Advanced tissue staining system and method with humidity control

Abstract

This invention discloses a sample preparation apparatus and method for depositing reagents onto biological specimens. [Solution] A sample processor comprising: a body including an inner surface defining a chamber having an opening on the side of the body and a volume for housing at least one microscope slide within the body; a door including a first position for covering the opening of the body and a second position for 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 connected to the chamber. A system comprising at least one sample processor and at least one reagent outside the body of at least one sample processor, and a method comprising exposing a sample on a microscope slide in a sealed chamber to a pressure higher than ambient and a humidity higher than 60%, and processing the sample.

Description

Technical Field

[0001] An automated system for depositing reagents on biological specimens.

Background Art

[0002] In various scenarios, the processing and examination of biological specimens are required for diagnostic purposes. Generally, pathologists and other diagnosticians collect samples from patients, study them, and use microscopes and other devices to evaluate the samples at the cellular level. Pathology and other diagnostic processes typically include a number of processing steps, including the collection of biological samples such as blood and specimens, sample preparation, preparation of microscope slides, staining of samples on microscope slides, examination, re-examination or re-staining, collection of additional samples, re-examination of samples, and finally the provision of diagnostic findings.

[0003] Sample (e.g., specimen) stainers or processors can operate at various levels of automation to process human or animal sample specimens for histological or pathological applications. At various stages of sample processing, various types of chemical reagents can be used, and various systems have been developed for supplying reagents to slides containing specimens. Examples of known reagent supply systems include low-volume dispensers, manual injection into reagent tanks, or bulk containers connected to the stainer via piping.

[0004] Known systems have various drawbacks. For example, manual injection or draining of reagents into the reagent tank is susceptible to cross-contamination, time-consuming, and requires precision in injection, thereby reducing the overall efficiency and accuracy of the sample processing system. Another drawback is that manual injection and draining of reagents can be messy, requiring cleaning up spills and resulting in instrument downtime. A further drawback is that manually selecting and applying the correct reagents carries a significant risk of human error, increasing the likelihood of reagent selection and application errors, leading to false positive or false negative analytical results, reducing not only test accuracy and operational efficiency but also misdiagnosis. [Brief explanation of the drawing]

[0005] Embodiments of the present invention are shown as examples and are not limited to those shown in the accompanying drawings. In the accompanying drawings, similar references indicate similar elements. It should be noted that references to “an” or “one” embodiments in this disclosure do not necessarily refer to the same embodiment, but rather mean at least one. [Figure 1] This shows a perspective side view of the sample processor with the main door in the open position. [Figure 2] This is a perspective side view of the sample processor, with the main door of the sample processor in the closed position and the slide bed inside raised. [Figure 3] Figure 1 shows a top perspective view of the slide bed of the sample processor located inside the chamber of the main unit, and the mechanism that controls the movement of the slide bed, separated from the other components of the sample processor. [Figure 4] Figure 1 shows a top perspective view of the slide bed of the sample processor located inside the chamber of the main unit, and the mechanism that controls the movement of the slide bed, separated from the other components of the sample processor. [Figure 5] Figure 1 shows a perspective view of the lower part of the main body of the sample processing unit. [Figure 6]Figure 1 shows a perspective view of a sample processing system equipped with several sample processing units similar to the one shown in Figure 1. [Figure 7] This shows a perspective left side view of the carousel assembly of the sample processing system in its separated state. [Figure 8] Figure 7 shows a portion of the gantry of the carousel assembly in its separated state, and a perspective right side view of the x-direction (longitudinal direction) drive mechanism. [Figure 9] Figure 7 shows a perspective rear view of the U-shaped bracket and lateral drive support bracket of the carousel assembly in its separated state. [Figure 10] Figure 7 is a perspective rear view of a portion of the carousel assembly. [Figure 11] This shows a side perspective view of the arm assembly of the carousel assembly, separated from the carousel. [Figure 12] Figure 6 shows a perspective front left side view of the storage rack of the sample processing system, separated from the other components of the system. [Figure 13] Figure 12 shows a representative example of a reagent cartridge that can be operated for storage in a storage rack, a side perspective view of the reagent cartridge, and Figure 6 shows its use in a sample processing system. [Figure 14] Figure 12 shows a perspective front right side view of a portion of the storage rack, including two storage cartridges stored within the storage rack. [Figure 15] Figure 12 shows a portion of a carousel assembly, including a pedestal or cartridge carrier plate separated from the base of the cylindrical part of the carousel assembly. [Figure 16] Figure 6 shows a front view of the service station of the sample processing system. [Modes for carrying out the invention]

[0006] The following paragraphs will describe the present invention in detail, with reference to the accompanying drawings. Throughout this specification, the embodiments and examples shown are not intended to limit the invention and should be considered illustrative. Furthermore, references to various aspects of the embodiments disclosed herein do not mean that all claimed embodiments or methods must include the aspects mentioned.

[0007] A sample processor is disclosed. The sample processor typically comprises a body including an inner surface that defines a chamber having an opening on the side of the body, and a volume for housing at least one microscope slide within the chamber. The sample processor also comprises a door including a first position for covering the opening of the chamber and a second position for 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 connected 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.

[0008] Figure 1 shows a perspective side view of the sample processor. The sample processor 112 comprises a body 120. In this typical example, the body 120 of the sample processor 112 is rectangular and comprises a top, base, and a pair of opposing side walls defining the length dimension (z direction), and a separate pair of opposing side walls defining the width dimension (x direction). The top, base, and the two pairs of side walls, together, define a chamber 125 for housing a single microscope slide within the chamber. Typically, the microscope slide may be a flat piece of glass having a thickness of 1 millimeter (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 may be approximately 80 mm to 100 mm (3.2 inches to 4 inches), and the width of the chamber 125 may be approximately 28 mm to 40 mm (1.1 inches to 1.6 inches). It should be understood that the body 120 may have a shape other than rectangular, as long as its shape is capable of accommodating a single slide. In another typical example, the body 120 may have dimensions such that it can accommodate 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 commonly used in staining or tissue processing processes for preparing tissue for staining. Typical metallic materials include, but are not limited to, stainless steel, zinc alloys, aluminum alloys, and silver. For example, silver material may be used to impart antimicrobial properties to the body 120. Other exemplary materials for the body 120 may include heat-conducting polymer materials, such as plastics or cellulosic materials (i.e., materials derived from or containing cellulose), ceramics, Teflon®, and glass. The body 120 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. In addition, please understand that the main body 120 may be composed of more than one of the materials mentioned above.Figure 1 also shows that the body 120 of the sample processor 112 has an opening 122 on one side for accessing the chamber 125. In the illustrated embodiment, the opening is located in the side wall (e.g., the front side wall of the body 120). A gasket or seal 135 made of rubber or other polymer material is positioned around the opening 122 of the body 120 in the illustrated state. The gasket or seal 135 may function to seal or substantially seal (e.g., airtight seal) the chamber 125 when the door covers the opening 122 of the body 120 (see Figure 2). Typically, the chamber 125 may be able to be completely sealed (i.e., airtight seal so that air or gas cannot escape from the chamber 125, and fluid-sealed so that fluid cannot escape from the chamber 125). Figure 2 shows a perspective side view of the sample processor with the door of the sample processor body in the closed position.

[0009] The sample processor 112 includes a door made of a plastic or metal material (e.g., stainless steel, zinc alloy, aluminum alloy, silver) having dimensions such as covering an opening 122 to the chamber 125. The door 130 includes a substantially rectangular portion having similar length (z-direction) and width (x-direction) dimensions as the sides of the body 120 defining the opening 122. One end of the door 130 (the upper end in the illustrated view) includes a clevis portion 132 projecting longitudinally (z-direction) from the substantially rectangular portion. The opposing second end is connected to the base of the body 120 by a hinge so that the door 130 can rotate between an open position in the horizontal direction (z-direction) and a closed position in the vertical direction (y-direction). The movement of the door 130 between the open and closed positions may be controlled, for example, by a motor that rotates an axis positioned through the hinge so that the door 130 rotates around the axis. A latch member 134 is connected to the upper surface of the body 120. In this example, the latch member 134 is a horizontal U-latch toggle clamp, which engages with the clevis portion 132 when the door 130 is in the vertical closed position, clamping the door 130 to the body 120. The latch member 134 and the clevis portion 132 may also be an electronic door latch mechanism and / or an electromechanical door latch mechanism, which may be electrically connected to a control unit that includes non-transient machine-readable commands for controlling the latching and opening / closing of the door 130.

[0010] A slide bed 115 is located within the chamber 125 of the main body 120. In this example, the slide bed 115 has a rectangular platen 1152 with a flat top surface having dimensions (e.g., the same as or slightly larger than the microscope slide (e.g., 1 mm to 2 mm larger) in length (z dimension) and width (x dimension)) such that a microscope slide lies horizontally when viewed on the platen 1152. A protruding lip 1153 of the y dimension surrounds one z-side and the first end (left end or front end in the illustrated state) of the platen 1152. A platform 1151, having dimensions similar to the microscope slide (e.g., 75 mm × 25 mm), is located on and connected to the platen 1152. The platform 1151 supports the microscope slide (microscope slide 150) on it. The platform 1151 has smaller z and x dimensions than the platen 1152. Because the z and x dimensions of the platform 1151 are smaller than those of the platen 1152, a groove (groove 1157) is created between the edge of the platform 1151 and the lip 1153 protruding from the edge of the platen 1152. One or both ends of the platen 1152 (the z-dimension ends) may also have an opening (opening 1158) that penetrates the platen 1152 to allow the reagent introduced onto the platform 1151 to drain.

[0011] As shown in Figure 1, the second end of the slide bed 115 (the right end in the illustrated view) includes a step portion 1154 located in a different plane from the platen 1152 (in the higher y-plane in the illustrated view). The step portion 1154 is separated from the platen 1152 by an inclined portion 1155 positioned at an angle of approximately 20° to 45°.

[0012] Figure 1 shows a microscope slide 150 positioned on the platform 1151 of the 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 so that the sample is away from the platen 1152 (upward in the illustrated state) or facing the platen 1152 (downward in the illustrated state).

[0013] Figure 3 shows a top perspective view of the slide bed 115 and the mechanism that controls the movement of the slide bed 115, separated from the other components of the sample processor 112. Referring to Figure 3, in this example, the slide bed 115 is operable to rotate longitudinally in one direction, for example, to remove liquid. Figure 3 shows a shaft 142 connected at one end to a rotary motor 140 (stepper, brushed DC, or brushless servo) and equipped with a collar 144 around the second opposing end of the shaft 142. The collar 144 is located below the slide bed 115. In one example, the collar 144 has an xy cross-sectional shape of a Fibonacci spiral. Typically, a Fibonacci spiral expands (or moves further from the origin) by a certain coefficient for every quarter turn. In this configuration, as the collar rotates (for example, clockwise), only the widest point or quarter of the spiral shape contacts the bottom surface of the slide bed 115, and the collar 144 is positioned below the slide bed 115 so that the collar 144 lifts the slide bed 115 at the widest point it can contact and lift it. The point of contact of the slide bed 115 by the collar 144 at its widest point does not have to be at the midpoint of the x dimension of the slide bed, but may be shifted by a small distance (e.g., 1 mm to 2 mm) to one side (e.g., the left side in the illustrated configuration) so that the lifting of the slide bed 115 by the collar 144 raises one side of the slide bed 115 so that the slide bed 115 tilts downward to the other z dimension side as shown in Figure 2. The raised z dimension side of the slide bed 115 has a lip 1153 on the edge of the platen 1152, while the other lowered side does not have a lip 1153. The inclination of the slide bed 115 allows any excess fluid (e.g., reagents) that may be on the microscope slide 150 on the slide bed 115, or on the slide bed 115 itself, to be drained from the lowered z-side.

[0014] As shown in Figures 1-3, the rotary motor 140 is located outside the body 120. The rotary motor 140 is connected to a bracket 160. The bracket 160 is fixed to and connected to a platform 152, which is connected to the side of the body 120 opposite to the side with the opening 122. The shaft 142 extends from the rotary motor 140 through the opening in the body 120 such that the shaft 142 and a portion of the collar 144 enter inside the chamber 125. The opening in the body 120 through which the shaft 142 is positioned may be sealed, for example, with a gasket (i.e., air or gas cannot escape from the chamber 125, and fluid is sealed so that fluid cannot escape from the chamber 125).

[0015] 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 having a rotary motor 1552 (stepper, brushed DC, or brushless servo), and a lead screw 1554 having a captive precision nut 1556. The rotary motor 1552 is disposed below the platform 152 and connected to the platform 152 in this example. The rotary motor 1552 is connected to the precision nut 1556, and the lead screw is threaded into the precision nut 1556. The distal end of the lead screw (right side in the illustrated state) is connected to a bracket 160. The sample processor 112 also includes rods 162 and 164 that are parallel to each other, each fixedly connected to a bracket 169 inside the chamber 125 at the proximal end (left side in the illustrated state) and to the bracket 160 at the distal end (right side in the illustrated state). The bracket 169 is disposed below the step 1154 of the slide bed 115 and connected to the step 1154. The openings in the body 120 for the rods 162 and 164 may be sealed, for example, with gaskets (i.e., hermetically sealed so that air or gas cannot escape from the chamber 125 and fluid sealed so that fluid cannot escape from the chamber 125).

[0016] 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 rotary nut 1556 on the lead screw 1554 to move the lead screw 1554 in the z-direction. The movement of the lead screw 1554 causes the bracket 160 to also move in the z-direction. The sample processor 112 further includes a pair of rails or tracks 166 on the platform 152. The bracket 160 is connected to the pair of rails or tracks 166 and can move in the z-direction relative to the rails and tracks in response to the movement directed by the linear actuator 155.

[0017] The linear actuator 155 is fixed to a platform 152 that is connected to the side of the main body 120 opposite to the side having the opening 122 and is connected to the platform 152. When the door 130 is in the open position (see FIG. 1), the linear actuator can move the slide bed 115 from a position within the chamber 125 of the main body 120 to a position outside the chamber, as shown in FIG. 4. When the slide bed 115 is outside the main body 120, the microscope slide may be placed on the empty slide bed or, if present, removed from the slide bed. When the slide bed is outside the main body 120, one or more treatments can also be introduced to the sample on the slide bed.

[0018] The sample processor 112 may function as a humidifier capable of manipulating and maintaining humidity to reduce the evaporation of reagents and the drying of samples (e.g., tissue). Typical humidity levels may be relative humidity above 50%, e.g., above 60% up to 100%, e.g., 70% to 100%, e.g., 80% to 100%, or e.g., 90% to 100%. In the example shown in Figure 1, the body 120 includes a chamber 125 having dimensions for housing a reservoir below the slide bed 115. The reservoir may be filled with water to provide humidity within the chamber 125. Figure 1 shows a valve 156 connected to a conduit 157 extending from an external point on the body 120 through the bottom wall of the body 120 to an internal point on the chamber 125 (e.g., a few millimeters inside the chamber 125). A fluid (e.g., water) source may be connected to the valve 156 to introduce fluid into the chamber 125. The conduit 157 may also be equipped with a flow meter to monitor the amount of fluid being introduced into the chamber 125. In one example, the valve and flow meter may be electrically connected to a control unit that includes non-transient machine-readable commands for introducing a constant volume of fluid into the chamber 125 through valve 156, if present. Also, a conduit 158 ​​extends from the chamber 125 through the base wall of the body 120, which may function as a drain for discharging the fluid contents of the reservoir within the chamber 125. The conduit 158 ​​is connected at its distal end to a drain valve 159 located outside the body 120. In one example, valve 159 may be electrically connected to a control unit that includes non-transient machine-readable commands for operating (opening and closing) the valve.

[0019] The sample processor 112 in Figure 1 also includes a heating element 154. In the example shown in Figure 1, the heating element 154 is an input heater directly mounted in the reservoir of the chamber 125. In another example, the heating element 154 may be located above or within the conduit 157 and may heat the fluid supplied to the reservoir of the chamber 125. The heating element 154 may be an electrically driven resistance heating element. The heating element 154 may be electrically connected to a control unit that includes non-transient machine-readable commands for powering and controlling the heating element, for example, via a thermostat. The ability to heat the fluid in the reservoir (e.g., water) allows the chamber 125 of the sample processor 112 to produce high temperature and humidity by generating water vapor. An ultrasonic humidifier may also be placed in the reservoir and powered to evaporate and humidify the chamber 125 by releasing reservoir droplets within the chamber 125.

[0020] Another technique for introducing humidity into the chamber 125 of the sample processor 112 is to introduce air or an inert gas (at ambient temperature or heated) through a fluid reservoir to create a humidified environment. Typically, air or an inert gas from the ambient or a heat source may be connected to the drain valve 159, or air or an inert gas may be introduced into the reservoir through the conduit 158. A further alternative is to use an ultrasonic humidifier to release tiny water droplets in the air that evaporate into water vapor, thereby humidifying the chamber 125.

[0021] The volume of fluid in the reservoir can be reduced by introducing humidity from the reservoir in the chamber 125 of the sample processor 112. For example, when humidity is introduced into the chamber, water evaporates. To monitor the fluid level in the reservoir, the sample processor 112 may be equipped with a sensor (e.g., a float sensor) in the chamber that sends a signal indicating the fluid level in the reservoir to, for example, the control unit. When the fluid level drops to a predetermined point (volume decreases), additional fluid is added to the reservoir (for example, a non-transient machine-readable command from the control unit instructs the introduction of a certain volume of fluid (e.g., water) into the chamber 125 via the valve 156).

[0022] The sample processor 112 may also include a humidity sensor within the chamber 125. Typically, the humidity sensor may be connected to the upper wall of the main body 120 inside the chamber 125 and provide an indication of the humidity level inside the chamber 125. The humidity sensor may be connected to a visual display unit such as a display (e.g., a liquid crystal display) outside the chamber 120, or to a control unit which may include non-intermittent machine-readable commands for controlling the humidity level (e.g., bringing about, decreasing, or maintaining a certain amount of humidity inside the chamber).

[0023] Another option for introducing humidity into the chamber 125 of the sample processor 112 is to introduce humidity from an external source rather than from a reservoir within the chamber 125. Steam generated in an external boiler may be supplied to the chamber 125, for example, through a conduit 157. Air or an inert gas (at ambient temperature or heated) may be bubbling through an external reservoir (at ambient temperature or heated) to produce humidified air with a desired moisture level that can be supplied to the chamber 125 through a conduit 157, etc. Furthermore, an ultrasonic generator can generate water droplets (at ambient temperature or heated) which can be supplied to the chamber 125 through a conduit 157, etc.

[0024] Sample preparation techniques may involve processing samples (such as tissue samples on microscope slides) at pressures and / or temperatures other than ambient pressure. Typical pressures for a particular sample preparation operation may range from 1 standard atmosphere (atm) (ambient pressure) to 3 atm (14.7 pounds / square inch (psi) to 44.1 psi), e.g., 1 atm to 2 atm (14 psi to 29.4 psi), or e.g., 1 atm to 2 atm, e.g., 1.7 atm (25 psi). Typical temperatures for a particular sample preparation operation may range from 20°C (approximately ambient temperature) to 150°C, e.g., 20°C to 150°C, e.g., 30°C to 140°C, e.g., 40°C to 130°C, e.g., 50°C to 120°C, e.g., 60°C to 110°C, e.g., 70°C to 150°C, e.g., 100°C to 140°C, e.g., 110°C to 140°C, or e.g., 120°C to 130°C.

[0025] To increase the pressure inside the sample processor 112, air or an inert gas may be introduced into the chamber 125 of the body 120 when the door 130 is in the closed position and the body 120 is airtightly sealed (see Figure 2). The body 120 of the sample processor 112 may be connected to a compressor or pump 170, which is a source of compressed air or an inert gas. Typically, the sample processor 112 may have a fixture 172 (e.g., a valve or a valve and conduit) located on the body 120 of the chamber 125. Figures 1 and 2 show a fixture 172 connected to the body 120 at the top wall of the body. It should be understood that the fixture 172 may be connected to another wall (e.g., a side wall, a bottom wall). The compressor or pump 170 may be connected to the fixture 172 via a conduit, e.g., a plastic conduit or a metal conduit. In this example, a pressure regulating unit 174, a pressure release valve 175, and a pressure gauge 176 are located in the conduit between the compressor or pump 170 and the fixture 172. The pressure regulating unit 174 can be used to adjust (e.g., set) a desired or predetermined pressure in the chamber 125. The pressure regulating unit 174 can maintain the pressure in the chamber 125 at a stable or constant level (e.g., high pressure), or at a pulsed level of increased pressure. The pressure release valve 175 can be used to release excess pressure accumulated in the chamber or to return the chamber 125 to ambient pressure. The pressure gauge 176 can be used to indicate the pressure level in the chamber 125 to the operator of the sample processor 112. The pressure gauge 176 in the illustrated embodiment includes a sensor and a display. It should be noted that the pressure gauge 176 does not necessarily have a display at the connection point in the conduit between the fixture 172 and the compressor 170. The pressure gauge 176 is electrically connected to a monitor that displays, for example, the pressure value read by a sensor inside the conduit.

[0026] Another technique for increasing the pressure inside chamber 125 is to change the volume of chamber 125. This may be done, for example, by compressing one or more of the top, bottom, or side walls of the body 120. For example, the upper portion of the side wall of body 120 may have bellows-like sides to allow expansion and contraction of the side wall. The bellows-like sides allow a downward force acting on the top of body 120 to compress the bellows-like portion of the side wall like an accordion, reducing the volume of chamber 125 and increasing the pressure inside chamber 125 when the compression occurs with the door 130 closed.

[0027] The sample processor 112 can change the temperature inside the chamber 125. One way to increase the temperature inside the chamber 125 is by heating the fluid in the reservoir, as shown above with respect to generating a humidity level inside the chamber 125. In addition to this technique, or as an alternative, the slide bed 115 may have heating elements, such as thermocouples, in contact with the underside of the slide bed 115. Another heating technique involves one or more heating elements for heating the peripheral area around the slide bed 115. Examples include resistive electric heating elements or infrared heating elements located inside the chamber 125. A further technique is a heat jacket wrapped around the outside of the body 120 for heating the chamber 125 from the outside. The heat source may be connected to a control unit that controls the heat source in relation to the control unit and enables non-temporary machine-readable commands to control the temperature inside the chamber 125.

[0028] Sample preparation, such as tissue processing to prepare tissue samples on microscope slides for pathological evaluation, typically involves many steps. Typically, such steps include heating the tissue sample to adhere it 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 using dyes or labels to color the tissue sections so they can be viewed under a microscope and evaluated. Typical dyes include hematoxylin, eosin, Masson's trichrome, modified GMS silver stain, Schiff periodate, and Perls Prussian blue iron. Other staining methods, though not limited to these, include immunohistochemistry or in-situ hybridization targeting specific proteins or DNA / RNA sequences within the sample.

[0029] Many of these steps in sample preparation involve contacting the tissue sample with one or more reagents. These reagents 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, stains, e.g., 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 may be in their natural form, purified, concentrated, diluted, or otherwise prepared. Additional primary reagents may include any other substances such as single molecules like fluorescent dyes, enzymes, conjugates (e.g., biotin, avidin, streptavidin), metals (e.g., silver or gold particles), dyes, stains, radiotagging molecules, or signaling molecules or reporter molecules.

[0030] Referring to the tissue processing unit 112, the distribution of reagents to the sample on the microscope slide may be performed using a microscope slide located either outside or inside the chamber 125, or a combination of inside and outside the chamber 125, depending on the reagent. Bulk reagents may, for example, typically be distributed onto a microscope slide located inside the chamber 125. Figure 1 shows an opening 121 that penetrates the top of the main body 120. The opening 121 may be connected to a conduit (not shown) to which reagents can be connected for distribution from outside the main body 120 and the chamber 125. One reagent may be connected to the conduit, or multiple reagents may be connected to the conduit, for example, through a manifold. The opening 121 is directly above the inclined portion 1155 of the slide bed 115. Reagents introduced through the opening 121 may come into contact with the inclined portion 1155 and flow by gravity onto the slide 150, or flow by gravity below the slide 150 if the slide is positioned with the sample side down. Additionally, one or more nozzles may be present inside the chamber 125, connected to the conduit through the opening 121. Such one or more nozzles may be operable to distribute the spray or curtain flow (broad laminar flow) of reagent inside the chamber 125. Such one or more nozzles may direct the reagent flow to the upper surface of the slide 150 (when the microscope slide is positioned sample-side up as shown), or to the inclined section 1155 and / or the stepped section 1154 (when the microscope slide is positioned sample-side down as shown), or to purge reagent or conduit so that the purged reagent flows directly from the inclined section 1155 to the groove 1157, for example, when the microscope slide is positioned sample-side up.

[0031] Figure 5 shows a perspective top view of the upper lower side of the body 120, illustrating an alternative to, or in addition to, the opening 121, another technique for distributing reagents above or below the microscope slide inside the chamber 125. A number of fluid connectors 190 (e.g., 4 to 8 fluid connectors) are positioned protruding from one side of the upper part. The fluid connectors 190 may be fittings or couplings that allow fluid conduits (e.g., polymer piping connected thereto). Typically, the fluid connectors 190 may protrude from the right side of the upper part of the body 120 (opposite the door 130) as illustrated in Figure 1. The lower upper part of the body 120 is provided with a number of conduits 191 arranged longitudinally along the length of the upper part. One of the individual fluid connectors 190 is fluidly connected to the conduits 190 so that fluid can be supplied to the conduits 191 through the fluid connectors 190. The conduits 191 may be piping materials such as metal (e.g., copper, aluminum, stainless steel). Each conduit 191 has an opening 192 along its length, which may discharge fluid from the conduit in the direction of the slide bed 125. Each opening in the conduit may be equipped with a nozzle for controlling the direction and velocity of the flow. The distribution of reagent from each conduit may be a flow, spray, or liquid curtain to optimally cover the sample on the microscope slide or the entire surface of the microscope slide.

[0032] In one example, bulk reagents may be individually connected to the fluid connector 190. The bulk reagents may be contained in individual containers and connected to each of the fluid connectors 190, for example, through conduits running between each bulk reagent container and the fluid connector. The bulk reagents may be supplied to the fluid connectors by using pumps as needed, such as a separate in-line pump for each bulk reagent container connected to the fluid connector. Non-transient machine-readable commands related to the control unit may control the metering of reagents from the bulk reagent containers, for example, by a timer or by individual in-line flow meters (e.g., flow meters in the conduits between the bulk reagent containers and the fluid connectors). The temperature of the dispensed reagents may be changed or controlled before dispensing, as needed, by preheating or cooling. Typical techniques for changing the temperature of the dispensed reagents include heating or cooling the reagent containers before dispensing (e.g., refrigeration of the containers for cooling, oven or hot plate for heating), an external heater, or a ribbon heater wrapped around the conduits between the containers and their respective conduits 191.

[0033] An example of a bulk reagent is a washing solution such as water, or a mixture of water and a surfactant and / or buffer. The washing solution can be used to wash a microscope slide, the entire microscope slide, or a sample on the slide bed 115 (with or without a microscope slide on it). Typically, to wash the slide bed 115 with or without a microscope slide on the platform 1151, the washing solution can be introduced through the opening 121 at the top of the body 120 (see Figure 1) and brought into contact with the inclined section 1155, allowing the washing solution to flow directly into the groove 1157 without flowing over the microscope slide. The washing solution in the groove 1157 is eventually discharged through an opening at the base of the slide bed 115 while the slide bed is horizontal or inclined (or both).

[0034] The bulk reagents distributed to the chamber 125 of the main body 120 may be distributed at a temperature below ambient temperature, at ambient temperature, or above ambient temperature. Higher temperatures may be achieved, for example, by heating the conduits that transfer the reagents to the chamber 125 (e.g., a resistance heating section around the conduits whose output is controlled by a command from the control unit), or by having a separate reservoir for preheating the reagents to a predetermined high temperature.

[0035] In one example, the dispensing of the primary reagent may be performed with the sample and at least a portion of the microscope slide containing the sample outside the chamber 125 of the main body 120. Typically, the door 130 of the main body 120 can move from a closed position to an open position. With the door 120 in the open position, the slide bed 115 can move 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 the inside to the outside of the chamber 125 may be controlled by a control unit that includes non-temporary machine-readable commands, such as commanding a linear actuator 155 to first open the door 130 and then move the slide bed 115 to the position outside the chamber 125.

[0036] When a portion of the slide bed 115 containing a microscope slide with a tissue sample is outside the chamber 125, the reagent can be dispensed in various ways. Such methods include, but are not limited to, overhead dispensing by a thermal or piezo inkjet printhead, dispensing by a spray nozzle, dispensing by a microelectromechanical dispensing mechanism, dispensing by puncturing a reagent container, and dispensing by a dropper mechanism. An example of dispensing by a thermal or piezo inkjet printhead is described in U.S. Patent Application Publication No. 2023 / 0055997 (Application No. 17 / 790,040), titled "Automated Staining System and Reaction Chamber," which is incorporated herein by reference. Examples of dispensing by a spray nozzle, and dispensing by puncturing a reagent container and dropper mechanism, are described in U.S. Patent No. 10,295,444 (Application No. 14 / 579,858), also titled "Automated Staining System and Reaction Chamber," which is incorporated herein by reference.

[0037] The microscope slide may be placed with the sample facing upward (away from the slide bed) or downward (facing the slide bed). The distribution of the reagent from the bulk reagent or primary reagent described above may be distributed directly onto the sample or slide if the sample is facing upward, or if the sample is facing downward, the reagent may be distributed onto the slide bed 115 so that it can move the sample by capillary action.

[0038] Occasionally, excess reagent, including the washing 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 main body 120, which can function as a drain for discharging the fluid contents of the reservoir in the chamber 125. The conduit 158 ​​is connected at its distal end to a drain valve 159 located outside the main body 120.

[0039] Figure 6 shows a perspective view of one embodiment of the sample processing system. The sample processing system 200 comprises a housing 202 for enclosing and storing various components of the processing system 200. The housing 202 comprises a reaction compartment 204 and a storage compartment 201. The reaction compartment 204 is separated from the storage compartment 201 by a platform 205 that forms the base of the reaction compartment 204. In addition to the platform 205, opposing side walls protrude from the platform 205, and a cover connects the ends of each side wall. The cover, side walls, and platform 205 together define the compartment in which sample processing takes place. Access to components within the reaction compartment 204 may be obtained using a cover member 208 and a door member 210.

[0040] The reaction compartment 204 is sized to accommodate a storage rack for storing a number of reagent cartridges (e.g., has an internal volume). The storage rack 206 may be mounted on the platform 205 or on one of the side walls of the reaction compartment 204 (e.g., the rear side wall in the illustrated configuration). The storage rack 206 may be used to store reagent cartridges. Typical reagent cartridges are single-use cartridges, such as inkjet cartridges containing a volume of reagent that can be used for pathological or histological processing. The storage rack 206 includes, for example, an array of slots for storing individual reagent cartridges in a column-and-row array. The storage rack 206 may include a refrigeration section for storing reagent cartridges under refrigeration. A typical refrigeration section may include a compressor that condenses refrigerant vapor, forcing the vapor into a coil to liquefy it and cool the storage rack slots.

[0041] The reaction compartment 204 is sized to accommodate multiple sample processors 112. Each sample processor 112 may be as shown above with respect to Figures 1-5 and the accompanying documentation. Figure 6 typically shows 30 sample processors 112 arranged in a 15x2 configuration in the xz plane on the platform 205. It should be understood that the number and configuration of sample processors depend in part on the area dedicated to the reaction compartment 204. Therefore, it is assumed that the number of sample processors, as well as their configuration, may vary. Above the sample processors 112 in the illustrated configuration is a carousel assembly comprising a gantry 214 and a carousel 215. The carousel 215 can accommodate / hold a number of reagent cartridges and is operable to dispense reagents from each reagent cartridge onto each slide in the sample processor 112. The carousel 215 is operable on the gantry 214 to place reagent cartridges on individual sample processors 112 and to move reagent cartridges to and from storage racks 206.

[0042] The sample processing system 200 also includes a control unit 209. The control unit 209 includes non-transient machine-readable commands that control the operation of the sample processing system, including, but not limited to, loading / unloading reagent cartridges in the storage rack 206 and loading / unloading reagent cartridges in the carousel 215. Figure 6 shows the control unit 209 located outside the housing 202. It should be understood that the control unit 209 may be located outside the housing 202 or may be an internal component of the housing 202.

[0043] Figure 6 typically shows 30 sample processors 112 arranged in a 15x2 configuration on a plane (xz plane), where the sample processors 112 in one row are arranged back-to-back with respect to the other row. The first of the two rows may have sample processors 112, each with an outward-facing door 130 (away from the storage 206). The second of the two rows may have sample processors 112, each with an inward-facing door 130 (towards the storage 206). The back-to-back configuration allows each door 130 of the sample processor to be moved to the open position, as described above, and the slide bed of the sample processor to be positioned outside the chamber 125 of the sample processor body 120. Each sample processor 112 may be connected to the platform 105 of the reaction compartment 104 of the housing 102.

[0044] Referring to Figure 6, in addition to the sample processor 112, the reaction compartment 204 of the housing 202 of the processing system 200 also includes a gantry 214 supporting the carousel 115. The gantry 214 and the carousel 215 are collectively referred to as the carousel assembly. Figure 7 shows a perspective left side view of the carousel assembly in a separated state. The gantry 214 includes two vertical (y-direction) columns 2142 connected to the base of the reaction compartment 204. The vertical columns 2142 are separated by an x-direction distance greater than the distance covered by the row of sample processors 112 in the reaction compartment 204. Above the sample processor 112, two horizontal supports 2144 are positioned between the vertical columns 2142. The horizontal support sections 2144 are typically cylindrical in shape, extending along the x-direction distance of the vertical column 2142, and each is parallel to the base of the reaction compartment 204. The horizontal support sections 2144 are connected to the vertical column 2142 by end brackets 2145 (e.g., inverted L-shaped brackets). The horizontal support sections 2144 are separated by a distance in the z-direction selected for the z-direction movement of the carousel 215, as detailed below. Each horizontal support section 2144 between the end brackets 2145 is connected by a U-shaped bracket 2146 (e.g., inverted U-shaped in the illustrated configuration). The U-shaped bracket 2146 has two legs separated by a base. The horizontal support sections 2144 are connected to the base by linear bearings 2147. A linear bearing 2147 is connected to the upper or exposed side of the base of a U-shaped bracket 2146, allowing the U-shaped bracket 2146 to move in the x-direction on a horizontal support 2144. The base of the U-shaped bracket 2146 has an opening 2148 through which it passes, for example, a rectangular opening. A tab 21493 is also connected to one end of the upper or exposed side of the base of the U-shaped bracket 2146. The tab 21493 protrudes upward (y-direction) from the base. The tab 21493 is connected to a timing belt 2140, which is used to move the U-shaped bracket 2146 in the x-direction (longitudinal direction).

[0045] A lateral drive support bracket 2149 is connected to the base of a U-shaped bracket 2146 located below the horizontal support portion 2144. The lateral drive support bracket 2149 is U-shaped (for example, inverted U-shaped in the illustrated configuration) as defined by its base and side walls. The upper side of the lateral drive support bracket 2149 has an opening 21499 through it in the illustrated configuration. The base of the lateral drive support bracket 2149 has a width in the x-direction that is smaller than the corresponding width of the base of the U-shaped bracket 2146, so that the side walls of the lateral drive support bracket 2149 are positioned between the side walls of the U-shaped bracket 2146, and the side walls of the lateral drive support bracket 2149 are connected to each of the side walls of the U-shaped bracket 2146, for example, by screws, rivets, or welds. Inside each side wall of the lateral drive support bracket 2149, there is a lateral linear guide extending to the z-length of the side wall or 70% to 90% of the z-length. Each lateral linear guide 21492 is located at a similar y-distance from the end of the side wall, which is connected to the side wall by, for example, screws, rivets, or welds. The carousel 215 is connected to each lateral linear guide 21492.

[0046] The carousel 215 can move in three directions relative to the gantry 214. The carousel 215 can move in the x direction (longitudinal direction) as the U-shaped bracket 2146 moves. The carousel 215 can move in the y direction (vertical direction) as the end bracket 2145 moves up and down on the vertical column 2142. The carousel 215 can move in the z direction (lateral direction) as the carousel 215 moves along each of the lateral linear guides 21492 of the lateral drive support bracket 2149.

[0047] Figure 8 shows a perspective right side view of a portion of the gantry 214 to illustrate the drive mechanism in the x-direction (longitudinal direction). In this figure, the gantry 214 includes a horizontal support 2144 connected to a vertical column 2142 by an end bracket 2145. A gear 2141, which rotates in the xz plane, is connected to the top of each end bracket on one side of the gantry 214 (the left side as shown in Figure 8). One end of the gear 2141 is connected to the shaft of a motor 2143, which can be operated to rotate one gear clockwise or counterclockwise. A timing belt 2140 is positioned around the gear 2141 and extends above one of the horizontal support 2144. The timing belt 2140 can be operated to move in the x-direction (longitudinal direction) by the gear 2141. The timing belt 2140 is connected to a tab 21493 attached to a U-shaped bracket 2146 via screws, rivets, pins, etc. (see Figure 7). By connecting the timing belt 2140 to the U-shaped bracket 2146, the motor 2143 can move the U-shaped bracket 2146, and as a result, the lateral drive support bracket 2149 and the carousel 115 can be moved in the x-direction (longitudinal direction).

[0048] Figure 9 shows a perspective rear view of the separated U-shaped bracket 2146 and lateral drive support bracket 2149. Figure 9 shows that the linear bearing 2147 is connected to the upper or exposed side of the base of the U-shaped bracket 2146. The linear bearing 2147 supports the horizontal support 2144 (see Figure 7). Three linear bearings 2147 are shown, one linear bearing at one end of the U-shaped bracket 2146 supporting one horizontal support 2144, and two linear bearings 2147 at the opposite end of the base supporting the other horizontal support 2144, with the z-direction separation of one linear bearing from the two linear bearings corresponding to the z-direction distance between the horizontal support 2144 (see Figure 6). The base of the U-shaped bracket 2146 has an opening 2148 (for example, a rectangular opening) through it, between one linear bearing 2147 and two linear bearings 2147. A tab 21493 is connected to one end of the base of the U-shaped bracket 2146, either the upper or exposed side. The tab 21493 protrudes upward (y-direction) from the base. The tab 21493 is connected to the timing belt 2140, which is used to move the U-shaped bracket 2146 in the x-direction (longitudinal direction) (see Figure 7).

[0049] Figure 9 also shows the z-direction (lateral) drive mechanism. Figure 9 shows a lateral drive support bracket 2149 connected to a U-shaped bracket 2146 and positioned below the U-shaped bracket. Inside each of the side walls 21494A and 21494B of the lateral drive support bracket 2149, there is a lateral linear guide that extends for a portion of the z-direction length of the side wall of the lateral drive support bracket 2149 (e.g., 70% to 90% of the z-direction length). Each lateral linear guide 21492 is located at a similar y-direction distance from the end of the side wall (side walls 21494A and 21494B) that is connected to the side wall by, for example, screws, rivets, welds, etc.

[0050] The z-direction (lateral) drive mechanism shown in Figure 9 also includes two gears 21493 connected to the outside of the side wall 21494A (left side wall in the visible view) of the lateral drive support bracket 2149. In Figure 9, only one of the two gears 21493 can be seen at one end (rear end) of the side wall 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 side wall 21494A of the lateral drive support bracket 2149. Each of the two gears 21493 rotates in the yz plane. One of the two gears 21493 is connected to a worm gear 21496, which is rotated by the shaft of a motor 21495, and the motor 21495 can be operated to rotate clockwise or counterclockwise. The timing belt 21497 is positioned around the gear 21493 and extends along the side wall 21494A of the lateral drive support bracket 2149. The timing belt 21497 is operable to move in the z direction (lateral direction) by the gear 21493.

[0051] Figure 10 is a perspective rear view of a portion of the carousel 215. This figure shows a portion of the carousel 215 that connects to the lateral drive support bracket 2149 of the gantry 214. The carousel 215 comprises a main bracket 21510 having a rectangular shape with a length dimension (x dimension) and a width dimension (z dimension), defined by a pair of opposing side walls positioned inside the lateral drive support bracket 2149. Side walls 21511 and 21514 define the length dimension, and side walls 21512 and 21513 define the width dimension. The main bracket 21510 also comprises an upper portion 21515 that connects to each side wall and has through-openings for the cylindrical portion 2151. A z-shaped bracket 2153 is connected to the side wall 21512 of the main bracket 21510. The z-shaped bracket 2153 has a base portion 21531 that protrudes horizontally (x direction) at a distance d from the side wall 21512, an intermediate portion 21532 that protrudes vertically (y direction), and a top portion 21533 that protrudes horizontally (x direction) from the intermediate portion 21532. Because the z-shaped bracket 2153 protrudes at a distance d from the side wall 21512, the intermediate portion 21532 and the top portion 21533 can be positioned outside the side wall (side wall 21494A) of the lateral drive support bracket 2149 when the main bracket 21510 is placed inside the lateral drive support bracket 2149. A timing belt 21497 (see Figure 9) is connected to the top 2153 (for example, via screws, rivets, pins, etc.) so that the motor 21495 can move the main bracket 21510 of the carousel 215 in the z direction (lateral direction). A lateral sliding bearing 2154 is mounted on the side wall 21512, which is operable to engage with a lateral linear guide 21492 connected to the inside of the side wall 21494A of the lateral drive support bracket 2149 (see Figure 9). A roller 2159 protrudes outward from the side wall 21513 (opposite side wall 21512). The roller 2159 engages within the lateral linear guide 21492 on the side wall 21494B of the lateral drive support bracket 2149 and is operable to rotate in the yz plane.

[0052] As described above, the main bracket 21510 includes an upper portion 21515 having a through-opening for the cylindrical portion 2151. The cylindrical portion 2151 has cut or inserted teeth around its upper portion. A slewing bearing 2155 is located in the upper portion 21515 of the main bracket 21510. The slewing bearing 2155 includes an outer ring and an inner ring, the inner ring incorporating a gear having cut or inserted teeth that mesh with the teeth around the upper portion of the cylindrical portion 2151. A gear 2156 is located on the upper surface of the slewing bearing 2155 and connected to it. The gear 2156 rotates in the xz plane and can be operated to rotate the inner ring of the slewing bearing 2155 in the same plane, thereby rotating the cylindrical portion 2151. The main bracket 21510 remains stationary (does not rotate). The gear 2156 is rotated by a motor 2157. Motor 2157 is mounted on the upper portion 21515 of the main bracket 21510 and has a shaft extending from there that rotates in the yz plane. The shaft is connected to a worm gear 2158 that meshes with gear 2156, causing gear 2156 to rotate in the xz plane. Referring to Figure 7, the base of the cylindrical portion 2151 of the carousel 215 is equipped with a pedestal or cartridge carrier plate 2152 that engages with and is operable to house a number of reagent cartridges. The rotation of the cylindrical portion 2151 by motor 2157 rotates the pedestal 2152.

[0053] Referring again to Figure 7, the gantry 214 comprises two vertical columns 2142. The vertical columns 2142 are shown together with rectangular housings 21422 arranged around lead screws 21424. Each lead screw 21424 is connected to its respective end bracket 2145 and driven (rotates clockwise or counterclockwise) by its respective stepping motor (motor 21425), with one stepping motor slave-connected to the other stepping motor. The rotation of the lead screws 21424 provides y-direction movement of the end bracket 2145, and correspondingly provides y-direction movement of the horizontal support 2144 and carousel 215.

[0054] As described above, the carousel 215 can move in three directions relative to the gantry 214. The carousel 215 can move in the x-direction (longitudinal direction) as the U-shaped bracket 2146 moves, driven by motor 2143. The carousel 215 can move in the y-direction (vertical direction) as the end bracket 2145 moves up and down on the vertical column 2142, driven by stepper motor 21425. The carousel 215 can move in the z-direction (lateral direction) as the carousel 215 moves along each of the lateral linear guides 21492 of the lateral drive support bracket 2149, which is driven by motor 21495. Motors 2143, 21425, and 21495 are controlled by non-temporary machine-readable commands in the control unit 209 that command their operation (e.g., direction of rotation, execution time, etc.).

[0055] The carousel 215 is operable to automatically load / unload, engage, or accommodate / disengage or release a number of reagent cartridges on the base 2152. Referring to Figure 7, the carousel 215 can automatically load / unload reagent cartridges by using an arm assembly 218. Figure 11 is a side perspective view of the arm assembly 218 separated from the gantry 214 and the carousel 215. The arm assembly 218 includes an attachment bracket 2182 attached to the outer surface of the side wall 21511 of the main bracket 21510 (for example, attached to the midpoint of the side wall 21511 (see, for example, Figure 10)) via bolts, screws, rivets or pins. A short actuator 2184 is connected to the top of the attachment bracket 2182, and a long actuator 2186 is connected to the bottom of the attachment bracket 2182. In Figure 7, the long actuator 2186 protrudes almost vertically (horizontally in the illustrated configuration) from the attachment bracket 2182, and the short actuator 2184 protrudes almost diagonally (for example, at a 45° angle) from the attachment bracket 2182 to connect with the long actuator 2186. A cartridge engagement head 2183 is connected to the end of the long actuator 2186. The cartridge engagement head 2183 has a pair of finger portions separated by a distance d1 on opposite sides, so that the finger portions surround the protruding portion of the reagent cartridge (described below), engage with the reagent cartridge, and move it.

[0056] Figure 11 shows that the upper portion of the attachment bracket 2182 has a clevis portion 21822 and the lower portion has a clevis portion 21823. One end of the short actuator 2184 is connected to the clevis portion 21822 so as to be able to rotate around a clevis pin, screw, or bolt, for example. Similarly, one end of the long actuator 2186 is connected to the clevis portion 21823 so as to be able to rotate around a clevis pin, screw, or bolt, for example. The short actuator 2184 and the long actuator 2186 each have an electrically operated telescopic body (e.g., a body with three stages of continuously small cylinders or columns). The second end of the short actuator 2184 is connected to the smallest stage or to the plunger of the long actuator 2186 by linkage 2185. Linkage 2185 is close to the engagement head 2183. The connection position of the short actuator 2184 to the long actuator 2186 is selected such that, when the short actuator 2184 is fully retracted, the short actuator 2184 rotates the long actuator 2186 by a few degrees (e.g., up to 10°, e.g., 2° to 8°) around the clevis portion 21823, and the distal end of the long actuator 2186 with the engaging head moves toward (lifts) toward the clevis portion 21822. The long actuator 2186 may extend in a configuration that is lifted to a position above the reagent cartridge. The short actuator 2184 may then extend to rotate the long actuator 2186 in the opposite direction (i.e., rotate the long actuator toward the clevis portion 21822), and the engaging head may be lowered toward the reagent cartridge to grasp the reagent cartridge.

[0057] As described above and shown in Figure 6, the sample processing system 200 comprises a housing 202 for enclosing and storing various components of the processing system 200, including a storage rack 206. The storage rack 206 may be used to store reagent cartridges (e.g., reagent cartridge 217). Figure 12 shows a perspective front left side view of the storage rack 206 separated from the other components of the housing 202. The storage rack 206 comprises a housing 2062 having slots facing the reaction compartment 204 and the carousel 215. The storage rack 206 contains an array of slots for storing individual reagent cartridges. Figure 12 shows an array of slots in the order of 5 rows × 25-30 columns. The array of rows and columns allows each slot to have an address (e.g., designated by row and column numbers) so that the system can know the location of a reagent cartridge in the storage rack 206, locate the reagent cartridge, or return the reagent cartridge to a specific slot in the storage rack 206. In Figure 12, reagent cartridges (reagent cartridge 217) are fixed in all slots of the array. The outer surface of each reagent cartridge may include an identifier, such as a barcode, which contains identification information about the reagent contained in the reagent cartridge, and other information such as the expiration date, if possible. The identifier is read by a reader (e.g., a barcode reader), and the read information is provided electronically to the control unit 209. One example is a reader on a carousel 215 electronically connected to the control unit 209. The identifier on the reagent cartridge (e.g., reagent cartridge 217) may have a rewritable IC chip that can store the identity of the reagent, lot number, expiration date, and number of uses.

[0058] Figure 13 shows a side perspective view of a reagent cartridge 217, a typical example of a reagent cartridge that can be operated for storage in a storage rack 206, and its use in a sample processing system 200. Typically, the reagent cartridge 217 has a z-depth of approximately 67.4 mm, an x-width of 5 to 10 mm, and a y-height of 98.5 mm. In another example, the reagent cartridge 217 has similar depth and width, and a height of 70.8 mm (H2 is smaller than H1). The reagent cartridge 217 may also be a drop-on-demand (e.g., inkjet) cartridge, such as a thermal drop-on-demand cartridge or a piezoelectric drop-on-demand cartridge, and the reagent cartridge has individual dedicated printheads positioned at the base of the reagent cartridge 217 in the illustrated configuration.

[0059] The reagent cartridge 217 contains a certain volume of reagent and may have a dedicated printhead. Each cartridge may be a single-use cartridge. In this context, a single-use cartridge means that once the volume of reagent in the cartridge is dispensed or used, the cartridge with its printhead is discarded or disposed of rather than being refilled with a certain volume of reagent. The reagent cartridge may contain (or be supplied with) a volume of reagent suitable for dispensing the reagent onto one or more samples (e.g., tissue samples) on a slide. An example of a single-use cartridge is a thermal inkjet cartridge. Referring to Figure 13, the reagent cartridge 217 comprises an outer shell or body 2171 having a substantially rectangular shape, constructed from a plastic material (e.g., rigid plastic or polymer). Figure 13 shows that the reagent cartridge 217 has a side 2172 and an opposing side 2173 representing the yz dimension, and a side 2174 and an opposing side 2175 representing the xy dimension. Side 2174 contacts and engages with the carousel 215. The reagent cartridge 217 includes a printhead 2178 that can be operated to eject reagent from the cartridge. The printhead 2178 may be located on or near the nose or base 2179 of the reagent cartridge 217 (towards the bottom in the illustrated configuration) so that when the reagent cartridge is inserted into the carousel 215, the ejection of reagent occurs through the base 2179 of the reagent cartridge. The portion of the nose or base 2179 containing the printhead 2178 (the printhead region) may extend in a stepped manner downward from the rest of the base 2179. The printhead 2178 of the reagent cartridge 217 includes nozzles or an array of nozzles from which the reagent is ejected or discharged by an inkjet process (e.g., a thermal inkjet process). A typical array of nozzles is a linear array of nozzles (e.g., one or more rows) that can discharge reagent in a single line or row, for example, across a microscope slide. In a thermal inkjet printhead, heat can be used to create bubbles of reagent vapor that can be exploded as they pass through the nozzles of the printhead.Each nozzle may have a diameter of 20 to 80 microns, for example, about 20 to 50 microns.

[0060] The reagent cartridge 217 also includes a contact 2170 on its side 2174. The contact 2170 is designed to mate with a contact in a dot associated with the carousel (see Figure 15 and related text). The contact 2170 allows the reagent cartridge to be controlled by the control unit 209, for example, with respect to the discharge or ejection of reagent through the nozzle and the amount of reagent discharged.

[0061] The reagent cartridge 217 shown in Figure 13 is equipped with a pair of transfer guides on each of its sides 2172 and 2173. While the transfer guide on side 2172 has been described, it should be understood that the transfer guide on side 2173 is similar. The transfer guide 2176 has a substantially rectangular solid structure, for example, made of plastic material, and has a width W1 that extends across the width of side 2172 parallel to the upper surface of the reagent cartridge 217. The transfer guide 2176 has a thickness T1 and length L1 sufficient to support the reagent cartridge 217 within the storage rack 106. Typical thickness T1 is approximately 0.2 mm to 1 mm, and typical length L1 is approximately 3 mm to 10 mm. The transfer guide 2176 is equipped with an engaging projection 21762 that protrudes vertically upward when viewed from above the transfer guide. As illustrated, the transfer guide 2176 is connected to the body 2171 (e.g., via adhesive) or is a portion of the body 2171 at a distance from the top of the side 2172 such that the entire transfer guide 2176, including the engaging projection 21762 as shown, is below the upper surface of the reagent cartridge 217. The transfer guide 2177 is connected to the body 2171 of the reagent cartridge 217 (e.g., via adhesive) or is a portion of the body 2171 at a position below the transfer guide 2176 as shown. The transfer guide 2176 has a width W2 extending across the width of the side 2172 parallel to the upper surface of the reagent cartridge 217, and has a thickness T2 and length L2 sufficient to support the reagent cartridge 217 in the storage rack 206. A typical thickness T2 is similar to the thickness T1 of the transfer guide 1176, for example, about 0.2 mm to 1 mm, and a typical length L2 is about 3 mm to 8 mm. The transfer guide 2177 is positioned parallel to the transfer guide 2176 along the side 2172, and is separated from the transfer guide 2176 by a gap L3 sufficient for the arms of the cartridge support to slide between the transfer guides. The transfer guides 2176 and 2177 may each have a rounded or curved front end (the end closest to the side 2174 of the reagent cartridge 217) to assist in positioning the arms of the cartridge support between the transfer guides.The base of the transfer guide 2177 also includes a notch or docking groove 21772 and a thin-walled section 21774 (with a thickness less than a certain thickness, t2) extending from the front end of the transfer guide to a point just ahead (1 mm or 2 mm ahead) of the notch or docking groove 21772. The thin-walled section 21774 may have a side wall angled backward from the top of the transfer guide 2177 toward the base. Finally, the reagent cartridge 217 includes a frame locking bump 21792, which is a triangular prism with a triangular base parallel to the sides 2172 and 2173, respectively. The transfer guides 2176, 2177, and 21792 may each be made from a rigid plastic material, either attached to the reagent cartridge 217 by, for example, an adhesive, or being part of the reagent cartridge 217 formed by, for example, a molding process.

[0062] Figure 14 shows a perspective front right side view of a portion of the storage rack 206. In this figure, the storage rack 206 includes a cartridge frame support 2064 extending between vertical columns 2063. The storage rack 206 is mounted on the housing 202 with its slots facing the reaction compartment 204 and the carousel 215. The cartridge frame support 2064 is an L-shaped body, with the base 20642 of the L-shaped body facing outwards. The base 20642 of the frame support 2064 has a pair of openings or holes 2065 that pass through the base 20642, which are used to secure reagent cartridges to the frame support 2064. Figure 14 shows reagent cartridges 217A and 217B connected to the cartridge frame support 2064. The reagent cartridges are connected to the cartridge frame support 2064 using the cartridge frame. Figure 14 shows cartridge frame 2060B supporting reagent cartridge 217B, and cartridge frame 2060C connected to cartridge frame support 2064 but not supporting a reagent cartridge. Note that a separate cartridge frame supports reagent cartridge 217A, but such a cartridge frame is obscured from view.

[0063] Each cartridge frame (e.g., cartridge frame 2060B and cartridge frame 2060C) includes a shoulder portion 20602, which is a relatively thin (e.g., 1 mm to 3 mm) rectangular body having an x-length greater than the width of the reagent cartridge. The shoulder portion 20602 has two openings or holes 20605, which align with a pair of openings or holes 2065 in the base 20642 of the frame support 2064, allowing the shoulder portion 20602 to connect to the base 20642 of the cartridge frame support 2064 via the use of a pin 20601. The pin 20603 is, for example, an expander pin (e.g., plastic) having a distal end protruding from the cartridge frame and a body, the distal end being operable to slide into the opening or hole 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 cartridge frame support 2064. Pin 20603 may be a captive pin (meaning the pin is permanently fixed to the cartridge frame) or it may be freely introduced into both the shoulder portion 20602 of the cartridge frame and the base portion 20642 of the cartridge frame support portion 2064. Each cartridge frame (e.g., cartridge frame 2060B and cartridge frame 2060C) is designed to be removable from the base portion 20642 of the cartridge frame support portion 2064 by similar but opposite forces required to insert the pin.

[0064] The two arm sections 20603 project vertically (in the x-direction) from the shoulder section 20602. Each arm section 20603 has dimensions (e.g., height in the y-direction and thickness in the x-direction) that allow it to fit between the transport guides 2176 and 2177 on each side of the reagent cartridge, so that the reagent cartridge can slide in and out of the cartridge frame. The arm sections 20603 are spaced apart from each other by a distance slightly greater than the width of the reagent cartridge (e.g., if the reagent cartridge is 6 mm wide, the arm sections 20603 are spaced 6.3 mm to 7 mm apart from each other). The length of the arm section 20603 measured from the shoulder section 20602 (in the z-direction) is less than the depth of the reagent cartridge, for example, approximately half the depth of the reagent cartridge. Projecting vertically downward (in the y-direction) from the shoulder section 20602 in the illustrated configuration, each cartridge frame is equipped with a spine section 20606. The spine portion 20606 has a typical width of approximately 1 mm to 4 mm (x direction), a thickness of approximately 0.4 mm to 0.5 mm (z direction), and a length (y direction) that is longer than the height of the portion of the reagent cartridge measured between the base of the reagent cartridge located behind the printhead area and the bottom of the transport guide 2177 above it (e.g., 1 mm to 2 mm longer). The leg portion 20607 protrudes perpendicularly (z direction) from the base of the spine portion 20606. The shape at the interface between the spine portion and the leg portion may reflect the posterior side wall and the transition area of ​​the base of the reagent cartridge. In Figure 14, the posterior side wall and the transition area of ​​the base of the reagent cartridge 217B are curved, and the interface between the spine portion and the leg portion defines an opposite contour. The leg portion 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) that extends to the length of the base of the reagent cartridge excluding the print head area. A raised portion 20608 is positioned along a portion of the length dimension of the leg portion 20607, and the raised portion 20608 typically protrudes upward by 0.2 mm to 0.6 mm from the surface of the leg portion 20607, and has a typical triangular prism shape with a triangular base on the yz surface.The raised portion 20608 is positioned on the leg portion 20607 at a distance from the spine portion 20606 that is greater than the distance from the rear side of the reagent cartridge (reagent cartridge 217, Figure 13) to the front edge of the frame locking bump 21792, such that when the reagent cartridge is placed in the cartridge frame (for example, reagent cartridge 217B in cartridge frame 2069B), the raised portion 20608 is in front of the frame locking bump protruding from the base of the cartridge. The pad platform 20609 is connected to the end of the leg portion 20607 of the cartridge frame. The pad platform 20609 may be a rectangular body having a rectangular surface or top (xz plane) larger than the printhead area. A typical area (xz dimension) of the pad platform is 225 mm². 2 ~400mm 2 To that extent, an absorbent material (e.g., sponge) may be placed on the surface or top of the pad platform 20609 that can contact the printhead of the reagent cartridge, receive runoff from the printhead (e.g., excess reagent on the surface of the printhead), and protect the printhead from drying out.

[0065] The main body of the cartridge frame (e.g., cartridge frame 2060B, cartridge frame 2060C) may be made of a rigid plastic material. Referring to Figure 14, the spine portion 20606 and the leg portion 20607 may have dimensions (e.g., thickness, width) and / or connections (e.g., 90° joints) that provide spring tension to the leg portion 20607, allowing the leg portion 20607 to move when the reagent cartridge is connected or removed. As described above, the reagent cartridge is equipped with a frame locking bump 21792 protruding from its base (reagent cartridge 217, see Figure 13). When the reagent cartridge is placed within the cartridge frame (i.e., in response to a force applied to the reagent cartridge toward the spine portion 20606 of the cartridge frame), the arm portion 20603 of the cartridge frame slides between the transport guides 2176 and 2177 on opposite sides of the cartridge until the frame locking bump 21792 at the base of the reagent cartridge contacts the projection 20608. If the force continues to be applied toward the spine portion 20606, the leg portion 20607 moves downward (due to the force of the frame locking bump 21792 on the leg portion), causing the projection 20608 to move downward, and the frame locking bump 21792 to pass over the projection 20608. Once the frame locking bump 21792 has passed over the projection 20608, the leg portion 20607 returns to its original position (moves upward), allowing the projection 20607 to secure or capture the reagent cartridge within the cartridge frame. Separating the reagent cartridge from the cartridge frame is achieved in a similar manner. When force is applied to the reagent cartridge away from the spine 20606, the leg 20607 moves downward (due to the force of the frame locking bump 21792 on the leg), causing the projection 20608 to move downward, and the frame locking bump 21792 to pass over the projection 20608.

[0066] Reagent cartridges (e.g., reagent cartridge 217A, reagent cartridge 217B) may be supplied as an assembly comprising the reagent cartridge and a cartridge frame (e.g., cartridge frame 2060B, cartridge frame 2060C). The assembly may be supplied to the consumer packaged together with the reagent cartridge in the cartridge frame, or it may be supplied separately with assembly instructions.

[0067] Referring to Figures 7, 11, 12, and 14, the arm assembly 218 can be used to move reagent cartridges in and out of the storage rack 206. For example, a reagent cartridge assembly (reagent cartridges connected to a cartridge frame) may be supplied to the reaction compartment 204 by an operator or robot (e.g., supplied to a platform 205 inside the reaction compartment 204). The control unit 209 includes non-temporary machine-readable commands that instruct the operation of various motors (e.g., direction of rotation, execution time, etc.) to move the carousel 215, which includes the arm assembly 218, to a position such that it grasps the supplied reagent cartridge assembly and places the reagent cartridge assembly in the storage rack 206. These motors include a motor 2143 that moves the carousel 215 in the x direction, a motor 21495 that moves the carousel 215 in the z direction, a motor 21425 that moves the carousel 215 in the y direction, and a motor 2157 that rotates the base 2152. Once the carousel 215 is positioned as desired, the machine-readable command also includes a command to instruct the arm assembly 218 connected to the carousel 215 to grasp the reagent cartridge assembly and transport the reagent cartridge assembly to the storage rack 206. The command may further include a command to place the reagent cartridge assembly at a predetermined address within the storage rack 206. The arm assembly 218 is equipped with a cartridge engagement head 2183 at its distal end. Based on a command from the control unit 209, the cartridge engagement head 2183 is operable to position itself above the reagent cartridge 217 so that a pair of finger portions extending from the cartridge engagement head 2183 surrounds and engages with the engagement projections 21762 of the transport guides 2176 on each side of the reagent cartridge 217 (see Figure 13). The pairs of finger portions on the cartridge engagement head 2183 of the arm assembly 218 (see Figure 11) may be spaced apart on their opposing sides by a distance slightly smaller than the distance between the engagement protrusions 21762 on each side of the reagent cartridge 217.Typically, the pair of finger portions on the cartridge engagement head 2183 are biased toward their greater distance from each other, but can be bent outward to a greater distance to engage with the engaging projections 21762 on the opposing sides of the reagent cartridge 217. The biased nature of the opposing finger portions on the cartridge engagement head 2183 acts like a spring clamp, holding the reagent cartridge by the engaging projections 21762. To place the reagent cartridge assembly in the storage rack 206, the command instructs the arm assembly 218 to align the pin 20603 in the cartridge assembly with a pair of predetermined openings or holes 20605 in the base 20642 of the frame support 2064, and to apply sufficient force to the reagent cartridge assembly to insert into the corresponding pin in the base 20642 of the frame support 2064.

[0068] To transfer the reagent cartridge from the storage rack 206 to the carousel 215, the control unit 209 includes a machine-readable command to the arm assembly to position itself on the reagent cartridge (e.g., the front side of the reagent cartridge) and to grasp the reagent cartridge (via the cartridge engaging head 2183, which surrounds and engages with the projections 21762 of the transfer guide 2176 on each side of the reagent cartridge 217). At this point, the reagent cartridge assembly, comprising the reagent cartridge and the cartridge frame, is mounted on the storage rack 206. When the cartridge engagement head 2183 grips the engagement projections 21762 of the transport guides 2176 on each side of the reagent cartridge 217, the arm assembly 218 applies force away from the storage rack (and away from the spine 20606 of the cartridge frame), and the force of the frame locking bumps 21792 of the reagent container 217 applied to the legs 20607 causes the legs 20607 of the cartridge frame to flex (move downward), the projections 20608 to move downward, and the frame locking bumps 21792 to pass over the projections 20608. Once the cartridge is separated from its cartridge frame, commands associated with the control unit 209 instruct the arm assembly 218 to feed the cartridge into the carousel 215.

[0069] Figure 15 shows a portion of a carousel 215 comprising a pedestal or cartridge carrier plate 2152 separated from the base of a cylindrical section 2151. The pedestal or cartridge carrier plate 2152 is operable to engage with and house a number of reagent cartridges. The pedestal 2152 has a typical decagonal shape with slots 2153 on each side for reagent cartridges. It should be understood that the shape and number of reagent cartridges that the carousel can accommodate can vary. Around each slot 2153 are docks 2154 protruding from the surface of the pedestal 2152 (the upper surface in the illustrated view). Figure 15 shows three docks 2154. It should be understood that the pedestal 2152 may have the same number of docks as slots. Each dock 2154 is configured to house a reagent cartridge within it. Figure 15 shows a reagent cartridge 217 fixed to one dock 2154. Each dock 2154 comprises a rear wall having an outer surface facing the center of the base 2152, and two opposing side walls connected to the rear wall. The rear wall slopes from top to bottom, and the bottom of the rear wall is close to the center of the base 2152. The side walls have a thickness t d The dock 2154, having a thickness less than the thickness of the transfer guides 2176 and 2177 on the reagent cartridge (see Figure 13). The upper portion of each side wall extends from the distal end of the side wall to a portion near the proximal end (near but not the back wall) and has a lateral slot 21542 that defines an arm portion 21544. Each arm portion 21544 has dimensions such that it is positioned between the transfer guides 2176 and 2177 on the reagent container 217 and can support the reagent container. The dock 2154, with its arm portions 21544, may be constructed from a plastic (polymer) material.

[0070] The inner surface of the rear wall of each dock 2154 is provided with contacts that engage with the contacts 2170 of the reagent cartridge (reagent cartridge 217). The contacts are electrically connected to the control unit 209, which allows the control unit 209 to individually control the reagent cartridges in each dock 2154 on the carousel 215.

[0071] In the illustrated configuration, cartridge locks 2155 are connected to the two opposing side walls of each dock 2154, located at a point below the arm portion 21544. The cartridge lock 2155 comprises two parallel arm portions 21552 separated by a shoulder portion 21554. The shoulder portion 21554 has a width similar to, or slightly greater than, the width of the dock 2154, so that the arm portions 21552 can be positioned outside and connected to the respective opposing side walls of the dock 2154. Figure 15 shows the arm portions 21552 connected to the side walls by pins 21555 (e.g., pins, screws, or rivets), such that the length of the portion of each arm portion 21552 from the shoulder portion 21554 to the pin 21555 (distal portion) is greater than the length of the portion of each arm portion 21552 from the pin 21555 to the proximal end (the end furthest from the shoulder portion 21554). The connection of the cartridge lock 2155 to the dock 2154 is such that the shoulder portion 21554 can pivot upward and downward without contacting the rear wall of the dock 2154 as shown (for example, the shoulder portion 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 substantially rectangular and protrudes perpendicularly to the shoulder portion 21554 in the proximal direction. The proximal portion of each arm 21552 may protrude upward from the distal portion at an angle such that the angle γ defined between the distal and proximal portions is approximately 150° to 175°. The proximal portion of each arm 21552 may be substantially rectangular and may have a proximal end having a projection 21556, which is an upwardly projecting triangular prism having a triangular base parallel to the side of each arm. The projection 21556 is sized to fit into a notch or docking groove 21772 within the reagent cartridge transfer guide 2177 (see Figure 13). The cartridge lock 2155 may be spring-driven at each of the pins 2155 so that the shoulder portion is closer to the surface of the base 2152. In this configuration, at least a portion of the projection 21556 extends above the base of the notch defining the arm portion 21544 of each dock 2154.When a downward force is applied to the protrusion 21556, the protrusion moves downward and the shoulder moves upward. Releasing this downward force causes movement in the opposite direction.

[0072] An imager, such as a camera, may be connected to the base or cartridge carrier plate 2152. Typically, the imager may be placed in one of the slots 2153 instead of the dock and cartridge. Alternatively, the imager may be connected to the underside of the carrier plate 2152. The imager may 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)) when the microscope slide is removed from the chamber 125 of the main body 120 (e.g., when the door 120 moves to the open position), and the slide bed 115 may move from a position inside the chamber 125 to a position outside the chamber 125. Image acquisition may be controlled by the control unit by commands such as capturing an image of the identifier on the microscope slide before the microscope slide first moves into the chamber 125, an image of the sample on the microscope slide after the dewaxing operation, determining the position of the sample on the microscope slide (e.g., by searching for the sample (e.g., a stained sample)), and then determining where to dispense the reagent (e.g., primary reagent) and / or after the primary staining operation.

[0073] Referring again to Figures 7, 11, and 15, the transfer of reagent cartridges by the arm assembly 218 from the storage rack 206 or from the platform 205 inside the housing 202 is described. The control unit 209 includes non-transient machine-readable commands that include commanding the arm assembly to engage a reagent cartridge (e.g., reagent cartridge 217) with the cartridge engagement head 2183 of the arm assembly engagement projection 21762 on the reagent cartridge transfer guide 2176. Such commands also include commands to transport the reagent cartridge to one of the docks 2154 on the base 2152 of the carousel 215, aligning the reagent cartridge transfer guides 2176 and 2177 with one arm portion 21554 of the dock 2154 (aligning the transfer guides 2176 and 2177 above and below each arm portion 21554, respectively). Once aligned, the command further includes instructions to slide the reagent cartridge into the arm portion 21554 (proximal to distal) so that the nose or base 2179 of the reagent cartridge 217 faces inward (for example, facing the center of the base 2152). The arm assembly 218 applies sufficient force toward the center of the base 2152 to slide the reagent cartridge into the arm portion 21554. A thickness t greater than the thickness t2 of the transport guide 2177 d The transfer guide 2177, having the dock locking groove 21772, contacts the proximal portion of each arm 21552 of the cartridge lock 21555, causing each arm to rotate around each pin 21555 and pushing the proximal portion of the arm downward. When the portion of the transfer guide 2177 having the dock locking groove 21772 is directly above the projections 21556 of each arm 21552 of the cartridge lock 21555, the biasing of the cartridge lock causes each arm 21552 of the cartridge lock 21555 to rotate in opposite directions around the pin 21555 and engage the projections 21556 with the locking groove 21772. At this point, the reagent cartridge is secured to the dock 2154, and commands related to the control unit 209 instruct the arm assembly 218 to release its engagement with each engaging projection 21762.

[0074] Before a reagent cartridge is sent to a dock (dock 2154) on the carousel 215 for a dispensing operation, or before it is returned from the dock to the storage rack 206, the reagent cartridge may be directed to a service station. Figure 16 shows a service station 2190 adjacent to the storage rack 206, mounted on the rear side wall of the reaction compartment 204 in the illustrated configuration. The service station 2190 provides an area on the printhead of the reagent cartridge that can be inspected and cleaned before and / or after use in a dispensing operation for dispensing reagents from the reagent cartridge onto a microscope slide. Figure 16 shows a front view of the service station 2190. In this example, the service station 2190 includes a rear wall 21901. Pulley supports 21903 and 21904 are connected to the rear wall 21901. Pulley supports 21903 and 21904 each include an upper roller and a lower roller, respectively. Belt 21905 is positioned on the upper rollers of pulley support 21903 and pulley support 21904, respectively. Belt 21906 is positioned on the lower rollers of pulley support 21903 and pulley support 21904, respectively. Rail 21902 is positioned between and connected to pulley support 21903 and pulley support 21904, respectively. Carriages 21907 and 21908 are slidably connected to rail 21902 and belts 21905 and 21906. Carriages 21907 and 21908 may each have a configuration for securing reagent cartridges similar to that of dock 2154 (see Figure 18).

[0075] In the example shown in Figure 16, carriage 21907 has a length L1 and a width W1 (e.g., L1 is 100 mm and W1 is 60 mm) for a first-size reagent cartridge, and carriage 21908 has a length L2 and a width W2 (e.g., L2 is 72 mm and W2 is 60 mm) for a second-size reagent cartridge. Note that the service station 2190 may have only one carriage, or if it has multiple carriages, the carriages may accommodate reagent cartridges of the same or different lengths and widths. The base or rear side of carriages 21907 and carriage 21908 in their respective illustrated configurations are equipped with electronic contacts or pins that can be operated to mate with the receiving portion (contact 2170) on the front side of the reagent cartridge, as well as the inner surface of the rear wall of each dock 2154 of the carousel 215, which has contacts that mate with the contact 2170 on the reagent cartridge. Figure 19 shows the contact or pin 21914 of carriage 21907 and the contact or pin 21915 of carriage 21908.

[0076] In one example, the reagent cartridge (reagent cartridge 217) has dimensions of length and width that fit snugly within the carriage 21907 or carriage 21908. As described above with respect to Figure 15, the front of the reagent cartridge (reagent cartridge 217) is equipped with an electronic pin receptacle 22794 to mate with the electronic contacts or pins 21917 of the carriage 21907. The front of the reagent cartridge may also be equipped with two diagonally spaced alignment sockets or openings that align with the alignment pins 21917 within the carriage 21907 to assist in the alignment of the reagent cartridge within the carriage 21907 or carriage 21908.

[0077] Figure 16 shows carriages 21907 and 21908, respectively, connected to pulley supports 21903 and 21904 via belts 21905 and 21906. Belts 21905 and 21906 allow carriages 21907 and 21908 to move independently laterally or translationally along rail 21902. Such movement allows each carriage 21907 to transport the reagent container attached to it to the spitton 21909 and wiping station (wiping station 21912 or wiping station 21913). The spitton 21909 provides a container for dispensing reagents into the reagent cartridges in carriages 21907 and 21908. Wiping stations 11912 and 11913 may each be rectangular containers containing a ribbon of a length between the rollers, with the ribbon exposed on the top or side of the container in the illustrated configuration. The ribbon has a first side which is cloth or a similar absorbent material. The width of the ribbon may be at least the same as the printhead of the reagent cartridge. The cloth or similar absorbent material provides an area for cleaning or wiping the printhead (e.g., excess reagent on the printhead). After the wipe operation by the printhead of the reagent cartridge on a portion of the ribbon, the ribbon may be advanced by a command from the control unit 109 that commands the movement of the rollers in wiping station 21912 or 21913.

[0078] Each carriage is electrically connected and can communicate with the control unit 209. Carriage 21907 or carriage 21908 is equipped with electronics for operating reagent cartridges similar to the electronics in dock 2154 and dispensing reagents under the direction of non-temporary machine-readable commands associated with the control unit 209. When a reagent cartridge is connected to carriage 21907 or carriage 21908, commands from the control unit 209 may, for example, instruct the dispensing of reagents from the reagent cartridge in spitton 21909 and contact between the printhead of the reagent cartridge and the ribbon of wiping station 21912 or wiping station 21913.

[0079] In the operation, a command from the control unit 209 may instruct the movement of one of the carriages 21907 or carriage 21908 by belts 21905 and 21906 on the spitton 21909. At that time or around that time, a command from the control unit 209 may instruct the arm assembly 218 to engage with the reagent cartridge (e.g., reagent cartridge 217) and place the reagent cartridge in the moved carriage (e.g., carriage 21907). Further commands from the control unit 209 may then include instructing the electronics in carriage 21907 to distribute or discharge a certain amount of reagent from the reagent cartridge (e.g., enough to wet the printhead and prevent it from clogging) into the spitton 21909. Following the dispensing operation, the control unit 209 may instruct the reagent cartridge to be carried to the wiping station 21912 or 21913 and to be cleaned of any residual reagent on the printhead of the reagent cartridge by a wiping operation with the printhead on the ribbon of the wiping station. After wiping, the control unit 209 may instruct the arm assembly 218 to engage the reagent container and to supply the carousel 215 to the dock (dock 2154) or to the storage rack 206 for the dispensing operation.

[0080] The above discussion describes reagent distribution technology using inkjet technology. This distribution alternative involves a distribution cartridge connected to a cartridge pump assembly, which pumps the reagent from the distribution cartridge onto the sample. Another distribution alternative is pipetting from a reagent container to the sample.

[0081] The following describes a typical operation of the sample processing system, referring to Figures 1-15. First, individual microscope slides, each containing at least one tissue sample, are transported to the reaction compartment 204 by an operator or robot. Each microscope slide is placed individually in the sample processor (sample processor 112). A non-transient machine-readable command from the control unit 209 may instruct the door (door 130) of the sample processor body 120 to open, and then the linear actuator 155 of the sample processor 112 to move the slide bed 115 from an inside position in the chamber (chamber 125) of the body 120 to an outside position in the chamber. The microscope slides may then be placed with the tissue sample side facing upward (facing the top of the body 120) or downward (facing the slide bed 115). Once the slide is placed on the slide bed 115, non-transient machine-readable commands from the control unit 209 may instruct an imager (e.g., an imager connected to the pedestal or cartridge carrier plate 2152) to capture an image of the identifier on the microscope slide, and further commands may instruct the slide bed to return to the inside of the chamber 125 (instructing a linear actuator to move the slide bed 115 inside the chamber 125) and to close the doors 130 of each reaction station 112.

[0082] Microscope slides containing tissue samples delivered to reaction compartment 104 may be embedded in an embedding medium (e.g., paraffin) or processed to remove the embedding medium and adhere the tissue sample to the slide (i.e., pre-treated to remove paraffin and adhere the tissue sample to the slide). When slides with tissue samples embedded in an embedding medium such as paraffin are delivered to chamber 125, non-transient machine-readable commands from control unit 209 may instruct the system to perform adhesion and deparaffinization (dewaxing) protocols on the embedded tissue sample. Typically, the command may instruct the slide with the embedded tissue sample to be heated, for example, using hot water introduced into a container in chamber 125 and / or a slide heating unit connected to the slide bed 115 (e.g., below or above the slide bed 115) as part of the firing operation. The heat treatment must be sufficient to adhere the sample on the slide to the slide (glass slide) or to further adhere it, and, where possible, to soften the embedding medium associated with the section on the slide. Typically, the slide may be heated to a temperature of around 55°C to 70°C.

[0083] After heat treatment, the control may instruct the system to remove heat from chamber 125. If the reservoir below the slide bed 115 is filled with hot water, the control unit 209 may instruct the system to open drain valve 159 (see Figure 1) so that the hot water can be discharged through conduit 158 ​​to the waste collection unit. If the slide heating unit is used, the control unit 209 may instruct the system to turn off the slide heating unit. Subsequent instructions from the control unit 209 may instruct the system to expose the embedded tissue sample on the slide to a dewaxing solution such as xylene in a volume sufficient to cover the sample portion of the slide. The dewaxing solution such as xylene may be stored as a bulk reagent in a container in storage compartment 201 located below reaction compartment 204 (see Figure 6). The dewaxing solution container may be connected to a fluid connector 190 (see Figure 5) located at the top of the main body 120 of the reaction compartment containing the embedded tissue sample on the slide. Commands associated with the control unit 209 may instruct the dewaxing solution to be transferred (e.g., pumped) from the dewaxing solution container to the respective fluid connectors 190, onto the surface of the slide in the reaction compartment if the tissue sample is facing upward, or onto the slide bed 115 if the tissue sample is facing downward (facing the slide bed). After the distribution of the dewaxing solution, commands associated with the control unit 209 may instruct the tissue sample to be immersed in the dewaxing solution for a certain period of time (e.g., 1 to 5 minutes). After the immersion time, commands associated with the control unit 209 may instruct the slide bed 115 to be tilted by the rotary motor 140 to drain the dewaxing solution from the tissue sample and / or the slide bed 115 (see Figure 3).

[0084] After a period for removing the dewaxing solution and paraffin from the surface of the slide, further commands associated with the control unit 209 may instruct the valve 159 (see Figure 1) to open and discharge the dewaxing solution through the conduit 158 ​​to the waste collection unit. In another example, the dewaxing protocol may involve sequentially dispensing multiple reagents. For example, the first reagent applied to the tissue sample on the slide may be xylene. After the xylene treatment and subsequent removal, the dewaxing protocol may specify exposing the tissue sample to alcohol (e.g., ethanol). In such a case, the container containing xylene is connected to the first fluid connector 190 on the top of the main body 120, and the container containing alcohol is connected to the second fluid connector 190.

[0085] After the dewaxing process, commands associated with the control unit 209 may instruct the tissue sample to be rinsed with a certain volume of washing solution (e.g., water or other aqueous washing solution). The washing solution may be supplied to the tissue sample by connecting a container containing the washing solution to a fluid connector (fluid connector 190) on the main body 120. The washing solution may also contain a certain amount of a staining agent, such as eosin, to stain the sample on the slide. Generally, following the dewaxing operation, the embedding material in the section is removed, and the sample remains on the slide as a substantially colorless object. By adding a certain amount of a staining agent, such as eosin, to the washing solution, the presence and location of the sample on the slide can be detected. After the washing process, commands associated with the control unit 209 may instruct the slide bed 115 to rotate to remove the washing solution from the surface of the slide, and the washing solution to be discharged into the waste collection unit through the conduit 158 ​​and valve 159.

[0086] Following the washing process, non-transient machine-readable commands from the control unit 209 may instruct the door (door 130) of the sample processor body 120 to open, and then the linear actuator 155 of the sample processor 112 to move the slide bed 115 from its position inside the chamber (chamber 125) of the body 120 to its position outside the chamber. Additional commands from the control unit 209 may instruct an imager (e.g., an imager connected to a pedestal or cartridge carrier plate 2152) to capture an image of the sample and, if possible, an identifier on the microscope slide, and then further commands may instruct the slide bed to return to the inside of the chamber 125 (instructing the linear actuator to move the slide bed 115 inside the chamber 125), and to close the doors 130 of each reaction station 112. Furthermore, commands may instruct the position of the sample or a portion thereof on the microscope slide to be identified and stored for use in the staining operation.

[0087] Following the washing process and, if possible, the capture of images of the sample and identifier, commands associated with the control unit 209 may instruct the tissue sample to be subjected to an antigen retrieval process to reverse the antigen masking effect by aldehyde fixation. A container containing the antigen retrieval solution, such as a Tris-based or citrate-based retrieval solution, may be stored as a bulk reagent in a storage compartment 201 located below the reaction compartment 204 and connected via a conduit to a fluid connector (fluid connector 190) on the main body 120 to provide the antigen retrieval solution to the tissue sample. Commands associated with the control unit 209 may also instruct the antigen retrieval process to be carried out at high temperature and, optionally, high pressure. Typically, commands may instruct a slide containing the tissue sample to be heated to a temperature of, for example, 100°C to 130°C using the slide heating section in the chamber 125. The command may further instruct the reaction compartment to be subjected to high pressure, e.g., 1 standard atmosphere (atm) (15 pounds / square inch (psi) to 1.7 atm (25 psi)), by introducing air or an inert gas into the chamber 125 using a compressor or pump 170 (see Figure 1), for example, by a fixture 172 (e.g., a valve or valve and conduit) located inside the main body 120. By utilizing high pressure, the antigen retrieval process can be reduced to, for example, a process time of 5 minutes, compared to a conventional process time of 45 minutes or more under atmospheric pressure conditions. In another example, the antigen retrieval process may be carried out at a high humidity level, e.g., 70% to 100% relative humidity. As described above, humidity may be increased by including a fluid (e.g., water) below the slide bed 115 in the chamber 125 of the main body. Before providing the antigen retrieval solution to the surface of the tissue sample, commands from the control unit 209 may instruct the valve 156 to open, allowing the fluid in the chamber and a specific volume of the fluid to be introduced into the chamber 125 through the valve 156. Steam generated in an external boiler may be supplied to the chamber 125, for example, through a conduit 157.Commands from the control unit may instruct the heating element 154 to heat the fluid. Alternatively, humidified air with a desired moisture level may be generated by bubbling air or an inert gas (at ambient temperature or heated) through an external reservoir (at ambient temperature or heated) and supplying it to the chamber 125 through a conduit 157 or the like. Furthermore, the ultrasonic generator can generate water droplets (at ambient temperature or heated) which can be supplied to the chamber 125 through a conduit 157 or the like.

[0088] Once the antigen retrieval process is complete, commands associated with the control unit 209 may instruct the slide bed 115 to rotate to remove any fluid in the chamber 125 used to generate the desired humidity level from the conduit 158 ​​and valve 159 into the waste collection unit, and to tilt the slide bed 115 to remove the antigen retrieval solution from the surface of the slide and to discharge it from the conduit 158 ​​and valve 159 into the waste collection unit. Furthermore, commands may then instruct the tissue sample to rinse with a certain volume of washing solution, such as water or washing buffer, such as TBS or phosphate-buffered saline containing a surfactant. After washing, commands associated with the control unit 209 may instruct the slide bed 115 to rotate to remove the washing solution from the surface of the microscope slide and to discharge it from the conduit 158 ​​and valve 159 into the waste collection unit.

[0089] In the staining process, commands associated with the control unit 209 may instruct the motor associated with the sample processor 112, which contains the microscope slide with the sample ready for staining, to open the door (door 130) of the main body 120. Subsequently, additional commands from the control unit 209 may instruct the slide bed 115 to move outside the chamber (chamber 125) of the main body 120. If not previously done, further commands from the control unit 209 may instruct the position of the sample or a portion thereof on the microscope slide for staining to be determined based on the captured image of the sample on the microscope slide after the washing operation.

[0090] Before or after the microscope slide is moved outside the chamber for the staining process, commands associated with the control unit 209 may instruct the retrieval of a reagent cartridge from the storage rack 206 and to load or dock the reagent cartridge into one of the docks 2154 on the base 2152 of the carousel 215. Further commands associated with the control unit 209 may instruct the loaded reagent cartridge, positioned on the base 2152 with the nose or base portion of the reagent cartridge, to be positioned over the tissue sample on the raised slide. Such commands include instructing the motor 2157 to rotate the cylindrical portion 2151, and accordingly rotate the base 215 and motor 2143, to move the carousel 215 longitudinally. Once positioned, commands may instruct the reagent from the reagent cartridge to be dispensed (e.g., printed) onto the sample at a predetermined position on the sample or a portion thereof. Typically, a drop-on-demand printhead, such as a thermal inkjet printhead in a reagent cartridge, may dispense reagents such as detection agents or antibodies in droplets having volumes of 1 picoliters (pL) to 10 nanoliters (nL), or 1 pL to 5 nL, or 1 pL to 1 nL, or 1 pL to 500 pL, or 1 pL to 250 pL, or 1 pL to 100 pL, or 1 pL to 50 pL. Typically, an inkjet cartridge can supply at least 15 microliters (μL) per square inch (at least 15 μL) per pass, and a single pass is the dispensing (ejection) of reagent from multiple nozzles in the printhead of the inkjet cartridge, either while the reagent cartridge (carousel) and slide are stationary, or while at least one of the reagent cartridge (carousel) and slide moves in one direction to expand the dispensing area on the slide. Typically, the control unit 209 instructs the print head of the reagent cartridge to distribute multiple droplets (i.e., droplets from multiple nozzles) to generate a larger volume of reagent per pass.Typical feed rates passing through a thermal inkjet printhead include 15 μL to 30 μL / square inch per pass, 15 μL to 25 μL / square inch per pass, and 15 μL to 20 μL / square inch per pass.

[0091] Commands associated with the control unit 209 may also instruct the staining process to be carried out at high temperature and possibly high pressure. Typically, a command may instruct the slide containing the tissue sample to be heated to a desired temperature using the slide heating section in the chamber 125. The command may further instruct the reaction compartment to be subjected to high pressure, e.g., 1 standard atmosphere (atm) (15 pounds / square inch (psi) to 2 atm (30 psi)), by introducing air or an inert gas into the chamber 125 using a compressor or pump 170 (see Figure 1), for example, by a fixture 172 (e.g., a valve or valve and conduit) located in the main body 120. In another example, the staining process may be carried out at a high humidity level, e.g., 70% to 100% relative humidity. As described above, humidity by the techniques described above with respect to the antigen retrieval process may be instructed by a command from the control unit 209 for the staining process.

[0092] After the staining process, commands associated with the control unit 209 may instruct the movement of the reagent cartridge and carousel from their positions above the slide, return the slide bed 115 and microscope slide to the chamber (chamber 125), and close the door (door 130) of the main body 120. Additional commands associated with the control unit 209 may instruct the incubation period of the sample on the microscope slide to be extended (e.g., to allow the primary antibody to bind to the target antibody). Incubation may be performed in a humidified environment. After the incubation period, commands associated with the control unit 209 may instruct the rinsing of the tissue sample with a certain volume of washing solution to remove unreacted / unconjugated reagents. After rinsing, commands associated with the control unit 209 may instruct the rotatable slide bed 115 to a non-horizontal position within the chamber 125 to remove the washing solution from the surface of the slide. Subsequently, additional commands may instruct the rotatable slide solution to be discharged into the waste collection unit through the conduit 158 ​​and valve 159. Once the staining process of the tissue sample on the microscope slide is complete, commands associated with the control unit 209 may instruct the system to alert the user that the microscope slide is ready to be removed. Subsequently, additional commands from the control unit 209 may instruct the door 130 of the main body 120 of the sample processor 112 to open and the slide bed 115 to move the microscope slide on it to a position outside the chamber (chamber 125) so that an operator or robot can retrieve the microscope slide. Examples

[0093] Example 1

[0094] The use of high pressure in sealed sample processors, such as sample processor 112, was evaluated for the antigen retrieval process compared to a control at ambient pressure. Table 1 lists the samples, conditions, and results. At 25 psi (1.7 atm), the antigen retrieval process completed in 5 or 10 minutes, achieving satisfactory results comparable to the control at ambient pressure, which completed in 30 minutes. The control conditions were ambient pressure, a temperature of 80°C to 90°C, and a humidity of 80% to 100%. [Table 1]

[0095] Example 2

[0096] The use of high pressure in sealed sample processors, such as sample processor 112, was evaluated for reducing antigen staining time compared to a control at ambient pressure. Table 2 lists the samples, conditions, and results. At 25 psi (1.7 atm), the process was completed in 2 minutes, another in 5 minutes, and a third in 15 minutes, all of which were satisfactory results comparable to the control, which was completed in 30 minutes at ambient pressure, ambient temperature, and 80-100% humidity. [Table 2]

[0097] This specification includes the following embodiments:

[0098] Appearance 1 A sample processing device, A body comprising an inner surface defining a chamber having an opening on the side of the body, and a volume for housing at least one microscope slide within the body, A door, including a first position for covering the opening of the main body and a second position for exposing a portion of the chamber through the opening, A slide bed positioned inside the chamber, A sample processing apparatus comprising an internal humidity generating unit located within a chamber, and one of the external humidity generating units connected to the chamber.

[0099] Appearance 2 The sample processor according to embodiment 1, wherein the sample processor includes an internal humidity generating unit, and the internal humidity generating unit includes a reservoir below the slide bed.

[0100] Appearance 3 A sample processing apparatus according to embodiment 1 or embodiment 2, further comprising a heat source.

[0101] Pattern 4 A sample processing apparatus according to any one of embodiments 1 to 3, wherein the heat source comprises a heating section for heating the fluid in the reservoir.

[0102] Appearance 5 The sample processing apparatus according to embodiment 3, wherein the heat source comprises a heating unit for directly or indirectly heating the slide bed.

[0103] Appearance 6 A sample processor according to any one of embodiments 1 to 5, further comprising a pressure source that can be operated to raise the pressure inside the chamber above the ambient pressure.

[0104] Appearance 7 The sample processor according to embodiment 6, wherein the pressure source is operable to maintain the pressure in the chamber at at least 25 psi (1.7 atm).

[0105] Appearance 8 A sample processing apparatus according to embodiment 6 or 7, wherein the pressure source is a compressor connected to the main body and in fluid communication with the main body, which can be operated to introduce air into the chamber.

[0106] Appearance 9 The sample processing apparatus according to embodiment 1, wherein the sample processing apparatus is equipped with an external humidity generating unit.

[0107] Appearance 10 A sample processor according to embodiment 9, further comprising at least one heat source.

[0108] Appearance 11 A sample processing apparatus according to embodiment 9 or 10, wherein the heat source comprises a heating section for directly or indirectly heating the slide bed.

[0109] Appearance 12 A sample processor according to any one of embodiments 9 to 11, wherein at least one heat source is operable to maintain the temperature inside the chamber at at least 100°C.

[0110] Appearance 13 A sample processing apparatus according to any one of embodiments 1 to 12, wherein the main body comprises an outer surface and an opposing inner surface, the outer surface comprises a plurality of hose connection parts connected to the outer surface, and the inner surface comprises a plurality of nozzles that communicate fluidly with one of the plurality of hose connection parts.

[0111] Appearance 14 A sample processor according to any one of embodiments 1 to 13, further comprising a nozzle inside the chamber, the nozzle being operable to connect to a conduit outside the main body, and the nozzle being operable to dispense a reagent toward a slide bed in a spray or curtain flow manner.

[0112] Appearance 15 A sample processing apparatus according to any one of embodiments 1 to 14, wherein one of the internal humidity generating unit and the external humidity generating unit can be operated to raise the humidity inside the chamber to more than 60%.

[0113] Appearance 16 A sample processing system comprising at least one of the sample processors described in any of embodiments 1 to 15, further comprising at least one reagent outside the body of at least one sample processor, and connected to a conduit extending into the chamber of at least one sample processor.

[0114] Appearance 17 The sample processing system according to embodiment 16, wherein at least one reagent can be heated to a temperature higher than the ambient temperature.

[0115] Appearance 18 A sample processing system according to embodiment 16 or embodiment 17, wherein at least one sample processor is housed in a reaction compartment, and the sample processing system comprises a refrigerated storage rack that can be operated to store a number of reagent cartridges.

[0116] Appearance 19 Exposing the sample on the microscope slide inside the sealed chamber to higher pressure and humidity than 60% of the ambient temperature, A method comprising processing a sample.

[0117] Appearance 20 The method according to embodiment 19, wherein processing the sample includes contacting the sample with a reagent.

[0118] Appearance 21 The method according to embodiment 19 or embodiment 20, wherein the sample contains a staining agent.

[0119] Appearance 22 The method according to any one of embodiments 19 to 21, wherein contacting the sample with a reagent includes distributing the sample by a thermal inkjet process.

[0120] Appearance 23 The method according to embodiment 22, wherein the dispensing comprises dispensing one or more reagents in an amount of at least 15 microliters (μL) per square inch per pass.

[0121] Pattern 24 The method according to any one of embodiments 19 to 23, wherein processing the sample includes exposing antigenic sites within or on the sample.

[0122] Appearance 25 The method according to any one of embodiments 19 to 23, further comprising exposing the sample to a temperature higher than the ambient temperature.

[0123] The present invention has been described in the aforementioned specification with reference to specific embodiments thereof. However, it will be apparent that various modifications and changes can be made without departing from the broad spirit and scope of the invention as described in the appended claims. For example, the reagent cartridges disclosed herein (e.g., reagent cartridge 217) may contain a solvent or water instead of a reagent and may be used for purposes other than, for example, staining a sample on a microscope slide. Accordingly, this specification and the drawings should be considered illustrative rather than restrictive.

Claims

1. A sample processing device, A body comprising an inner surface defining a chamber having an opening on its side, and a volume for housing at least one microscope slide within the body, A door, including a first position for covering the opening of the main body and a second position for exposing a portion of the chamber through the opening, A slide bed arranged in the chamber, A sample processing apparatus comprising an internal humidity generating unit located within the chamber, and one of an external humidity generating unit connected to the chamber.

2. The sample processor according to claim 1, wherein the sample processor comprises an internal humidity generating unit, and the internal humidity generating unit comprises a reservoir below the slide bed.

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

4. The sample processing apparatus according to claim 3, wherein the heat source comprises a heating section for heating the fluid in the reservoir.

5. The sample processing apparatus according to claim 3, wherein the heat source comprises a heating section for directly or indirectly heating the slide bed.

6. The sample processing apparatus according to claim 1, further comprising a pressure source that can be operated to raise the pressure inside the chamber to a level higher than the surrounding pressure.

7. The sample processor according to 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 processing apparatus according to claim 6, wherein the pressure source comprises a compressor connected to the main body and in fluid communication with the main body, which can be operated to introduce air into the chamber.

9. The sample processor according to claim 1, wherein the sample processor comprises an external humidity generating unit.

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

11. The sample processing apparatus according to claim 10, wherein the heat source comprises a heating section for directly or indirectly heating the slide bed.

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

13. The sample processing apparatus according to claim 1, wherein the main body comprises an outer surface and an opposing inner surface, the outer surface comprises a plurality of hose connection portions connected to the outer surface, and the inner surface comprises a plurality of nozzles that communicate fluidly with each of the plurality of hose connection portions.

14. The sample processor according to claim 1, further comprising a nozzle in the chamber, wherein the nozzle is operable to connect to a conduit outside the main body, and the nozzle is operable to distribute a reagent toward the slide bed in a spray or curtain flow manner.

15. The sample processing apparatus according to claim 1, wherein one of the internal humidity generating unit and the external humidity generating unit is operable to raise the humidity inside the chamber to more than 60%.

16. A sample processing system comprising at least one of the sample processors described in claim 1, further comprising at least one reagent outside the body of the at least one sample processor, and connected to a conduit extending into the chamber of the at least one sample processor.

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

18. The sample processing system according to claim 16, wherein the at least one sample processor is housed in a reaction compartment, and the sample processing system comprises a refrigerated storage rack that can be operated to store a number of reagent cartridges.

19. Exposing the sample on the microscope slide inside the sealed chamber to higher pressure and humidity than 60% of the surrounding environment, A method comprising processing the aforementioned sample.

20. The method according to claim 19, wherein processing the sample includes contacting the sample with a reagent.

21. The method according to claim 20, wherein the sample comprises a staining agent.

22. The method according to claim 20, wherein contacting the sample with a reagent includes distributing the sample by a thermal inkjet process.

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

24. The method according to claim 19, wherein processing the sample includes exposing antigenic sites within or on the sample.

25. The method according to claim 19, further comprising exposing the sample to a temperature higher than the ambient temperature.

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