Advanced tissue staining system and method with humidity controller

Abstract

A sample processor includes: a body including an inner surface defining a chamber having an opening in a side of the body and including a volume therein for receiving at least one microscope slide; a door including a first position covering the opening of the body and a second position exposing a portion of the chamber through the opening; a slide bed disposed in the chamber; an internal humidity generator disposed in the chamber and one of an external humidity generator coupled to the chamber. A system includes at least one sample processor, at least one reagent outside the body of the at least one sample processor, and a method comprising: subjecting a sample on a microscope slide in a sealed chamber to pressure greater than ambient and humidity greater than 60%; and processing the sample.

Description

Technical Field

[0001] An automated system for depositing reagents on biological samples. Background Technology

[0002] In various settings, biological samples require processing and testing for diagnostic purposes. Generally, pathologists and other diagnostic physicians collect and study samples from patients, examining them under a microscope and evaluating them at the cellular level using other equipment. The pathological and other diagnostic processes typically involve numerous processing steps, including collecting biological samples such as blood and other specimens, preparing samples, preparing microscope slides, staining the samples on the microscope slides, examining them, retesting or restaining them, collecting additional samples, re-examining the samples, and ultimately providing a diagnostic result.

[0003] Sample (e.g., specimen) staining processors or staining machines can operate at varying levels of automation to process human or animal specimens for histological or pathological purposes. Various types of chemical reagents can be used at different stages of specimen processing, and various systems have been developed for delivering reagents to the specimen containing the slide. Examples of known reagent delivery systems include small-volume dispensers, manually poured reagent containers, or bulk containers connected to the staining machine via tubing.

[0004] The system is known to have various drawbacks. For example, manually pouring or emptying reagents into reagent containers is prone to cross-contamination, time-consuming, and requires precise pouring, thus reducing the overall efficiency and accuracy of the sample processing system. Another drawback is that manually pouring and emptying reagents can be careless, requiring the cleanup of spills and causing instrument downtime. Yet another drawback is that manually selecting and applying the correct reagents introduces a significant risk of human error, increasing the likelihood of incorrect reagent selection and application, leading to false positive or false negative test results. This not only reduces testing accuracy and operational efficiency but also leads to misdiagnosis. Attached Figure Description

[0005] Embodiments of the present invention are illustrated in the accompanying drawings by way of example rather than limitation, in which the same reference numerals indicate similar elements. It should be noted that references to "a" or "an" embodiment in this disclosure do not necessarily refer to the same embodiment, and such references imply at least one.

[0006] Figure 1 A perspective side view of the sample processor is shown, with the door of the sample processor body in the open position.

[0007] Figure 2 A perspective side view of the sample processor is shown, in which the door of the sample processor body is in the closed position and the slide bed therein is raised.

[0008] Figure 3 The interior of the main body's cavity is shown. Figure 1 A top perspective view of the sample processor's slide bed and the mechanism for controlling the movement of the slide bed, which is isolated from other components of the sample processor.

[0009] Figure 4 The exterior of the main body's cavity is shown. Figure 1 A top perspective view of the sample processor's slide bed and the mechanism for controlling the movement of the slide bed, which is isolated from other components of the sample processor.

[0010] Figure 5 It shows Figure 1 A perspective top view of the main body of the sample processor from the bottom.

[0011] Figure 6 The diagram illustrates several similar... Figure 1 A perspective view of the sample processing system of the sample processor.

[0012] Figure 7 A left perspective view of the turntable assembly of the sample processing system is shown separately.

[0013] Figure 8 It shows Figure 7 A right-side perspective view of a portion of the turntable assembly's frame, and the isolated x-direction (longitudinal) drive mechanism.

[0014] Figure 9 The isolation was shown Figure 7 A perspective rear view of the U-shaped bracket and the lateral drive support bracket of the turntable assembly.

[0015] Figure 10 yes Figure 7 A perspective rear view of a portion of the turntable assembly.

[0016] Figure 11 A side perspective view of the arm assembly of the turntable assembly, which is isolated from the turntable, is shown.

[0017] Figure 12 It shows isolation from other components of the system. Figure 6 A perspective left front view of the storage rack of the sample processing system.

[0018] Figure 13 The diagram shows a representation operable for storing Figure 12 In the storage rack and used for Figure 6 A side perspective view of the reagent kit in the sample processing system.

[0019] Figure 14 It shows Figure 12A perspective front view of the storage rack containing the two kits stored therein.

[0020] Figure 15 It shows Figure 12 The turntable assembly includes a base or box support plate that is isolated from the base of the turntable assembly's column.

[0021] Figure 16 It shows Figure 6 A front view of the service station of the sample processing system. Detailed Implementation

[0022] In the following paragraphs, the invention will be described in detail by way of example with reference to the accompanying drawings. Throughout this specification, the embodiments and examples shown should be considered exemplary and not as limitations on the invention. Furthermore, references to various aspects of the embodiments disclosed herein do not imply that all claimed embodiments or methods must include the referenced aspects.

[0023] A sample processor is disclosed. The sample processor typically includes a body comprising an inner surface defining a chamber, the chamber including an opening in a side of the body, and including a volume therein for receiving at least one microscope slide. The sample processor also includes: a door including a first position covering the opening of the chamber and a second position exposing a portion of the chamber through the opening; a slide bed disposed within the chamber; and one of an internal humidity generator disposed within the chamber and an external humidity generator coupled to the chamber. The sample processor may be a standalone sample processor or may be combined with one or more other similar sample processors as part of a sample processing system.

[0024] Figure 1A perspective side view of the sample processor is shown. The sample processor 112 includes a body 120. In this typical example, the body 120 of the sample processor 112 is rectangular and includes a top, a base, and a pair of opposing sidewalls defining a length dimension (z-direction) and a separate pair of opposing sidewalls defining a width dimension (x-direction). The top, base, and both pairs of sidewalls together define a chamber 125 for accommodating a single microscope slide. Typically, the microscope slide can be a plate of glass with a thickness of 1 mm (0.04 inches), a length of 75 mm (approximately 3 inches), and a width of 26 mm (approximately 1 inch). The length of the chamber 125 can be approximately 80 mm to 100 mm (3.2 inches to 4 inches), and the width of the chamber 125 can be approximately 28 mm to 40 mm (1.1 inches to 1.6 inches). It should be understood that the body 120 can have shapes other than rectangular, as long as the shape is capable of accommodating a single slide. In another typical example, the body 120 may have dimensions for accommodating multiple slides (e.g., two slides, three slides, four slides) within the chamber 125. The body 120 may be made of a material that is chemically inert to reagents typically used in staining or tissue preparation processes to prepare tissue for staining. Typical metallic materials include, but are not limited to, stainless steel, zinc alloys, aluminum alloys, and silver. For example, silver can be used to impart antimicrobial properties to the body 120. Other exemplary materials for the body 120 may include thermally conductive polymeric materials such as plastics or cellulose (i.e., cellulose-based or containing) materials, ceramics, Teflon, glass, etc. The body 120 may be formed by any process known in the art, such as injection molding, machining, or any other manufacturing process suitable for producing the desired features. Furthermore, it should be understood that the body 120 may consist of more than one of the above-described materials. Figure 1 The body 120 of the sample processor 112 is also shown to include an opening 122 on one side for access to a chamber 125. In the illustrated embodiment, the opening is in a side wall (e.g., the front side wall of the body 120). As observed, a gasket or seal 135 of rubber or other polymeric material is disposed around the opening 122 of the body 120. When a door covers the opening 122 in the body 120, the gasket or seal 135 can be used to seal or substantially seal (e.g., hermetically seal) the chamber 125 (see [link to documentation]). Figure 2 Typically, chamber 125 can be completely sealed (i.e., hermetically sealed so that no air or gas can escape from chamber 125, and fluid-sealed so that no fluid can escape from chamber 125). Figure 2 A perspective side view of the sample processor is shown, with the door of the main body of the sample processor in the closed position.

[0025] The sample processor 112 includes a door, for example, made of plastic or metal (e.g., stainless steel, zinc alloy, aluminum alloy, silver), having an opening 122 that covers a chamber 125. The door 130 includes a generally rectangular portion having length (z-direction) and width (x-direction) dimensions similar to the sides of the body 120 defining the opening 122. One end of the door 130 (as observed at the top) includes a hook portion 132 (or clevis portion) projecting longitudinally (z-direction) from the generally rectangular portion. The opposite second end is hinged to the base of the body 120 so that the door 130 can rotate between a horizontal (z-direction) open position and a vertical (y-direction) closed position. Movement of the door 130 between the open and closed positions can be controlled by a motor, for example, rotating an axis through which the hinge is set so that the door 130 rotates on the axis. A latching member 134 is attached to the top surface of the body 120. In this example, latch member 134 is a horizontal U-shaped latch elbow clamp that engages with hook portion 132 when door 130 is in the vertically closed position, clamping door 130 to body 120. It should be understood that latch member 134 and hook portion 132 may be electronic and / or electromechanical latch mechanisms, electrically connected to a controller containing non-transitory, machine-readable instructions for controlling the latch of door 130 and for opening and closing.

[0026] A slide bed 115 is disposed within a chamber 125 of the body 120. In this example, the slide bed 115 comprises a rectangular pressure plate 1152 having a flat top surface with dimensions suitable for accommodating a microscope slide placed horizontally for observation on the pressure plate 1152 (e.g., length (z-dimension) and width (x-dimension) equal to or slightly larger than the microscope slide (e.g., 1 mm to 2 mm larger than the microscope slide)). A y-dimension protruding lip 1153 surrounds one z-dimension side and a first end (such as the observed left or front end) of the pressure plate 1152. A platform 1151 is disposed on and connected to the pressure plate 1152, and the platform 1151 is sized similarly to the microscope slide (e.g., 75 mm x 25 mm). The platform 1151 will support the microscope slide (microscope slide 150) thereon. The z-dimension and x-dimension of the platform 1151 are smaller than those of the pressure plate 1152. The smaller z and x dimensions of platform 1151 relative to pressure plate 1152 form a groove (groove 1157) between the edge of platform 1151 and a lip 1153 projecting from the edge of pressure plate 1152. One or both ends (z-dimensional ends) of pressure plate 1152 may also include an opening (opening 1158) therethrough to allow the discharge of reagents introduced on platform 1151.

[0027] like Figure 1As shown, the second end of the slide bed 115 (as observed at the right end) includes a stepped portion 1154 in a plane different from the pressure plate 1152 (as observed in the higher y-dimensional plane). The stepped portion 1154 is separated from the pressure plate 1152 by a ramp 1155 positioned at an angle of approximately 20° to 45°.

[0028] Figure 1 A microscope slide 150 is shown placed on a platform 1151 of a slide bed 115. The microscope slide 150 may have a sample (e.g., a tissue sample) on it, and the microscope slide may be positioned on a pressure plate 1152 with the sample facing away from the pressure plate 1152 (as observed, facing upward) or facing the pressure plate 1152 (as observed, facing downward).

[0029] Figure 3 A top perspective view of the slide bed 115 is shown, along with the mechanism for controlling the movement of the slide bed 115, isolated from other components of the sample processor 112. (Reference) Figure 3 In this example, the slide bed 115 is operable to rotate longitudinally in one direction to, for example, remove liquid. Figure 3 A shaft 142 is shown, which is connected at one end to a rotary motor 140 (stepper motor, brushed DC motor, or brushless servo motor), and includes a collar 144 surrounding a second opposite end of the shaft 142. The collar 144 is positioned below a wafer bed 115. In one example, the collar 144 has an xy-cross-sectional shape of a Fibinacci spiral. A Fibinacci spiral typically becomes wider (or farther from its origin) with each quarter turn. In this configuration, the collar 144 is positioned below the wafer bed 115 such that when the collar rotates (e.g., clockwise), only the widest point or quadrant (or quarter circle) of the spiral shape contacts the bottom surface of the wafer bed 115, and at the widest point, the wafer bed 115 is lifted, which allows the collar 144 to contact and lift the wafer bed 115. The contact point between the collar 144 at its widest point and the slide bed 115 may not be at the midpoint of the slide bed in the x-axis, but may be offset to one side (e.g., the left side as observed) by a small distance (e.g., 1 mm to 2 mm), so that the lifting of the collar 144 onto the slide bed 115 causes one z-axis side of the slide bed 115 to be lifted, so that the slide bed 115 tilts downward to the other z-axis side, as... Figure 2 As shown in the diagram, the raised z-dimensional side of the slide bed 115 includes a lip 1153 at the edge of the pressure plate 1152, while the lowered side may not include a lip 1153. The tilting of the slide bed 115 allows for the removal of excess fluid (e.g., reagents) from the microscope slide 150 on the slide bed 115 or from the slide bed 115 itself, to drain the lowered z-dimensional side.

[0030] like Figures 1 to 3 As shown, a rotary motor 140 is located outside the body 120. The rotary motor 140 is connected to a bracket 160. The bracket 160 is fixed and connected to a platform 152, which is connected to the side of the body 120 opposite to the side containing the opening 122. A shaft 142 extends from the rotary motor 140 through the opening in the body 120 such that a portion of the shaft 142 and a collar 144 are inside a chamber 125. The opening in the body 120 through which the shaft 142 passes can be sealed, for example, with a gasket (i.e., hermetically sealed so that no air or gas can escape from the chamber 125, and fluid-sealed so that no fluid can escape from the chamber 125).

[0031] The sample processor 112 also includes a mechanism for moving the slide bed 115 in the z-direction. The sample processor 112 includes a linear actuator 155 comprising a rotary motor 1552 (stepper motor, brushed DC motor, or brushless servo motor) and a threaded lead screw 1554 having a locking precision nut 1556. In this example, the rotary motor 1552 is positioned below and connected to the platform 152. The rotary motor 1552 is connected to the precision nut 1556, and the lead screw is screwed into the precision nut 1556. The distal end of the lead screw (as observed on the right side) is connected to a bracket 160. The sample processor 112 also includes rods 162 and 164 parallel to each other, each rod being fixedly connected at its proximal end (as observed on the left end) to a bracket 169 within the chamber 125 and at its distal end (as observed on the right side) to a bracket 160. The support 169 is positioned below and connected to the step 1154 of the slide bed 115. The openings in the body 120 for the rods 162 and 164 can be sealed, for example, with gaskets (i.e., hermetically sealed so that no air or gas can escape from the chamber 125, and fluid-sealed so that no fluid can escape from the chamber 125).

[0032] When the rotor of the rotary motor 1552 of the linear actuator 155 rotates, the linear actuator converts the rotation of the motor into linear motion by moving the rotating nut 1556 on the lead screw 1554, thereby causing the lead screw 1554 to move in the z-direction. The movement of the lead screw 1554 causes the support 160 to also move in the z-direction. The sample processor 112 also includes a pair of guide rails or tracks 166 on the platform 152. The support 160 is connected to the pair of guide rails or tracks 166 and can move in the z-direction on the guide rails and tracks in response to the movement directed by the linear actuator 155.

[0033] Linear actuator 155 is connected to platform 152, which is connected to the side of body 120 opposite to the side containing opening 122. When door 130 is in the open position (see...) Figure 1 The linear actuator can move the wafer bed 115 from a position inside the chamber 125 of the main body 120 to a position outside the chamber, such as... Figure 4 As shown in the diagram. When the slide bed 115 is outside the body 120, microscope slides can be placed on an empty slide bed, or removed from the slide bed if present. When the slide bed is outside the body 120, one or more processing methods can also be introduced onto the samples on the slide bed.

[0034] The sample processor 112 can be used as a humidifier capable of controlling and maintaining humidity to reduce reagent evaporation and sample (e.g., tissue) drying. Typical humidity levels can be relative humidity above 50%, such as above 60% to 100%, such as 70% to 100%, such as 80% to 100%, or such as 90% to 100%. Figure 1 In the example shown, the body 120 includes a chamber 125 having dimensions capable of accommodating a reservoir beneath the slide bed 115. The reservoir can be filled with water to generate humidity within the chamber 125. Figure 1 A valve 156 is shown connected to a conduit 157, which extends from a point outside the body 120 through the bottom wall of the body 120 to a point inside the chamber 125 (e.g., a few millimeters inside the chamber 125). A fluid (e.g., water) source can be connected to the valve 156 to introduce fluid into the chamber 125. The conduit 157 may also include a flow meter to monitor the amount of fluid introduced into the chamber 125. In one example, the valve 156 and the flow meter (if present) may be electrically connected to a controller containing non-transitory machine-readable instructions to introduce a volume of fluid into the chamber 125 through the valve 156. Furthermore, a conduit 158 ​​extends from the chamber 125 through the base wall of the body 120 and can serve as a discharge pipe for discharging the fluid contents of a reservoir in the chamber 125. The distal end of the conduit 158 ​​is connected to a discharge valve 159 outside the body 120. In one example, the valve 159 may be electrically connected to a controller containing non-transitory machine-readable instructions for actuating the valve (opening, closing).

[0035] Figure 1 The sample processor 112 also includes a heating element 154. Figure 1In the example shown, heating element 154 is an immersion heater directly mounted in the reservoir of chamber 125. In another example, heating element 154 may be positioned on or within conduit 157 to heat fluid delivered to the reservoir of chamber 125. Heating element 154 may be an electrically resistive heating element. Heating element 154 may be electrically connected to a controller containing non-transitory machine-readable instructions to power and control the heating element, for example, a thermostat. The ability to heat fluid (e.g., water) in the reservoir allows chamber 125 of sample processor 112 to generate humidity at elevated temperatures by producing water vapor. An ultrasonic humidifier may also be placed in the reservoir and powered to expel reservoir droplets within chamber 125 that evaporate and humidify chamber 125.

[0036] Another technique for generating humidity in chamber 125 of sample processor 112 is to introduce air or an inert gas (ambient gas or heated gas) into a fluid reservoir to create a humid environment. Typically, air or an inert gas from the environment or a heating source can be connected to an exhaust valve 159, and the air or inert gas can be introduced into the reservoir through conduit 158. Another alternative is to use an ultrasonic humidifier to expel tiny water droplets into the air, which evaporate into water vapor, thereby humidifying chamber 125.

[0037] Humidity generated from the reservoir in chamber 125 of sample processor 112 causes a reduction in the volume of fluid in the reservoir. For example, water evaporates as it generates humidity in the chamber. To monitor the liquid level in the reservoir, sample processor 112 may include a sensor, such as a float sensor, in the chamber to send a signal indicating the liquid level in the reservoir to a controller, such as a controller. When the liquid level drops (volume decreases) to a predetermined point, additional fluid is added to the reservoir (e.g., a non-transitory machine-readable instruction from the controller instructs a certain volume of fluid (e.g., water) to be introduced into chamber 125 through valve 156).

[0038] The sample processor 112 may also include a humidity sensor in chamber 125. Indicatively, the humidity sensor may be connected to the top wall of the body 120 inside chamber 125 and provide an indication of the humidity level in chamber 125. The humidity sensor may be connected to a visual indicator outside chamber 120, such as a display (e.g., a liquid crystal display), or to a controller that may contain non-transitory, machine-readable instructions for controlling the humidity level (e.g., generating, reducing, or maintaining humidity within the chamber).

[0039] Another option for generating humidity in chamber 125 of sample processor 112 is to generate humidity from an external source rather than from a reservoir in chamber 125. Steam generated in an external boiler can be supplied to chamber 125, for example, via conduit 157. Air or an inert gas (ambient or heated) can be bubbled through an external reservoir (ambient or heated) to generate humid air at a desired humidity level that can be supplied to chamber 125, for example, via conduit 157. Additionally, an ultrasonic generator can generate water droplets (ambient or heated) that can be supplied to chamber 125, for example, via conduit 157.

[0040] Sample processing techniques can involve processing samples (such as tissue samples on microscope slides) under conditions different from ambient pressure and / or different from ambient temperature. Typical pressures for some sample processing operations can be from 1 atmosphere (atm) (ambient) to 3 atmospheres (14.7 psi to 44.1 psi), such as 1 atm to 2 atm (14 psi to 29.4 psi), or such as between 1 atm and 2 atm, such as 1.7 atm (25 psi). Typical temperatures for some sample processing operations can be from 20°C (approximately ambient) to 150°C, such as between 20°C and 150°C, such as 30°C to 140°C, such as 40°C to 130°C, such as 50°C to 120°C, such as 60°C to 110°C, such as 70°C to 150°C, such as 100°C to 140°C, such as 110°C to 140°C, or such as 120°C to 130°C.

[0041] To increase the pressure in the sample processor 112, air or inert gas can be introduced into the chamber 125 of the body 120 when the door 130 is in the closed position and the body 120 is hermetically sealed (see [reference]). Figure 2 A compressor or pump 170 is connected to the body 120 of the sample processor 112, which can serve as a source of compressed air or inert gas. Typically, the sample processor 112 may include fittings 172 (e.g., valves or valves and conduits) disposed in the body 120 to the chamber 125. Figure 1 and Figure 2A fitting 172 is shown attached to the top wall of the main body 120. It should be understood that it can be attached to another wall (e.g., a side wall, bottom wall). A compressor or pump 170 can be connected to fitting 172 via a conduit (e.g., a plastic or metal conduit). In this example, a pressure regulator 174, a pressure relief valve 175, and a pressure gauge 176 are disposed in the conduit between the compressor or pump 170 and fitting 172. The pressure regulator 174 can be used to regulate (e.g., set) a desired or predetermined pressure in chamber 125. The pressure regulator 174 can allow a stable or constant pressure (e.g., elevated pressure) or increasing pressure pulses in chamber 125. The pressure relief valve 175 can be used to release excess pressure accumulated in chamber 125 or to restore chamber 125 to ambient pressure. The pressure gauge 176 can be used to indicate the pressure level in chamber 125 to the operator of sample processor 112. The pressure gauge 176 in the illustrated embodiment includes a sensor and a display. It is understood that the pressure gauge 176 may not be included in the display at the conduit connection point between the connector 172 and the compressor 170. The pressure gauge 176 is, for example, electrically connected to a monitor that displays the pressure value read by a sensor in the conduit.

[0042] Another technique for increasing the pressure in chamber 125 is to change the volume of chamber 125. This can be done, for example, by compressing one or more of the top, bottom, or sidewalls of body 120. For example, the upper portion of the sidewall of body 120 may have folded sides to allow the sidewalls to expand and contract. The folded sides allow a downward force to be applied to the top of body 120 to compress the folded portion of the sidewall like an accordion, thereby reducing the volume of chamber 125, and the compression is completed when door 130 is in the closed position, thereby increasing the pressure in chamber 125.

[0043] The sample processor 112 can alter the temperature within chamber 125. One method to raise the temperature within chamber 125 is by heating a fluid within a reservoir, as described above regarding the generation of humidity levels within chamber 125. In addition to this technique or as an alternative, the slide bed 115 may include a heater, such as a thermocouple, in contact with the underside of the slide bed 115. Another heating technique involves one or more heaters to heat the ambient area surrounding the slide bed 115. Examples include a resistance heater or an infrared heater positioned within chamber 125. Another technique is a heating jacket wrapped around the exterior of body 120 to heat chamber 125 from the outside. One or more heat sources may be connected to a controller to allow machine-readable, non-transitory commands associated with the controller to control the heat sources and regulate the temperature within chamber 125.

[0044] Sample preparation, such as the preparation of tissue samples for pathological evaluation on microscope slides, typically involves numerous steps. These steps typically include heating to adhere the tissue sample to the microscope slide, dewaxing to remove paraffin and expose the sample, antigen retrieval to expose antigenic sites in or on the tissue sample, and one or more staining operations to stain the tissue sections with dyes or markers and make them visible under a microscope to allow for sample evaluation. Typical dyes include hematoxylin, eosin, Masson's trichrome, modified GMS silver stain, periodic acid Schiff, and Perls Prussian blue iron. Other staining methods include, but are not limited to, immunohistochemistry or in situ hybridization to target specific protein or DNA / RNA sequences in the sample.

[0045] Many of these steps in sample processing involve contacting a tissue sample with one or more reagents. These include bulk reagents and primary reagents. Examples of bulk reagents include, but are not limited to, Tris-buffered saline (TBS), sodium citrate saline (SSC), distilled water, dewaxing solution, alcohol, and xylene. Examples of primary reagents include, but are not limited to, staining agents such as hematoxylin and eosin, any type of antibody, probe, nucleic acid (RNA, DNA, or oligonucleotide), ligand, ligand receptor, enzyme or enzyme substrate, or any other molecule suitable for the desired use. Reagents can be in natural, purified, concentrated, diluted, or otherwise regulated forms. Additional primary reagents may contain signaling molecules such as fluorescent dyes, enzymes, conjugates (e.g., biotin, avidin, streptoavidin), metals (e.g., silver or gold particles), dyes, staining agents, radiolabeled molecules, or any other substance such as a signaling molecule or reporter molecule.

[0046] Referring to tissue processor 112, the dispensing of reagents onto samples on microscope slides can be performed depending on the reagent and whether the microscope slide is outside or inside chamber 125, or a combination of both. For example, bulk reagents can typically be dispensed onto microscope slides inside chamber 125. Figure 1An opening 121 is shown passing through the top of the body 120. A conduit (not shown) may be connected to the opening 121, and a reagent may be connected to the conduit to dispense the reagent from outside the body 120 and chamber 125. One reagent may be connected to the conduit, or multiple reagents may be connected to the conduit via, for example, a manifold. The opening 121 is directly above the inclined surface 1155 of the slide bed 115. If the sample side of the slide is down, the reagent introduced through the opening 121 may contact the inclined surface 1155 and flow onto or under the slide 150 under gravity. The interior of chamber 125 may also have one or more nozzles connected to the conduit through the opening 121. Such one or more nozzles may be operable to dispense a spray or curtain flow (broad laminar flow) of reagent within chamber 125. One or more nozzles of this type can direct the reagent flow onto the top surface of slide 150 (as observed when the microscope slide is positioned with the sample side up) or onto the bevel 1155 and / or the stepped portion 1154 (as observed when the microscope slide is positioned with the sample side down), or when cleaning reagents or conduits so that the cleaned reagents enter directly from the bevel 1155 into the groove 1157, such as when the microscope slide is positioned with the sample side up.

[0047] Figure 5 A perspective top-side view of the top underside of the body 120 is shown, illustrating another technique, as an alternative to or in addition to the opening 121, for dispensing reagent(s) onto or under a microscope slide within the chamber 125. A plurality of fluid connectors 190 (e.g., 4 to 8 fluid connectors) are arranged protruding from one side of the top. The fluid connectors 190 may be fittings or couplings that allow fluid conduits (e.g., polymer tubing) to be attached. Typically, as... Figure 1 As shown, the fluid connector 190 protrudes from the right side of the top of the body 120 (the side opposite to the door 130). The underside of the top of the body 120 includes a plurality of conduits 191 arranged longitudinally across the length of the top. Each fluid connector in the fluid connector 190 is fluidly connected to a conduit 191 so that fluid can be delivered through the fluid connector 190 to the conduit 191. The conduit 191 may be a tubing material such as metal (e.g., copper, aluminum, stainless steel). Each conduit 191 may have an opening 192 along its length to discharge fluid from the conduit in the direction of the slide bed 125. Each opening in the conduit may contain a nozzle to control the flow direction and rate. Reagent dispensing from each conduit may be a flow, a spray, or a liquid curtain to provide optimal coverage of the sample on the microscope slide or the entire surface of the microscope slide.

[0048] In one example, bulk reagents can be individually connected to fluid connectors 190. The bulk reagents can be contained in a single container and connected to individual fluid connectors in fluid connector 190 via conduits extending, for example, between the respective bulk reagent container and the fluid connector. The bulk reagents can be supplied to the fluid connectors as needed using pumps, such as a single inline pump for each bulk reagent container connected to the fluid connector. Non-transitory machine-readable instructions associated with a controller can control the metering of reagents from the bulk reagent containers, such as by a timer or by a single inline flow meter (e.g., a flow meter in the conduit between the bulk reagent container and the fluid connector). The temperature of the dispensed reagent can be changed or controlled by preheating or cooling before dispensing, as needed. Typical techniques for changing the temperature of the reagent to be dispensed include heating or cooling the reagent container before dispensing (e.g., refrigeration for cooling the container, an oven or hot plate for heating), an external heater or strip heater wrapped around the conduit between the container and the corresponding conduit 191.

[0049] An example of a bulk reagent is a cleaning solution, such as water or a mixture of water and surfactants and / or buffers. The cleaning solution can be used to clean samples on microscope slides, entire microscope slides, or slide beds 115 (with or without microscope slides). Typically, to clean slide beds 115 with or without microscope slides on platform 1151, the cleaning solution can be applied through an opening 121 at the top of body 120 (see [link to documentation]). Figure 1 The cleaning solution is introduced to contact the inclined surface 1155, which allows the cleaning solution to flow directly into the groove 1157 without passing through the microscope slide. Whether the slide bed is horizontal or inclined (or both), the cleaning solution in the groove 1157 will eventually drain out from one or more openings in the substrate of the slide bed 115.

[0050] Bulk reagents dispensed into chamber 125 of body 120 can be dispensed at temperatures below ambient, ambient, or elevated (above ambient). Elevated temperatures can be achieved, for example, by heating the conduit that transfers the reagent into chamber 125 (e.g., a resistance heater surrounding the conduit and whose output is controlled by instructions from a controller) or by having a separate reservoir for preheating the reagent to a defined elevated temperature.

[0051] In one example, reagent dispensing of the primary reagent can be performed with at least a portion of the sample and the microscope slide containing the sample located outside the chamber 125 of the body 120. Typically, the door 130 of the body 120 can be moved from a closed position to an open position. When the door 120 is in the open position, the slide bed 115 can be moved from a position inside the chamber 125 to a position outside the chamber 125. The opening of the door 130 and the movement of the slide bed 115 from a position inside the chamber 125 to a position outside the chamber 125 can be controlled by a controller containing non-transitory machine-readable instructions to initially open the door 130 and then instruct a linear actuator 155 to move the slide bed 115 to a position outside the chamber 125.

[0052] Once a portion of the slide bed 115 containing the microscope slides for tissue samples is outside the chamber 125, reagent dispensing can be performed by various methods. Such methods include, but are not limited to, dispensing via a thermal or piezoelectric inkjet printhead, via a nozzle, via a microelectromechanical dispensing mechanism, and via overhead dispensing through a piercing reagent container and a dripping mechanism. Example of dispensing via a thermal or piezoelectric inkjet printhead is described in U.S. Patent Publication 2023 / 0055997 (Serial No. 17 / 790,040), entitled "Automated Staining System and Reaction Chamber," which is incorporated herein by reference. Example of dispensing via a nozzle and via a piercing reagent container and a dripping mechanism is described in U.S. Patent No. 10,295,444 (Serial No. 14 / 579,858), also entitled "Automated Staining System and Reaction Chamber," which is incorporated herein by reference.

[0053] Microscope slides can be positioned with the sample facing upwards (away from the slide bed) or downwards (facing the slide bed). Reagents dispensed from above, whether in bulk or as primary reagents, can be dispensed directly onto the sample or slide when the sample is facing upwards, or onto slide bed 115 when the sample is facing downwards, so that the reagents can migrate to the sample via capillary action.

[0054] Sometimes, excess reagents, including cleaning solution, may be discharged from the sample processor 112. As described above, a conduit 158 ​​extends from the chamber 125 through the base wall of the body 120, and the conduit 158 ​​can serve as a discharge port for the fluid contents of the reservoir in the chamber 125. The distal end of the conduit 158 ​​is connected to a discharge valve 159 outside the body 120.

[0055] Figure 6The illustration shows a perspective view of an embodiment of a sample processing system. The sample processing system 200 includes a housing 202 for encapsulating and storing various components of the system. The housing 202 includes a reaction compartment 204 and a storage compartment 201. The reaction compartment 204 is separated from the storage compartment 201 by a platform 205 forming the base of the reaction compartment 204. In addition to the platform 205, opposing sidewalls project from the platform 205, and covers connect the ends of each of the sidewalls. The covers, sidewalls, and platform 205 together define a compartment where sample processing takes place. A cover member 208 and a door member 210 can be used to access components within the reaction compartment 204.

[0056] The dimensions (e.g., internal volume) of reaction compartment 204 are designed to accommodate a storage rack for storing multiple reagent kits. The storage rack 206 may be mounted on platform 205 or attached to a side wall of reaction compartment 204 (e.g., the rear side wall as observed). Storage rack 206 can be used to store reagent kits. Typical reagent kits are disposable cartridges, such as inkjet cartridges containing a volume of reagents that can be used for pathological or histological processing. The array of slots in storage rack 206 stores individual reagent kits, for example, in a row-column array. Storage rack 206 may include a refrigeration device to store the reagent kits in a refrigerated state. A typical refrigeration device may include a compressor that compresses refrigerant vapor and forces the vapor through a coil, where the vapor liquefies and cools the storage rack slots.

[0057] The reaction chamber 204 is sized to accommodate multiple sample processors 112. Each sample processor 112 can be configured as described above. Figures 1 to 5 As described in the accompanying text. Figure 6 Typically shown are 30 sample processors 112 arranged in a 15×2 configuration in a plane (xz plane) on platform 205. It should be understood that the number and configuration of sample processors will depend in part on the dedicated area of ​​reaction compartment 204. Therefore, it is conceivable that the number of sample processors can vary with their configuration. As observed, a turntable assembly comprising bench 214 and turntable 215 is positioned above the sample processors 112. Turntable 215 is operable to place / accommodate multiple reagent kits and dispensing reagents from the respective kits onto corresponding slides in the sample processors 112. Turntable 215 is operable to move on bench 214 to position reagent kits on the individual sample processors 112 and to load / unload reagent kits from / to storage rack 206.

[0058] The sample processing system 200 also includes a controller 209. The controller 209 contains non-transitory machine-readable instructions for controlling the operation of the sample processing system, including but not limited to loading / unloading reagent kits in the storage rack 206 and the loading / unloading turntable 215. Figure 6 The controller 209 is shown outside the housing 202. It should be understood that the controller 209 may be a component outside or inside the housing 202.

[0059] Figure 6 Typically, 30 sample processors 112 are arranged in a 15×2 configuration in a plane (xz plane), with the sample processors 112 in one row arranged back-to-back relative to the other row. The first row of two rows may have sample processors 112, each with an outward-facing door 130 (away from the storage rack 206). The second row of two rows may have sample processors 112, each with an inward-facing door 130 (towards the storage rack 206). The back-to-back configuration allows each door 130 of the sample processor to be moved to an open position and allows the sample processor's slide bed to be positioned outside the chamber 125 of the sample processor's body 120, as described above. Each sample processor 112 may be connected to the platform 105 of the reaction compartment 104 of the housing 102.

[0060] refer to Figure 6 In addition to the sample processor 112, the reaction chamber 204 of the housing 202 of the processing system 200 also includes a stand 214 supporting the turntable 115. The stand 214 and the turntable 215 together describe the turntable assembly. Figure 7A left perspective view of the individual turntable assembly is shown. The stand 214 comprises two vertical (y-direction) columns 2142 connected to the base of the reaction chamber 204. The x-direction distance between the vertical columns 2142 is greater than the distance covered by a row of sample processors 112 in the reaction chamber 204. Two horizontal supports 2144 are disposed between the vertical columns 2142 above the sample processors 112. Each of the horizontal supports 2144 is typically cylindrical in shape and extends the x-direction distance of the vertical columns 2142 and is parallel to the base of the reaction chamber 204. The horizontal supports 2144 are connected to the vertical columns 2142 by end brackets 2145 (e.g., inverted L-shaped brackets). The horizontal supports 2144 are separated by a z-direction distance selected for the z-direction travel of the turntable 215, as will be described in detail below. A U-shaped (e.g., inverted U-shaped as observed) bracket 2146 is connected to each of the horizontal supports 2144 between the end brackets 2145. The U-shaped support 2146 comprises two legs separated from a base. A horizontal support 2144 is connected to the base via a linear bearing 2147. The linear bearing 2147 is connected to the upper or exposed side of the base of the U-shaped support 2146 and allows the U-shaped support 2146 to move in the x-direction on the horizontal support 2144. The base of the U-shaped support 2146 includes an opening 2148, such as a rectangular opening, passing through it. A tab 21493 is also connected to one end of the upper or exposed side of the base of the U-shaped support 2146. The tab 21493 projects upward (in the y-direction) from the base. The tab 21493 is connected to a timing belt 2140 for moving the U-shaped support 2146 in the x-direction (longitudinal direction) (see...). Figure 7 ).

[0061] A lateral drive support bracket 2149 is connected to the base of a U-shaped bracket 2146 below a horizontal support member 2144. The lateral drive support bracket 2149 is U-shaped (e.g., an inverted U-shape as observed) defined by a base and sidewalls. As observed, the top side of the lateral drive support bracket 2149 has an opening 21499 passing through it. The base of the lateral drive support bracket 2149 has an x-direction width smaller than the corresponding width of the base of the U-shaped bracket 2146, such that the sidewalls of the lateral drive support bracket 2149 are positioned between the sidewalls of the U-shaped bracket 2146, and the sidewalls of the lateral drive support bracket 2149 are connected to the corresponding sidewalls of the U-shaped bracket 2146 via, for example, screws, rivets, or welding. A lateral linear guide extends within each of the sidewalls of the lateral drive support bracket 2149, extending 70% to 90% of the z-direction length of the sidewall. Each lateral linear guide 21492 is connected to the end of a sidewall at a similar y-direction distance by, for example, screws, rivets, or welding to the sidewall. A turntable 215 is connected to each lateral linear guide 21492.

[0062] Turntable 215 can move in three directions on the platform 214. Turntable 215 can move in the x-direction (longitudinal) as the U-shaped support 2146 moves. Turntable 215 can move in the y-direction (vertical) as the end support 2145 moves up or down along the vertical column 2142. Turntable 215 can move in the z-direction (lateral), and turntable 215 moves along each lateral linear guide 21492 in the lateral drive support bracket 2149.

[0063] Figure 8 A perspective right view of a portion of the platform 214 is shown to illustrate the x-direction (longitudinal) drive mechanism. In this view, the platform 214 includes a horizontal support 2144 connected to a vertical column 2142 via an end bracket 2145. A gear 2141 rotating in the xz plane is located on one side of the platform 214 (e.g., Figure 8 The timing belt 2140 is attached to the top of each end bracket (shown on the left side). One of the gears 2141 is connected to the shaft of the motor 2143, and the motor is operable to rotate the gear in a clockwise or counterclockwise direction. The timing belt 2140 is disposed around the gear 2141 and extends above one of the horizontal supports 2144. The timing belt 2140 can be moved in the x-direction (longitudinal direction) via the gear 2141. The timing belt 2140 is connected via screws, rivets, pins, etc., to the tab 21493 attached to the U-shaped bracket 2146 (see...). Figure 7 The connection between the timing belt 2140 and the U-shaped bracket 2146 allows the motor 2143 to move the U-shaped bracket 2146, and thus laterally drive the support bracket 2149 and the turntable 115 in the x-direction (longitudinal direction).

[0064] Figure 9 A perspective rear view of the individual U-shaped bracket 2146 and the lateral drive support bracket 2149 is shown. Figure 9 The linear bearing 2147 is shown connected to the upper or exposed side of the base of the U-shaped bracket 2146. The linear bearing 2147 supports the horizontal bracket 2144 (see...). Figure 7 Three linear bearings 2147 are shown, one of which is on one end of a U-shaped bracket 2146 to support a horizontal support 2144, and two linear bearings 2147 are on opposite ends of the base to support another horizontal support 2144, and the z-direction spacing between the one linear bearing and the two linear bearings is equal to the z-direction distance between the horizontal supports 2144 (see [reference]). Figure 6The base of the U-shaped bracket 2146 includes an opening 2148, such as a rectangular opening, between one linear bearing 2147 and two linear bearings 2147. A tab 21493 is also attached to one end of the base of the U-shaped bracket 2146 on the upper or exposed side. The tab 21493 projects upward (in the y-direction) from the base. The tab 21493 is connected to a timing belt 2140 for moving the U-shaped bracket 2146 in the x-direction (longitudinal direction) (see...). Figure 7 ).

[0065] Figure 9 The diagram also illustrates the z-direction (lateral) drive mechanism. Figure 9 A lateral drive support bracket 2149 is shown attached to and positioned below a U-shaped bracket 2146. A lateral linear guide is located inside each of the sidewalls 21494A and 21494B of the lateral drive support bracket 2149, extending a portion (e.g., 70% to 90% of the z-direction length) of the sidewall. Each lateral linear guide 21492 is at a similar y-direction distance from the end of the sidewall (sidewalls 21494A and 21494B) connected to the sidewall by, for example, screws, rivets, or welding.

[0066] Figure 9 The z-direction (lateral) drive mechanism shown also includes two gears 21493, which are connected to the exterior of the side wall 21494A of the lateral drive support bracket 2149 (as seen on the left side wall). Figure 9 In this design, only one of the two gears 21493 is visible at one end (rear end) of the sidewall 21494A of the lateral drive support bracket 2149. The second of the two gears 21493 is located at the opposite end (front end) of the sidewall 21494A of the lateral drive support bracket 2149. Each of the two gears 21493 rotates in the yz plane. One of the gears 21493 is connected to a worm gear 21496, which is rotated by the shaft of a motor 21495, and the motor 21495 is operable to rotate clockwise or counterclockwise. A timing belt 21497 is positioned around the gear 21493 and extends along the sidewall 21494A of the lateral drive support bracket 2149. The timing belt 21497 is operable to move in the z-direction (lateral direction) via the gear 21493.

[0067] Figure 10This is a perspective rear view of a portion of turntable 215. This view illustrates a portion of turntable 215 connected to a transverse drive support bracket 2149 of the platform 214. Turntable 215 includes a rectangular main support 21510 having a length dimension (x-dimension) and a width dimension (z-dimension) defined by opposing pairs of sidewalls positioned within the transverse drive support bracket 2149. Sidewalls 21511 and 21514 define the length dimension, and sidewalls 21512 and 21513 define the width dimension. The main support 21510 also includes a top portion 21515 connected to each sidewall and having an opening therethrough for a column 2151. Z-shaped bracket 2153 is connected to the sidewall 21512 of the main bracket 21510. The Z-shaped bracket 2153 has: a base 21531 that protrudes horizontally (x-direction) d from the sidewall 21512; a middle portion 21532 that protrudes vertically (y-direction); and a apex 21533 that protrudes horizontally (x-direction) from the middle portion 21532. When the main bracket 21510 is positioned within the lateral drive support bracket 2149, the protrusion of the Z-shaped bracket 2153 away from the sidewall 21512 at a distance d allows the middle portion 21532 and the apex 21533 to be positioned outside the sidewall (sidewall 21494A) of the lateral drive support bracket 2149. Timing belt 21497 (see...) Figure 9 The main support 21510 of the turntable 215 is connected to the vertex 2153 (e.g., via screws, rivets, pins, etc.), which allows the motor 21495 to move the turntable 215 in the z-direction (lateral direction). A lateral plate bearing 2154 is also attached to the sidewall 21512, and the lateral plate bearing 2154 is operable to engage with the interior of the sidewall 21494A connected to the lateral support bracket 2149 (see...). Figure 9 The lateral linear guide 21492 engages with the lateral drive support 2149. The roller 2159 protrudes outward from the sidewall 21513 (opposite to the sidewall 21512). The roller 2159 is operable to engage within the lateral linear guide 21492 of the sidewall 21494B of the lateral drive support 2149 and to rotate in the yz plane.

[0068] As described above, the main support 21510 includes a top portion 21515 having an opening therethrough for the column 2151. The column 2151 includes teeth that are cut or inserted around its top portion. A slewing bearing 2155 is disposed on the top portion 21515 of the main support 21510. The slewing bearing 2155 includes an outer ring and an inner ring, the inner ring being coupled to a gear having teeth that mesh with the teeth surrounding the top portion of the column 2151. A gear 2156 is disposed on and connected to the top surface of the slewing bearing 2155. The gear 2156 is operable to rotate in the xz plane and in the same plane rotates the inner ring of the slewing bearing 2155, and thus rotates the column 2151. The main support 21510 remains stationary (does not rotate). The gear 2156 is rotated by a motor 2157. Motor 2157 is mounted to the top portion 21515 of main bracket 21510 and has a shaft extending therefrom that shaft that rotates in the yz plane. The shaft is connected to a worm gear 2158, which meshes with gear 2156 to rotate gear 2156 in the xz plane. (Reference) Figure 7 The base of the column 2151 of the turntable 215 includes a base or cassette carrier plate 2152 operable to engage and accommodate multiple kits. The base 2152 is rotated by the rotation of the column 2151 of the motor 2157.

[0069] Refer again Figure 7 The platform 214 comprises two vertical columns 2142. The vertical columns 2142 are shown having rectangular housings 21422 arranged around lead screws 21424. Each lead screw 21424 is connected to a corresponding end bracket 2145 and is driven (clockwise or counterclockwise rotation) by a corresponding stepper motor (motor 21425), with one stepper motor subordinate to the other. Rotation of the lead screw 21424 provides y-direction movement of the end bracket 2145, and correspondingly provides y-direction movement of the horizontal support 2144 and the turntable 215.

[0070] As described above, turntable 215 can move in three directions on the stand 214. Turntable 215 can move in the x-direction (longitudinal) via motor 2143 as the U-shaped support 2146 moves. Turntable 215 can move in the y-direction (vertical) as the end support 2145 moves up or down along the vertical column 2142 via stepper motor 21425. Turntable 215 can move in the z-direction (lateral), and turntable 215 moves along each lateral linear guide 21492 of the lateral drive support bracket 2149 driven by motor 21495. Each of motors 2143, 21425, and 21495 is controlled by non-transitory machine-readable instructions in controller 209 that direct their operation (e.g., direction of rotation, running time, etc.).

[0071] The turntable 215 is operable to automatically load / unload and engage or accommodate / disengage or de-accommodate multiple kits on the base 2152. (Reference) Figure 7 The turntable 215 can automatically load / unload the reagent kit using the arm assembly 218. Figure 11 A side perspective view of the arm assembly 218, isolated from the platform 214 and turntable 215, is shown. The arm assembly 218 includes an attachment bracket 2182, which is mounted to the outer surface of the side wall 21511 of the main support 21510 via, for example, bolts, screws, rivets, or pins (e.g., mounted at the midpoint of the side wall 21511). Figure 10 The short actuator 2184 is connected to the top of the attachment bracket 2182, and the long actuator 2186 is connected to the bottom of the attachment bracket 2182. Figure 7 In this assembly, a long actuator 2186 protrudes generally vertically (as observed horizontally) from an attachment bracket 2182, and a short actuator 2184 protrudes generally diagonally (e.g., at a 45-degree angle) from the attachment bracket 2182 to attach to the long actuator 2186. A cassette engagement head 2183 is connected to the end of the long actuator 2186. The cassette engagement head 2183 has paired fingers on its opposite sides with a separation distance d1 that allows the fingers to surround the protrusions of the kit (described below) and engage and move the kit.

[0072] Figure 11The top portion of the attachment bracket 2182 includes a hook portion 21822, and the bottom portion includes a hook portion 21823. One end of the short actuator 2184 is connected to the hook portion 21822 in a manner such that the hook portion 21822 can rotate about the pin, screw, or bolt, for example, a hook pin, screw, or bolt. Similarly, one end of the long actuator 2186 is connected to the hook portion 21823 in a manner such that the hook portion 21823 can rotate about the pin, screw, or bolt, for example, a hook pin, screw, or bolt. Each of the short actuator 2184 and the long actuator 2186 includes an electrically actuated telescopic body (e.g., a three-stage body of a progressively smaller cylinder or pillar). A second end of the short actuator 2184 is connected to the minimum stage or plunger of the long actuator 2186 via a link 2185. The link 2185 approaches the engagement head 2183. The engagement position of the short actuator 2184 and the long actuator 2186 is selected such that when the short actuator 2184 is fully retracted, it will cause the long actuator 2186 to rotate a few degrees (e.g., up to 10 degrees, such as 2 to 8 degrees) around the hook portion 21823, resulting in the distal end of the long actuator 2186, including the engagement head, moving (lifting) toward the hook portion 21822. The long actuator 2186 can extend to a position above the kit in the lifting configuration. The short actuator 2184 can then extend to rotate the long actuator 2186 in the opposite direction (i.e., rotate the long actuator away from the hook portion 21822) to lower the engagement head onto the kit to grip it.

[0073] As described above and as Figure 6 As shown, the sample processing system 200 includes a housing 202 for encapsulating and storing various components of the processing system 200, including a storage rack 206. The storage rack 206 can be used to store reagent kits (e.g., reagent kit 217). Figure 12 A perspective left front view of a storage rack 206, isolated from other components of housing 202, is shown. Storage rack 206 includes housing 2062 containing slots facing reaction compartment 204 and turntable 215. Storage rack 206 accommodates an array of slots for storing individual reagent kits. Figure 12 An array of 5 rows and 25 to 30 columns of slots is shown. This array of rows and columns allows each slot to have an address (e.g., specified by row and column numbers) so that the system can know the address of the kit and locate it in storage rack 206, or return the kit to a specific slot within storage rack 206. Figure 12In this array, reagent kits (reagent kit 217) are located in all slots. The outer surface of each reagent kit may contain an identifier such as a barcode, which contains identification information about the reagents contained in the kit, as well as other possible information such as the expiration date. This identifier can be read by a reader (e.g., a barcode reader), and the read information is electronically provided to controller 209. An example is a reader electronically linked to a turntable 215 of controller 209. The identifier on the reagent kit (e.g., reagent kit 217) may have a rewritable IC chip that can store the reagent's identity, batch number, expiration date, and number of uses.

[0074] Figure 13 A side perspective view of reagent kit 217, representing a kit operable for use in storage rack 206 and in sample processing system 200, is shown. Typically, reagent kit 217 has a z-direction depth of approximately 67.4 mm, an x-direction width of 5 mm to 10 mm, and a y-direction height of 98.5 mm. In another example, reagent kit 217 has a similar depth and width and a height of 70.8 mm (H2 is less than H1). Reagent kit 217 can be a drop-on-demand (such as inkjet) kit, such as a thermal drop-on-demand kit or a piezoelectric drop-on-demand kit, and as observed, the kit contains a single dedicated printhead positioned at the base of reagent kit 217.

[0075] Reagent kit 217 can contain a volume of reagent and has a dedicated printhead. Each kit can be a single-use kit. In this case, a single-use kit means that once the reagent volume in the kit has been dispensed or used, the kit containing its printhead will be discarded or disposed of, rather than being refilled with a volume of reagent. The reagent kit can contain (be supplied) a volume of reagent suitable for dispensing reagent onto one or more samples (e.g., tissue samples) on a slide. An example of a single-use kit is a thermal inkjet cartridge. Reference Figure 13 The kit 217 comprises a shell or body 2171 having a generally rectangular shape made of a plastic material (e.g., hard plastic or polymer). Figure 13A kit 217 is shown comprising a side 2172 and an opposite side 2173 representing the yz dimension, and a side 2174 and an opposite side 2175 representing the xy dimension. Side 2174 contacts and engages with a turntable 215. Kit 217 includes a printhead 2178 operable to eject reagents from the kit. Printhead 2178 may be positioned at or near the nose or base 2179 of kit 217 (as observed on the bottom side) so that reagents are ejected through the base 2179 of the kit when the kit is inserted into the turntable 215. The portion of the nose or base 2179 containing printhead 2178 (printhead region) may extend beneath the remainder of base 2179 in a step-like manner. The printhead 2178 of kit 217 includes a nozzle or nozzle array through which reagents are ejected or ejected via an inkjet process (e.g., a thermal inkjet process). A typical nozzle array is a linear array (e.g., single or multiple rows) of nozzles that allows reagent to be dispensed in a row (or multiple rows) or line (or multiple lines), such as across a microscope slide. In a thermal inkjet printhead, heat can be used to form bubbles of reagent vapor, which burst as the reagent vapor is forced through the printhead nozzles. Each nozzle can have a diameter of approximately 20 to 80 micrometers, such as 20 to 50 micrometers.

[0076] The kit 217 also includes a contact 2170 on side 2174. The contact 2170 is designed to interact with the turntable (see [link]). Figure 15 The contact 2170 engages with a contact in the mating part associated with the associated text. Contact 2170 allows the reagent kit to be controlled by controller 209, for example, regarding the discharge or emission of reagent through the nozzle and the amount of reagent discharged.

[0077] Figure 13The kit 217 shown includes a pair of transfer guides on each of sides 2172 and 2173. The transfer guide on side 2172 is described, but it should be understood that the transfer guide on side 2173 is similar. Transfer guide 2176 has a generally rectangular solid structure, for example, made of plastic, and has a width W1 extending parallel to the top surface of kit 217 across the width of side 2172. Transfer guide 2176 has a thickness T1 and a length L1 sufficient to support kit 217 in 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. Transfer guide 2176 includes an engagement protrusion 21762 that projects vertically upward when viewed from the top side of the transfer guide. As observed, transfer guide 2176 is attached to body 2171 (e.g., via adhesive) or is part of body 2171, with a distance when viewed from the top of side 2172 such that the entire transfer guide 2176, including the engaging protrusion 21762, is below the top surface of kit 217. As observed, transfer guide 2177 is attached to body 2171 (e.g., via adhesive) or is part of body 2171 of kit 217 at a location below transfer guide 2176. Transfer guide 2176 has a width W2 extending across the width of side 2172 parallel to the top surface of kit 217, a thickness T2 sufficient to support kit 217 in storage rack 206, and a length L2. Typical thickness T2 is similar to thickness T1 of transfer guide 2176, for example, approximately 0.2 mm to 1 mm, and typical length l2 is approximately 3 mm to 8 mm. Transfer guide 2177 is arranged parallel to transfer guide 2176 along side 2172 and separated from transfer guide 2176 by a gap L3 sufficient to allow the arm of the kit holder to slide between the transfer guides. Each of transfer guide 2176 and transfer guide 2177 may have a rounded or curved front end (the end closest to side 2174 of kit 217) to help position the arm of kit holder between the transfer guides. The base of transfer guide 2177 also includes a notch or mating groove 21772 and a thinned portion 21774 (thickness less than thickness t2) from the front end of the transfer guide to a point directly in front of the notch or mating groove 21772 (1 mm or 2 mm forward). The thinned portion 21774 may have a rear-angled sidewall extending from the top of transfer guide 2177 toward the base. Finally, kit 217 includes frame locking bump 21792, which is a triangular prism with triangular bases correspondingly parallel to the sides 2172 and 2173.Each of the transfer guide 2176, transfer guide 2177 and frame locking bump 21792 may be made of a rigid plastic material that is attached to the kit 217 by, for example, an adhesive or formed as part of the kit 217 by, for example, a molding process.

[0078] Figure 14 A perspective front-right view of a portion of the storage rack 206 is shown. In this view, the storage rack 206 includes a cassette frame support 2064 extending between vertical columns 2063. The storage rack 206 is mounted to the housing 202, with the slot facing the reaction compartment 204 and the turntable 215. The cassette frame support 2064 is an L-shaped body, with the base 20642 of the L-shaped body facing outwards. Pairs of openings or holes 2065 through the base 20642 are provided in the base 20642 of the frame support 2064 to secure the kit to the frame support 2064. Figure 14 Kits 217A and 217B are shown connected to the box frame support 2064. The kits are connected to the box frame support 2064 via the box frame. Figure 14 A cassette frame 2060B supporting reagent kit 217B and a cassette frame 2060C connected to a cassette frame support 2064 but not supporting the reagent kit are shown. It can be understood that a separate cassette frame supports reagent kit 217A, but such cassette frames are obscured and not visible.

[0079] Each box frame (e.g., box frame 2060B and box frame 2060C) includes a shoulder 20602, which is a relatively thin (e.g., 1 mm to 3 mm) rectangular body having an x-direction length greater than the width of the kit. The shoulder 20602 has two openings or holes 20605 that can be aligned with a pair of openings or holes 2065 in the base 20642 of the box frame support 2064 to allow the shoulder 20602 to be attached to the base 20642 of the box frame support 2064 using a pin 20601. The pin 20603 is, for example, an expansion pin (e.g., plastic) having a distal end protruding from the box frame and a body, the distal end operable to slide into the opening or hole 2065, 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 20642 of the box frame support 2064. Pin 20603 can be a capture pin, meaning the pin is permanently fixed to the box frame, or it can be freely inserted into both the shoulder 20602 of the box frame and the base 20642 of the box frame support 2064. Each box frame (e.g., box frame 2060B and box frame 2060C) is designed to be removable from the base 20642 of the box frame support 2064 by using a similar but opposite force required by inserting the pin.

[0080] As observed (x-direction), two arms 20603 protrude vertically from the shoulder 20602. Each arm 20603 has dimensions (e.g., height in the y-direction and thickness in the x-direction) between transfer guides 2176 and 2177 on each side of the kit, allowing the arm to be mounted in a manner that allows the kit to slide in and out of the cassette frame. The arms 20603 are spaced apart from each other by a distance slightly greater than the width of the kit (e.g., when the kit has a width of 6 mm, the arms 20603 are spaced apart by 6.3 mm to 7 mm). The arms 20603 have a length (z-direction) less than the depth of the kit, measured from the shoulder 20602, such as approximately half the depth of the kit. Protruding vertically downward as viewed from the shoulder 20602 (y-direction), each cassette frame contains a ridge 20606. The ridge 20606 has a typical width (x-direction) of approximately 1 mm to 4 mm, a thickness of approximately 0.4 mm to 0.5 mm (z-direction), and a length (y-direction) longer than the height of a portion of the kit measured between the base of the kit behind the printhead region and the bottom of the transfer guide 2177 thereon, such as 1 mm to 2 mm in length. Legs 20607 project vertically from the base (z-direction) of the ridge 20606. The shape at the ridge-leg junction may reflect the transition between the rear sidewall of the kit and the base. Figure 14 In this kit 217B, the transition between the rear sidewall and the substrate is curved, and the ridge-leg junction defines opposite profiles. The leg 20607 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) extending beyond the substrate length of the kit, excluding the printhead area. A protrusion 20608 is provided along a portion of the length dimension of the leg 20607, protruding upwards from the surface of the leg 20607 by 0.2 mm to 0.6 mm, and has a typical shape of a triangular prism with a triangular base in the yz plane. The protrusion 20608 is positioned on the leg 20607 at a distance greater than that from the ridge 20606 than from the kit (kit 217, ...). Figure 13The distance from the rear side of the kit to the front edge of the frame locking protrusion 21792 is such that when the kit is positioned in the kit frame (e.g., kit 217B in kit frame 2069B), the protrusion 20608 faces forward of the frame locking protrusion projecting from the base of the kit. A pad platform 20609 is attached to the end of the leg 20607 of the kit frame. The pad platform 20609 can be a rectangular body with a rectangular face or top (xz plane) larger than the printhead area. A typical area (xz dimension) of the pad platform is approximately 225 mm² to 400 mm². An absorbent material (e.g., a sponge) can be disposed on the surface or top of the pad platform 20609, which can contact the printhead of the kit, receive outflows from the printhead (e.g., excess reagent on the printhead surface), and protect the printhead from drying out.

[0081] The main body of the box frame (e.g., box frame 2060B, box frame 2060C) can be made of rigid plastic material. (See reference) Figure 14 The spine 20606 and leg 20607 may have dimensions (e.g., thickness, width) and / or connections (e.g., 90° connection) that provide elasticity or spring tension to the leg 20607 so that the leg 20607 can move when the kit is attached or removed. As described above, the kit includes a frame locking bump 21792 protruding from its base (see...). Figure 13 The kit 217). When the kit is placed in the cassette frame (i.e., in response to a force applied to the kit in the direction toward the ridge 20606 of the cassette frame), the arms 20603 of the cassette frame slide between transfer guides 2176 and 2177 on the corresponding opposite sides of the kit until the frame locking protrusion 21792 of the kit base contacts the protrusion 20608. The continuous force in the direction toward the ridge 20606 causes the legs 20607 to move downward (by the force of the frame locking protrusion 21792 on the legs), thereby causing the protrusion 20608 to move downward and the frame locking protrusion 21792 to pass over the protrusion 20608. Once the frame locking protrusion 21792 has passed over the protrusion 20608, the legs 20607 return to their initial position (moving upward), thereby allowing the protrusion 20607 to secure or capture the kit in the cassette frame. Separation of the kit from the cassette frame is achieved in a similar manner. The force acting on the kit in a direction away from the spine 20606 will cause the leg 20607 to move downward (by the force of the frame locking protrusion 21792 on the leg), thereby causing the protrusion 20608 to move downward and the frame locking protrusion 21792 to pass over the protrusion 20608.

[0082] The reagent kits (e.g., kit 217A, kit 217B) may be supplied as a component comprising the reagent kit and a box frame (e.g., box frame 2060B, box frame 2060C). This component may be packaged together with the reagent kit in the box frame and supplied to the consumer, or it may be supplied separately with assembly instructions.

[0083] refer to Figure 7 , Figure 11 , Figure 12 and Figure 14 The arm assembly 218 can be used to move reagent kits into and out of the storage rack 206. As an example, the reagent kit assembly (the kit attached to the cassette frame) can be delivered by an operator or robot to the reaction compartment 204 (e.g., to the platform 205 within the reaction compartment 204). The controller 209 contains non-transitory machine-readable instructions that direct the operation of various motors (e.g., rotation direction, runtime, etc.) to bring the turntable 215, which includes the arm assembly 218, to a position to grasp the delivered reagent kit assembly and place it in the storage rack 206. These motors include a motor 2143 that moves the turntable 215 in the x-direction; a motor 21495 that moves the turntable 215 in the z-direction; a motor 21425 that moves the turntable 215 in the y-direction; and a motor 2157 that rotates the base 2152. The machine-readable instructions also include instructions to direct the arm assembly 218, attached to the turntable 215, to grasp the reagent kit assembly and transport it to the storage rack 206 when the turntable 215 is positioned as desired. The instructions may also include instructions to place the kit assembly at a predetermined address in the storage rack 206. The arm assembly 218 includes a cassette engagement head 2183 at its distal end. The cassette engagement head 2183 can be operated based on instructions from the controller 209 to be brought to a position above the kit 217 so that pairs of fingers extending from the cassette engagement head 2183 surround and engage engagement protrusions 21762 of the transfer guide 2176 on each side of the kit 217 (see [link to documentation]). Figure 13 The paired fingers on the housing engagement head 2183 of the arm assembly 218 (see...) Figure 11The spacers on opposite sides may be slightly smaller than the distance between the engagement protrusions 21762 on each side of the kit 217. Typically, the paired fingers on the kit engagement head 2183 are biased to the distance they are separated, but may bend outward a greater distance to engage the engagement protrusions 21762 on opposite sides of the kit 217. The biasing nature of the opposing fingers on the kit engagement head 2183 is similar to the action of a spring clip to hold the kit through the engagement protrusions 21762. To place the kit assembly into the storage rack 206, the instruction guide arm assembly 218 aligns the pin 20603 in the kit assembly with a defined pair of openings or holes 20605 in the base 20642 of the frame support 2064, and applies sufficient force to the kit assembly to insert the pin into the corresponding base 20642 of the frame support 2064.

[0084] To transfer the reagent kit from storage rack 206 to turntable 215, controller 209 includes machine-readable instructions that guide the arm assembly to be positioned at the reagent kit (e.g., the front side of the reagent kit) and grasp the reagent kit (via reagent engagement head 2183, which surrounds and engages the protrusion 21762 of transfer guide 2176 on each side of reagent kit 217). At this point, the reagent kit assembly, including the reagent kit and the kit frame, is mounted in storage rack 206. Once the cassette engagement head 2183 engages the engagement protrusion 21762 of the transfer guide 2176 on each side of the reagent kit 217, the arm assembly 218 applies a force in a direction away from the storage rack (and away from the ridge 20606 of the cassette frame) to deflect (cause downward movement) the legs 20607 of the cassette frame via the force of the frame locking protrusion 21792 on the legs 20607, thereby causing the protrusion 20608 to move downward and the frame locking protrusion 21792 to pass through the protrusion 20608. Once the cassette is separated from its cassette frame, an instruction associated with the controller 209 directs the arm assembly 218 to deliver the cassette to the turntable 215.

[0085] Figure 15 A portion of the turntable 215 is shown, comprising a base or box carrier plate 2152 isolated from the base of the pillar 2151. The base or box carrier plate 2152 is operable to engage and accommodate multiple kits. The base 2152 has a typical decagonal shape and has slots 2153 for kits on each side. It should be understood that the shape and number of kits that the turntable can accommodate can vary. A mating portion 2154 protruding from the surface of the base 2152 (such as the upper surface observed) surrounds each slot 2153. Figure 15 Three docking portions 2154 are shown. It should be understood that the base 2152 may have as many docking portions as the slots. Each docking portion 2154 is configured to receive a reagent kit therein. Figure 15A kit 217 is shown disposed in a docking portion 2154. Each docking portion 2154 includes a rear wall having an outer surface facing the center of a base 2152 and two opposing sidewalls connected to the rear wall. The rear wall slopes from top to bottom, with the bottom of the rear wall closer to the center of the base 2152. The thickness td of the sidewalls is less than the thickness of the transfer guides 2176 and 2177 on the kit (see [reference]). Figure 13 Each sidewall has an upper portion that accommodates a lateral slot 21542 extending from the distal end of the sidewall to a portion near the proximal end (near but not beyond the rear wall) to define an arm portion 21544. Each arm portion 21544 has dimensions that allow the arm portion 21544 to be positioned between transfer guides 2176 and 2177 on the reagent container 217 and to support the reagent container. The mating portion 2154 containing the arm portion 21544 may be made of a plastic (polymer) material.

[0086] The inner surface of the rear wall of each docking section 2154 includes contacts that mate with contacts 2170 on the reagent kit (reagent kit 217). The contacts are electrically connected to the controller 209, thereby allowing the controller 209 to control the reagent kit in each docking section 2154 on the turntable 215 respectively.

[0087] As observed, the lock 2155 is connected to the two opposing sidewalls of each mating portion 2154 at a point below the arm portion 21544. The lock 2155 comprises two parallel arms 21552 separated by the shoulder portion 21554. The width of the shoulder portion 21554 is similar to or slightly larger than the width of the mating portion 2154 so that the arms 21552 can be positioned and connected to the exterior of the respective opposing sidewalls of the mating portion 2154. Figure 15Arms 21552 are shown connected to the sidewalls via pins 21555 (e.g., pins, screws, or rivets), such that the length of the portion of each arm 21552 from the shoulder 21554 to the pin 21555 (distal portion) is greater than the length of the portion of each arm 21552 from the pin 21555 to the proximal end (the end furthest from the shoulder 21554). The connection of the lock 2155 to the mating portion 2154 allows the shoulder 21554 to pivot upward and downward, as observed, without contacting the rear wall of the mating portion 2154 (e.g., the shoulder 21554 is 0.1 mm to 0.5 mm from the outer surface of the rear wall). The distal portion of each arm 21552 is generally rectangular and projects vertically proximally from the shoulder 21554. The proximal portion of each arm 21552 can project upward at an angle relative to the distal portion, such that the angle γ defined between the distal and proximal portions is approximately 150° to 175°. The proximal portion of each arm 21552 may be generally rectangular and includes a proximal end with a protrusion 21556, which is, for example, an upwardly projecting triangular prism with a triangular base parallel to the side of the respective arm. The size of the protrusion 21556 is adapted to the notch or mating groove 21772 in the transfer guide 2177 of the kit (see...). Figure 13 The lock 2155 can be spring-biased at each of the pins 2155, with the shoulder closer to the surface of the base 2152. In this configuration, at least a portion of the protrusion 21556 extends above the base of the recess of the arm portion 21544 defining each mating portion 2154. A downward force on the protrusion 21556 will cause the protrusion to move downward and the shoulder to move upward. Releasing such a downward force will cause the opposite movement.

[0088] An imager, such as a camera, can be attached to the base or cassette support plate 2152. Typically, the imager can be placed in one of the slots 2153, rather than in the docking section and cassette. Alternatively, the imager can be attached to the underside of the support plate 2152. When the microscope slide is removed from the chamber 125 of the body 120 (e.g., when the door 120 is moved to the open position and the slide bed 115 can be moved from a position inside the chamber 125 to a position outside the chamber 125), the imager can be oriented to capture an image of the microscope slide (e.g., an image of the entire microscope slide, an image of an identifier on the microscope slide (e.g., a label (e.g., a barcode)), and / or an image of a sample on the microscope slide). Image capture can be controlled by the controller using instructions to, for example, capture images of the identifiers on the microscope slide before the slide is initially moved into chamber 125, capture images of the sample on the microscope slide after the dewaxing operation, in order to locate the sample on the microscope slide (e.g., via a detection sample (e.g., a stained sample)) to determine where reagents (e.g., primary reagents) are subsequently dispensed and / or after the primary staining operation.

[0089] Refer again Figure 7 , Figure 11 and Figure 15The document describes the transfer of reagent kits from a storage rack 206 or from a platform 205 within a housing 202 via an arm assembly 218. A controller 209 contains non-transitory machine-readable instructions instructing the arm assembly to engage a reagent kit (e.g., reagent kit 217) with a cassette engagement head 2183 of the arm assembly, wherein the cassette engagement head 2183 engages a protrusion 21762 on a transfer guide 2176 of the reagent kit. Such instructions also include instructions to transport the reagent kit to a docking portion 2154 on a base 2152 of a turntable 215, and instructions to align transfer guides 2176 and 2177 of the reagent kit with an arm portion 21554 of one of the docking portions 2154 (aligning transfer guides 2176 and 2177 above and below each arm portion 21554 accordingly). Once aligned, the instructions also include sliding the reagent kit into arm portion 21554 (along a proximal-to-distal direction) so that the nose or base 2179 of reagent kit 217 is turned inward (e.g., towards the center of base 2152). Arm assembly 218 applies a force sufficient to slide the reagent kit into arm portion 21554 in the central direction of base 2152. Transfer guide 2177, with a thickness td greater than the thickness t2 of transfer guide 2177, will contact the proximal portion of each arm 21552 of the compartment lock 2155, causing each arm to rotate about each pin 21555 and push the proximal portion of the arm downward. When the portion of the transfer guide 2177 containing the mating locking groove 21772 is directly positioned above the protrusion 21556 of each arm 21552 of the box lock 2155, the biasing of the box lock will cause each arm 21552 of the box lock 2155 to rotate in opposite directions about the pin 21555, and cause the protrusion 21556 to engage the locking groove 21772. At this time, the kit is secured in the mating portion 2154, and the command associated with the controller 209 will instruct the arm assembly 218 to release its engagement with each engaging protrusion 21762.

[0090] The kit can reach the service station before it is delivered to the docking section (docking section 2154) on the turntable 215 for dispensing operations or returned from the docking section to the storage rack 206. Figure 16 A service station 2190, as observed, is mounted to the rear sidewall of reaction compartment 204 adjacent to a storage rack 206. Service station 2190 provides an area for testing and cleaning the reagent kit printhead before and / or after use in dispensing operations to dispense reagents from it onto microscope slides. Figure 16A front view of service station 2190 is shown. In this example, service station 2190 includes a rear wall 21901. Pulley supports 21903 and 21904 are connected to the rear wall 21901. Each of pulley supports 21903 and 21904 includes an upper roller and a lower roller. A belt 21905 is disposed on the upper roller of each of pulley supports 21903 and 21904. A belt 21906 is disposed on the lower roller of each of pulley supports 21903 and 21904. A guide rail 21902 is disposed between and connected to each of pulley supports 21903 and 21904. Brackets 21907 and 21908 are slidably connected to guide rail 21902 and straps 21905 and 21906. Each of brackets 21907 and 21908 may have a configuration that secures the reagent kit similar to docking section 2154 (see...). Figure 15 ).

[0091] exist Figure 16 In the example shown, for a first-size kit, tray 21907 has a length L1 and a width W1, for example, L1 of 100 mm and W1 of 60 mm; for a second-size kit, tray 21908 has a length L2 and a width W2, for example, L2 of 72 mm and W2 of 60 mm. It should be noted that service station 2190 may be equipped with only one tray, or if multiple trays are included, the trays may accommodate kits of the same or different lengths and widths. As observed from each of trays 21907 and 21908, the base or back surface contains electronic contacts or pins operable to mate with a receiver (contact 2170) on the front side of the kit, similar to the inner surface of the rear wall of each mating portion 2154 of the turntable 215 containing contacts that mate with the contacts 2170 on the kit. Figure 16 The contacts or pins 21914 in bracket 21907 and 21915 in bracket 21908 are shown.

[0092] In one example, the kit (kit 217) has length and width dimensions that fit snugly within tray 21907 or tray 21908. (See above regarding...) Figure 15 The kit (kit 217) is described to include an electronic pin socket 22794 at the front for mating with electronic contacts or pins 21917 in the bracket 21907. The front of the kit may also include two diagonally spaced alignment slots or openings that align with alignment pins 21917 in the bracket 21907 to aid in aligning the kit with the bracket 21907 or bracket 21908.

[0093] Figure 16 A bracket 21907 and a bracket 21908 are shown connected to each of pulley supports 21903 and 21904 via belts 21905 and 21906. Belts 21905 and 21906 can independently move laterally or translate brackets 21907 and 21908 along guide rail 21902. Such movement allows each of the brackets 21907 to carry the reagent container attached thereto to an inkwell 21909 and a wiping station (wiping station 21912 or wiping station 21913). Inkwell 21909 provides a container for dispensing reagents in the brackets 21907 or 21908. Each of wiping stations 11912 and 11913 can be a container (e.g., a rectangular container holding a section of glass ribbon between rollers, with the glass ribbon exposed on the top or sides of the container, as observed). The ribbon has a first side that serves as a cloth or similar absorbent material. The width of the ribbon can be at least as wide as the printhead of the kit. The cloth or similar absorbent material provides a cleaning or wiping area for wiping the printhead (e.g., removing excess reagent from the printhead). After a wiping action by the printhead of the kit on a portion of the ribbon, the ribbon can be advanced by instructions from controller 109 directing the movement of rollers in wiping stations 21912 or 21913.

[0094] Each tray can be electrically connected to and communicate with controller 209. Trays 21907 and 21908 house electronics that operate the reagent kit to dispense reagents, similar to the electronics in docking section 2154, under the guidance of non-transitory machine-readable instructions associated with controller 209. When the reagent kit is connected to tray 21907 or tray 21908, instructions from controller 209 can direct the dispensing of reagents from the reagent kit, for example, dispensing them into contact between inkwell 21909 and the ribbon of the reagent kit's printhead and wipe station 21912 or wipe station 21913.

[0095] In the operational method, instructions from controller 209 may guide either tray 21907 or tray 21908 to move above ink reservoir 21909 via tapes 21905 and 21906. At this time, or before or after, instructions from controller 209 may instruct arm assembly 218 to engage the reagent kit (e.g., kit 217) and mount the kit in the moving tray (e.g., tray 21907). Further instructions from controller 209 may then include instructions to instruct electronics in tray 21907 to dispense or eject a certain amount of reagent into ink reservoir 21909 (e.g., an amount sufficient to wet the printhead and ensure it is not clogged). After the dispensing operation, instructions from controller 209 may instruct the kit to be carried to wipe station 21912 or wipe station 21913 to clean residual reagent from the printhead of the kit via a wiping operation on the printhead on the tape of the wipe station. After wiping, instructions from controller 209 can guide arm assembly 218 to engage reagent container and deliver the reagent container to docking part (docking part 2154) on turntable 215 for dispensing operation or delivery to storage rack 206.

[0096] The above discussion described reagent dispensing techniques using inkjet technology. One dispensing alternative includes a dispensing cartridge connected to a cartridge pump assembly that pumps reagent from the dispensing cartridge onto the sample. Another dispensing alternative may include pipette transfer from a reagent container to the sample.

[0097] The following description is for reference. Figures 1 to 15 Typical operation of the described sample processing system. Initially, an operator or robot brings one or more individual microscope slides, each containing at least one tissue sample, into reaction compartment 204. Each microscope slide is then placed in a sample processor (sample processor 112). Non-transitory machine-readable instructions from controller 209 can instruct the door (door 130) of the body 120 of the sample processor to open, and then instruct the linear actuator 155 of sample processor 112 to move the slide bed 115 from a position inside the chamber (chamber 125) of the body 120 to a position outside the chamber. The microscope slides can then be positioned such that the tissue sample is facing upwards (towards the top of the body 120) or downwards (towards the slide bed 115). Once the slide is placed on the slide bed 115, non-transitory machine-readable instructions from the controller 209 can instruct the imager (e.g., an imager connected to the base or cassette support plate 2152) to capture an image of the identifier on the microscope slide, and further instructions can then instruct the slide bed to return to the interior of the chamber 125 (instructing the linear actuator to move the slide bed 115 within the chamber 125) and instruct the closing of the door 130 of the corresponding reaction station 112.

[0098] Microscope slides containing tissue samples brought to reaction chamber 104 may be embedded in an embedding agent (e.g., paraffin), or may be treated to remove the embedding agent and adhere the tissue sample to the slide (i.e., pretreatment to remove paraffin and adhere the tissue sample to the slide). When the slide is brought to chamber 125 containing tissue samples embedded in an embedding agent such as paraffin, non-transitory machine-readable instructions from controller 209 may instruct the system to perform an adhesion and dewaxing (dewaxing) procedure on the embedded tissue sample. Typically, as part of a baking operation, the instructions may instruct the slide containing the embedded tissue sample to be heated using, for example, hot water introduced into a reservoir in chamber 125 and / or connected to a slide heater connected to slide bed 115 (e.g., below or above slide bed 115). The heat treatment should be sufficient to allow the sample on the slide to adhere or further adhere to the slide (glass slide) and to soften the embedding medium associated with the section on the slide. Typically, the slide can be heated to a temperature of approximately 55°C to 70°C.

[0099] After heat treatment, instructions can be given to remove heat from chamber 125. If the reservoir below the slide bed 115 is full of hot water, instructions from controller 209 can instruct drain valve 159 (see [link]). Figure 1 The hot water is discharged through conduit 158 ​​to the waste collector. If one or more slide heaters are used, instructions from controller 209 can direct the shutdown of one or more slide heaters. Subsequent instructions from controller 209 can direct the embedded tissue sample on the slide to be exposed to a volume of dewaxing solution, such as xylene sufficient to cover a portion of the slide sample. The dewaxing solution, such as xylene, can be stored as a bulk reagent in a container in storage compartment 201 below reaction compartment 204 (see [link to storage compartment 201]). Figure 6 The dewaxing solution container can be connected to a fluid connector 190 on top of the body 120 of the reaction compartment that contains the embedded tissue sample on the slide (see...). Figure 5 Instructions associated with controller 209 can direct the transfer (e.g., pumping) of the dewaxing solution from the dewaxing solution container to the corresponding fluid connector 190, and, if the tissue sample is facing upwards, to the slide surface in the reaction compartment, or if the tissue sample is facing downwards (towards the slide bed), to the slide bed 115. Following the dispensing of the dewaxing solution, instructions associated with controller 209 can direct the tissue sample to immerse in the dewaxing solution for a period of time (e.g., one to five minutes). After the immersion time, instructions associated with controller 209 can direct the slide bed 115 to tilt via rotary motor 140 to drain the dewaxing solution from the tissue sample and / or slide bed 115 (see [link to relevant documentation]). Figure 3 ).

[0100] After a period of time following the removal of the dewaxing solution and paraffin from the substrate surface, further instructions associated with controller 209 can direct valve 159 (see [link to controller 209]). Figure 1 The dewaxing solution is then discharged through conduit 158 ​​into a waste collector. In another example, the dewaxing protocol may involve the sequential dispensing of several reagents. For example, the first reagent applied to the tissue sample on the slide may be xylene. After xylene treatment and its subsequent removal, the dewaxing protocol may specify exposing the tissue sample to an alcohol (e.g., ethanol). In such a case, a container holding xylene would be connected to a first fluid connector 190 on top of the body 120, and a container holding alcohol would be connected to a second fluid connector 190.

[0101] Following the dewaxing process, instructions associated with controller 209 can direct the tissue sample to be rinsed with a specified volume of cleaning solution, such as water or other aqueous cleaning solution. A container holding the cleaning solution can be connected to a fluid connector (fluid connector 190) on body 120 to supply the cleaning solution to the tissue sample. The cleaning solution may also contain a staining agent, such as eosin, to stain the sample on the slide. Generally, after the dewaxing operation, the embedding material in the slide is removed, leaving a sample on the slide that appears as a nearly colorless object. Adding a staining agent (such as eosin) to the cleaning solution can detect the presence and location of the sample on the slide. After the cleaning process, instructions associated with controller 209 can direct the slide bed 115 to rotate to remove the cleaning solution from the slide surface and direct the cleaning solution to be discharged through conduit 158 ​​and valve 159 to a waste collector.

[0102] Following the cleaning process, non-transitory machine-readable instructions from controller 209 can instruct the door (door 130) of the sample processor body 120 to open, and then instruct the linear actuator 155 of sample processor 112 to move the slide bed 115 from a position inside the chamber (chamber 125) of body 120 to a position outside the chamber. Further instructions from controller 209 can instruct the capture of an image of the sample and possible identifiers on the microscope slide by an imager (e.g., an imager attached to the base or cassette support plate 2152), and further instructions can then instruct the slide bed to return to the interior of chamber 125 (instructing the linear actuator to move the slide bed 115 within chamber 125) and instruct the closing of the door 130 of the corresponding reaction station 112. Further instructions can instruct the positioning and storage of the sample or a portion thereof on the microscope slide for use in staining operations.

[0103] Following the cleaning process and possible image capture of the sample and identifiers, instructions associated with controller 209 can direct an antigen retrieval process on the tissue sample to reverse the antigen masking effect of aldehyde fixation. A container holding the antigen retrieval solution (such as a retrieval solution based on tris(hydroxymethyl)aminomethane or citrate) may be stored as a bulk reagent in storage compartment 201 below reaction compartment 204 and connected via a conduit to a fluid connector (fluid connector 190) on body 120 to provide the antigen retrieval solution to the tissue sample. Instructions associated with controller 209 can direct the application of the antigen retrieval solution to the surface of the tissue sample. Instructions associated with controller 209 can also direct the execution of the antigen retrieval process at elevated temperatures and potentially elevated pressures. Typically, instructions can direct the heating of a slide containing the tissue sample to a temperature, for example, approximately 100°C to 130°C, using one or more slide heaters in chamber 125. The instructions may further direct the introduction of air or inert gas into chamber 125 by means such as using a compressor or pump 170, or by means such as through fittings 172 (e.g., valves or valves and conduits) disposed in body 120 (see [link to documentation]). Figure 1 This allows the reaction chamber to reach an increased pressure, such as 1.0 atmospheres (15 pounds per square inch (psi) to 1.7 atmospheres (25 psi)). Compared to previous treatment times of 45 minutes or longer under atmospheric conditions, the increased pressure allows the antigen retrieval process to be accelerated to, for example, 5 minutes. In another example, the antigen retrieval process can be performed at an increased humidity level (such as 70% to 100% relative humidity). As described above, humidity can be increased by including fluid (e.g., water) below the slide bed 115 in the main chamber 125. Before providing the antigen retrieval solution to the surface of the tissue sample, instructions from controller 209 can direct valve 156 to open to allow fluid to enter the chamber, and a volume of fluid is introduced into chamber 125 through valve 156. Steam generated in an external boiler can be supplied to chamber 125, for example, through conduit 157. Instructions from the controller can direct heating element 154 to heat the fluid. Alternatively, air or an inert gas (ambient or heated) can be bubbled through an external reservoir (ambient or heated) to generate humid air at a desired humidity level that can be supplied to chamber 125, for example, through conduit 157. Furthermore, an ultrasonic generator can generate water droplets (ambient or heated) that can be supplied to chamber 125, for example, through conduit 157.

[0104] Once the antigen retrieval process is complete, instructions associated with controller 209 can direct any fluid in chamber 125 used to generate the desired humidity level to drain through conduit 158 ​​and valve 159 into the waste collector, and tilt slide bed 115 to remove the antigen retrieval solution from the slide surface, draining it through conduit 158 ​​and valve 159 into the waste collector. Further instructions can then direct the tissue sample to rinse with a predetermined volume of washing solution, such as water or washing buffer, such as TBS or phosphate-buffered saline containing surfactants. After rinsing, instructions associated with controller 209 can direct slide bed 115 to rotate to remove the washing solution from the surface of the microscope slide, draining it through conduit 158 ​​and valve 159 into the waste collector.

[0105] For the staining process, instructions associated with controller 209 can direct a motor associated with sample processor 112, which houses the microscope slide containing the sample to be stained, to open the door (door 130) of body 120. Further instructions from controller 209 can then direct slide bed 115 to move outside the chamber (chamber 125) of body 120. If this has not been completed previously, further instructions from controller 209 can direct the determination of the location of the sample or a portion thereof on the microscope slide for staining based on captured images of the sample on the microscope slide after the cleaning operation.

[0106] Before or after the microscope slide is removed from the chamber used for the staining process, instructions associated with controller 209 can direct the retrieval of the kit from storage rack 206 and the loading or docking of the kit onto one of the docking portions 2154 on the base 2152 of turntable 215. Further instructions associated with controller 209 can direct the positioning of the kit loaded on base 2152 such that the nose or base of the kit is positioned above the tissue sample on the raised slide. Such instructions include directing motor 2157 to rotate column 2151 and correspondingly rotating base 215 and motor 2143 to move turntable 215 in the longitudinal direction. Once positioned, instructions can direct reagents from the kit to be sprayed (e.g., printed) onto the sample or a portion thereof at a predetermined location. Typically, the on-demand drop-type printhead in the kit, such as a thermal inkjet printhead, can dispense reagents, such as assay reagents or antibodies, in droplets with volumes ranging from 1 picoliter (pL) to 10 nanoliters (nL), or 1 pL to 5 nL, or 1 pL to 1 nL, or 1 pL to 500 pL, or 1 pL to 250 pL, or 1 pL to 100 pL, or 1 pL to 50 pL. Typically, the inkjet cartridge can deliver 15 microliters (μL) per square inch or more (at least 15 μL) per pass, wherein a single pass dispenses (ejects) reagents from multiple nozzles in the printhead of the inkjet cartridge when the kit (rotary) and slide are stationary or when at least one of the kit (rotary) and slide is moving unidirectionally to expand the dispensing area on the slide. Typically, controller 209 directs the printhead of the kit to dispense multiple droplets (i.e., droplets from multiple nozzles) to produce a larger volume of reagent per pass. Typical delivery volumes via thermal inkjet printheads range from 15 μL to 30 μL per square inch, from 15 μL to 25 μL per square inch, and from 15 μL to 20 μL per square inch.

[0107] Instructions associated with controller 209 can also direct the staining process to be performed at elevated temperatures and potentially elevated pressures. Typically, instructions may direct the heating of a slide containing a tissue sample to a desired temperature using one or more slide heaters in chamber 125. Instructions may further direct the introduction of air or inert gas into chamber 125 via means such as using a compressor or pump 170, or via means such as fittings 172 (e.g., valves or valves and conduits) disposed in body 120 (see [link to relevant documentation]). Figure 1 This allows the reaction chamber to reach increased pressures, such as 1.0 atmospheres (15 pounds per square inch (psi) to 2 atmospheres (30 psi)). In another example, the staining process can be performed at increased humidity levels, such as 70% to 100% relative humidity. As described above, for the staining process, humidity levels can be directed via instructions from controller 209, achieved through techniques such as those described above regarding the antigen retrieval process.

[0108] Following the staining process, instructions associated with controller 209 direct the kit and turntable away from the position above the slide, and instruct the slide bed 115 and microscope slides to return to the chamber (chamber 125) and close the door (door 130) of body 120. Further instructions associated with controller 209 may instruct the sample on the microscope slide to extend the incubation period (e.g., to allow the primary antibody to bind to the target antigen). Incubation can be performed in a humid environment. After any incubation period, instructions associated with controller 209 may instruct the tissue sample to be rinsed with a volume of washing solution to remove any unreacted / unbound reagents. After rinsing, instructions associated with controller 209 may instruct the slide bed 115 to rotate to a non-horizontal position within chamber 125 to remove the washing solution from the slide surface. Further instructions may then instruct the washing solution to be discharged through conduit 158 ​​and valve 159 to a waste collector. Once all staining of the tissue sample on the microscope slide is complete, instructions associated with controller 209 may instruct the system to alert the user that the microscope slide is ready for removal. Then, additional instructions from controller 209 can instruct the door 130 of the body 120 of sample processor 112 to open and move the slide bed 115 thereon to a position outside the chamber (chamber 125) to allow an operator or robot to retrieve the microscope slides.

[0109] Example:

[0110] Example 1

[0111] The antigen retrieval process was evaluated using elevated pressure in a sealed sample processor, such as sample processor 112, relative to a control under ambient pressure. Table 1 describes the samples, conditions, and results. At 25 psi (1.7 atm), the antigen retrieval process was completed within 5 or 10 minutes, showing satisfactory and comparable results to the control under ambient pressure, which was completed within 30 minutes. The control conditions were ambient pressure, temperature of 80 to 90°C, and humidity of 80% to 100%.

[0112] Table 1

[0113]

[0114] Example 2

[0115] The reduction in antibody staining time was evaluated using elevated pressure in a sealed sample processor, such as sample processor 112, relative to a control under ambient pressure. Table 2 describes the samples, conditions, and results. At 25 psi (1.7 atm), one process was completed in 2 minutes, another in 5 minutes, and a third in 15 minutes, and the results were satisfactory and comparable to a control that was completed in 30 minutes under ambient pressure, ambient temperature, and 80% to 100% humidity.

[0116] Table 2

[0117]

[0118] aspect

[0119] The instruction manual includes the following aspects:

[0120] 1. A sample processor, comprising:

[0121] A body comprising an inner surface defining a chamber having an opening in a side of the body, and including a volume therein for receiving at least one microscope slide;

[0122] The door includes a first position that covers an opening in the body and a second position that exposes a portion of the chamber through the opening;

[0123] The slide bed is located in the chamber; and

[0124] One of an internal humidity generator installed in the chamber and an external humidity generator connected to the chamber.

[0125] 2. The sample processor according to aspect 1, wherein the sample processor includes an internal humidity generator, and the internal humidity generator is included in a reservoir below the slide bed.

[0126] 3. The sample processor according to aspect 1 or aspect 2 further includes a heat source.

[0127] 4. The sample processor according to any one of aspects 1 to 3, wherein the heat source includes a heater to heat the fluid in the reservoir.

[0128] 5. The sample processor according to aspect 3, wherein the heat source includes a heater to directly or indirectly heat the slide bed.

[0129] 6. The sample processor according to any one of aspects 1 to 5 further includes a pressure source operable to increase the pressure in the chamber to above ambient level.

[0130] 7. The sample processor according to aspect 6, wherein the pressure source is operable to maintain the pressure in the chamber at at least 25 psi (1.7 atm).

[0131] 8. The sample processor according to aspect 6 or aspect 7, wherein the pressure source includes a compressor coupled to and in fluid communication with the body, the body being operable to introduce air into the chamber.

[0132] 9. The sample processor according to aspect 1, wherein the sample processor includes an external humidity generator.

[0133] 10. The sample processor according to aspect 9 further includes at least one heat source.

[0134] 11. The sample processor according to aspect 9 or aspect 10, wherein the heat source includes a heater to directly or indirectly heat the slide bed.

[0135] 12. The sample processor according to any one of aspects 9 to 11, wherein the at least one heat source is operable to maintain the temperature in the chamber at at least 100°C.

[0136] 13. The sample processor according to any one of aspects 1 to 12, wherein the body includes an outer surface and an opposing inner surface, wherein the outer surface includes a plurality of hose connectors coupled thereto, and the inner surface includes a plurality of nozzles in fluid communication with a respective hose connector of the plurality of hose connectors.

[0137] 14. The sample processor according to any one of aspects 1 to 13 further includes a nozzle in the chamber operable to connect to a conduit outside the body, and the nozzle operable to dispense reagents as a spray or curtain flow onto the slide bed.

[0138] 15. The sample processor according to any one of aspects 1 to 14, wherein one of the internal humidity generator and the external humidity generator is operable to generate a humidity greater than 60% in the chamber.

[0139] 16. A sample processing system comprising at least one of the sample processors according to any one of aspects 1 to 15, and further comprising at least one reagent external to the body of the at least one sample processor and coupled to a catheter extending into a chamber of the at least one sample processor.

[0140] 17. The sample processing system according to aspect 16, wherein the at least one reagent can be heated to a temperature above ambient.

[0141] 18. The sample processing system according to aspect 16 or aspect 17, wherein the at least one sample processor is housed in a reaction compartment, and the sample processing system includes a refrigerated storage rack operable to store a plurality of reagent kits.

[0142] 19. A method comprising:

[0143] The sample on the microscope slide in the sealed chamber was subjected to pressure greater than ambient pressure and humidity greater than 60%; and

[0144] Process the sample.

[0145] 20. The method according to aspect 19, wherein processing the sample includes contacting the sample with a reagent.

[0146] 21. The method according to aspect 19 or aspect 20, wherein the reagent includes a staining agent.

[0147] 22. The method according to any one of aspects 19 to 21, wherein contacting the sample with the reagent comprises dispensing the reagent via a thermal inkjet process.

[0148] 23. The method according to aspect 22, wherein dispensing comprises dispensing one or more reagents in an amount of at least 15 microliters (μL) per square inch per dispensing.

[0149] 24. The method according to any one of aspects 19 to 23, wherein processing the sample includes exposing antigenic sites in or on the sample.

[0150] 25. The method according to any one of aspects 19 to 23, further comprising subjecting the sample to a temperature higher than that of the environment.

[0151] In the foregoing description, the invention has been described with reference to specific embodiments thereof. However, it will be apparent that various modifications and alterations may be made therein without departing from the broader spirit and scope of the invention as set forth in the appended claims. For example, the kits disclosed herein (e.g., kit 217) may contain solvents or water instead of reagents and may be used for purposes other than, for example, staining samples on microscope slides. Therefore, the description and drawings are to be considered illustrative rather than restrictive.

Claims

1. A sample processor, comprising: A body comprising an inner surface defining a chamber, the chamber including an opening in a side of the body, and including a volume therein for receiving at least one microscope slide; A door, comprising a first position covering an opening of the body and a second position exposing a portion of the chamber through the opening; A slide bed, which is disposed in the chamber; One of an internal humidity generator disposed in the chamber and an external humidity generator connected to the chamber.

2. The sample processor of claim 1, wherein the sample processor includes an internal humidity generator, and the internal humidity generator includes a reservoir below the slide bed.

3. The sample processor according to claim 2, further comprising a heat source.

4. The sample processor of claim 3, wherein the heat source comprises a heater to heat the fluid in the reservoir.

5. The sample processor of claim 3, wherein the heat source comprises a heater to directly or indirectly heat the slide bed.

6. The sample processor of claim 1, further comprising a pressure source operable to increase the pressure within the chamber to above ambient level.

7. The sample processor of claim 6, wherein the pressure source is operable to maintain the pressure in the chamber at at least 25 psi (1.7 atm).

8. The sample processor of claim 6, wherein the pressure source comprises a compressor coupled to and in fluid communication with the body, the compressor being operable to introduce air into the chamber.

9. The sample processor according to claim 1, wherein the sample processor includes an external humidity generator.

10. The sample processor of claim 1, further comprising at least one heat source.

11. The sample processor of claim 10, wherein the heat source comprises a heater to directly or indirectly heat the slide bed.

12. The sample processor of claim 10, wherein the at least one heat source is operable to maintain the temperature in the chamber at at least 100°C.

13. The sample processor of claim 1, wherein the body comprises an outer surface and an opposing inner surface, wherein the outer surface comprises a plurality of hose connectors connected thereto, and the inner surface comprises a plurality of nozzles in fluid communication with a corresponding hose connector of the plurality of hose connectors.

14. The sample processor of claim 1, further comprising a nozzle in the chamber, the nozzle being operable to connect to a conduit outside the body, and the nozzle being operable to dispense reagents toward the slide bed in the form of a spray or curtain flow.

15. The sample processor of claim 1, wherein one of the internal humidity generator and the external humidity generator is operable to generate a humidity greater than 60% in the chamber.

16. A sample processing system comprising at least one of the sample processors according to claim 1, and further comprising at least one reagent external to the body of the at least one sample processor and coupled to a catheter extending into a chamber of the at least one sample processor.

17. The sample processing system of claim 16, wherein the at least one reagent can be heated to a temperature above ambient.

18. The sample processing system of claim 16, wherein the at least one sample processor is housed in a reaction compartment, and the sample processing system includes a refrigerated storage rack operable to store a plurality of reagent kits.

19. A method comprising: The sample on the microscope slide in the sealed chamber is subjected to pressure greater than the ambient pressure and humidity greater than 60%. as well as Process the sample.

20. The method of claim 19, wherein processing the sample comprises contacting the sample with a reagent.

21. The method of claim 20, wherein the reagent comprises a staining agent.

22. The method of claim 20, wherein contacting the sample with the reagent comprises dispensing the reagent via a thermal inkjet process.

23. The method of claim 22, wherein dispensing comprises dispensing one or more reagents in an amount of at least 15 microliters (μL) per square inch per dispensing.

24. The method of claim 19, wherein processing the sample includes exposing antigen sites in or on the sample.

25. The method of claim 19, further comprising subjecting the sample to a temperature higher than that of the environment.

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