• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
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  • 优先权
    • 专利摘要:
    mixing system for mixing biological samples with additives. it is a device for mixing biological samples contained in flexible storage bags (104) at a controlled temperature, comprising a holder (105) for holding a storage bag containing a biological sample to be mixed; means for transmitting an offset to a sample in a storage bag in the holder to mix the sample; and temperature control means to keep the samples at a controlled temperature during the sample. the means for transmitting displacement to a sample comprises at least one inflatable/deflatable bag (102, 103) (air bag) which, when inflated, contacts the surface of a portion of a storage bag to progressively compress the bag. and move the contained sample to another part of the storage bag.
    公开号:BR112015028167B1
    申请号:R112015028167-2
    申请日:2013-09-09
    公开日:2021-06-22
    发明作者:Julien Pierre Camisani；Olivier WARIDEL
    申请人:Biosafe S.A.；
    IPC主号:
    专利说明:

    Field of Invention
    [001] The present invention relates to an automated mixing system, and in particular to a system capable of safely, uniformly, homogeneously and efficiently mixing biological samples such as whole blood, placental/umbilical cord blood, marrow bone, apheresis product or stromal vascular fraction (FVE) contained in a flexible collection, freezing, storage or transfer bag, especially during the addition of an organosulfur compound such as dimethyl sulfoxide (DMSO) or other biological additives. During the entire process, the automated system maintains the biological samples at a stabilized temperature.
    [002] Such procedures are often performed in hospital environments and in medical or biological laboratories. Common types of manipulations of blood or biological samples include: preparation for long-term storage, thawing after long-term storage, preparation before transplantation, cell culture expansion, adipose tissue manipulations, or other similar applications. Background of the Invention
    [003] The role of stem cells in transplants or cell therapies in regenerative medicine has expanded rapidly. In the area of transplants, the current therapeutic strategy requires that progenitor cells be cryopreserved for practically all autologous transplants and many allogeneic transplants. The cryopreservation process is of importance for all types of stem cell collection and, over the years, freezing and thawing techniques have proven to be effective and have a long-term storage capacity with a high survival rate for biological cells . Cryopreservation process
    [004] The cryopreservation process consists of storing a biological fluid in nitrogen in the liquid or vapor phase usually at -196°C in mechanical freezers. The survival rate is controlled and the concentrated stem cells are frozen at a typical rate of 1-2°C/min.
    [005] In order to freeze and store the concentrated cells at the mentioned temperatures, it is necessary to add an organosulfur compound, such as dimethyl sulfoxide (DMSO), to the biological sample. In cryobiology, DMSO cryoprotectant is used in the preservation of organs, tissues and cell suspensions, preventing damage to living cells by freezing. It inhibits the formation of intra and extracellular crystals, and therefore cell death.
    [006] Without cryoprotective additives, up to 90% of frozen cells would become inactive. In general, a mixture of 25% DMSO is added to the hematopoietic stem cells prior to cryopreservation.
    [007] In a standardized environment, such as in umbilical cord blood banks, or in a hospital setting after an autologous apheresis collection, there is a need to add a cryoprotectant before long-term storage in liquid or vapor nitrogen. In general, a sterile, cooled DMSO is added to the blood bag over the course of 10 to 15 minutes. While the biological sample must be kept at a stable temperature, DMSO must be added gradually to protect the cells from harmful osmotic stress due to the high DMSO concentrations and prevent an exothermic reaction that occurs as the concentrated DMSO solution is mixed with the cell solution. Furthermore, it is important to ensure that the DMSO or biological additive is homogeneously mixed with the blood bag or biological sample during the addition in order to ensure an efficient protective effect during cryopreservation.
    [008] Apart from the cryopreservation preparation needs, many applications require additives to be mixed with biological samples. For example, in research or cell therapy laboratories, concentrated cell products generally need to be mixed with solutions of culture media for cell proliferation, or washing or dilutions of cell products enriched with wash buffers such as sodium chloride ( NaCl) or Ringer's lactate solutions. In this configuration, again, there is a need to ensure proper graded, smooth and homogeneous mixing under controlled stabilized temperature.
    [009] Another possible application is the thawing of cryopreserved samples. Currently, most allogeneic umbilical cord blood units and autologous apheresis units are thawed using a conventional bain-marie technique, which consists of disposing, under water at 37° Celsius, blood bags taken from liquid nitrogen or steam. In this method, water is the thermal transfer vector for the bag, and therefore has a possible risk of microbiological contamination. It is therefore desirable to have a repeatable system capable of defrosting samples using a dry-tempering system, keeping them at a stabilized temperature of 37°C or preset, to ensure an efficient defrost, through which a bag of blood is mixed gently throughout the process.
    [010]Thus, the risk of microbiological contamination is reduced and the product is not subject to operator variability during mechanical agitation of the bags in the water.
    [011] In the area of storage in stromal vascular fraction banks, many steps are required to extract a patient's adipose tissue, digest and process the fat until the stromal vascular fraction is concentrated with mesenchymal stem cells and is ready for storage in bank. Within these steps, the adipose tissue should, in general, be washed with a wash buffer solution, such as Ringer's lactate or sodium chloride, and should be digested at a stabilized temperature of 37°C with collagenase enzymes. Therefore, it would be desirable to have an automated system that is capable of programming a stabilized temperature, pumping additives into the adipose tissue and ensuring an even and homogeneous mixing of biological samples.
    [012]Currently, the mixing process is still extremely operator dependent, and there remains a general need to provide an automated system capable of ensuring safe, efficient and homogeneous mixing, especially when adding biological additives to blood products or other types of biological samples. State of the art
    [013]The most common mixing technologies for biological samples these days are shaking techniques or a mechanical arm movement interacting with the biological sample.
    [014]The Biosafe S.A. CoolmixTM device is an automated mixing device that enables the preparation of stem cells for cryopreservation. The system uses a mixing mechanism through the intermediary of a mechanical arm moving up and down, so a vortex motion is created when a surface of the bag is compressed by the metal arm.
    [015] Known systems suffer from the limitations that they can produce rapid movements or high gravitational acceleration of the manipulated cells or products, and there is a risk of mechanical friction or gross agitation of the manipulated cells or products, making it difficult to customize the devices. Disclosure of the Invention
    [016] As stated in the claims, the invention proposes an improved automated system to ensure a safe, regular and homogeneous mixing of collection, freezing, storage or transfer bags containing blood or a biological solution, especially during the injection of an organosulfur compound as dimethyl sulfoxide (DMSO) or other biological additives.
    [017] According to a main aspect of the invention, there is provided a device for mixing biological samples contained in flexible collection, freezing, storage or transfer bags (hereinafter "storage bags") at a controlled temperature, comprising:
    [018] A support to support a storage bag containing a biological sample to be mixed;
    [019] Means for transmitting a displacement to a sample in a storage bag on the holder to mix the sample; and
    [020] Temperature control means to keep samples at a controlled temperature during mixing.
    [021] The device according to the invention is characterized in that the means for transmitting displacement to a sample comprise at least one inflatable/deflatable bag (hereinafter "air bag") which, when inflated, comes into contact with the surface of a part of a storage bag to progressively compress the storage bag and move the contained samples to another part of the storage bag. Additional aspects of the invention are set out in the claims.
    [022] The invention also concerns the general mixing apparatus and instrumentation capable of mixing, smoothly and homogeneously, a small or large bag, or two or more bags at the same time.
    [023] The invention proposes a mixing system composed of one or more pneumatic air bags in contact with biological blood sample bags. Air-based bags are inflated and deflated at various frequencies and with customized profiles depending on the types of blood bags, volume and sensitivity of both products to be mixed. This action results in the compression of the biological sample onto a defined surface with a distributed force.
    [024] The present invention offers hospital environments, medical and biological laboratories an automated system capable of uniformly mixing samples, and unlike existing agitators, ensures that there is no rapid movement and high gravitational accelerations of the cells or products handled. The technique used with the present invention is to apply gentle pressure to a predefined surface that is quite large, which results in creating an efficient vortex effect, ensuring homogeneous mixing of the sample.
    [025] The compression performed by an inflated air bag ensures a force distributed over the surface area, which results in smooth and homogeneous mixing of the biological sample, with less risk of mechanical friction or gross agitation of the cells or products handled.
    [026] In addition, the device of the invention can accommodate a variety of bag sizes used for manipulations The present invention encompasses a wide variety of blood or biological bags of different sizes, either by projecting pneumatic air bags according to sizes bags needed to be manipulated, or by integrating a set of air bags to cover a wide range of bag sizes.
    [027]Pneumatic air bags can also be inflated and deflated with a custom profile adapted to specific blood bag sizes. In addition, air-based bag manufacturing techniques are inexpensive compared to the complex mechanisms of agitation or mechanical movement. For air bags, elastomers such as thermoplastic polyurethane or poly(vinyl chloride) (PVC) are generally used and manufactured by conventional thermoplastic methods. A bag
    [028] Taking as an example a freezing bag containing 20 mL of biological samples, refer to WO 2009/138966 (Biosafe), in which the mixing movement is performed by pressurizing and depressurizing an air bag containing a membrane of resistant silicon with compressed air.
    [029]The function of the mixing bag is to provide a vertical push and pull movement transmitted to the bag to be mixed. By compressing a force distributed over an extended surface, a narrow path is created which results in the creation of a considerable vortex effect, ensuring efficient and homogeneous mixing. Double compartment bags, due to their construction, already have a narrow path connecting the smaller and larger compartments. This narrow path also creates the desired vortex effect.
    [030]The air is supplied from a pneumatic system driven by electrovalves and a pneumatic pump. By doing this, it is possible to control the rate of inflation and deflation and the speed of movement of the air bag, which ensures an optimized mixing of biological samples.
    [031] The device body typically has an aluminum plate, on which cryopreservation bags or other types of bags are placed. Biological Bags are mechanically constrained by a cover plate containing an air mixing bag.
    [032] An aluminum plate forming a device support is fixed on top of a set of Peltier elements sized to provide sufficient cooling or heating capacity to the device. Thermal insulation around the Peltier element is also provided. Heat is then exchanged with the rest of the device via a heat exchanger and an airflow cooling system. Multiple scholarships
    [033]The system can be designed to be able to mix two or more cryo-resistant bags at the same time. Various air-based pneumatic bags could be inflated or deflated synchronously or asynchronously according to the needs of the market. In order to control the pneumatic system, a central pneumatic pump with several electrovalves is used to separately control each air bag. big bags
    [034]The system is also capable of mixing a large set of pouches: freezing, storage or transfer pouches. Mixing movement is ensured by two or multiple pneumatic air bags. If two vertical air bags are used for pushing and pulling, they could be placed on either side of the biological sample. By gently compressing one side surface at a time, and alternating both sides, the fluid will move from one side to the other side of the bag. Thus, the biological sample mixed with additive is homogeneously mixed throughout the entire process.
    [035] Optional compression lips can be used to ensure the creation of a satisfactory vortex for large volume bags. Lips could be used to firmly grip large bags in a defined line over the bag, virtually creating two compartments connected with a small narrow path, or to narrow the width of the bag in half, for example, creating a narrow path across the entire bag. Brief Description of Drawings
    [036] Features, aspects and advantages of the present invention will become apparent from the following detailed description, when considered in combination with the accompanying drawings, in which:
    [037] FIG. 1 is a diagram illustrating the principle of mixing biological pockets by inflation or deflation of air pockets;
    [038] FIG. 2A is a schematic vertical cross-sectional view illustrating the principle of mixing a biological sample, illustrating the deflated pneumatic bag;
    [039] FIG. 2B is a schematic vertical cross-sectional view illustrating the principle of mixing a biological sample illustrating the inflated air bag;
    [040] FIG. 3A is a schematic view illustrating the homogeneous mixing principle and vortex effect of a small single-compartment pouch;
    [041] FIG. 3B is a schematic view illustrating the homogeneous mixing principle and vortex effect of a small double compartment pouch;
    [042] FIG. 4 is a schematic vertical cross-sectional view illustrating the principle of homogeneous mixing of a large, large volume blood bag in a resting mode with the air bags deflated;
    [043] FIG. 4B is a schematic cross-sectional view illustrating the principle of homogeneous mixing of a large volume bag when the left side of the blood bag is pressed by an inflated air bag, creating a vortex effect and movement to the right side;
    [044] FIG. 4C is a schematic cross-sectional view illustrating the principle of homogeneous mixing of a large volume bag when the right side of the blood bag is pressed by an inflated air bag, creating a left side vortex and movement effect;
    [045] FIG. 5A is a schematic view illustrating the homogeneous mixing principle and vortexing effect of a large transfer bag and FIG. 5B shows a variant;
    [046] FIG. 6 is a block diagram illustrating a fluid mixing system configuration in accordance with one embodiment of the present invention;
    [047] FIG. 7 is a flowchart illustrating a sequence of the pumping and mixing process of the system in accordance with the present embodiment;
    [048] FIGS. 8A and 8B show graphs of different inflation/deflation frequencies;
    [049] FIG. 9 is a general perspective view of an embodiment of a device according to the invention with its visible support, once the cover is in an open position;
    [050] FIGS. 10A and 10B show a possible configuration for fitting large and small cryopouches onto a baseplate; and
    [051] FIG. 11 is a schematic view of a chassis construction. Detailed Description
    [052] Hereinafter, an embodiment of the present invention will be described in detail with reference to the drawings. In the embodiment described below, an automated mixing system for biological fluids will be explained by way of examples.
    [053] FIG. 1 is a diagram illustrating the principle of mixing biological bags by inflating or deflating bags with air. As shown in FIG. 1, the automated mixing system comprises a base plate 105 with, for example, a blood storage bag 104 disposed thereon. At the top, there is a lid 101 supporting a pneumatic bag 102. When the pneumatic bag 102 is inflated as indicated by 103, the pneumatic bag applies even pressure over the blood bag 104, when the pneumatic bag 102 is thawed if it is not in contact with the blood bag 104.
    [054] FIG. 2A is a schematic vertical cross-sectional view illustrating the principle of an automated mixing system using a pneumatic bag. Here, a baseplate 212 has a biological sample (blood) 216,217 disposed thereon. When the cover 211 is closed, a compression lip 215 creates a narrow path 218 for the biological fluid. The blood bag can be broken down into three parts: a small reservoir 216, the narrow path 218, and a large reservoir 217.
    [055]In the illustrated position, the pneumatic air bag 214 is deflated and is not in contact with the blood bag. This happens when the system is at rest or after an inflation phase.
    [056]The pneumatic bag 214 is controlled by ambient or compressed air coming from a pneumatic system connected by means of a pneumatic tube 213.
    [057] FIG. 2B is a schematic vertical cross-sectional view illustrating the principle of mixing a biological sample by inflating the pneumatic bag 214.
    [058] To reach this position, the compressed air fed by a pneumatic system is actuated through the air tube 221 in order to inflate the air bag 222. Once the air bag is inflated, the membrane of the bag air is in contact with the small reservoir of the blood bag 225 and evenly distributed pressure is applied to the surface of the small reservoir 223.
    [059] The biological fluid moves into the large volume reservoir 224 with a higher pressure due to the narrow path 226. A vortex effect will ensure efficient and homogeneous mixing due to the narrow path due to the bag shape and construction of the compression lip.
    [060] FIG. 3A is a schematic view illustrating the homogeneous mixing principle and vortex effect of a single compartment bag 302 disposed on a base plate 301. The inflation/deflation air bag 305 is viewed virtually from above, as indicated in dotted lines .
    [061] When a small single compartment bag needs to be mixed, a compression lip 306 is required and creates a narrow path 304, virtually creating a small and large reservoir on both sides. When the air bag 305 is inflated and is in contact with the small virtual reservoir, fluid moves into the large reservoir via the narrow path 304 and a vortex effect 303 is created. This vortex effect ensures efficient biological mixing.
    [062]This vortex effect is important to ensure a smooth and homogeneous mixture when the sample is mixed, and especially while an additive is pumped into the 302 bag via a 307 inlet tube.
    [063] FIG. 3B is a schematic view illustrating the homogeneous mixing principle and vortex effect of a dual compartment bag 312 disposed on a base plate 311. An inflation/deflation air bag 315 is seen virtually from above, as indicated in dotted lines .
    [064]When a small double compartment needs to be mixed, by the construction of the bag, there is already a narrow path 314 and the compression lip 316 is not needed. When the air bag 315 is inflated and is in contact with the small reservoir, fluid moves into the large reservoir via the narrow path 314 and a vortex effect 313 is created. This vortex effect is important to ensure a smooth and homogeneous mixture when the sample is mixed, and especially while an additive is pumped into the 312 bag via a 317 inlet tube.
    [065] FIG. 4 is a schematic vertical cross-sectional view illustrating the principle of homogeneous mixing of a large volume blood bag. The universal baseplate is represented by 401, and the coverage by 400.
    [066]The large volume blood bag is virtually separated into a left reservoir 406 and a right reservoir 407 by the intermediary of a narrow channel 409 created by compression lips 408 in baseplate 401 and cover 400. The two volume reservoirs Virtual machines may have equivalent or different volumes depending on the shape of the bag or the volume to be mixed.
    [067] A pneumatic system is composed of two bags left 404 and right 405 and by two air tubes left 402 and, respectively, right 403 connected to a pneumatic device. In the illustrated position, air bags 404, 405 are not in contact with the blood bag.
    [068] FIG. 4B is a schematic cross-sectional view illustrating the principle of homogeneous mixing of a large volume bag when the left side of the blood bag 414 is pressed by an inflated air bag 412, creating a fluid effect and a vortex effect. from reservoir 414 towards right reservoir 413. In this configuration, compressed air comes from air tube 410 and inflates left air bag 412. Right air bag 415 is deflated and is not in contact with the blood bag .
    [069] FIG. 4B is a schematic cross-sectional view illustrating the principle of homogeneous mixing of a large volume bag when the right side of the blood bag 424 is pressed by an inflated air bag 423, creating a fluid effect and a vortex effect of the fluid from the right reservoir 424 towards the left reservoir 425. In this configuration, compressed air comes from the air tube 421 and inflates the right air bag 423. The left air bag 422 is deflated and is not in contact with the blood bag.
    [070] FIG. 5A is a schematic view illustrating the homogeneous mixing principle and vortex effect of a large transfer bag 502 disposed on a base plate 501. A surface of the inflation/deflation air bag 503 is seen virtually from above, as indicated in dotted line. In order to create two separate virtual reservoirs, compression lips 506 are needed and create a narrow path 504 for the fluid. When an air bag is inflated with air, it pushes the equivalent volume of fluid over the other reservoir through the narrow path 504. During the inflation phase of a side air bag 503, the fluid passing through the narrow path 504 creates a 505 vortex effect on the other side of the blood bag. Once the air bag 503 is fully inflated on one side, it deflates and the other side of the air bag inflates, creating the same vortex effect on the other side of the blood bag. An alternating movement ensures a homogeneous mixing of the blood bag. This vortex effect is important to ensure a homogeneous mix, especially while an additive is pumped into the bag via a 507 connective tube.
    [071] FIG. 5B is a schematic view illustrating a variant of creating a vortex effect on a large transfer bag. This vortex effect is created by narrowing the path between two sides of the bag across the entire width of the bag. Baseplate 511 has large blood bag 512 disposed thereon. A surface of the inflation/deflation air pocket 513 is seen virtually from above, as indicated in dotted lines.
    [072] In order to create two separate virtual reservoirs, the compression lips 514 form a slightly tight path between the two sides of the bag and the narrow fluid path 516. When one side of the air bag is inflated, it will be in contact with a side surface, pushing fluid into the other reservoir via the narrow path 516. During the inflation phase of a surface 513, fluid moving through the narrow path will create a vortex effect on the other side of the bag. blood 515. As in FIG. 5A, a vortex effect is created when one side is inflated, and a reciprocating motion ensures a homogeneous mixing of the blood bag 512. This vortex effect is important to ensure a smooth and homogeneous mixing when the sample is mixed, and especially while an additive is pumped into the bag via a connecting tube 517.
    [073] FIG. 6 is a block diagram illustrating a fluid mixing system configuration in accordance with the present embodiment. As shown in FIG. 6, the system is composed of a set of pneumatic air bags of different sizes 110, and an automated system 100 controlling the air flow in the pneumatic bags with appropriate electronic components.
    [074]A versatile platform with a set of multiple air bags is used in order to cover a wide variety of shapes and volume of blood bags. The A1 111 and A2 112 blood bags are the same size and are used to mix two small compartment bags simultaneously. The B 113 and C 114 air bags are two larger pneumatic bags capable of mixing both sides of a large blood bag.
    [075]The main control system 100 (Fig. 6) includes a power supply 120 to supply electrical power to the main CPU and the system, a Central Processing Unit (CPU) 121 and a memory 126 to control and monitor the mixing system. This includes a pneumatic system with solenoid valves 115-116-117-118 and a pneumatic pump 124, electronic controllers 122 and feedback pressure sensors 125, thermal control 134 with controller 133 and thermal feedback sensors 135, and finally peristaltic pumps 131-132 and controller 130 for adding additives to blood bags.
    [076]The pneumatic system is controlled by the CPU 121, which determines which bag will inflate or deflate and with what frequency and profile. The instructions provided to the CPU 121 are stored in the memory part 126. A first action is the control of the pump 124 by means of a drive circuit 122 to generate compressed air for the air bags. Several 115-118 valves are controlled through a 123 actuation circuit and have the function of inflating or deflating each bag separately. Valve 118 is the main valve controlling the flow of air to all air bags. Solenoid valve 115 simultaneously controls the A1 111 and A2 112 air bags. These two bags are inflated or deflated at the same time to mix two small bags synchronously. Solenoid valves 116, and 117 respectively, control two larger air bags 113, 114 separately to mix both sides of a large volume blood bag. An alternating movement ensures mixing of large bags. A pressure sensor 125 constantly monitors the pneumatic system and provides information to the CPU 121 for control management.
    [077] A thermal control system ensures a stabilized temperature for biological sample bags. It is composed of a thermal control 134 driven by electronics 133. The temperature sensor 135 provides information to the CPU 121 to control the thermal system.
    [078] Two 131-132 peristaltic pumps are also implemented in the system. They are controlled by the pump drive circuit 130, and are used to pump additive fluids into the blood bags. Two peristaltic pumps are required when two volume bags are used simultaneously.
    [079] FIG. 7 is a flowchart illustrating a system pumping and mixing process flow in accordance with the present embodiment; The program according to this flowchart is pre-stored in a memory part 126, and the mixing process is performed as the CPU 121 reads this program from the memory part 126 and executes the instructions sequentially.
    [080]As shown in FIG. 7, when the power is turned on and an application is started, the system boots to S100. When the system is ready to execute instructions, a first action is to stabilize the temperature at a predetermined value in S101. Once the temperature is stabilized, and a biological bag is correctly inserted into the device, the S102 mixing process, as well as the pumping of the biological additive, can be started. During the mixing process, the air bags are constantly inflated in S103 and deflated in S104. Bag inflation is managed by compressed air and stops when a pressure threshold reaches a prescribed level. Bag deflation is managed by an exhaust valve and stops when a second pressure threshold is reached.
    [081]During the mixing and pumping phase, there is an S105 control checking whether a desired volume of additive or a time limit has been reached. If limitations have not been met, the process continues and the air bag inflates S103 and deflates S104 sequentially.
    [082]At the end of the process, sufficient additive fluid was added to the blood bag or a mixing time limit was reached. In this state S106, the peristaltic pumps 132, 132 and the bag mixture stop working, and then the process ends. Typical examples of pouch blending are described as follows.
    [083] A small volume bag (eg 87 X 66 mm) containing a biological sample (eg 20 mL) is mixed with a small surface pushed and pulled by an air bag. Since the surface in contact is small, the movement needs to be dynamic and repetitive. An average frequency of 0.5 Hz, or mixing every two seconds is adequate. An air bag is inflated by means of a pneumatic system, and once a maximum pressure of, say, 300 mBar is reached, an escape valve quickly deflates the air bag. Then, the system repeats the same cycle every two seconds, as shown in Fig. 8A.
    [084] To mix a typical large volume of approximately 100 milliliters of biological sample in a large bag (measuring, for example, approximately 240 X 145 mm), a slower movement with lower pressure is required. A typical average frequency of 0.1 Hz, or mixing every ten seconds is adequate. An air bag is inflated by means of a pneumatic system, and once a maximum pressure of 100 mBar is reached, an escape valve quickly deflates the air bag. Then, the system repeats the same cycle every ten seconds, as shown in Fig. 8B.
    [085] FIG. 9 shows an embodiment of the device according to the invention with its cover 930 open. The device comprises a chassis 920 on which a base plate 901 is mounted. The 901 baseplate is adapted to hold two small cryopouches or a large biopouch and has 915 permanent center lips to constrict the center of a large cryopouch. On the front of chassis 920 is a 922 touch screen to control device operation. 940 peristaltic pumps are also visible to feed additives during operation.
    [086] The cover 930 is pivotally mounted on the chassis 920 by a hinge 931. The cover/chassis are provided with means to lock the cover 330 in a closed position on the chassis 320 to prevent the cover from being opened/raised as a consequence. the inflation of a 952/933 air bag during mixing. These locking means can be manually or automatically activated to lock or unlock before or after mixing.
    [087]As illustrated, in this example, cover 930 supports two sets of large 932 and small 933 air bags. The two large air bags 932 and small air bags 933 fit either side of the permanent lip 915 in bracket 901. Between each large air bag 932 and each small air bag 933 in cover 930 is a space 935 for the attachment of removable lips that can be fitted and removed by the operator and that can be conveniently magnetically held in place near the 930 metal cover.
    [088] Behind chassis 920 is a vertical frame with two shanks 950 whose height is merely greater than the top of cover 930 when open, as illustrated.
    [089] FIGS. 10A and 10B show possible configurations for fitting large and small cryopouches to a particular 1001 baseplate measuring, for example, 240 X 145 mm.
    [090]As illustrated in FIG. 10A, a single large cryopouch 1002 can cover virtually the entire baseplate 1001. In this case, during mixing, the cryopouch will be divided along part of its central portion by the permanent lip 915 (Fig. 9).
    [091]As illustrated in Fig. 10B, two small cryobags 1003 and 1004 measuring, for example, 87 X 64 mm, can fit into the baseplate 1001. The small cryobag 1003 is not split, so in this case the operator will fit a removable magnetic lip at 935 (Fig. 9) to form a construction across part of the width of the small cryobag 1003. On the other hand, the small cryobag 1004 already has an integrated split where its two sides are welded together, therefore, there is no need to fit a removable lip.
    [092] FIG. 11 illustrates an interior side view of the underside of chassis 1120. The front of the device is to the left of FIG. 11 and its rear part on the right. Chassis 1120 mounts on legs 1122 and 1124 in an unequal length, giving the device a few degree tilt, with the front part lowered.
    [093] On top of chassis 1120 is a slanted baseplate 1101 which rests on two Peltier 1126 elements which, in turn, rest on a gridded/notched metal heatsink 1128. Heatsink 1128 is placed over an 1130 fan that, when operated, removes hot air from the heatsink. Air enters from below and exits from the sides. The desired temperature for the 1101 baseplate, and therefore for the samples being mixed, can be set by the operator.
    [094]Using the 922 touch screen, the operator can also set the mixing time and the inflation/deflation frequency, as well as the possible feed of an additive.
    权利要求:
    Claims (9)
    [0001]
    1. Device for mixing biological samples contained in flexible storage bags (104) at a controlled temperature, flexible storage bags (104) which can serve, in addition to storage, for collection, storage with freezing or transfer of samples biologicals, the device comprising: a) a holder (105) for holding a storage pouch (104) containing a biological sample to be mixed; b) means for transmitting an offset to a sample in a storage bag (104) on the holder (105) to mix the sample; and c) temperature control means for keeping the samples at a controlled temperature during mixing; wherein d) said means for transmitting displacement to a sample comprises at least one inflatable/deflatable bag (102, 103) which, when inflated, contacts the surface of a portion of a storage bag (104) to progressively compressing the storage bag (104) and moving the contained sample to another part of the storage bag (104); CHARACTERIZED by the fact that the support (105) is a base plate (105) where the storage bag (104) can be placed, the inflatable/deflatable bag (102, 103) is located under a cover (101) that fits. fits over the support (105), the inflatable/deflatable bag (102, 103) being located over the location of a supported storage bag (104) and under the cover (101), the cover (101) is pivotally mounted on the support (105) between a closed position and an open position, and the device further comprises means for locking the cover (101) in the closed position on the support (105) to prevent the cover from opening as a result of inflation of the inflatable bag/ inflatable (102, 103) during mixing.
    [0002]
    Device according to claim 1, CHARACTERIZED in that it further comprises means for feeding an additive to the biological sample in a storage bag (104) placed in the support (105), before and/or during mixing.
    [0003]
    Device according to claim 1 or 2, characterized in that it additionally comprises a lip that projects from the cover (101) and/or from the support (105) for constricting a storage bag (104) in the support (105).
    [0004]
    Device according to claim 3, CHARACTERIZED in that it comprises at least one removable lip which can be removably attached to the cover (101) and/or the support (105).
    [0005]
    5. Device according to claim 3 or 4, CHARACTERIZED by the fact that the support (105) is configured to receive a large storage bag (104) or two small storage bags (104), the support (105) and/or the cover (101) having a lip that constricts a central portion of the storage bag (104) large when fitted and into which the small storage bags (104) can be fitted on either side.
    [0006]
    6. Device, according to any one of the preceding claims, CHARACTERIZED by the fact that the temperature control means comprise at least one Peltier element located under the support (105) above a heat sink.
    [0007]
    7. Method of mixing biological samples in flexible storage bags (104) in a device, according to any one of the preceding claims, maintained at a controlled temperature in the device, CHARACTERIZED in that it comprises transmitting displacement to a sample in a storage bag (104) by repeatedly inflating and deflating an inflatable/deflatable bag (102, 103) so that when the inflatable/deflatable bag (102, 103) is inflated, it contacts the surface of a part of a storage bag (104) for progressively compressing the storage bag (104) and moving the contained sample to another part of the storage bag (104), wherein during said inflation of the inflatable/deflatable bag (102, 103), the device cover (101) is retained in its closed position by said means for locking the same.
    [0008]
    8. Method according to claim 7, CHARACTERIZED by the fact that an additive is provided to the sample contained in the storage bag (104) during mixing.
    [0009]
    9. Use of the device as defined in any one of claims 1 to 6, CHARACTERIZED for mixing biological samples selected from whole blood, placental/umbilical cord blood, bone marrow, apheresis product or stromal vascular fraction (FVE) .
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    法律状态:
    2018-03-06| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2018-03-13| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2018-03-20| B06I| Publication of requirement cancelled [chapter 6.9 patent gazette]|Free format text: ANULADA A PUBLICACAO CODIGO 6.6.1 NA RPI NO 2462 DE 13/03/2018 POR TER SIDO INDEVIDA. |
    2019-10-22| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2021-05-11| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2021-06-22| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 09/09/2013, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    IB2013053652|2013-05-07|
    IBPCT/IB2013/053652|2013-05-07|
    PCT/IB2013/058403|WO2014181158A1|2013-05-07|2013-09-09|Mixing system for mixing biological specimens with additives|
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