Advanced tissue staining systems and methods

Abstract

A system comprising: a turntable including a plurality of mounting stations sized to receive at least one fluid dispensing cartridge; and a receiving assembly positioned below the turntable, the receiving assembly including a plurality of reaction stations, each of the plurality of reaction stations including: a body including length and width dimensions of a chamber together defining a cavity for receiving a single slide; and a cover including a first position covering the cavity and a second position exposing a portion of the cavity. A method comprising moving the cover of a reaction station to expose a single microscope slide containing a sample, and dispensing one or more reagents onto the sample.

Description

Cross-reference to related applications

[0001] This non-provisional patent application claims the benefit of pending U.S. Provisional Patent Application No. 63 / 740,927, filed on December 31, 2024, entitled "Advanced Tissue Staining System and Method," the contents of which are incorporated herein by reference in their entirety. Technical Field

[0002] An automated system for depositing reagents on biological specimens. Background Technology

[0003] In various settings, biological specimens require processing and testing for diagnostic purposes. Generally, pathologists and other diagnostic physicians collect and study samples from patients, evaluating them at the cellular level using microscopy and other equipment. The pathological and other diagnostic processes typically involve numerous processing steps, including collecting biological samples such as blood and tissue, preparing samples, preparing microscope slides, staining the samples on the slides, examining them, retesting or restaining them, collecting additional samples, re-examining the samples, and ultimately providing a diagnostic result.

[0004] Sample (e.g., tissue) staining processors or staining machines can operate at different levels of automation to process human or animal tissue specimens for histological or pathological purposes. Various types of chemical reagents can be used at various levels of tissue processing, and various systems have been developed for delivering reagents to slides containing the specimen. Examples of known reagent delivery systems include small-volume dispensers, manually poured reagent containers, or bulk containers connected to the staining machine via tubing.

[0005] The system is known to have various drawbacks. For example, manually pouring or emptying reagents into or out of the reagent container is susceptible to cross-contamination, time-consuming, and requires precise pouring, thus reducing the overall efficiency and accuracy of the tissue processing system. Another drawback is that manually pouring and emptying reagents can be careless, requiring cleanup of spills and subsequent instrument downtime. Yet another drawback is that manually selecting and applying the correct reagents introduces a significant risk of human error and increases the likelihood of incorrect reagent selection and application, leading to false positive or false negative results. This not only reduces testing accuracy and operational efficiency but also leads to misdiagnosis. Attached Figure Description

[0006] Embodiments of the present invention are illustrated in the accompanying drawings by way of example rather than limitation, in which the same reference numerals indicate similar elements. It should be noted that references to "a" or "an" embodiment in this disclosure do not necessarily refer to the same embodiment, and such references imply at least one.

[0007] Figure 1 A perspective top-side view of the sample processing system is shown.

[0008] Figure 2 It shows the relationship with Figure 1 A perspective top-side view of a single reaction station in a sample processing system with the reaction compartments separated, wherein the reaction station's lid is in the closed position.

[0009] Figure 3 It shows Figure 2 A perspective top-side view of the reaction station, with the reaction station's cover in the open position.

[0010] Figure 4 It shows Figure 2 A side view of the reaction station with the lid of the reaction station in the closed position.

[0011] Figure 5 The diagram shows Figure 2 The top-side perspective view of the reaction station, in which the main body of the reaction station has been removed and the chambers of the substructures of the reaction station are illustrated.

[0012] Figure 6A It shows Figure 2 A side perspective view of the reaction station, in which the tray of the reaction station is supported by legs in the highest position.

[0013] Figure 6B It shows that it contains and Figure 2 Side perspective view of the reaction station isolation legs and tray support assembly.

[0014] Figure 7A It shows Figure 2 A side view of the reaction station including the main body, legs and tray, and showing the tray supported by the legs in the first or lowest position.

[0015] Figure 7B It shows Figure 2 A side view of the reaction station, including the main body, legs, and tray, and showing the tray supported by the legs in a second position.

[0016] Figure 7C It shows Figure 2 A side view of the reaction station, including the main body, legs, and tray, and showing the tray supported by the legs in a third position.

[0017] Figure 7D It shows Figure 2 A side view of the reaction station including the main body, legs and tray, showing the tray supported by the legs at the fourth or highest position.

[0018] Figure 8 It shows Figure 2 A perspective top-side view of the reaction station, including the main body, legs, and tray, showing the tilted tray.

[0019] Figure 9A It shows crossing Figure 8 The line 9-9' Figure 2 A side view of a portion of the reaction station, illustrating a tray moving downwards in a horizontal (untilted) orientation.

[0020] Figure 9B It shows crossing Figure 8 The line 9-9' Figure 2 A side view of a portion of the reaction station, illustrating a tray moving downwards in an inclined orientation.

[0021] Figure 10 Shown separately Figure 1 The left-hand perspective view of the turntable assembly of the sample processing system.

[0022] Figure 11 Shown separately Figure 10 The right-side perspective view of the platform portion of the turntable assembly is shown, and the x-direction (longitudinal) drive mechanism is illustrated.

[0023] Figure 12 Shown separately Figure 10 A perspective rear view of the U-shaped bracket and the lateral drive support bracket of the turntable assembly.

[0024] Figure 13 Shown separately Figure 10 A perspective rear view of the turntable portion of the turntable assembly.

[0025] Figure 14 It shows the relationship with Figure 10 Side perspective view of the turntable assembly's stand and the turntable-isolated arm assembly.

[0026] Figure 15 Shown separately Figure 1 A perspective front left view of the storage rack of the sample processing system.

[0027] Figure 16 The diagram shows an operable device for storing... Figure 15 In the storage rack and used in Figure 1 A side perspective view of the reagent kit used to dispense reagents in the sample processing system.

[0028] Figure 17 It shows Figure 15 The right front perspective view of a portion of the storage shelf, illustrating two similar structures housed within it. Figure 16 The reagent kit.

[0029] Figure 18 It shows Figure 13 Part of the turntable includes a support or box carrier plate isolated from the base of the column, and the kit is illustrated in the mating part of the support or box carrier plate.

[0030] Figure 19 It shows Figure 1 A front view of the service station of the sample processing system. Detailed Implementation

[0031] In the following paragraphs, the invention will be described in detail by way of example with reference to the accompanying drawings. Throughout this specification, the embodiments and examples shown should be considered exemplary and not limiting of the invention. Furthermore, references to various aspects of the embodiments disclosed herein do not imply that all claimed embodiments or methods must include the referenced aspects.

[0032] Figure 1 The illustration shows a perspective view of a sample processing system. The sample processing system 100 includes a housing 102 for accommodating and storing various components of the system. The housing 102 includes a reaction compartment 104 and a storage compartment 101. The reaction compartment 104 is separated from the storage compartment 101 by a platform 105 forming the base of the reaction compartment 104. In addition to the platform 105, opposing sidewalls extend from the platform 105, and covers connect the ends of each of the sidewalls. The covers, sidewalls, and platform 105 together define the compartment for sample processing. Components within the reaction compartment 104 are accessible via a cover member 108 and a door member 110 (as shown, on the front of the housing 102).

[0033] The dimensions (e.g., internal volume) of reaction compartment 104 are designed to accommodate a storage rack for storing multiple reagent kits. The storage rack 106 may be mounted on platform 105 or to a side wall of reaction compartment 104 (e.g., the rear side wall as shown). Storage rack 106 can be used to store reagent kits. A representative reagent kit is a single-use kit, such as a thermal inkjet cartridge, which contains a volume of reagent that can be used for pathological or histological processing. Storage rack 106 accommodates an array of slots to store individual reagent kits in, for example, column and row arrays. Storage rack 106 may include a cooling device to store reagent kits in a refrigerated state. A representative cooling device may include a compressor that compresses refrigerant vapor and forces the vapor through a coil, where the vapor liquefies and cools the storage rack slots.

[0034] The dimensions of the reaction compartment 104 are designed to accommodate multiple reaction stations 112. Figure 1 Representatively shown are 30 reaction stations 112 arranged in a 15×2 configuration in a plane (xz plane) on platform 105. It will be understood that the number and configuration of reaction stations will depend in part on the area dedicated to reaction compartment 104. Therefore, it is contemplated that the number of reaction stations can vary with their configuration. As shown, a turntable assembly comprising a bench 114 and a turntable 115 is positioned above the reaction stations 112. The turntable 115 is operable to accommodate / accommodate multiple reagent kits and to dispense reagents from the respective kits onto corresponding slides in the reaction stations 112. The turntable 115 is operable to move on the bench 114 to position reagent kits above the individual reaction stations 112 and to load / unload reagent kits from / to the storage rack 106.

[0035] The sample processing system 100 also includes a controller 109. The controller 109 contains non-transient machine-readable instructions to control the operation of the sample processing system, including, but not limited to, loading / unloading reagent kits in the storage rack 106 and loading / unloading reagent kits in the turntable 115. Figure 1 A controller 109 is shown outside the housing 102. It should be understood that the controller 109 may be a component outside or inside the housing 102.

[0036] Figure 2 and Figure 3 A perspective view of a reaction station separated from reaction chamber 104 is shown. Reaction station 112 includes a body 120. The body 120 of reaction station 112 includes a base defining a length dimension (z-direction) and a pair of opposing sidewalls, and a separate pair of opposing sidewalls defining a width dimension (x-direction), and the base and the two pairs of sidewalls together define a chamber 125 (see [reference]). Figure 3 The chamber is designed to house a single slide. Typically, the slide can be a flat piece of glass with a thickness of 1 mm (0.04 inches), a length of 75 mm (approximately 3 inches), and a width of 26 mm (approximately 1 inch). The length of the chamber can be approximately 80 mm to 100 mm (3.2 inches to 4 inches), and the width of the chamber can be approximately 28 mm to 40 mm (1.1 inches to 1.6 inches). Figure 3A slide 150 within chamber 125 is shown. Body 120 can be made of a material that is chemically inert to reagents commonly used in the staining process. Representative metallic materials include, but are not limited to, stainless steel, zinc alloys, aluminum alloys, and silver. For example, silver can be used to impart antimicrobial properties to body 120. Other exemplary materials for body 120 may include thermally conductive polymeric materials such as plastics or cellulose (i.e., cellulose-based or including) materials, ceramics, Teflon®, glass, etc. Body 120 can be formed by any process known in the art, such as injection molding, machining, or any other manufacturing process suitable for producing the desired features. Furthermore, it should be understood that body 120 can consist of more than one of the materials discussed above.

[0037] Each of the reaction stations 112 also includes a cover 130, made of, for example, plastic or metal material (e.g., stainless steel, zinc alloy, aluminum alloy, silver), having dimensions covering the chamber 125. The cover 130 includes a generally rectangular portion having length (z-direction) and width (x-direction) dimensions similar to those of the body 120. One end of the cover 130 also includes a U-shaped clamping portion 132 extending longitudinally (z-direction) from the generally rectangular portion. As shown, a gasket or seal 135 of rubber or other polymer material is disposed on the upper surface of the body 120. When the cover 130 is in position contacting the gasket or seal 135 on the body 120, the gasket or seal 135 can be used to seal (e.g., hermetically and fluidly) or substantially seal the chamber 125 (see Figure 120). Figure 2 , Figure 4 ).

[0038] The main body 120 of reaction station 112 is mounted on substructure 140. Substructure 140 is shown as a rectangular member, for example, made of plastic or metal (e.g., stainless steel, aluminum alloy, zinc alloy), comprising a base defining a chamber and two pairs of opposing sidewalls, the tops of which contact the base of the main body 120. In this example, substructure 140 has a length dimension (z-direction) similar to that of the main body 120. A portion of the main body 120 extends longitudinally in a cantilever manner beyond the end of substructure 140, thereby exposing a portion of the chamber of substructure 140. Figure 5 A top-side perspective view of the reaction station 112 with the main body 120 removed is shown. (See diagram.) Figure 5 As shown, gear 155 is disposed in a cavity of substructure 140 behind the main body 120 (on the side of the main body opposite the cantilever portion). Gear 155 is shown centered on shaft 160 between longitudinally opposite sidewalls of substructure 140 (sidewalls defining...). Figure 2 and Figure 3(Length in the z-direction). Shaft 160 is connected to the opposite side of substructure 140 by screws, bolts, pins, or rivets 165. The opposite side of gear 155 is parallel to the opposite sidewall of substructure 140. The outer periphery of gear 155 includes cutting teeth or gear teeth. Gear 155 is driven (rotated) by motor 170, which in this example is located below substructure 140. Motor 170 includes a protruding shaft connected to worm gear 157. Worm gear 157 includes threads that engage with gear 155 and drive gear 155 in a clockwise or counterclockwise direction.

[0039] A bracket 145 is connected to the longitudinally opposite sidewalls of substructure 140 and the opposite sidewalls of cover 130 (one bracket is connected to the outer side of each sidewall). The bracket 145 is illustrated as a rectangular member, for example, of a plastic or metal material (e.g., stainless steel, aluminum alloy, zinc alloy). Each bracket 145 is connected at its first end to one side of substructure 140 by bolts, pins, rivets, or screws 146, which allows the bracket to rotate on the bolts, pins, rivets, or screws (e.g., the diameter of the opening through the bracket 145 is larger than the outer diameter of the bolt, pin, or screw 146). A counterweight (counterweight 147) may be provided between each bracket 145 and the corresponding sidewall of the substructure to counteract the weight of cover 130 when cover 130 pivots / rotates. The second end of each bracket 145 is connected to the corresponding longitudinally opposite side of cover 130 by bolts, pins, rivets, or screws 149. Bolts, pins, rivets, or screws 149 can pivotally connect the bracket to cover 130. A bracket or drive rod 175 is connected to the U-shaped clamp portion 132 of the cover 130. The first end of the drive rod 175 is connected to a gear 155 in a fixed position. The second end of the drive rod 175 is connected to the U-shaped clamp portion 132 of the cover 130 by bolts, pins, rivets, or screws 176. The drive rod 175, gear 155, worm gear 157, and motor 170 cause the cover to move from a first position covering (closing) the chamber 125 (see...). Figure 2 , Figure 4 ) moved to a second position, part of the exposed chamber (see Figure 3 As the cover 130 moves between positions, the bracket 145 and the drive rod 175 support the cover 130.

[0040] When the cover 130 is in the first position covering the chamber 125 of the body 120, rotation of the gear 155 driven by the motor 170 (e.g., counterclockwise rotation) causes the drive rod 175 to rotate, thereby pivoting and rotating the cover 130 to move it from the first position to a second position. When the cover 130 is in the second position, the support 145 can be substantially parallel to the sidewall of the substructure 140. Rotation of the gear 155 in the opposite direction (e.g., clockwise rotation) by the motor 170 causes the drive rod 175 to rotate, which in turn rotates the cover 130 to move it from the second position to the first position.

[0041] As described above, the chamber 125 of the body 120 is sized to accommodate a microscope slide (a single microscope slide only) for processing. Biological samples can be mounted or fixed onto the microscope slide for processing. Figure 3 and Figure 6A and Figure 6B As illustrated, in order to support microscope slides in chamber 125, each reaction station includes a tray 180 mounted on a foot 185. In one example, the tray 180 is a planar structure with a cross-shaped or shaped form having four defined ends. Each end may have an upward protrusion (e.g., linear or inverted L-shaped) to restrain the slide on the tray.

[0042] The support leg 185 is attached to the base of the tray 180 at, for example, the midpoint of the tray. In this manner, the support leg 185 extends through the base of the body 120 into the chamber 125. The opening in the base of the body 120 through which the support leg 185 extends can be sealed, for example, with a gasket (e.g., hermetically sealed and liquid-sealed). The support leg 185 can be a linear actuator or can be connected to a linear actuator operable to move the tray 180 between multiple locations relative to the chamber 125 (e.g., moving the tray 180 between multiple depths of the chamber 125). In one example, the support leg 185 is operable to, for example... Figures 7A to 7D The side view illustration shows the movement of tray 180 between four positions: tray 180 and the slide thereon are in a first position at a first depth in chamber 125. Figure 7A The tray 180 and the slide thereon are in a second position within the chamber 125 at a second depth less than the first depth (i.e., the tray can rise from the first depth to the second depth or descend from the second depth to the first depth). Figure 7B The tray 180 and the slide thereon are located in a third position within the chamber 125 at a depth less than the second depth (i.e., the tray can rise from the second depth to the third depth or descend from the third depth to the second depth). Figure 7C ); and the tray 180 and / or the carrier on it are located outside the chamber 125 (i.e., above the body 120 and above the seal 135) in a fourth position. Figure 7D ). Figure 3 The diagram shows reaction station 112, in which tray 180 is supported in a second position by legs 185. Figure 6A In the reaction station 112 shown in the figure, the tray 180 is supported by the legs 185 at the fourth position.

[0043] Tray 180 may be formed of a material with sufficient structural strength and neutral processing properties to support the slide, hold the reagent, and be compatible with the reagent and the temperature used during use. Typically, tray 180 may be made of a metallic material. Other exemplary materials for tray 180 may comprise thermally conductive polymeric materials such as plastics or cellulose (i.e., cellulose-based or including cellulose) materials, ceramics, Teflon®, glass, etc. Typically, tray 180 may be made of polyoxymethylene thermoplastics such as DELRIN (a registered trademark of EI DuPont, Wilmington, ., of Delaware). Tray 180 may be formed by any process known in the art, such as injection molding, machining, or any other manufacturing process suitable for producing the desired characteristics. Additionally, it should be understood that reaction tray 180 may consist of more than one of the materials discussed above, and such materials may be the same or different for the constituent materials of both tray 180 and body 120. Figure 6A As shown, the leg 185 extends vertically and includes a portion below the substructure 140, a portion passing through the base and chamber of the substructure 140, and a portion extending through the base of the body 120 into the chamber 125 to connect to the tray 180. The opening in the base of the body 120 through which the leg 185 extends can be sealed, for example, with a gasket (e.g., an airtight seal and a liquid seal). The opening in the base of the substructure 140 can also be sealed.

[0044] Figure 6B A side perspective view of a slide support assembly comprising a leg 185 and a tray 180, detached from the reaction station 112, is shown. The leg 185 can be connected to the base of the tray 180 via a pivot or hinged connector 1852. In one example, the pivot connector 1852 allows the tray 180 to rotate to a tilted position. In one example, the tray 180 can rotate along its length (z-direction length), for example, from 20 degrees to 45 degrees. Figure 8 The tray 180 is shown in an inclined position (after it has been rotated from a horizontal position (0 degrees) to an inclined position, for example, 20 to 45 degrees relative to the horizontal (see the cross-section of the illustration), represented by an angle α). The pivoting of the tray 180 in the first position to the angle α of 20 to 45 degrees allows any excess reagent on the slide 150 on the tray 180 to be removed from the slide. Figure 9A and Figure 9B It shows Figure 8 The cross-sectional view of the carrier support passing through line 9-9'. Figure 9A and Figure 9B The illustration shows one method of placing tray 180 in an inclined position. In this example, the sidewall of body 120 includes a section representing the first position of the slide (…). Figure 7A The depth of the second position () Figure 7BThe inner surface of the tray 150 extends into the depth of the tray 180. The protrusion 123 may be a spring or elastic body (e.g., plastic) having a length such that, for example, it prevents the longitudinal edge of the tray 150 and the tray 180 from moving past it when the tray 150 is moved from the second position to the first position by the foot 185. Figure 9A The tray 180 and slide 150 are representatively shown in the second position. When the support leg 185 moves the tray 180 and slide 150 downward between the second and first positions (as shown), one side of the tray 180 / slide 150 (the left side as shown) will contact the protrusion 123 and will be prevented from moving downward. The pivot connector between the support leg 185 and the tray 180 will allow the other side of the tray 180 / slide 150 (the right side as shown) to continue descending until the tray 180 / slide 150 tilts to an angle α representing the first position. Moving the tray 180 / slide 150 upward from the first position to the second position will reverse this process. The upward movement will initially cause the tray 180 / slide 150 to return to the horizontal position (i.e., initially moving the right side of the tray 180 / slide 150 upward as illustrated until the surface of the tray 180 / slide 150 is horizontal above the protrusion 123). The pivot connector may have a ratchet stop mechanism that locks when the tray 180 is rotated to the horizontal position, allowing the tray 180 / carrier 150 to remain horizontal when the legs raise the tray 180 / carrier 150 to the third position. Figure 7C ).

[0045] When tray 180 and slide 150 are in Figure 9B When in the tilted position shown, any excess fluid (e.g., reagent) on the slide 150 can be drained toward the bottom of the chamber 125 of the body 120. Figure 9A and Figure 9B A discharge tube 121 at the base of the main body is shown. The discharge tube 121 may include a conduit connected thereto with a valve that can be opened or closed. Typically, this valve may be connected to a controller 109, and the controller 109 may include non-transient machine-readable instructions to electrically actuate the valve to an open position when or after the tray 180 and slide 150 are in an inclined position, to discharge any excess fluid (e.g., reagent) from the chamber 125. The conduit may be connected to a waste container to collect any excess fluid (e.g., reagent).

[0046] Refer again Figure 6BOne or more slide heaters 1802 are disposed on the underside of the tray 180 (the side opposite to the side supporting the slide 150). The slide heater 1802 is, for example, an electric (joule) heater (e.g., 12 volts, 24 volts). The heater can be selected to rapidly heat the microscope slide to the desired temperature. Representative temperatures for certain sample handling operations may be 20°C (approximately ambient) to 150°C, such as between 20°C and 150°C, such as 30°C to 140°C, such as 40°C to 130°C, such as 50°C to 120°C, such as 60°C to 110°C, such as 70°C to 150°C, such as 100°C to 140°C, such as 110°C to 140°C, or such as 120°C to 130°C. Representative tissue processing temperatures include 120°C to 130°C for pressure antigen retrieval; approximately 90°C to 100°C for ambient pressure antigen retrieval; and 20°C to 40°C for ambient temperature staining. A heat sink 1804 is also located on the underside of the tray 180. The heat sink 1804 may be made of a highly thermally conductive material (e.g., metal), which dissipates heat applied to the tray 180 (e.g., via the slide heater 1802) to cool the tray 180 for processing operations that do not require heating of the microscope slide surface or require ambient temperature incubation. Rinsing the microscope slides with a cleaning buffer or water after elevated temperature processing also helps to rapidly cool them.

[0047] The foot 185 is, for example, a linear actuator comprising an outer tube 1854 and an inner tube 1855 at least partially disposed within the outer tube 1854. The inner tube 1855 can move relative to the outer tube 1854 in the y-direction (vertical direction), for example, when energized. The foot 185 may have an electric motor 1856 (e.g., a direct current (DC) motor) at its base operable to move the inner tube 185 in the y-direction. The electric motor 1856 can be connected to a controller 109 and operated based on non-transient machine-readable instructions associated with the controller 109. Additional instructions associated with the controller 109 may include instructions to control the slide heater 1802 to heat the tray 180 for elevated temperature treatment, and instructions to introduce a cleaning buffer or water after the elevated temperature treatment to rinse the microscope slide.

[0048] Referring again to cover 130, cover 130 may include a plurality of fluid connectors 131 (e.g., four to eight fluid connectors) extending from the top surface of the cover. The fluid connectors 131 may be arranged in a row along one end of the top side of cover 130 (see...). Figure 2The fluid connector 131 may be a fitting or coupling that allows a fluid conduit (e.g., a polymer pipe) to be connected to it. The underside of the cover 130 includes a plurality of conduits 137 arranged longitudinally across the length of the tray 180. Each fluid connector 131 is fluidly connected to a conduit 137 so that fluid can be delivered to the conduit 137 through the fluid connector. The conduit 137 may be a pipe material such as metal (e.g., copper, aluminum, stainless steel). Each conduit 137 may have multiple openings along its length to discharge fluid from the conduit toward the tray 180 when the cover 130 is in a first position (e.g., covering chamber 125). Each opening in the conduit may include a nozzle to control the flow direction and rate.

[0049] In one example, the bulk reagent can be individually connected to fluid connector 131. Examples of bulk reagents include, but are not limited to, distilled water, hematoxylin, Tris-buffered saline, and dewaxing solution. The bulk reagent can be contained in a single container stored in storage compartment 101 below reaction compartment 104 (see [link to storage compartment 131]). Figure 1 Bulk reagent sources can be connected to a single fluid connector 131 via conduits extending, for example, between the respective bulk reagent container and the fluid connector. For each bulk reagent container connected to the fluid connector, the bulk reagent can be supplied to the fluid connector as needed using a pump, such as a single inline pump. Non-transient machine-readable instructions associated with controller 109 can control the metering of reagents from the bulk reagent container, such as via a timer or via a single online flow meter (e.g., a flow meter in the conduit between the bulk reagent container and the fluid connector).

[0050] Reaction station 112 can be used as a humidifier, allowing the manipulation and maintenance of humidity levels within chamber 125 to reduce reagent evaporation and sample (e.g., tissue) drying. Representative humidity levels can be relative humidity above 50%, such as above 60% to 100%, such as 70% to 100%, such as 80% to 100%, or such as 90% to 100%. Figures 2 to 4In the example shown, the body 120 of reaction station 112 includes a chamber 125, which is sized to accommodate a reservoir beneath tray 180 when tray 180 is in its lowest position (first position). The reservoir may be filled with fluid (e.g., water) to create humidity in chamber 125. Typically, a fluid source (water) may be connected to a fluid connector 131. The conduit between the fluid source and the fluid connector may include a flow meter to measure the amount of fluid introduced into chamber 125. In one example, a valve connector (valve connector 131) and a flow meter (if present) may be electrically connected to a controller 109 containing non-transient machine-readable instructions to introduce a volume of fluid into chamber 125 via the valve connector. When introduced or heated, for example, by a heater in the reservoir of chamber 125, the introduced fluid may be at an elevated temperature (e.g., 80°F to 120°F). Discharge pipe 121 (see...) Figure 4 The discharge pipe 121 also extends from chamber 125 through the base wall of body 120 and can be used as a discharge pipe to drain the fluid contents of the reservoir in chamber 125. The discharge pipe 121 may include a valve outside chamber 125. In one example, the discharge valve may be electrically connected to controller 109, which contains non-transient machine-readable instructions to actuate the discharge valve (open, close).

[0051] As described above, in some cases it may be desirable to raise the temperature in reaction station 112 above ambient temperature. One way to achieve this is by heating tray 180 using a plate heater 1802. In addition to, or as an alternative to, the use of a plate heater 1802, the temperature in chamber 125 can be increased by heating fluid in a reservoir, as described above regarding generating a humidity level in chamber 125. Another heating technique may include one or more heaters positioned on one or more sidewalls of body 120 within chamber 125 to heat the ambient area surrounding tray 180. Examples include resistive electric heaters or infrared heaters positioned within chamber 125. A further technique is a heating sheath wrapped around the exterior of body 120 to heat chamber 125 from the outside. One or more heat sources may be connected to controller 109 to allow machine-readable, non-transient commands associated with the controller to control the heat sources and regulate the temperature in chamber 125.

[0052] Figure 1Representatively shown are 30 reaction stations 112 arranged in a 15x2 configuration in a plane (xz plane). The first row of two rows shows reaction stations 112, each with a cover 130 in a second (closed or covered) position. The second row of two rows shows reaction stations 112 with their respective covers in the open position. Each reaction station 112 can be connected to a platform 105 of a reaction compartment 104 of the housing 102.

[0053] refer to Figure 1 In addition to the reaction station 112, the reaction compartment 104 of the housing 102 of the processing system 100 also includes a platform 114 supporting the turntable 115. The platform 114 and the turntable 115 are collectively referred to as the turntable assembly. Figure 10 A perspective left-hand view of the individual turntable assembly is shown. The stand 114 includes two vertical (y-direction) columns 1142 connected to the base of the reaction chamber 104. The vertical columns 1142 are separated by a distance in the x-direction greater than the distance occupied by a row of reaction stations 112 in the reaction chamber 104. Two horizontal supports 1144 are disposed between the vertical columns 1142 at a position above the reaction stations 112. The horizontal supports 1144 are typically each cylindrical and extend the x-direction distance of the vertical columns 1142 and are each parallel to the base of the reaction chamber 104. The horizontal supports 1144 are connected to the vertical columns 1142 via end brackets 1145 (e.g., inverted L-shaped brackets). As will be described in detail below, the separation distance of the horizontal supports 1144 in the z-direction is selected relative to the z-direction travel of the turntable 115. U-shaped brackets 1146 (e.g., inverted U-shaped as shown) are connected to each of the horizontal supports 1144 between the end brackets 1145. The U-shaped support 1146 comprises two legs separated by a base. A horizontal support 1144 is connected to the base via a linear bearing 1147. The linear bearing 1147 is connected to the upper or exposed side of the base of the U-shaped support 1146 and allows the U-shaped support 1146 to move in the x-direction on the horizontal support 1144. The base of the U-shaped support 1146 includes a penetrating opening 1148, such as a rectangular opening. A tab 11493 is also connected to one end of the upper or exposed side of the base of the U-shaped support 1146. The tab 11493 extends upward (in the y-direction) from the base. The tab 11493 is connected to a timing belt 1140 for moving the U-shaped support 1146 in the x-direction (longitudinal direction).

[0054] A lateral drive support bracket 1149 is connected to the base of a U-shaped bracket 1146 below a horizontal support member 1144. The lateral drive support bracket 1149 is a U-shape (e.g., an inverted U-shape as shown) defined by its base and sidewalls. As shown, the top side of the lateral drive support bracket 1149 has a penetrating opening 11499. The base of the lateral drive support bracket 1149 is narrower in the x-direction than the corresponding width of the base of the U-shaped bracket 1146, such that the sidewalls of the lateral drive support bracket 1149 are positioned between the sidewalls of the U-shaped bracket 1146, and the sidewalls of the lateral drive support bracket 1149 are connected to the corresponding sidewalls of the U-shaped bracket 1146 via, for example, screws, rivets, or welding. Inside each sidewall of the lateral drive support bracket 1149 is a lateral linear guide that extends the entire length of the sidewall in the z-direction, or 70% to 90% of the z-direction length. Each lateral linear guide 11492 is equidistant in the y-direction from the end of the sidewall that is connected to the sidewall by, for example, screws, rivets, or welding. A turntable 115 is connected to each lateral linear guide 11492.

[0055] Turntable 115 can move in three directions on the platform 114. Turntable 115 can move in the x-direction (longitudinal) as the U-shaped support 1146 moves. Turntable 115 can move in the y-direction (vertical) as the end support 1145 moves vertically on the vertical column 1142. Turntable 115 can move in the z-direction (lateral) as each of the transverse linear guides 11492 in the transverse drive support bracket 1149 moves along the transverse drive support bracket 1149.

[0056] Figure 11 A perspective right-side view of a portion of the platform 114 is shown to illustrate the drive mechanism in the x-direction (longitudinal). In this view, the platform 114 includes a horizontal support 1144 connected to a vertical column 1142 via an end bracket 1145. A gear 1141, rotating in the xz plane, is located on one side of the platform 114. Figure 11 The timing belt 1140 is attached to the top of each end bracket (shown on the left side). One of the gears 1141 is connected to the shaft of the motor 1143, and the motor is operable to rotate the gear clockwise or counterclockwise. The timing belt 1140 is disposed around the gear 1141 and extends above one of the horizontal supports 1144. The timing belt 1140 is operable to move in the x-direction (longitudinal direction) via the gear 1141. The timing belt 1140 is connected via screws, rivets, pins, etc. (see...) Figure 10 The timing belt 1140 is connected to the tab 11493 attached to the U-shaped bracket 1146. The connection of the timing belt 1140 to the U-shaped bracket 1146 allows the motor 1143 to move the U-shaped bracket 1146 in the x-direction (longitudinal direction), and thereby move the lateral drive support bracket 1149 and the turntable 115.

[0057] Figure 12 A perspective rear view of the individual U-shaped bracket 1146 and the lateral drive support bracket 1149 is shown. Figure 12 A linear bearing 1147 is shown connected to the upper or exposed side of the base of a U-shaped bracket 1146. The linear bearing 1147 supports a horizontal support 1144. Three linear bearings 1147 are shown, one on one end of the U-shaped bracket 1146 to support one horizontal support 1144, and two linear bearings 1147 on opposite ends of the base to support another horizontal support 1144, with the z-direction spacing between the one linear bearing and the two linear bearings equal to the z-direction distance between the horizontal supports 1144 (see [reference]). Figure 10 The base of the U-shaped bracket 1146 includes a penetrating opening 1148, such as a rectangular opening, between the one linear bearing 1147 and the two linear bearings 1147. A tab 11493 is also attached to one end of the upper or exposed side of the base of the U-shaped bracket 1146. The tab 11493 extends upward (in the y-direction) from the base. The tab 11493 is connected to a timing belt 1140 for moving the U-shaped bracket 1146 in the x-direction (longitudinal direction) (see...). Figure 10 ).

[0058] Figure 12 The diagram also illustrates the z-direction (lateral) drive mechanism. Figure 12 A lateral drive support bracket 1149 is shown attached to and positioned below a U-shaped bracket 1146. A lateral linear guide 11492 is located on the inner side of each of the sidewalls 11494A and 11494B of the lateral drive support bracket 1149, extending a portion (e.g., 70% to 90% of the z-direction length) of the sidewall. Each lateral linear guide 11492 is equidistant in the y-direction from the end of the sidewall (sidewalls 11494A and 11494B) connected to it by, for example, screws, rivets, or welding.

[0059] Figure 12 The z-direction (lateral) drive mechanism shown also includes two gears 11493 connected to the exterior (as shown on the left side wall) of the lateral drive support bracket 1149, 11494A. Figure 12Only one of the two gears 11493 is visible at one end (rear end) of the side wall 11494A of the lateral drive support bracket 1149. The second gear 11493 is located at the opposite end (front end) of the side wall 11494A of the lateral drive support bracket 1149. Each of the two gears 11493 rotates in the yz plane. One of the two gears 11493 is connected to a worm gear 11496 that rotates on the shaft of a motor 11495, and the motor 11495 is operable to rotate clockwise or counterclockwise. A timing belt 11497 is arranged around the gear 11493 and extends along the side wall 11494A of the lateral drive support bracket 1149. The timing belt 11497 is operable to move in the z-direction (lateral direction) via the gear 11493.

[0060] Figure 13 This is a perspective rear view of a portion of turntable 115. This view illustrates a portion of turntable 115 connected to a transverse drive support bracket 1149 of the platform 114. Turntable 115 includes a rectangular main support 11510 having a length dimension (x-dimension) and a width dimension (z-dimension) defined by opposing pairs of sidewalls positioned within the transverse drive support bracket 1149. Sidewalls 11511 and 11514 define the length dimension, and sidewalls 11512 and 11513 define the width dimension. The main support 11510 also includes a top portion 11515 connected to each sidewall and having a through opening for a column 1151. Z-shaped bracket 1153 is connected to the sidewall 11512 of the main bracket 11510. The Z-shaped bracket 1153 has a base 11531 extending horizontally (x-direction) a distance d from the sidewall 11512; a middle portion 11532 extending vertically (y-direction); and a apex portion 11533 extending horizontally (x-direction) from the middle portion 11532. When the main bracket 11510 is positioned within the lateral drive support bracket 1149, the distance d from the sidewall 11512 of the Z-shaped bracket 1153 allows the middle portion 11532 and the apex portion 11533 to be positioned on the outside of the sidewall (sidewall 11494A) of the lateral drive support bracket 1149. Timing belt 11497 (see...) Figure 12 The main support 11510 of the turntable 115 is connected to the apex 1153 (e.g., via screws, rivets, pins, etc.), which allows the motor 11495 to move the turntable 115's main support 115 in the z-direction (lateral direction). A lateral lathe bearing 1154 is also attached to the sidewall 11512 and is operable to engage with a lateral linear guide 11492, which is connected to the inside of the sidewall 11494A of the lateral support bracket 1149 (see...). Figure 12Roller 1159 extends outward from sidewall 11513 (opposite to sidewall 11512). Roller 1159 is operable to engage within the lateral linear guide 11492 of the sidewall 11494B of the lateral drive support 1149 and to rotate in the yz plane.

[0061] As described above, the main support 11510 includes a top portion 11515 having an opening for penetration of the column 1151. The column 1151 includes cut or inserted teeth around its top portion. A swivel bearing 1155 is disposed on the top portion 11515 of the main support 11510. The swivel bearing 1155 includes an outer ring and an inner ring, the inner ring including a gear with cut or inserted teeth that meshes with the teeth around the top portion of the column 1151. A gear 1156 is disposed on and connected to the top surface of the swivel bearing 1155. The gear 1156 is operable to rotate in the xz plane and rotates the inner ring of the swivel bearing 1155 in the same plane, thus rotating the column 1151. The main support 11510 remains stationary (does not rotate). The gear 1156 is rotated by a motor 1157. Motor 1157 is mounted to the top portion 11515 of main bracket 11510 and has a shaft extending therefrom that shaft that rotates in the yz plane. This shaft is connected to a worm gear 1158 that meshes with gear 1156 to rotate gear 1156 in the xz plane. (Reference) Figure 10 The base of the column 1151 of the turntable 115 includes a foot or box carrier plate 1152 operable to engage and accommodate multiple kits. Rotation of the column 1151 driven by the motor 1157 causes the foot 1152 to rotate.

[0062] Refer again Figure 10 The platform 114 includes two vertical columns 1142. The vertical columns 1142 are shown having rectangular housings 11422 arranged around lead screws 11424. Each lead screw 11424 is connected to a corresponding end bracket 1145 and is driven (clockwise or counterclockwise rotation) by a corresponding stepper motor (motor 11425), with one stepper motor driven by the other. Rotation of the lead screw 11424 provides y-direction movement of the end bracket 1145, and correspondingly provides y-direction movement of the horizontal support 1144 and the turntable 115.

[0063] As described above, turntable 115 can move in three directions on the stand 114. Turntable 115 can move in the x-direction (longitudinal) via motor 1143, as the U-shaped support 1146 moves. Turntable 115 can move in the y-direction (vertical) via stepper motor 11425, as the end support 1145 moves up and down at the vertical column 1142. Turntable 115 can move in the z-direction (lateral), and turntable 115 moves along each lateral linear guide 11492 of the lateral drive support brackets 1149 driven by motor 11495. Each of motors 1143, 11425, and 11495 is controlled by non-transient machine-readable instructions in controller 109 that direct their operation (e.g., direction of rotation, running time, etc.).

[0064] Turntable 115 is operable to automatically load / unload and engage / disengage or de-engage multiple kits on legs 1152. Reference Figure 10 The turntable 115 can automatically load / unload the reagent kit using the arm assembly 118. Figure 14 A side perspective view of the arm assembly 118, isolated from the platform 114 and turntable 115, is shown. The arm assembly 118 includes an outer surface of a side wall 11511 of the main support 11510, mounted via, for example, bolts, screws, rivets, or pins (e.g., mounted at the midpoint of the side wall 11511). Figure 13 The attachment bracket 1182. A short actuator 1184 is connected to the top of the attachment bracket 1182, and a long actuator 1186 is connected to the bottom of the attachment bracket 1182. Figure 10 In this assembly, a long actuator 1186 extends substantially vertically (horizontally as shown) from an attachment bracket 1182, and a short actuator 1184 extends substantially diagonally (e.g., at a 45-degree angle) from the attachment bracket 1182 to engage with the long actuator 1186. A cassette connector 1183 is attached to the end of the long actuator 1186. The cassette connector 1183 has paired fingers on its opposite sides with a separation distance d1, which allows the fingers to surround and engage around the protrusion of the kit (described below) and to move the kit.

[0065] Figure 14The attachment bracket 1182 is shown with a top portion comprising a U-shaped clamp portion 11822 and a bottom portion comprising a U-shaped clamp portion 11823. One end of the short actuator 1184 is connected to the U-shaped clamp portion 11822 by, for example, a U-shaped clamp pin, screw, or bolt, enabling it to rotate about the pin, screw, or bolt. Similarly, one end of the long actuator 1186 is connected to the U-shaped clamp portion 11823 by, for example, a U-shaped clamp pin, screw, or bolt, enabling it to rotate about the pin, screw, or bolt. Each of the short actuator 1184 and the long actuator 1186 comprises an electrically actuated telescopic body (e.g., a three-stage body, each stage being a successively smaller cylinder or post). A second end of the short actuator 1184 is connected to the smallest stage or plunger of the long actuator 1186 via a link 1185. The link 1185 approaches the engagement head 1183. The connection position of the short actuator 1184 and the long actuator 1186 is selected such that when the short actuator 1184 is fully retracted, it will cause the long actuator 1186 to rotate a few degrees (e.g., up to 10 degrees, such as 2 to 8 degrees) around the U-shaped clamp portion 11823, resulting in the distal end of the long actuator 1186, including the engagement head 1183, moving (lifting) toward the U-shaped clamp portion 11822. The long actuator 1186 can extend to a position above the kit in the lifted configuration. The short actuator 1184 can then extend to rotate the long actuator 1186 in the opposite direction (i.e., rotate the long actuator away from the U-shaped clamp portion 11822) to lower the engagement head 1183 onto the kit to grip it.

[0066] As described above and as Figure 1 As shown, the sample processing system 100 includes a housing 102 for accommodating and storing various components of the processing system 100, including a storage rack 106. The storage rack 106 can be used to store reagent kits (e.g., reagent kit 117). Figure 15 A perspective front left-hand view of a storage rack 106, isolated from other components of housing 102, is shown. Storage rack 106 includes housing 1062, which contains slots facing reaction compartment 104 and turntable 115. Storage rack 106 accommodates an array of slots for storing individual reagent kits. Figure 15 An array of slots with 5 rows and 25 to 30 columns is shown. This array of rows and columns allows each slot to have an address (e.g., specified by row and column numbers) so that the system can know the location of the kit and locate it in storage rack 106, or return the kit to a specific slot in storage rack 106. Figure 15In this configuration, reagent kits (reagent kit 117) are disposed in all slots of the array. The outer surface of each reagent kit may have an identifier, such as a barcode, containing identification information about the reagents contained in the kit, as well as other possible information such as expiration date. This identifier can be read by a reader (e.g., a barcode reader), and the read information is electronically provided to controller 109. One example is a reader electronically linked to a turntable 215 of controller 109. The identifier on the reagent kit (e.g., reagent kit 117) may have a rewritable IC chip capable of storing reagent identification, batch number, expiration date, and number of uses.

[0067] Figure 16 A side perspective view of reagent kit 117 is shown, illustrating its operability for storage in storage rack 106 and use in processing system 100. Typically, reagent kit 117 has a z-direction depth of approximately 67.4 mm, an x-direction width of 5 mm to 10 mm, and a y-direction height of 98.5 mm. In another example, reagent kit 117 has a similar depth and width, and a height of 70.8 mm (H2 < H1). Reagent kit 117 can be a drop-on-demand reagent kit, such as a thermal drop-on or piezoelectric drop-on reagent kit, and as shown, the kit includes a single dedicated printhead positioned at the base of reagent kit 117.

[0068] Reagent kit 117 can contain a volume of reagent and has a dedicated printhead. Each cartridge can be a single-use cartridge. In this context, a single-use cartridge means that once the volume of reagent in the cartridge has been dispensed or used, the cartridge containing its printhead is discarded or disposed of, rather than being refilled with a new volume of reagent. The reagent kit can contain (be supplied) a volume of reagent suitable for dispensing the reagent onto one or more samples (e.g., tissue samples) on a slide. An example of a single-use cartridge is a thermal inkjet cartridge. Another example is a piezoelectric inkjet cartridge. Reference Figure 16 The kit 117 comprises a shell or body 1171 having a generally rectangular shape made of a plastic material (e.g., hard plastic or polymer). Figure 16The illustrated kit 117 includes a side 1172 and an opposite side 1173 representing the yz dimension, and a side 1174 and an opposite side 1175 representing the xy dimension. Side 1174 contacts and engages with a turntable 115. The kit 117 includes a printhead 1178 operable to dispense reagents from the kit. The printhead 1178 may be positioned at or near the nose or base 1179 of the kit 117 (as shown on the bottom side) so that reagent ejection occurs through the base 1179 of the kit when the kit is inserted into the turntable 115. The portion of the nose or base 1179 containing the printhead 1178 (printhead region) may extend in a stepped manner below the remainder of the base 1179. The printhead 1178 of the kit 117 includes nozzles or an array of nozzles through which reagents are ejected or dispensed, typically via a thermal inkjet process. A typical nozzle array is a linear array of nozzles (e.g., single or multiple rows) to allow reagents to be emitted in rows (one or more rows) or lines (one or more lines), for example, on a scale spanning the substrate. In a thermal inkjet printhead, heat can be used to generate bubbles of reagent vapor, which explode when driven through the printhead nozzles. Each nozzle can have a diameter of approximately 20 micrometers to 80 micrometers, for example, 20 micrometers to 50 micrometers.

[0069] The kit 117 also includes a contact 1170 on the side 1174. The contact 1170 is designed to interact with the turntable (see [link]). Figure 18 The contact 1170 engages with a contact in a mating part associated with the associated text. Contact 1170 allows the reagent kit to be controlled by controller 109, the control being, for example, regarding the discharge or emission of the reagent through the nozzle and the amount of reagent discharged.

[0070] Figure 16The kit 117 shown includes a pair of transfer guides on each of sides 1172 and 1173. The transfer guide on side 1172 has been described, but it should be understood that the transfer guide on side 1173 is similar. Transfer guide 1176 has, for example, a generally rectangular solid structure of plastic material, and its width W1 extends parallel to the top surface of kit 117 across the width of side 1172. Transfer guide 1176 has a thickness T1 and a length L1 sufficient to support kit 117 in storage rack 106. A representative thickness T1 is from approximately 0.2 mm to 1 mm, and a representative length L1 is from approximately 3 mm to 10 mm. Transfer guide 1176 includes an engagement protrusion 11762 that extends vertically upward when viewed from the top side of the transfer guide. As shown, transfer guide 1176 is attached to body 1171 (e.g., via adhesive) or a portion of body 1171, positioned at a distance from the top of side 1172, such that the entire transfer guide 1176, including the engagement protrusion 11762, is below the top surface of kit 117. As shown, below transfer guide 1176, transfer guide 1177 is attached to body 1171 (e.g., via adhesive) or a portion of body 1171 of kit 117. The width W2 of transfer guide 1177 extends across the width of side 1172 parallel to the top surface of kit 117, and the thickness T2 and length L2 of transfer guide 1177 are sufficient to support kit 117 in support storage rack 106. A representative thickness T2 is similar to the thickness T1 of transfer guide 1176, for example, approximately 0.2 mm to 1 mm, and a representative length L2 is approximately 3 mm to 8 mm. Transfer guide 1177 is arranged parallel to transfer guide 1176 along side 1172, and the gap L3 separating it from transfer guide 1176 is sufficient to allow the arm of the kit support to slide between the transfer guides. Each of transfer guides 1176 and 1177 may have a rounded or curved front end (the end closest to side 1174 of kit 117) to help position the arm of kit support between the transfer guides. The base of transfer guide 1177 also includes a notch or mating groove 11772 and a thinned portion 11774 (thickness less than thickness t2) from the front end of the transfer guide to a point directly forward (1 mm or 2 mm forward) of the notch or mating groove 11772. The thinned portion 11774 may have an inclined rear sidewall from the top of transfer guide 1177 toward the base. Finally, the kit 117 includes a frame locking bump 11792, which is a triangular prism having triangular bases parallel to the sides 1172 and 1173, respectively.Each of the transfer guide 1176, transfer guide 1177, and frame locking bump 11792 may be made of a rigid plastic material, and the transfer guide 1176, transfer guide 1177, and frame locking bump 11792 may be attached to the kit 117 by, for example, an adhesive, or formed as part of the kit 117 by, for example, a molding process.

[0071] Figure 17 A perspective front right-side view of a portion of the storage rack 106 is shown. In this view, the storage rack 106 includes a cassette frame support 1064 extending between vertical columns 1063. The storage rack 106 is mounted to the housing 102 with its slot facing the reaction compartment 104 and the turntable 115. The cassette frame support 1064 is an L-shaped body, with the base 10642 of the L-shaped body facing outwards. Pairs of openings or holes 1065 through the base 10642 for securing reagent kits to the frame support 1064 are provided in the base 10642 of the frame support 1064. Figure 17 Kits 117A and 117B are shown connected to the box frame support 1064. The kits are connected to the box frame support 1064 via the box frame. Figure 17 A box frame 1060B supporting reagent kit 117B and a box frame 1060C connected to a box frame support 1064 but not supporting the reagent kit are shown. It can be understood that a separate box frame supports reagent kit 117A, but such box frames are obscured and not visible.

[0072] Each box frame (e.g., box frame 1060B and box frame 1060C) includes a shoulder 10602, which is a relatively thin (e.g., 1 mm to 3 mm) rectangular body with a length in the x-direction greater than the width of the kit. The shoulder 10602 has two openings or holes 10605 that can be aligned with a pair of openings or holes 1065 in the base 10642 of the box frame support 1064 to allow the shoulder 10602 to be connected to the base 10642 of the box frame support 1064 by the use of a pin 10603. The pin 10601 is, for example, an expander pin (e.g., plastic) having a distal end extending from the box frame and a body, the distal end operable to slide into the opening or hole 1065, and the body having a diameter similar to or larger than said opening or hole to secure the pin by applying force in the direction of the base 10642 of the box frame support 1064. Pin 10601 can be a captive pin, meaning the pin is permanently fixed to the box frame, or it can be freely inserted into both the shoulder 10602 of the box frame and the base 10642 of the box frame support 1064. Each box frame (e.g., box frame 1060B and box frame 1060C) is designed to be removed from the base 10642 of the box frame support 1064 by using a similar but opposite force required to insert the pin.

[0073] As shown (x-direction), two arms 10603 extend vertically from the shoulder 10602. The dimensions of each arm 10603 (e.g., height in the y-direction and thickness in the x-direction) are such that the arm fits between transfer guides 1176 and 1177 on each side of the kit to allow the kit to slide in and out of the cassette frame. The distance between each arm 10603 and the others is slightly greater than the width of the kit (e.g., when the kit has a width of 6 mm, the arms 10603 are separated from each other by 6.3 mm to 7 mm). The arms 10603 have a length (z-direction) less than the depth of the kit when measured from the shoulder 10602, for example, this length is approximately half the depth of the kit. Each cassette frame includes a ridge 10606 extending vertically downward (y-direction) when viewed from the shoulder 10602. The ridge 10606 has a representative width (x-direction) of approximately 1 mm to 4 mm, a thickness of approximately 0.4 mm to 0.5 mm (z-direction), and a length (y-direction) longer than the height of the kit portion measured between the kit base and the transfer guide 1177 behind the printhead region, for example, 1 mm to 2 mm longer. Legs 10607 extend vertically (z-direction) from the base of the ridge 10606. The shape at the ridge-leg junction reflects the transition between the rear sidewall and the base of the kit. Figure 17In this kit 117B, the transition between the rear sidewall and the base is curved, and the spine-leg connection defines opposite profiles. The leg 10607 may have a thickness of approximately 0.5 mm to 1.5 mm (y-direction); a width of 1 mm to 3 mm (x-direction); and its length (z-direction) extends the length of the kit base excluding the printhead area. A protrusion 10608 is provided along a portion of the length dimension of the leg 10607, typically extending upwards from the surface of the leg 10607 by a distance of 0.2 mm to 0.6 mm, and has a representative triangular prism shape in the yz plane, with a triangular base. The protrusion 10608 is positioned on the leg 10607 at a distance greater than that from the spine 10606 than from the kit (kit 117, Figure 16 The distance from the rear side of the kit to the front edge of the frame locking protrusion 11792 is such that when the kit is positioned in the kit frame (e.g., kit 117B in kit frame 1069B), the protrusion 10608 is forward of the frame locking protrusion extending from the base of the kit. The pad platform 10609 is attached to the end of the leg 10607 of the kit frame. The pad platform 10609 can be a rectangular body with a rectangular face or top (xz plane) larger than the printhead area. A representative area (xz dimension) of the pad platform is approximately 225 mm². 2 up to 400 mm 2 An absorbent material (e.g., a sponge) may be placed on the surface or top of the pad platform 10609. This absorbent material may contact the printhead of the kit, receive outflows from the printhead (e.g., excess reagent on the surface of the printhead), and protect the printhead from drying out.

[0074] The main body of the box frame (e.g., box frame 1060B, box frame 1060C) can be made of rigid plastic material. (Reference) Figure 17 The dimensions (e.g., thickness, width) and / or connections (e.g., 90° connection) of the spine 10606 and legs 10607 can provide spring tension to the legs 10607 so that the legs 10607 can move when the kit is attached or removed. As described above, the kit includes a frame locking protrusion 11792 extending from its base (see [link to kit description]). Figure 16The kit 117). When the kit is placed into the cassette frame (i.e., in response to a force applied to the kit in the direction toward the ridge 10606 of the cassette frame), the arm 10603 of the cassette frame slides between transfer guides 1176 and 1177 on the respective opposite sides of the kit until the frame locking protrusion 11792 at the base of the kit contacts the protrusion 10608. The continuous force in the direction toward the ridge 10606 causes the leg 10607 to move downward (by the force of the frame locking protrusion 11792 on the leg) so that the protrusion 10608 moves downward and the frame locking protrusion 11792 passes the protrusion 10608. Once the frame locking protrusion 11792 has passed the protrusion 10608, the leg 10607 returns to its initial position (moving upward) to allow the protrusion 10607 to hold or capture the kit in the cassette frame. Separation of the kit from the cassette frame is achieved in a similar manner. The force acting on the kit in a direction away from the spine 10606 will cause the leg 10607 to move downward (by the force of the frame locking bump 11792 on the leg) so that the protrusion 10608 moves downward and the frame locking bump 11792 passes over the protrusion 10608.

[0075] The kits (e.g., kit 117A, kit 117B) may be supplied as a component comprising the kit and a box frame (e.g., box frame 1060B, box frame 1060C). This component may be packaged together with the kit in the box frame and supplied to the consumer, or it may be supplied separately with instructions for assembly.

[0076] refer to Figure 10 , Figure 14 , Figure 15 and Figure 17The arm assembly 118 can be used to move reagent kits into and out of the storage rack 106. As an example, the reagent kit assembly (the kit attached to the cassette frame) can be delivered by an operator or robot to the reaction compartment 104 (e.g., to the platform 105 inside the reaction compartment 104). The controller 109 contains non-transient machine-readable instructions that direct the operation of various motors (e.g., rotation direction, runtime, etc.) to bring the turntable 115, which includes the arm assembly 118, to a position to grasp the delivered reagent kit assembly and place it in the storage rack 106. These motors include a motor 1143 for moving the turntable 115 in the x-direction; a motor 11495 for moving the turntable 115 in the z-direction; a motor 11425 for moving the turntable 115 in the y-direction; and a motor 1157 for rotating the support leg 1152. When the turntable 115 is positioned as desired, the machine-readable instructions also include instructions to direct the arm assembly 118 attached to the turntable 115 to grasp the reagent kit assembly and transport it to the storage rack 106. The instruction may also include an instruction to place the kit assembly at a predetermined address in the storage rack 106. The arm assembly 118 includes a cassette engagement head 1183 at its distal end. The cassette engagement head 1183 can be operated based on instructions from the controller 109 to be brought to a position above the kit 117 such that paired fingers extending from the cassette engagement head 1183 surround and engage the engagement protrusion 11762 of the transfer guide 1176 on each side of the kit 117 (see [link to documentation]). Figure 16 The paired fingers on the box joint 2183 of the arm assembly 218 (see...) Figure 14 The spaced (separated) distance on opposite sides is slightly smaller than the distance between the engagement protrusions 21762 on each side of the kit 217. Typically, the paired fingers on the kit engagement head 2183 are biased to the distance they are separated, but can bend outward a greater distance to engage the engagement protrusions 21762 on opposite sides of the kit 217. The biasing property of the opposing fingers on the kit engagement head 2183 acts like a spring clip to hold the kit through the engagement protrusions 21762. To place the kit assembly into the storage rack 106, the instruction guide arm assembly 118 aligns the pin 10603 in the kit assembly with a defined pair of openings or holes 10605 in the base 10642 of the frame support 1064 and applies sufficient force to the kit assembly to insert the pin into the corresponding position in the base 10642 of the frame support 1064.

[0077] To transfer the reagent kit from storage rack 106 to turntable 115, the controller 109 includes a machine-readable instruction guide arm assembly positioned on the reagent kit (e.g., the front side of the kit) and gripping the kit (via reagent engagement heads 1183 that surround and engage the protrusions 11762 of transfer guides 1176 on each side of the kit 117). At this point, the kit assembly, including the kit and the cassette frame, is mounted in storage rack 106. Once the cassette engagement heads 1183 grip the engagement protrusions 11762 of transfer guides 1176 on each side of the kit 117, the arm assembly 118 applies a force in a direction away from the storage rack (and away from the ridge 10606 of the cassette frame) to deflect the legs 10607 of the cassette frame (causing downward movement) through the force of the frame locking protrusions 11792 of the reagent container 117 on the legs 10607, causing the protrusions 10608 to move downward and the frame locking protrusions 11792 to pass over the protrusions 10608. Once the box is separated from its box frame, the instruction guide arm assembly 118 associated with the controller 109 delivers the box to the turntable 115.

[0078] Figure 18 A portion of the turntable 115 is shown, including a leg or box carrier plate 1152 isolated from the base of the column 1151. The leg or box carrier plate 1152 is operable to engage and accommodate multiple kits. The leg 1152 has a characteristic decagonal shape, with a slot 1153 for kits on each side. It should be understood that the shape and number of kits that the turntable can accommodate can vary. Surrounding each slot 1153 is a mating portion 1154 extending from the surface of the leg 1152 (such as the upper surface shown). Figure 18 Three docking portions 1154 are shown. It should be understood that the foot 1152 may have as many docking portions as the slot. Each docking portion 1154 is configured to receive a reagent kit therein. Figure 18 A kit 117 is shown disposed in a docking portion 1154. Each docking portion 1154 includes a rear wall having an outer surface facing the center of a foot 1152 and two opposing side walls connected to the rear wall. The rear wall slopes from top to bottom, with the bottom of the rear wall closer to the center of the foot 1152. The side walls have a thickness less than that of the transfer guides 1176 and 1177 on the kit (see [reference]). Figure 16 The thickness td of the sidewall. The upper portion of each sidewall receives a lateral slot 11542, which extends from the distal end of the sidewall to a portion near the proximal end (near but not to the rear wall) to define an arm portion 11544. The dimensions of each arm portion 11544 allow the arm portion 11544 to be positioned between transfer guides 1176 and 1177 on the reagent container 117 and to support the reagent container. The mating portion 1154 containing the arm portion 11544 may be made of a plastic (polymer) material.

[0079] The inner surface of the rear wall of each docking section 1154 contains contacts that mate with contacts 1170 on the reagent kit. These contacts are electrically connected to a controller 109 to allow the controller 109 to individually control the reagent kit in each docking section 1154 on the turntable 115.

[0080] As shown, the lock 1155 is connected to the two opposing sidewalls of each mating portion 1154 at a point below the arm portion 11544. The lock 1155 includes two parallel arms 11552 separated by a shoulder portion 11554. The width of the shoulder portion 11554 is similar to or slightly larger than the width of the mating portion 1154 so that the arms 11552 can be positioned and connected to the exterior of the respective opposing sidewalls of the mating portion 1154. Figure 18 Arms 11552 are shown connected to the sidewall via pins 11555 (e.g., pins, screws, or rivets), such that the portion length of each arm 11552 from the shoulder 11554 to the pin 11555 (distal portion) is greater than the portion length of each arm 11552 from the pin 11555 to the proximal end (the end furthest from the shoulder 11554). As shown, the connection of the lock 1155 to the mating portion 1154 allows the shoulder 11554 to pivot upward and downward without contacting the rear wall of the mating portion 1154 (e.g., the shoulder 11554 is 0.1 mm to 0.5 mm from the outer surface of the rear wall). The distal portion of each arm 11552 is generally rectangular and extends proximally from the shoulder 11554. The proximal portion of each arm 11552 can extend upward at an angle relative to the distal portion, such that the angle γ defined between the distal and proximal portions is approximately 150° to 175°. The proximal portion of each arm 11552 may be generally rectangular and includes a proximal end with a protrusion 11556, which is, for example, an upwardly extending triangular prism with a triangular base parallel to the side of the respective arm. The protrusion 11556 is sized to fit into a notch or mating groove 11772 in the transfer guide 1177 of the kit (see [link]). Figure 16 The lock 1155 can be spring-biased at each of the pins 1155, with the shoulder closer to the surface of the foot 1152. In this configuration, at least a portion of the protrusion 11556 extends above the base of the notch defining the arm portion 11544 of each mating portion 1154. A downward force on the protrusion 11556 will cause the protrusion to move downward and the shoulder to move upward. Releasing such a downward force will cause the opposite movement.

[0081] A slide reader and / or imager, such as a camera, can be attached to a foot or cassette support plate 1152. Typically, the slide reader / imager can be placed in one of the slots 1153, rather than in the docking section and cassette. Alternatively, the slide reader / imager can be attached to the underside of the support plate 1152. The slide reader can be oriented to read identifiers (e.g., labels (e.g., barcodes)) on the microscope slide, while the imager can be oriented to capture images of the microscope slide (e.g., an image of the entire microscope slide), images of identifiers on the microscope slide (e.g., for subsequent reading via, for example, controller 109), and / or when the microscope slide is visible in or outside the chamber 125 of the body 120 (e.g., when the cover 130 is moved to the open position and the tray 180 is moved to a third or fourth position (see...)). Figure 7C and Figure 7D Images of samples on microscope slides. Reading of the identifiers on the microscope slides can be controlled by controller 109, which can instruct the slide identification reader to read images of the identifiers on the microscope slides and / or the identifiers captured by the imager. Typically, reading or capturing images and then reading the identifiers on the microscope slides when they are initially placed in the reaction station allows controller 109 to determine the processing protocol for the samples on the microscope slides. Image capture can be controlled by controller 109 using instructions, for example, capturing images of the identifiers on the microscope slides before the microscope slides are initially moved into chamber 125, or capturing images of the samples on the microscope slides after the dewaxing operation, to position the samples on the microscope slides (e.g., via detection of samples (e.g., stained samples)) to determine where reagents (e.g., master reagents) are subsequently dispensed and / or after the master staining operation.

[0082] Refer again Figure 10 , Figure 14 and Figure 18The document describes the transfer of reagent kits from a storage rack 106 or from a platform 105 within a housing 102 via an arm assembly 118. The controller 109 includes non-transient machine-readable instructions instructing the arm assembly 118 to engage a reagent kit (e.g., reagent kit 117) with a cassette connector 1183 of the arm assembly, wherein the cassette connector 1183 engages a protrusion 11762 on a transfer guide 1176 of the reagent kit. Such instructions also include instructions to transport the reagent kit to a mating portion 1154 on a foot 1152 of a turntable 115, and instructions to align transfer guides 1176 and 1177 of the reagent kit with arm portions 11554 of a mating portion 1154 (aligning transfer guides 1176 and 1177 respectively above and below each arm portion 11554). Once aligned, the instructions also include sliding the reagent kit into the arm portion 11554 (in the proximal-to-distal direction) so that the nose or base 1179 of the reagent kit 117 is oriented inward (e.g., towards the center of the leg 1152). The arm assembly 118 applies a force sufficient to slide the reagent kit into the arm portion 11554 in the central direction of the leg 1152. A thickness t is greater than the thickness t2 of the transfer guide 1177. d The transfer guide 1177 contacts the proximal portion of each arm 11552 of the box lock 1155, causing each arm to rotate about each pin 11555 and pushing the proximal portion of the arm downward. When the portion of the transfer guide 1177 containing the mating locking groove 11772 is directly above the protrusion 11556 of each arm 11552 of the box lock 1155, the biasing of the box lock will cause each arm 11552 of the box lock 1155 to rotate in opposite directions about the pin 11555, and cause the protrusion 11556 to engage the locking groove 11772. At this time, the kit is secured in the mating portion 1154, and the command associated with the controller 109 releases the guide arm assembly 118 from its engagement with each engaging protrusion 11762.

[0083] The reagent kit can reach the service station before being delivered to the docking section (docking section 1154) on the turntable 115 for dispensing or returned from the docking section to the storage rack 106. As shown, Figure 1 A service station 1190 is shown attached to an adjacent storage rack 106 mounted to the rear sidewall of reaction chamber 104. Service station 1190 provides an area in which the printhead of the reagent kit can be tested and cleaned before and / or after use in dispensing operations from which reagents are dispensed onto microscope slides. Figure 19A front view of service station 1190 is shown. In this example, service station 1190 includes a rear wall 11901. Pulley supports 11903 and 11904 are connected to the rear wall 11901. Each of pulley supports 11903 and 11904 includes an upper roller and a lower roller. A belt 11905 is disposed on the upper roller of each of pulley supports 11903 and 11904. A belt 11906 is disposed on the lower roller of each of pulley supports 11903 and 11904. A guide rail 11902 is disposed between and connected to each of pulley supports 11903 and 11904. Carriages 11907 and 11908 are slidably connected to guide rail 11902 and belts 11905 and 11906. Each of carriages 11907 and 11908 has a configuration similar to docking section 1154 with a fixative cartridge (see [link]). Figure 18 ).

[0084] exist Figure 19 In the example shown, for a first-sized kit such as 100 mm L1 and 60 mm W1, carriage 11907 has a length L1 and a width W1, and for a second-sized kit such as 72 mm L2 and 60 mm W2, carriage 11908 has a length L1 and a width W1. It should be noted that service station 1190 may be equipped with only one carriage, or if multiple carriages are included, each carriage may accommodate kits of the same or different lengths and widths. As shown, the base or back of each of carriages 11907 and 11908 includes electronic contacts or pins operable to mate with a receiver (contact 1170) on the front side of the kit, similar to the inner surface of the rear wall of each mating portion 1154 of turntable 115, which includes contacts that mate with the contacts 1170 on the kit. Figure 19 The contact or pin 11914 in carriage 11907 and the contact or pin 11915 in carriage 11908 are shown.

[0085] In one example, the kit (kit 117) has length and width dimensions that fit snugly within carriage 11907 or carriage 11908. (As mentioned above regarding...) Figure 18 The kit (kit 117) is described to include an electronic pin receiver 12794 at the front for mating with electronic contacts or pins 11917 in carriage 11907. The front of the kit may also include two diagonally spaced alignment sockets or openings that align with locating pins 11917 in carriage 11907 to aid in aligning the kit with carriage 11907 or carriage 11908.

[0086] Figure 19 Each of carriages 11907 and 11908 is shown connected to pulley supports 11903 and 11904 via belts 11905 and 11906. Belts 11905 and 11906 can independently move laterally or translate carriages 11907 and 11908 along guide rail 11902. Such movement allows each of carriages 11907 to bring the attached reagent container to a dispensing pool 11909 and a wiping station (wiping station 11912 or wiping station 11913). Dispensing pool 11909 provides a vessel for dispensing reagents from the reagent kit in carriages 11907 or 11908. Each of wiping stations 11912 and 11913 can be a container, as shown, with the ribbon exposed on the top or side of the container (e.g., a rectangular container holding a length of ribbon between rollers). The first side of the ribbon is made of cloth or a similar absorbent material. The width of the ribbon can be at least as wide as the printhead of the kit. The cloth or similar absorbent material provides a cleaning or wiping area for wiping the printhead (e.g., wiping away excess reagent on the printhead). After the wiping action of the printhead of the kit on a portion of the ribbon, the ribbon is advanced by a command from the controller 109 to move the rollers in the guiding wiping stations 11912 or 11913.

[0087] Each carriage can be electrically connected to and communicate with controller 109. Similar to the electronics in docking unit 1154, carriages 11907 and 11908 house electronics to operate the reagent kit to dispense reagents under the guidance of non-transient machine-readable instructions associated with controller 109. When the reagent kit is connected to carriage 11907 or carriage 11908, instructions from controller 109 can direct reagents to be dispensed from the reagent kit into, for example, the dispensing pool 11909, and onto the ribbon between the printhead of the reagent kit and wipe station 11912 or wipe station 11913.

[0088] In the service station operation, instructions from controller 109 can guide one of carriages 11907 or 11908 to move above the dispensing reservoir 11909 via belts 11905 and 11906. At this time, before, or after, instructions from controller 109 can instruct arm assembly 118 to engage the reagent kit (e.g., kit 117) and mount the kit in the moving carriage (e.g., carriage 11907). Further instructions from controller 109 can then include further instructions to instruct electronics in carriage 11907 to dispense or dispense a certain amount of reagent into the dispensing reservoir 11909 (e.g., an amount sufficient to wet the printhead and ensure it is not clogged). After the dispensing operation, instructions from controller 109 can instruct the kit to be taken to wiping station 11912 or wiping station 11913 to remove residual reagent from the printhead of the kit by wiping the printhead on the wiping station belt. After wiping, instructions from controller 109 can direct arm assembly 118 to engage reagent container and deliver the reagent container to docking part (docking part 1154) on turntable 115 for dispensing operation or delivery to storage rack 106.

[0089] The above discussion described a reagent dispensing technique using inkjet technology. One dispensing alternative includes a dispensing cartridge connected to a cartridge pump assembly that pumps reagents from the dispensing cartridge onto the sample. Another dispensing alternative may involve pipette transfer from a reagent container to the sample.

[0090] The following description is for reference. Figures 1 to 18 The sample processing system described is a representative operation. Initially, individual microscope slides(s), each containing at least one tissue sample, are brought into reaction compartment 104 by an operator or robot. Each slide is placed individually in a reaction station (reaction station 112). Non-transient machine-readable instructions from controller 109 can direct the motor associated with each reaction station 112 to drive the corresponding gear 155 to open the lid (lid 130) of the reaction compartment. Further non-transient machine-readable instructions from controller 109 can then direct the legs (legs 185) of the corresponding reaction compartment to raise the tray (tray 180) in the reaction compartment to a third or fourth position (see [link]). Figure 7C and Figure 7DThe slide is received from an operator or robot. The slide can be positioned with the tissue sample side up (facing cover 130). Once the slide is placed on tray 180, non-transient machine-readable instructions from controller 109 can instruct the identifier on the microscope slide to be read by a slide identification reader, or to capture an image of the identifier via an imager and have the captured image read by controller 109 (e.g., a slide identification reader / imager connected to leg 185 or box carrier plate 1152). Further instructions can then direct the leg to lower the tray to, for example, a second position, and instruct motor 180 to close cover 130 of the corresponding reaction station 112. Typically, reading or capturing an image and then reading the identifier allows controller 109 to determine the processing protocol for the sample on the microscope slide. Instructions from the controller can instruct that the identifiers of each of the multiple slides in the respective reaction stations (reaction station 112) of the sample processing system be read before processing any of the slides can begin, or that processing of each sample on a microscope slide can begin once the identifiers on the microscope slides have been read independently, or regardless of whether the identifiers on another microscope slide in a reaction station of the sample processing system have been read. The independent processing of microscope slides in a single reaction station allows, for example, a reaction station to be loaded with microscope slides and begin processing while samples on other microscope slides contained in other reaction stations of the sample processing system have already been processed.

[0091] Microscope slides containing tissue samples brought to reaction chamber 104 may be embedded in an embedding agent (e.g., paraffin), or may be treated to remove the embedding agent and adhere the tissue sample to the slide (i.e., pretreatment to remove paraffin and adhere the tissue sample to the slide). In the case where the slide is brought to reaction chamber 104, the slide has tissue samples embedded in an embedding agent such as paraffin, and non-transient machine-readable instructions from controller 109 can instruct the system to perform an adhesion and dewaxing (dewaxing) procedure on the embedded tissue sample. Typically, the instructions can instruct the slide containing the embedded tissue sample to be heated using slide heater 1802 as part of a baking operation. The heat treatment should be sufficient to allow the sample on the slide to adhere or further adhere to the slide (glass slide) and may soften the embedding medium associated with the section on the slide. Typically, the slide can be heated to a temperature of approximately 55°C to 70°C.

[0092] After heat treatment, an instruction may direct the slide heater 1802 to shut off, exposing the embedded tissue sample on the slide to a volume sufficient to cover the sample portion of the slide in a dewaxing solution such as xylene. The dewaxing solution, such as xylene, can be stored as a bulk reagent in a container in storage compartment 101 below reaction compartment 104 (see [link to documentation]). Figure 1The dewaxing solution container can be connected to a fluid connector 131 on the lid 130 of the reaction chamber containing the embedded tissue sample on the slide. Instructions associated with controller 109 can direct the transfer (e.g., pumping) of the dewaxing solution from the dewaxing solution container to the corresponding fluid connector 131 and onto the surface of the slide in the reaction chamber. After the dewaxing solution has been dispensed, instructions associated with controller 109 can direct the tissue sample to soak in the dewaxing solution for a period of time (e.g., one to five minutes). After the soaking time, instructions associated with controller 109 can direct the foot 185 to move the tray 180 containing the slide to a first position where the slide is tilted or deflected to a non-horizontal position in the reaction chamber to remove the dewaxing solution and paraffin from the slide surface (e.g., see...). Figure 8 After the dewaxing solution and paraffin are removed from the surface of the slide, further instructions associated with controller 109 can direct foot 185 to move the slide to a second or third position within the reaction compartment. Further instructions associated with controller 109 can direct a valve associated with drain pipe 121 to open, discharging the dewaxing solution into a waste container, for example, in storage compartment 101.

[0093] In another example, the dewaxing protocol may involve sequentially dispensing several reagents. For example, the first reagent applied to the tissue sample on the slide may be xylene. After the xylene treatment and its subsequent removal, the dewaxing protocol may specify exposing the tissue sample to an alcohol (e.g., ethanol). In such a case, the container holding the xylene would be connected to a first fluid connector 131 on the lid 130 of the reaction compartment, and the container holding the alcohol would be connected to a second fluid connector 131 on the lid 130.

[0094] The dewaxing process can also be performed under elevated humidity. Typically, before, or before or after, a tissue sample on a slide is exposed to a volume of dewaxing solution or one or more sequencing reagents, instructions from controller 109 can direct the introduction of a fluid such as water (e.g., hot water) into the reservoir portion of chamber 125 (below tray 180 when tray 180 is in the lowest position (first position) within the chamber). Instructions from controller 109 can further control the discharge of the reservoir to remove the fluid after a dewaxing process involving elevated humidity.

[0095] Following the dewaxing process, instructions associated with controller 109 can direct the tissue sample to be rinsed with a volume of cleaning solution, such as water or other aqueous cleaning solution. A container holding the cleaning solution can be connected to a fluid connector (fluid connector 131) on the lid 130 of the reaction chamber to supply the cleaning solution to the tissue sample. The cleaning solution may also contain a staining agent, such as eosin, to stain the sample on the slide. Generally, after the dewaxing operation, the embedding material in the slide is removed, leaving the sample as a nearly colorless object on the slide. The addition of a staining agent such as eosin to the cleaning solution allows for the presentation and positioning of the sample on the slide. After the cleaning process, instructions associated with controller 109 can direct foot 185 to move the tray 180 containing the slide to a first position, where the slide is tilted or deflected to a non-horizontal position within the reaction chamber to remove the cleaning solution from the surface of the slide. Further instructions associated with controller 109 can direct a valve associated with drain tube 121 to open to drain the cleaning solution into a waste container.

[0096] Following the cleaning process and possible image capture of the sample and identifiers, instructions associated with controller 109 can direct foot 185 to move tray 180 containing the slide to a second or third position, and the tissue sample then undergoes an antigen retrieval process to reverse the antigen masking effect of aldehyde fixation. A container containing an antigen retrieval solution (such as a tris- or citrate-based retrieval solution) can be stored as a bulk reagent in storage compartment 101 below reaction compartment 104 and connected via a conduit to a fluid connector (fluid connector 131) on the lid 130 of the reaction compartment to provide the antigen retrieval solution to the tissue sample. Instructions associated with controller 109 can direct the application of the antigen retrieval solution to the surface of the tissue sample. Instructions associated with controller 109 can also direct the antigen retrieval process to be performed at elevated temperatures and possibly at elevated pressures. Typically, instructions can direct the heating of the slide containing the tissue sample to a temperature of approximately 100°C to 121°C using slide heater 1802. The instructions may further direct the introduction of air or inert gas into the reaction chamber via, for example, a fluid connector (fluid connector 131) (e.g., from a compressed air or inert gas source connected to the fluid connector), to bring the reaction chamber to, for example, an increased pressure of 1.0 atm (15 pounds per square inch (psi) to 1.7 atm (25 psi)). Compared to previous treatment times of 45 minutes or longer under atmospheric conditions, the increased pressure accelerates the antigen retrieval process to, for example, a treatment time of five minutes.

[0097] The antigen retrieval process can also be performed at elevated humidity levels, such as 70% to 100% relative humidity. Typically, before a tissue sample on a slide is exposed to a volume of antigen retrieval solution, instructions from controller 109 can direct the introduction of a fluid, such as water (e.g., hot water), into the reservoir portion of chamber 125. Instructions from controller 109 can further control the discharge of the reservoir to remove the fluid after the antigen retrieval process involving elevated humidity. For example, controller 109 can direct the opening of a valve associated with discharge tube 121 to drain the fluid from the reservoir into a waste container before or simultaneously with tilting tray 180 and discharging the antigen retrieval solution.

[0098] Once the antigen retrieval process is complete, instructions associated with controller 109 can direct foot 185 to move tray 180 containing slides to a first position, where the slides are tilted or deflected into a non-horizontal position within the reaction chamber to remove the antigen retrieval solution from the slide surface. Further instructions can then direct foot 1985 to return the tray to a second or third position. Further instructions associated with controller 109 can direct a valve associated with drain tube 121 to open, discharging the antigen retrieval solution into a waste container. Further instructions can then direct the tissue sample to be rinsed with a volume of washing solution, such as water or washing buffer, such as TBS or phosphate-buffered saline containing surfactants. After rinsing, instructions associated with controller 109 can again direct foot 185 to move tray 180 containing slides to the first position, where the slides are tilted or deflected into a non-horizontal position within the reaction chamber to remove the washing solution from the slide surface. Further instructions can then direct foot 1985 to return the tray to a second or third position in preparation for the staining process. Further instructions associated with controller 109 can direct the valve associated with discharge pipe 121 to open, thereby discharging the cleaning solution into the waste container.

[0099] For the staining process, commands associated with controller 109 can instruct a motor associated with reaction station 112, which houses slides containing samples to be stained, to drive a corresponding gear 155 to open the lid (lid 130) of the reaction chamber. Further commands from controller 109 can then instruct the legs (legs 185) of the reaction chamber to raise a tray (tray 180) within the reaction chamber to a fourth position, in which tray 180 and / or the slides on it are outside the chamber (chamber 125) (see [link]). Figure 7D If this has not been completed previously, further instructions from controller 109 can guide the determination of the location of the sample for staining or a portion thereof on the microscope slide based on the captured image of the sample on the microscope slide after the cleaning operation.

[0100] Before or after the slide is raised in preparation for the staining process, instructions associated with controller 109 may direct the retrieval of the reagent kit from storage rack 106 and the loading or docking of the reagent kit onto one of the docking portions 1154 on the legs 1152 of turntable 115. Further instructions associated with controller 109 may direct the positioning of the reagent kit loaded on the legs 1152 such that the nose or base of the kit is positioned above the tissue sample on the raised slide. Such instructions include directing motor 1157 to rotate column 1151, and correspondingly rotating legs 115 and motor 1143 to move turntable 115 in the longitudinal direction. Once positioned, instructions may direct the spraying (printing) of reagent from the kit onto a predetermined location on or a portion of the sample. Typically, the on-demand drop-type printhead in the kit, such as a thermal printhead, can dispense reagents such as detection reagents or antibodies in droplets having volumes of 1 picoliter (pL) to 10 nanoliters (nL), or 1 pL to 5 nL, or 1 pL to 1 nL, or 1 pL to 500 pL, or 1 pL to 250 pL, or 1 pL to 100 pL, or 1 pL to 50 pL. Typically, the inkjet cartridge can deliver 15 microliters (μL) per square inch or more (at least 15 μL) at a time, where each time refers to dispensing (jetting) reagent once from multiple nozzles in the printhead of the inkjet cartridge, either when the kit (rotary) and slide are stationary, or when at least one of the kit (rotary) and slide is moving unidirectionally to expand the dispensing area on the slide. Typically, the controller 109 directs the printhead of the kit to dispense multiple drops (i.e., multiple drops from multiple nozzles) to produce a larger volume of reagent each time. Representative delivery volumes via thermal inkjet printheads include 15 µL to 30 µL per square inch, 15 µL to 25 µL per square inch, and 15 µL to 20 µL per square inch.

[0101] Following the staining process, instructions associated with controller 109 may direct the kit and turntable to move away from the position above the slides, and instruct the reaction compartment's legs (legs 185) to lower the tray (tray 180) containing the stained slides to a second or third position inside the chamber (chamber 125), and close the reaction compartment's lid (lid 130). Further instructions associated with controller 109 may instruct the sample on the slides to extend the incubation period (thus, for example, allowing the first antibody to bind to the target antigen). After any incubation period, instructions associated with controller 109 may instruct the tissue sample to be rinsed with a volume of washing solution to remove any unreacted / unbound reagents. After rinsing, instructions associated with controller 109 may instruct leg 185 to move the tray 180 containing the slides to a first position, where the slides are tilted or deflected to a non-horizontal position within the reaction compartment to remove the washing solution from the slide surface. Then, further instructions can direct the support leg 1985 to return the tray to a second or third position in preparation for possible (one or more) additional dyeing processes. Further instructions associated with the controller 109 can direct the valve associated with the discharge pipe 121 to open, so as to discharge the cleaning solution and any excess dye into the waste container.

[0102] Once all staining of the tissue sample on the slide is complete, instructions associated with controller 109 can direct the system to alert the user that the slide can be removed. Further instructions from controller 109 can then instruct the legs (legs 185) of the reaction chamber to raise the tray (tray 180) in the reaction chamber to a fourth position, in which tray 180 and / or the slides on it are outside the chamber (chamber 125) to allow an operator or robot to retrieve the slides.

[0103] The staining process can also be performed at elevated humidity levels, such as 70% to 100% relative humidity. Typically, before the tissue sample on the slide is exposed to one or more staining agents, instructions from controller 109 can direct the introduction of a fluid, such as water (e.g., hot water), into the reservoir portion of chamber 125. Instructions from controller 109 can further control the discharge of the reservoir to remove the fluid after the staining process involving elevated humidity. For example, controller 109 can direct the opening of a valve associated with discharge line 121 to drain fluid from the reservoir into a waste container before or simultaneously with tilting tray 180 and draining any excess staining agent. The staining process can also be performed under elevated pressure. The instructions associated with controller 109 can direct the introduction of air or inert gas into the reaction chamber, for example, via a fluid connector (fluid connector 131) (e.g., from a source of compressed air or inert gas connected to the fluid connector), before exposing the tissue sample to the staining agent, to bring the reaction chamber to an increased pressure, for example, 1.0 atmospheres (atm) (15 pounds per square inch (psi) to 1.7 atm (25 psi)).

[0104] all aspects This instruction manual covers the following aspects: 1. A system comprising: A rotary table comprising multiple mounting stations, the mounting stations being sized to accommodate at least one fluid dispensing box; and A receiving assembly, positioned below the turntable, includes multiple reaction stations, each of which includes: The body, the length and width of which together define a chamber for accommodating a single wafer; and The cover includes a first position that covers the chamber and a second position that exposes a portion of the chamber.

[0105] 2. The system according to aspect 1, wherein each of the plurality of reaction stations includes a slide support, wherein the slide support includes a first depth in the chamber and a different second depth in the chamber.

[0106] 3. The system according to aspect 2, wherein when the cover of one of the plurality of reaction stations is in a second position, the slide support of said one of the plurality of reaction stations is operable to move from a first depth to a second depth.

[0107] 4. The system according to aspect 2, wherein each of the plurality of slide supports is operable to rotate.

[0108] 5. The system according to any one of aspects 2 to 4, wherein the substrate support includes a heating unit.

[0109] 6. The system according to any one of aspects 1 to 5, wherein the cover includes an outer surface and an opposing inner surface, wherein the outer surface includes a plurality of hose connectors connected thereto, and the inner surface includes a plurality of conduits connected thereto, wherein each of the plurality of hose connectors is connected to a corresponding one of the plurality of conduits.

[0110] 7. The system according to any one of aspects 1 to 6, wherein the turntable can be translated linearly in three dimensions.

[0111] 8. The system according to any one of aspects 1 to 7, wherein the turntable is rotatable about a central axis.

[0112] 9. The system according to any one of aspects 1 to 8, wherein the turntable and the receiving assembly are housed in a housing, and the system further includes a cassette holder operable to accommodate a plurality of fluid dispensing cassettes.

[0113] 10. The system according to any one of aspects 1 to 9, wherein the turntable is operable to retrieve the fluid dispensing cartridge from the cartridge holder and return the fluid dispensing cartridge to the cartridge holder.

[0114] 11. The system according to aspect 10, wherein the turntable is linearly translatable in three dimensions, and the cartridge holder is positioned relative to the turntable in the housing such that retrieving the fluid dispensing cartridge from the cartridge holder or returning the fluid dispensing cartridge to the cartridge holder requires the turntable to be translated in a first dimension of the three dimensions.

[0115] 12. The system according to any one of aspects 1 to 11 further includes a cooling unit connected to the box holder.

[0116] 13. A method comprising: The cover of the reaction station of the processor assembly is moved from a first position covering the reaction chamber to a second position exposing a portion of the reaction chamber, wherein the reaction chamber comprises only a single microscope slide on which a sample is mounted, and the reaction station is one of a plurality of reaction stations in the processing assembly; A turntable is translated above multiple reaction stations of the processing component, the turntable including at least one of a slide identification reader and an imager connected thereto; Read the identifier on the microscope slide or read the image of the identifier using a slide identification reader; The processing plan for the sample on the microscope slide is determined based on the read identifier; One or more reagent dispensing cartridges are retrieved from the storage rack via the turntable, each of the one or more reagent dispensing cartridges containing the reagents required to perform the treatment protocol; and One or more reagents are dispensed onto a sample on a microscope slide.

[0117] 14. The method according to aspect 13, after reading information provided on each of the plurality of carriers, the method includes moving the cover to a first position.

[0118] 15. The method according to aspect 13 or aspect 14, wherein before dispensing one or more reagents onto a sample on a microscope slide, the method includes moving the cap to a second position.

[0119] 16. The method according to any one of aspects 13 to 15, wherein the method includes raising the microscope slide in a chamber before dispensing one or more reagents onto a sample on a microscope slide.

[0120] 17. The method according to any one of aspects 13 to 16, further comprising, after dispensing one or more reagents onto a sample on a microscope slide, returning one or more fluid dispensing cartridges to a storage rack via a turntable.

[0121] 18. The method according to any one of aspects 13 to 17, wherein the reaction station is a first reaction station, and at least one or more of the plurality of reaction stations include a single microscope slide comprising a sample and an identifier, and wherein the method comprises, before dispensing the one or more reagents onto the sample on the microscope slide in the first reaction station: Images of identifiers or reading identifiers on microscope slides in at least one or more of the multiple reaction stations are read using a slide identification reader; and Based on the read identifier, determine the processing method for samples on microscope slides in at least one or more of the plurality of reaction stations.

[0122] 19. The method according to any one of aspects 13 to 18, wherein the dispensing includes dispensing via a thermal inkjet process.

[0123] 20. The method according to aspect 19, wherein dispensing comprises dispensing one or more reagents each time in an amount of at least 15 microliters (µL) per square inch.

[0124] In the foregoing description, the invention has been described with reference to specific embodiments thereof. However, it will be apparent that various modifications and alterations may be made therein without departing from the broader spirit and scope of the invention as set forth in the appended claims. For example, the kits disclosed herein (e.g., kit 408) may contain solvents or water instead of reagents and may be used for purposes other than, for example, staining samples on slides below. Therefore, the description and drawings are to be considered illustrative rather than restrictive.

Claims

1. A system comprising: A turntable comprising multiple mounting stations, the multiple mounting stations being sized to accommodate at least one fluid dispensing box; as well as A receiving assembly, positioned below the turntable, the receiving assembly comprising a plurality of reaction stations, each of the plurality of reaction stations comprising: The body includes a length dimension and a width dimension, which together define a chamber therein for receiving a single wafer; as well as The cover includes a first position covering the chamber and a second position exposing a portion of the chamber.

2. The system of claim 1, wherein each of the plurality of reaction stations includes a slide support, wherein the slide support includes a first depth in the chamber and a different second depth in the chamber.

3. The system of claim 2, wherein when the cover of one of the plurality of reaction stations is in the second position, the slide support of the one of the plurality of reaction stations is operable to move from the first depth to the second depth.

4. The system according to claim 2, wherein the carrier support includes a heating unit.

5. The system of claim 1, wherein the turntable is capable of linear translation in three dimensions.

6. The system of claim 1, wherein the turntable is rotatable about a central axis.

7. The system of claim 1, wherein the turntable and the receiving assembly are housed in a housing, and the system further includes a cassette holder operable to accommodate a plurality of fluid dispensing cassettes.

8. The system of claim 7, wherein the turntable is operable to retrieve the fluid dispensing cartridge from the cartridge holder and return the fluid dispensing cartridge to the cartridge holder.

9. The system of claim 8, wherein the turntable is linearly translatable in three dimensions, and the cartridge holder is positioned relative to the turntable in the housing such that retrieving the fluid dispensing cartridge from the cartridge holder or returning the fluid dispensing cartridge to the cartridge holder requires translation of the turntable in a first dimension of the three dimensions.

10. The system of claim 9, further comprising a refrigeration unit coupled to the box holder.

11. A method comprising: The cover of the reaction station of the processor assembly is moved from a first position covering the reaction chamber to a second position exposing a portion of the reaction chamber, wherein the reaction chamber comprises only a single microscope slide on which a sample is mounted, and the reaction station is one of a plurality of reaction stations in the processing assembly; A turntable is translated above the plurality of reaction stations of the processing assembly, the turntable including at least one of a slide identification reader and an imager connected thereto; The slide reader reads the identifier on the microscope slide or reads an image of the identifier. The processing plan for the sample on the microscope slide is determined based on the read identifier; One or more reagent dispensing kits are retrieved from the storage rack via the turntable, each of the one or more reagent dispensing kits containing the reagents required to perform the treatment protocol; as well as The one or more reagents are dispensed onto the sample on the microscope slide.

12. The method of claim 11, wherein after reading information provided on each of the plurality of carriers, the method includes moving the cover to the first position.

13. The method of claim 11, wherein before dispensing the one or more reagents onto the sample on the microscope slide, the method includes moving the cap to the second position.

14. The method of claim 11, wherein before dispensing the one or more reagents onto the sample on the microscope slide, the method includes raising the microscope slide in the chamber.

15. The method of claim 11, further comprising: After dispensing the one or more reagents onto the sample on the microscope slide, the method includes returning the one or more fluid dispensing cartridges to the storage rack via the turntable.

16. The method of claim 11, wherein the reaction station is a first reaction station, and at least one or more of the plurality of reaction stations include a single microscope slide comprising a sample and an identifier, and wherein the method comprises, before dispensing the one or more reagents onto the sample on the microscope slide in the first reaction station: The slide identification reader reads the identifier on the microscope slide in at least one or more of the plurality of reaction stations or reads an image of the identifier; as well as Based on the read identifier, a processing plan for the sample on the microscope slide in at least one or more of the plurality of reaction stations is determined.

17. The method of claim 11, wherein the dispensing comprises dispensing via a thermal inkjet process.

18. The method of claim 17, wherein dispensing comprises dispensing the one or more reagents at a rate of at least 15 microliters (µL) per square inch each time.

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