, in which:
providing a device having a housing, said housing configured to support a vacuum chamber and a drilling module, the housing comprising a recess having an opening;
the placement of the housing recess adjacent to the individual's skin;
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2/23 activation of the vacuum in the vacuum chamber to place the skin in the recess;
the accumulation of an increased volume of the fluid sample on the skin placed in the recess, where the recess is configured to present a size or shape that allows the increased volume of the fluid sample to be accumulated;
extending one or more piercing elements through the opening to penetrate the skin; and maintaining the device adjacent to the skin for an amount of time sufficient to place the fluid sample in the device.
[5]
A device according to claim 3, in which the fluid sample comprises blood from the subject.
[6]
A device according to claim 3, in which the recess functions as a suction cavity to position the skin and increase the capillary pressure differential.
[7]
Device according to claim 3, in which the increased volume of the fluid sample depends on a volume and / or surface area of the skin that is positioned in the recess.
[8]
Device according to claim 7, in which the volume of skin within the recess varies from about 0.4 cm ³ to about 4.0 cm ³ .
[9]
Device according to claim 7, in which the surface area of the skin in contact with the recess varies from about 3.2 cm ² to about 7.2 cm ² .
[10]
A device according to claim 3, in which the increased volume of the fluid sample depends on a vacuum pressure in the vacuum chamber.
[11]
Device according to claim 10, in which the vacuum pressure in the vacuum chamber varies from about -4 psig to about -15 psig.
[12]
Device according to claim 3, in which the increased volume of the fluid sample on the skin placed in the recess is at least about 50 pL before penetration of the skin.
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3/23
[13]
Device according to claim 3, in which the increased volume of the fluid sample in the skin placed in the recess, of an increased capillary pressure and with the aid of a vacuum, allow the fluid sample to be removed from the skin and collected at a daily flow rate m of at least 30 pL / min.
[14]
Device according to claim 13, in which the fluid sample is collected at one at a daily flow rate of at least 100 pL / min.
[15]
A device according to claim 13, in which the fluid sample is collected at a daily flow rate of at least 150 pL / min.
[16]
A device according to any one of claims 13-15, in which the flow rate m / day is sustained at least until about 150300 pL of the fluid sample has been collected.
[17]
Device according to claim 3, in which the size and / or shape of the recess are configured in such a way as to allow the skin to substantially conform to the recess.
[18]
A device according to claim 17, in which a space between the skin and the recess is negligible when the skin is positioned in the recess.
[19]
A device according to claim 17, in which a surface of the recess is substantially in contact with the skin positioned in the recess.
[20]
A device according to claim 3, in which a size of the recess is at least twice the size of the opening inside the recess.
[21]
A device according to claim 20, in which the size of the opening in the recess varies from about 1.5 mm to about 6 mm, and the size of the recess in its outermost periphery ranges from about 10 mm to about 60 mm.
[22]
22. The device of claim 3, wherein a surface area of the recess is substantially larger than an area of the opening.
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4/23
[23]
23. The device of claim 22, wherein the surface area of the recess is at least ten times the area of the opening.
[24]
24. The device of claim 22, wherein the surface area of the recess varies from about 75 mm ² to about 2900 mm ² , and the opening area varies from about 1.5 mm ² to about 30 mm ² .
[25]
25. The device of claim 3, wherein an area of the skin directly under the opening is at least 1.5 times smaller than a total area of the skin positioned in the recess.
[26]
26. The device of claim 25, wherein the area of the skin directly under the opening is at least 5 times smaller than the total area of the skin positioned in the recess.
[27]
27. The device of claim 3, wherein the recess comprises a concave cavity.
[28]
28. The device of claim 27, wherein the concave cavity has a volume ranging from about 1.0 cm ³ to about 5.0 cm.
[29]
29. The device of claim 3, wherein the recess is in the form of a spherical hood.
[30]
Device according to claim 29, in which a base diameter of the spherical cap is varied from about 10 mm to about 60 mm.
[31]
31. The device of claim 29, wherein the height of the spherical cap varies from about 3 mm to about 30 mm.
[32]
32. The device of claim 29, wherein the spherical cap is a hemisphere.
[33]
33. The device of claim 29, wherein the opening is at an apex of the spherical cap-shaped recess is rich.
[34]
34. The device of claim 3, wherein the recess comprises one or more fillets configured to increase the suction of the vacuum to the skin and to reduce vacuum leakage.
[35]
35. The device of claim 34, wherein the thread extends continuously along a periphery of the recess.
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5/23
[36]
36. The device of claim 34, wherein the fillet of the recess is configured to be in contact with the skin when the skin is positioned in the recess.
[37]
37. The device of claim 3, wherein a vacuum pressure of at least about -1 psig is provided in order to position the skin in the recess and fill it completely.
[38]
38. Device according to claim 3, in which the skin is positioned in the recess by vacuum and completely fills the recess in less than 1 second.
[39]
39. Device according to claim 3, in which the skin is positioned in the recess by vacuum and completely fills the recess in no more than 5 seconds.
[40]
40. Device according to claim 3, in which (1) the size or shape of the recess or (2) a vacuum pressure are configured to obtain a minimum capillary pressure in the skin positioned in the recess.
[41]
41. The device according to claim 3, in which (1) the size or shape of the recess or (2) a vacuum pressure is configured to obtain a minimum tension on the skin positioned in the recess.
[42]
42. The device of claim 3, in which it is supported and held in place on the subject's skin with the aid of an adhesive.
[43]
43. The device of claim 3, in which it is supported and held in place on the subject's skin with the aid of a vacuum.
[44]
44. Device according to claim 3, in which it is configured for use on an individual's upper arm.
[45]
45. The device of claim 44, in which it is configured to remain in position on the subject's arm regardless of any movement or changes in the subject's arm orientation.
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[46]
46. Device according to claim 3, in which it is able to collect 250 µL of fluid sample from the individual in less than 1 minute 45 seconds.
[47]
47. Device according to claim 3, in which it is able to collect at least 175 µL to 300 µL of fluid sample from the subject in less than 3 minutes.
[48]
48. Device according to claim 3, in which it is able to collect at least 200 µL of fluid sample from the individual in less than 5 minutes.
[49]
49. Device according to claim 3, in which it is configured to collect the fluid sample at a rate that is dependent on the size or shape of the recess and / or the vacuum pressure.
[50]
50. Device according to claim 3, in which the recess is configured having a size and shape that allows an increased volume of the fluid sample to accumulate on the skin positioned in the recess.
[51]
51. M is all according to claim 4, in which the recess is configured having a size and shape that allow the increased volume of fluid sample to be accumulated.
[52]
52. Device according to claim 3, in which (1) the size and shape of the recess and (2) a vacuum pressure are configured to obtain a minimum capillary pressure in the skin positioned in the recess.
[53]
53. Device according to claim 3, in which (1) the size and shape of the recess and (2) a vacuum pressure are configured to obtain a minimum tension in the skin positioned in the recess.
[54]
54. Device according to claim 3, in which it is configured to collect the fluid sample at a rate that is dependent on the size and shape of the recess.
Petition 870190064472, of 07/09/2019, p. 16/54
7/23
[55]
55. Device according to claim 42, in which it is supported and held in place on the subject's skin mainly with the aid of a vacuum.
[56]
56. Device for collecting a fluid sample from an individual, in which:
an accommodation comprising:
a piercing activator configured to activate one or more skin piercing elements; and a vacuum activator separate from the drilling activator and configured to activate an evacuated vacuum chamber prior to activation of one or more piercing elements by the drilling activator.
[57]
57. M is all for collecting a fluid sample from an individual, in which:
placing a packaged device with an evacuated vacuum chamber and one or more piercing elements in the individual's skin area;
the activation of the evacuated vacuum chamber to effect a vacuum pressure in the skin area;
perforation of the skin area after activation of the vacuum; and maintaining vacuum pressure during and after penetration of the individual's skin area, in order to place the skin fluid sample in the device.
[58]
58. The device of claim 56, wherein the drilling activator and the vacuum activator are two separate components.
[59]
59. The device of claim 58, in which the vacuum activator comprises a first entry interface into the housing, and the drilling activator comprises a second entrance interface into the housing.
[60]
60. The device of claim 59, wherein at least one of the first input interface or the second input interface comprises a button.
Petition 870190064472, of 07/09/2019, p. 17/54
8/23
[61]
61. The device of claim 58, wherein the vacuum activator comprises a first inlet interface and the drilling activator comprises a second inlet interface, and where at least one enters the first inlet interface or the second inlet interface. entry is remote to the accommodation.
[62]
62. The device of claim 56, wherein the perforation activator is configured to activate the one or more perforating elements after the skin is positioned in the recess.
[63]
63. The device of claim 56, wherein the perforation activator is configured to activate the one or more perforating elements after the skin is positioned in the recess by the vacuum for a predetermined period of time.
[64]
64. The device of claim 63, wherein the predetermined period of time varies from about 1 second to about 60 seconds.
[65]
65. The device of claim 56, wherein the housing comprises the vacuum chamber pr is evacuated, and the vacuum activator is configured to activate the vacuum in the vacuum chamber pr is evacuated.
[66]
66. The device of claim 56, in which the perforation activator is configured to activate the one or more perforating elements only after the vacuum has been activated.
[67]
67. The device according to claim 56, in which the perforation activator is locked and unable to activate the one or more perforating elements before activating the vacuum.
[68]
68. The device of claim 67, wherein the drilling activator comprises a locking mechanism coupled to the vacuum activator.
[69]
69. The device of claim 68, wherein the locking mechanism is configured in such a way that the drilling activator is initially in a locked state.
Petition 870190064472, of 07/09/2019, p. 18/54
9/23
[70]
70. The device of claim 69, wherein the vacuum activator functions as a key to unlock the drilling activator, and the drilling activator is simultaneously unlocked when the vacuum activator is activated.
[71]
71. The device according to claim 56, in which the vacuum activator is configured to activate the vacuum by establishing fluid communication with the pre-evacuated vacuum chamber.
[72]
72. The device of claim 71, wherein the vacuum activator is configured to pierce a foil seal or open a valve to establish fluid communication with the pre-evacuated vacuum chamber.
[73]
73. The device of claim 56, wherein the vacuum activator is located in the housing in such a way that the vacuum activator is configured to be pressed in a first direction, and the drilling activator is located in the housing in such a way that the drill trigger is configured for is pressed in a second direction.
[74]
74. The device of claim 73, wherein the first and second directions are substantially the same.
[75]
75. The device of claim 73, wherein the first and second directions are substantially different.
[76]
76. The device of claim 73, wherein the first and second directions are substantially parallel to each other.
[77]
77. The device of claim 73, wherein at least one of the first or second directions does not extend to the subject's skin.
[78]
78. The device of claim 77, wherein the second direction does not extend to the subject's skin.
[79]
79. The device of claim 73, wherein at least one between the first direction or the second direction extends substantially parallel to the subject's skin.
Petition 870190064472, of 07/09/2019, p. 19/54
10/23
[80]
80. The device of claim 79, wherein the first direction and the second direction both extend substantially parallel to the subject's skin.
[81]
81. The device of claim 73, wherein at least one between the first direction or the second direction extends in one direction of the gravitational force.
[82]
82. Device according to claim 81, in which the first direction and the second direction both extend in the direction of the gravitational force.
[83]
83. The device of claim 56, in which the drilling activator and the vacuum activator are located on the same side of the housing, and are ergonomically accessible to the individual when the device is mounted on an individual's arm.
[84]
84. The device of claim 83, in which the drilling activator is located in a housing cover, and the vacuum activator is located in a housing base where the vacuum chamber is located.
[85]
85. Device according to claim 56, in which the drilling activator and the vacuum activator are located on different sides of the housing, and are ergonomically accessible to the individual when the device is mounted on an individual's arm.
[86]
86. M is all for collecting a fluid sample from an individual, in which:
with the aid of a fluid collection device:
perforation of the individual's skin and placement of the individual's fluid sample in a matrix disposed inside a fluid collection device deposit chamber, where the placement of the fluid sample is aided or increased using (1) force gravitational, (2) vacuum force, (3) a pressure difference between the capillary pressure and the internal pressure of the device, and (4) drainage behavior of the fluid sample together with the matrix.
Petition 870190064472, of 07/09/2019, p. 20/54
11/23
[87]
87. Device for collecting a sample of fluid from an individual's skin and placing the sample in a deposit chamber, in which the flow of fluid from the skin to a matrix in the deposit chamber is preferably increased by (1) gravitational force , (2) vacuum force, (3) a pressure differential between the capillary pressure and the internal pressure of the device, and (4) drainage behavior of the fluid sample together with the matrix.
[88]
88. The device of claim 87, comprising: a container for containing one or more piercing elements, in which the container is in fluid communication with the deposit chamber.
[89]
89. Device according to claim 88, in which the deposit and container chamber are initially at ambient pressure, before the activation of a vacuum from a pre-vacuum chamber is evacuated located in the device.
[90]
90. Device according to claim 89, in which the deposit chamber, the vacuum chamber, and the container are configured to be equalized to an internal pressure that is less than the ambient pressure after the vacuum has been activated.
[91]
91. The device of claim 90, wherein the internal pressure is higher than the initial vacuum pressure of the evacuated vacuum chamber.
[92]
92. The device of claim 91, wherein the internal pressure is about -5.5 psig, and the vacuum seal pressure is about -12 psig.
[93]
93. The device of claim 90, wherein the internal pressure is configured to position the skin in a recess of the housing.
[94]
94. The device of claim 93, in which the internal pressure is configured to draw blood from capillary beds to the skin being positioned in the recess.
Petition 870190064472, of 07/09/2019, p. 21/54
12/23
[95]
95. The device of claim 94, wherein a differential pressure is created between the capillary pressure and the internal pressure when the skin is penetrated by one or more perforating elements of the device.
[96]
96. Device according to claim 95, in which the internal pressure increases as the fluid sample is withdrawn from the skin towards the deposit chamber and the container.
[97]
97. The device of claim 96, wherein the internal pressure in the container increases more rapidly compared to an internal collection pressure of the deposit chamber and the vacuum chamber.
[98]
98. The device of claim 96, wherein the internal pressure in the container increases substantially more than the internal collection pressure of the deposit chamber and the vacuum chamber.
[99]
99. Device according to claims 97 and 98, in which the substantially increased internal pressure of the container inhibits the flow of the fluid sample into the container.
[100]
100. Device according to claims 97 and 98, in which the substantially increased internal pressure of the container results in a preferential flow of the fluid sample towards the deposit chamber instead of towards the container.
[101]
101. Device according to claims 97 and 98, in which the substantially increased internal pressure of the container causes the flow of the fluid sample to the container to be slow or interrupted, while the fluid sample continues to flow towards the chamber deposits under the influence of the pressure differential.
[102]
102. Device according to claims 97 and 98, in which (1) a volume of the container and (2) a volume collected from the deposit chamber and the vacuum chamber are configured in such a way that minimum quantities of the fluid sample flow towards and into the container.
[103]
103. The device of claim 102, wherein a ratio of the volume of the container to the volume collected from the deposit chamber and the vacuum chamber varies from about 1: 5 to about 1:15.
Petition 870190064472, of 07/09/2019, p. 22/54
13/23
[104]
104. Device according to claim 95, in which the one or more piercing elements are configured to penetrate the skin in order to generate cuts, and the pressure differential can allow deeper cuts and the cuts can be kept open under tension.
[105]
105. Device according to claim 104, in which the pressure differential is configured to increase the size of the cuts so as to enable a higher flow rate and volume of the fluid sample to be collected from the skin.
[106]
106. Device to penetrate an individual's skin, in which:
one or more piercing elements supported by a mobile piercing cable by two or more spring elements;
an implantation spring positioned to implant the one or more piercing elements through an opening in the device; and a retraction spring positioned to retract the one or more piercing elements back to the device, where a length of the one or more piercing elements is less than about 20 mm, and the depth of penetration of the one or more piercing elements is about 2 mm.
[107]
107. M is all for penetrating the skin of an individual, in which:
providing the device as defined in claim 1;
positioning the individual's skin in a recess of the device;
activating the implantation spring and implantation of one or more perforating elements through the opening in the device;
penetration of the individual's skin using one or more perforating elements; and using the retraction spring to retract the one or more spring elements back to the device.
[108]
108. The device of claim 106, wherein two or more piercing elements are supported by a cable in a random configuration.
Petition 870190064472, of 07/09/2019, p. 23/54
14/23
[109]
109. Device according to claim 108, in which the two or more piercing elements have random orientations in relation to each other.
[110]
110. Device according to claim 109, in which the two or more piercing elements comprise beveled edges which are randomly oriented with respect to each other.
[111]
111. The device according to claim 110, in which the chamfered edges of the two or more piercing elements are yes, but are mutually striking.
[112]
112. The device of claim 111, wherein the chamfered edges of the two or more piercing elements are at an acute or oblique angle to each other.
[113]
113. The device of claim 106, wherein the two or more piercing elements are supported by a cable in a predefined configuration.
[114]
114. The device of claim 113, wherein the two or more piercing elements have predefined orientations with respect to each other.
[115]
115. The device of claim 113, wherein the two or more piercing elements comprise beveled edges that are oriented relative to each other in a predefined manner.
[116]
116. Device according to claim 113, in which the chamfered edges of the two or more piercing elements are yes intertwined.
[117]
117. The device of claim 106, in which additionally: a vacuum activator configured to activate a vacuum to position the skin in a recess of the device.
[118]
118. Device according to claim 117, in which a drilling activator is configured to activate the implantation spring only after the vacuum activator is activated.
Petition 870190064472, of 07/09/2019, p. 24/54
15/23
[119]
119. The device of claim 106, wherein the piercing elements comprise two or more lancets.
[120]
120. Device according to claim 119, in which the two or more lancets have the same chamfer angle.
[121]
121. Device according to claim 119, in which the two or more lancets have different chamfer angles.
[122]
122. Device according to claim 120 or 121, in which the chamfer angle (s) varies from about 10 degrees to about 60 degrees.
[123]
123. The device of claim 119, wherein the two or more lancets comprise faces having the same chamfer length.
[124]
124. The device of claim 119, wherein the two or more lancets comprise chamfered faces having different chamfer lengths.
[125]
125. Device according to claim 123 or 124, in which the chamfer length (s) varies from about 2 mm to about 10 mm.
[126]
126. The device of claim 106, in which two or more piercing elements are configured to generate cuts in the skin that extend in different directions along the skin and that are not parallel to each other.
[127]
127. The device of claim 106, wherein the one or more piercing elements comprise needles and / or microneedles.
[128]
128. Device according to claim 106, in which the implantation spring is configured to move and cause the piercing elements to penetrate the individual's skin at speeds ranging from about 0.5 m / s to about 2.0 m / s.
[129]
129. Device according to claim 106, in which the implantation spring is configured to move and cause the elements
Petition 870190064472, of 07/09/2019, p. 25/54
16/23 perforators penetrate the individual's skin with a force ranging from about 1.3 N to about 24.0 N.
[130]
130. The device of claim 106, wherein a spring force of the retraction spring is less than a spring force of the implantation spring.
[131]
131. The device of claim 130, wherein the implantation spring has a spring rate of about 2625 N / m, and the retraction spring has a spring rate of about 175 N / m.
[132]
132. The device of claim 106, wherein the implantation spring is configured to cause the one or more piercing elements to penetrate the skin at depths ranging from about 0.5 mm to about 3 mm.
[133]
133. The device of claim 106, wherein the retraction spring is configured to retract the perforating elements of the individual's skin at speeds ranging from about 0.1 m / s to about 1.0 m / s.
[134]
134. Device according to claim 106, in which the length of the one or more piercing elements is about 12.7 mm.
[135]
135. Device for monitoring the collection of fluid samples from an individual, in which:
a housing comprising a cartridge chamber;
a cartridge operationally coupled to the cartridge chamber; components to penetrate the individual's skin and withdraw the fluid sample from the skin into the cartridge; and a flow meter in the housing that allows the individual or a user to monitor a progress of fluid sample collection in real time as the fluid sample is collected into the cartridge.
[136]
136. M is all for monitoring an individual's fluid sample collection, in which:
Petition 870190064472, of 07/09/2019, p. 26/54
17/23 providing (1) a housing comprising a cartridge chamber, (2) a cartridge operably coupled to the cartridge chamber, (3) components to penetrate the individual's skin and withdraw the fluid sample from the skin to inside the cartridge, and (4) a flow meter in the housing; and monitoring, with the aid of the flow meter, a progress of fluid sample collection in real time as the fluid sample is collected into the cartridge.
[137]
137. Device according to claim 135, in which the flow meter is provided in a cover that covers a base of the housing.
[138]
138. Device according to claim 137, in which the flow meter is not obscured by a housing cover.
[139]
139. Device according to claim 135, in which the flow meter is close to the cartridge chamber.
[140]
140. The device of claim 139, wherein the flow meter is substantially aligned with a cartridge located inside the cartridge chamber.
[141]
141. Device according to claim 140, in which the flow meter comprises a plurality of windows arranged parallel to a longitudinal axis of the cartridge.
[142]
142. The device of claim 141, wherein the plurality of windows are made of an optically transparent material.
[143]
143. The device of claim 142, in which the fluid sample is visible through the windows and sequentially fills each window as the fluid sample is being collected for the cartridge.
[144]
144. Device according to claim 143, in which each window is indicative of a known amount of fluid sample that is collected.
[145]
145. Device according to claim 143, in which the fluid sample collection is complete when the fluid sample is visible in all windows.
Petition 870190064472, of 07/09/2019, p. 27/54
18/23
[146]
146. Device according to claim 141, in which the plurality of windows comprises three or more windows.
[147]
147. Device according to claim 140, in which the flow meter comprises a single window arranged parallel to a longitudinal axis of the cartridge.
[148]
148. The device of claim 147, wherein the window is made of an optically transparent material.
[149]
149. Device according to claim 148, in which the fluid sample is visible through the window and continuously fills the window as the fluid sample is being collected into the cartridge.
[150]
150. The device of claim 149, wherein the fluid sample collection is complete when the fluid sample is visible through the entire window.
[151]
151. Cartridge assembly comprising a cartridge for containing one or more matrices for storing a fluid sample;
a cartridge holder releasably coupled to the cartridge, where the cartridge assembly is releasably coupled to a device used to collect the fluid sample.
[152]
152. Device for collecting a fluid sample from an individual, in which:
a housing comprising a deposit chamber and a vacuum chamber pr is evacuated, where the deposit chamber is configured to receive and releasably couple the cartridge assembly as defined in claim 1, and the deposit chamber is in fluid communication with the vacuum chamber.
[153]
153. Fluid sample collection kit, in which:
the device as defined in claim 152; and the cartridge assembly according to claim 151.
[154]
154. Assembly of fluid sample collection, which comprises
Petition 870190064472, of 07/09/2019, p. 28/54
The device as defined in claim 152; and the cartridge assembly as defined in claim 151, releasably coupled to said device.
[155]
155. Assembly according to claim 154, in which a cartridge inlet port is releasably coupled and in fluid communication with a device channel, and the fluid sample is collected from the individual's penetrated skin and transported through is s from the channel to the cartridge.
[156]
156. M is for collecting a fluid sample from an individual, in which:
releasably coupling the cartridge assembly as defined in claim 1 to the device according to claim 2;
placing the device adjacent to the individual's skin;
activation of the vacuum in the vacuum chamber to position the skin in a recess of the housing;
the use of one or more piercing elements of the device to penetrate the skin;
maintaining the device adjacent to the skin for an amount of time sufficient to place the fluid sample in the device and collect the fluid sample in the cartridge; and uncoupling the cartridge assembly from the device after a certain amount of the fluid sample has been collected in the cartridge.
[157]
157. Assembly according to claim 154, in which the cartridge holder is releasably coupled to the cartridge by means of a quick release mechanism.
[158]
158. Assembly according to claim 157, in which the quick release mechanism comprises one or more spring clips on the cartridge holder.
Petition 870190064472, of 07/09/2019, p. 29/54
20/23
[159]
159. Assembly according to claim 154, in which the cartridge assembly is capable of being coupled and detached from the deposit chamber without the use of tools.
[160]
160. Assembly according to claim 154, in which the cartridge assembly is capable of being coupled and detached from the deposit chamber by using no more than the movement steps.
[161]
161. Assembly according to claim 154, in which the cartridge assembly is coupled to the deposit chamber before collecting the individual's fluid sample.
[162]
162. Assembly according to claim 154, in which the cartridge assembly is detached from the deposit chamber after the individual's fluid sample has been collected into the cartridge.
[163]
163. Cartridge according to claim 151, in which additionally two or more matrices for collecting and storing the fluid sample.
[164]
164. Cartridge according to claim 163, in which the two or more matrices are arranged in a configuration that allows the fluid sample to pass between and along the two or more matrices.
[165]
165. Cartridge according to claim 164, in which the two or more arrays are arranged substantially in parallel with each other.
[166]
166. Cartridge according to claim 165, in which the two or more dies are separated by a space of about 0.5 mm.
[167]
167. Cartridge according to claim 151, in which at least one of the matrices is capable of collecting at least 60 µL of fluid sample.
[168]
168. Cartridge according to claim 167, in which each of the two or more arrays is capable of collecting at least 60 µL of fluid sample.
[169]
169. Cartridge according to claim 151, in which in addition one or more absorbent pads configured to be in fluid communication with one or more matrices, where one or more
Petition 870190064472, of 07/09/2019, p. 30/54
21/23 more absorbent pads are used to hold the excess fluid sample.
[170]
170. Cartridge according to claim 169, in which one or more absorbent pads assist in ensuring that a predefined volume of fluid sample is collected and maintained in one or more matrices, regardless of the volume of fluid sample entering the cartridge at is a predefined track.
[171]
171. Cartridge according to claim 170, in which one or more arrays include two arrays which are each configured to hold about 7 µL of fluid sample.
[172]
172. Cartridge according to claim 171, in which each of the two arrays is configured to hold and hold about 75 μl of fluid sample as the fluid sample inlet volume increases to more than 15 μl at is a predefined track.
[173]
173. Cartridge according to claim 172, in which the predefined range is from about 150 µL to about 300 µL.
[174]
174. Cartridge according to claim 172, in which the predefined range is greater than 300 µL.
[175]
175. Cartridge according to claim 169, in which the one or more absorbent pads are capable of holding at least 100 µL of excess fluid sample.
[176]
176. A cartridge according to claim 151, in which the cartridge holder comprises a cartridge flap which is configured to be releasably coupled to a distal end of the deposit chamber.
[177]
177. Cartridge according to claim 176, in which the cartridge tab is configured in such a way that the individual or a user is able to (1) support the cartridge assembly by holding the cartridge tab, (2) coupling the assembly of cartridge to the device by pressing the cartridge tab, and / or (3) uncoupling the cartridge assembly from the device by pulling on the cartridge tab.
Petition 870190064472, of 07/09/2019, p. 31/54
22/23
[178]
178. Carrying sleeve in which an opening is configured to be coupled to a cartridge flap included with the cartridge of claim 13;
a dual support-release mechanism inside the sleeve, where the dual support-release mechanism comprises: (a) a retaining element configured for is coupled to a corresponding combination feature in the cartridge and fixing the cartridge inside the sleeve and (b ) a release element configured to cause spring clips on the cartridge holder to release and thereby decouple the cartridge from the cartridge holder.
[179]
179. Carrying sleeve according to claim 178, in which the dual support-release mechanism allows the cartridge holder to be removed from the sleeve opening while the cartridge is held in place within the sleeve, without exposing the tapes to the middle environment.
[180]
180. Carrying glove according to claim 178, in which additionally a desiccant inside the glove.
[181]
181. Transport assembly comprising the transport sleeve of claim 178; and the cartridge as defined in claim 163 coupled to said carrying sleeve.
[182]
182. Transport assembly according to claim 181, in which the cartridge flap is configured to hermetically seal the opening of the sleeve.
[183]
183. Assembly according to claim 154, in which the cartridge is oriented in such a way that the flow of the fluid sample into the cartridge is further aided by gravity.
[184]
184. Assembly according to claim 154, in which the cartridge comprises a luer-type adjustment that is coupled to the device when the cartridge is inserted into the deposit chamber.
[185]
185. Cartridge according to claim 151, in which one or more arrays comprise absorbent paper.
Petition 870190064472, of 07/09/2019, p. 32/54
23/23
[186]
186. Transport glove according to claim 178, which is sized and formatted to accommodate user or patient identity (ID) labels.
[187]
187. Cartridge assembly according to claim 151, which one or more of the matrices comprise a stabilizing chemistry.
[188]
188. A cartridge assembly according to claim 187, in which a first matrix comprises a first stabilization chemistry and a second matrix comprises a second stabilization chemistry different from the first stabilization chemistry.
[189]
189. Cartridge assembly according to claim 151, in which one or more of the matrices does not comprise stabilization chemistry.

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法律状态:
2021-04-20| B11A| Dismissal acc. art.33 of ipl - examination not requested within 36 months of filing|

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2021-07-06| B11Y| Definitive dismissal - extension of time limit for request of examination expired [chapter 11.1.1 patent gazette]|

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2021-10-13| B350| Update of information on the portal [chapter 15.35 patent gazette]|

优先权:

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申请号 | 申请日 | 专利标题

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US201762444764P| true| 2017-01-10|2017-01-10|

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US62/444,764|2017-01-10|

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US201762468906P| true| 2017-03-08|2017-03-08|

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