Advanced tissue staining systems and methods

Abstract

To provide tissue staining systems and methods. [Solution] A system comprising a carousel having a plurality of mounting stations sized to receive at least one fluid distribution cartridge, and a receiving assembly located beneath the carousel and comprising a plurality of reaction stations, each of which reaction stations comprises a body having length and width dimensions that together define a chamber for accommodating a single slide, and a lid including a first position covering the chamber and a second position in which a portion of the chamber is exposed. A method comprising moving the lid of a reaction station to expose a single microscope slide containing a sample, and dispensing one or more reagents to the sample.

Description

Technical Field

[0001] Cross - reference to Related Applications This non - provisional patent application claims the benefit of the pending U.S. Provisional Patent Application No. 63 / 740,927, titled "ADVANCED TISSUE STAINING SYSTEM AND METHOD," filed on December 31, 2024, the content of which is incorporated herein in its entirety.

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

Background Art

[0003] In various scenarios, the processing and examination of biological specimens are required for diagnostic purposes. Generally, pathologists and other diagnosticians collect samples from patients, study them, and use microscopes and other devices to evaluate the samples at the cellular level. Pathology and other diagnostic processes typically involve a number of processing steps, including the collection of biological samples such as blood and tissue, sample preparation, preparation of microscope slides, staining of samples on microscope slides, examination, re - examination or re - staining, collection of additional samples, re - examination of samples, and ultimately the provision of diagnostic findings.

[0004] Sample (e.g., tissue) staining processors or stainers can operate at various levels of automation to process human or animal sample specimens for histological or pathological purposes. Various types of chemical reagents can be used at various stages of tissue processing, and various systems have been developed for supplying reagents to slides containing specimens. Examples of known reagent supply systems include small - volume dispensers, manual injection into reagent tanks, or those using bulk containers connected to the stainer via piping.

Summary of the Invention

Problems to be Solved by the Invention

[0005] Known systems have various drawbacks. For example, manual injection or draining of reagents into the reagent tank is susceptible to cross-contamination, time-consuming, and requires precision in injection, thereby reducing the overall efficiency and accuracy of the tissue processing system. Another drawback is that manual injection and draining of reagents can be messy, requiring cleaning up spills and resulting in equipment downtime. A further drawback is that manually selecting and applying the correct reagents carries a significant risk of human error, increasing the likelihood of reagent selection and application errors, leading to false positive or false negative assay results, reducing not only test accuracy and operational efficiency but also misdiagnosis. [Brief explanation of the drawing]

[0006] Embodiments of the present invention are shown as examples and are not limited to those shown in the accompanying drawings. In the accompanying drawings, similar references indicate similar elements. It should be noted that references to “an” or “one” embodiments in this disclosure do not necessarily refer to the same embodiment, but rather mean at least one.

[0007] [Figure 1] A perspective view of the sample processing system is shown. [Figure 2] Figure 1 shows a perspective upper side view of a single reaction station separated from the reaction compartment of the sample processing system, with the reaction station lid in the closed position. [Figure 3] Figure 2 shows a perspective upper side view of the reaction station with the lid of the reaction station in the open position. [Figure 4] Figure 2 shows a side view of the reaction station with the lid closed. [Figure 5] Figure 2 shows an upper side perspective view of the reaction station with the main body removed, and the lower chamber structure of the reaction station is shown. [Figure 6A]Figure 2 shows a side perspective view of the reaction station, where the reaction station's tray is supported by a base at its highest point. [Figure 6B] Figure 2 shows a side perspective view of the slide support assembly, which includes a base and tray, separated from the reaction station. [Figure 7] (A) A partial side view of the reaction station of Figure 2, comprising the main body, base and tray, showing the tray supported by the base at the first, i.e., lowest position. (B) A partial side view of the reaction station of Figure 2, comprising the main body, base and tray, showing the tray supported by the base at the second position. (C) A partial side view of the reaction station of Figure 2, comprising the main body, base and tray, showing the tray supported by the base at the third position. (D) A partial side view of the reaction station of Figure 2, comprising the main body, base and tray, showing the tray supported by the base at the fourth, i.e., highest position. [Figure 8] Figure 2 shows a partial perspective upper side view of the reaction station, which includes the main unit, base, and tray, and shows the inclined tray. [Figure 9] (A) A side view of a portion of the reaction station in Figure 2, passing through line 9-9' in Figure 8, showing a tray moving downward in a horizontal (un-tilted) orientation. (B) A side view of a portion of the reaction station in Figure 2, passing through line 9-9' in Figure 8, showing a tray moving downward in an inclined orientation. [Figure 10] Figure 1 shows a perspective left side view of the carousel assembly of the sample processing system in its separated state. [Figure 11] Figure 10 shows a perspective right side view of a portion of the gantry of the carousel assembly in its separated state, illustrating the drive mechanism in the x-direction (longitudinal direction). [Figure 12] Figure 10 shows a perspective rear view of the U-shaped bracket and lateral drive support bracket of the carousel assembly in its separated state. [Figure 13] Figure 10 shows a perspective rear view of a portion of the carousel in the carousel assembly in its separated state. [Figure 14]Figure 10 shows a side perspective view of the gantry of the carousel assembly and the arm assembly separated from the carousel. [Figure 15] Figure 1 shows a perspective view of the front left side of the storage rack of the sample processing system in its separated state. [Figure 16] Figure 15 shows a side perspective view of a reagent cartridge, which is a typical example of a reagent cartridge that is stored in a storage rack and operated for use when dispensing reagents in the sample processing system shown in Figure 1. [Figure 17] Figure 15 shows a perspective view of a portion of the storage rack, specifically the front right side view, and shows two reagent cartridges similar to those in Figure 16 that are housed inside the storage rack. [Figure 18] Figure 13 shows a portion of the carousel, which includes a pedestal or cartridge carrier plate separated from the base of the cylindrical section, and shows the reagent cartridges in the dock of the pedestal or cartridge carrier plate. [Figure 19] Figure 1 shows a front view of the service station of the sample processing system. [Modes for carrying out the invention]

[0008] The following paragraphs will describe the present invention in detail, with reference to the accompanying drawings. Throughout this specification, the embodiments and examples shown are not intended to limit the invention and should be considered illustrative. Furthermore, references to various aspects of the embodiments disclosed herein do not mean that all claimed embodiments or methods must include the aspects mentioned.

[0009] Figure 1 shows a perspective view of the sample processing system. The sample processing system 100 comprises a housing 102 for enclosing and storing various components of the processing system 100. The housing 102 comprises a reaction compartment 104 and a storage compartment 101. The reaction compartment 104 is separated from the storage compartment 101 by a platform 105 that forms the base of the reaction compartment 104. In addition to the platform 105, opposing side walls protrude from the platform 105, and a cover connects the ends of each side wall. The cover, side walls, and platform 105 together define the compartment in which sample processing takes place. Access to components within the reaction compartment 104 may be obtained using a cover member 108 and a door member 110 (located at the front of the housing 102 in the illustrated configuration).

[0010] The reaction compartment 104 is sized to accommodate a storage rack for storing a number of reagent cartridges (e.g., having an internal volume). The storage rack 106 may be mounted on the platform 105 or on one of the side walls of the reaction compartment 104 (e.g., the rear side wall in the illustrated configuration). The storage rack 106 may be used to store reagent cartridges. Typical reagent cartridges are single-use cartridges, such as thermal inkjet cartridges containing a volume of reagent that can be used for pathological or histological processing. The storage rack 106 includes, for example, an array of slots for storing individual reagent cartridges in a column-and-row array. The storage rack 106 may include a refrigeration section for storing reagent cartridges under refrigeration. A typical refrigeration section may include a compressor that condenses a refrigerant vapor, liquefies the vapor through a coil, and cools the storage rack slots.

[0011] Reaction compartment 104 is sized to accommodate a plurality of reaction stations 112 therein. FIG. 1 illustratively shows 30 reaction stations 112 arranged in a 15×2 configuration in the plane (xz plane) on platform 105. It should be understood that the number and configuration of the reaction stations partially depend on the area dedicated to reaction compartment 104. Thus, it is envisioned that the number of reaction stations may vary, as may their configuration. In the illustrated state, a carousel assembly including gantry 114 and carousel 115 is disposed above reaction stations 112. Carousel 115 is operable to accommodate / hold a number of reagent cartridges and dispense reagents from each reagent cartridge onto respective slides within reaction stations 112. Carousel 115 is operable on gantry 114 to place reagent cartridges above individual reaction stations 112 and move to load reagent cartridges from storage rack 106 and unload them back to storage rack 106.

[0012] Sample processing system 100 also includes a control unit 109. Control unit 109 includes non - transient machine - readable instructions that control the operation of the sample processing system, including, but not limited to, the loading / unloading of reagent cartridges in storage rack 106 and the loading / unloading of reagent cartridges in carousel 115. FIG. 1 shows control unit 109 outside housing 102. It should be understood that control unit 109 may be outside housing 102 or may be a component inside housing 102.

[0013] Figures 2 and 3 are perspective views of a reaction station separated from reaction compartment 104. The reaction station 112 comprises a body 120. The body 120 of the reaction station 112 comprises a base and a pair of opposing side walls defining a length dimension (z direction), and another pair of opposing side walls defining a width dimension (x direction). The base and the two pairs of side walls together define a chamber 125 (see Figure 3) that houses a single slide within the chamber. Typically, the slide may be a flat piece of glass having a thickness of 1 millimeter (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 may be approximately 80 mm to 100 mm (3.2 inches to 4 inches), and the width of the chamber may be approximately 28 mm to 40 mm (1.1 inches to 1.6 inches). Figure 3 shows a slide 150 in the chamber 125. The body 120 may be made of a material that is chemically inert to reagents commonly used in the staining process. Typical metallic materials include, but are not limited to, stainless steel, zinc alloys, aluminum alloys, and silver. For example, silver material may be used to impart antimicrobial properties to the body 120. Other exemplary materials for the body 120 include heat-conducting polymer materials, such as plastics or cellulosic materials (i.e., materials derived from or containing cellulose), ceramics, Teflon®, and glass. The 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. In addition, it should be understood that the body 120 may be composed of more than one of the materials described above.

[0014] Each of the reaction stations 112 also includes a lid of plastic or metallic material (e.g., stainless steel, zinc alloy, aluminum alloy, silver) having dimensions that cover the chamber 125. The lid 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 lid 130 also includes a clevis portion 132 that projects in the length direction (z-direction) from the generally rectangular portion. A gasket or seal 135 of rubber or other polymeric material is disposed on the upper surface of the body 120 in the illustrated state. The gasket or seal 135 may serve to seal (e.g., hermetically seal and fluid seal) or substantially seal the chamber 125 when the lid 130 is in a position contacting the gasket or seal 135 on the body 120 (see FIGS. 2 and 4).

[0015] The main body 120 of the reaction station 112 is attached to a substructure 140. The substructure 140 is shown as a rectangular member of, for example, a plastic or metal material (e.g., stainless steel, aluminum alloy, zinc alloy), and comprises a base defining a chamber and two pairs of opposing side walls, the upper part of which contacts the base of the main body 120. In this example, the substructure 140 has the same length dimension (in the z direction) as the main body 120. A portion of the main body 120 protrudes longitudinally in a cantilever manner beyond the end of the substructure 140, leaving a portion of the chamber of the substructure 140 exposed. Figure 5 shows an upper side perspective view of the reaction station 112 with the main body 120 removed. As shown in Figure 5, within the chamber of the substructure 140 located at the rear of the main body 120 (rear of the main body side opposite the cantilever portion), a gear 155 is shown centered on an axis 160 between opposing longitudinal side walls of the substructure 140 (side walls defining the z-direction length in Figures 2 and 3). The axis 160 is connected to the opposing side of the substructure 140 by screws, bolts, pins, or rivets 165. The opposing side of the gear 155 is parallel to the opposing side wall of the substructure 140. The outer circumference of the gear 155 is provided with cutting teeth or cogs. In this example, the gear 155 is driven (rotated) by a motor 170 located below the substructure 140. The motor 170 has a protruding shaft connected to a worm gear 157. The worm gear 157 has helical threads that engage with the gear 155 in a clockwise or counterclockwise direction to drive the gear 155.

[0016] Brackets 145 are connected to the opposing longitudinal side walls of the substructure 140 and the opposing side walls of the lid 130 (one bracket is connected to the outside of each side wall). The brackets 145 are shown as rectangular members of, for example, plastic or metal material (e.g., stainless steel, aluminum alloy, zinc alloy). The first end of each bracket 145 is connected to the side of the substructure 140 via a bolt, screw, rivet or pin 146, which allows the bracket to rotate on the bolt, pin, rivet or screw (for example, the diameter of the opening through the bracket 145 is greater than the outer diameter of the bolt, pin or screw 146). Counterweights (counterweights 147) may be placed between each bracket 145 and the corresponding side wall of the substructure to counteract the weight when the lid 130 pivots / rotates. The second end of each bracket 145 is connected to each of the opposing longitudinal side surfaces of the lid 130 via a bolt, pin, rivet or screw 149. A bolt, pin, rivet, or screw 149 may pivotally connect the bracket to the lid 130. The bracket or a drive lever 175 is connected to the clevis portion 132 of the lid 130. The drive lever 175 has a first end that is fixedly connected to a gear 155. The second end of the drive lever 175 is connected to the clevis portion 132 of the lid 130 via a bolt, pin, rivet, or screw 176. The drive lever 175, gear 155, worm gear 157, and motor 170 enable the lid to move from a first position that covers (surrounds) the chamber 125 (see Figures 2 and 4) to a second position that exposes part of the chamber (see Figure 3). The bracket 145 and the drive lever 175 support the lid 130 as it moves between those positions.

[0017] When the lid 130 is in a first position covering the chamber 125 of the main body 120, the motor 170 rotates the gear 155 (for example, counterclockwise) to rotate the drive lever 175, causing the lid 130 to swivel and rotate so that it moves from the first position to the second position. When the lid 130 is in the second position, the bracket 145 may be substantially parallel to the side wall of the substructure 140. The motor 170 rotates the gear 155 in the opposite direction (for example, clockwise) to rotate the drive lever 175, causing the lid 130 to rotate so that it moves from the second position to the first position.

[0018] As described above, the chamber 125 of the main body 120 is sized to accommodate a microscope slide for processing (only a single microscope slide). The biological sample may be placed on the microscope slide for processing or fixed in place. As shown in Figures 3, 6A, and 6B, each reaction station is equipped with a tray 180 mounted on a base 185 to support the microscope slide within the chamber 125. In one example, the tray 180 is a planar structure having a cross shape or form defining four ends. Each end may have an upward projection (e.g., straight or inverted L-shape) for enclosing the slide on the tray.

[0019] The base 185 is connected to the base of the tray 180, for example, at the midpoint of the tray 180. In this way, the base 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 base 185 extends may be sealed with a gasket or the like (e.g., hermetically sealed and liquidally sealed). The base 185 may be a linear actuator, or may be connected to a linear actuator that can be operated to move the tray 180 between multiple positions relative to the chamber 125 (e.g., to move the tray 180 between multiple depths of the chamber 125). In one example, the base 185 can be operated to move the tray 180 between the following four positions, as shown in the side views of Figures 7A to 7D. That is, a first position (Figure 7A) in which the tray 180 and the slide on it are at a first depth in the chamber 125; a second position (Figure 7B) in which the tray 180 and the slide on it are at a second depth less than the first depth in the chamber 125 (i.e., the tray may rise from the first depth to the second depth, or descend from the second depth to the first depth); a third position (Figure 7C) in which the tray 180 and the slide on it are at a third depth less than the second depth in the chamber 125 (i.e., the tray may rise from the second depth to the third depth, or descend from the third depth to the second depth); and a fourth position (Figure 7D) in which the tray 180 and / or the slide on it are outside the chamber 125 (i.e., above the main body 120 and above the sealing portion 135). Figure 3 shows the reaction station 112 in which tray 180 is supported by a base 185 in a second position. Figure 6A shows the reaction station 112 in which tray 180 is supported by a base 185 in a fourth position.

[0020] Tray 180 may be formed from a material having sufficient structural strength and process-neutral properties to support the slide, hold the reagents, and accommodate the reagents and temperatures used during use. Typically, tray 180 may be made of a metallic material. Other exemplary materials for tray 180 may include plastic or cellulosic (i.e., cellulose-derived or containing cellulose) materials, ceramics, Teflon®, glass, and other heat-conducting polymer materials. Typically, tray 180 may be made of a polyoxymethylene thermoplastic such as DELRIN (a registered trademark of EIDuPont de Nemours and Co., Wilmington, Del.). Tray 180 can be formed by any process known in the art, such as injection molding, machining, or other manufacturing processes suitable for producing the desired features. In addition, it should be understood that reaction tray 180 may consist of more than one of the materials described above, and such materials may be the same or different for tray 180 and body 120, respectively. As shown in Figure 6A, the base 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 into the chamber 125 through the base of the main body 120 and connecting to the tray 180. The opening in the base of the main body 120 through which the base 185 extends may be sealed with a gasket or the like (e.g., hermetically sealed and liquidally sealed). The opening in the base of the substructure 140 may also be sealed.

[0021] Figure 6B shows a side perspective view of a slide support assembly comprising a base 185 and a tray 180 separated from the reaction station 112. The base 185 may be connected to the base of the tray 180 via a pivot or articulated connector 1852. In one example, the pivot connector 1852 allows the tray 180 to be rotated to an inclined position. In one example, the tray 180 may be rotated along its length (z-direction length), for example, 20 to 45 degrees. Figure 8 shows the tray 180 in an inclined position (after rotation from a horizontal position (0 degrees) to an inclined position represented by an angle α of, for example, 20 to 45 degrees relative to the horizontal (see cross section in the inset)). The pivot position of the tray 180 to an angle α of 20 to 45 degrees in the first position may allow excess reagent on the slide 150 on the tray 180 to be removed from the slide. Figures 9A and 9B show cross sections of the slide support through line 9-9' in Figure 8. Figures 9A and 9B illustrate one method of positioning the tray 180 in an inclined position. In this example, the side wall of the body 120 is provided with a tab or protrusion 123 that protrudes from the inner surface between depths representing the first position (Figure 7A) and the second position (Figure 7B) of the slide. The protrusion 123 may be a spring or elastic body (e.g., plastic) having a length such that the longitudinal edges of the slide 150 and tray 180 move beyond it when the slide 150 is moved from the second position to the first position by the base 185. Figure 9A typically shows the tray 180 and slide 150 in the second position. As the base 185 moves the tray 180 and slide 150 downward between the second position and the first position (as shown), one side of the tray 180 / slide 150 (the left side as shown) comes into contact with the protrusion 123, stopping its downward movement. The pivot joint connector between the base 185 and the tray 180 allows the other side of the tray 180 / slide 150 (the right side in the illustrated configuration) to continue descending until the tray 180 / slide 150 is tilted to an angle α that represents the first position. Moving the tray 180 / slide 150 upward from the first position to the second position reverses this process.Upward movement first returns the tray 180 / slide 150 to the horizontal position (i.e., first move the right side of the tray 180 / slide 150 upward until the surface of the tray 180 / slide 150 is horizontal on the raised portion 123 in the illustrated state). The pivot coupling connector may have a ratchet locking mechanism, and when the tray 180 rotates to the horizontal position, the connector locks so that the tray 180 / slide 150 remains horizontal when the base raises the tray 180 / slide 150 to a third position (Figure 7C).

[0022] When the tray 180 and slide 150 are in the tilted position shown in Figure 9B, excess fluid (such as reagents) on the slide 150 may be discharged toward the bottom of the chamber 125 of the body 120. Figures 9A and 9B show a drain 121 located at the base of the body. The drain 121 may have a conduit to which a valve that can be opened and closed is connected. Typically, the valve may be connected to a control unit 109, which may include non-intermittent machine-readable commands to electrically operate the valve to the open position when the tray 180 and slide 150 are in the tilted position, or thereafter, to discharge excess fluid (such as reagents) from the chamber 125. The conduit may be connected to a waste container for collecting the excess fluid (such as reagents).

[0023] Referring again to Figure 6B, the slide heating unit 1802 is located on the underside of the tray 180 (the side opposite to the side supporting the slide 150). The slide heating unit 1802 is, for example, an electric (Joule) heating unit (e.g., 12 volts, 24 volts). The heating unit may be selected to rapidly heat the microscope slide to a desired temperature. Typical temperatures for a particular sample processing operation may be 20°C (approximately ambient temperature) to 150°C, e.g., 20°C to 150°C, e.g., 30°C to 140°C, e.g., 40°C to 130°C, e.g., 50°C to 120°C, e.g., 60°C to 110°C, e.g., 70°C to 150°C, e.g., 100°C to 140°C, e.g., 110°C to 140°C, or e.g., 120°C to 130°C. Typical tissue processing temperatures include 120°C to 130°C for pressurized antigen retrieval, approximately 90°C to 100°C for atmospheric pressure antigen retrieval, and 20°C to 40°C for room temperature staining. A heat sink 1804 is positioned below the tray 180. The heat sink 1804 may be made of a highly thermally conductive material (e.g., metal) that can dissipate the heat applied to the tray 180 (e.g., by the slide heating unit 1802) and cool the tray 180 for processing operations that do not require a heated microscope slide surface or processing operations that require incubation at ambient temperature. Rapid cooling may be assisted by rinsing the microscope slide after high-temperature processing with washing buffer or water.

[0024] The base 185 is a linear actuator comprising, for example, an outer tube 1854 and an inner tube 1855 at least partially positioned within the outer tube 1854. The inner tube 1855 can be operated, for example, by electrical energization to move in the y-direction (up and down direction) relative to the outer tube 1854. The base 185 may have an electric motor 1856 (e.g., a direct current (DC) motor) at its base that can be operated to move the inner tube 185 in the y-direction. The electric motor 1856 may be connected to a control unit 109 and operated based on non-temporary machine-readable commands associated with the control unit 109. Additional commands associated with the control unit 109 may include commands to control the slide heating unit 1802 to heat the tray 180 for a high-temperature process, and commands to introduce a washing buffer or water to rinse the microscope slide after the high-temperature process.

[0025] Referring again to the lid 130, the lid 130 may be provided with a number of fluid connectors 131 (e.g., 4 to 8 fluid connectors) extending from the upper surface of the lid. The fluid connectors 131 may be arranged in a row along one end of the upper side of the lid 130 (see Figure 2). The fluid connectors 131 may also be fixtures or connectors that allow fluid conduits (e.g., polymer piping) to be connected to fixtures or connectors. The underside of the lid 130 is provided with a number of conduits 137 arranged longitudinally along the length of the tray 180. One of the individual fluid connectors 131 is fluidly connected to the conduits 137 so that fluid can be supplied to the conduits 137 through the fluid connectors. The conduits 137 may be piping materials such as metal (e.g., copper, aluminum, stainless steel). Each conduit 137 may have an opening along its length to allow fluid to be discharged from the conduit toward the tray 180 when the lid 130 is in a first position (e.g., covering the chamber 125). Each opening in the conduit may be equipped with a nozzle for controlling the direction and velocity of the flow.

[0026] In one example, bulk reagents may be individually connected to the fluid connector 131. Examples of bulk reagents include, but are not limited to, distilled water, hematoxylin, Tris-buffered saline, and dewaxing solution. The bulk reagents may be contained in individual containers stored in a storage compartment 101 located below the reaction compartment 104 (see Figure 1). The bulk reagent source may be connected to one of the fluid connectors 131, for example, via a conduit running between each bulk reagent container and the fluid connector. The bulk reagents may be supplied to the fluid connector by using a pump as needed, such as a separate in-line pump for each bulk reagent container connected to the fluid connector. Non-transient machine-readable commands associated with the control unit 109 may control the metering of reagents from the bulk reagent containers, for example, by a timer or by individual in-line flow meters (e.g., flow meters in the conduit between the bulk reagent container and the fluid connector).

[0027] The reaction station 112 may also function as a humidor, allowing for manipulation and maintenance of humidity levels within the chamber 125 to reduce evaporation of reagents and drying of samples (e.g., tissues). Typical humidity levels may be relative humidity above 50%, e.g., above 60% up to 100%, e.g., 70% to 100%, e.g., 80% to 100%, or e.g., 90% to 100%. In the example shown in Figures 2-4, the body 120 of the reaction station 112 includes a chamber 125 having dimensions to accommodate a reservoir below the tray 180 when the tray 180 is in its lowest position (first position) within the chamber. The reservoir may be filled with a fluid (e.g., water) to bring humidity into the chamber 125. Typically, a fluid source (water) may be connected to a fluid connector 131. A conduit between the fluid source and the fluid connector may include a flow meter for measuring the amount of fluid introduced into the chamber 125. In one example, a valve connector (valve connector 131) and a flow meter may be electrically connected to a control unit 109, which includes non-transient machine-readable commands for introducing a specific volume of fluid into the chamber 125 through the valve connector, if present. The fluid being introduced may be hot (e.g., 80°F to 120°F) when introduced or when heated, for example, by a heating element in the reservoir of the chamber 125. A drain 121 may also extend from the chamber 125 through the base wall of the body 120 (see Figure 4), which may function as a drain for discharging the fluid contents of the reservoir in the chamber 125. The drain 121 may have a valve on the outside of the chamber 125. In one example, the drain valve may be electrically connected to a control unit 109, which includes non-transient machine-readable commands for operating (opening and closing) the drain valve.

[0028] As described above, it may be desirable to raise the temperature inside the reaction station 112 above the ambient temperature. One way to do this is to use a slide heating unit 1802 to heat the tray 180. In addition to, or as an alternative to, the temperature inside the chamber 125 may be raised by heating the fluid in the reservoir, as described above with respect to generating a humidity level inside the chamber 125. Another heating technique may include one or more heating units positioned on the side walls of the body 120 inside the chamber 125 to heat the area surrounding the tray 180. Examples include resistive electric heating units or infrared heating units positioned inside the chamber 125. Further technique is a heat jacket wrapped around the outside of the body 120 to heat the chamber 125 from the outside. The heat source may be connected to the control unit 109, and the heat source and the temperature inside the chamber 125 may be controlled by non-temporary machine-readable commands associated with the control unit 109.

[0029] Figure 1 typically shows 30 reaction stations 112 arranged in a 15x2 configuration on a plane (xz plane). The first of two rows shows reaction stations 112, each with a lid 130 in a second (closed or covered) position. The second of two rows shows reaction stations 112 with their individual lids in the open position. Each reaction station 112 may be connected to the platform 105 of the reaction compartment 104 of the housing 102.

[0030] Referring 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 gantry 114 supporting the carousel 115. The gantry 114 and the carousel 115 are collectively referred to as the carousel assembly. Figure 10 shows a perspective left side view of the carousel assembly in its separated state. The gantry 114 includes two vertical (y-direction) columns 1142 connected to the base of the reaction compartment 104. The vertical columns 1142 are separated by an x-direction distance greater than the distance covered by the rows of reaction stations 112 within the reaction compartment 104. Above the reaction stations 112, between the vertical columns 1142, are two horizontal supports 1144. The horizontal support sections 1144 are typically cylindrical in shape, extending along the x-direction distance of the vertical column 1142, and each is parallel to the base of the reaction compartment 104. The horizontal support sections 1144 are connected to the vertical column 1142 by end brackets 1145 (e.g., inverted L-shaped brackets). The horizontal support sections 1144 are separated by a z-direction distance selected for the z-direction movement of the carousel 115, as detailed below. Each horizontal support section 1144 between the end brackets 1145 is connected by a U-shaped bracket 1146 (e.g., inverted U-shaped in the illustrated configuration). The U-shaped bracket 1146 has two legs separated by a base. The horizontal support sections 1144 are connected to the base by linear bearings 1147. A linear bearing 1147 is connected to the upper or exposed side of the base of the U-shaped bracket 1146, allowing the U-shaped bracket 1146 to move in the x-direction on the horizontal support 1144. The base of the U-shaped bracket 1146 has an opening 1148 through it, for example, 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 bracket 1146. The tab 11493 protrudes upward (y-direction) from the base. The tab 11493 is connected to a timing belt 1140, which is used to move the U-shaped bracket 1146 in the x-direction (longitudinal direction).

[0031] A lateral drive support bracket 1149 is connected to the base of a U-shaped bracket 1146 located below the horizontal support portion 1144. The lateral drive support bracket 1149 is U-shaped (for example, inverted U-shaped in the illustrated configuration) as defined by its base and side walls. The upper side of the lateral drive support bracket 1149 has an opening 11499 through it in the illustrated configuration. The base of the lateral drive support bracket 1149 has an x-width smaller than the corresponding width of the base of the U-shaped bracket 1146, so that the side walls of the lateral drive support bracket 1149 are positioned between the side walls of the U-shaped bracket 1146, and the side walls of the lateral drive support bracket 1149 are connected to the respective side walls of the U-shaped bracket 1146, for example, by screws, rivets, or welds. Inside each side wall of the lateral drive support bracket 1149, there is a lateral linear guide extending over the z-length of the side wall or 70% to 90% of the z-length. Each lateral linear guide 11492 is located at a similar y-distance from the end of the side wall, connected to the side wall, for example, by screws, rivets, or welding. The carousel 115 is connected to each lateral linear guide 11492.

[0032] The carousel 115 can move in three directions relative to the gantry 114. The carousel 115 can move in the x direction (longitudinal direction) as the U-shaped bracket 1146 moves. The carousel 115 can move in the y direction (vertical direction) as the end bracket 1145 moves up and down on the vertical column 1142. The carousel 115 may also move in the z direction (lateral direction) as the carousel 115 moves along each of the lateral linear guides 11492 of the lateral drive support bracket 1149.

[0033] Figure 11 shows a perspective right side view of a portion of the gantry 114 to illustrate the drive mechanism in the x-direction (longitudinal direction). In this figure, the gantry 114 includes a horizontal support 1144 connected to a vertical column 1142 by an end bracket 1145. A gear 1141, which rotates in the xz plane, is connected to the top of each end bracket on one side of the gantry 114 (the left side as shown in Figure 11). One end of the gear 1141 is connected to the shaft of a motor 1143, which can be operated to rotate one gear clockwise or counterclockwise. A timing belt 1140 is positioned around the gear 1141 and extends above one of the horizontal support 1144. The timing belt 1140 can be operated to move in the x-direction (longitudinal direction) by the gear 1141. The timing belt 1140 is connected to a tab 11493 attached to a U-shaped bracket 1146 via screws, rivets, pins, etc. (see Figure 10). By connecting the timing belt 1140 to the U-shaped bracket 1146, the motor 1143 can move the U-shaped bracket 1146, and as a result, the lateral drive support bracket 1149 and the carousel 115 can be moved in the x-direction (longitudinal direction).

[0034] Figure 12 shows a perspective rear view of the U-shaped bracket 1146 and the lateral drive support bracket 1149 in their separated state. Figure 12 shows that the linear bearing 1147 is connected to the upper or exposed side of the base of the U-shaped bracket 1146. The linear bearing 1147 supports the horizontal support 1144. Three linear bearings 1147 are shown, one linear bearing at one end of the U-shaped bracket 1146 supporting one horizontal support 1144, and two linear bearings 1147 at the opposite end of the base supporting the other horizontal support 1144, with the z-direction separation of one linear bearing from the two linear bearings corresponding to the z-direction distance between the horizontal support 1144 (see Figure 10). The base of the U-shaped bracket 1146 has an opening 1148 (for example, a rectangular opening) through it between one linear bearing 1147 and two linear bearings 1147. A tab 11493 is connected to one end of the base of the U-shaped bracket 1146, either the upper or exposed side. The tab 11493 protrudes upward (y-direction) from the base. The tab 11493 is connected to the timing belt 1140, which is used to move the U-shaped bracket 1146 in the x-direction (longitudinal direction) (see Figure 10).

[0035] Figure 12 also shows the z-direction (lateral) drive mechanism. Figure 12 shows a lateral drive support bracket 1149 connected to a U-shaped bracket 1146 and positioned below the U-shaped bracket. Inside each of the side walls 11494A and 11494B of the lateral drive support bracket 1149, there is a lateral linear guide that extends for a portion of the z-direction length of the side wall of the lateral drive support bracket 1149 (e.g., 70% to 90% of the z-direction length). Each lateral linear guide 11492 is at a similar y-direction distance from the end of the side wall (side walls 11494A and 11494B) that is connected to the side wall by, for example, screws, rivets, or welding.

[0036] The z-direction (lateral) drive mechanism shown in Figure 12 also includes two gears 11493 connected to the outside of the side wall 11494A (left side wall in the illustrated view) of the lateral drive support bracket 1149. In Figure 12, only one of the two gears 11493 can be seen at one end (rear end) of the side wall 11494A of the lateral drive support bracket 1149. The second of the two gears 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, which is rotated by the shaft of a motor 11495, and the motor 11495 can be operated to rotate clockwise or counterclockwise. The timing belt 11497 is positioned 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) by the gear 11493.

[0037] Figure 13 is a perspective rear view of a portion of the carousel 115. This figure shows a portion of the carousel 115 that connects to the lateral drive support bracket 1149 of the gantry 114. The carousel 115 comprises a main bracket 11510 having a rectangular shape with a length dimension (x dimension) and a width dimension (z dimension), defined by a pair of opposing side walls positioned inside the lateral drive support bracket 1149. Side walls 11511 and 11514 define the length dimension, and side walls 11512 and 11513 define the width dimension. The main bracket 11510 also comprises an upper portion 11515 that connects to each side wall and has through-openings for the cylindrical portion 1151. A z-shaped bracket 1153 is connected to the side wall 11512 of the main bracket 11510. The z-shaped bracket 1153 has a base portion 11531 that protrudes horizontally (x direction) at a distance d from the side wall 11512, an intermediate portion 11532 that protrudes vertically (y direction), and a top portion 11533 that protrudes horizontally (x direction) from the intermediate portion 11532. Because the z-shaped bracket 1153 protrudes at a distance d from the side wall 11512, the intermediate portion 11532 and the top portion 11533 can be positioned outside the side wall (side wall 11494A) of the lateral drive support bracket 1149 when the main bracket 11510 is placed inside the lateral drive support bracket 1149. A timing belt 11497 (see Figure 12) is connected to the top 1153 (for example, via screws, rivets, pins, etc.) so that the motor 11495 can move the main bracket 11510 of the carousel 115 in the z direction (lateral direction). A lateral sliding bearing 1154 is mounted on the side wall 11512, which is operable to engage with a lateral linear guide 11492 connected to the inside of the side wall 11494A of the lateral drive support bracket 1149 (see Figure 12). A roller 1159 protrudes outward from the side wall 11513 (opposite side wall 11512). The roller 1159 engages within the lateral linear guide 11492 on the side wall 11494B of the lateral drive support bracket 1149 and is operable to rotate in the yz plane.

[0038] As described above, the main bracket 11510 includes an upper portion 11515 having a through-opening for the cylindrical portion 1151. The cylindrical portion 1151 has cutting teeth or insertion teeth around its upper portion. A slewing bearing 1155 is positioned in the upper portion 11515 of the main bracket 11510. The slewing bearing 1155 includes an outer ring and an inner ring, the inner ring incorporating a gear having cutting teeth or insertion teeth that mesh with the teeth around the upper portion of the cylindrical portion 1151. A gear 1156 is positioned on the upper surface of the slewing bearing 1155 and connected to the slewing bearing 1155. The gear 1156 rotates in the xz plane and can be operated to rotate the inner ring of the slewing bearing 1155 in the same plane, thereby rotating the cylindrical portion 1151. The main bracket 11510 remains stationary (does not rotate). The gear 1156 is rotated by a motor 1157. The motor 1157 is mounted on the upper portion 11515 of the main bracket 11510 and has a shaft extending from there, which rotates in the yz plane. The shaft is connected to a worm gear 1158 that meshes with gear 1156, causing gear 1156 to rotate in the xz plane. Referring to Figure 10, the base of the cylindrical portion 1151 of the carousel 115 has a pedestal or cartridge carrier plate 1152 that engages with and is operable to accommodate a number of reagent cartridges. The rotation of the cylindrical portion 1151 by the motor 1157 causes the pedestal 1152 to rotate.

[0039] Referring again to Figure 10, the gantry 114 comprises two vertical columns 1142. The vertical columns 1142 are shown together with rectangular housings 11422 arranged around lead screws 11424. Each lead screw 11424 is connected to its respective end bracket 1145 and driven (rotating clockwise or counterclockwise) by its respective stepper motor (motor 11425), with one stepper motor slave-connected to the other stepper motor. The rotation of the lead screws 11424 provides y-direction movement of the end bracket 1145, and correspondingly provides y-direction movement of the horizontal support 1144 and carousel 115.

[0040] As described above, the carousel 115 can move in three directions relative to the gantry 114. The carousel 115 can move in the x-direction (longitudinal direction) as the U-shaped bracket 1146 moves by the motor 1143. The carousel 115 can move in the y-direction (vertical direction) as the end bracket 1145 moves up and down on the vertical column 1142 as the stepper motor 11425 moves. The carousel 115 may also move in the z-direction (lateral direction) as the carousel 115 moves along each of the lateral linear guides 11492 of the lateral drive support bracket 1149, which is driven by the motor 11495. The motors 1143, 11425 and 11495 are each controlled by non-temporary machine-readable commands in the control unit 109 that command their operation (e.g., direction of rotation, execution time, etc.).

[0041] The carousel 115 is operable to automatically load / unload, engage, or accommodate / disengage or release multiple reagent cartridges on a base 1152. Referring to Figure 10, the carousel 115 can automatically load / unload reagent cartridges by using an arm assembly 118. Figure 14 is a side perspective view of the arm assembly 118 separated from the gantry 114 and carousel 115. The arm assembly 118 includes an attachment bracket 1182 attached to the outer surface of the side wall 11511 of the main bracket 11510 (for example, attached to the midpoint of the side wall 11511 (see, for example, Figure 13)) via bolts, screws, rivets or pins. 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. In Figure 10, the long actuator 1186 protrudes almost vertically (horizontally in the illustrated configuration) from the attachment bracket 1182, and the short actuator 1184 protrudes almost diagonally (for example, at a 45° angle) from the attachment bracket 1182 to connect with the long actuator 1186. A cartridge engagement head 1183 is connected to the end of the long actuator 1186. The cartridge engagement head 1183 has a pair of finger portions separated by a distance d1 on opposite sides, so that the finger portions surround the protruding portion of the reagent cartridge (described below), engage with the reagent cartridge, and move it.

[0042] Figure 14 shows that the upper portion of the attachment bracket 1182 has a clevis portion 11822 and the lower portion has a clevis portion 11823. One end of the short actuator 1184 is connected to the clevis portion 11822 so that it can rotate around a clevis pin, screw, or bolt, for example. Similarly, one end of the long actuator 1186 is connected to the clevis portion 11823 so that it can rotate around a clevis pin, screw, or bolt, for example. The short actuator 1184 and the long actuator 1186 each have an electrically operated telescopic body (e.g., a body with three stages of continuously small cylinders or supports). The second end of the short actuator 1184 is connected to the smallest stage or to the plunger of the long actuator 1186 by linkage 1185. Linkage 1185 is close to the engagement head 1183. The connection position of the short actuator 1184 to the long actuator 1186 is selected such that, when the short actuator 1184 is fully retracted, the short actuator 1184 rotates the long actuator 1186 by a few degrees (e.g., up to 10°, e.g., 2° to 8°) around the clevis portion 11823, and the distal end of the long actuator 1186 with the engaging head 1183 moves toward (lifts) toward the clevis portion 11822. The long actuator 1186 may extend in a configuration that is lifted to a position above the reagent cartridge. The short actuator 1184 may then extend to rotate the long actuator 1186 in the opposite direction (i.e., rotate the long actuator toward the clevis portion 11822), and the engaging head 1183 may be lowered toward the reagent cartridge to grasp the reagent cartridge.

[0043] As described above and shown in Figure 1, the sample processing system 100 comprises a housing 102 for storing various components of the processing system 100, which include a storage rack 106. Reagent cartridges (e.g., reagent cartridge 117) may be stored in the storage rack 106. Figure 15 shows a perspective front left side view of the storage rack 106 separated from the other components of the housing 102. The storage rack 106 comprises a housing 1062 with slots facing the reaction compartment 104 and the carousel 115. The storage rack 106 includes an array of slots for storing individual reagent cartridges. Figure 15 shows an array of slots in the order of 5 rows × 25-30 columns. The array of rows and columns allows each slot to have an address (e.g., designated by row and column numbers) so that the system can know the location of a reagent cartridge in the storage rack 106, locate a reagent cartridge, or return a reagent cartridge to a specific slot in the storage rack 106. In Figure 15, reagent cartridges (reagent cartridge 117) are fixed in all slots of the array. The outer surface of each reagent cartridge may include an identifier, such as a barcode, which contains identification information about the reagent contained in the reagent cartridge, and other information such as the expiration date, if possible. The identifier may be read by a reader (e.g., a barcode reader), and the read information may be provided electronically to the control unit 109. One example is a reader on a carousel 215 electronically connected to the control unit 109. The identifier on the reagent cartridge (e.g., reagent cartridge 117) may have a rewritable IC chip that can store the identity of the reagent, lot number, expiration date, and number of uses.

[0044] Figure 16 shows a side perspective view of a reagent cartridge 117, a typical example of a reagent cartridge that can be operated for storage in a storage rack 106, and its use in a processing system 100. Typically, the reagent cartridge 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, the reagent cartridge 117 has similar depth and width, and a height of 70.8 mm (H2 is smaller than H1). The reagent cartridge 117 may also be a drop-on-demand cartridge, such as a thermal drop-on-demand cartridge or a piezoelectric drop-on-demand cartridge, and the reagent cartridge has individual dedicated printheads positioned at the base of the reagent cartridge 117 in the illustrated configuration.

[0045] The reagent cartridge 117 contains a certain volume of reagent and may have a dedicated printhead. Each cartridge may be a single-use cartridge. In this context, a single-use cartridge means that once the volume of reagent in the cartridge is dispensed or used, the cartridge with its printhead is discarded or disposed of rather than being refilled with a certain volume of reagent. The reagent cartridge may contain (or be supplied with) 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. Referring to Figure 16, the reagent cartridge 117 comprises an outer shell or body 1171 having a substantially rectangular shape, constructed from a plastic material (e.g., rigid plastic or polymer). Figure 16 shows that the reagent cartridge 117 comprises a side 1172 and an opposing side 1173 representing the yz dimension, and a side 1174 and an opposing side 1175 representing the xy dimension. Side 1174 contacts and engages with the carousel 115. The reagent cartridge 117 includes a printhead 1178 that can be operated to eject reagent from the cartridge. The printhead 1178 may be located on or near the nose or base 1179 (bottom side in the illustrated configuration) of the reagent cartridge 117 so that when the reagent cartridge is inserted into the carousel 115, the ejection of reagent occurs through the base 1179 of the reagent cartridge. The portion of the nose or base 1179 containing the printhead 1178 (printhead region) may extend in a stepped manner downward from the rest of the base 1179. The printhead 1178 of the reagent cartridge 117 includes a nozzle or array of nozzles from which reagent is ejected or discharged by a thermal inkjet process. A typical array of nozzles is a linear array of nozzles (e.g., one or more rows) that can discharge reagent in a single line or row across a slide, for example.In a thermal inkjet printhead, heat may be used to create bubbles of reagent vapor, which may then explode as they pass through the printhead nozzles. Each nozzle may have a diameter of 20 to 80 microns, for example, 20 to 50 microns.

[0046] The reagent cartridge 117 also includes a contact 1170 on its side 1174. The contact 1170 is designed to mate with a contact in a dot associated with a carousel (see Figure 18 and related text). The contact 1170 allows the reagent cartridge to be controlled by the control unit 109, for example, with respect to the discharge or ejection of reagent through the nozzle and the amount of reagent discharged.

[0047] The reagent cartridge 117 shown in Figure 16 is equipped with a pair of transfer guides on each of its sides 1172 and 1173. While the transfer guide on side 1172 has been described, it should be understood that the transfer guide on side 1173 is similar. The transfer guide 1176 has a substantially rectangular solid structure, for example, made of plastic material, and has a width W1 that extends across the width of side 1172 parallel to the upper surface of the reagent cartridge 117. The transfer guide 1176 has a thickness T1 and length L1 sufficient to support the reagent cartridge 117 within the storage rack 106. Typical thickness T1 is approximately 0.2 mm to 1 mm, and typical length L1 is approximately 3 mm to 10 mm. The transfer guide 1176 is equipped with an engaging projection 11762 that protrudes vertically upward when viewed from above. As shown, the transfer guide 1176 is connected to the body 1171 (e.g., via adhesive) or is a portion of the body 1171 at a distance from the top of the side 1172 such that the entire transfer guide 1176, which includes the engaging projection 11762 as shown, is below the upper surface of the reagent cartridge 117. The transfer guide 1177 is connected to the body 1171 of the reagent cartridge 117 (e.g., via adhesive) or is a portion of the body 1171 located below the transfer guide 1176 as shown. The transfer guide 1177 has a width W2 extending across the width of the side 1172 parallel to the upper surface of the reagent cartridge 117, and has a thickness T2 and length L2 sufficient to support the reagent cartridge 117 in the storage rack 106. A typical thickness T2 is similar to the thickness T1 of the transfer guide 1176, for example, about 0.2 mm to 1 mm, and a typical length L2 is about 3 mm to 8 mm. The transfer guide 1177 is positioned parallel to the transfer guide 1176 along the side 1172, and is separated from the transfer guide 1176 by a gap L3 sufficient for the arms of the cartridge support to slide between the transfer guides. The transfer guides 1176 and 1177 may each have a rounded or curved front end (the end closest to the side 1174 of the reagent cartridge 117) to assist in positioning the arms of the cartridge support between the transfer guides.The base of the transfer guide 1177 also includes a notch or docking groove 11772 and a thin-walled section 11774 (with a thickness less than a certain thickness, t2) extending from the front end of the transfer guide to a point just ahead (1 mm or 2 mm ahead) of the notch or docking groove 11772. The thin-walled section 11774 may have a side wall angled backward from the top of the transfer guide 1177 toward the base. Finally, the reagent cartridge 117 includes a frame locking bump 11792, which is a triangular prism with a triangular base parallel to the sides 1172 and 1173, respectively. The transfer guides 1176, 1177, and 11792 may each be made from a rigid plastic material, either attached to the reagent cartridge 117 by, for example, adhesive, or being part of the reagent cartridge 117 formed by, for example, a molding process.

[0048] Figure 17 shows a perspective front right side view of a portion of the storage rack 106. In this figure, the storage rack 106 includes a cartridge frame support 1064 extending between vertical columns 1063. The storage rack 106 is mounted on the housing 102 with its slots facing the reaction compartment 104 and the carousel 115. The cartridge frame support 1064 is an L-shaped body, with the base 10642 of the L-shaped body facing outwards. The base 10642 of the frame support 1064 has a pair of openings or holes 1065 that pass through the base 10642, which are used to secure reagent cartridges to the frame support 1064. Figure 17 shows reagent cartridges 117A and 117B connected to the cartridge frame support 1064. The reagent cartridges are connected to the cartridge frame support 1064 using cartridge frames. Figure 17 shows cartridge frame 1060B supporting reagent cartridge 117B, and cartridge frame 1060C connected to cartridge frame support 1064 but not supporting a reagent cartridge. Note that a separate cartridge frame supports reagent cartridge 117A, but such a cartridge frame is obscured from view.

[0049] Each cartridge frame (e.g., cartridge frame 1060B and cartridge frame 1060C) includes a shoulder portion 10602, which is a relatively thin (e.g., 1 mm to 3 mm) rectangular body having an x-length greater than the width of the reagent cartridge. The shoulder portion 10602 has two openings or holes 10605, which align with a pair of openings or holes 1065 in the base 10642 of the frame support 1064, allowing the shoulder portion 10602 to connect to the base 10642 of the cartridge frame support 1064 via the use of a pin 10603. The pin 10601 is, for example, an expander pin (e.g., plastic) having a distal end protruding from the cartridge frame and a body, the distal end being operable to slide into the opening or hole 1065, and the body having a diameter similar to or larger than the opening or hole to secure the pin by applying force in the direction of the base 10642 of the cartridge frame support 1064. Pin 10601 may be a captive pin (meaning the pin is permanently fixed to the cartridge frame) or it may be freely introduced into both the shoulder portion 10602 of the cartridge frame and the base portion 10642 of the cartridge frame support portion 1064. Each cartridge frame (e.g., cartridge frame 1060B and cartridge frame 1060C) is designed to be removable from the base portion 10642 of the cartridge frame support portion 1064 by the use of similar but opposite forces required to insert the pin.

[0050] The two arm sections 10603 project vertically (in the x-direction) from the shoulder section 10602 in the illustrated configuration. Each arm section 10603 has dimensions (e.g., height in the y-direction and thickness in the x-direction) such that it can be positioned between the transfer guides 1176 and 1177 on each side of the reagent cartridge, allowing the reagent cartridge to slide in and out of the cartridge frame. The arm sections 10603 are spaced apart from each other by a distance slightly greater than the width of the reagent cartridge (e.g., if the reagent cartridge is 6 mm wide, the arm sections 10603 are spaced 6.3 mm to 7 mm apart from each other). The length (in the z-direction) of the arm sections 10603, measured from the shoulder section 10602, is less than the depth of the reagent cartridge, for example, approximately half the depth of the reagent cartridge. Projecting vertically downward (in the y-direction) from the shoulder section 10602 in the illustrated configuration, each cartridge frame is equipped with a spine section 10606. The spine portion 10606 has a typical width of approximately 1 mm to 4 mm (x direction), a thickness of approximately 0.4 mm to 0.5 mm (z direction), and a length (y direction) that is longer than the height of the portion of the reagent cartridge measured between the base of the reagent cartridge located behind the printhead area and the bottom of the transport guide 1177 above it (e.g., 1 mm to 2 mm longer). The leg portion 10607 protrudes perpendicularly (z direction) from the base of the spine portion 10606. The shape at the interface between the spine portion and the leg portion may reflect the posterior side wall and the transition area of ​​the base of the reagent cartridge. In Figure 17, the posterior side wall and the transition area of ​​the base of the reagent cartridge 117B are curved, and the interface between the spine portion and the leg portion defines an opposite contour. The leg portion 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 a length (z-direction) that extends to the length of the base of the reagent cartridge excluding the print head area. A raised portion 10608 is positioned along a portion of the length dimension of the leg portion 10607, and the raised portion 10608 typically protrudes upward by 0.2 mm to 0.6 mm from the surface of the leg portion 10607, and has a typical triangular prism shape with a triangular base on the yz surface.The raised portion 10608 is positioned on the leg portion 10607 at a distance from the spine portion 10606 that is greater than the distance from the rear side of the reagent cartridge (reagent cartridge 117, Figure 16) to the front edge of the frame locking bump 11792, such that when the reagent cartridge is placed in the cartridge frame (for example, reagent cartridge 117B in cartridge frame 1069B), the raised portion 10608 is in front of the frame locking bump protruding from the base of the cartridge. The pad platform 10609 is connected to the end of the leg portion 10607 of the cartridge frame. The pad platform 10609 may be a rectangular body having a rectangular surface or top (xz plane) larger than the print head area. The typical area (xz dimension) of the pad platform is approximately 225 mm² to 400 mm². An absorbent material (e.g., sponge) may be placed on the surface or top of the pad platform 10609 that can contact the printhead of the reagent cartridge, receive runoff from the printhead (e.g., excess reagent on the surface of the printhead), and protect the printhead from drying out.

[0051] The main body of the cartridge frame (e.g., cartridge frame 1060B, cartridge frame 1060C) may be made of a rigid plastic material. Referring to Figure 17, the spine portion 10606 and the leg portion 10607 may have dimensions (e.g., thickness, width) and / or connections (e.g., 90° joints) that provide spring tension to the leg portion 10607 so that the leg portion 10607 can move when the reagent cartridge is connected to or removed. As described above, the reagent cartridge is equipped with a frame locking bump 11792 protruding from its base (see reagent cartridge 117, Figure 16). When the reagent cartridge is placed within the cartridge frame (i.e., in response to a force applied to the reagent cartridge toward the spine portion 10606 of the cartridge frame), the arm portion 10603 of the cartridge frame slides between the transport guides 1176 and 1177 on opposite sides of the cartridge until the frame locking bump 11792 at the base of the reagent cartridge contacts the projection 10608. If the force continues to be applied toward the spine portion 10606, the leg portion 10607 moves downward (due to the force of the frame locking bump 11792 on the leg portion), causing the projection 10608 to move downward, and the frame locking bump 11792 to pass over the projection 10608. Once the frame locking bump 11792 has passed over the projection 10608, the leg portion 10607 returns to its original position (moves upward), allowing the projection 10607 to secure or capture the reagent cartridge within the cartridge frame. Separating the reagent cartridge from the cartridge frame is achieved in a similar manner. When force is applied to the reagent cartridge away from the spine 10606, the leg 10607 moves downward (due to the force of the frame locking bump 11792 on the leg), causing the projection 10608 to move downward, and the frame locking bump 11792 to pass over the projection 10608.

[0052] Reagent cartridges (e.g., reagent cartridge 117A, reagent cartridge 117B) may be supplied as assemblies comprising the reagent cartridges and cartridge frames (e.g., cartridge frame 1060B, cartridge frame 1060C). The assemblies may be supplied to the consumer packaged together with the reagent cartridges in the cartridge frames, or they may be supplied separately with assembly instructions.

[0053] Referring to Figures 10, 14, 15, and 17, the arm assembly 118 may be used to move reagent cartridges in and out of the storage rack 106. For example, a reagent cartridge assembly (reagent cartridges connected to a cartridge frame) may be supplied to the reaction compartment 104 by an operator or robot (e.g., supplied to a platform 105 inside the reaction compartment 104). The control unit 109 includes non-temporary, machine-readable commands that instruct the operation of various motors (e.g., direction of rotation, execution time, etc.) to move the carousel 115, which includes the arm assembly 118, to a position such that it grasps the supplied reagent cartridge assembly and places the reagent cartridge assembly in the storage rack 106. These motors include a motor 1143 that moves the carousel 115 in the x direction, a motor 11495 that moves the carousel 115 in the z direction, a motor 11425 that moves the carousel 115 in the y direction, and a motor 1157 that rotates the base 1152. Once the carousel 115 is positioned as desired, the machine-readable command also includes a command to instruct the arm assembly 118 connected to the carousel 115 to grasp the reagent cartridge assembly and transport the reagent cartridge assembly to the storage rack 106. The command may further include a command to place the reagent cartridge assembly at a predetermined address within the storage rack 106. The arm assembly 118 is equipped with a cartridge engagement head 1183 at its distal end. Based on a command from the control unit 109, the cartridge engagement head 1183 is operable to position itself above the reagent cartridge 117 so that a pair of finger portions extending from the cartridge engagement head 1183 surrounds and engages with the engagement projections 11762 of the transport guides 1176 on each side of the reagent cartridge 117 (see Figure 16). The pairs of finger portions on the cartridge engagement head 2183 of the arm assembly 218 (see Figure 14) may be spaced apart on opposing sides by a distance slightly smaller than the distance between the engagement protrusions 21762 on each side of the reagent cartridge 217.Typically, the pair of finger portions on the cartridge engagement head 2183 are biased toward their greater distance from each other, but can be bent outward to a greater distance to engage with the engaging projections 21762 on the opposing sides of the reagent cartridge 217. The biased nature of the opposing finger portions on the cartridge engagement head 2183 acts like a spring clamp, holding the reagent cartridge by the engaging projections 21762. To place the reagent cartridge assembly in the storage rack 106, the command instructs the arm assembly 118 to align the pin 10603 in the cartridge assembly with a pair of predetermined openings or holes 10605 in the base 10642 of the frame support 1064, and to apply sufficient force to the reagent cartridge assembly to insert into the corresponding pin in the base 10642 of the frame support 1064.

[0054] To transfer the reagent cartridge from the storage rack 106 to the carousel 115, the control unit 109 includes a machine-readable command to the arm assembly to position itself on the reagent cartridge (e.g., the front side of the reagent cartridge) and to grasp the reagent cartridge (via the cartridge engaging head 1183, which surrounds and engages with the projections 11762 of the transfer guide 1176 on each side of the reagent cartridge 117). At this point, the reagent cartridge assembly, comprising the reagent cartridge and the cartridge frame, is mounted on the storage rack 106. When the cartridge engagement head 1183 grips the engagement projections 11762 of the transport guides 1176 on each side of the reagent cartridge 117, the arm assembly 118 applies force away from the storage rack (and away from the spine 10606 of the cartridge frame), and the force of the frame locking bumps 11792 of the reagent container 117 applied to the legs 10607 causes the legs 10607 of the cartridge frame to flex (move downward), the projections 10608 to move downward, and the frame locking bumps 11792 to pass over the projections 10608. Once the cartridge is separated from its cartridge frame, commands associated with the control unit 109 instruct the arm assembly 118 to feed the cartridge into the carousel 115.

[0055] Figure 18 shows a portion of a carousel 115 comprising a pedestal or cartridge carrier plate 1152 separated from the base of a cylindrical section 1151. The pedestal or cartridge carrier plate 1152 is operable to engage with and accommodate a number of reagent cartridges. The pedestal 1152 has a typical decagonal shape with slots 1153 on each side for reagent cartridges. It should be understood that the shape and number of reagent cartridges that can accommodate the carousel may vary. Around each slot 1153 are docks 1154 protruding from the surface of the pedestal 1152 (the upper surface in the illustrated view). Figure 18 shows three docks 1154. It should be understood that the pedestal 1152 may have the same number of docks as slots. Each dock 1154 is configured to accommodate a reagent cartridge within it. Figure 18 shows a reagent cartridge 117 fixed to one dock 1154. Each dock 1154 comprises a back wall having an outer surface facing the center of the base 1152, and two opposing side walls connected to the back wall. The back wall slopes from top to bottom, with the bottom of the back wall close to the center of the base 1152. The side walls have a thickness td, which is less than the thickness of the transfer guides 1176 and 1177 on the reagent cartridge (see Figure 16). The upper portion of each side wall extends from the distal end of the side wall to a portion near the proximal end (near but not the back wall) and comprises a lateral slot 11542 defining an arm portion 11544. Each arm portion 11544 has dimensions such that it is positioned between the transfer guides 1176 and 1177 on the reagent container 117 and can support the reagent container. The dock 1154 with the arm portions 11544 may be constructed from a plastic (polymer) material.

[0056] The inner surface of the back wall of each dock 1154 is provided with a contact that mates with a contact 1170 on the reagent cartridge. The contact is electrically connected to the control unit 109, which allows the control unit 109 to individually control the reagent cartridges in each dock 1154 on the carousel 115.

[0057] In the illustrated configuration, cartridge locks 1155 are connected to the two opposing side walls of each dock 1154, located at a point below the arm portion 11544. The cartridge lock 1155 comprises two parallel arm portions 11552 separated by a shoulder portion 11554. The shoulder portion 11554 has a width similar to, or slightly greater than, the width of the dock 1154, so that the arm portions 11552 can be positioned outside and connected to the respective opposing side walls of the dock 1154. Figure 18 shows the arm portions 11552 connected to the side walls by pins 11555 (e.g., pins, screws, or rivets), such that the length of the portion of each arm portion 11552 from the shoulder portion 11554 to the pin 11555 (distal portion) is greater than the length of the portion of each arm portion 11552 from the pin 11555 to the proximal end (the end furthest from the shoulder portion 11554). The connection of the cartridge lock 1155 to the dock 1154 is such that the shoulder portion 11554 can pivot upward and downward without contacting the rear wall of the dock 1154 as shown (for example, the shoulder portion 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 substantially rectangular and protrudes perpendicularly from the shoulder portion 11554 in the proximal direction. The proximal portion of each arm 11552 may protrude upward from the distal portion at an angle 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 substantially rectangular and may have a proximal end having a projection 11556, which is an upwardly projecting triangular prism with a triangular base parallel to the side of each arm. The projection 11556 is sized to fit into a notch or docking groove 11772 within the reagent cartridge transfer guide 1177 (see Figure 16). The cartridge lock 1155 may be spring-driven at each of the pins 1155 so that the shoulder portion is closer to the surface of the base 1152. In this configuration, at least a portion of the projection 11556 extends above the base of the notch defining the arm portion 11544 of each dock 1154.When a downward force is applied to the protrusion 11556, the protrusion moves downward and the shoulder moves upward. Releasing this downward force causes movement in the opposite direction.

[0058] A slide identification reader and / or imager, such as a camera, may be connected to the base or cartridge carrier plate 1152. Typically, instead of a dock and cartridge, the slide identification reader / imager may be placed in one of the slots 1153. Alternatively, the slide identification reader / imager may be connected to the underside of the carrier plate 1152. The slide identification reader may be oriented to read identifiers (e.g., labels (e.g., barcodes)) on the microscope slide when the microscope slide is visible inside or outside the chamber 125 of the main body 120 (e.g., when the lid 130 moves to the open position and the tray 180 moves to a third or fourth position (see Figures 7C and 7D)), while the imager may be oriented to capture images of the microscope slide (e.g., an image of the entire microscope slide, an image of identifiers on the microscope slide (e.g., for subsequent reading by, for example, the control unit 109), and / or an image of the sample on the microscope slide). The reading of identifiers on the microscope slide may be controlled by a control unit 109 which can instruct that identifiers on the microscope slide be read by a slide identification reader and / or that images of the identifiers be captured by an imager. Typically, the control unit 109 may determine the processing protocol for the sample on the microscope slide by reading or capturing an image when the microscope slide is first placed in the reaction station, and then reading the identifiers on the microscope slide. Image capture may be controlled by the control unit 109 by commands such as capturing an image of the identifiers on the microscope slide before the microscope slide is first moved into the chamber 125, or capturing an image of the sample on the microscope slide after the dewaxing operation, determining the position of the sample on the microscope slide (e.g., by detecting the sample (e.g., a stained sample)), and then determining where to distribute the reagents (e.g., primary reagents) and / or after the primary staining operation.

[0059] Referring again to Figures 10, 14, and 18, the transfer of reagent cartridges by the arm assembly 118 from the storage rack 106 or from the platform 105 inside the housing 102 is described. The control unit 109 includes non-transient machine-readable commands that include commanding the arm assembly 118 to engage a reagent cartridge (e.g., reagent cartridge 117) with the cartridge engagement head 1183 of the arm assembly engagement projection 11762 on the reagent cartridge transfer guide 1176. Such commands also include commands that transport the reagent cartridge to one of the docks 1154 on the base 1152 of the carousel 115, aligning the reagent cartridge transfer guides 1176 and 1177 with one arm portion 11554 of the dock 1154 (aligning the transfer guides 1176 and 1177 above and below each arm portion 11554, respectively). Once aligned, the command further includes instructions to slide the reagent cartridge into the arm portion 11554 (proximal to distal) so that the nose or base 1179 of the reagent cartridge 117 faces inward (for example, facing the center of the base 1152). The arm assembly 118 applies sufficient force toward the center of the base 1152 to slide the reagent cartridge into the arm portion 11554. The transport guide 1177, having a thickness td greater than the thickness t2 of the transport guide 1177, contacts the proximal portion of each arm portion 11552 of the cartridge lock 11555, rotating each arm portion around each pin 11555 and pushing the proximal portion of the arm portion downward. When the portion of the transport guide 1177 equipped with the dock locking groove 11772 is directly above the projections 11556 of each arm portion 11552 of the cartridge lock 1155, the biasing of the cartridge lock causes each arm portion 11552 of the cartridge lock 1155 to rotate in opposite directions around the pin 11555, engaging the projections 11556 with the locking groove 11772. At this point, the reagent cartridge is secured to the dock 1154, and commands associated with the control unit 109 instruct the arm assembly 118 to release its engagement with each engaging projection 11762.

[0060] Before a reagent cartridge is sent to a dock (dock 1154) on the carousel 115 for a dispensing operation, or before it is returned from the dock to the storage rack 106, the reagent cartridge may be directed to a service station. Figure 1 shows a service station 1190 adjacent to the storage rack 106, mounted on the rear side wall of the reaction compartment 104 in the illustrated configuration. The service station 1190 provides an area on the printhead of the reagent cartridge that can be inspected and cleaned before and / or after use in a dispensing operation for dispensing reagents from the reagent cartridge onto a microscope slide. Figure 19 shows a front view of the service station 1190. In this example, the service station 1190 includes a rear wall 11901. Pulley supports 11903 and 11904 are connected to the rear wall 11901. Pulley supports 11903 and 11904 each include an upper roller and a lower roller, respectively. Belt 11905 is positioned on the upper rollers of pulley support 11903 and pulley support 11904, respectively. Belt 11906 is positioned on the lower rollers of pulley support 11903 and pulley support 11904, respectively. Rail 11902 is positioned between and connected to pulley support 11903 and pulley support 11904, respectively. Carriages 11907 and 11908 are slidably connected to rail 11902 and belts 11905 and 11906. Carriages 11907 and 11908 may each have a configuration for securing reagent cartridges similar to that of dock 1154 (see Figure 18).

[0061] In the example shown in Figure 19, carriage 11907 has a length L1 and width W1 (e.g., L1 is 100 mm and W1 is 60 mm) for a first-size reagent cartridge, and carriage 11908 has a length L1 and width W1 (e.g., L2 is 72 mm and W2 is 60 mm) for a second-size reagent cartridge. Note that the service station 1190 may have only one carriage, or if it has multiple carriages, the carriages may accommodate reagent cartridges of the same or different lengths and widths. The base or rear side of carriages 11907 and carriage 11908 in their respective illustrated states are equipped with electronic contacts or pins that can be operated to mate with the receiving portion (contact 1170) on the front side of the reagent cartridge, as well as the inner surface of the rear wall of each dock 1154 of the carousel 115, which has contacts that mate with the contact 1170 on the reagent cartridge. Figure 19 shows the contact or pin 11914 of carriage 11907 and the contact or pin 11915 of carriage 11908.

[0062] In one example, the reagent cartridge (reagent cartridge 117) has dimensions of length and width that fit snugly within the carriage 11907 or carriage 11908. As described above with respect to Figure 18, the front of the reagent cartridge (reagent cartridge 117) is equipped with an electronic pin receptacle 12794 to mate with the electronic contacts or pins 11917 of the carriage 11907. The front of the reagent cartridge may also be equipped with two diagonally spaced alignment sockets or openings that align with the alignment pins 11917 in the carriage 11907 to assist in the alignment of the reagent cartridge within the carriage 11907 or carriage 11908.

[0063] Figure 19 shows carriages 11907 and 11908, respectively, connected to pulley supports 11903 and 11904 via belts 11905 and 11906. Belts 11905 and 11906 may move carriages 11907 and 11908 independently laterally or translationally along rail 11902. Such movement allows each carriage 11907 to transport the reagent container attached to it to a spitton 11909 and a wiping station (wiping station 11912 or wiping station 11913). The spitton 11909 provides a container for dispensing reagents into reagent cartridges in carriages 11907 and 11908. Wiping stations 11912 and 11913 may each be containers (e.g., rectangular containers that house a ribbon of a length between the rollers, with the ribbon exposed on the top or side of the container in the illustrated configuration). The ribbon has a first side which is cloth or a similar absorbent material. The width of the ribbon may be at least the same as the printhead of the reagent cartridge. The cloth or similar absorbent material provides an area for cleaning or wiping the printhead (e.g., excess reagent on the printhead). After the printhead of the reagent cartridge has wiped a portion of the ribbon, the ribbon may be advanced by a command from the control unit 109 that commands the movement of the rollers in the wiping station 11912 or 11913.

[0064] Each carriage may be electrically connected and communicate with the control unit 109. Carriages 11907 and 11908 are equipped with electronics for operating reagent cartridges similar to the electronics in dock 1154, and distribute reagents under the direction of non-transient machine-readable commands associated with the control unit 109. When a reagent cartridge is connected to carriage 11907 or carriage 11908, commands from the control unit 109 may, for example, instruct the distribution of reagents from the reagent cartridge in spitton 11909 and contact between the printhead of the reagent cartridge and the ribbon of wiping station 11912 or wiping station 11913.

[0065] In the operation of the service station, a command from the control unit 109 may instruct the movement of one of the carriages 11907 or carriage 11908 by belts 11905 and 11906 on the spitton 11909. At that time or around that time, a command from the control unit 109 may instruct the arm assembly 118 to engage with the reagent cartridge (e.g., reagent cartridge 117) and place the reagent cartridge in the moved carriage (e.g., carriage 11907). Further commands from the control unit 109 may then include an instruction to the electronics in carriage 11907 to distribute or discharge the amount of reagent in the reagent cartridge (e.g., enough to wet the print head and prevent it from clogging) into the spitton 11909. Following the dispensing operation, the control unit 109 may instruct the reagent cartridge to be carried to the wiping station 11912 or 11913 and to be cleaned of any residual reagent on the printhead of the reagent cartridge by a wiping operation with the printhead on the ribbon of the wiping station. After wiping, the control unit 109 may instruct the arm assembly 118 to engage the reagent container and to supply the carousel 115 to the dock (dock 1154) or to the storage rack 106 for the dispensing operation.

[0066] The above discussion describes reagent distribution technology using inkjet technology. This distribution alternative involves a distribution cartridge connected to a cartridge pump assembly, which pumps the reagent from the distribution cartridge onto the sample. Another distribution alternative is pipetting from a reagent container to the sample.

[0067] The following describes a typical operation of the sample processing system, with reference to Figures 1-18. First, individual microscope slides, each containing at least one tissue sample, are transported to the reaction compartment 104 by an operator or robot. Each slide is placed individually in a reaction station (reaction station 112). Non-transient machine-readable commands from the control unit 109 may instruct each reaction station 112 and its associated motor to drive their respective gears 155 to open the lids (lids 130) of the reaction compartments. Additional non-transient machine-readable commands from the control unit 109 may then instruct the base (base 185) of each reaction compartment to raise the tray (tray 180) inside the reaction compartment to a third or fourth position (see Figures 7C and 7D) to receive the slides from the operator or robot. The slides may be placed with the tissue sample side facing upwards (orientation of the lid 130). When a slide is placed on the tray 180, non-transient machine-readable commands from the control unit 109 may instruct either the slide identification reader to read the identifier on the microscope slide, or the control unit 109 to read the image of the identifier by an imager (e.g., a slide identification reader / imager connected to the base 185 or cartridge carrier plate 1152). Further commands may then instruct the base to lower the tray to, for example, a second position, and the motor 180 to close the lids 130 of each reaction station 112. Typically, the control unit 109 may determine the processing protocol for the sample on the microscope slide by reading the image, or by capturing the image and then reading the identifier.Commands from the control unit may instruct the reading of the identifier of each of the multiple slides in each reaction station (reaction station 112) of the sample processing system before processing of any of the multiple slides begins, or processing may begin for each sample on a microscope slide once the identifier on that microscope slide has been read, either independently or regardless of whether an identifier on another microscope slide in the reaction station of the sample processing system has been read. By proceeding with the processing of microscope slides in each reaction station independently, for example, microscope slides can be loaded into a reaction station and processing can begin while samples on other microscope slides housed in other reaction stations in the sample processing system are already being processed.

[0068] Microscope slides containing tissue samples delivered to reaction compartment 104 may be embedded in an embedding agent (e.g., paraffin) or processed to remove the embedding agent and adhere the tissue sample to the slide (i.e., pre-treated to remove paraffin and adhere the tissue sample to the slide). When slides with tissue samples embedded in an embedding agent such as paraffin are delivered to reaction compartment 104, non-transient machine-readable commands from control unit 109 may instruct the system to perform adhesion and deparaffinization (dewaxing) protocols on the embedded tissue sample. Typically, the command may instruct the slide containing the embedded tissue sample to be heated using the slide heating unit 1802 as part of a firing operation. The heat treatment must be sufficient to adhere the sample on the slide to the slide (glass slide), or to further adhere it, and, where possible, to soften the embedding medium associated with the section on the slide. Typically, the slide may be heated to a temperature of approximately 55°C to 70°C.

[0069] After heat treatment, the command may instruct the slide heating unit 1802 to be turned off and the embedded tissue sample on the slide to be exposed to a dewaxing solution such as xylene in a volume sufficient to cover the sample portion of the slide. The dewaxing solution such as xylene may be stored as a bulk reagent in a container in a storage compartment 101 located below the reaction compartment 104 (see Figure 1). The dewaxing solution container may be connected to a fluid connector 131 on the lid 130 of the reaction compartment containing the embedded tissue sample on the slide. Commands associated with the control unit 109 may instruct the dewaxing solution to be transferred (e.g., pumped) from the dewaxing solution container to the respective fluid connectors 131 and onto the surface of the slide in the reaction compartment. After the distribution of the dewaxing solution, commands associated with the control unit 109 may instruct the tissue sample to be immersed in the dewaxing solution for a certain period of time (e.g., 1 to 5 minutes). After the immersion time, commands associated with the control unit 109 may instruct the base 185 to move the tray 180 containing the slide to a first position. In the first position, the slide is tilted or flexed to a non-horizontal position within the reaction compartment to remove the dewaxing solution and paraffin from the surface of the slide (see, for example, Figure 8). After the period for removing the waxing solution and paraffin from the surface of the slide, further commands associated with the control unit 109 may instruct the base 185 to move the slide to a second or third position within the reaction compartment. Further commands associated with the control unit 109 may instruct the valve associated with the drain 121 to open and discharge the dewaxing solution into, for example, a waste container in the storage compartment 101.

[0070] 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 xylene treatment and subsequent removal, the dewaxing protocol may specify exposing the tissue sample to alcohol (e.g., ethanol). In such a case, the container containing xylene is connected to a first fluid connector 131 on the lid 130 of the reaction compartment, and the container containing alcohol is connected to a second fluid connector 131 on the lid 130.

[0071] Furthermore, the dewaxing process may be carried out at high humidity. Typically, the control unit 109 may instruct that a fluid such as water (e.g., heated water) be introduced into the reservoir portion of the chamber 125 (below the tray 180 if the tray 180 is in the lowest position (first position) in the chamber) before the tissue sample on the slide is exposed to a certain volume of dewaxing solution or before performing a protocol of two or more consecutive reagents, or before or after one of the reagents if the tissue sample is exposed to a certain volume of two or more consecutive reagents. The control unit 109 may also further control the discharge of the reservoir to remove the fluid after the dewaxing process, which involves an increase in humidity.

[0072] After the dewaxing process, commands associated with the control unit 109 may instruct the tissue sample to be rinsed with a certain volume of washing solution (e.g., water or other aqueous washing solution). The washing solution may be supplied to the tissue sample by connecting a container containing the washing solution to a fluid connector (fluid connector 131) on the lid 130 of the reaction compartment. The washing solution may also contain a certain amount of a staining agent, such as eosin, to stain the sample on the slide. Generally, following the dewaxing operation, the embedding material in the section is removed, and the sample remains on the slide as a substantially colorless object. Adding a certain amount of a staining agent, such as eosin, to the washing solution may allow the presence and position of the sample on the slide to be detected. After the washing process, commands associated with the control unit 109 may instruct the base 185 to move the tray 180 containing the slide to a first position. In the first position, the slide is tilted or flexed to a non-horizontal position within the reaction compartment to remove the washing solution from the surface of the slide. Further commands related to the control unit 109 may instruct it to open the valve associated with the drain 121 and discharge the cleaning solution into the waste container.

[0073] After the washing process and, if possible, the acquisition of images of the sample and identifier, commands associated with the control unit 109 may instruct the base 185 to move the tray 180 containing the slide to a second or third position, and then to perform an antigen retrieval process on the tissue sample to reverse the antigen masking effect by aldehyde fixation. A container containing an antigen retrieval solution, such as a Tris-based or citrate-based retrieval solution, may be stored as a bulk reagent in a storage compartment 101 below the 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. Commands associated with the control unit 109 may also instruct the antigen retrieval solution to be provided to the surface of the tissue sample. Commands associated with the control unit 109 may also instruct the antigen retrieval process to be performed at high temperature and, optionally, high pressure. Typically, commands may instruct the slide containing the tissue sample to be heated to a temperature of approximately 100°C to 121°C using the slide heating unit 1802. The command may further instruct the reaction compartment to be subjected to high pressure, for example, 1.0 atmosphere (atm) (15 pounds / square inch (psi) to 1.7 atm (25 psi)), by introducing air or an inert gas into the reaction compartment via a fluid connector (fluid connector 131) (for example, by introducing air or an inert gas from a compressed air or inert gas source connected to the fluid connector). By utilizing high pressure, the antigen retrieval process can be reduced to, for example, 5 minutes, compared to the conventional process time of 45 minutes or more under atmospheric pressure conditions.

[0074] Furthermore, the antigen retrieval process may be carried out at high humidity, for example, at a relative humidity of 70% to 100%. Typically, commands from the control unit 109 may instruct that a fluid, such as water (e.g., heated water), be introduced into the reservoir portion of the chamber 125 before the tissue sample on the slide is exposed to a certain volume of antigen retrieval solution. Commands from the control unit 109 may also control the discharge of the reservoir to remove the fluid after the antigen retrieval process, which involves increased humidity. For example, the control unit 109 may instruct that the valve associated with the drain 121 be opened to discharge the fluid in the reservoir into a waste container before or simultaneously with the discharge of the antigen retrieval solution by tilting the tray 180.

[0075] Once the antigen retrieval process is complete, commands associated with the control unit 109 may instruct the base 185 to move the tray 180 containing the slides to a first position. In the first position, the slides tilt or flex to a non-horizontal position within the reaction compartment to remove the antigen retrieval solution from the surface of the slides. Subsequently, additional commands may instruct the base 1985 to return the tray to a second or third position. Further commands associated with the control unit 109 may instruct the valve associated with the drain 121 to open and discharge the antigen retrieval solution into the waste container. Further commands may then instruct the tissue sample to be rinsed with a certain volume of washing solution, e.g., water or washing buffer, e.g., TBS or phosphate-buffered saline containing a surfactant. After washing, commands associated with the control unit 109 may instruct the base 185 to move the tray 180 containing the slides back to the first position. In the first position, the slides tilt or flex to a non-horizontal position within the reaction compartment to remove the washing solution from the surface of the slides. Subsequently, additional instructions may be given to the base 1985 in preparation for the staining process to return the tray to a second or third position. Further instructions related to the control unit 109 may be given to open the valve related to the drain 121 to discharge the washing solution into the waste container.

[0076] In the staining process, commands associated with the control unit 109 may instruct a motor associated with the reaction station 112, which contains the slide with the sample ready for staining, to drive the corresponding gear 155 to open the lid (lid 130) of the reaction compartment. Further commands from the control unit 109 may then instruct the pedestal (pedestal 185) of the reaction compartment to raise the tray (tray 180) within the reaction compartment to a fourth position where the tray 180 and / or the slide on it are outside the chamber (chamber 125) (see Figure 7D). If not previously done, further commands from the control unit 109 may instruct the position of the sample or portion of it on the microscope slide for staining to be determined based on the captured image of the sample on the microscope slide after the washing operation.

[0077] In preparation for the staining process, before or after raising the slide, commands associated with the control unit 109 may instruct the removal of a reagent cartridge from the storage rack 106 and the loading or docking of the reagent cartridge in one of the docks 1154 on the base 1152 of the carousel 115. Further commands associated with the control unit 109 may instruct the loaded reagent cartridge, positioned on the base 1152 with the nose or base portion of the reagent cartridge, to be positioned over the tissue sample on the raised slide. Such commands include instructing the motor 1157 to rotate the cylindrical portion 1151, and accordingly rotate the base 115 and motor 1143, thereby moving the carousel 115 longitudinally. Once positioned, commands may instruct the reagent from the reagent cartridge to be dispensed (printed) onto the sample at a predetermined position on the sample or a portion thereof. Typically, a drop-on-demand printhead, such as a thermal printhead in a reagent cartridge, may dispense reagents such as detection agents or antibodies in droplets having volumes of 1 picoliters (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, an inkjet cartridge can supply at least 15 microliters (μL) per square inch (at least 15 μL) per pass, where a pass is the dispensing (ejection) of reagent from multiple nozzles in the inkjet cartridge's printhead, either while the reagent cartridge (carousel) and slide are stationary, or while at least one of the reagent cartridge (carousel) and slide moves in one direction to expand the dispensing area on the slide. Typically, the control unit 109 instructs the print head of the reagent cartridge to distribute multiple droplets (i.e., multiple droplets from multiple nozzles) to generate a larger volume of reagent per pass.Typical feed rates passing through a thermal inkjet printhead include 15 μL to 30 μL / square inch per pass, 15 μL to 25 μL / square inch per pass, and 15 μL to 20 μL / square inch per pass.

[0078] After the staining process, commands associated with the control unit 109 may instruct the reagent cartridge and carousel to move from their positions above the slides, the reaction compartment base (base 185) to lower the tray (tray 180) containing the stained slides to a second or third position inside the chamber (chamber 125), and to close the reaction compartment lid (lid 130). Additional commands associated with the control unit 109 may instruct the incubation period of the sample on the slides to be extended (for example, to allow the primary antibody to bind to the target antibody). After the incubation period, commands associated with the control unit 109 may instruct the tissue sample to be rinsed with a certain volume of washing solution to remove unreacted / unconjugated reagents. After rinsing, commands associated with the control unit 109 may instruct the base 185 to move the tray 180 containing the slides to a first position. In the first position, the slides are tilted or flexed to a non-horizontal position within the reaction compartment to remove the washing solution from the surface of the slides. Subsequently, additional instructions may be given to the base 1985 to return the tray to a second or third position in preparation for any additional staining processes. Further instructions related to the control unit 109 may be given to open the valve related to the drain 121 to discharge the washing solution and excess stain into the waste container.

[0079] Once the staining process for the tissue sample on the slide is complete, commands associated with the control unit 109 may instruct the system to alert the user that the slide is ready to be removed. Subsequently, additional commands from the control unit 109 may instruct the reaction compartment base (base 185) to raise the tray (tray 180) within the reaction compartment to a fourth position where the tray 180 and / or the slide on it are outside the chamber (chamber 125), so that an operator or robot can remove the slide.

[0080] Furthermore, the staining process may be carried out at high humidity, for example, at a relative humidity of 70% to 100%. Typically, commands from the control unit 109 may instruct that a fluid, such as water (e.g., heated water), be introduced into the reservoir portion of the chamber 125 before one or more stains are performed on the tissue sample on the slide. Commands from the control unit 109 may also control the discharge of the reservoir to remove the fluid after the staining process, which involves an increase in humidity. For example, the control unit 109 may instruct that the valve associated with the drain 121 be opened to discharge the fluid in the reservoir into a waste container before or simultaneously with tilting the tray 180 to discharge excess stain. The staining process may also be carried out under high pressure. Commands related to the control unit 109 may also instruct the reaction compartment to be subjected to high pressure, for example, 1.0 atmosphere (atm) (15 pounds / square inch (psi) to 1.7 atm (25 psi)), by introducing air or an inert gas into the reaction compartment via a fluid connector (fluid connector 131) (for example, introducing air or an inert gas from a compressed air or inert gas source connected to the fluid connector) before staining the tissue sample. manner

[0081] This specification includes the following embodiments:

[0082] 1. A carousel having multiple mounting stations sized to accept at least one fluid distribution cartridge, A receiving assembly located beneath the carousel and comprising multiple reaction stations, Each of the above-mentioned multiple reaction stations, The main body has length and width dimensions that together define a chamber for housing a single slide, A system comprising a lid having a first position that covers the chamber and a second position that exposes a portion of the chamber.

[0083] 2. The system according to embodiment 1, wherein each of the multiple reaction stations is provided with a slide support, the slide support including a first depth within the chamber and a different second depth within the chamber.

[0084] 3. The system according to embodiment 2, wherein when the lid of one of the reaction stations is in a second position, the sliding support of one of the reaction stations is operable to move from a first depth to a second depth.

[0085] 4. The system according to embodiment 2, wherein each of the multiple slide support parts can be operated to rotate.

[0086] 5. The system according to any one of embodiments 2 to 4, wherein the slide support portion includes a heating unit.

[0087] 6. The system according to any one of embodiments 1 to 5, wherein the lid comprises an outer surface and an opposing inner surface, the outer surface comprises a plurality of hose connectors connected to the outer surface, the inner surface comprises a plurality of conduits connected to the inner surface, and each of the plurality of hose connectors is connected to each of the plurality of conduits.

[0088] 7. The system according to any one of embodiments 1 to 6, wherein the carousel is capable of linear translation in three dimensions.

[0089] 8. The system according to any one of embodiments 1 to 7, wherein the carousel is rotatable about a central axis.

[0090] 9. The system according to any one of embodiments 1 to 8, wherein the carousel and receiving assembly are housed within a housing, and the system further comprises a cartridge rack that can be operated to accommodate a plurality of fluid distribution cartridges.

[0091] 10. The system according to any one of embodiments 1 to 9, wherein the carousel is operable to remove a fluid distribution cartridge from the cartridge rack and return the fluid distribution cartridge to the cartridge rack.

[0092] 11. The system according to embodiment 10, wherein the carousel is capable of linear translation in three dimensions, and the cartridge rack is positioned within the housing relative to the carousel such that in order to remove or return a fluid distribution cartridge from the cartridge rack, the carousel must be translated into a first of the three dimensions.

[0093] 12. The system according to any one of embodiments 1 to 11, further comprising a refrigeration unit connected to a cartridge rack.

[0094] 13. Moving the lid of the reaction station of the processor assembly from a first position covering the reaction chamber to a second position where a portion of the reaction chamber is exposed, wherein the reaction chamber contains only a single microscope slide with a sample on the slide, and the reaction station is one of several reaction stations in the processing assembly. A carousel is translated over multiple reaction stations of a processing assembly, wherein the carousel comprises at least one of a slide identification reader and an imager connected to the slide identification reader. The slide identification reader reads identifiers on the microscope slide or reads images of identifiers, Based on the read identifier, the processing protocol for the sample on the microscope slide is determined, The process involves using a carousel to remove one or more reagent dispensing cartridges from a storage rack, each of which contains the reagents necessary to perform the processing protocol. Distributing one or more reagents onto a sample on a microscope slide, A method that includes this.

[0095] 14. The method according to embodiment 13, wherein the method includes reading the information provided for each of the multiple slides, and then moving the lid to a first position.

[0096] 15. The method according to embodiment 13 or embodiment 14, wherein the method includes moving the lid to a second position before dispensing one or more reagents onto a sample on a microscope slide.

[0097] 16. The method according to any one of embodiments 13 to 15, wherein the method includes raising a microscope slide in a chamber before distributing one or more reagents onto a sample on a microscope slide.

[0098] 17. The method according to any one of embodiments 13 to 16, wherein the method comprises distributing one or more reagents onto a sample on a microscope slide, and then returning one or more fluid dispensing cartridges to a storage rack by a carousel.

[0099] 18. The reaction station is a first reaction station, and at least one of a plurality of reaction stations contains a single microscope slide containing a sample and an identifier, and before distributing one or more reagents onto the sample on the microscope slide within the first reaction station, the method The slide identification reader reads identifiers on microscope slides in at least one of multiple reaction stations, or reads images of identifiers. The method according to any one of embodiments 13 to 17, comprising determining a processing protocol for a sample on a microscope slide in at least one of a plurality of reaction stations based on an identifier read.

[0100] 19. The method according to any one of embodiments 13 to 18, wherein the distribution includes distribution by a thermal inkjet process.

[0101] 20. The method according to embodiment 19, wherein the dispensing comprises dispensing one or more reagents in an amount of at least 15 microliters (μL) per square inch per pass.

[0102] The present invention has been described in the aforementioned specification with reference to specific embodiments thereof. However, it will be apparent that various modifications and changes can be made without departing from the broad spirit and scope of the invention as described in the appended claims. For example, the reagent cartridges disclosed herein (e.g., reagent cartridge 408) may contain a solvent or water instead of a reagent and may be used for purposes other than, for example, staining a sample on a slide beneath them. Accordingly, this specification and the drawings should be considered illustrative rather than restrictive.

Claims

1. A carousel comprising multiple mounting stations sized to accept at least one fluid distribution cartridge, The system comprises a receiving assembly located beneath the carousel and comprising a plurality of reaction stations, Each of the above-mentioned multiple reaction stations, The main body has length and width dimensions that together define a chamber for housing a single slide, A system comprising a lid including a first position that covers the chamber and a second position in which a portion of the chamber is exposed.

2. The system according to claim 1, wherein each of the plurality of reaction stations is provided with a slide support, the slide support includes a first depth within the chamber and a different second depth within the chamber.

3. The system according to claim 2, wherein when the lid of one of the plurality of reaction stations is in the second position, the slide support of 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 slide support portion comprises a heating unit.

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

6. The system according to claim 1, wherein the carousel is rotatable about a central axis.

7. The system according to claim 1, wherein the carousel and the receiving assembly are housed within a housing, and the system further comprises a cartridge rack that can be operated to accommodate a plurality of fluid distribution cartridges.

8. The system according to claim 7, wherein the carousel is operable to remove a fluid distribution cartridge from the cartridge rack and return the fluid distribution cartridge to the cartridge rack.

9. The system according to claim 8, wherein the carousel is capable of linear translation in three dimensions, and the cartridge rack is positioned within the housing relative to the carousel such that in order to remove a fluid distribution cartridge from the cartridge rack or return it to the cartridge rack, the carousel must be translated into a first of the three dimensions.

10. The system according to claim 9, further comprising a refrigeration unit connected to the cartridge rack.

11. Moving the lid of a reaction station, which is one of several reaction stations in a processing assembly, from a first position covering a reaction chamber containing only a single microscope slide with a sample on the slide, to a second position where a portion of the reaction chamber is exposed, Translating a carousel comprising at least one of a slide identification reader and an imager connected to the slide identification reader, over the plurality of reaction stations of the processing assembly, The slide identification reader reads an identifier on the microscope slide, or reads an image of the identifier. Based on the identifier read, a processing protocol for the sample on the microscope slide is determined, The carousel retrieves one or more reagent dispensing cartridges from a storage rack, each containing the reagents necessary to perform the processing protocol. Distributing one or more reagents onto the sample on the microscope slide, A method that includes this.

12. The method according to claim 11, wherein after reading the information provided for each of the plurality of microscope slides, the method includes moving the lid to a first position.

13. The method according to claim 11, wherein the method includes moving the lid to a second position before distributing the one or more reagents onto the sample on the microscope slide.

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

15. The method according to claim 11, wherein, after distributing the one or more reagents onto the sample on the microscope slide, the method further includes returning the one or more fluid dispensing cartridges to the storage rack using the carousel.

16. The reaction station is a first reaction station, and at least one of the plurality of reaction stations includes a single microscope slide containing a sample and an identifier, and before distributing the one or more reagents onto the sample on the microscope slide within the first reaction station, the method is performed The slide identification reader reads the identifier on the microscope slide in at least one of the plurality of reaction stations, or reads an image of the identifier. The method according to claim 11, comprising determining a processing protocol for the sample on the microscope slide in at least one of the plurality of reaction stations based on the identifier read.

17. The method according to claim 11, wherein the distribution is carried out by a thermal inkjet process.

18. The method according to claim 17, wherein the dispensing comprises dispensing one or more reagents in an amount of at least 15 microliters (μL) per square inch per pass.

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