apparatus, system and method of automated pigmentation and reaction chamber

专利摘要:
AUTOMATED PIGMENTATION SYSTEM AND REACTION CHAMBER. The present invention relates to an apparatus including a reagent cartridge and a reaction chamber, the reagent cartridge having a removably positioned reagent capsule for dispensing a reagent to the reaction chamber. A system including a linearly translatable mounting assembly having a plurality of mounting stations sized to receive at least one fluid dispensing cartridge, a linearly translatable bulky reagent dispensing assembly having a plurality of bulky reagent dispensing nozzles coupled thereto and a receiving set positioned under the assembly set and the bulky reagent distribution set, the receiving set including a plurality of reaction stations. A method including determining an inventory of an automated sample processing system, downloading a process protocol from a central controller to the automated sample processing system, operating the automated sample processing system based on the protocol of processing and independently of the central controller for the automated sample processing system, the operation of the automated sample processing system (...).
公开号:BR102012021902B1
申请号:R102012021902-6
申请日:2012-08-30
公开日:2020-12-15
发明作者:Xuan S. Bui；Anthony L. Hartman；Toshiyuki Fujimaki；Shinji Tokudaiji；Yoshitake Okabe；Yoshitada Mizusawa
申请人:Sakura Finetek U.S.A., Inc；
IPC主号:

专利说明:

Field
[0001] An automated pigmentation system, in particular an automated pigmentation system for processing biological species. Background
[0002] In various configurations, processing and testing of biological species is necessary for diagnostic purposes. Generally speaking, pathologists and other diagnosticians collect and study samples from patients, and use microscopic examination, and other devices to determine samples at cell levels. Numerous steps are typically involved in pathology and other diagnostic processes, including the collection of biological samples such as blood and tissue, sample processing, preparation of microscopic slides, pigmentation, examination, retesting or further pigmentation, collection of additional samples, new examining samples, and, finally, offering diagnostic findings.
[0003] Tissue processors can be operated with varying levels of automation to process species of human or animal tissue for use in histology or pathology. Various types of chemical reagents can be used at various stages of tissue processing and several systems have been developed for distributing reagents to slides containing species. Examples of known reagent delivery systems include small quantity release dispensers, manual dumping into reagent containers, or through bulky containers connected with a processor via piping.
[0004] There are several disadvantages of the known systems. For example, manual dumping into, or draining, reagent containers is time-consuming and requires mirror precision, thereby reducing the overall efficiency of the tissue processing system. Another disadvantage is that manual dumping and draining of reagents can be a dirty task, requiring spill cleanup and consequent instrument shutdown time. An additional disadvantage is that manual selection of the correct reagent requires operator attention and accuracy and there is an increased possibility of reagent application errors, resulting in a reduction in test accuracy and operational efficiency. Brief Description of Drawings
[0005] The modalities of the invention are illustrated by means of examples and not by means of limiting the figures of the attached drawings in which similar references indicate similar elements. It should be noted that references to "one" modality in that description should not necessarily refer to the same modality, and such references mean at least one.
[0006] Figure 1 illustrates a perspective view of an embodiment of a sample processing system;
[0007] Figure 2 illustrates a perspective view of a modality of a sample processing system with reaction stations;
[0008] Figure 3A illustrates a perspective view of a reaction chamber modality;
[0009] Figure 3B shows a side view of the reaction chamber of figure 3A;
[0010] Figure 4A illustrates a perspective view of an embodiment of a reaction chamber and reagent cartridge of a sample processing system;
[0011] Figure 4B illustrates a perspective view of a modality of a reaction chamber and reagent cartridge of a sample processing system;
[0012] Figure 5A illustrates a perspective view of a reaction chamber modality;
[0013] Figure 5B shows a side perspective view of a reaction chamber modality;
[0014] Figure 6A illustrates a perspective view of a reaction chamber modality;
[0015] Figure 6B illustrates a perspective view of a reaction chamber modality;
[0016] Figure 7 illustrates a top perspective view of an embodiment of a reagent cartridge;
[0017] Figure 8 shows a bottom perspective view of the reagent cartridge of figure 7;
[0018] Figure 9A illustrates a perspective view of an embodiment of a reagent and support dispensing capsule;
[0019] Figure 9B illustrates a perspective view of the reagent and support dispensing capsule of figure 9A;
[0020] Figure 10A illustrates a cross-sectional side view of an embodiment of a capsule pressure mechanism during operation;
[0021] Figure 10B illustrates a cross-sectional side view of an embodiment of a capsule pressure mechanism during operation;
[0022] Figure 10c illustrates a cross-sectional side view of an embodiment of a capsule pressure mechanism during operation;
[0023] Figure 10d shows a cross-sectional side view of an embodiment of a capsule pressure mechanism during operation;
[0024] Figure 11 is a perspective view of a modality of a reaction station in a sample processing system;
[0025] Figure 12 illustrates a perspective view of an embodiment of a temperature modification set;
[0026] Figure 13 illustrates a perspective view of a modality of the entire reaction station;
[0027] Figure 14 illustrates a front perspective view of an embodiment of an interlocking assembly;
[0028] Figure 15 illustrates a perspective view of an embodiment of an upper fluid distribution system and a capsule pressure mechanism;
[0029] Figure 16A illustrates a perspective view of an embodiment of an upper fluid distribution system;
[0030] Figure 16B illustrates a perspective view of an embodiment of an upper fluid distribution system;
[0031] Figure 17 illustrates a top view of an embodiment of a bulky fluid distribution set;
[0032] Figure 18 illustrates a top view of an embodiment of a fluid distribution system;
[0033] Figure 19 illustrates a schematic diagram of an embodiment of a sample processing system including a bulky reagent sensor assembly;
[0034] Figure 20 is an illustration of an embodiment of an automated sample processing system;
[0035] Figure 21 illustrates a flow chart of a modality of a sample processing procedure;
[0036] Figure 22 illustrates a flow chart of a modality of a sample processing procedure;
[0037] Figure 23 illustrates a modality of a monitor associated with a sample processing procedure;
[0038] Figure 24 illustrates a modality of a monitor associated with a sample processing procedure;
[0039] Figure 25A illustrates a perspective view of an embodiment of a drainage system for draining the sample processing system;
[0040] Figure 25B illustrates a side view of the drainage drainage system of figure 25A;
[0041] Figure 25C illustrates a rear side view of the drainage drainage system in figure 25A. Detailed Description
[0042] In the following paragraphs, the present invention will be described in detail by way of example with reference to the attached drawings. Throughout this description, preferred embodiments and illustrated examples should be considered as illustrative, rather than as limitations of the present invention. In addition, reference to various aspects of the modalities described here does not mean that all claimed modalities or methods must include those aspects.
[0043] Figure 1 illustrates a perspective view of an embodiment of a sample processing system. The sample processing system 100 includes a housing 102 for enclosing and storing the various components of the processing system 100. Housing 102 includes a reaction compartment 104 and a storage compartment 106. Reaction compartment 104 defines a compartment within the sample processing takes place. Cover element 108 and port element 110 can be used to gain access to components within reaction compartment 104.
[0044] Reaction compartment 104 is dimensioned to accommodate a plurality of reaction stations 112. Reaction stations 112 can slide in and out of reaction compartment 104 to facilitate access to reaction chambers 114 mounted thereon. In some embodiments, 30 reaction stations 112 are positioned linearly within reaction compartment 104. In other embodiments, reaction stations 112 are arranged in rows within reaction compartment 104. For example, where 30 reaction stations 112 are provided, each row can include 15 reaction stations 112. Although 30 reaction stations 112 are described, it is contemplated that any number of reaction stations 112 can be positioned within the reaction compartment 104 which is considered desirable.
[0045] Each of the reaction stations 112 includes one of the reaction chambers 114 mounted thereon. Reaction chambers 114 are sized to support a slide for further processing. A biological sample can be assembled to slide for processing purposes. During processing, a pigment or other processing fluid is applied to the sample. In some embodiments, the processing fluid can be applied to the sample by a reagent cartridge attached directly to each of the reaction stations 112. In other embodiments, the sample processing system 100 may include a mobile mounting assembly 116 for mounting of fluid dispensing cartridges (not shown) above reaction stations 112. Fluid dispensing cartridges may include a fluid such as a reagent that must be applied to the sample. In addition, bulky containers 118 can be mounted below reaction stations 112. Bulky containers 118 can be reagent containers, empty containers or any other bulky container deemed desirable. A reagent from bulky containers 118 can be further dispensed into the sample during processing.
[0046] System 100 may additionally include an air inlet assembly 120 and an air outlet assembly 122 to help control a temperature within the reaction compartment 104. Processing of the samples within the reaction compartment 104 generates heat. As the temperature inside the reaction compartment 104 the evaporation rate of any processing fluid used in the reaction stations also increases. In addition, the increased temperature can have a negative impact on reagent stability. To help maintain a desired temperature within the reaction compartment 104 (that is, a temperature that does not accelerate evaporation), an air inlet assembly 120 and an air outlet assembly 122 can be used to circulate air through the reaction compartment 104. In this regard, the air inlet assembly 120 may include vent 124 mounted along one side of a housing wall 102 to help draw ambient air into reaction compartment 104. The air outlet 122 can be mounted on a wall on the opposite side of housing 102 and includes one or more fans 126 coupled to an air outlet vent formed through the wall to help draw air out of reaction compartment 104. It is further contemplated that the filters can be incorporated into the air inlet assembly 120 and / or the air outlet assembly 122 to prevent contaminants from entering the reaction compartment 104. Ambient air circulates through the reaction compartment 104 as described helps to maintain a desired processing temperature within the reaction compartment 104.
[0047] Figure 2 illustrates a perspective view of a modality of a sample processing system with the reaction stations. Processing system 200 includes reaction stations 202. Any number of reaction stations 202 can be positioned within processing system 200. For example, in one embodiment, 30 reaction stations 202 can be positioned within processing system 200. Each of the reaction stations 202 can be independent of the other. In this respect, each of the reaction stations 202 can slide in and out of the processing system 200 separately so that a user can easily access a desired station from among the reaction stations 202 (for example, see figure 1 with a station reaction 112 partially slid out of processing system 100).
[0048] Each of the reaction stations 202 of the sample processing system 200 can include a support element 204. The support element 204 can be mounted on an upper surface of the reaction station 202. The support element 204 can be designed to support reaction chamber 206 and reagent cartridge 208. As previously discussed, reaction chamber 206 is designed to support a slide having a biological sample mounted on it. A fluid can flow into the reaction chamber 206 by virtue of one or a combination of capillarity (i.e., capillary action) (such as where the fluid enters a section in which the slide is positioned adjacent to the reaction chamber 206) , pressure differential applied by a reaction chamber inlet or outlet port 206, vacuum pulse and a fixed quantity pump, as applied through one of the ports, and gravity (such as where the fluid flows from the reagent cartridge 208 positioned above reaction chamber 206).
[0049] The reagent cartridge 208 may contain a primary reagent that must be applied to the slide having a sample mounted on it. Representatively, reagent cartridge 208 may contain reagents suitable for a potentially unlimited variety of procedures, including immunohistochemistry procedures, pigmentation procedures, in situ hybridization procedures, other histochemical procedures, etc. Examples of primary reagents (also called probes, labels or controls) that can be contained within reagent cartridge 208 include, without limitation, any type of antibodies, probes, nucleic acids (RNA, DNA or oligonucleotides), ligands, ligand receptors , enzymes or enzyme substrates or any other molecule suitable for a desired use. The reagents can be in a natural, purified, concentrated, diluted, or conditioned form. In one embodiment, the addition of signal molecules such as fluorescent dyes, enzymes, conjugates (for example, biotin, avidin, streptavidin), metals (such as silver or gold particles), dyes, pigments, radiolabelled molecules, or any other substance such as signaling or reporting molecules.
[0050] The reagent cartridge 208 can be additionally used to facilitate the application of one or more secondary reagents on the slide. In one embodiment, the secondary reagents are distributed from above on a drip and flow surface of the reagent cartridge 208, for example, by a fluid distribution cartridge, as discussed in more detail below. Examples of secondary reagents that can be distributed on the slide, alone or in combination with other secondary reagents, or in combination with one or more primary reagents or bulk reagents include, without limitation, any type of antibodies, probes, nucleic acids (RNA, DNA , or oligonucleotides), ligands, ligand receptors, enzymes, or enzyme substrates or any other molecule suitable for a desired use. The reagents can be in a natural, purified, concentrated, diluted or otherwise conditioned form. In addition, signal molecules such as fluorescent dyes, enzymes, conjugates (for example, biotin, avidin, streptavidin), metals (such as silver or gold particles), dyes, pigments, radiolabeled molecules, or any other substances such such as signaling or reporting molecules can also be distributed.
[0051] In other additional embodiments, one or more of a bulky type of reagent can be applied to a slide positioned in reaction chamber 206. In some embodiments, bulky reagents are stored in containers and distributed into the reaction chamber 206 through a piping system directing fluids into a reaction chamber inlet port 206. Additionally, bulky reagents can be dispensed from an upper bulky reagent dispenser in reaction chamber 206 through reagent cartridge 208 fixed to it. In other additional embodiments, bulky reagents can be delivered from reagent reservoir 210 to reaction chamber 206 through piping including a pump incorporated into reaction station 202. Examples of bulky reagents that can be delivered alone or in combination with other bulky reagents, or in combination with one or more primary reagents or secondary reagents include, without limitation, the following: Tris Buffered Saline (TBS), distilled water or wax removal solution.
[0052] Figure 3A illustrates a perspective view of a reaction chamber modality. Reaction chamber 300 may be a tray sized to hold a sample and / or a slide. As used here, the reaction chamber, sample holding tray and slide holding tray are used interchangeably for reaction chamber 300. In the illustrated embodiment, reaction chamber 300 is configured to be a holding tray for microscopic slide, but it should be appreciated that reaction chamber 300 should not be limited to this and can be configured to hold any sample or sample container. According to one aspect of the embodiment, the reaction chamber 300 functions as a slide holding and positioning system that can be used in processing a substrate such as a tissue sample.
[0053] In one embodiment, the reaction chamber 300 can be used several times. In other embodiments, the reaction chamber 300 may be disposable. Reaction chamber 300 can be formed from a material having sufficient structural strength and neutral process properties to support a slide, retain and be compatible with the reagents and temperatures employed during use. Representatively, in one embodiment, the reaction chamber 300 can be made of a hydrophilic material to facilitate capillary action as will be discussed in greater detail below and have sufficient hardness to withstand scratches created by the glass sheets located therein. In one embodiment, the reaction chamber 300 may be made of a metallic material. For example, reaction chamber 300 can be made of silver, steel or aluminum. A silver material can be used to impart antimicrobial properties to the reaction chamber 300. In the case of an aluminum reaction chamber 300, the aluminum surface can be anodized to create a hydrophilic surface. A hydrophilic surface facilitates the capillary action of a fluid between the slide and the reaction chamber 300. In some embodiments, the anodized surface can be thick, for example, greater than 10 μm, additionally still, between about 10 μm and about 35 μm, for example, about 30 μm. In addition to rendering the surface hydrophilic, it is recognized that the anodized surface can increase the corrosion resistance and wear resistance of the reaction chamber 300.
[0054] Other illustrative materials of reaction chamber 300 may include polymeric heat transfer materials such as plastic or cellulose (i.e., materials based on or comprising cellulose), ceramic, Teflon®, glass, etc. Representatively, reaction chamber 300 can be made of a polyoxymethylene thermoplastic such as DELRIN (a registered trademark of E.I. DuPont de Nemours and Co., Wilmington, Del). The reaction chamber 300 can be formed by any process known in the art such as injection molding, machining, or any other manufacturing process suitable for generating the desired characteristics of the reaction chamber 300. Additionally, it should be appreciated that the chamber Reaction 300 may consist of more than one of the materials discussed above.
[0055] The reaction chamber 300 can optionally include an identifier that is human or machine readable. Representative identifiers may include, but are not limited to, legible identifiers by sight, magnetic field, touch, etc. In some embodiments, the identifier identifies a reagent to be used with respect to a slide positioned in reaction chamber 300, for example, a primary reagent. In other additional embodiments, the identifier identifies the samples within the reaction chamber 300 or a processing protocol to be performed on the sample.
[0056] Specific characteristics of the reaction chamber 300 may include a plate 302. Plate 302 may be a substantially flat surface sized to support plate 322. Plate 322 may have a dimension of length 75 mm and a dimension of width of 25 mm and a thickness of 1 mm. Sample processing (for example, biological species) on slide 322 can take place between slide 322 and plate 302. In this respect, slide 322 can be positioned on plate 302 so that a surface of slide 322 containing the species is facing for plate 302. Plate 302 can be sized so that an entire blade processing area (that is, non-frozen blade area) is positioned on plate 302. In this respect, where a sample occupies the entire processing area of blade, the entire sample can be processed. The plate 302 may include a drip surface 330 at one end to receive a reagent applied to the plate 302 from above. An opposite end of the plate 302 can include a cut-out part 332 to facilitate gripping the blade 322 positioned on the plate 302.
[0057] The fluid inlet port 316 can be formed through the plate 302 over a length dimension for applying a fluid to the plate 302 from below (e.g., a bulky reagent reservoir). Fluid outlet ports 312, 314 can additionally be formed through plate 302 to facilitate removal of fluids from plate 302. Fluid can be supplied or removed from plate 302 using fluid inlet port 316 or fluid outlet 312, 314 through a fluid delivery system such as a pipe or tubes including passages, a pump and valves positioned below reaction chamber 300.
[0058] Wall 304 may be formed around a portion of plate 302 to help retain a processing fluid applied to plate 302. As shown in Figure 3A, a wall 304 is formed around the ends and one side forming a length dimension of the plate 302. It is contemplated, however, that the wall 304 can be formed around any parts of the plate 302 necessary to facilitate the retention of a processing fluid. Wall 304 may be of sufficient height to retain fluids that can accumulate within a corner of plate 302 and adjacent wall 304. Representatively, wall 304 should be of sufficient height to retain from about 25 μl to about 200 μl in reaction chamber 300, approximately 25 μl to 35 μl. In that respect, the wall 304 may have a height of about 4 mm to about 7 mm, for example, from 4.8 mm to 6.5 mm.
[0059] The wall 304 can form the fold 328 along one end of the plate 302 having a reagent drip surface 330. The fold 328 defines an angle 334 along the end of the plate 302 to help direct a fluid distributed to the reagent drip surface 330 along the edge of the plate 302 and between the plate 322 and the plate 302. The angle 334 of the fold 328 not only helps to direct the fluid towards the plate 322, but additionally helps to slow the flow of a fluid distributed to the reagent drip surface 330 of the plate 302 so that the fluid does not flow through the top of the slide 322. Representatively, the angle 334 can be from about 15 degrees to about 35 degrees, preferably , from about 20 degrees to about 30 degrees. In an embodiment in which the reaction chamber 300 is configured to contain a slide (for example, a microscope slide), the drip surface 330 has a length dimension (Il) of the order of 10.5 mm and a dimension of width (wl) of 13 mm, and a width dimension (w2) of 7.8 mm.
[0060] Wall 304 may also include protrusion 320 to help distance blade 322 from wall 304. Distance from blade 322 by a distance from wall 304 helps to introduce and drain fluids between blade 322 and plate 302 In particular, if the edge of the slide 322 is flush with the part of the wall 304 near the point of fluid introduction (for example, reagent drip surface 330), the fluid cannot flow freely along the edge of the slide 322 and the capillary action cannot remove the fluid under the edge of the blade 322. In this respect, the protuberance 320 can be dimensioned to space the blade 322 by a distance of about 1 mm to about 2 mm, for example, 1.5 mm, from wall 304.
[0061] Reaction chamber 300 may additionally include spacer nodules 306, 308 and spacer 310 to facilitate fluid movement between blade 322 and plate 302. Spacer nodules 306, 308 and spacer 310 can be extend from a surface of plate 302 and create a space between plate 302 and slide 322. The space allows fluids (for example, a reagent distributed from plate 302) to be drawn between slide 322 and plate 302 by capillary action. It should be understood that the smaller the space, the greater the capillary action. In this respect, in some embodiments, the spacer nodes 306, 308 may have a height different from the height of the spacer bar 310. This difference in height causes the blade 322 to be supported at an angle to the plate 302. The capillary action it is therefore stronger near the end of the blade 322 closer to the plate 302 than the other.
[0062] Representatively, a height of the spacer nodules 306, 308 may be greater than the height of the spacer bar 310 so that a space near an end of the blade 322 where a fluid is applied from above the chamber reaction 300 will be higher. In this regard, a large volume of fluid can be applied to the plate 302 on the drip surface 330 and initially removed between the blade and the plate 302 by capillary action. Reducing the height of space towards the opposite end of blade 322 (opposite the drip surface 330) will help to draw fluid across the entire surface of blade 322. This space additionally helps to draw fluid introduced through the inlet port. of fluid 316 from plate 302 across the entire surface of blade 322. In other embodiments, spacer nodes 306, 308 and spacer 310 may be the same height. It is noted that the height can be adjusted depending on the desired capillary action. For example, where greater capillary strength is desired, the height of the spacer nodes 306, 308 and / or spacer 310, can be reduced in order to increase capillary strength.
[0063] Fluid inlet port 316 can be used to introduce fluid directly between blade 322 and plate 302. Fluid out ports 312, 314 can be used to drain fluid between blade 322 and plate 302. In some embodiments, fluid outlet ports 312, 314 and fluid inlet port 316 are positioned along one side of plate length dimension 302. Fluid inlet port 316 may be between ports fluid outlet ports 312, 314. The positioning of fluid outlet ports 312, 314 and fluid inlet port 316 is important for controlling fluid dispersion between blade 322 and plate 302. Representatively, it is it is preferable that the outlet ports 312, 314 are sufficiently far from their respective edges of the plate 302 so as not to suck air along the edge of the blade 322. Additionally, it is preferable that at least one of the outlet ports 312, 314 is within an area of ten they are of high surface (for example, near the spacer bar 310) so that an ideal amount of fluid can be removed. Additionally, it is preferred that outlet ports 312, 314 are positioned at opposite ends of plate 302 so that fluids can be drawn across a length of plate 302 at substantially the same rate. This is in comparison with the tapering effect that occurs if the fluid is removed through a single outlet port positioned, for example, in the middle of plate 302. The fluid bottleneck in a single outlet port is not desirable as it results large areas of the blade and plate 302 drying. Although a fluid inlet port 316 and two fluid outlets 312, 314 are illustrated in Figure 3A, it will be contemplated that any number of outlet and inlet ports can be formed through plate 302 depending, for example, on dispersion of desired fluid and / or plate size 302. Additional details regarding the dispersion of the fluid between blade 322 and plate 302 will be discussed with reference to figure 6A and figure 6B.
[0064] In some embodiments, the reaction chamber 300 can be positioned inside the casing 318. The casing 318 can be sized to attach to the bottom of the cup 302 and / or wall 304. The casing 318 can be used to help seal the reaction chamber 300 to an underlying support element (for example, support element 404 shown in figure 4A) and prevent leakage of reagent below the reaction chamber 300. The wrap 318 can be made of the same or different material that of reaction chamber 300. Representatively, in some embodiments, wrap 318 may be made of a silicone material, or any other similar material, suitable for creating a seal between reaction chamber 300 and the element support element (for example, support element 404 illustrated in figure 4A).
[0065] Figure 3B shows a side view of the reaction chamber in figure 3A. As can be seen from figure 3B, the height, h1, of the spacer node 308 can be greater than the height, h2, of the spacer bar 310. In this respect, the blade 322 is positioned at an angle to the plate 302 The space 324 formed between blade 322 and plate 302 is therefore greater at one end than at the other. In some embodiments, the gap 324 is larger between an end of the slide 322 and the plate 302 where fluid 326 is introduced (for example, near the reagent drip surface 330). Representatively, in one embodiment, the height, h1, of the spacer node 308 can be approximately 0.23 mm and the height, h2, of the spacer bar 310 can be approximately 0.18 mm. In additional embodiments, the height, h1, can be from about 0.15 mm to about 0.3 mm, and the height, h2, can be from 0.1 mm to about 0.25 mm.
[0066] Spacer node 308 can be of any shape and dimensions sufficient to create a space between blade 322 and plate 302. Representatively, spacer node 308 can be substantially square in shape. The spacer node 306 may have a substantially similar shape.
[0067] The spacer bar 310 can have any shape and dimensions sufficient to create a space between the blade 322 and the plate 302 and additionally to prevent the flow of a liquid beyond the spacer bar 310. In one embodiment, the spacer bar 310 can have an elongated rectangular shape with a wide dimension, w. It is important that the spacer 310 has a length and width, w, sufficient to prevent a fluid between the blade 322 and the plate 302 from passing beyond the spacer 310. In this respect, the spacer 310 has a dimension of equal length at a width of the plate 302. A width, w, of the spacer bar 310 can be from about 1 mm to about 3 mm, preferably around 2 mm. In addition to blocking fluid flow, the spacer bar 310 helps eliminate air bubbles between plate 302 and blade 322 by directing air bubbles towards an edge of blade 322. As will be discussed in more detail with reference to figures 5A and 5B, plate 302 can be positioned at an angle so that plate 302 has a vertical and horizontal chamfer. In that respect, one side of the plate 302 at one end of the spacer bar 310 may be larger than one side of the plate 302 at the opposite end of the spacer bar 310. Air bubbles trapped between the plate 302 and the blade 322 will want to rise in the towards the highest side of plate 302. Spacer bar 310 can help guide any air bubbles towards the highest side and outward between blade 322 and plate 302.
[0068] Figures 4A and 4B illustrate a perspective view of a reaction chamber and the reagent cartridge of a sample processing system. The sample processing system 400 includes a support element 404 to support the reaction chamber 406 and the reagent cartridge 408. The support element 404 is attached to a reaction station of the system 400 and includes the bottom 410 and the upper part 412. The lower part 410 is dimensioned to support the reaction chamber 406 in the horizontal and vertical angles as will be discussed in greater detail below. The reaction chamber 406 can be fixedly mounted to the lower part 410. The upper part 412 is sized to support the reagent cartridge 408 above a reagent drip surface of the reaction chamber 406. The reagent cartridge 408 can be removably attached to the upper part 412 so that reagent cartridge 408 can be removed and / or replaced as desired by a user. A reagent contained within reagent cartridge 408 or applied to reagent cartridge 408 can flow through reagent cartridge 408 and into reaction chamber 406.
[0069] In some embodiments, the lower part 410 and the upper part 412 can be integrally formed pieces that form a substantially Z-shaped profile. The support element 404 can be formed from any material having sufficient strength to support reaction chamber 406 and reagent cartridge 408 and processing within reaction chamber 406. Representatively, support element 404 can be made of a metallic or plastic material. The support element 404 can be formed by any process known in the art such as injection molding, machining or any other suitable manufacturing process to generate the desired characteristics of the support element 404.
[0070] The reaction chamber 406 can be substantially the same as the reaction chamber 300 described with reference to figure 3A. The slide 422 can be positioned in the reaction chamber 406 as shown in figure 4A. During operation, a reagent is dispensed from reagent cartridge 408 onto the reagent drip surface (see reagent drip surface 330 shown in figure 3A) of reaction chamber 406. Capillary action causes the flow of reagent between the blade 422 and plate 402.
[0071] Figure 4B illustrates additional details of reagent cartridge 408 previously discussed with reference to figure 4A. Reagent cartridge 408 can be a cartridge that contains a reagent or other processing fluid to be applied to slide 422. In that respect, reagent cartridge 408 can include reagent recess 414. Reagent recess 414 can have any shape desired depth or orientation so that the reagents contained therein are directed into the reaction chamber 406. In one embodiment, the reagent is contained within capsule 416 inserted into reagent recess 414. Where capsule 416 is cylindrical, the reagent recess 414 may additionally include a cylindrical shape. The reagent recess 414 includes an open bottom so that it is in fluid communication with the outlet channel 418 extending from a bottom of reagent cartridge 408. When the cap 416 within the reagent recess 414 is punctured, a reagent (e.g., liquid reagent) inside capsule 416 is expelled into reagent recess 414 and descends through outlet channel 418 to a drip surface of reaction chamber 406 where it flows into plate 402.
[0072] The reagent cartridge 408 can help to further route a fluid dispensed from an upper fluid dispensing cartridge to a drip surface of the reaction chamber 406. In this respect, a reagent cartridge 408 can include a channel 420 in fluid communication with outlet channel 418. Channel 420 extends from an upper surface of reagent cartridge 408 through reagent cartridge 408 to outlet channel 418. A fluid (for example, a reagent) dispensed into channel 420 from an upper fluid distributor it travels through reagent cartridge 408 and exits through outlet channel 418 to reaction chamber 406. Since both channels 420 and reagent recess 414 are in communication fluid with outlet channel 418, the fluids dispensed from each are mixed into outlet channel 418 before being mixed in reaction chamber 406. In that respect, outlet channel 41 8 serves as a mixing chamber for two or more fluids delivered from reagent cartridge 408.
[0073] In some embodiments, two or more fluids can be delivered into channel 420 from an upper fluid distributor. In this respect, the channel 420 may be of a dimension of width (w1) sufficient to receive two or more fluids. Representatively, the channel 420 can have a width of about 10 mm to about 15 mm, preferably about 12.5 mm. Additionally, it is contemplated that a bottom shape of channel 420 may have a non-reflecting curve to minimize the splash of fluids distributed into channel 420.
[0074] Capsule 416 may be attached to reagent cartridge 408 with holder 424. Holder 424 may include an elongated connector 426 such as a strap that attaches to capsule 416. In one embodiment, capsule 416 is removably attached to the connector 426 of support 424. In other embodiments, capsule 416 is attached to connector 426. Reagent cartridge 408 may include a notch 430 sized to receive support 424. In addition, a groove 432 can be formed within reagent cartridge 408 between the notch 430 and the reagent recess 414. The connector 426 can be inserted into the groove 432 when the holder 424 is attached to the reagent cartridge 408 so that the capsule 416 is securely aligned within the reagent recess 414 by a reaction force of connector 426.
[0075] The identifier 428 can be replaced on the support 424 as illustrated in figure 4B. The identifier 428 will be discussed in more detail with reference to figure 9A. Reference cartridge 408 and capsule 416 will be discussed in more detail with reference to figures 7 to 9.
[0076] The reagent cartridge 408 can be made of the same or different material as the reaction chamber 406. Representatively, the reagent cartridge 408 can be made of a plastic, metallic or ceramic material and formed by any process known in the art such as injection molding, machining or any other manufacturing process suitable for the generation of desired characteristics.
[0077] Figures 5A and 5B are seen in perspective illustrating the horizontal and vertical angles of a modality of a reaction chamber. Reaction chamber 506 is positioned at horizontal angle 534 and vertical angle 536 to facilitate movement of the fluid (eg reagent) between slide 522 and plate 502. Figures 5A and 5B illustrate reaction chamber 506 positioned at bottom 510 of support element 504. Bottom 510 is sized to receive and position reaction chamber 506 at horizontal angle 534 and at vertical angle 536. Horizontal angle 534 refers to the angle of an edge of reaction chamber 506 defining a dimension of length of the reaction chamber 506 with respect to the ground level. Vertical angle 536 refers to the angle of a surface of reaction chamber 506 defining plate 502 at ground level. The horizontal angle 534 is shown in figure 5A and the vertical angle 536 is shown in figure 5B. The horizontal angle 534 can be from about 5 degrees to about 15 degrees, for example, from 6 degrees to 8 degrees, and in another example, about 7 degrees. The vertical angle 536 can be from about 15 degrees to about 45 degrees, for example, from 20 degrees to 30 degrees, and in another example, about 29 degrees.
[0078] As previously discussed, the horizontal angle 534 and vertical angle 536 of the reaction chamber 506 help direct the dispersion of fluid or movement between plate 502 and slide 522. In particular, vertical angle 536 causes the edge 538 of the plate 502 forming the length dimension and the adjacent reagent drip surface 530 are positioned higher than an opposite edge 540 of the plate 502. The horizontal angle 534 causes the end 542 of the drip surface to reagent adjacent to plate 530 is positioned lower than the opposite end 544 of plate 502. Since the corner 546 of plate 502 is higher than the diagonally opposite corner 548, air bubbles trapped between plate 522 and plate 502 can climb towards the upper edge / edge of blade 522 and escape. In addition, when a fluid (eg, reagent) is dispensed from the highest drip surface 530, gravity draws the fluid down towards the corner 548 of the plate 502. As the fluid flows towards the corner 548 , it flows along the edge 542 of the plate and the adjacent end of the blade 522 and is removed between the blade 522 and the plate 502 by the capillary action. Since the fluid is between the blade 522 and the plate 502, the capillary action further removes the fluid against gravity along the length of the blade 522 towards the uppermost corner 546 of the plate 502.
[0079] The horizontal angle 534 of the plate 502 also facilitates the drainage of the reaction chamber 506 preventing the fluid from accumulating along the lower edge of the plate 522. Instead, the fluid is drawn towards the inner corner 548 of the plate 502 where a fluid outlet port is positioned so that fluid can be removed through the outlet port. In addition, any excess fluid is contained along the inner corner 548, preventing it from flowing over the top of the blade 522.
[0080] Figures 6A and 6B illustrate a perspective view of a reaction chamber modality. The reaction chamber 600 can be substantially the same as the reaction chamber 300 described in reference to figure 3A. Reaction chamber 600 may include a plate 602 sized to support blade 622 therein. Plate 602 may include a reagent drip surface 630 at one end for receiving a reagent applied to plate 602 from above. An opposite end of the plate 602 can include a cutout portion 632 to facilitate gripping the blade 622 positioned on the plate 602.
[0081] Wall 604 can be formed around part of plate 602 to retain a reagent located on plate 602. Wall 604 can be of sufficient height to retain fluids that can accumulate within a corner formed by plate 602 and wall 604. Wall 604 can form fold 628 having an angle 634 along one end of plate 602. Wall 604 can also include protrusion 620 to help distance blade 622 from wall 604.
[0082] Spacer nodes 606, 608 and spacer 610 can extend from a surface of plate 602 and create a space between plate 602 and blade 622. Fluid outlet ports 612, 614 and port fluid inlet 616 can be formed through plate 602.
[0083] Figure 6A illustrates a fluid flow path between blade 622 and plate 602 when fluid is introduced from a fluid distribution cartridge positioned above reaction chamber 600. In particular, the fluid (for example, reagent) can be distributed on the reagent drip surface 630. Due to the horizontal and vertical angles of the reaction chamber 300 beyond the fold 628 of the wall 604 as previously discussed, the fluid follows the flow path 640 along the fold 628 of the wall 604 and an edge of the blade 622. The fold 628 of the wall 604 provides an inclination (angle 634) that slows down the flow of fluid from the reagent drip surface 630 towards the blade 622. In particular, in the absence of the fold 628 , the fluid will flow directly from the reagent 630 drip surface down the edge of slide 622. Such a large amount of fluid will flow at such a speed that part of the fluid will flow above one side of slide 622 opposite the plate 602. The angle 634 of the fold 628 of the wall 604 and the horizontal and vertical angles of the reaction chamber 600 help to slow the fluid down and spread it along the edge of the blade 622 to prevent such excessive flow.
[0084] Some fluid continues along the wall 604 to the lower corner of the blade 622 while some fluid is removed immediately between the blade 622 and the plate 602 by means of capillary action. The fluid that accumulates between the wall 604 and the lower corner of the blade 622 is also removed between the blade 622 and the plate 602 by capillary action. The fluid that is withdrawn immediately between the blade 622 and the plate 602 flows along the flow path 640a while the fluid that initially accumulates at the corner of the blade 622 follows the flow path 640b. The flow path 640a and 640b eventually converges to form a single wavefront 642 that runs through the length of the blade 622 towards an opposite end of the blade 622. The introduction of the fluid between the blade 622 and the plate 602 at two points allows the fluid to cover a substantial width of the slide 622 across the entire length of the slide 622. In this respect, the wavefront 642 of the fluid is substantially homogeneous across the entire length of the slide 622, thereby maximizing fluid coverage .
[0085] Figure 6B illustrates a fluid flow path between blade 622 and plate 602 when fluid is introduced through fluid inlet port 616. Fluid inlet port 616 is positioned off center with respect to a distance between the spacer bar 610 and an opposite end of the reaction chamber 600. Positioning the fluid inlet port 616 in this way achieves a desired balance between the speed with which the fluid introduced through the fluid inlet port 616 travels through the blade 622, the fluid cover and the amount of air bubbles trapped between the blade 622 and the plate 602. In particular, it has been found that when fluid is introduced through an inlet port positioned at a greater distance from the spacer bar 610 (for example, 20 mm), fluid travels through blade 622 at a lower speed and more air bubbles remain trapped between blade 622 and plate 602 than where the fluid is introduced through an entrance door positioned closer to the spacer bar 610 (for example, 5 mm). The introduction of the fluid at a lower speed (for example, where the inlet port 616 is at a greater distance from the spacer bar 610) allows a more homogeneous wavefront to travel through the blade and therefore better blade coverage. When the inlet port is positioned closer to the spacer bar 610, the fluid flows at a higher speed and there are fewer air bubbles, but the fluid fills starting from the spacer bar 610 and continues through the blade 622 at an undesirable angle.
[0086] As illustrated in figure 6B, when the fluid is introduced through the inlet port 616 positioned off center (for example, 15 mm to about 20 mm from the spacer bar 610), the fluid follows the flow path 644 in a vertical direction across a blade width 622. The flow path 644 has a substantially homogeneous wavefront 642 allowing for optimal blade coverage.
[0087] Figure 7 illustrates a top perspective view of one embodiment of a reagent cartridge. The reagent cartridge 700 is substantially the same as the reagent cartridge 408 described with reference to figure 4B except that in this embodiment the reagent capsule is removed so that the characteristics of the reagent recess 714 can be seen more clearly. In that regard, reagent cartridge 700 includes housing 702 which attaches to a support element as described with reference to figure 4A. Housing 702 includes reagent recess 714, channel 720 and notch 730. Reagent recess 714 and channel 720 converge to form outlet channel 718.
[0088] As previously discussed, the notch 730 is sized to receive a support (see support 424 of figure 4B) that is connected to the reagent capsule. Figure 7 illustrates the notch 730 having partitions 734, 736 dimensioned to receive the support arms (see arms 922, 924 of figure 9A) extending from the underside of the support. The support arms are inserted into partitions 734, 736 to position and hold the support in the notch 730 and, in turn, the reagent capsule within the reagent recess 714. The reagent recess 714 includes a protrusion 738 formed within the recess reagent 714 to support a reagent capsule positioned there. As can be seen from figure 7, the projection 738 extends from the wall of the reagent recess 714, but not close to the opening of recess 714 in order to allow a reagent distributed from the capsule to travel through the recess of reagent 714 for outlet channel 718.
[0089] Housing 702 further defines groove 732 extending between notch 730 and reagent recess 714. Groove 732 is sized to receive the connector connecting the holder to the reagent capsule as discussed previously. The placement of a holder within the notch 730 and a connector within the groove 732 facilitates the alignment of the reagent capsule within the recess 714.
[0090] Figure 8 illustrates a bottom perspective view of the reagent cartridge of figure 7. From this view it can be seen that the tongues 840, 842 extend from the housing 702 below the partitions 734, 736, respectively. The tabs 840, 842 are dimensioned to position and hold the reagent cartridge 700 on top of the support element (see upper part 412 of support element 404 of figure 4A). In that respect, the support element may include partitions into which the tabs 840, 842 can be removably inserted. The tabs 840, 842 and, in turn, the reagent cartridge 700, can be removed from the top by pulling the reagent cartridge in a direction away from the support element.
[0091] Partitions 734, 736 can be dimensioned to receive the arms extending from the underside of the support as shown in figure 9B. In this regard, partitions 734, 736 help to secure the holder to reagent cartridge 700. The support arms can be removed from partitions 734, 736 by pulling the holder in a direction along housing 702. Alternatively, the holder can press fit into partitions 734, 736 in order to release support from partitions 734, 736.
[0092] Reagent recess 714 connects to outlet channel 718 through reagent recess channel 846. Reagent recess channel 846 provides an inclined surface over which a reagent, for example, from a capsule positioned within the reagent recess 714 can travel in the direction of outlet channel 718. reagent recess channel 846 converges with channel 720.
[0093] Channel 720 includes an inclined first part 848 and an inclined second part 850. The inclined first part 848 is at an inclination of about 30 degrees with respect to the horizontal plane. The second inclined portion 850 extends from the first inclined portion at a right angle towards the reagent recess channel 846 and is additionally at an inclination of approximately 30 degrees. The dimensions of channel 720 and reagent recess channel 846 are selected so that the fluids that travel along the channels converge with each other and mix before being delivered to an underlying reaction chamber. In that regard, multiple fluids can be mixed together and distributed to outlet 844 of outlet channel 718. Additionally, it is preferable that the various flow paths of reagent cartridge 700 (for example, recess channel 846, channel 720 and outlet channel 718) have a round tubular dimension to inhibit the trapping of fluids traveling through the flow paths and to minimize splash when the fluid is distributed within the flow paths.
[0094] Figure 9A illustrates a perspective view of an embodiment of a reagent and support dispensing capsule. Capsule 900 includes container 902 sized to hold a reagent in it. The seal 930 can be positioned through the opening of the container 902 to retain the reagent. Inside the capsule 900 there is a plunger 904. The plunger 904 can be an elongated structure having an end attached to the closed end of the container 902 and an opposite end extending towards the opening of the container 902. The end of the plunger 904 positioned in the opening of the container 902 can be adapted to pierce through the seal 930 formed through the opening of the container 902. Representatively, the end of the plunger 904 can have one or more tips extending from the end. During operation, a force is applied to the closed end of the container 902 causing the container 902 to disassemble and push the plunger 904 in a direction of the seal 930. The plunger 904 contacts and punctures the seal 930, thereby opening the end of the container 902 to allow the release of the reagent contained therein.
[0095] Reagent capsule 900 can be attached to support 910 by connector 906 as previously discussed. In this respect, the connector 906 can have the clamping end 908 that fits into the receiving partition 916 formed by the support 910. The support 910 can have the upper side 912 and the rear side 914 that are formed at right angles to each other. In that regard, when support 910 is attached to the reagent cartridge (for example, reagent cartridge 700 of figure 7), the upper side 912 is positioned within the notch (for example, notch 730 of figure 7) formed along an upper side of the reagent cartridge. The rear side 914 of support 910 overlaps with a rear side of the reagent cartridge.
[0096] The identifiers 918, 920 can be positioned on the support 910. The identifiers 918, 920 may contain machine-understandable codes, such as those provided by radio frequency identification (RFID) indicators, format identifiers, color identifiers , numbers or words, other optical codes, bar codes, etc. The identifiers 918, 920 can be used to identify, for example, the contents of the capsule 920 and / or a processing protocol. Additionally, one or more of the identifiers 918, 920 may contain patient and history information, information regarding biological samples on the slides, arrival and departure times of the biological samples, tests performed on the samples, diagnoses made and so on. Identifiers 918, 920 can contain the same information or different information.
[0097] In some embodiments, one or more of the identifiers 918, 920 can be removable so that the identifier can be attached to another item in the system. For example, identifier 918 may contain information identifying a reagent contained within capsule 902 and / or a processing protocol. The 920 identifier can contain the same information. Before processing a slide using the contents (eg, reagent) of the 902 capsule, the identifier 918 can be removed from the holder 810 and positioned on the slide. Alternatively, identifier 918 can be positioned on the slide after processing. The reagent and / or process carried out on the slide can then be readily determined from identifier 918 on the slide. The ability to transfer identifiers in this way helps to prevent processing and identification errors.
[0098] Figure 9B illustrates a perspective view of the reagent and support dispensing capsule of figure 9A. From this view, support arms 922, 924 extending from a lower surface of support 910 can be seen. When support 910 is positioned within the notch (for example, notch 730 in figure 7) of the reagent cartridge (for example, reagent cartridge 700 in figure 7), the support arms 922, 924 fit within the partitions (for example , partitions 734, 736, of figure 7) formed in the notch of the reagent cartridge to hold support 910, and in turn, capsule 900 in place. The support arms 922, 924 grip the wall of the reagent cartridge forming partitions 734, 736 (see figure 8), respectively to lock support 910 in place. In that respect, the support arms 922, 924 can have any size or dimensions complementary to the partitions 734, 736 and the reagent cartridge 700.
[0099] Figures 10A to 10D illustrate a cross-sectional side view of a capsule pressure mechanism during operation. Figure 10A illustrates a capsule pressure mechanism 1000 in an elevated position so that it does not come into contact with the underlying reagent capsule 1024. The capsule pressure mechanism 1000 includes housing 1002 to support the components of the pressure mechanism 1000 The components of the pressure mechanism 1000 may include piston 1004 having a head member 1006 positioned at one end. The spring element 1008 can additionally be positioned around an opposite end of the piston 1004 to orient the piston 1004 in an elevated position.
[00100] Crankshaft 1010 can be attached to piston 1004 to drive the vertical movement of piston 1004. Crankshaft 1010 can be rotationally attached to piston 1004 at one end and gear 1012 at an opposite end. The gear 1012 can be rotated by the lateral movement of the sliding arm 1014. The sliding arm 1014 can include teeth along one of the teeth that are complementary to the teeth of the gear 1012. The lateral movement of the sliding arm 1014 causes the teeth of the arm slide 1014 engage the teeth of gear 1012 and rotating gear 1012 in a clockwise or counterclockwise direction. The rotation of the gear 1012, in turn, causes the end of the crankshaft 1010 fixed to the piston 1004 to move vertically. When the end of the crankshaft 1010 moves in an upward direction, piston 1004 is raised and when the crankshaft 1010 moves in a downward direction, piston 1004 is lowered. The lateral movement of the sliding arm 1014 can be driven by the driver 1016. The driver 1016 can be any type of drive mechanism capable of driving the lateral movement of the sliding arm 1014. Representatively, the driver 1016 can be a unit including a motor and a gear that can be engaged with a gear located on the opposite side of the sliding arm 1014.
[00101] Reagent cartridge 1018 can be positioned below the capsule pressure mechanism 1000. Reagent cartridge 1018 can be substantially the same as reagent cartridge 408 described with reference to figure 4B. In that regard, reagent cartridge 1018 includes reagent recess 1022 to retain reagent capsule 1024. Reagent cartridge 1018 additionally includes channel 1020. Reagent capsule 1024 includes container 1030 having a sealed end with seal 1026. The seal 1026 can be any type of seal capable of being pierced by the plunger 1028 to release the contents into the reagent capsule 1024. Representatively, the seal 1026 can be a heat seal made of a metal foil or plastic material.
[00102] In some embodiments, the breaking of the seal 1026 and the release of a reagent from the reagent capsule 1024 is carried out by a two-step process as illustrated in figures 10B, 10c and 10d. In particular, during operation, the pressure mechanism 1000 drives piston 1004 vertically in a direction of reagent capsule 1024. Head 1006 of piston 1004 presses reagent capsule 1024, disassembling capsule 1024 and driving plunger 1028 through the seal 1026 as shown in figure 10B. A piston pitch length 1004 is controlled so that once the seal 1026 is broken, the vertical movement of piston 1004 is reversed and piston 1004 is raised as shown in figure 10c. During the initial downward piston pass, only a small amount of reagent from the 1024 capsule is released. The elevation of piston 1004 allows a small amount of air to enter the capsule 1024. The downward vertical movement of piston 1004 is then restarted and piston head 1006 of piston 1004 completely disassembles capsule 1024 causing the ejection of all content held inside the capsule. 1024 as illustrated in figure 10d.
[00103] It has been found that breaking the seal and releasing the entire contents of capsule 1024 with a pitch of piston 1004 causes part of the reagent held within capsule 1024 to escape from capsule 1024 resulting in the loss of some reagent. Such an outlet can be reduced or eliminated by using a first piston pass to pierce the seal 1026, allowing some air to enter the 1024 capsule and then a second piston pass to eject the remaining contents of the 1024 capsule. reagent has been ejected from capsule 1024, piston 1004 is lifted back to its initial position as shown in figure 10A.
[00104] Figure 11 is a perspective view of a reaction station in a sample processing system. Reaction station 1100 includes a support element 1102 having reaction chamber 1104 and reagent cartridge 1106 positioned therein. Support element 1102, reaction chamber 1104 and reagent cartridge 1106 can be substantially the same as support element 404, reaction chamber 406 and reagent cartridge 408 described with reference to figure 4A.
[00105] As can be seen from this view, reaction station 1100 additionally includes reservoir 1108. Reservoir 1108 can be used to hold a bulky reagent that must be supplied to reaction chamber 1104 during processing. In this respect, reservoir 1108 is attached to support element 1102 and is in fluid communication with reaction chamber 1104. Typically, in illustrative processing systems, there are several reagents that must be applied to the reaction chamber at various times during processing. Such reagents are normally contained in bulky containers and separate supply lines must run from the container to each reaction chamber. Reservoir 1108, however, eliminates the need for multiple supply lines. Instead, as will be described in more detail with reference to figures 16A, 16B and 17, the supply lines for each bulky container run to a single volume dispenser. The volume distributor can then be positioned over reservoir 1108 to distribute the desired bulky reagent into reservoir 1108. Aliquots of the fluid contained within reservoir 1108 can then be removed and applied to reaction chamber 1104 according to the processing protocol . Such a configuration is particularly advantageous where multiple reaction chambers are present in the system as it allows the desired fluid to be applied to each reaction chamber at any time. This occurs in contrast to typical processing systems in which the application of a fluid from the bulky vessel to a reaction chamber can be delayed until the application of the fluid to another reaction chamber is completed.
[00106] Reservoir 1108 can have adequate dimensions to hold a volume of liquid necessary to complete processing inside reaction chamber 1104. For example, reservoir 1108 can hold a volume, for example, up to 10 ml, in some modalities about 6 ml. Aliquots of, for example, 50 microliters can be transferred from reservoir 1108 to reaction chamber 1104 at desired times during processing. A supply line (not shown) can run from reservoir 1108 to reaction chamber 1104 along support member 1102 to transfer fluid from reservoir 1108 to reaction chamber 1104.
[00107] Dump line 1110 can be connected to reservoir 1108. Dump line 1110 can facilitate removing excess fluid from reservoir 1108 and / or changing a fluid held within reservoir 1108.
[00108] Reaction station 1100 may additionally include a temperature modification set 1112 for the heating and cooling reaction chamber 1104. It is important when processing a sample inside reaction chamber 1104 that the reaction chamber plate 1104 can be heated and cooled as desired. Rapid cooling is important during, for example, antigen recovery, particularly after the steps involving heating the reaction chamber 1104. In this respect, the temperature modification set 1112 is positioned below the reaction chamber 1104. The set temperature modification 1112 may include a thermoelectric cooler (TEC) (see TEC 1206, 1204 described with reference to figure 12), heat tank 1114 and fan 1116 as will be discussed in more detail with reference to figure 12.
[00109] Figure 12 illustrates a perspective view of an embodiment of a temperature modification set. The temperature modification set 1200 can include reaction chamber 1202, TEC 1204 and 1206, heat tank 1208 and fan 1214. TEC 1204 and 1206 can be positioned in a side-by-side configuration along an underside of the reaction chamber 1202. TEC 1204 and 1206 can be used to heat or cool reaction chamber 1202. To cool reaction chamber 1202, heat from one side of TEC 1204 and 1206 in contact with reaction chamber 1202 is transferred to the opposite side of TEC 1204 and 1206. To heat reaction chamber 1202, the heat transfer is reversed since it is transferred from the side of TEC 1204 and 1206 opposite reaction chamber 1202 to the side in contact with the reaction chamber 1202. TEC 1204 and 1206 can be any TEC device such as the one commercially available from Ferrotec Corporation under model number 9501/071 / 040BS / L300.
[00110] Heat tank 1208 and fan 1214 can facilitate heat transfer within TEC 1204 and 1206. In particular, heat tank 1208 can include a base part 1210 attached to a surface of TEC 1204 and 1206 and fin part 1212. The base part 1210 can be a solid block made of a heat transfer material, for example, aluminum. In that respect, the base part 1210 can be used to increase the heating capacity of the heat tank 1208. The fin part 1212 extends from the base part 1210. The heat from TEC 1204 and 1206 is absorbed by the part of base 1210 and dissipated into the air through the fin part 1212. The TEC 1204 and 1206 and the heat deposit 1208 allow direct cooling and / or heating of the reaction chamber 1202.
[00111] The fan 1214 is positioned so that it blows air into the fin part 1212 to facilitate heat dissipation. A fan speed 1214 can be set or controlled by a user and modified depending on the desired heat dissipation level. Representatively, where the rapid cooling of the TEC 1204 and 1206, and, in turn, the reaction chamber 1202, is desirable, a fan speed 1214 can be increased in order to increase air circulation through the fin 1212. In that regard, the temperature modification set 1200 may be able to rapidly cool reaction chamber 1202 from a temperature of 98 ° C to 10 ° C in 5 minutes, for example, in less than 3 minutes.
[00112] In some embodiments, the temperature modification set 1200 may additionally include one or more thermistors. Representatively, thermistors 1216 and 1218 can be interchanged between reaction chamber 1202 and TEC 1204 and 1206, respectively. Thermistors 1216 and 1218 can be used to monitor and / or control the temperature of the temperature modification set 1200. In particular, thermistors 1216 and 1218 can measure a temperature in the reaction chamber 1202. The temperature can be used to determine whether a temperature of TEC 1204 and 1206 must be maintained or modified.
[00113] Figure 13 illustrates a perspective view of a modality of the entire reaction station. Reaction station 1300 includes a reaction station similar to reaction station 1100 previously discussed with reference to figure 11 and includes temperature change set 1302 similar to modification set 1200 previously discussed with reference to figure 12. The reaction station 1300 includes support element 1304 having reaction chamber 1306 and reagent cartridge 1308 positioned therein. The reaction station 1300 additionally includes a reservoir 1310. A TEC device (not shown), a heat tank 1314 and a fan 1312 as previously discussed with reference to figure 12 are positioned under reaction chamber 1306.
[00114] The reaction station 1300 additionally includes the identification platform 1316 and the handle part 1320. The identification platform 1316 is positioned at one end of the reaction station 1300 that is viewed by a user. The identification platform 1316 can include the identifier 1318 that identifies the reaction station 1300. As previously discussed, the sample processing system can include more than one reaction station 1300 so that the processing of multiple samples can take place at a time . It is, therefore, desirable to identify each reaction station 1300 with the identifier 1318 so that the user and / or the system can identify the reaction station by processing a particular sample and / or the sample location. The 1318 identifier can be any of the previously discussed types of identifiers, for example, radio frequency identification (RFID) indicators, format identifiers, color identifiers, numbers or words, other optical codes, bar codes, etc.
[00115] As previously discussed with reference to figure 1, reaction station 1300 can slide in and out of a reaction compartment (see reaction compartment 104 shown in figure 1) formed by a housing (see housing 102 illustrated in figure 1) to facilitate access to reaction chamber 1306 mounted on it. The rail element 1322 can be connected to the housing and provide a surface along which the reaction station 1300 can slide. Representatively, the rail element 1322 may include a channel for orienting reaction station 1300 into and out of the reaction compartment. Handle 1320 extending from one end of reaction station 1300 can be used to slide reaction station 1300 into and out of the reaction compartment.
[00116] Interlock set 1324 can be connected to one end of reaction station 1300 opposite handle 1320. Figure 13 illustrates a rear side view of interlock set 1324. Interlock set 1324 can be any type of locking system interlock capable of locking the 1300 reaction station inside the reaction compartment and preventing its removal. In some embodiments, the 1324 interlock assembly may include an electromechanical locking system. Representatively, interlocking assembly 1324 may include a bistable solenoid. It is desirable for the 1324 interlock assembly to remain locked in the event of a power failure to prevent improper removal of the 1300 reaction station. Representatively, in the event of a power failure, the 1324 interlock assembly remains in position locked until a user purposefully unlocks the 1324 interlock assembly. The 1324 interlock assembly can serve as a secondary locking system for each individual reaction station 1300 while a primary locking system can be provided to lock the system housing (for example, example, cover element 108 and door element 110 of reaction compartment 104 discussed with reference to figure 1). The primary locking system can unlock the system in the event of a power failure to allow a user to access each 1300 reaction station, however, removal of the 1300 reaction station can still be prevented by the 1324 interlock assembly.
[00117] Figure 14 illustrates a front perspective view of the interlocking assembly described with reference to figure 13. Interlocking assembly 1324 may include an electromechanical locking system 1412. In some embodiments, the electromechanical locking system 1412 may be a bistable solenoid as commercially available from Takano Co, LTD under product number TSB-0805-SS1. The frame element 1326 to support the bistable solenoid 1412 can be attached to the rail element 1322 of the reaction compartment. The bistable solenoid 1412 can generally include the solenoid housing 1414 attached to the frame element 1326. The thrust pin 1416 can extend from an upper end of housing 1414 and the plunger 1418 can extend from a lower end of the housing 1414. The thrust pin 1416 and the plunger 1418 are connected and move simultaneously in a vertical direction. The push pin 1416 is used to lock or unlock the reaction station 1300 and the plunger 1418 is used to detect the lock or unlock the reaction station 1300.
[00118] The locking arm 1328 of the reaction station 1300 can include the opening 1420 dimensioned to receive the push pin 1416. The opening 1420 is positioned inside the locking arm 1328 so that when the sensor of the reaction station 1330 detects the presence of the locking arm 1328, the opening 1420 is aligned with the push pin 1416. The push pin 1416 can then be advanced towards the locking arm 1328 and through the opening 1420 to lock the reaction station 1300 in place . The bistable solenoid 1412 allows the push pin 1416 to be held in the locked position even after the power is disconnected. Where energy is lost and unlocking of interlocking assembly 1324 is desired, a tool can be used to dislodge the push pin 1416 from inside the opening 1420.
[00119] The 1330 reaction station sensor can be used to detect the presence of the 1330 reaction station inside the reaction compartment. The 1330 reaction station sensor including detection arms 1402 and 1404 is attached to the frame element 1326. A space can be provided between the detection arms 1402 and 1404 on the 1330 reaction station sensor to receive the 1328 locking arm Detection arms 1402 and 1404 can include sensor elements to detect the presence or absence of locking arm 1328. Representatively, arm 1402 can emit a laser beam in the direction of a beam detector on arm 1404. When the laser beam is interrupted by the locking arm 1328, the detector in the arm 1404 no longer detects the beam of the arm 1402. The system is then alerted that the reaction station 1300 is in position and can be locked in place. Similarly, when the laser beam is detected by the laser beam detector on arm 1404 (i.e., locking arm 1328 is not between arms 1402, 1404), interlock assembly 1324 remains in the unlocked position. The reaction station sensor may include a variety of types of sensors and / or switches, including, but not limited to, optical sensors and readout switches.
[00120] The interlock sensor 1406 for detecting the position (locked or unlocked) of the interlock assembly 1324 can be additionally attached to the frame element 1326. Similar to the sensor of the reaction station 1330, the interlock sensor 1406 can include lock arms detection 1408 and 1410. Detection arm 1408 may include a laser beam directed at a laser beam detector on arm 1410. In this respect, detection arms 1408 and 1410 can detect the position (locked or unlocked) of the interlock 1324.
[00121] The information on the position of the reaction station obtained from the sensor of the reaction station 1330 and / or interlock sensor 1406 can be used to detect the introduction of a new slide in the system during processing. For example, in a mode in which there are 30 1300 reaction stations within the system, a user can initially position the slides at 20 1300 reaction stations. The remaining 10 reaction stations may be empty. Each of the 1300 reaction stations is initially scanned to determine whether a slide and the corresponding reagent cartridge are positioned there. The appropriate processing protocols will additionally be carried out in only a few stations having slides and reagent cartridges in them. If, during processing, a user wishes to add a slide to one of the empty reaction stations, the user opens the reaction chamber and slides a reaction station out, places the slide and the reagent cartridge in the station and then slides the same inside. The sensors detect that one of the 1300 reaction stations has been removed and slid back into a locked position. Based on this information, the system then begins to scan the station and process the new slide.
[00122] Figure 15 illustrates a perspective view of an embodiment of an upper fluid distribution system and capsule pressure mechanism. The fluid delivery system 1500 generally includes the fluid delivery set 1502 used to deliver a fluid to a reaction chamber of an underlying reaction station. The fluid distribution set 1502 is attached to the mounting set 1506. The capsule pressure mechanism 1504 to facilitate the release of a reagent from a reagent capsule into a reagent cartridge in the reaction station can be additionally attached to the assembly set 1506. The fluid distribution set 1502 and the capsule pressure mechanism 1504 can be positioned within the assembly stations (see assembly stations 1618 in figure 16A) of the assembly assembly 1506. Despite a set of fluid distribution 1502 and capsule pressure mechanism 1504 are illustrated in figure 15, it is contemplated that any number of fluid distribution assemblies 1502 and capsule pressure mechanisms 1504 can be mounted on mounting assembly 1506. Representatively, in one embodiment, mounting assembly 1506 may include at least 20 mounting stations having at least 19 fluid distribution sets 1 502 and at least one capsule pressure mechanism 1504 mounted thereon. In some embodiments that have two capsule pressure mechanisms, the capsule pressure mechanism 1504 can be mounted on one side of the mounting assembly 1506 opposite a second capsule pressure mechanism.
[00123] The assembly set 1506 can be substantially the same as the assembly set 116 described with reference to figure 1. In one embodiment, the assembly set 1506 can be a carousel that is rotatable about a central geometric axis of in order to align the fluid distribution set 1502 and / or capsule pressure mechanism 1504 with a reagent cartridge or a reagent capsule positioned below the assembly set 1506. The assembly set 1506 can also be linearly translated so that the fluid distribution assembly 1502 and the capsule pressure mechanism 1504 can move from one reaction station to the next.
[00124] The fluid distribution set 1502 can be any fluid distribution set 1502 suitable for delivering a fluid to an underlying reagent cartridge. Representatively, in one embodiment, fluid delivery set 1502 may include fluid delivery cartridge 1508 connected to cartridge pump set 1510. Fluid delivery cartridge 1508 may include a container for holding a fluid (for example, example, a reagent) connected to a tube element for dispensing the fluid in an underlying reagent cartridge. The cartridge pump assembly 1510 can be a pump mechanism sized to pump fluid from the fluid delivery cartridge 1508.
[00125] The capsule pressure mechanism 1504 can also be mounted on the assembly set 1506. The capsule pressure mechanism 1504 can be substantially the same as the capsule pressure mechanism 1000 described with reference to figures 10A to 10D. In that regard, the capsule pressure mechanism 1504 can include housing 1516 and piston 1512. The flexible element 1514 can be additionally positioned around piston 1512 to orient piston 1512 in an elevated position. A driver (not shown) as previously discussed with reference to figures 10A to 10D can be positioned concentrically inward from the cap pressure mechanism 1504 to drive the movement of piston 1512.
[00126] During operation, assembly set 1506 moves from one reaction station to the next and can additionally rotate to align fluid distribution set 1502 and capsule pressure mechanism 1504 with the desired station. In some embodiments, the assembly assembly 1506 having the fluid distribution cartridges can complete one cycle (for example, complete one pass through each reaction station) every 3 minutes. In this respect, where there are 30 reaction stations, the assembly set 1506 passes through each reaction station every 6 seconds, with approximately 2 to 3 seconds in each reaction station for reagent distribution.
[00127] Figures 16A and 16B illustrate perspective views of an embodiment of an upper fluid distribution system. Referring to figure 16A, fluid delivery system 1600 generally includes fluid delivery set 1602 and bulk reagent dispenser 1604. Fluid delivery set 1602 is substantially similar to fluid delivery set 1502 described with reference to figure 15. In this respect, the fluid distribution set 1602 includes a mounting set that is rotatable and linearly translated through the underlying reaction stations 1606. Mounting stations 1618 are provided in the mounting set for mounting the distribution cartridges reagent and / or capsule pressure mechanisms.
[00128] Fluid delivery system 1600 additionally includes bulky fluid delivery set 1604. Bulky fluid delivery set 1604 is used to deliver bulky fluids into bulky fluid reservoirs 1614 of reaction stations 1606 as discussed with reference to figure 11. In this respect, the bulky fluid distribution set 1604 includes a nozzle holder 1608 to support nozzles 1610. Nozzles 1610 are connected to supply line 1612. Each of the supply lines 1612 is connected to a respective bulky container. As previously discussed with reference to figure 11, a single supply line 1612 of a desired bulky container can be used to fill the reservoirs of bulky fluid 1614. In this respect, each of the supply lines 1612 can be connected by fluid to a container different bulky. The number of nozzles 1610 and associated supply lines 1612 can vary depending on the number of different bulky fluids desired. Representatively, in one embodiment, six nozzles 1610 and six supply lines 1612 extending from six different bulky containers can be connected to the nozzle holder 1608.
[00129] Nozzle support 1608 can be linearly translated through the underlying reaction stations 1606. In this respect, nozzle support 1608 can be mobilely connected by support arms 1620 to support rail 1616. Support rail 1616 can extend along a rear end of reaction stations 1606. Nozzle support 1608 extends from support rail 1616 through reaction stations 1606. Nozzle support 1608 and associated supply lines 1612 and nozzles 1610 can be moved along the support rail 1616 by other x geometrical axes and positioned over the desired bulk fluid reservoir 1614. Once the nozzle support 1608 is positioned over the desired bulk fluid reservoir 1614, one of the nozzles 1610 associated with the desired bulky fluid can be actuated to deliver the desired bulky fluid into the 1614 bulky fluid reservoir. and bulky fluid 1604 moves independently of fluid distribution set 1602. In that respect, during operation, bulky fluid distribution set 1604 can be one or more stations ahead of fluid distribution set 1602.
[00130] The fluid distribution system 1600 can additionally include a reagent cartridge digitizer 1622 attached to the nozzle holder 1608. The reagent cartridge digitizer 1622 can be any type of digitizer suitable for reading identifiers such as the radio frequency identification (RFID), format identifiers, color identifiers, numbers or words, other optical codes, bar codes, etc. associated with the reagent cartridges positioned in the reaction stations 1606 (for example, the identifier 920 shown in figure 9A). In that regard, the reagent cartridge scanner 1622 includes a reading window at the end 1624. When the reagent cartridge 1634 is positioned on one of the mounting bases 1632, an identifier positioned along one end of the reagent cartridge 1634 is aligned with the reading window at the end 1624. The identifier can be read by the reagent cartridge scanner 1622 through the reading window. The reagent cartridge scanner 1622 moves horizontally along support rail 1616 from one reaction station 1606 to the next by reading an identifier associated with a reagent cartridge mounted on each reaction station 1606. Although the cartridge scanner reagent 1622 is illustrated mounted on the nozzle holder 1608, it is further contemplated that the reagent cartridge digitizer 1622 and the nozzle holder 1608 can be mounted on different holder assemblies so that they are independently movable.
[00131] In addition to the reagent cartridge digitizer 1622, the fluid delivery system 1600 may include the digitizer blade 1628. Although only one digitizer blade 1628 is illustrated in figure 16A, it is understood that the dispensing system of fluid 1600 includes a second blade scanner as shown in figure 18 which is substantially the same as the blade scanner 1628. The blade scanner 1628 can be any type of scanner suitable for reading identifiers such as radio frequency identification indicators ( RFID), format identifiers, color identifiers, numbers or words, other optical codes, bar codes, etc., associated with slide 1638 positioned at reaction station 1606. The slide scanner 1628 can be attached to the distribution set fluid 1602 positioned above reaction station 1606 by the 1630 digitizer holder. The 1630 digitizer holder can be attached to a non-rotating support member of the fluid distribution set 1602 so that it moves linearly together with the fluid distribution set 1602, but does not rotate. In that regard, the 1628 slide digitizer can be moved from one reaction station 1606 to the next together with the fluid distribution set 1602. Alternatively, the 1628 slide digitizer can be moved in a linear and rotating manner along with the fluid distribution set 1602. In other additional embodiments, the scanner support 1630 of the blade scanner 1628 can be directly attached to the rail 1616 so that it can be moved independently of the fluid distribution set 1602.
[00132] Mirror 1626 can be positioned inside each reaction station 1606 to facilitate the reading of identifier 1640 associated with slide 1638 (see figure 16B) positioned inside reaction station 1606. As illustrated in figure 16B, identifier 1640 is located at one end of slide 1638, preferably in a frozen region of slide 1638. Slide 1638 is positioned inside reaction chamber 1646 of reaction station 1606 so that the sample mounted on slide 1638 and identifier 1640 are facing low. The mirror 1626 is positioned below the edge of the slide 1638 including the identifier 1640 so that the image 1642 of the identifier 1640 is reflected in the mirror 1626. The mirror 1626 is positioned so that the image 1642 is reflected in the direction of the blade digitizer 1628 as illustrated by arrow 1644. The blade scanner 1628 reads identifier 1640 by scanning image 1642 of identifier 1640 from mirror 1626. In some embodiments, mirror 1626 can be a disposable mirror that can be removed and replaced with a new one. mirror by a user. As such, if the 1626 mirror is scratched or becomes unsuitable for use, the user can readily replace it without requiring maintenance. Alternatively, mirror 1626 can be fixedly mounted within reaction station 1606. As will be discussed in more detail with reference to figures 22 to 24, the information obtained by the reagent cartridge digitizer 1622 from the identifier on the reagent cartridge and the blade digitizer 1628 from identifier 1640 on blade 1638 can be used to verify a processing protocol performed on the sample mounted on blade 1638.
[00133] Figure 17 illustrates a top view of an embodiment of the bulky fluid distribution set. The bulky fluid distribution set 1604 is substantially the same as the bulky fluid distribution set described with reference to figure 16A. From this view, the positioning of the nozzles 1610 through the bulky fluid reservoir 1614 of the reaction station 1606 can be observed. It is noted that the reagent cartridge digitizer 1622 and the reagent cartridge mounting element 1632 are omitted so that the relationship between nozzles 1610 and the bulk fluid reservoir 1614 can be observed more clearly. Once positioned as shown, a desired fluid from the bulky reagent container can be pumped through supply line 1612 and exits through nozzle 1610 to desired reservoir 1614. Once the desired amount of fluid is pumped into reservoir 1614, the bulky fluid distribution set 1604 can be moved in the direction of arrow 1620 to the next reaction station for dispensing the same reagent or a different reagent into the reservoir.
[00134] Figure 18 illustrates a top view of an embodiment of a fluid distribution system. The geometry and mechanism of the 1800 fluid delivery system varies depending on the operation of the fluid delivery set selected for use with the 1800 system. The 1800 system includes mounting set 1802 having a plurality of mounting stations 1804 where the cartridge 1806 fluid distributor can be mounted. Mounting set 1802 can be substantially the same as mounting set 1506 described with reference to figure 15. Fluid delivery cartridge 1806 can be substantially the same as fluid distribution cartridge 1502 described with reference, for example, to figure 15.
[00135] Mounting stations 1804 preferably include mounting openings 1808 for selectively positioning a plurality of fluid distribution cartridges 1806. In one embodiment, one or more mounting stations 1804 may include mounting opening 1834 sized for the positioning of the 1836 capsule pressure mechanism. The cartridge pump assembly as well as a cartridge pump assembly 1510 previously discussed with reference to figure 15 is mounted at each of the 1804 stations holding the 1806 fluid distribution cartridges. Actuators 1814 and 1816 of the 1820 actuator assembly can be aligned with the 1806 cartridge assembly to activate the pump assembly when desired. In addition, one of the 1814 or 1816 actuators can be aligned with the 1836 capsule pressure mechanism. Since there are two drivers 1814 and 1816, the reagent from the two different fluid distribution cartridges 1806 can be distributed at the same time at different locations. Alternatively, one of the drivers 1814 and 1816 can be aligned with a 1806 fluid delivery cartridge while the other is aligned with the 1836 capsule pressure mechanism to facilitate dispensing the reagent from both the 1806 cartridge and a capsule mounted on one of the reaction stations 1812. In other additional embodiments, two capsule pressure mechanisms 1836 can be mounted on the assembly set 1802 and the actuators 1814 and 1816 aligned with each of the capsule pressure mechanisms 1836.
[00136] System 1800 further includes a bulky fluid delivery set 1824. The bulky fluid delivery set 1824 can be substantially the same as the bulky fluid delivery set 1604 described with reference to figure 16A. In that regard, the bulky fluid delivery set 1824 includes a nozzle holder 1826 having nozzles 1830 and a reagent cartridge digitizer 1832 positioned therein. The nozzle support 1826 slides along the support rail 1828 as previously discussed with reference to figure 16A.
[00137] The fluid delivery system 1800 also includes a receiving set 1810 having a plurality of reaction stations 1812. Reaction stations 1812 may be similar to the reaction stations previously discussed. Generally speaking, the receiving set 1810 is positioned under the mounting set 1802 and the bulky fluid distributor 1824 taking advantage of gravity to distribute the fluids delivered from the fluid distribution cartridges 1806 and the bulky fluid distributor 1824. Preferably , the mounting set 1802, the bulky fluid distributor 1824 and the receiving set 1810 are movable with respect to each other so that the plurality of cartridges 1806 and the bulky fluid distributor 1824 can be positioned to distribute fluids in any one of the desired reaction stations 1812. Any combination of mobility of the 1802 mounting set, 1824 bulky fluid distributor and 1812 reaction stations can be selected. For example, each of the 1802 mounting kits and bulky fluid distributor 1824 can be mobile while reaction stations 1812 are stationary. Alternatively, reaction stations 1812 can be mobile and mounting assembly 1802 and bulk fluid distributor 1824 stationary. Additionally, as previously discussed, the 1802 mounting assembly can be a carousel that is rotatable about a central geometric axis in order to align the 1806 cartridges with the desired reaction station 1812. The 1802 mounting assembly can also be linearly translated so that you can move from one 1812 reaction station to the next. The bulky fluid dispenser 1824 can be additionally linearly moved so that it can move from one 1812 reaction station to the next one in front of or behind the 1802 mounting set. The 1812 reaction stations can all be the same type of items, just like as blades or alternatively they may include different types of items such as blades and containers.
[00138] In an example of the 1800 delivery system operation, the 1802 mounting assembly is rotated so that the individual 1806 cartridges or 1836 capsule pressure mechanism are selectively positioned adjacent to one or both of the 1820 driver assemblies. embodiments, the system 1800 may include a plurality of driver assemblies 1820 that are positioned adjacent to each cartridge 1806 and capsule pressure mechanism 1836 so that rotation of the assembly set 1802 to align each cartridge 1806 and capsule pressure mechanism 1836 with the 1820 driver assembly is not required.
[00139] The 1820 actuator assembly can be any activation device that activates the 1806 cartridge to emit a controlled amount of fluid. Representatively, the driver assembly 1820 may include a piston mechanism that aligns with, for example, a driver of the cartridge pump assembly or capsule pressure mechanism.
[00140] Mounting set 1802 can be moved and rotated relative to receiving set 1810 so that an individual cartridge 1806 can be selectively positioned above reaction station 1812. A cartridge 1806 is positioned above one of the receiving elements 1812, the driver assembly 1820 drives the cartridge 1806 to deliver a controlled amount of fluid to the reaction station 1812.
[00141] As seen in figure 18, in one embodiment, the assembly set 1802 is rotatably attached to the support element 1822 while the drive set 1820 is attached to the support element 1822 so that the 1806 cartridges and the capsule pressure 1836 are rotated with respect to the driver assembly 1820. The driver assembly 1820 is attached to the support element 1822, optionally under the 1802 mounting assembly. Preferably, the support element 1822 can be moved horizontally so that the 1806 cartridges and the capsule pressure mechanism 1836 can both be rotated and translated with respect to the receiving elements 1812. In this way, a chosen cartridge 1806 can be selectively positioned above any reaction station 1812. Similarly, a pressure mechanism of chosen capsule 1836 can be positioned above a desired reaction station 1812.
[00142] Blade scanners 1838, 1840 can also be attached to support element 1822 so that they can be moved from one reaction station 1812 to the next together with the 1802 mounting set. In one embodiment, blade scanners 1838, 1840 can be positioned along opposite sides of the 1802 mounting set. In other additional embodiments, the 1838 blade scanners can be positioned within the 1800 distribution system on any material suitable for reading the identifiers on slides positioned within the system of distribution 1800.
[00143] Although reaction stations 1812 are illustrated in a linear fashion within the receiving set 1810, it is further contemplated that reaction stations 1812 can be divided into two or more rows. In this regard, the driver assembly 1820 can optionally include two or more drivers, for example, two drivers 1814, 1816 used to deliver fluid to two rows of the receiving elements. In operation, driver 1814 is adapted to deliver fluids to reaction stations 1812 in one row and driver 1816 is adapted to deliver fluids to reaction stations 1812 in another row. It is further contemplated that any number of triggers and / or receiving elements can be employed.
[00144] Figure 19 illustrates a schematic diagram of a sample processing system including a bulky reagent sensor assembly. During sample processing, there may be several reagents that are needed in large quantities. For example, processing may require reagents to rinse off antibodies or detection reagents such as distilled water and storage solutions. Such reagents are stored in bulky containers within the system. In addition, the reagent is disposed of in bulky containers. It is often difficult for a user to determine the amount of reagent remaining within each of the bulky containers or whether a reagent dump container is full. This can result in the user failing to replace (or refill) a bulky container. The operation of the system can, in turn, be delayed since the desired reagent is not available or a waste container is too full to accept more waste.
[00145] In this respect, the 1900 sample processing system may include a bulky reagent sensor set 1902. The bulky reagent sensor set 1902 may include sensors 1904, 1906, 1908 and 1910 to detect the amount of liquid (for example, reagent) within bulky containers 1912, 1914, 1916 and 1918, respectively. In some embodiments, sensors 1904, 1906, 1908 and 1910 can be sensors that are capable of measuring a weight of bulky containers 1912, 1914, 1916 and 1918 positioned therein. Representatively, one or more of the sensors 1904, 1906, 1908 and 1910 can be a load cell weight sensor that converts a force applied to the sensor by the weight of the container into an electrical signal as available from Minebea Co. , Miyota-machi Ltd, Kitasaku-gun, Nagano, Japan.
[00146] A weight and volume of each of the bulky containers 1912, 1914, 1916 and 1918 can be known. In addition, the type of liquid inside the bulky containers 1912, 1914, 1916 and 1918 and the density of the liquid can also be known. To determine a volume of liquid within, for example, the bulky container 1912, the weight of the bulky container 1912 (in the absence of the liquid) can be subtracted from the weight measured by the sensor 1904 (mass of the bulky and liquid container). The weight of the liquid inside the container 1912 and the density of the liquid can then be used to calculate the volume of the fluid inside the container 1912. A determination of how full or empty the container can then be determined by subtracting the volume of liquid in the container 1912 from the volume of the known container. Although the measurement of a liquid inside the bulky container 1912 is described here, a similar calculation can be performed using the bulky containers 1914, 1916 and 1918 and the sensors 1906, 1908 and 1910, respectively, to measure a volume of liquid within the bulky containers 1914, 1916 and 1918. Additionally, although four weight sensors 1904, 1906, 1908 and 1910 are illustrated in figure 19, it is contemplated that the number of sensors may vary depending on the number of bulky containers desired in the system.
[00147] In other additional embodiments, the 1900 system may include a 1920, 1922, 1924 and 1926 light source to facilitate visual inspection of a liquid level within containers 1912, 1914, 1916 and 1918, respectively. One or more of the 1920, 1922, 1924 and 1926 light sources can be a light emitting diode (LED) positioned near a respective container. Alternatively, one or more light sources 1920, 1922, 1924 and 1926 can be any light source capable of illuminating containers 1912, 1914, 1916 and 1918 so that a liquid level can be viewed. It is further contemplated that a material from containers 1912, 1914, 1916 and 1918 can be selected to facilitate visual inspection of a liquid within the container. Representatively, containers 1912, 1914, 1916 and 1918 can be made of a semi-transparent or transparent material.
[00148] The operation of the 1900 processing system and the bulky reagent sensor assembly 1902 will now be described. According to one embodiment, the bulky container 1812 can be a waste container and each of the bulky containers 1914, 1916, 1918 can hold a reagent. A reagent from one or more of the bulky containers 1914, 1916, 1918 can be dispensed into the 1928 reservoir of a desired reaction station by the bulky reagent distributor 1930. The 1932, 1934, 1936 pumps can be associated with each supply line 1938, 1940, 1942, respectively, from the bulky reagent dispenser 1930 to pump the reagent from the respective bulky container. Once a desired reagent is inside the 1928 reservoir, the reagent can be pumped into the 1944 reaction chamber with the aid of the 1946 pump. After processing with the reagent in the 1944 reaction chamber is completed, the reagent can be pumped at from reaction chamber 1944 to the bulky 1912 dump container using the 1948 pump through the 1950 solenoid valve. In addition, since the reagent inside the 1928 reservoir is no longer needed, it can be drained into the container bulky 1912 with the aid of the 1948 pump by switching the 1950 solenoid valve line.
[00149] The 1904 sensor can continuously or periodically calculate a dumping volume inside the bulky container 1912. When the volume of the liquid inside the bulky container 1912 is above a predetermined level (for example, the container is full), the alert system the user. Similarly, sensors 1906, 1906, 1910 can continuously or periodically calculate a volume of liquid within bulky containers 1914, 1916, 1918, respectively. When the volume of liquid is below a predetermined level (for example, the container is empty), the system alerts the user. Upon receipt of the alert, the user can refill, replace or empty the bulky container. In addition, the system can automatically switch from an empty reagent container to one that has a sufficient amount of desired liquid. The system can also automatically switch from a bulky dump container that is full to one that is empty. In this respect, where the user cannot immediately serve bulky containers, processing can continue uninterrupted.
[00150] Figure 20 is an illustration of a modality of an automated sample processing system. The automated sample processing system 2000 includes a control computer 2002 in communication with a plurality of pigmentation devices 2004 and can provide a centralized user interface to control the plurality of pigmentation devices 2004. Pigmentation devices 2004 can be used to process biological species as previously discussed. The 2002 control computer can communicate with the 2004 pigmentation devices in any way known to the art, for example, the 2002 control computer can communicate with the 2004 pigmentation devices through a 2006 high-speed hub. high speed 2006 allows the 2000 system to quickly transport information between the plurality of pigmentation devices 2004 and other components such as the control computer 2002. For example, pigmentation devices 2004 can download pigmentation protocols to be applied to slides located at the reaction stations on the pigmentation devices 2004 through a network formed by the data lines 2008 and the high speed cube 2006. It will be appreciated that the control computer 2002 and the pigmentation devices 2004 can be configured to communicate through wired or wireless, for example, the system can use 2008 data lines, as described the above, which can be conventional conductors or optical fibers. In addition, components can communicate wirelessly using radio frequency communication, such as BLUETOOTH® (a registered trademark of Bluetooth SIG, Inc, Bellevue, Washington) or any other wireless technology.
[00151] The control computer 2002 can also communicate with one or more local databases 2010 so that data can be transferred to and from the local databases 2010. For example, the local database 2010 can store a plurality of pigmentation protocols that are designed to be performed by the reaction stations of the 2004 pigmentation devices. The pigmentation protocols may include a series of pigmentation operations that must be performed on slides positioned within the reaction stations. The pigmentation protocols implemented by the reaction stations on the 2004 pigmentation devices can be chosen based on the information obtained from the identifiers (for example, bar codes, radio frequency identification (RFID) devices, etc.) associated with the system components (for example, on microscopic slides, reagent cartridges, fluid distribution cartridges, reagent containers, etc.). The 2002 control computer can process the identification data received from the reaction stations on the pigmentation devices 2004 and retrieve the pigmentation protocols from the local database 2010 and transmit the pigmentation protocols to the reaction stations on the pigmentation devices 2004. In addition, the control computer 2002 can use local databases 2010 to store the information received from the reaction stations of the pigmentation devices 2004, such as reports and / or situation information.
[00152] The control computer 2002 can also communicate with one or more remote databases 2012 and / or a server 2014. The control computer 2001 can communicate with remote database 2012 directly or through the server 2014, which can be a laboratory information system (LIS). The control computer 2002 can communicate with server 2014 over a 2016 network. As noted above, server 2014 can communicate with remote database 2012. Server 2014 and remote database 2012 can be used to provide protocols to be used by the reaction stations in the pigmentation devices 2004 in a similar way to the local database 2010 or to supplement the protocols provided by the local database 2010.
[00153] The automated processing system 2000 can optionally include one or more printers 2018. The 2018 printer can communicate directly with the control computer 2002, as illustrated, or directly with the pigmentation devices 2004. Additionally, the pigmentation devices 2004 can each have a dedicated 2018 printer that can be integrated with the pigmentation device or multiple independent 3004 pigmentation devices can share one or more printers.
[00154] The automated reagent dispensing system 2000 can also include a flatbed or portable scanner 2020 for reading the identifiers that can be included by all components of the system (for example, on microscope slides, reagent cartridges, fluid distribution, reagent containers, etc.). Any type of digitizer 2020 can be used, being able to interpret the identifiers. For example, the 2020 scanner can be an RFID scanner, a 2D or 1D barcode scanner, or any other type of scanner known in the art. The 2020 digitizer can communicate directly with the 2002 control computer or 2004 pigmentation devices and each component can have a dedicated digitizer.
[00155] The system can also be powered by a 2022 uninterruptible power supply. The 2022 uninterruptible power supply can be used to limit the system's susceptibility to general power outages that can invalidate tests that are interrupted. Such an interruption in energy can also result in the tissue samples becoming unusable, which may require additional species collection. The 2022 power supply can be used to power any or all components of the 2000 automated processing system.
[00156] Although the 2002 control computer is illustrated in a network with multiple pigmentation devices 2004 in figure 20, it should be appreciated that the pigmentation devices 2004 can be combined in a single unit with an on-board control computer, in addition to any other component described above in the automated reagent delivery system. Such a combination can provide a compact, independent unit that can be used to process smaller volumes of biological species.
[00157] As previously discussed, one or more processing protocols can be downloaded to the pigmentation devices 2004. The reaction stations on the pigmentation devices 2004 can then implement the processing protocol on the slides located in the reaction stations of the pigmentation devices 2004 regardless of the 2002 control computer. In this respect, if the 2002 control computer stops (for example, breaking or freezing), the processing protocol being run on a slide inside the reaction stations on the 2004 pigmentation devices can continue smoothly. uninterrupted.
[00158] Additionally, a processing protocol performed at the reaction stations of the pigmentation devices 2004 can be monitored by the control computer 2002. For example, once a pigmentation operation designed by the processing protocol is completed at a reaction station on one or more of the pigmentation devices 2004, a pigmentation status report can be sent to the 2002 control computer notifying the 2002 control computer that the pigmentation operation has been completed. In some modalities, a report is sent to the 2002 control computer at regular intervals (for example, every 2 to 3 seconds). All pigmentation operations completed within the ranges can be reported to the 2002 control computer. In this respect, a pigmentation operation that takes more than 3 seconds, for example, 5 seconds, will not be reported to the 2002 control computer in the report. sent while the operation is still pending (that is, the report sent 2 to 3 seconds in the 5-second operation). Instead, the performance of the pigmentation operation will be reported to the 2002 control computer with the subsequent report issued after the pigmentation operation has been completed. Alternatively, a pigmentation operation can be reported at any time before completion. Additionally, if the 2004 pigmentation device is unable to send the pigmentation status report at a regular interval (for example, control computer 2002 loses power), reports that have not been sent will be compiled on the 2004 pigmentation device and sent together to the 2002 control computer when the report is resumed (for example, power is restored).
[00159] A pigmentation file for each of the operations performed on the pigmentation devices 2004 can be created by the control computer 2002 based on the status report and displayed on the control computer 2002. In this aspect, the control computer 2002 can display all pigmentation files completed on 2004 pigmentation devices, the pigmentation file may include, for example, identification information for system components (eg, microscopic slides, reagent cartridge, fluid distribution cartridges, fluid containers) bulky reagent, etc.). Representatively, the pigmentation file can include information regarding fluid distribution cartridges or bulky reagent containers such as a list of reagents within the system that can be used during the operation of the 2004 pigmentation devices. reagent can include, for example, the identity of an antibody (for example, a primary antibody) within the reagent cartridge attached to a reaction chamber. The slide information may include, for example, a patient identification number or information regarding an agent such as an antibody that must be applied to the slide.
[00160] Figure 21 illustrates a flowchart of a modality of a sample processing procedure. Sample processing is started once an initial condition is detected. The sample processing procedure 2100 can include an initialization procedure that occurs once an initialization condition has been detected (block 2102). An initial condition can be, for example, closing the cover in the housing of a pigmentation device included in the automated reagent delivery system, receiving an initial signal from a control computer, or any other condition. If an initial condition is not detected, the automated reagent delivery system can continuously check whether an initial condition has been detected until an initial condition is detected.
[00161] The initialization procedure occurs after an initial condition is detected and may include taking an inventory of system components, for example, reaction stations, reaction chambers, reagent cartridges, fluid distribution cartridges and / or containers of bulky reagent (block 2104). The inventory of fluid distribution cartridges, reagent cartridges and bulky containers can be carried out by scanning the identifiers located at the reaction stations, cartridges and containers within the system. Representatively, scanning can be performed by the reagent cartridge scanner 1608 and / or blade scanner 1628 located in the linearly translated assembly set as illustrated in figure 16A. In the case of the blade scanner 1628, the blade scanner 1628 can move with the assembly set along the reaction stations and scan the identifiers located on the slides associated with it. This allows the system to determine which reaction stations include species and can additionally allow the system to identify the appropriate agent (eg, primary antibody) to be applied to the slide. After digitizing the identifiers, the assembly set returns to a home position. Additionally, by scanning the reagent cartridges using, for example, the reagent cartridge scanner 1608, the system can identify the type and amount of reagent present in each reagent cartridge. A determination as to the appropriate processing protocol to be applied to the slide can be made using the information.
[00162] Additionally, the determination of the fluid volume level, for example, of bulky containers, obtained from the sensors can be part of the inventory procedure. Keeping a history of the amount of liquid that has been dispensed from the bulky containers can further assist in determining the level of fluid volume within the containers. After determining the fluid volume level, a signal can be sent to provide the user with an indication of how much and what types of fluids are stored in the containers. Where the system determines that a container is empty or contains an insufficient amount of fluid to perform a predetermined pigmentation process, the system can initiate a replacement signal indicating that one or more containers have an insufficient amount of fluid and need to be replaced or refilled . The system can additionally automatically select a different container that contains a sufficient volume of desired fluid, if available, so that processing can continue uninterrupted.
[00163] Once the inventory procedure is completed, the instruction sequences are received by the reaction stations (block 2106) and the pigmentation protocols discharged for each reaction station are run (block 2108). A pigmentation protocol can include a sequence of processing operations including, in any order and at various times, the distribution of a primary reagent from a reagent cartridge associated with a reaction station, the distribution of a secondary reagent from of a fluid dispensing cartridge mounted on the top mounting assembly, dispensing an additional reagent from a bulky fluid dispensing assembly positioned above the reaction station and / or dispensing a reagent into the reaction station through the entrance doors inside the reaction station.
[00164] Figure 22 illustrates a flowchart of a modality of a sample processing procedure. Typically, an operator, such as a laboratory technician, is entrusted with the responsibility of ensuring that a slide having a sample mounted on it has been located within the correct reaction station and processed according to a processing protocol designated for that station . If, however, the operator erroneously places the slide at the wrong station, the wrong processing protocol can be performed on the slide sample. Such an error may not be discovered until the slide has been removed from the station and analyzed, for example, by pathologists days or in some cases weeks later. Since the slide is no longer in the station, it can be difficult to determine the processing protocol performed on the slide and, in turn, whether the slide should be reprocessed or if processing should be performed on a new slide with a new sample. . Such an error can therefore cause significant delays in the resulting analysis and reporting. Additionally, where the error in processing is not detectable by the pathologist upon review of the sample, the error may go unnoticed which results in an incorrect recommendation or wrong diagnosis.
[00165] The sample processing procedure illustrated in figure 22 can be used to verify a processing protocol performed on a sample mounted on a slide. In this respect, procedure 2200 may include placing a first identifier on a front side of a slide (that is, the side with the sample mounted on it) (block 2202). The first identifier can be, for example, an identifier such as the identifier 1640 described with reference to figure 16B. The identifier can include information such as patient information and / or the name of an agent, for example, an antibody, to be applied to the slide. The slide is then placed with the back side up (that is, the side opposite the sample) in a reaction chamber mounted to a reaction station for processing (block 2204). Once the slide is in place, a reagent cartridge is mounted in the reaction chamber (block 2206). The reagent cartridge can be a reagent cartridge such as reagent cartridge 408 described with reference to figure 4A. The reagent cartridge may have a second identifier, such as the identifier 920 described with reference to figure 9A, positioned thereon. The second identifier can identify, for example, an antibody associated with the reagent cartridge. The antibody can, for example, be found inside a capsule (see, reagent capsule 900 of figure 9A) attached to the reagent cartridge.
[00166] The first identifier located on the slide is digitized (block 2208) and the second identifier located on the reagent cartridge is digitized (block 2210). A processing protocol to be applied to the sample on the slide is determined based on the information obtained from the second identifier (block 2212). Representatively, the second identifier can identify a reagent within the reagent cartridge. Alternatively, the processing protocol to be applied to the sample on the slide can be determined based on the information from the first identifier. The control computer can then use this information to select a processing protocol that can be run using the identified reagent. It is contemplated that an operator can select a protocol based on the identified reagent. The processing protocol selected can be performed on the sample found on the slide (block 2214). The information obtained from the first identifier located on the slide can be associated with the information obtained from the second identifier located on the reagent cartridge to confirm the processing protocol performed on the sample on the slide (block 2216). The information of the first identifier and the second identifier can be associated during sample processing according to the processing protocol or upon completion of processing. The associated information can be displayed on the control computer so that the operator can determine whether the correct processing protocol has been assigned to the correct blade.
[00167] Figure 23 illustrates a modality of a monitor associated with a sample processing procedure. Monitor 2300 illustrates the information obtained from the first identifier and the information obtained from the second identifier. In this regard, monitor 2300 includes reagent cartridge identification table 2302 and slide identification table 2304. Reagent cartridge identification table 2302 includes station identification column 2306 and reagent identification column 2308 The station identification column 2306 identifies the reaction station where the reagent cartridge is located. The reagent identification column 2308 identifies a reagent located in the reagent cartridge. Representatively, by reviewing the reagent identification table 2302 illustrated in figure 23 an operator will understand that a reagent cartridge having an LCA antibody is located at stations 2, 16 and 17, a reagent cartridge holding the CD30 antibody is located at stations 3 and 5, a reagent cartridge holding the Desmin antibody is located at station 9, a reagent cartridge holding the Cytokeratin7 antibody is located at station 10 and a reaction cartridge holding the Vimentin antibody is located at station 12.
[00168] Similarly, the slide identification table 2304 includes the slide identification column 2312 and the reagent identification column 2310. Upon review of the slide identification table 2304 illustrated in figure 23, an operator will understand that the LCA antibody must be applied to a slide located at stations 2, 16 and 17, the CD30 antibody must be applied to a slide located at stations 3 and 5, Desmin antibody must be applied to a slide located at stations 9, the Cytokeratin7 antibody should be applied to a slide located at station 10 and the Vimentin antibody should be applied to a slide located at station 12.
[00169] Reagent identification table 2302 and slide identification table 2304 are juxtaposed so that the rows having the same number of stations are aligned. As a result, the operator can easily review reagent identification table 2302 and slide identification table 2304 and determine whether the appropriate antibody has been applied to the appropriate slide. For example, the slide identification table 2304 provides that the slide located at station 2 must receive the LCA antibody. Reagent identification table 2306 indicates that the antibody located in step 2 was LCA. Based on this information, the operator can confirm that a processing protocol using ACL has been properly assigned to the slide at station 2.
[00170] Reagent identification table 2302 and slide identification table 2304 can be saved and associated with information from another round to provide tracking information. In other words, reagent identification table 2302 illustrates which reagent has been associated with a particular station and slide identification table 2304 illustrates which reagent you wish to distribute on the slide. Saving this information (for example, data from the tables generated before processing) is an indication of the processing performed on a slide. A pigmentation file, as previously described with reference to figure 20, can include the tracking information.
[00171] Based on the information provided by monitor 2300, the operator can choose to reload the stations and start another round by clicking the start button 2314. Alternatively, the operator can choose to rescan existing samples by clicking on the rescan button 2316. Finally, a operator can choose to cancel the round or display by clicking the cancel button 2318.
[00172] Figure 24 illustrates a monitor modality associated with a sample processing procedure. Monitor 2400 illustrates a modality in which there is a mismatch of reagent information. Monitor 2400 is substantially similar to monitor 2300 in that it includes reagent identification table 2402 having station identification column 2406 and reagent identification column 2408. Additionally, monitor 2400 includes slide identification table 2402 having a slide identification column 2412 and a reagent identification column 2410. The monitor 2400 additionally includes a round start button 2414, a rescan button 2416 and a cancel button 2418.
[00173] As can be seen from blade identification table 2404, the slide located in station 2 requires the CD30 antibody and the slide located in step 3 requires the LCA antibody. Reagent identification table 2402, however, indicates that the antibody located in step 2 was LCA and the antibody located in station 3 was CD30. In this way, the wrong antibody, and, in turn, the processing protocol, was assigned to the slide at station 2 and the slide at station 3. Based on this information, the operator can replace the slide at station 2 with a slide requiring ACL and blade in station 3 with a blade requiring CD30 and rescan the slides. Alternatively, the operator can replace the reagent cartridges with the reagent cartridges having the appropriate antibody. Additionally, the operator can replace the identifier on the slide with an identifier that adequately identifies the reagent applied to the slide sample. Other variations of mismatch are additionally contemplated and can be displayed on the 2400 monitor, for example, a slide can be placed in a station without any reagent cartridge such as station 1.
[00174] It is additionally contemplated that in some modalities, the 2002 control computer can automatically alert a user about the lack of combination. Representatively, the 2002 control computer can be programmed to detect a mismatch between reagent identification table 2402 and slide identification table 2404. When a mismatch is detected, an alarm may sound to alert the user that the reagent identified by the identifier on the slide has not been applied to the slide.
[00175] A device, such as the 2002 control computer, for carrying out the operations can be specially built for the necessary purpose or it can comprise a general purpose computer selectively activated or reconfigured by a computer program stored on the computer. Such a computer program may be stored on a computer-readable storage medium, such as, but not limited to, any type of disk including floppy disks, optical disks, CD-ROMs, and magneto-optical disks, read-only memories (ROMs) , random access memories (RAMs), EPROMs, EEPROMs, magnetic or optical cards, Flash memory devices including universal serial bus (USB) storage devices (for example, USB key devices) or any type of media suitable for storage of electronic instructions, each of which can be coupled to a computer system bus.
[00176] Figures 25A, 25B and 25C illustrate perspective views of an embodiment of a drain drain system within the sample processing system. Dump drain system 2500 may include dump containers 2502, 2504. Dump containers 2502, 2504 may be similar to the bulky containers 118 described with reference to figure 1. Although two dump containers 2502, 2504 are illustrated, the The following description can apply to any number of dump containers positioned within the sample processing system. In addition, although the containers are described as dumping containers, it is contemplated that the containers can be any type of bulky container used to hold any type of fluid (for example, a reagent or washing fluid).
[00177] Dump containers 2502, 2504 can be positioned within the sample processing system below the reaction compartment while maintaining the reaction stations as described with reference to figure 1. Dump containers 2502, 2504 can rest on the plate sensor plate 2514. The sensor plate 2514 can be similar to the sensor 1904 described with reference to figure 19. In this respect, the sensor plate 2514 can be used to detect a fluid level inside the waste containers 2502, 2504. The tubes drainage tubes 2506, 2508 can be aligned with the dump containers 2502, 2504, respectively, to help direct a dump fluid from the reaction stations into the dump containers 2502, 2504. During operation, it may be desirable whether to raise or lower the drain pipes 2506, 2508 depending on whether filling or removing waste containers 2502, 2504 is desired. For example, during a processing operation it is desirable that the drain pipes 2506, 2508 are lowered into the waste containers 2502, 2504 so that the waste is deposited directly into the containers 2502, 2504. The drain pipes 2506, 2508 they are then raised to facilitate changing, replacing or emptying the waste containers 2502, 2504. In this respect, the levers 2510, 2512 are attached to the drain pipes 2506, 2508, respectively, to raise or lower the drain pipes 2506, 2508 Figure 25A illustrates an embodiment where lever 2510 is lowered and drain tube 2506 is lowered into dump container 2502 while lever 2512 is raised and drain tube 2508 is raised above dump container 2504.
[00178] Drain tubes 2506, 2508 are connected by fluid to connection tubes 2516, 2518, respectively, as illustrated in figure 25B. Connecting tubes 2516, 2518 provide a fluid conduit for the discharge to flow from the reaction stations to drain tubes 2506, 2508. Connecting tubes 2516, 2518 can have a modifiable configuration so that they provide an inclined conduit downwards when the drain pipes 2506, 2508 are raised above the drain containers 2502, 2504 and an inclined duct upwards when the drain pipes 2506, 2508 are raised above the drain containers 2502, 2504. Each of the drain pipes connection 2516, 2518 can be independent of each other and therefore modified independently. In that regard, connection pipe 2518 can be a joined pipe having a first joint 2528 near drain pipe 2508 and a second joint 2530 away from drain pipe 2508. Connection pipe 2518 may be made of sections of a rigid material such as a metal or rigid plastic material or a more flexible material such as a flexible plastic connected by joints 2528, 2530. Alternatively, connection tube 2518 may be a tube formed integrally made of a flexible plastic material that is modified in the absence of joints and therefore joints 2528 and 2530 can be omitted. When the drain pipe 2508 is raised, for example to remove the waste containers 2504, the part of the connection pipe 2518 between the first joint 2528 and the drain pipe 2508 is raised above the part of the connection pipe 2518 between the second gasket 2530 and the vertical connection element 2526 while the part of the connection pipe 2518 between the first gasket 2528 and the second gasket 2530 has an upward inclined orientation. The connection pipe 2516 can be additionally connected in a similar way to the connection pipe 2518. Figures 25A, 25B and 25C illustrate a modality in which the drain pipe 2508 is raised and, in turn, the connection pipe 2518 includes a raised and tilted part previously discussed, while drain pipe 2506 is lowered so that connecting pipe 2516 has an inclined downward orientation. In the case of a flexible plastic tube, similar regions of connection tubes 2516, 2518 may have elevated and inclined orientations as previously discussed.
[00179] The flow of fluids through the 2500 drainage system is substantially a passive process driven primarily by gravity. As such, the ability to change the orientation of the connection tubes 2516, 2518 helps to control a flow of fluid through the drain tubes 2506, 2508 in addition to the fluid back into the associated reaction stations. In particular, when the drain tube 2506 is lowered and, in turn, the connection tube 2516 has a downward sloping configuration, gravity triggers the flow of a dump fluid from the 2550 dump drain through the reaction station. from the vertical connection element 2524 and into the connection element 2516. Since the connection element 2516 is tilted downwards, the fluid drained from the reaction station flows easily into the drain tube 2506 and is deposited inside the dump container 2502. When connecting element 2518 is in an upward-sloping configuration (that is, when the drain pipe 2508 is raised) the fluid may stop flowing, and in some cases, start flowing away from the pipe drain 2508 back to the 2522 dump drain from the associated reaction station. Interruption or reversal of the fluid flow may be desirable when, for example, the 2504 dump container is being removed or replaced with another container as it prevents the dump from dripping onto the 2514 sensor plate and / or the operator. It is recognized, however, that when a fluid level within connection element 2518 reaches a level within vertical connection element 2526 above the highest point of connection element 2518 (for example, gasket 2528), the fluid begins to flow. flow in one direction of the drain tube 2508 so that the fluid does not flow back into the associated reaction station. Such a feature is desirable, for example, where an operator forgets to lower the drain tube 2508 into the drain container 2504 before starting the processing operation. Once sufficient fluid level begins to collect within vertical connection element 2526 (that is, a fluid level above the highest point of connection element 2518), fluid will begin to flow through connection element 2518 and into the waste container 2504 through the drain tube 2508, thus preventing the dumping from returning into the reaction station.
[00180] The algorithms and displays presented here are not inherently related to any particular computer or other device. Various general purpose systems can be used with the programs according to the teachings presented here or they can prove to be convenient for the construction of a more specialized device to carry out the described method. In addition, the invention is not described with reference to any particular programming language. It will be appreciated that a variety of programming languages can be used to implement the teachings of the invention as described here.
[00181] A computer-readable medium includes any mechanism for storing information in a computer-readable form. For example, a computer-readable medium includes read-only memory (ROM), random access memory (RAM), magnetic storage media, optical storage media, flash memory devices, or other machine-accessible storage medium .
[00182] It should also be appreciated that reference throughout the specification to "a modality" or "one or more modalities", for example, means that a particular characteristic can be included in the practice of the invention. Similarly, it should be noted that in the description, several characteristics are sometimes grouped into a single modality, figure, or description for the purpose of sequencing the description and helping to understand various inventive aspects. This method of description, however, is not interpreted as reflecting an intention that the invention will require more features than are expressly recited in each claim. Instead, as the following claims reflect, inventive aspects can be found in less than all the characteristics of a single described modality. Accordingly, the following claims of the Detailed Description are expressly incorporated here in that Detailed Description, like each independent claim as a separate embodiment of the invention.
[00183] In the above report, the invention was described with reference to specific modalities. It will, however, be evident that various modifications and changes can be made without departing from the broader spirit and scope of the invention as presented in the appended claims. For example, a reagent cartridge as described here (for example, a 408 reagent cartridge) may contain a solvent or water instead of a reagent and used for purposes other than, for example, pigmenting a sample on an underlying slide . The report and drawings are, accordingly, considered in an illustrative rather than restrictive way.

权利要求:
Claims (56)
[0001]
1. Apparatus, comprising: a reagent cartridge (408, 700, 1634) having a housing (702) that defines a recess holding reagent (414, 714) and a reagent targeting channel (418, 718), characterized by the fact that the recess holding reagent (414, 714) is fluidly connected to a first inclined surface connecting the recess holding reagent (414, 714) to an outlet channel (420, 720) extending from a lower side of the housing (702), and the reagent directing channel (418, 718) comprises a first inclined part (848) and a second inclined part (850) connecting the reagent directing channel (418, 718) to the outlet channel (420 , 720), the second inclined portion (850) extends from the first inclined portion (848) at a substantially right angle and towards the first inclined surface, such that the first inclined surface and the second inclined portion (850) converge with each other in the outlet channel (420, 720); and a reaction chamber (206, 300, 406, 506, 600) having a plate (302, 402, 502, 602) sized to receive a slide (322, 422, 522, 622), the plate (302, 402, 502, 602) defining a reagent drip surface (330, 530, 630) to receive a reagent distributed from the reagent cartridge (408, 700, 1634).
[0002]
2. Apparatus according to claim 1, characterized by the fact that the recess holding reagent (414, 714) is sized to receive a reagent capsule (416, 900, 1024) having a reagent contained therein, and the first sloping part (848) and the second sloping part (850) have the same slope and a round tubular surface through which a fluid flows into the outlet channel (420, 720).
[0003]
3. Apparatus according to claim 2, characterized in that the reagent capsule (416, 900, 1024) comprises a removable container (902, 1030) and a plunger (904, 1028) designed to break a seal ( 930, 1026) of the container (902, 1030) when the container (902, 1030) is disassembled.
[0004]
4. Apparatus according to claim 1, characterized by the fact that it further comprises: a first identifier (918) and a second identifier (920) coupled to the reagent cartridge (408, 700, 1634), the first identifier (918) ) and the second identifier (920) comprising information that identifies a reagent contained within the reagent cartridge (408, 700, 1634) and where one of the first identifier (918) and second identifier (920) is removable.
[0005]
5. Apparatus according to claim 1, characterized by the fact that the plate (302, 402, 502, 602) consists of a hydrophilic material.
[0006]
6. Apparatus according to claim 1, characterized by the fact that the plate (302, 402, 502, 602) consists of a metallic material having at least one corrosion-resistant or antimicrobial property.
[0007]
7. Apparatus according to claim 1, characterized by the fact that the plate (302, 402, 502, 602) is positioned at a horizontal angle with respect to the ground level of about 5 degrees to 15 degrees.
[0008]
8. Apparatus according to claim 1, characterized by the fact that the plate (302, 402, 502, 602) is positioned at a vertical angle with respect to the ground level from 15 degrees to 45 degrees.
[0009]
9. Apparatus according to claim 1, characterized by the fact that it further comprises at least one spacer element (306, 308, 310) extending from a plate surface (302, 402, 502, 602) to create an uneven space between the plate (302, 402, 502, 602) and a blade (322, 422, 522, 622) positioned on the plate (302, 402, 502, 602).
[0010]
10. Apparatus according to claim 1, characterized by the fact that it also comprises a bulk reagent reservoir (1108) coupled to the reaction chamber (206, 300, 406, 506, 600), the bulk reagent reservoir (1108) ) in fluid communication with the reaction chamber (206, 300, 406, 506, 600).
[0011]
11. Apparatus according to claim 1, characterized by the fact that the reaction chamber (206, 300, 406, 506, 600) further comprises: a first fluid outlet port (312), a second outlet port fluid (314) and a fluid inlet port (316) extending across the plate (302, 402, 502, 602), where the fluid inlet port (316) is positioned between the first fluid outlet port (312) and the second fluid outlet port (314).
[0012]
12. Apparatus according to claim 1, characterized by the fact that it also comprises a set of temperature modification coupled to the plate (302, 402, 502, 602) to modify a temperature of the reaction chamber (206, 300, 406 , 506, 600).
[0013]
13. Apparatus according to claim 12, characterized by the fact that the temperature change set (1112, 1200) comprises a thermoelectric cooler (TEC) (1024, 1206).
[0014]
Apparatus according to claim 12, characterized in that the temperature modifying set (1112, 1200) comprises a heat tank (1208) and a fan (1214) for controlling a temperature of the modifying set of temperature (1112, 1200).
[0015]
15. Apparatus according to claim 12, characterized by the fact that the temperature modification set (1112, 1200) comprises a thermistor (1216, 1218) for monitoring a reaction chamber temperature (206, 300, 406, 506, 600).
[0016]
16. Apparatus comprising: a reagent cartridge (408, 700, 1634) comprising a housing (702) that defines a recess holding reagent (414, 714) and a reagent targeting channel (418, 718), characterized by the fact that that the recess holding reagent (414, 714) is fluidly connected to a first inclined surface connecting the recess holding reagent (414, 714) to an outlet channel (420, 720) extending from a lower side of the housing ( 702), and the reagent directing channel (418, 718) comprises a first inclined part (848) and a second inclined part (850) connecting the reagent directing channel (418, 718) to the outlet channel (420, 720), the second inclined portion (850) extends from the first inclined portion (848) at a substantially right angle and towards the first inclined surface, such that the first inclined surface and the second inclined portion (850) converge one with the other in the outlet channel (420, 720); and a reagent capsule (416, 900, 1024) removably positioned within the recess retaining reagent (414, 714).
[0017]
17. Apparatus according to claim 16, characterized by the fact that the reagent cartridge (408, 700, 1634) further comprises a reagent directing channel (418, 718), the reagent retention recess and the channel reagent targeting (418, 718) in fluid communication with an outlet channel (420, 720) to direct a reagent out of the reagent cartridge (408, 700, 1634).
[0018]
18. Apparatus according to claim 16, characterized in that the reagent capsule (416, 900, 1024) comprises a removable container (902, 1030) and a plunger (904, 1028) designed to break a seal ( 930, 1026) of the container when the container is disassembled.
[0019]
19. Apparatus according to claim 16, characterized by the fact that it also comprises a support set (424) coupled to the capsule (416, 900, 1024), the support set (424) dimensioned to hold the capsule (416 , 900, 1024) to the reagent cartridge (408, 700, 1634).
[0020]
20. Apparatus according to claim 19, characterized in that the support set (424) comprises an identifier (428) identifying a reagent contained within the capsule (416, 900, 1024).
[0021]
21. Apparatus according to claim 19, characterized by the fact that the capsule (416, 900, 1024) is removably coupled to the support assembly (424).
[0022]
22. Apparatus, comprising: a plate (302, 402, 502, 602) sized to receive a slide (322, 422, 522, 622) in a reaction chamber (206, 300, 406, 506, 600), a pair spacer nodes (306, 308) and a spacer bar (310, 610) extending from a plate surface (302, 402, 502, 602); and characterized by the fact that at least one exit door (314) and at least one entrance door (316) extending across the plate (302, 402, 502, 602), in which the spacer bar (310, 610) has a dimension of length equal to a width of the plate (302, 402, 502, 602) and in which a difference in a height of the spacer node pair (306, 308) and height of the spacer bar (310, 610) is operable to form an uneven space between the plate (302, 402, 502, 602) and a blade (322, 422, 522, 622) when a blade (322, 422, 522, 622) is positioned on the plate (302, 402 , 502, 602).
[0023]
23. Apparatus according to claim 22, characterized in that the plate (302, 402, 502, 602) defines a fluid drip surface (330, 530, 630) at one end to receive a fluid distributed in the plate (302, 402, 502, 602) from above.
[0024]
24. Apparatus according to claim 22, characterized in that the at least one spacer element (306, 308, 310) is a spacer bar (310, 610) extending across a width dimension of the plate (302 , 402, 502, 602), the spacer bar (310, 610) comprising a dimension of sufficient width to prevent fluid from traveling through the spacer bar (310, 610).
[0025]
25. Apparatus according to claim 22, characterized in that the pair of spacer nodes (306, 308) are positioned at one end of the plate (302, 402, 502, 602) and one of the pair of spacer nodes spacer (306, 308) is positioned a distance from the other of the pair of spacer nodes (306, 308) at one end of the plate (302, 402, 502, 602) and the spacer bar (310, 610) is positioned in a opposite end of the plate (302, 402, 502, 602).
[0026]
26. Apparatus according to claim 22, characterized in that it further comprises a wall (304) positioned around a part of the plate (302, 402, 502, 602), the wall (304) comprising a sufficient height to retain a fluid distributed to the plate (302, 402, 502, 602).
[0027]
27. Apparatus according to claim 22, characterized in that the plate (302, 402, 502, 602) comprises a hydrophilic surface.
[0028]
28. Apparatus according to claim 22, characterized by the fact that the plate (302, 402, 502, 602) consists of a metal or a plastic material.
[0029]
29. Apparatus according to claim 22, characterized in that the at least one outlet port (314) is a first outlet port (314) positioned at one end of the plate (302, 402, 502, 602) and a second outlet port (314) is positioned at an opposite end of the plate (302, 402, 502, 602), at least one inlet port (316) is positioned between the first outlet port (314) and the second exit door (314).
[0030]
30. System comprising: a linearly translatable mounting assembly (116, 1506, 1802) having a plurality of mounting stations (1618, 1804) sized to receive at least one fluid distribution cartridge (1508, 1806); a linearly translatable bulky reagent dispensing assembly (1064, 1824) having a plurality of bulky reagent dispensing nozzles (1610, 1830) coupled thereto; and characterized by the fact that a receiving set (1810) positioned under the mounting set (116, 1506, 1802) and the bulky reagent distribution set (1064, 1824), the receiving set (1810) including a plurality reaction stations (1604, 1824), wherein each of the plurality of reaction stations (1604, 1824) is configured to contain the apparatus as defined in claim 1.
[0031]
31. System according to claim 30, characterized by the fact that at least one of the plurality of assembly stations (1618, 1804) is sized to receive a reagent capsule pressure mechanism (1000, 1504, 1836) .
[0032]
32. System according to claim 30, characterized by the fact that the translatable mounting assembly (116, 1506, 1802) is also rotatable about an axis of rotation that is linearly translatable.
[0033]
33. System according to claim 30, characterized in that each of the plurality of bulky reagent dispensing nozzles (1610, 1830) is fluidly coupled to a bulky reagent container (1614).
[0034]
34. System according to claim 30, characterized by the fact that the reagent cartridge (408, 700, 1634) sized to receive and direct a fluid distributed from the fluid distribution cartridge (1508, 1806) to the reaction chamber (206, 300, 406, 506, 600).
[0035]
35. System according to claim 30, characterized by the fact that it also comprises a plurality of temperature modification sets (1112, 1200, 1302) located in a respective station among the plurality of reaction stations (202, 1300, 1606, 1812).
[0036]
36. System according to claim 35, characterized by the fact that temperature modification sets (1112, 1200, 1302) are selectively controlled to heat and cool the plurality of reaction stations (202, 1300, 1606, 1812 ).
[0037]
37. System according to claim 35, characterized by the fact that the plurality of temperature modification sets (1112, 1200, 1302) are thermoelectric coolers (TEC).
[0038]
38. System according to claim 30, characterized by the fact that it also comprises a bulky container (1912, 1914, 1916, 1918) and a sensor (1902) coupled to the bulky container (1912, 1914, 1916, 1918) for determine a fluid level in the bulky container (1912, 1914, 1916, 1918).
[0039]
39. System according to claim 30, characterized by the fact that the sensor (1902) is a weight sensor.
[0040]
40. System according to claim 30, characterized by the fact that it also comprises a locking set (1324) coupled to each of the reaction stations (202, 1300, 1606, 1812) to lock the reaction stations (202 , 1300, 1606, 1812) in position.
[0041]
41. System according to claim 40, characterized by the fact that the locking assembly (1324) is an electromechanical locking system (1412) that remains locked in the event of a power failure.
[0042]
42. System according to claim 30, characterized by the fact that it also comprises a drainage drain assembly (2500) having a modifiable fluid conduit (2506, 2508) dimensioned to prevent the return of the dumping into the plurality of reaction stations (202, 1300, 1606, 1812).
[0043]
43. Method comprising: determining an inventory of an automated sample processing system (100, 400, 1600, 1800), determining an inventory comprising retrieving information from an identifier (918, 920) associated with at least a reaction station (202, 1300, 1606, 1812) in the automated sample processing system (100, 400, 1600, 1800) and at least one sensor (1902) associated with at least one bulky container (1912, 1914, 1916 , 1918) in the automated sample processing system (100, 400, 1600, 1800); download a processing protocol from a central controller (2002) to the automated sample processing system (100, 400, 1600, 1800); operate the automated sample processing system (100, 400, 1600, 1800) based on the processing protocol and independently of the central controller (2002); and distribute a reagent from the automated sample processing system (100, 400, 1600, 1800), characterized by the fact that at least one reaction station (202, 1300, 1606, 1812) is configured by the presence of the device as defined in claim 16.
[0044]
44. Method according to claim 43, characterized in that the determination of an inventory comprises the digitization of an identifier (918, 920) included in the reagent cartridge (408, 700, 1634) associated with at least one station reaction (202, 1300, 1606, 1812).
[0045]
45. Method, according to claim 43, characterized by the fact that the determination of an inventory also comprises the digitization of an identifier (918, 920) included in a fluid distribution cartridge (1508, 1806) used in the system of automated sample processing (100, 400, 1600, 1800).
[0046]
46. Method, according to claim 43, characterized by the fact that the information retrieved from the sensor (1902) comprises information regarding a volume of liquid inside the bulky container (1912, 1914, 1916, 1918).
[0047]
47. Method according to claim 43, characterized in that the operation of the automated sample processing system (100, 400, 1600, 1800) comprises the switching of a first bulky container (1912, 1914, 1916, 1918 ) to a second bulky container (1912, 1914, 1916, 1918) when it is determined from the sensor (1902) that the first bulky container (1912, 1914, 1916, 1918) is empty.
[0048]
48. Method according to claim 43, characterized in that the distribution of a reagent comprises the distribution of reagents from a linearly translatable bulky fluid distribution set (1064, 1824) coupled by fluid to at least one bulky container (1912, 1914, 1916, 1918).
[0049]
49. Method according to claim 43, characterized in that the distribution of a reagent comprises the distribution of the reagent from a reagent capsule (416, 900, 1024) and the distribution of a reagent from the capsule reagent (416, 900, 1024) comprises: dispensing an initial amount of reagent contained within the capsule (416, 900, 1024) by advancing a plunger (904, 1028) coupled to the capsule (416, 900, 1024) through a seal (930, 1026) formed in the capsule (416, 900, 1024); and dispensing a remaining amount of reagent contained within the capsule (416, 900, 1024) by disassembling the capsule (416, 900, 1024).
[0050]
50. Method, according to claim 43, characterized by the fact that the download comprises the download of the processing protocol for at least one reaction station (202, 1300, 1606, 1812).
[0051]
51. Method, according to claim 50, characterized by the fact that at least one reaction station (202, 1300, 1606, 1812) implements the processing protocol independently of the central controller (2002).
[0052]
52. Method, according to claim 43, characterized by the fact that it further comprises: monitoring a situation of the processing protocol performed in at least one reaction station (202, 1300, 1606, 1812); and create a file of each of the processes carried out according to the processing protocol at the reaction station (202, 1300, 1606, 1812).
[0053]
53. Method comprising: reflecting an image (1642) of a first identifier (918) located on a slide (322, 422, 522, 622) in the direction of a digitizer (1628); digitize the first identifier (918) with the digitizer (1628); and digitizing a second identifier (920) located on a reagent cartridge (408, 700, 1634) associated with the slide (322, 422, 522, 622), characterized by the fact that the reagent cartridge (408, 700, 1634 ) is configured by the apparatus as defined in claim 16.
[0054]
54. Method, according to claim 53, characterized by the fact that it further comprises: digitizing a third identifier located in a reaction station (202, 1300, 1606, 1812) associated with the slide (322, 422, 522, 622 ) and the reagent cartridge (408, 700, 1634); and comparing the information obtained from the first identifier (918), the second identifier (920) and the third identifier to determine a processing protocol performed on the slide (322, 422, 522, 622).
[0055]
55. Method, according to claim 53, characterized by the fact that the reflection comprises reflecting the image (1642) in a mirror (1626).
[0056]
56. Method according to claim 55, characterized in that the mirror (1626) is removably mounted to a reaction station (202, 1300, 1606, 1812) that supports the slide (322, 422, 522 , 622).

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DK2573542T3|2021-02-01|

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CN103018081B|2017-11-03|

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AU2012202090A1|2013-04-04|

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公开号 | 申请日 | 公开日 | 申请人 | 专利标题

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法律状态:
2014-07-01| B03A| Publication of a patent application or of a certificate of addition of invention [chapter 3.1 patent gazette]|

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2018-12-11| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

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2019-11-19| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

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2020-05-19| B07A| Application suspended after technical examination (opinion) [chapter 7.1 patent gazette]|

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2020-09-08| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

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2020-12-15| 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 30/08/2012, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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US13/238,511|US8932543B2|2011-09-21|2011-09-21|Automated staining system and reaction chamber|

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US13/238,511|2011-09-21|

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