Automated staining system and reaction chamber

Abstract

This invention provides a method for an automated system for placing reagents in biological specimens. [Solution] The present invention is a method comprising the steps of: exposing a sample on a slide in a processing unit assembly; transferring the slide to a print station 1270 of the processing unit assembly by a robot 1255; and applying a reagent to the exposed sample in the print station 1270 by a thermal inkjet printing process.

Description

Technical Field

[0001] (Cross - reference to Related Applications) This application claims the priority of U.S. Provisional Patent Application No. 62 / 956,015, filed on December 31, 2019, the entire content of which is incorporated herein by reference.

[0002] The present invention relates to an automated system for placing reagents on biological specimens.

Background Art

[0003] In various settings, the processing and analysis of biological specimens are required for diagnostic purposes. Generally, pathologists and other diagnosticians collect samples from patients for study and evaluate the samples at the cellular level using microscopy and other devices. A number of processing steps are generally required in pathology and other diagnostic processes, including the collection of biological samples such as blood and tissue, sample preparation, preparation of microscope slides, staining of samples on microscope slides, examination, re - analysis or re - staining, collection of additional samples, re - examination of samples, and the presentation of final diagnostic results.

[0004] Sample (e.g., tissue) stainers or processors can be operated at various levels of automation to process human or animal tissue specimens for use in histology or pathology. Various types of chemical reagents are used at various stages of tissue processing, and various systems have been developed for delivering reagents to specimen storage slides. Examples of well - known reagent delivery systems include low - volume dispensing, manual injection into reagent baths, or bulk containers connected to the stainer via tubing.

[0005] Well-known systems exhibit various shortcomings. For example, manual injection into reagent trays and subsequent draining are prone to cross-contamination, time-consuming, and require injection precision, thereby reducing the overall efficiency and accuracy of the tissue processing system. Another disadvantage is that manual injection and draining of reagents are prone to contamination, requiring cleaning up spilled liquids and resulting in equipment downtime. A further disadvantage is that manual selection and application of the correct reagents carries a significant risk of human error, increasing the likelihood of reagent selection and application errors, which can lead to false positive or false negative test results, resulting not only in reduced analytical accuracy and operational efficiency but also in misdiagnosis. [Brief explanation of the drawing]

[0006] Embodiments of the invention are illustrated in the accompanying drawings, where similar reference numerals refer to similar elements, not as limitations but as examples. It should be noted that any reference in this disclosure of “an” or “one” embodiment does not necessarily refer to the same embodiment, but rather means at least one. [Figure 1] A perspective view of a sample processing system, also called a processing unit assembly or processing assembly, is shown. [Figure 2] Figure 1 shows a top view of the processing assembly with the upper outer portion of the processing assembly removed to expose the internal compartments of the processing assembly. [Figure 3] Figure 1 shows an enlarged upper front view of the core module or core section of the processing assembly, with the upper outer portion of the outer housing removed to expose the internal compartments of the core module or core section, and shows the slide basket inside the core module or core section. [Figure 4] Figure 1 shows an upper left perspective view of a scanning and / or imaging device that may be located in the core module or slide identification station of the processing assembly. [Figure 5] Figure 4 shows an upper left perspective view of the scanning and / or imaging device with the base, support, track, and base removed. [Figure 6]Figure 4 shows an upper perspective view of the scanning and / or imaging device with the base, support, track, and base removed, and shows the lift mechanism in the downward or return position below the slide in the slide basket. [Figure 7] Figure 4 shows an upper perspective view of the scanning and / or imaging device with the base, support, track, and base removed, and shows the lift mechanism in an upward or forward position below the slide in the slide basket. [Figure 8] Figure 1 shows an enlarged upper front view of a portion of the staining module or staining section of the processing assembly, with the upper outer portion of the outer housing removed to expose the internal compartments of the module, and is an enlarged view showing a portion of the staining module or staining section including the antigen retrieval station. [Figure 9] Figure 1 shows a front perspective view of the robotic mechanism of the staining module or staining section and the slide identification station of the processing unit assembly. [Figure 10] Figure 1 shows a front perspective view of a portion of the print station housed in the dyeing module or dyeing section of the processing unit assembly, illustrating the robotic mechanism for loading slides into the print station. [Figure 11] Figure 1 shows a front view enlargement of the print station components, including the humidifier rack assembly, housed in the staining module or staining section of the processing assembly. [Figure 12A] Figure 11 shows the humidifier rack assembly at line 12-12', illustrating the slide platen on the slide carrier linear rail and the slide on the slide platen at the lower position of the printer. [Figure 12B] Figure 11 shows the humidifier rack assembly at line 12-12', illustrating the slide platen on the slide carrier linear rail and the slide on the slide platen at the lower position of the humidifier housing. [Figure 13] Figure 11 shows a magnified front view of a portion of the humidifier rack assembly, showing the printer and two reagent cartridges connected to it. [Figure 14A]Figure 11 shows a front view of the first reagent cartridge that may be used in the printer with the humidifier rack assembly. [Figure 14B] Figure 11 shows a bottom view of the first reagent cartridge shown in Figure 14A, which can be used in a printer with the humidifier rack assembly shown in Figure 11. [Figure 14C] Figure 11 shows a front view of a second reagent cartridge that may be used in a printer with the humidifier rack assembly. [Figure 14D] Figure 11 shows a bottom view of the first reagent cartridge, which can be used in a printer with the humidifier rack assembly shown in Figure 14C. [Figure 15] Figure 11 shows a magnified front view of the humidifier rack assembly for the printer, without the reagent cartridges connected to the printer. [Figure 16] Figure 1 shows a front view enlargement of the reagent storage cabinet and the robotic mechanism adjacent to the reagent storage cabinet, each of which houses the staining module or staining section of the processing assembly. The reagent storage cabinet includes a carousel for storing reagent cartridges. [Figure 17] Figure 16 shows an upper front view of a carousel that may be installed in the reagent storage cabinet. [Figure 18] Figure 17 shows a front view of the carousel after disassembly. [Figure 19] Figures 14A to 14D show an upper perspective view of the cap of a reagent cartridge printhead suitable for the first or second reagent cartridge shown. [Figure 20] Figures 14A to 14D show cross-sectional views of the cap of a reagent cartridge printhead suitable for the first or second reagent cartridge shown. [Figure 21] Figure 1 is a top view of the cap removal and storage station housed in the staining module or staining section of the processing unit assembly. The cap removal and storage station consists of an array of cells, each capable of storing a reagent cartridge cap. [Figure 22]Shows the cell of the cap removal and storage station of FIG. 21 and the reagent cartridge above the cell in the process of removing the cap that covers the print head of the reagent cartridge. [Figure 23] Shows the cell and the reagent cartridge of FIG. 22 following the placement of the cap on the cell in the process of removing the cap that covers the print head of the reagent cartridge. [Figure 24] Shows the cell and the reagent cartridge of FIG. 22 following the removal and holding of the cap in the cell and the separation of the reagent cartridge from the cell in the process of removing the cap that covers the print head of the reagent cartridge. [Figure 25] Shows a side view of the service station housed in the staining module or staining section of the processing assembly of FIG. 1. The service station includes two reagent cartridge carriers, a spit cup, and two wiper assemblies. [Figure 26] Shows the movement of one of the two reagent cartridge carriers above the spit cup in the service station of FIG. 25 in the process of loading the reagent cartridge and providing service to the reagent cartridge. [Figure 27] Shows the service station of FIG. 26 following the attachment of the reagent cartridge to the reagent cartridge carrier above the spit cup in the process of providing service to the reagent cartridge. [Figure 28] Shows the movement of the reagent cartridge carrier from above the spit cup to the wiping station in the service station of FIG. 25 in the process of providing service to the reagent cartridge. [Figure 29] Shows an enlarged front view of the wiping station in the service station of FIG. 25. The front cover of the wiping station has been removed. [Figure 30]The enlarged front view of the upper part of the core module or core section of the processing assembly in FIG. 1, with the upper outer part of the external housing removed to expose the internal partition of the core module or core section of the processing assembly, shows a slide basket carried from the staining module or staining section to the dehydration station inside the core module or core section. [Figure 31] FIG. 11 shows a front view of a reagent cartridge 1279A that can be used in a printer in a humidifier rack assembly.

Best Mode for Carrying Out the Invention

[0007] In the following paragraphs, the invention will be described in detail by way of example with reference to the accompanying drawings. Throughout this description, the embodiments and examples shown should be considered as typical examples rather than limitations on the present invention. Further, references to various aspects of the embodiments disclosed herein do not necessarily mean that all claimed embodiments or methods must include the aspects referred to.

[0008] FIG. 1 shows a perspective view of a sample processing system, also referred to as a processor assembly. The processing assembly 100 is a modular assembly that includes a core module 110 connected to and in communication with a staining module 120. Alternatively, the modular assembly may also include each module of a core sub-module (core module 110) and a staining sub-module (staining module 120). For the clarity of discussion, in the following description of the processing assembly 100, reference will be made to the core module 110 and the staining module 120 as if they were separate modules that are combined to form the processing assembly 100.

[0009] Each of the core module 110 and the staining module 120 includes an external housing that encloses and stores various components of the processing assembly 100 and contains internal compartments for the automated processing of the sample (biological sample (e.g., tissue sample)) on the slide. The core module 110 includes, but is not limited to, a compote for sorting the slide into a desired processing sequence or recovery process, and may include, but is not limited to, components for dewaxing and baking the sample (e.g., tissue sample) on the slide from the microtome unit, and optionally dehydrating the sample (sample) on the slide after printing one or more reagents. The staining module 120 may be, for example, an immunohistochemical staining unit. Generally, immunohistochemical staining requires a process that selectively identifies antigens (e.g., proteins) in cells of a tissue section or cytological specimen by introducing antibodies that bind (e.g., specifically bind) to the antigen. For example, visualization of antibody-antigen interactions can be achieved by conjugating antibodies or other staining reagents to enzymes that can catalyze the color reaction or to phosphors that fluoresce when visible under appropriate lighting conditions. The staining module 120 may include an antigen retrieval station for exposing the antigen of the specimen, a print station for placing one or more reagents on the specimen (sample) on the slide, a reagent cabinet for storing reagents when not in use at the print station, and optionally, one or more coverslip mounters for attaching coverslips to the specimen on the slide.

[0010] Referring to Figure 1, the external front view of the core module 110 of the processing assembly 100 includes a shelf or flat section 112 in which one or more baskets of specimens or microscope slides are arranged and loaded into the core module 110 through an inlet opening 115 and discharged from the core module 110 through an outlet opening 125. Specimens or microscope slides are generally thin, flat pieces of glass, typically 75 millimeters in length (length dimension) and 26 millimeters in width (width dimension) (e.g., 3 inches long and 1 inch wide) and about 1 millimeter (0.04 inches thick). Typically, the slide baskets may be TISSUE-TEK PRISMA registered trademark slide baskets for 10 or 20 slides, commercially available from Sakura Finetek USA, Inc. The length dimension of the specimen slides is longer than the height dimension of the TISSUE-TEK PRISMA registered trademark slide basket. When one or more slides are placed in a TISSUE-TEK PRISMA slide basket, they are oriented longitudinally so that the ends of the slides protrude from the TISSUE-TEK PRISMA slide basket. Each of the entry opening 115 and exit opening 125 is sized to receive / discharge one slide basket at a time, or multiple slide baskets (e.g., three or four slide baskets) at a time. The external front view of the core module 110 also shows an opening 114 adjacent to the entry opening 115. The opening 114 is sized to pass through when receiving or discharging an empty basket. Thus, the opening 114 may have a height dimension greater than the height dimension of an empty TISSUE-TEK PRISMA slide basket, but smaller than the height dimension of a TISSUE-TEK PRISMA slide basket containing one or more slides.By making the height of the opening smaller than the height of the TISSUE-TEK PRISMA (registered trademark) slide basket, which includes the slide, the risk of mistakenly placing the slide basket through the opening 114 is reduced.

[0011] Figure 1 shows the core module 110, including an interface 135 located on the front side of the core module 110 above the shelf 112. The interface 135 is a computer interface, including, for example, a graphical user interface, that is electronically linked to a controller or processor associated with the operation of the processing assembly 100. The insert in Figure 1 shows a controller or processor 136 connected to the interface 135 and a memory 137 coupled to the processor or computer 136. The interface 135 acts to enable human operation and control of the core module 110 and staining module 120 of the processing assembly 100, and can provide feedback information about the operation of the core module 110 and staining module 120. Below the shelf 112 of the core module 110 is a drawer or door 113 that provides access to the bottom of the module where bulk reagents and waste can be stored. The processor 136 may be electrically or wirelessly linked to a network such as a laboratory information system (LIS) that records, manages, and stores data for a clinical laboratory.

[0012] Figure 1 shows a staining module 120 connected to a core module 110 in a juxtaposed configuration. The staining module 120 includes a shelf 112 and an opening 1251 extending from the shelf 112, providing access to the staining module for delivering or discharging reagent cartridges (e.g., inkjet reagent cartridges). Above the opening 1251, one or more windows 122 may be provided, providing visual access to the interior of the staining module 120 (the internal compartment where sample processing takes place). One or more windows 122 may be fixed to the module body so that they cannot be opened, or they may be fixed to the body so that one or more windows can be opened (e.g., by hinge connection at one end or edge). When one or more windows 122 can be opened, one or more windows 122 may be used to obtain access to components within the staining module 120. Below the one or more windows 122 and shelves 112 of the staining module 120 are provided drawers or doors 123 and 124, which provide access to the bottom of the module where containers for bulk reagents and waste can be stored. Bulk reagents can be dispensed to stations in the core module 110 or the staining module 120 via piping that includes one or more pumps (not shown). Examples of bulk reagents that can be dispensed alone or in combination with other bulk reagents include, but are not limited to, Tris-buffered saline (TBS), sodium citrate saline (SSC), distilled water, dewaxing solution, alcohol, or xylene. One or more pumps may be connected to conduits that supply, for example, tanks in either module.

[0013] Figure 2 shows a top front view of the processing assembly 100 with the upper outer portions of the external housings of the core module 110 and the staining module 120 removed. Referring to Figure 2, the processing assembly 100 includes a shelf section 112 that transitions to a roughly horizontal processing platform 1101 of the core module 110, which includes a sorting station 105, a slide identification station 1120, an exposure or baking and dewaxing station 1110, and a dewatering station 1130. Typically, when a basket of slides is introduced into the core module 110 (e.g., through an introduction opening 115 (see Figure 1)), the basket is transported to the sorting station 105 or the slide identification station 1120. The sorting station 105 may store one or more empty baskets. Empty baskets can be introduced into the core module 110 through an opening 114. At the slide identification station 1120, the labels of each slide in a slide basket containing one or more slides are identified individually (e.g., scanned, read, and / or imaged). Information obtained through the identification process is communicated to the controller or processor 136. After scanning, reading, and / or imaging, a classification process may be performed in which the slides are returned to the basket or placed in a different basket. Slide classification may cause slides from a particular patient (case) to be placed together in one basket, rather than together with slides from one or more other cases. Alternatively or additionally, slides may be classified according to the processing treatment they undergo in the processing assembly 100. For example, a slide processing protocol may require the sample on the slide to undergo at least one of two antigen retrieval treatments before staining. Typically, some samples require antigen retrieval at a low pH (e.g., sodium citrate at pH 4-6), while others require antigen retrieval at a high pH (e.g., Tris-EDTA at pH 8-12). It is assumed that antigen retrieval is performed in the processing assembly 100 with one or more slides in the basket.Therefore, slides containing samples requiring a low pH for antigen retrieval are placed into one basket at the sorting station 105, while slides containing samples requiring a high pH for antigen retrieval are placed into a separate basket. Slides can be transported by a robotic mechanism 1140 that is operable to move in the x-direction on rail 1145. Rail 1145 can be mounted so as to slide perpendicularly to rail 1146 so that rail 1145 is operable for movement in the y-direction between the front and rear of the processing assembly 100. Rail 1146 can be mounted at its ends to the front and rear of the side wall of the processing assembly 100.

[0014] Once the samples on the slides are identified and the slides are optionally sorted into the desired slide baskets, the slide baskets are transported from the sorting station 105 or the slide identification station 1120 to the baking and dewaxing station 1110, where the slides in the slide baskets are processed as a group to adhere the samples to the slides and then expose the samples (first exposure). The robotic mechanism 1140 may transport the slide baskets from the slide sorting station 105 or the identification station 1120 to the baking and dewaxing station 1110, and within that station. Following the adhesion of the samples to the slides and dewaxing of the slide baskets, the robotic mechanism 1140 is used to transport the slide baskets again from the core module 110 to the staining module 120.

[0015] Continuing to refer to Figure 2, the staining module 120 includes a generally horizontal processing platform 1201 which includes a glass coverslip mounting station 1230A, a film coverslip mounting station 1230B, an antigen retrieval station 1240, and a print station 1270. Typically, a robotic mechanism 1140 is used to automatically introduce / transport the basket of slides (e.g., from the core module 110) into the staining module 120. Inside the staining module 120, the basket of slides may be delivered to the antigen retrieval station 1240, where the slides may undergo antigen retrieval at high temperature and pressure to expose antigen sites in or on the sample (second exposure). From the antigen retrieval station 1240, the slides are transported individually to the print station 1270. At print station 1270, slides are individually cleaned and then inkjet printed to print target exposure antigens of the sample and reagents such as antibodies that bind to other enzymes and reagents, which can provide a colored appearance for identification and subsequently verification of proper reagent application to the specimen via a vision system. Slides may be printed one at a time using a robotic mechanism 1255 that moves along rail 12553 to load individual slides into the printer. Following the printing process at print station 1270, the slides are loaded into a slide basket. The slide basket is then transported back to core module 110 for buffer storage or dewatering at dewatering station 1130. Buffer storage or dewatering may be performed simultaneously on any slide in the slide basket. Following dewatering, the slide basket containing the processed slides is optionally transported to glass coverslip mounting station 1230A or film coverslip mounting station 1230B, where a coverslip may be added to each slide in the slide basket. Following the installation of any cover slip, the slide basket can be ejected from the outlet 125 of the core module 110.

[0016] Figure 3 shows a magnified upper front view of the module with the upper outer portion of the outer housing removed to expose the internal compartment of the core module 110 of the processing assembly 100. For illustrative purposes, Figure 3 shows five slide baskets (slide basket 210A, slide basket 210B, slide basket 210C, slide basket 210D, slide basket 210E). Slide baskets 210D and 210E are located in the sorting station 105 of the core module 110. Slide basket 210C is located in the slide identification station 1120. Slide basket 210B is located in the baking / dewaxing station 1110. Slide basket 210A is located in the slide identification station 1121. In this figure, slide baskets 210A, 210B, and 210C each contain slides, while slide baskets 210D and 210E are empty. The presence of at least slide baskets 210A, 210B, and 210C within the core module 110 at different stations indicates that the core module and processing assembly 100 can more broadly process multiple slides (e.g., multiple slide baskets containing one or more slides) at different stations simultaneously or in close proximity. An example of a slide basket is the TISSUE-TEK PRISMA registered trademark slide basket for 10 or 20 slides, commercially available from Sakura Finetek USA, Inc. These slide baskets may accommodate removable handles attached to each end. In the following discussion, the slide baskets in processing assembly 100 do not necessarily have handles.

[0017] As described above, the slide basket 210C is located inside the entrance 115 of the slide identification station 1120. During loading, an operator or robot may deliver one or more slide baskets, such as a TISSUE-TEK PRISMA® registered trademark slide basket containing 10 or 20 slides, to the entrance 115. A robotic device capable of operating to deliver slide baskets to the processing assembly 100 is described in PCT / IB2020 / 059562, filed on 12 October 2020, entitled "Automatic Transfer Between Tissue Processing Modules," which is incorporated herein by reference. A conveyor 1102A, such as a belt conveyor system, may be provided in part of the processing platform 1101 and shelf section 112 within the entrance 115. The conveyor 1102A includes two or more pulleys, and a closed loop of belt 11021 rotates around the pulleys. The pulleys are positioned below the shelf section 112 / processing platform 1101 such that the upper or exposed side of the belt 11021 may be on the plane of the shelf section 112 / processing platform 1101. The belt 11021 may have an outer (upper) surface that is on a plane similar to the plane of the processing platform 1101, and has a width approximately the same as the entrance 115 so as to accommodate three or more baskets. One or both of the pulleys may be connected to a motor to rotate the pulleys forward (towards the core module 110) or backward (from the core module 110). The motors may be connected to a processor 136. The executable instructions of the processor 136 may include instructions to move the belt 11021 forward or backward. A sensor on the entrance 115 side (e.g., a photo-eye sensor) may detect the presence of a basket and communicate with the processor 136. Depending on whether one or more baskets (for example, slide basket 210C, slide basket 210D, and slide basket 210E) are present at the entrance 115, the executable instructions of the processor 136 cause one or both pulleys of the conveyor system 1102 to rotate the belt 11021 and transport one or more slide baskets to the sorting station 105.Alternatively, one or more sensors on conveyor 1102A detect the presence of one or more slide baskets on it and activate conveyor 1102A. A slide basket introduced into inlet 115 may contain one or more slides. Two or more slide baskets are introduced at once to the sorting station 105 via inlet 115 and conveyor 1102A. When a slide basket containing slides is transported to core module 110, executable instructions from processor 136 may include instructions to instruct robotic mechanism 1140 to grasp a slide basket containing slides (e.g., slide basket 210C) and transport it to a position within the sorting station 105. Figures 2 and 3 show a robotic transport assembly including a rail or track 1145 and a robotic mechanism 1140 mounted on the bottom of the rail or track. The robotic mechanism 1140 is operable to move in the x-direction on the rail or track 1145. The rail or track 1145 is mounted on rail or track 1146 and slidable in the y-direction thereon. The rails or tracks 1146 can be fixed to the opposing front and rear walls of the core module 110, or to the opposing front and rear walls of the dyeing module 120 when the core module 110 and the dyeing module 120 are a single integrated module. Depending on the arrangement of the rails or tracks 1146 and the length of the rails or tracks 1145, the robotic mechanism 1140 can be moved separately to a position above the conveyor 1102A and to a position above the sorting station 105. The robotic mechanism 1140 may include an end effector capable of securely gripping or engaging with the slide basket. For example, the end effector of the robotic mechanism 1140 may have a projecting arm, blade, or fork that can be operated to grip both sides of the slide basket and then transport the slide basket between the conveyor 1102A and the sorting station 105. The robotic mechanism 1140 includes a robotic controller 1141 (see Figure 3) that can control the robotic movements (e.g., the movement of the robotic mechanism 1140 on the track 1145) and the processing tasks performed by the robotic mechanism 1140. The robotic controller 1141 is linked to the processor 136 either by wire or wirelessly.Machine-readable instructions are transmitted between the processor 136 and the robot controller 1141 (for example, from the processor 136 to the robot controller 1141) to instruct the robot controller and robot mechanism 1140 to perform a desired protocol. The robot controller 1141 may send one or more signals to the processor 136 after confirming the instructions and / or completing the operation instructed by the processor 136. In this example, the program instructions transmitted from the processor 136 to the robot controller 141 may be to move to a position above the slide basket (for example, slide basket 210C) on the conveyor 1102A, to grasp or engage with the slide basket by, for example, gripping both sides of the slide basket, and to transport the slide basket to the sorting station 105.

[0018] In addition to introducing slide baskets for storing slides, it is desirable to introduce one or more empty slide baskets into the core module 110 and to have one or more such empty baskets present in the classification station 105. The empty slide baskets serve as destinations for one or more slides during the classification operation. In the diagram shown in Figure 3, slide baskets 210D and 210E are empty. Slide baskets 210D and 210E are introduced into the core module 110 through an opening 114 that may have a height dimension greater than that of an empty slide basket (e.g., an empty TISSUE-TEK PRISMA slide basket) but smaller than that of the same slide basket containing one or more slides. A conveyor 1102B, such as a belt conveyor system similar to conveyor 1102A, may be provided in the processing platform 1101 and a portion of the shelf section 112 within the inlet 114. Executable instructions from processor 136 or one or more sensors on conveyor 1102B may cause conveyor 1102B to be operated to transport one or more empty slide baskets to sorting station 105. When empty slide baskets are transported to core module 110, executable instructions from processor 136 may include instructions to the robotic mechanism 1140 to grasp or mate with an empty slide basket on conveyor 1102B (e.g., slide basket 210D, slide basket 210E) and transport the empty slide basket to a location within sorting station 105. To make the location of the empty slide baskets known, empty slide baskets may be placed in a designated area of ​​sorting station 105 separate from the slide baskets that store slides.

[0019] The executable instructions of the processor 136 may also include instructions to instruct the robotic mechanism 1140 to transport the slide basket (e.g., slide basket 210C) containing the slides from the classification station 105 to the slide identification station 1120, to the opposing front and rear walls of the staining module 120. Depending on the arrangement of the rails or tracks 1146 and the length of the rails or tracks 1145, the robotic mechanism 1140 can move separately to a position above the classification station 105 and to a position above the slide identification station 1120. In this example, the program instructions sent from the processor 136 to the robotic controller 141 may be to move to a position above the slide basket 210C at the classification station 105, grasp or engage with the slide basket, for example by gripping both sides of the slide basket, and transport the slide basket 210C to the slide identification station 1120. In Figure 3, the slide basket 210C is being transported from the classification station 105 to the slide identification station 1120 by the robotic mechanism 1140.

[0020] The first slide identification station 1120 typically includes a scanning and / or imaging device similar to that described in U.S. Patent Application No. 16 / 370879, filed March 29, 2019, entitled “Stand Alone Slide Identification Reader,” which may be incorporated herein by reference. U.S. Patent Application No. 16 / 370879 describes a device that receives a basket of slides, such as a TISSUE-TEK PRISMA registered trademark slide basket for 10 or 20 slides, and automatically lifts each slide in the basket individually to read and / or capture images of labels on the slides.

[0021] Figure 4 shows an upper left perspective view of a scanning and / or imaging device that may be located in the slide identification station 1120. The slide identification station 1120 is located adjacent to or near the input section 115 of the core module 110 and includes a device 300 similar to the device described in U.S. Patent Application No. 16 / 370879, with the external housing removed. The device 300 includes a track 324 on which the slide basket 210C can be placed on the core module 110 by manual or robotic means. To illustrate the features of the slide identification system, only the two slides of the slide basket 210C are shown. Figure 4 shows the device 300 including a base 302, which is typically shown as having a rectangular plate shape. Projecting vertically from the base 302 is a support 304, also having a rectangular plate shape. Displaced on the support 304 are the track 324 and the tray 310 (shown by dashed lines). At one end of the tray 310, a base portion 306 protrudes from the support 304 above the tray 310. A sensor 401 is attached to the base portion 306. Connected to the base portion 306 and protruding from it by a distance at least equal to the length of the slide basket is a bracket 301 that holds the screen 303 at the opposite end.

[0022] The tray 310 is typically made of relatively thin aluminum. The side walls of the tray 310 protrude vertically from its bottom and are spaced apart to accommodate the basket 210C. The sliding basket 210C includes side wall supports 235A and 235B on both sides. The side wall supports 235A and 235B are arrow-shaped, with the tips of the arrows pointing outward (from the basket 210). The side walls of the tray 310 have shapes corresponding to the shapes of the side wall supports 235A and 235B so that the sliding basket 210C fits into the tray 310.

[0023] Figure 5 shows the apparatus 300 of Figure 4 with the bracket 301, bottom 302, support 304, track 324, and base 306 removed. As shown, the bottom of the tray 310 has an opening for most of its length. Distributed within the opening is a belt, such as a plastic belt, or a track 320. In one embodiment, the belt 320 is mounted on rollers 325A and 325B. The rollers 325A and 325B may be separated by a distance approximately equal to the length of the tray 310. Each of the rollers 325A and 325B may have several equally spaced saw teeth defining its outer circumference. One side of the belt 320 (the side facing the rollers 325A and 325B) has similarly spaced saw teeth that can be actuated to engage with the saw teeth of the rollers. The spacing of the teeth on the rollers and belt 320 is similar to the spacing of the notches 245 on the slide baskets 210C, which isolate the longitudinally arranged slides from each other so that the belt can stop at each notch 245 on the slide baskets 210C. The rollers 325B may be connected to the motor 330 by a rod or spindle 332. In one example, the motor 330 is an electric stepper motor that can be operated to rotate the rollers 325B. The rollers 325A are disposed on the spindle 333 and are rotatable therein.

[0024] Figures 4 and 5 also show the motorized assembly for lifting the individual slides of the slide basket 210C. The device 300, in this example, includes a U-shaped push bar 350, with one end of the push bar 350's vertical projection positioned to move vertically over the opening at the bottom of the tray 310 and the opening and bottom 230 of the basket 210C. The other vertical projection of the push bar 350 is positioned outside the tray 310. A connecting rod 360 is connected to the push bar 350 at one end and to an L-shaped rotating arm 370 at the second end. The rotating arm 370 is connected to a motor 380 through a rod 382. In one embodiment, the motor 380 is an electric motor that can be operated to rotate the rod 382. The rotation of the rod 382 rotates the rotating arm 370. The rotating arm 370 is pivotably connected to the connecting rod 360, and the rotation of the rotating arm 370 moves the connecting rod 360 up and down. The vertical movement of the connecting rod 360 is transmitted to a push bar 350, which moves up and down on its own due to the rotation of the motor 380. The upward movement advances the vertical arm of the push bar 350 inward and outward of the slide basket 210C (inward and outward of the bottom of the slide basket), lifting the individual slides (e.g., slide 290) of the slide basket 210C perpendicular (Y direction) to the position where one end of the slide fits into the bottom of the slide basket 210C. When an individual slide (slide 290) is lifted out of the slide basket 210C, an area 2901 of the slide is exposed and can be read and / or detected (e.g., scanned and imaged) by the sensor 401.

[0025] Figures 6 and 7 show an upper perspective view of the apparatus 300 with the basket 301, bottom 302, screen 303, support 304, track 324, and base 306 removed, illustrating the lifting and returning of the slide in the basket 210. Referring to Figures 6 and 7, these figures show a push bar 350 including vertical projections 3502 and 3504 isolated by a lateral projection 3503. In this embodiment, the vertical projection 3502 of the push bar 350 has a width that can be housed within the slide basket 210C (for example, through the opening in the bottom 230 of the slide basket 210C) and a thickness that is approximately equal to the thickness of the slide 290 but not as thick as the width of the notch 245. Figure 6 shows the vertical portion 3502 of the push bar 350 located below the slide basket 210C (below the bottom of the slide basket) and the slide 290 placed in a slot in the bottom 230 of the slide basket 210C. In Figure 6, the rotating arm 370 is in the lower position. Figure 7 shows the rotating arm 370 in the upper position. Moving the rotating arm 370 from the lower position to the upper position causes the connecting rod 360 to lift the push bar 350 upward by a typical distance of about 63 mm to 75 mm (2.5 inches to 3 inches). The slide in the slide basket can be lifted by a distance sufficient to expose the section on the slide (the section is a specimen embedded and surrounded by an embedding medium (e.g., paraffin)) along with the label on the slide. This exposure of the section allows an image of the section to be captured by the sensor 401. When the push bar 350 is lifted, a portion 3502 of the push bar 350 enters the slide basket 210C and presses against the end of the slide 290, pushing the slide 290 upward so that one end of the slide 290 is no longer adjacent to or in contact with the bottom 230 of the slide basket 210C. The vertical movement of the push bar 350 is guided by the linear guide 385. The slide 290 is in an upper position, and the outer portion of the slide basket 210C is longer than the other slides that can be nested in the slide basket 210C. The portion of the slide 2901 can be detected (e.g., scanned and imaged) by the sensors described above.

[0026] When a slide basket (e.g., slide basket 210C) is placed on the track 324 of the device 300 at the slide identification station 1120 so that it rests on a portion of the belt 320, the belt 320 engages with the sawtooth (sawtooth 250, see Figure 4) at the bottom of the slide basket, and the detection sensor 345 detects the presence of the basket. Then (for example, when the detection sensor 345 sends a signal to the motor 330), the motor 330 automatically moves the belt 320 forward, causing the basket 210C to move forward towards the sensor 401. As the slide basket 210C moves forward, the detection sensor 340 detects the presence of a slide inside the slide basket 210C, and the motor 380 activates to push the push bar 350 upward to lift the slide inside the slide basket 210C. The detection sensor 331 detects the forward movement of the push bar 350. The signal from the detection sensor 331 to the sensor 401 warns of the rising slide, and the sensor 401 detects (e.g., reads, images) information about the rising slide. After detection, the slide descends into the basket 210C (block 470), and the motor 330 moves the belt 320 forward, advancing the slide basket 210C until another slide in the basket 210 is detected by the detection sensor 340. When a slide is detected, the slide rises and is detected.

[0027] The device 300 may be electrically connected to a processor 136 that coordinates the movements of motors 330 and 380. The processor 136 is operable to receive or acquire signals from each of the detection sensors 331, 340, and 345. The processor 136 stores non-temporary machine-readable commands that, when executed, raise the push bar 350 and cause sensor 401 to detect (e.g., read, image) the slide raised by the push bar 350. The executable commands also include commands to lower the push bar 350 by a distance to position it below another slide position in the slide basket 210C, and then to lower the stepper motor 380. The executable commands may further include commands to eject the slide basket 210C from the tray 310 when all slides in the basket have been individually detected by sensor 401.

[0028] Sensor 401 may be connected to the memory of processing assembly 100 (e.g., memory 137) and / or to a clinical laboratory information system (LIS), which is a software system for recording, managing, and storing data for the clinical laboratory. If sensor 401 is, for example, a barcode reader or scanner, sensor 401 may be operated to read and optionally record one or more barcodes printed on a slide (e.g., slide label or frosted area of ​​the slide). This information may include, but is not limited to, patient data (name, attending physician at admission, ordering department, specimen type, etc.) and staining or other protocols for the specimen on the slide (e.g., number received). The information read by sensor 401 is transmitted to processor 136 or LIS, and the system can track the slide and subsequently perform the necessary staining or other preparation protocols for the specimen. The read information may also be displayed on display 135 and stored in memory 137. It is recognized that a barcode reader or scanner is an example of a sensor that can be operated to detect information from a slide. In another embodiment, sensor 401 may be a camera or other reader (e.g., a radio frequency identification (RFID) reader). Typically, sensor 401 may include a reader 4012 and a scanner / imager 4014, as shown in Figure 4. The reader 4012 is a barcode reader or scanner (or other reader or scanner for identification information on the slide), and the scanner / imager 4014 is operable to capture (e.g., scan) an image of the sample on the slide. The screen 303 behind the slide may be a rectangular body approximately the size (length and width dimensions) of the slide or a portion of the slide (e.g., the slide portion lifted from the basket). The screen 303 is positioned behind the lifted slide and may be a solid color, such as gray or black, to provide a background that enhances detection by sensor 401 about information on the lifted slide. Once the slide is first introduced into the core module 110, the sample on the slide is placed in and / or permeated with an embedding medium such as paraffin, commonly called a section. Embedding material generally occupies a larger area on the slide surface than the sample placed within the embedding material.The executable instructions of the processor 136 instruct the scanner / imager 4014 to read the label or other identifying information on the slide and capture an image of a portion of the section, including the whole, so that the first possible identification of the section sample can be determined. The captured image of the section may be stored in memory 137. Often, due to the embedding material such as paraffin, the section sample may exhibit a different color (e.g., high opacity) from the surrounding embedding material (e.g., paraffin). The processor 136 may use this color difference to estimate the position of the sample on the slide. For example, the executable instructions of the processor 136 may include an instruction to overlay a grid on the stored image captured by the scanner / imager 4014 and detect the section sample by the color difference from the embedding material (e.g., using wavelength difference). The approximate position of the sample is determined using the grid and associated Cartesian coordinates, and this position may be stored in component 137. Furthermore, the total number of slides in the processing system 100 may be scanned so that the processor 136 can determine it, or the processor 136 may maintain a record of the number of slides in a basket that have been processed by the processing system 100.

[0029] In some cases, it is desirable to classify slides within a basket into two or more baskets. Examples include, but are not limited to, classifying slides based on case (e.g., patient) and classifying slides based on staining or other protocols (e.g., antigen retrieval). One method by which slides can be classified is performed following detection of the slide at the slide identification station 1120. Once information about the slide or the sample on the slide is detected (e.g., scanned), this information can be used to classify the slide into a specific basket. For example, if the processor 136 or another LIS determines, based on information detected from the slide at the slide identification station 1120, that the slide should be moved from slide basket 210C to another basket, the executable instructions of the processor 136 may include an instruction to the robotic mechanism 1140 to move the slide to slide basket 210D or slide basket 210E at the classification station 105. The robotic mechanism 1140 shown in Figures 2 and 3 may include an end effector capable of securely gripping the slide (e.g., gripping both edges of the slide) and transporting the slide between slide baskets. To assist in grasping slides, slides can be grasped when they are in an elevated or lifted position within the basket 210C at the slide identification station 1120 (for example, when they are raised or lifted by the push bar 350). This may occur immediately after or after information is detected (for example, after all slides in the basket have been detected). As described above, the robotic mechanism 1140 includes a robotic controller 1141 (see Figure 3 or 5) that can control robotic movements (for example, the movement of the robotic mechanism 1140 on the track 1145 and the processing tasks performed by the robotic mechanism 1140). The robotic controller 1141 is linked to the processor 136 either wired or wirelessly. In this example, machine-readable program instructions sent from the processor 136 to the robotic controller 141 may involve moving to an elevated position above the slide basket 210C, grasping a lifted slide, and transporting such a slide to the slide basket 210D.As described above, the robotic mechanism 1140 can be used at various points in time to grasp and transport individual slides together with individual slide baskets. The robotic mechanism 1140 may use a single end effector to accomplish any task, such as an end effector having two protruding arms, blades, or forks whose separation distance can be adjusted depending on whether the end effector was attempting to grasp a basket (wide) or a slide (narrow). Alternatively, the robotic mechanism 1140 may be provided with access to different end effectors to perform a certain task. For example, one end effector may have protruding arms, blades, or forks for grasping the slide basket on both sides of the slide basket, while another end effector may be a vacuum suction device for grasping individual slides through a vacuum suction connection to the surface of the slide. Independent end effectors may be stored within the processing assembly 1000, and executable instructions from the processor to the robotic mechanism 1140 (e.g., the robot controller 1141) may include instructions for the robotic mechanism to select the appropriate end effector before performing a task.

[0030] Once all slides in a slide basket (e.g., slide basket 210C) are detected by sensor 401 and optionally classified (e.g., some are removed from slide basket 210C and placed in slide basket 210D), the slide basket 210C can be removed by the robotic mechanism 1140 from the slide identification station 1120 by moving the robotic mechanism 1140. From the slide identification station 1120, the protocol may transfer the slide basket (e.g., slide basket 210C) to the baking / dewaxing station 1110. Rails or tracks 1145 may be positioned at a height sufficient to allow the end effectors of the robotic mechanism 1140 (e.g., two protruding arms, blades, or forks spaced a distance apart to grip both sides of slide basket 210C) to be operated on those sides of slide basket 210C, grasp the slide basket, and then move upward to raise the slide basket with a handle. Then the slide basket (for example, slide basket 210C) rises and is transferred to the baking and dewaxing station 1110.

[0031] Prior to staining / printing a sample on a slide (e.g., a tissue sample), paraffin-embedded samples may be baked to allow the sample to be placed on the slide, and then deparaffinized (dewaxed) to expose the sample and allow an aqueous solution to permeate it (first exposure). In the baking and dewaxing station 1110, slide baskets, each containing one or more slides containing paraffin-embedded samples, can undergo a series of operations to bake and dewax the samples. These operations are performed while the slides are in the slide baskets, allowing multiple samples to be baked and dewaxed together. Typically, the baking and dewaxing station 1110 includes three tanks or compartments, each with its own dedicated lid. Each lid may be connected to a hinge that can be automatically operated via commands from the processor 136. Figure 3 typically shows the lids of an open tank or compartment 1112, tank or compartment 1114, and closed tank or compartment 1116. Figure 3 also shows the end effectors of the robotic mechanism 1140, which are two protruding arms, blades, or forks that grip the slide basket 210B, and the robotic mechanism 1140 that positions the slide basket 210B into the volume of the tank or compartment. The tank or compartment 1112 is operable to heat the slides in the slide basket as part of a baking operation. The heat treatment should be sufficient to cause the specimen on the slide to adhere or be additionally adhere to the slide (glass slide) and, if possible, to soften the section on the slide and the associated embedding medium. Typically, a resistance heating element sufficient to raise the temperature within the volume of the tank or compartment 1112 to a temperature of about 55°C to 70°C may be laid on one or more sides of the outer surface of the tank or compartment 1112. The tank or compartment 1114 contains a dewaxing solution, such as xylene, in a volume sufficient to immerse the specimen portion of the slide arranged longitudinally in the slide basket. The tank or compartment 1114 may be a series of tanks or compartments containing similar or different dewaxing solutions. An example of multiple tanks or compartments for tank or compartment 1114 is a first tank or compartment for storing a certain volume of xylene and a second tank or compartment for storing a certain volume of alcohol (e.g., ethyl alcohol).The tank or compartment 1116 contains a certain volume of cleaning solution, such as water or another aqueous cleaning solution.

[0032] Under the control of executable instructions in processor 136, the baking and dewaxing process may proceed automatically. Such instructions may include the individual opening of one or more lids of a tank or compartment, the placement of a slide basket into the tank or compartment, the duration of an operation (e.g., baking, dewaxing, etc.), the removal of the slide basket from the tank or compartment, and the closing of one or more lids. As an example of a baking and dewaxing process to adhere and dewax the slides of a slide basket, the lid of the tank or compartment 1112 is automatically opened, the slide basket (slide basket 210B) is placed in the tank or compartment 1112 by the robotic mechanism 1140, and the slide basket undergoes a baking process (e.g., for 5 to 60 minutes) sufficient to adhere the sample to the individual slides and dissolve the paraffin on each slide. The robotic mechanism 1140 then transfers the slide basket to the tank or compartment 1112 and defits it. The door or lid is then automatically closed over the top of the tank or compartment 1112 for the duration of the baking operation. Following the baking operation, the door or lid on the tank or compartment 1112 may automatically open, and the robotic mechanism 1140 may engage with the slide basket (e.g., slide basket 210B) and transfer the slide basket to the tank or compartment 1114. The door or lid on the tank or compartment 1114 may automatically operate and open, and the robotic mechanism 1140 transfers the slide basket to the tank or compartment 1114 and disengages the slide basket. The tank or compartment 1114 may contain one or more dewaxing solutions of a certain volume sufficient to immerse at least the samples on the slides of the slide basket in the dewaxing solution. Following the automatic transfer of the slide basket to the tank or compartment 1114, the door or lid of the tank may automatically close. The slides of the basket may undergo a typical dewaxing operation for, for example, 3 to 5 minutes. The tank or compartment 1114 may include a stirrer (e.g., a magnetic stirrer) for agitating one or more dewaxing solutions during the dewaxing operation.Alternatively, instead of disengaging the slide basket when transferring it to the tank or compartment 1114 with the door or lid of the tank or compartment 1114 remaining open, the robotic mechanism 1140 may raise and lower the slide basket during the dewaxing operation to agitate the one or more dewaxing solutions in the tank or compartment. Following the dewaxing operation, the robotic mechanism 1140 automatically transfers the slide basket to the tank or compartment 1116. The door or lid of the tank or compartment 1114 is then automatically closed, and the door or lid of the tank or compartment 1116 is automatically opened, allowing the robotic mechanism 1140 to transfer the slide basket to the tank or compartment 1116. The tank or compartment 1116 can contain one or more cleaning solutions of a certain volume sufficient to immerse at least the samples on the slides in the slide basket in the cleaning solution. The slides in the basket can undergo a typical cleaning operation for 3 to 5 minutes. The door or cover associated with the tank or compartment 1116 is closed during the cleaning operation, allowing the cleaning solution to be agitated. Alternatively, the robotic mechanism 1140 may maintain engagement with the slide basket during the cleaning operation, and the slide basket may be repeatedly raised and lowered to agitate the cleaning solution.

[0033] Following the processing of slides stored in a slide basket at the baking and dewaxing station 1110, the slide basket may be transferred to the staining module 120. The slide basket may be transferred using a robotic transfer assembly such as a robotic mechanism 1140. As illustrated in Figure 2, the staining module 120 is provided with rails or tracks 1146 (extending, e.g., from the front wall to the back wall), and / or rails or tracks 1145 oriented perpendicular to the rails or tracks 1146 may have a length extending to a portion of the staining module 120. Machine-readable program instructions are sent between the processor 136 and the robotic controller 1141 (e.g., from the processor 136 to instruct the robotic controller 1141) to implement a protocol for transferring the slide basket (e.g., slide basket 210A or 210B, Figure 3) from the baking and dewaxing station 1110 to the antigen retrieval station 1240 (see Figure 2) in the staining module 120. The robotic mechanism 1140 can grasp the slide basket with its end effector, the rail or track 1145 can move to the front of the processing assembly 100, and the robotic mechanism 1140 can be transported on the rail or track 1140 to the staining module 120 at an adjacent position above the antigen retrieval station 1240.

[0034] Figure 8 shows a magnified view of a portion of the staining module 120, including the antigen retrieval station 1240. In the antigen retrieval station 1240, the slide can undergo antigen retrieval treatment at high temperature and pressure to expose antigenic sites in or on the sample (second exposure). The antigen retrieval station 1240 may include one or more chambers for storing retrieval agents. Two or more chambers provide the opportunity to use the same or different retrieval agents. Typically, one chamber may store a low pH antigen retrieval solution (e.g., sodium citrate retrieval solution at pH 6), and the other chamber may store a high pH antigen retrieval solution (e.g., Tris retrieval solution at pH 8 to pH 10). Figure 8 shows two chambers, chamber 1241 and chamber 1243, juxtaposed on the processing platform 1201. Rotatably connected to the sides of chambers 1241 and 1243 are lids (lids 1245 and 1246, respectively) that can be automatically opened and closed by commands from the processor 136. Figure 8 shows lid 1245 in an open position that exposes the contents of chamber 1241, and lid 1246 in a closed position that covers the contents of chamber 1243. Lids 1245 and 1246 allow each chamber to be pressurized during the antigen retrieval process. Chambers 1241 and 1243, along with lids 1245 and 1246, are made of a material such as porcelain that can withstand the vigorous boiling of the antigen retrieval solution in each chamber, or they may include a liner of a material (the liner is exposed from the contents of the chamber).

[0035] Slides in a slide basket (e.g., slide basket 210A) can be transported to an antigen retrieval station 1240 by a robotic mechanism 1140. The robotic mechanism 1140 may be instructed, for example, by commands from a robotic controller 1141 which may be linked to a processor 136. The end effector 1142 of the robotic mechanism 1140 can grasp the slide basket on both sides and position the slide basket in chamber 1241 or chamber 1243 of the antigen retrieval station 1240 when their respective lids are opened. Once the slide basket is positioned, the lid (e.g., lid 1245) can be closed and the antigen retrieval process can proceed. The lid can be opened and closed automatically by executable commands from the processor 136 (for example, a command may instruct the lid hinge and associated electric motor to operate the lid to open and close). When lid 1245 is closed, a sealed chamber is formed, and the antigen retrieval process can be carried out under high pressure, such as 1.0 to 1.06 bar (15 psi) above atmospheric pressure. In a typical antigen retrieval treatment, a Tris or citrate-based retrieval solution can be used at temperatures ranging from 100°C to 121°C and high pressures exceeding atmospheric pressure, up to 1.06 bar, for 3 to 15 minutes. The use of high pressure can accelerate the antigen retrieval process to, for example, 5 minutes, compared to conventional treatment times of 45 minutes or more under atmospheric conditions in a similar tank.

[0036] To achieve high pressure and temperature, chambers 1241 and 1243 may have heating elements (e.g., induction or resistance heating elements 12412 around chamber 1241) installed on one or more sides of the outside of the chambers, which are sufficient to raise the temperature of the solution within the chamber's volume to the desired high temperature. Heating the antigen retrieval solution in a sealed chamber has the effect of increasing the pressure. Alternatively or additionally, the volume of each chamber may be reduced by closing the lids of each chamber and increasing the pressure of the gas (e.g., air) inside the chamber. In addition to the increase in heat and pressure, the antigen retrieval solution may be stirred during the antigen retrieval process or operation, for example, with a magnetic stirrer in the solution.

[0037] Figure 8 shows chambers 1241 and 1243 arranged in a jacket or large container 1244. The large container may be filled with water or other fluid to heat or cool the chambers. The fluid may be introduced into the container 1244 from an inlet 12442 and discharged from the container 1244 at an outlet 12444. The inlet 12442 may be connected to a fluid source (e.g., a water source), and the outlet 12444 may be connected to a waste or recycling tank. The temperature of the fluid may be lowered by an inline cooler or refrigerant as desired, and heated by an inline heater. The inlet 12442 and outlet 12444 may be controlled by valves (valve 12443 and valve 12445, respectively) linked to a processor 136. In examples where a fluid source is used to cool chambers 1241 and / or 1243, an antigen retrieval treatment may be performed in which the antigen retrieval solution in chambers 1241 and / or 1243 is heated to, for example, approximately 120°C (248°F) for 3 to 13 minutes. Following the heating treatment, a cooling fluid (e.g., water at or below ambient temperature) may be introduced from inlet 12442 into container 1244 to cool the antigen retrieval solution in chambers 1241 and / or 1243 to, for example, 50°C (122°F) or below. The fluid may be introduced into container 12442 for the cooling treatment and remain present around chambers 1241 and 1243, or the fluid may be circulated within the container (from inlet 12442 to outlet 12444) for the cooling treatment. Typical times for cooling the antigen retrieval solution from 120°C (248°F) to 50°C (122°F) using a cooling fluid of water at near ambient temperature are approximately 8 minutes or less, such as 5 minutes or 3 to 5 minutes. In another example, a heating fluid (e.g., water at a temperature higher than ambient temperature) is introduced from inlet 12442 to assist in raising the temperature of the antigen retrieval solution in chambers 1241 and / or 1243 during the antigen retrieval process. The heating fluid may then be replaced with the cooling fluid following the antigen retrieval process to cool the antigen retrieval solution. Optional heating coils 12412 may be placed around each of chambers 1241 and 1243 to assist in heating. The coils (e.g., coil 12412 around chamber 1241) may be controlled by processor 136. Although one container (container 1244) is shown around both chamber 1241 and chamber 1243, it is recognized that each chamber may be arranged in separate containers, each having a fluid inlet and outlet.

[0038] Chambers 1241 and 1243 can each be connected at their bottoms (below the processing platform 1201) to their respective supply and waste tanks so that the antigen retrieval solutions in chambers 1241 and 1243 are periodically replaced. The supply and waste tanks below the processing platform 1201 may house level sensors that are in communication with the processor 136. The liquid levels in the supply and waste tanks can be displayed on the screen of the display 135 so that the operator can visually check the liquid levels. When the supply tank is empty or nearly empty, the processor 136 may send an alert (e.g., an alert on the display 135, or an alarm) to the operator so that the supply tank can be replaced. Similarly, when the waste tank is full or nearly full, the processor 136 may send an alert (e.g., an alert on the display 135, or an alarm) to the operator so that the waste tank can be replaced.

[0039] Following antigen retrieval, a slide basket containing one or more slides may be transported to a washing or storage tank in preparation for staining. Figure 2 shows the robotic mechanism 1255 moving in the x-direction within the staining module 120 on a track or rail 12553 (two parallel tracks). The robotic mechanism 1255 may include a multi-joint arm having, for example, three, four, six or more rotational joints, which allow the arm to move along an arc-shaped path centered on the horizontal plane or rotate along the joint axis. Translational or linear joints allow the arm to move along the axial direction (along the joint axis). The robotic mechanism 1255 has end effectors 12552 at the ends of the arms that are operable to grip the slide basket on both sides and enable the movement and transport of the slide basket. The robotic mechanism 1255 may have a controller or processor 12551 operable to communicate with a processor 136. In one example, an executable instruction associated with the processor 136 instructs the robotic mechanism 1140 to retrieve a slide basket from chamber 1241 or chamber 1243 at the antigen retrieval station 1240. In another example, an instruction from the processor 136 instructs the robotic mechanism 1255 to acquire the slide basket from chamber 1241 or chamber 1243 and transport it directly to the washing tank 1247. Alternatively, the instruction may instruct the robotic mechanism 1140 to place the acquired slide basket in the antigen retrieval station 1240 adjacent to chamber 1241 or chamber 1243, or in an area 1200 that can be fitted with the end effector 12552 of the robotic mechanism 1255. The instruction associated with the processor 136 may then instruct the robotic mechanism 1255 to grasp the slide basket and transport it to the washing tank 1247.

[0040] Similar to robotic mechanism 1140, robotic mechanism 1255 may have access to a variety of end effectors for performing a particular task. For example, one end effector may have projecting arms, blades, or forks for gripping the slide basket on both sides of the slide basket, while another end effector may be a vacuum suction device for gripping individual slides through a vacuum suction connection to the slide surface. Independent end effectors may be stored within the processing assembly 100, and executable instructions from the processor to robotic mechanism 1255 (e.g., to robot controller 12551) may include instructions for the robotic mechanism to select the appropriate end effector before performing the task.

[0041] Typically, the washing tank 1247 may be analogous to a tank or compartment of the baking and dewaxing station 1110, which includes a volume or compartment having a size to accommodate one or more slide baskets and a dedicated lid. The lid may be connected to a hinge that can be operated automatically via instructions from the processor 136. Although one washing tank (washing tank 1247) is shown, it is recognized that the processing assembly 100 may include two or more washing tanks.

[0042] The washing tank 1247 may store a certain amount (volume) of washing solution, such as TBS or phosphate-buffered saline containing a surfactant. In certain situations, one or more individual slides may require priority over other slides. The washing tank 1247, which stores the washing buffer, provides an environment for holding slides prior to staining / printing operations. Such holding includes planned holding, such as when one or more slides with higher priority need to be transported to the print station before other slides that have been loaded and processed before the higher-priority slides. The washing tank 1247 may be connected at the bottom to a supply tank for supplying washing buffer and a waste tank for collecting used washing buffer. Access to the supply tank and waste tank (e.g., draining used washing buffer from the washing tank 1247 into the waste tank and refilling the washing tank 1247 with washing buffer from the supply tank) may be controlled by the processor 136. The supply tank and waste tank below the processing platform 1201 may house liquid level sensors in communication with the processor 136. The liquid levels in the supply tank and waste tank may be displayed on the screen of the display 135 so that the operator can visually check the liquid levels. When the supply tank is empty or nearly empty, the processor 136 may send an alert (e.g., an alert on the display 135 or an alarm) to the operator so that the supply tank may be replaced. Similarly, when the waste tank is full or nearly full, the processor 136 may send an alert (e.g., an alert on the display 135 or an alarm) to the operator so that the waste tank may be replaced.

[0043] The washing solution in the washing tank 1247 may also contain a staining agent such as eosin or hematoxylin that can at least temporarily color or stain the sample on the slide. The slides in the basket can be automatically transferred to the washing tank 1247 by the robotic mechanism 1255 (the slides may remain in the basket in the washing solution of the washing tank 1247). The slides are individually removed from the slide basket for staining / printing, and the basket remains in the washing tank 1247.

[0044] Prior to staining / printing, the sample on the slide may be detected again. In such an example, a basket containing one or more slides may be removed from the washing tank 1247 by a robotic mechanism 1255 based on an instruction from the processor 136 and transported to a slide identification station 1221. The slide identification station 1221 is similar to the slide identification station 1120 and may include a reader for scanning and reading slide identification information and a scanner / imager for capturing (e.g., scanning) an image of the sample on the slide. In an example where a staining agent such as eosin or hematoxylin is added to the solution in the washing tank 1247, the sample on the slide may be stained with a portion of this staining agent. The scanner / imager of the slide identification station 1221 is capable of capturing an image of the sample so that the position of the sample on the slide can be determined. Executable instructions from the processor 136 may instruct the robotic mechanism 1255 to acquire a slide basket containing one or more slides and transport the slide basket to the slide identification station 1221. In this process, the executable instructions of the processor 136 may instruct the scanner / imager of the slide identification station 1221 to capture an image of a portion of the sample on the slide, including the whole. The captured image of the sample may be stored in memory 137. The processor 136 may estimate the position of the sample on the slide from the stored image. For example, the executable instructions of the processor 136 may include an instruction to detect the sample by color difference relative to the color of the slide (e.g., using wavelength difference) by overlaying a grid on the stored image. The approximate position of the sample is determined using the grid and associated Cartesian coordinates, and this position may be stored in memory 137. Alternatively or additionally, the stored image of the sample captured by the slide identification station 1221 may be compared with an image previously captured and stored from the slide identification station 1120. Based on this comparison, performed by the analysis of the processor 136 and associated executable instructions, the position of the sample on the slide may be determined. To focus on injecting the printing medium onto the sample and minimize waste associated with printing in areas where the sample is not present, this positional information can be stored in memory 137 for later use in the staining / printing operation.If no staining agent is added to the washing solution, or if there is insufficient staining agent for the slide identification station 1221 to accurately capture the image, the sample memory / storage position information from the first slide identification station 1120 may be used in subsequent printing operations.

[0045] As described above with respect to the slide identification station 1120, the slide identification station 1221 includes a track on which a slide basket is placed, and the slides in the basket are raised or lifted one by one and detected by a sensor mounted on a base at one end, optionally assisted by a screen or background behind the slide (the lifted slide is between the sensor and the screen or background). Once a slide is detected (e.g., scanned / imaged), the end effector 12552 of the robotic mechanism 1255 may include an end effector capable of reliably gripping the raised or lifted slide (e.g., gripping both side edges or gripping one side or the back with a vacuum grip) and transporting it to the staining module 1270. This gripping and transport of the slide may be instructed by a command from the processor 136 to occur immediately after or after the information has been detected (e.g., after all slides in the slide basket have been detected). Alternatively, if all slides are detected, the processor 136 may instruct the robotic mechanism 1255 to grasp the slide basket at the slide identification station 1221 and return the slide basket to the washing tank 1247. The slides remain until it is desired that they be transported individually to the slide station 1270, at which point the processor 136 may instruct the robotic mechanism 1255 to grasp these slides individually and transport them from the slide basket in the washing tank 1247 to the print station 1270. The slides are transported individually to the print station 1270, while the other slides remain in the washing tank 1247.

[0046] Figure 9 shows a front perspective view of another example of the robotic mechanism 1255 and slide identification station 1221. As described above, the slide baskets for storing slides are located within the washing tank 1247, from which the slides are removed individually. Figure 9 shows the washing tank 1247 housing slide baskets 210F for storing several slides. As shown in the figure, the depth of the solution in the washing tank 1247 should be such that it covers a typical area on the slide from which the sample is stored. This typical area is approximately the central portion or central division of the slide. Figure 9 shows that a portion of each slide that does not contain a sample may be above the level of the solution in the washing tank 1247. This portion may be the slide label or slide identification portion. Figure 9 also shows the robotic mechanism 1255, which includes an end effector 12552 having a suction member at its end connected to a vacuum source associated with the robotic mechanism. Commands from the processor 136 may instruct the robotic mechanism 1255 to individually retrieve slides from the cleaning tank 1247 by gripping or grasping the slides on their face or back with a suction member (e.g., a suction member that contacts the slide identification portion). Figure 9 shows an end effector 12552 that holds the slides. Such commands include lifting the gripped or grasped slide and removing it from the slide basket 210F, and transporting the retrieved slides to the slide identification system 1221.

[0047] The slide identification station 1221 in the example shown in Figure 9 is similar to the slide identification station 1120 and may include a reader for scanning or reading slide identification information and a scanner / imager for capturing (e.g., scanning) an image of the sample on the slide. However, instead of receiving slides into a slide basket, the slide identification station 1221 receives slides individually. Receiving slides individually reduces fluid accumulation or leakage at the slide identification station compared to when a slide basket containing one or more slides is transported from the humid environment of the washing tank 1247 to the slide identification station 1221. Slides are placed on the slide identification station 1221 by their long side or longitudinal edge, which is supported by the end clamps of the stand 12214 or the vertical slots 12212 and 12213, respectively. The slide (e.g., slide 290) is placed such that the sample and slide identification on the slide are on the same side as the sensor 4010 or the barcode reader or scanner and imager. The sensor 4010 may be positioned at an angle to capture the sample on the slide along with the label. The slide identification station 1221 may also include a screen 3010 on the same side of the slide as the sensor 4010, and / or on the opposite side to block glare or unwanted light images from the sensor 4010. In an example where a stain is added to the washing solution at the baking / dewaxing station 1110, the sample on the slide may be stained with a portion of this stain. The scanner / imager of the slide identification station 1221 may read slide identification information on the slide and relay this information to the processor 136, which may then obtain an appropriate processing (staining / printing) plan for the sample on the slide. The slide identification station 1221 may also capture an image of the sample so that the position of the sample on the slide can be determined. Executable instructions from the processor 136 may instruct the scanner / imager of the slide identification station 1221 to capture an image of a portion of the sample, including the whole. In the described processing, an image of the sample on the slide may be captured after antigen retrieval processing prior to staining / printing.It is recognized that image capture (the second capture described, with the first capture performed at the slide identification station 1120) may alternatively precede the antigen retrieval process. In such an alternative, image capture of the sample may be performed after the slide basket, each containing one or more slides with samples, has been processed at the baking and dewaxing station 1110. In such an example, the tank 1116 of the baking and dewaxing station 1110 may optionally contain a staining agent such as eosin or hematoxylin that can at least temporarily stain or color the sample on the slide. Alternatively, the slide basket may be transferred directly from the baking and dewaxing station 1110 to the washing tank 1247, and from the washing tank 1247 to a slide identification station such as the slide identification station 1221 or slide identification station 1120.

[0048] Once the slide has been read / scanned and, if possible, imaged at the slide identification station, executable instructions from the processor 136 instruct the robotic mechanism 1255 to remove the slide from the slide identification station 1221 and transport it to the print station 1270. Figure 10 shows the end effector in the humidifier rack assembly 1272 of the print station 1270, which grips the slide 290 by vacuum connection and loads the slide into the slide carrier 12728A (on the platen portion of the slide carrier 12728A). Inkjet printing is performed at the print station 1270 to print reagents such as a primary antibody that conjugates a target exposure antigen to a sample or detection reagent (e.g., a secondary antibody, peroxidase complex, substrate) that reacts with or can be linked to a primary antibody. Figure 11 shows a front view of the components of the print station 1270. These components include, in this example, a humidifier rack assembly 1272 consisting of a rack (e.g., a metal rack) with a frame of opposing pairs of vertical supports 12722A, 12722B, 12722C, shown with five horizontal supports 1273 (e.g., horizontal supports 1273 between vertical supports 12722A and 12722B) that isolate each pair in the y-direction. The humidifier rack assembly also includes five horizontal supports 12724A, 12724B, 12724C, 12724D, 12724E that isolate opposing pairs of vertical supports in the x-direction and define a horizontal row. Connected to the upper surface of each horizontal support 12724A-12724E are slide carrier linear rails.For illustrative purposes, Figure 11 shows slide carrier linear rail 12725A as one of three slide carrier linear rails connected to the upper surface of support 12724A, slide carrier linear rail 12725B as one of three slide carrier linear rails connected to the upper surface of support 12724B, slide carrier linear rail 12725C as one of three slide carrier linear rails connected to the upper surface of support 12724C, slide carrier linear rail 12725D as one of three slide carrier linear rails connected to the upper surface of support 12724D, and slide carrier linear rail 12725E as one of three slide carrier linear rails connected to the upper surface of support 12724E. In one example, the humidifier rack assembly can accommodate up to five slide carrier linear rails connected to horizontal supports (e.g., supports 12724A, 12724B, 12724C, 12724D, or 12724E) and evenly spaced apart between vertical supports (e.g., between vertical supports 12722B and 12722C), while in another example, there may be up to eight slide carrier linear rails.

[0049] Figures 12A and 12B show cross-sections of portions of the humidifier rack assembly 1272 along line 12-12' in Figure 11. Figures 12A and 12B show slide carrier linear rails 12725A connected to the upper surface of support 12724A and having a proximal portion projecting forward from the vertical support 12722C and a distal portion projecting backward. Each slide carrier linear rail has a typically rectangular cross-section to which brackets are mounted so as to be slidable in the y-direction. Figure 12A typically shows a bracket 12727A on the linear rail 12725A in front of the vertical support 12722C, and Figure 12B typically shows a bracket 12727A in the rear of the vertical support 12722C. Each bracket (e.g., bracket 12727A) is electrically connected to a processor 136 and is actuated on the slide carrier linear rail (e.g., slide carrier linear rail 12725A) based on instructions from the processor 136. A slide platen is mounted on the upper surface of each bracket. Figures 12A and 12B show a slide platen 12728A connected to the upper surface of bracket 12727A. Each slide platen (e.g., slide platen 12728A) has dimensions to house a slide. The slide platen is oriented to house the slide, and its length is defined by the y-axis or x-axis (in Figures 12A and 12B, the x-axis is defined to penetrate the plane of the paper). Also connected to each slide carrier linear rail is a humidifier housing. Figures 12A and 12B show a humidifier housing 12729A positioned behind the vertical support 12727C. Each humidifier housing (e.g., humidifier housing 12729A) has a top wall, two side walls, and front and rear walls. When the slide platen is positioned behind the vertical support 12722C, the slide platen forms the bottom of each humidifier housing. Figure 12A defines the open position in which the slide and slide platen 12728A are exposed, and Figure 12B defines the closed position in which the slide and slide platen are inside the humidifier housing 12729A. The movement of the slide platen 12728A from the open position to the closed position, or from the closed position to the open position, on the slide carrier linear rail 12725A can be controlled by commands from the processor 136 that instruct the movement.

[0050] Each humidifier, defined by a humidifier housing (e.g., humidifier housing 12729A) and a slide carrier (e.g., slide carrier 12728A), is operable to create a humidity-controlled environment for the slide prior to and / or following the printing process, thereby reducing the evaporation of staining reagents from the sample on the slide. Typically, humidified air is supplied into or circulated within the humidifier by a control valve 12730 to maintain a certain humidity level, which can be monitored by a monitor linked to processor 136 (e.g., processor 136 may store executable instructions to control the rate of humidified air in the control valve). In one example, a conduit valve assembly may be connected to a (preferably heated) water source below the processing platform 1201. The conduit may extend to the wall of the humidifier (e.g., the rear wall in the figure). A fan or blower may introduce air and water into the conduit and into humidifier 1272.

[0051] As shown in Figure 12B, each humidifier includes a cleaning nozzle 1274, which is mounted inside the upper part of the humidifier housing (e.g., humidifier housing 12729A). The cleaning nozzle 1274 may be a spray nozzle or atomizer that can be operated to spray a solution, such as an aqueous solution containing one or more salts, one or more buffers, surfactants, preservatives, and other excipients in specified concentrations as needed. In the operating mode, it is expected that the slide surface will be immersed as needed before and / or after the reagent is printed onto the sample. In one example, a conduit-valve assembly may be connected to an aqueous solution supply tank below the processing platform 1201. The conduit may extend to the cleaning nozzle 1274. The flow of solution from the supply tank through the cleaning nozzle 1274 may be controlled by a valve 12741. The valve 12741 may be connected to a processor 136. When the slide is in the humidifier housing (e.g., humidifier housing 12729A), the processor 136 may signal valve 12741 to open and spray the aqueous solution into the inside of the humidifier housing. The humidifier housing may also include a fluid removal device, such as an air knife. The fluid removal device, which is an air knife, may deliver pressurized air or an inert gas onto the slide surface to remove excess aqueous solution on the slide, if desired. The pressurized air or inert gas may be mixed with moisture to resist drying of the specimen by exposure to air or gas. Figure 12A shows a valve 12732 and conduit system that can supply air or other gas to the humidifier housing 12729A from a pressurized air tank below the processing platform 1201. Valve 12732 may be controlled by a command from the processor 136.

[0052] Many detection tests, such as immunohistochemistry (IHC) tests in which the print station 1270 may be employed, can be performed at atmospheric or near-atmospheric temperatures. Some tests, such as certain in-situ hybridization (ISH) tests, typically require individual steps to be performed at high temperatures. The humidifier housing 12729A can accommodate testing at a variety of temperatures by including a temperature-controlled humidifier that can operate at non-atmospheric temperatures (above and below atmospheric temperature). A typical range of hybridization temperatures above atmospheric temperature might be 45–70°C for ISH processing, for example. Temperature control can be achieved with heating tape or cable, which may be embedded electrical wires, and can be controlled by commands from processor 136. An alternative or additional example of a temperature-controlled humidifier might be a dedicated tank that can operate to store a heating solution (e.g., a buffer solution). For example, a DNA lysis protocol might require the sample on the slide to be heated to a temperature of 90°C or higher. For example, a dedicated tank adjacent to humidifier 1372 could store a solution to be heated to the desired temperature and be controlled by commands from processor 136. Such a tank would enable relatively high-temperature processing protocols, such as DNA lysis.

[0053] The humidifier housing 12729A can be pressurized even when the slide is inside the humidifier housing. A pressure increase (above atmospheric pressure) can accelerate the reaction time between the target in or on the sample and the reagent, reducing the evaporation of the reagent. The pressure can be increased by forming a sealed chamber comprising the humidifier housing 12729A and a slide carrier (e.g., slide carrier 12728A) and introducing gas into this chamber.

[0054] Referring again to Figure 11, the horizontally positioned ink cartridge rails are located above each horizontal support 12724A-12724E and slide carrier linear rail 12725A-12725E. Figure 11 shows (based on the z direction) ink cartridge rail 1275A connected to vertical supports 12722B and 12722C above horizontal support 12724A and slide carrier linear rail 12725A, ink cartridge rail 1275B connected to vertical supports 12722B and 12722C above horizontal support 12724B and slide carrier linear rail 12725B, and above horizontal support 12724C and slide carrier linear rail 12725C The diagram shows an ink cartridge rail 1275C connected to vertical supports 12722B and 12722C, an ink cartridge rail 1275D connected to vertical supports 12722B and 12722C above horizontal support 12724D and slide carrier linear rail 12725D, and an ink cartridge rail 1275E connected to vertical supports 12722B and 12722C above horizontal support 12724E and slide carrier linear rail 12725E. Each ink cartridge rail is connected to a printer adapted to receive an ink cartridge. Figure 11 shows a printer 1276A connected to and extending forward from ink cartridge rail 1275A. The printer 1276A is sized to accommodate one or more connected ink cartridges, such as two ink cartridges of similar or different sizes (dimensions). Each printer is connected to the ink cartridge rail by a bracket that is operable to move in the x-direction. Each printer may house a sensor that captures an image of the sample on the slide at the slide carrier (platen of the slide carrier). Figure 13 shows a top perspective view of a portion of the humidifier rack assembly 1272, showing the ink cartridge rail 1275A and the printer 1276A connected thereto. The printer 1276A is connected to the ink cartridge rail 1275A through a bracket 1277A.The bracket 1277A is connected to the ink cartridge rail 1275A so that the bracket 1277A and the printer 1276A can slide (move in the x-direction on the ink cartridge rail 1275A). Figure 13 also shows the cable assembly 1278A connected to the printer 1276A. The cable assembly 1278A consists of a communication cable linking the printer 1276A to the processor 136, along with the power cable for the printer 1276A, so that commands from the processor 136 instruct the movement of the printer 1276A on the ink cartridge rail 1275A and the ejection of reagent onto the slide by one or more (e.g., two) reagent cartridges on the slide carrier linear rail (e.g., slide carrier linear rail 12725A). Figure 13 also shows a sensor 12761 that can be operated to capture an image of the slide below the printer 1276A in the figure. The cable assembly 1278A may also be connected to the sensor 12761 to provide power to the sensor and to serve as a communication link between the sensor 12761 and the processor 136.

[0055] Figure 13 further shows two reagent cartridges connected to printer 1276A. As described above, in one example, each printer can house one or more reagent cartridges and dispense reagents from one or more reagent cartridges as instructed by processor 136. In this example, printer 1276A includes reagent cartridge 1279A and reagent cartridge 1280A. Reagent cartridge 1279A has larger dimensions than reagent cartridge 1280A. Typically, reagent cartridge 1279A has a y-direction depth of about 67.4 mm, an x-direction width of 58 mm, and a z-direction height of 98.5 mm, while reagent cartridge 1280A has similar depth and width to reagent cartridge 1279A (e.g., w2 is equal to w1) and a height of 70.8 mm (H2 is less than H1). In another example, reagent cartridge 1280A may have similar depth and height to reagent cartridge 1279A, but with a smaller width. Typically, reagent cartridge 1280A contains a fixed volume of primary antibody, and reagent cartridge 1279A may contain a primary antibody or a detection reagent such as a secondary antibody, enzyme, or complex. Each reagent cartridge is a drop-on-demand cartridge, preferably a thermal drop-on-demand cartridge, and each cartridge includes a separate printhead. The printhead may be positioned at the bottom of each reagent cartridge so that when the reagent cartridge is inserted into the printer (e.g., printer 1276A), the contents of the reagent cartridge are ejected through the bottom of the cartridge.

[0056] Figures 14A and 14B show a side perspective view of reagent cartridge 1279A. Reagent cartridge 1280A, which has a similar depth and width to reagent cartridge 1279A but a smaller height, has a side view similar to that shown in Figures 14A and 14B. Figures 14C and 14D show a side perspective view of reagent cartridge 1281A, a third example of a reagent cartridge. Reagent cartridge 1281A has a depth of approximately 74.1 mm, a width of 38.8 mm, and a height of 70.8 mm.

[0057] Each reagent cartridge 1279A, 1280A, and 1281A may contain a fixed volume of reagent and have its own dedicated printhead. Each cartridge may be a disposable cartridge. In this context, a disposable cartridge means that once a fixed volume of reagent in the cartridge is dispensed or used, the cartridge, including the printhead, is discarded or disposed of rather than being replenished with another fixed volume of reagent. An example of a disposable cartridge is a thermal inkjet cartridge. Each of the reagent cartridges 1279A, 1280A, and 1281A may have a substantially rectangular outer shell or body made of a plastic material (e.g., rigid plastic or polymer). Figure 14A shows the back of reagent cartridge 1279A in contact with and mating with printer 1276A. Figure 14C similarly shows the back of reagent cartridge 1281A in contact with and mating with printer 1276A. Figure 15 shows the front or front view of printer 1276A, with no reagent cartridges connected. The front or front side of the printer 1276A includes pockets or openings 12762 and 12763, in which a reagent cartridge can be placed. Each pocket has a length L and width W (the taller of reagent cartridges 1279A and 1280A, and the taller and wider of reagent cartridges 1279A and 1281A) to accommodate a cartridge of the same dimensions as reagent cartridge 1279A. In one example, each pocket has a length dimension of approximately 72 mm and a width dimension W of approximately 60 mm. The bottom of each pocket includes an electronic contact or pin 12764 that can be operated to engage with a receiving portion on the back of the reagent cartridge. The bottom of each pocket includes four magnets 12765 spaced apart around the contact or pin 12764, each having a diameter of, for example, approximately 2 mm to 3 mm, and two alignment pins 12766 arranged diagonally at the bottom of each pocket.

[0058] Referring to Figure 14A, reagent cartridge 1279A has length and width dimensions that fit just into either pocket 12762 or pocket 12763 of printer 1276A. The rear or back of reagent cartridge 1279A includes an electronic pin receiving portion 12794 that engages with the electronic contacts or pins 12764 of the pocket of printer 12764. The rear or back of reagent cartridge 1279A also includes four strips, plates, or sheets 12795 of magnetic metal material (e.g., iron, steel) that are attracted to a magnet (e.g., magnet 12765) inside the pocket of printer 1276A. Each strip, plate, or sheet 12795 has dimensions that match the dimensions of magnet 12765. For example, if the magnet (magnet 12765) has a circular shape with a diameter of 2 to 3 mm, the strips, plates, or sheets 12795 may have a circular shape with a similar typical diameter, or a rectangular shape with a length and width of approximately 2 to 3 mm. Each strip, plate, or sheet 12795 is positioned around the pin receiving portion 12794 so as to be oriented with the opposing magnet 12765 above or inside the bottom of each pocket of the printer 1276A. The magnet 12765 may act to attract the reagent cartridge (e.g., reagent cartridge 1279A) to the correct position in the pocket of the printer 1276A by attracting the strip, plate, or sheet 12795. The rear or back of the reagent cartridge 1279A also includes two diagonally spaced sockets or openings 12796 that align with the alignment pins 12766 above or inside the bottom of each pocket. Alignment pins 12766 can assist in aligning reagent cartridge 1279A to the pockets of printer 1276A. It is recognized that the magnets at the bottom of each pocket of the printer and the strips, plates, or sheets 12795 inside or on the back of reagent cartridge 1279A may be reversed (for example, the magnets may be inside or on the back of reagent cartridge 1279A and the strips, plates, or sheets may be inside or on the bottom of each pocket of printer 1276A). The back of reagent cartridge 1280A includes similar components (e.g., pin receptacle, strips, plates, sheets, and alignment sockets or openings) oriented in a similar manner to reagent cartridge 1279A.

[0059] As described above, printer 1276A has pockets or openings 12762 and 12763, each having similar length and width dimensions to reagent cartridge 1279A. Figure 14C shows reagent cartridge 1281A having a smaller height dimension (e.g., 70.8 mm compared to 98.5 mm) and a smaller width dimension (e.g., 38.8 mm compared to 58 mm of reagent cartridge 1279A). The rear or back side of reagent cartridge 1281A includes an electronic pin receiving area 12804 that engages with the electronic contacts or pins 12764 of the pocket of printer 12764, however the rear or back area of ​​reagent cartridge 1280A is not large enough to accommodate a magnetic strip, plate, or sheet, or a matching socket, to attract and align the reagent cartridge into the pocket of printer 1276A. To utilize the aspiration and matching features, an optional spacer 12807 is fitted to the reagent cartridge 1281A such that the rear or back surface of the reagent cartridge 1281A is exposed when fitted. The spacer adds width to both sides (left and right) of the rear or back of the reagent cartridge, and each of the two-part bodies (two-part body 128072 and two-part body 128073) has a rear surface on a plane similar to the rear or back of the reagent cartridge 1281A, thereby providing the additional width. The spacer 12807 may be a single plastic material having a connector above or below the reagent container 1281A, either connecting the two two-part bodies or not connecting the two two-part bodies (i.e., each two-part body is connected to the corresponding side of the reagent cartridge 1281A). Each two-part body of the reagent spacer 12807 (two-part body 128072 and two-part body 128073) includes two strips, plates, or sheets 12805, an alignment socket 12806 that aligns / engages with the magnet 12765, and an alignment pin 12766 in the pocket of the printer 1276A, respectively. Like the reagent cartridge 1279A, each of the strips, plates, or sheets 12805 has dimensions that match the dimensions of the magnet 12765.Before the reagent cartridge is introduced into the processing assembly 100, the spacer 12807 may be placed on the reagent cartridge 1281A (for example, an operator may attach the spacer 12807 to the reagent cartridge 1280A).

[0060] Referring to Figures 14B and 14D, these figures show the bottoms of reagent cartridges 1279A and 1281A. The bottom of reagent cartridge 1280A is similar to that of reagent cartridge 1280A. The bottom of each reagent cartridge contains a printhead of nozzles or nozzle arrays from which the reagent is ejected or extruded through thermal inkjet processing. Reagent cartridge 1279A is shown with printhead 12798, and reagent cartridge 1280A is shown with printhead 12808. Each printhead contains a linear array of nozzles (e.g., a single or multiple horizontal rows) that enables the ejection of reagent in a linear or horizontal pattern, such as across a slide. In thermal inkjet printheads, heat may be used to form bubbles of reagent vapor that burst as they are extruded from the printhead nozzles. Each nozzle may have a diameter of approximately 20 to 80 microns, such as 20 to 50 microns. Referring to Figure 12A, when the slide is positioned vertically on the slide carrier 12728A (the longer dimension is indicated as "L"), the print head of the reagent cartridge 1279A is oriented toward the paper in the figure so that the reagent is ejected between the side edges of the slide onto the upper surface of the slide (the surface containing the sample) as the slide carrier moves (for example, toward the humidifier housing 12729A).

[0061] Figures 14B and 14D also illustrate the magnets fastened to the bottom of each cartridge. The magnets 12799 of reagent cartridge 1279A and 12809 of reagent cartridge 1280A (e.g., two screws each) may be made of a ferromagnetic material (e.g., alnico or ferrite) that forms its own paramagnetic field. Magnets 12799 and 12809 may be used to secure the cap to the bottom of each reagent cartridge, as described below. Figures 14B and 14D also illustrate the alignment hole or divot 12791 at the bottom of reagent cartridge 1279A and the alignment hole or divot 12801 at reagent cartridge 1281A. The two diagonally positioned alignment holes at the bottom of each reagent cartridge may be used to align the cap to the reagent cartridge through the cap's alignment pin, as described below.

[0062] Referring again to Figures 12A and 12B, the printing and storage operations are typically illustrated. To load a slide into the slide carrier 12728A, a command from the processor 136 may instruct a bracket 12727A on the slide carrier linear rail 12725A to move to a position away from the humidifier housing 12729A (the open position in Figure 12A). Then, based on the command from the processor 136, the end effector 12552 of the robotic mechanism 1255 loads the slide into the slide carrier 12728A of the staining module 1270. Then, a command from the processor 136 may instruct a bracket 12727A to move the slide carrier 12728A to a position below the humidifier housing 12729A (the closed position shown in Figure 12B) until the system is ready to print or dispense reagent onto a portion of the sample on the slide. When the system for printing or ejecting reagents onto a portion of the sample on the slide is ready, a command from processor 136 instructs bracket 12727A to move slide carrier 12728A to an opening position (shown in Figure 12A) spaced apart from humidifier housing 12729A. A command from processor 136 also instructs printer 1276A to move on ink cartridge rail 12725A to a position above slide carrier 12728A, so that the reagent cartridge 1279A or reagent cartridge 1280A / reagent cartridge 1281A of printer 1276A is above the sample on the slide. Figure 12A shows reagent cartridge 1279A above or above slide carrier 12728A. A further command instructs ejection of reagent onto the slide (or portion of the sample on the slide) on slide carrier 12728A. During a print or ejection operation, commands from the processor 136 may instruct the bracket 12727A to move the reagent cartridge 1279A on the slide carrier linear rail 12725A below the printhead so that a desired portion or area of ​​the sample on the slide receives the reagent. As described above with respect to Figures 14B and 14D, the printhead includes a linear array (e.g., a single or multiple horizontal rows) to enable the ejection of the reagent in a straight line or horizontal row, such as across the slide.The movement of the bracket 12727A on the slide carrier linear rail 12725A can be controlled by the processor 136 so that a desired area of ​​the sample can receive the reagent one row at a time or in a sweeping motion.

[0063] As described above, the humidifier rack assembly 1272 may include a plurality of ink cartridge rails, each located above the horizontal support and slide carrier linear rail (in the z direction). In one example, each ink cartridge rail houses a printer capable of holding and dispensing one or more reagent cartridges. Printer 1276A is typical, and as shown in Figure 13, printer 1276A may hold two reagent cartridges. Referring to Figure 11, five ink cartridge rails (ink cartridge rail 1275A, ink cartridge rail 1275B, ink cartridge rail 1275C, ink cartridge rail 1275D, ink cartridge rail 1275E) are shown, each housing a printer capable of dispensing reagents onto a sample on a slide, which is positioned on a platen on the slide carrier linear rail directly below the printer. Figure 11 shows three slide carrier linear rails in each transverse row defined by the horizontal support of the humidifier rack assembly 1272. As described above, each row houses one, two, three, four, five, or more slide carrier linear rails, and the slide platen is connected to each slide carrier linear rail. By providing a printer that can move linearly (in the x-direction) on each ink cartridge rail, the system enables multiple slides to be processed simultaneously.

[0064] Referring to Figure 2, adjacent to the print station 1270 is a reagent storage cabinet 1250. The reagent storage cabinet 1250 may be a refrigerated cabinet having slots for storing several reagent cartridges. Each reagent cartridge may contain a certain volume of reagent and have its own dedicated print head, and may be stored in the storage cabinet 1250 with a cap above or above each print head. Figure 16 shows an example of the reagent storage cabinet 1250. In this example, the reagent storage cabinet includes a carousel 1252 in which the reagent cartridges are stored. The carousel 1252 may encompass a tubular structure having a row of slots around a tubular structure in which the reagent cartridges can be placed. The carousel 1252 may be connected at the bottom to a rotating mechanism such as an electric belt pulley system controlled by the processor 136. Figure 16 typically shows a carousel with seven rows of slots and 18 slots around each row. Each slot may have an address so that the position of the reagent cartridges in the carousel can be grasped and confirmed. Figure 17 typically shows an empty carousel. As an example of addressing, Figure 17 shows rows numbered 1 through 7 with slots in each row labeled A through S. Figures 16 and 17 also show configurations in which the carousel 1252 has an arbitrary structure such that larger reagent cartridges (e.g., reagent cartridge 1279A having a width of 58 mm and a height of 98.5 mm) can be stored in rows 1 and 2, while smaller reagent cartridges (e.g., reagent cartridge 1280A having a width of 58 mm and a height of 70 mm) or reagent cartridge 1281A (e.g., having a width of 38.8 mm and a height of 70.8 mm) can be stored in rows 3 through 7. In another example, the reagent cartridge is not isolated within carousel 1252 due to its dimensions. For example, carousel 1252 consists of an inner carousel 12521 and an outer carousel 12522, as shown in the exploded view of Figure 18. When assembled, the upper part of a portion of the inner carousel 12521 is exposed (for example, the inner carousel 12521 is taller than the outer carousel 12522 so that two of its horizontal rows are above the outer carousel 12522 when assembled).In this example, the inner carousel 12521 includes rows 8 through 12 for holding additional reagent cartridges, in addition to rows 1 and 2 described. In the inner and outer carousel example, access to the slots / reagent cartridges in rows 8-12 of the inner carousel 12521 is provided through an opening 12523 along the length of the outer carousel 12522. The opening 12523 is wide enough for a robotic arm or end effector to place or remove a reagent carousel from one of the slots in rows 8 through 12 of the inner carousel 12521. Furthermore, the inner carousel 12521 and the outer carousel 12522 may rotate independently through an independent rotation mechanism that rotates independently based on instructions from the processor 136 (e.g., belt pulley mechanisms at the bottom of each of the inner and outer carousels 12521 and 12522). Each slot in the carousel 1252 (for example, each slot in the inner carousel 12521 and the outer carousel 12522) may be configured to have magnetic alignment pins similar to those in a printer pocket (see pocket 12762 in Figure 15) for aspirating and securing reagent cartridges.

[0065] The cabinet 1250 housing the carousel 1252 is a refrigerated cabinet and may include a refrigeration system that maintains the cabinet temperature, for example, 40°C. An example of a refrigeration system may include a refrigerant that changes from liquid to gas among its components, a compressor that converts the refrigerant gas into a refrigerant liquid, a condenser that cools the refrigerant gas into a refrigerant liquid, and a power supply. The cabinet 1250 may include a door 12501 (e.g., an automatic sliding door) through which reagent cartridges can be introduced into or removed from the carousel 1252.

[0066] A robotic mechanism 1260 may be positioned adjacent to the door side of the cabinet 1250. The robotic mechanism 1260 may include a controller 12605 that communicates with the processor 136, and an end effector 12602 that includes two blades extending from the end effector at a distance such that the end effector 12602 can grip both sides of a reagent cartridge through the blades. The robotic mechanism 1260 may include a multi-joint arm having, for example, three, four, six or more rotary joints that allow the arm to move along an arc-shaped path centered on the horizontal plane or to rotate along the joint axis. Translational or linear joints allow the arm to move axially (along the joint axis). Figure 17 shows the end effector 12602 of the arm of the robotic mechanism 1260 that grips a reagent cartridge and places the reagent cartridge into a slot in the carousel 1252, or removes the reagent cartridge from a slot in the carousel 1252.

[0067] As described above, the slots in the carousel 1252 of the storage cabinet 1250 consist of a series of horizontal and vertical columns, and each slot is addressed by its horizontal and vertical columns. The addresses may be stored in the processor 136. Each cartridge may contain an identifier such as a machine-readable identifier (e.g., a one-dimensional or two-dimensional barcode). The identifier may contain a lot number and a unique serial number. The identifier may be read prior to storage in the storage cabinet 1250 (e.g., by a barcode reader or scanner) (e.g., by a barcode reader or scanner outside the processing assembly 100). The read value may be sent to the processor 136 and stored there. The identifier may also provide information such as the expiration date of the reagent and / or some operations (prints) that may be performed on the cartridge. The processor 136 may assign the addresses (horizontal and vertical addresses) of the slots in the storage carousel 1252 to the cartridges. The display screen of interface 135 may show the slots and cartridges. An alarm or display indicator on interface 135 may provide an alert when a cartridge that should be present is not in the assigned slot.

[0068] Referring again to Figure 2, the reagent cartridges placed on the carousel 1252 of the cabinet 1250 can be delivered to the processing assembly 100 by an operator or robot. During loading, the operator or robot can deliver one or more reagent cartridges to the inlet 1251. A robotic device capable of operating to deliver reagent cartridges to the processing assembly 100 is described in international application PCT / IB2020 / 059562, filed on 12 October 2020, entitled "Automatic Transfer Between Tissue Processing Modules," which is incorporated herein by reference. A conveyor 12512, such as a belt conveyor system, may be provided on the processing platform 1201 of the staining module 120 at the inlet 1251 and in part of the shelf section 112. The conveyor 12512 may include two or more pulleys, along with a closed loop of a belt rotating around the pulleys. The pulleys are positioned below the shelf 112 / processing platform 1201 such that the upper or exposed side of the belt is in the same plane as the shelf 112 / processing platform 1201. The conveyor belt may have a width approximately the same as the inlet 1251, on which one or more reagent cartridges are placed, and an outer (upper) surface that is plane similar to the plane of the processing platform 1201. One or both pulleys may be connected to a motor to rotate the pulley forward (towards the staining module 120) or backward (from the staining module 120). The motor may be connected to a processor 136. The executable instructions of the processor 136 may include instructions to move the belt of the conveyor system 12512 forward or backward. A sensor associated with the belt or on one side of the inlet 1251 (e.g., a photoeye sensor) may detect the presence of a basket and communicate with the processor 136. If one or more reagent cartridges (e.g., basket 210C, basket 210D, basket 210E) are present at the inlet 1251, executable instructions from the processor 136 may cause the belt to rotate by one or both of the pulleys of the conveyor 12512 to transport one or more reagent cartridges to the staining module 120.The processor 136 may instruct the robotic mechanism 1260 to grasp the introduced reagent cartridge with the end effector 12602 and place the reagent cartridge in a position where it can be transported to the storage cabinet 1250, or to the print station 1270 before proceeding to the storage cabinet 1250. If the processor 136 instructs the robotic mechanism 1260 to place the introduced reagent cartridge in the storage cabinet 1250, the instruction further provides the address in the carousel 1252 where the reagent cartridge will be placed. In addition to placing the reagent cartridge in the storage cabinet 1250, the robotic mechanism 1260 may also be used to transfer the reagent cartridge from the print station 1270 or storage cabinet 1250 to the conveyor 12512 for removal from the staining module 120 of the processing assembly 100, for example, when the reagent cartridge has reached its expiration date, is no longer usable (e.g., the reagent cartridge is empty), or is no longer needed. The processor 136 can then instruct the conveyor 12512 to rotate the pulley and move the belt backward towards the entrance 1251.

[0069] The reagent cartridge is delivered to the print module 120 of the processing assembly 100 with the cap covering the print head. The reagent cartridge is also stored in the cabinet 1250 with the cap in the position that covers the print head. As described above with reference to Figures 14B and 14D, the reagent cartridges (e.g., reagent cartridge 1279A and reagent cartridge 1281A) include magnets fastened to the bottom of each cartridge. Magnet 12799 of reagent cartridge 1279A and magnet 12809 of reagent cartridge 1281A can be used to secure the cap to the bottom of each reagent cartridge. Reagent cartridge 1280A has a bottom similar to reagent cartridge 1279A. Figures 19 and 20 show an upper side perspective view and a side view of the caps that can be used with the reagent cartridges (e.g., reagent cartridge 1279A, reagent cartridge 1280A, reagent cartridge 1281A). The cap 1310 includes a plastic housing 13102 that defines a substantially linear bottom with two flat sections that separate a central section. Distributed in the flat sections and the central section is a plate 13104 made of a magnetic material such as iron (e.g., steel). The magnetic material of the plate 13104 is attracted to the magnet at the bottom of each reagent cartridge, securing the cap to the reagent cartridge. It is recognized that the magnet at the bottom of each reagent cartridge and the magnetic material of the cap 1310 may be reversed (for example, the magnet may be on the cap 1310, and the magnetic material attracted to the magnet may be at the bottom of each reagent cartridge). Distributed in the central section of the cap 1310 is a container 13105 made of an elastomer material such as silicone rubber. The container has length and width dimensions to accommodate the printhead of reagent cartridge 1279A, reagent cartridge 1280A, or reagent cartridge 1281A. Finally, Figures 19 and 20 show a cap 1310 having two diagonally arranged alignment pins 13106 that can be used to align the cap 1310 to the reagent cartridge through alignment holes or divots at the bottom of the printhead.

[0070] The cap covering the printhead of the reagent cartridge must be removed at the print station 1270 before the reagent cartridge is loaded into the printer (e.g., printer 1276A). Figure 2 shows a cap removal and storage station 1295 adjacent to the print station 1270 and storage cabinet 1250. Figure 21 shows a top view of one example representation of the cap removal and storage station 1295. In this example, the cap removal and storage station 1295 includes an area 12952, which is a grid framework defining several cells, each cell having an area large enough to store reagent cartridge caps inside. Each cell may have an address, typically represented by a row of numbers and a column of letters. The address allows the location of the reagent cartridge cap to be stored, for example, in memory 137 and accessed by the processor 136, so that the stored cap can be returned to the same reagent cartridge when desired. The reagent cartridge contains a solenoid (see solenoid 12953 in cell A1) that is operable for electrical action to overcome, eliminate, or reverse the magnetic attraction of the cap's metal to the magnet at the bottom of the reagent cartridge. Figure 22 shows a side perspective view of cell A1 in area 12952 of the cap opening station 1295, and together with Figures 23 and 24, illustrates the operation of removing the cap from the reagent cartridge. In Figure 22, solenoid 12953 in cell A1 may be turned off (operated to turn off by processor 136), and no cap is stored in the cell. Figure 22 shows a reagent cartridge 1281A having a cap 12802 at the bottom that covers, for example, a print head. The reagent cartridge 1281A may be positioned above cell A1 by a robotic mechanism 1260. For the reagent cartridge 1281A to be used in a print operation, the cap 12802 must be removed. As described above with reference to Figures 14B and 14D, the reagent cartridges (e.g., reagent cartridge 1279A, reagent cartridge 1280A, reagent cartridge 1281A) include a magnet fastened to the bottom of each cartridge, which secures the cap to the reagent cartridge by magnetic attraction.Figure 23 shows the robotic mechanism 1260 placed on the reagent cartridge 1281A or cap opening station 1295 in cell A1. Once the reagent cartridge, including the cap, is placed in the cell, a command from processor 136 may activate solenoid 12953 to eliminate, overcome, or disable the magnetic attraction between the magnet 12809 at the bottom of the reagent cartridge 1281A and its cap. One example is a command from processor 136 to pass an alternating current through solenoid 12953 to eliminate, overcome, or disable the magnetic attraction between the magnet 12809 at the bottom of the reagent cartridge 1281A and its cap. Following the elimination or overcoming of the magnetic attraction between the reagent cartridge and the cap, Figure 24 shows the robotic mechanism 1260 separating the reagent cartridge 1281A from the cap 12802. The reagent cartridge 1281A can then be transported to the print station 1270 or service station 1290 (see Figure 2). The cap 12802 remains in cell A1 of the cap removal and storage station 1295 until the reagent cartridge is returned to the storage cabinet 1250 or discarded (discharged from the staining module 120 of the processing assembly 100), at which point the same cap is reattached to the reagent cartridge 1281A by reversing the steps described with reference to Figures 22-24.

[0071] Before a reagent cartridge is delivered to the print station 1270 or returned from the print station 1270 to the storage cabinet 1250, the reagent cartridge may proceed to the service station. Figure 2 shows the service station 1290 adjacent to the cabinet 1250. The service station 1290 is the area where the print head of the reagent cartridge is inspected and cleaned prior to and / or after use in the print station 1270. Figure 25 shows a front view of the service station 1290. In this example, the service station 1290 includes a rear wall 12901. Connected to the rear wall 12901 are pulley supports 12903 and 12904. Each of the pulley supports 12903 and 12904 includes an upper roller and a lower roller. A belt 12905 is disposed on the upper roller of each of the pulley supports 12903 and 12904. A belt 12906 is disposed on the lower rollers of each of the pulley support 12903 and pulley support 12904. A rail 12902 is disposed between each of the pulley support 12903 and pulley support 12904 and connected to them. Carriages 12907 and 12908 are slidably connected to rail 12902 and belts 12905 and 12906. Carriages 12907 and 12908 may have a configuration for securing reagent containers similar to the pockets of the printer 1276 (see Figure 15). Carriage 12907 has a length L1 and a width W1 (for example, L1 is 100 mm and W1 is 60 mm) for a first-size reagent cartridge such as reagent cartridge 1280A, and carriage 12908 has a length L1 and a width W1 (for example, L2 is 72 mm and W2 is 60 mm) for a second-size reagent cartridge such as reagent cartridge 1280A. Since small cartridges such as reagent cartridge 1280A are placed on carriage 12908 together with a spacer on the reagent cartridge (for example, spacer 12807) that extends across the width of the reagent cartridge, it should be noted in this example that carriage 12907 and carriage 12908 have similar width dimensions.

[0072] The bottom or back of each carriage 12907 and carriage 12908 in the figures include electronic contacts or pins that can be operated to engage with the receiving portion on the back of the reagent cartridge. Figure 25 shows the contacts or pins 12914 of carriage 12907 and the contacts or pins 12915 of carriage 12908. The bottom of each pocket also includes four magnets 12916 spaced apart around their respective contacts or pins, each having a diameter of, for example, about 2 to 3 mm, and two alignment pins 12917 positioned diagonally at the bottom of each carriage.

[0073] In one example, reagent cartridge 1279A has length and width dimensions that fit just within carriage 12907. As described above with respect to Figure 14A, the rear or back of reagent cartridge 1279A includes an electronic pin receiving portion 12794 that engages with an electronic contact or pin 12764 of carriage 12907. The rear or back of reagent cartridge 1279A also includes four strips, plates, or sheets 12796 that are attracted to a magnet (e.g., magnet 12916) within carriage 12907. Magnet 12916 may act to attract the reagent cartridge (e.g., reagent cartridge 1279A) to the correct position within carriage 12907 by attracting the strips, plates, or sheets 12796 of reagent cartridge 1279A. The rear or underside of reagent cartridge 1279A also includes two diagonally spaced matching sockets or openings 12796 that align with the matching pins 12917 of carriage 12907 to assist in the alignment of reagent cartridge 1279A to carriage 12907. Reagent cartridge 1280A mates with carriage 12907, including an underside configuration similar to that of reagent cartridge 1279A.

[0074] As described above with respect to Figure 14C, reagent cartridge 1281A may have a smaller width dimension (e.g., 38.8 mm wide compared to the 58 mm wide reagent cartridge 1279A). The rear or back of reagent cartridge 1281A includes an electronic pin receiving section 12804 that engages with the electronic contacts or pins 12915 of carriage 12908, but the rear or back area of ​​reagent cartridge 1281A is not large enough to accommodate a magnetic strip, plate, or sheet, or a matching socket, in order to attract and align the reagent cartridge to carriage 12908. To utilize the aspiration and matching features of carriage 12908, an optional spacer 12807 is fitted to reagent cartridge 1281A, exposing the rear or back surface of reagent cartridge 1281A upon fitting. The spacer 12807 adds additional width to both sides (left and right) of the rear or back of the reagent cartridge, and the additional width is provided by two-part bodies (two-part body 128072 and two-part body 128073), each having a rear surface on a plane similar to the rear or back of reagent cartridge 1281A. Each two-part body of reagent spacer 12807 (two-part body 128072 and two-part body 128073) includes two strips, plates, or sheets 12805 and matching sockets 12806 that match / engage with the magnet 12765 and matching pin 12766 of carriage 12908, respectively.

[0075] Figure 25 shows carriages 12907 and 12908, respectively, connected to pulley supports 12903 and 12904 via belts 12905 and 12906. Belts 12905 and 12906 allow carriages 12907 and 12908 to move independently laterally or parallel on rail 12902. Such movement allows each carriage 12907 to transport the reagent container mounted on it to spitoon 12909 and then to a wiping station (wiping station 12912 or wiping station 12913). Each carriage can be electrically connected to and communicate with processor 136. Carriages 12907 and 12908 house electronic equipment that operates a reagent cartridge similar to printer 1276 to dispense reagents. When the reagent cartridge is connected to carriage 12907 or carriage 12908, instructions from processor 136 can be given to instruct the ejection of reagent from the reagent cartridge to, for example, spittoon 12909.

[0076] Figures 26, 27, and 28 illustrate the operations performed at service station 1290. In the operation, instructions from processor 136 may instruct the movement of either carriage 12907 or carriage 12908 by belts 12905 and 12906 above spitoon 12909. Figure 26 shows carriage 12907 being transported to the area above spitoon 12909. At this time or around this time, instructions from processor 136 may also instruct robotic mechanism 1260 to remove caps from reagent containers at cap removal and storage station 1295, and once the caps are removed, to place reagent cartridges on the moved carriage (e.g., carriage 12907). Figure 27 shows reagent cartridge 1279A placed on carriage 12907 above spitoon 12909. The instructions from processor 136 may include commands to the electronics of carriage 12907 to eject or discharge a certain amount of reagent (for example, enough to wet the printhead and ensure it does not become clogged) into the reagent cartridge onto spitoon 12909. Following the ejection operation, the instructions from processor 136 may include commands to transport reagent container 1279A to a wiping station where residual reagent on the printhead of reagent container 1279A can be cleaned by a wiping operation. Figure 28 shows the reagent cartridge 1279A on carriage 12907 above wiping station 12912. Wiping station 12912 houses a ribbon of cloth, tape, or absorbent material exposed on its upper surface. The width of the ribbon may be at least the width of the printhead of the reagent cartridge. Figure 29 shows a front view of wiping station 12912 with the front cover removed. Wiping station includes a feed roller 129122 containing a ribbon 129124 wound on a roller. The ribbon 129124 is fed from the feed roller 129122 through a series of tension rollers 129126 and 129127 to the contact roller 129125, and then to the winding roller 129123. The contact roller 129125 is located above the wiping station 12912 and is positioned so that the ribbon on the contact roller can come into contact with the print head of the reagent cartridge 1279A.In one example, upon contact, the ribbon 129124 does not move, but the printhead of the reagent cartridge 1279A moves on the ribbon 129124 (for example, from left to right) during the wiping operation. Following contact, the reagent cartridge 1279A moves from the wiping station to the spittoon 12909, as shown in Figure 27. The ribbon 129124 then advances from the feed roller 129122 to the take-up roller 129123, becoming a cleaning area for the ribbon to wipe another printhead. In another example, the printhead of the reagent cartridge 1279A is in contact with the ribbon 129124 and is momentarily stationary. The ribbon 129124 then advances from the feed roller 129122 to the take-up roller 129123. After the advance, the reagent cartridge 1279A moves from the wiping station to the spittoon 12909. The ribbon 129124 moves forward in the first example, or further forward if necessary in the second example, to create a cleaning area for another printhead. Following wiping, the reagent cartridge 1279A is removed from the service station 1290 and delivered to the print station 1270, for example by the robotic mechanism 1255, or returned from the print station 1270 to the storage cabinet 1250, for example by the robotic mechanism 1260. When the reagent cartridge 1279A is returned to the storage cabinet 1250, it is first transported to the cap removal and storage station 1295, where it is reattached with the cap prior to being loaded into the storage cabinet 1250.

[0077] The robotic mechanism 1255 may include a robotic arm including an end effector 12552 and a robotic controller 12551 that can control robotic movements (e.g., movement of the robotic mechanism 1255 and the required end effector 12552, and processing tasks performed by the robotic mechanism 1255). The robotic controller 12551 is linked to the processor 136 either wired or wirelessly. Machine-readable program instructions are sent between the processor 136 and the robotic controller 12551 (e.g., from the processor 136 to instruct the robotic controller 12551) to implement a desired protocol. After acknowledging the instructions and / or completing the operations instructed by the processor 136, the robotic controller 12551 may send one or more signals to the processor 136. One protocol may involve retrieving a reagent cartridge from service station 1290 or cap removal / storage station 1295 and placing the reagent cartridge in a specific opening slot on the printer on the ink cartridge rail at print station 1270 (see Figure 11, which shows printer 1276A connected to and extending forward from ink cartridge rail 1275A). The robot controller 12551 is provided with the location of the reagent cartridge, such as service station 1290 (spittoon 12909), or the address of the reagent cartridge at cap removal / storage station 1295 (e.g., cell row and column information), and instructs the end effector 12552 to proceed to the location where the reagent cartridge will be retrieved. The robot controller 12551 then receives another address for print station 1270 where the retrieved reagent cartridge will be placed, and subsequently guides the end effector 12552 to this address to place the retrieved reagent cartridge in the desired printer at print station 1270. Prior to the placement of the acquired reagent cartridge into the printer at print station 1270, the protocol may instruct the reagent cartridge identifier to be read to confirm that it is the desired reagent cartridge for a particular printer. Each reagent cartridge may have an identifier (e.g., a barcode) on its surface (see Figures 14B and 14D).The processing assembly may include a reader 1299 (e.g., a barcode reader or scanner) located near the print station 1270 or near the service station 1290 or the cap removal and storage station 1295. The reader 1299 provides reading information to the processor 136, which may include protocol instructions to verify that the acquired reagent cartridge is the desired reagent cartridge. The acquired reagent cartridge may then be placed on a printer (e.g., printer 1276A in Figure 11). The position of the reagent cartridge on the printer of the print station 1270 may be stored in a log in memory 137. Such a log may be used to verify whether a sample on a slide was printed with a specific reagent from the reagent cartridge. Interface 135 may also include a user-accessible screen displaying the printers of the print station 1270 and the reagent cartridges for each printer.

[0078] Another protocol may involve retrieving a reagent cartridge from the printer and placing the retrieved reagent cartridge in a specific slot in the storage cabinet 1250. Instructions from the processor 136 may instruct the robotic mechanism 1255 to retrieve the reagent cartridge from the print station 1270. The retrieved reagent cartridge is first carried to the reader 1299, which reads an identifier and may provide this information to the processor. The processor 136 may verify that the reagent cartridge was correctly retrieved from the printer at the print station 1270. Instructions may then instruct the robotic mechanism 1255 to carry the retrieved reagent cartridge from the print station 1270 to the service station 1290 for servicing (dispensing and wiping). Following servicing, the protocol may instruct the robotic mechanism 1260 to retrieve the reagent cartridge from the service station 1290 and carry it to a location (cell) in the cap removal and storage station 1295 where the reagent cartridge is reattached with the cap, based on stored information in memory 137 that associates the cell containing the cap with the reagent cartridge. Once the cap is placed on the reagent cartridge (through magnetic attraction of the cap to the magnet on the reagent cartridge), the processor 136 may instruct the robotic mechanism 1260 to place the reagent cartridge in a slot in the carousel 1252 of the reagent storage cabinet 1250 (see Figures 16 and 17). Based on the reagent cartridge identifier, its assigned slot address, and the actual slot address, the processor 136's machine-readable instruction may compare the assigned slot address with the actual address to confirm that the cartridge is in the correct slot. The instruction may include notification (e.g., an alarm) of confirmation of the correct or incorrect slot address at the user interface 135 of the processing assembly 100. The interface may also include a user-accessible screen displaying some or all of the slots in the storage cabinet 1250 and the reagent cartridge in each slot. The position of the reagent cartridge in the slot of the reagent storage cabinet 1250 may be stored in a log in memory 137.Such logs can later be used to verify whether the sample on the slide was printed using the specific reagent in the cartridge.

[0079] Each reagent cartridge may contain a chip that can store information such as the expiration date and the number of prints or operations. The number of prints or operations can be used to estimate the volume of reagent in the reagent cartridge. The number of print operations may change each time a print operation is performed using the reagent cartridge. Referring to Figure 17, adjacent to each slot in the storage cabinet 1250 may be an optical array 12502 (e.g., red, yellow, and green light-emitting diodes) that provides an indication of the volume of reagent in the reagent cartridge based on the number of prints or operations. For example, the chip associated with the reagent cartridge may be electronically connected to the optical array adjacent to the slot in the storage cabinet when the cartridge is fitted into the slot. The reagent cartridge may contain a volume of reagent suitable for, for example, 30 standard print operations (30 injections). The chip may be programmed to activate the green light of the RYG array when the number of print operations performed using the cartridge is zero to 10, yellow when the number of print operations performed is 11 to 20, and red when the number of print operations performed is 21 to 30. For example, when a cartridge is in the storage cabinet 1250 and provided to the processor 136, the chip on the reagent cartridge is read and the count is stored in memory 137. The print count of each reagent cartridge in the storage cabinet 1250 may also be provided by the processor 136 to the screen of interface 135. Alternatively or additionally, array 12502 may be used to warn of approaching reagent expiration dates (e.g., a red light is activated within one month of the expiration date).

[0080] For printing onto a sample on a slide, each slide carrier linear rail of the print station 1270 (e.g., slide carrier linear rail 12725A) is assigned an address based, for example, on a row-to-row and column-to-column matrix, and this address is stored in memory 137. The processor 136 and associated executable instructions include instructions that associate a slide with a slide carrier linear rail by its identifier and store the associated information. The processor 136 may also display the associated slide and slide carrier linear rail on display 135 so that the operator can visually confirm the print operation.

[0081] Slides can be printed one at a time using a printer that moves along a slide cartridge rail (e.g., slide cartridge rail 1275A in Figure 11). The printer (e.g., printer 1276A) may be instructed by a command from processor 136. This command is to move the slide to the humidifier housing and wash the sample on the slide with an aqueous solution (e.g., buffer solution). Following the washing, excess washing solution may be removed within the humidifier housing by gas or air spray. The processing command may then expose the slide from the humidifier housing (e.g., humidifier housing 12729A) and transfer the slide to the print area for, for example, placement of a primary antibody or detection reagent.

[0082] As described above, an image of the sample on the slide was acquired to show the sample's position and / or the target area of ​​the sample on the slide. These images can be analyzed by the processor 136 for the placement of a certain amount of reagent (e.g., primary antibody or detection reagent) onto the sample. The sample's position can be determined from the sample image acquired from the first slide identification station 1120, or from the sample image acquired from the second slide identification station 1121, or from both (e.g., by comparing one image with another). The image is analyzed to determine the sample's position by overlaying a grid and then identifying the sample on the grid by, for example, staining the sample (e.g., a sample stained with eosin in the washing tank 1247) or by a change in refractive index. Such analysis can provide a basis for determining where the printhead of the reagent cartridge (e.g., reagent cartridge 1279A) should print. Once the sample position is established, the sample area to which the reagent will be applied is determined, and the processor 136 and associated commands limit the application (injection) to this sample area. In this way, reagent application (injection) is limited to the area where the sample is present, rather than to a much wider area that would result in wasted reagent.

[0083] Drop-on-demand printheads used with reagent cartridges (e.g., reagent cartridge 1279A) can dispense reagents such as detection reagents or antibodies in droplets having volumes ranging from 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. Smaller volumes allow for targeted dispensing of reagents to identification areas of a sample on a slide (pre-identified by imaging or other techniques). For example, sample areas such as tissue sections that may contain specific antigens in cells can be identified. Such antigens can be selectively identified by introducing antibodies into the target area using drop-on-demand technology that binds to (e.g., specifically binds to) specific antigens, if present. For example, visualization of antibody-antigen interactions can be achieved by conjugating enzymes that can catalyze color reactions or phosphors that emit fluorescence when visible. The enzyme can be ejected together with the antibody, or later by a print-on-demand printhead. Targeted ejection of reagents such as antibodies or enzymes reduces antibody utilization, reagent carryover contamination, and associated waste compared to prior art that covers the entire sample area on the slide with the reagent.

[0084] In one example, a colorant or stain may be added to the reagent to enable a visual indication that the reagent has been applied as instructed. The colorant or stain may be specific to a particular reagent. For example, a colorant or stain may be added to the primary antibody solution in the reagent cartridge. Following the dispensing of the primary antibody solution onto the sample on the slide, the color of the primary antibody solution is detected and captured and sent to memory 137. Each printer of print station 1270 may house a sensor that can be operated to capture an image of the sample on the slide. Figure 13 shows printer 1276A (for example, located between reagent cartridges 1279A and 1280A) having the associated sensor 12761. The sensor 12761 is positioned to capture an image of the sample on the slide, while the slide is positioned horizontally on the platen of the slide carrier on the slide carrier linear rail. In another example, instead of having sensors such as sensor 12761 associated with each printer, a single sensor may capture an image of each sample on all rows of slides, such as a sensor slidably connected to a horizontal rail (e.g., between the robotic mechanism 1255 and the print station 1272) in front of the opening position where the slide and slide platen are exposed. Since the horizontal rail is slidably connected to the vertical rail, the horizontal rail can move up and down to capture images of the slides of various platens associated with the slide carrier linear rails of the horizontal supports 12724A-12724E. The vertical rail may be mounted on platform 1201. The vertical and horizontal rails are analogous to rails 1145 and 1146 rotated by 90°. Instructions from processor 136 may instruct sensor 12761 to capture an image of the sample on the slide after the reagent has been dispensed onto the sample when the slide carrier 12728A is in an opening position spaced apart from the humidifier housing 12729A (the opening position is shown in Figure 12A). Detection / capture of the reagent actually applied to the sample on the slide (for example, immediately after application) provides quality control that (1) the reagent has been applied and (2) the correct reagent has been applied (due to its inherent color characteristics). Instructions from processor 136 may be executed to evaluate the sample for colorants or stains that are known to be added to the reagent (e.g., primary antibody).If no colorant or stain is detected, the processor 136 sends an alert to the display 135 and interrupts the processing of a single or multiple samples on a slide in a slide carrier associated with a particular printer (e.g., additional printing and / or subsequent processing) to allow for evaluation of potential issues with a particular reagent cartridge or a particular printer.

[0085] Following the printing process at the print station, the printed slide may be returned to the humidifier housing for a culture period (for example, allowing a primary antibody to bind to a target antigen). Following the culture period, the slide is washed once or more with an aqueous solution to remove the washing fluid. Washing may remove any unreacted / unbound reagents, as well as any colorants or stains added to the reagents. Once the sample on the slide accepts additional reagents, executable instructions from the processor 136 instruct the slide to be exposed from the humidifier housing and returned to the lower print position of the printer, and the printing process is repeated. Following each print operation, the slide may be washed as described.

[0086] Once all printing operations on the slide are complete, the robotic mechanism 1255 may remove the slide from the slide cartridge rail (e.g., slide cartridge rail 1275A). Commands from the processor 136 may instruct the robotic mechanism 1255 to grasp / grip the slide with the end effector 12552 and return the slide to the slide identification station 1221 (see, for example, Figure 9). Commands from the processor 136 may instruct the slide identification station 1221 to scan the slide identification information and optionally capture an image of the sample on the slide. For example, in an example where a reagent is colored with a dye, capturing an image after the printing operation allows for analysis and verification of the operation at this point, and the slide accepts the desired reagent. Thus, executable commands from the processor 136 may analyze the sample for the presence of the desired reagent (e.g., based on the coloring of the sample).

[0087] After the slides have been scanned and optionally imaged and analyzed, the slides may be placed longitudinally in slide baskets, such as slide baskets located in an area (e.g., area 1200; see Figure 2) where slide baskets can be acquired by the robotic mechanism 1140. Area 1200 may have two or more slide baskets into which slides can be sorted following the print operation. Slides may be sorted according to the case (e.g., patient) or the type of reagent received during the print operation. For example, a certain reagent may not be suitable for the subsequent dehydration step, as described below, or may be more suitable for glass coverslips than film coverslips. The processor 136 and associated instructions include instructions for sorting slides into specific slide baskets based on sorting preferences (e.g., case, reagents to be placed, etc.).

[0088] Once one or more printed slides from the staining module 120 are loaded into the basket 210A, the basket 210A is transported from the staining module 120 to the core module 110. The processor 136 may track (e.g., count) the number of slides delivered to the staining module 120, removed from the basket, printed, and reloaded into the basket. Once it is confirmed that all slides have been reloaded into the basket, the processor 136 may instruct the robotic mechanism 1140 to transport the slide basket to the dewatering station 1130 of the core module 110. The robotic mechanism 1140 may be instructed, for example, by a robotic controller 1141, which may be a linked processor 136. The end effector 1142 of the robotic mechanism 1140 may grasp the slide basket on both sides and place the slide basket in chamber 1241 or chamber 1243 of the antigen retrieval station 1240 when the lid is opened.

[0089] Figure 30 shows an enlarged upper front view of the core module 110 of the processing assembly 100, with the upper outer portion of the outer housing removed to expose the internal compartment of the module, and the end effector of the robotic mechanism 1140 engaged with the slide basket 210G in the core module. Following the return of the slides from the slide basket 210G to the core module, the printed slides can undergo dewatering in the dewatering station 1130. In this example, the dewatering station houses several recessed tanks below the processing platform 1101. Each tank has an electrically operated lid, whose operation is directed by executable instructions from the processor 136. Each tank may also house a stirrer (e.g., a magnetic stirrer). Figure 30 shows tanks 1133, 1134, and 1136, each operable to store a certain volume of liquid reagent and each having dimensions to accommodate a slide basket (e.g., TISSUE-TEK PRISMA® slide basket). Tanks 1133, 1134, and 1136 may each contain a dehydrating reagent such as alcohol (e.g., 100 percent ethanol) or xylene. Typically, tank 1133 contains ethanol, tank 1134 contains ethanol, and tank 1136 contains xylene. The dehydration process may require sequentially transferring slide baskets, such as slide baskets 210G containing one or more printed slides, to tanks 1133, 1134, and 1136.

[0090] To initiate a dewatering process or protocol at the dewatering station 1130, a machine-readable command executed by the robot controller 1141 instructs the robot mechanism 1140 to transfer the slide basket (slide basket 210G) to the tank 1133. The robot mechanism 1140 includes a robot controller 1141 that can control the robot's movements (e.g., the movement of the robot mechanism 1140 on the track 1145 and the processing tasks performed by the robot mechanism 1140). The robot controller 1141 is linked to the processor 136 either wired or wirelessly. Machine-readable program commands are transmitted between the processor 136 and the robot controller 1141 (e.g., from the processor 136 to instruct the robot controller 1141) to automatically execute the desired protocol. The robot controller 1141 may send one or more signals to the processor 136 after acknowledging the command and / or completing the operation instructed by the processor 136. For the dewatering process, the protocol may involve transferring a slide basket (e.g., slide basket 210G) from tank 1133 to tank 1134, and then to tank 1136. Rails 1145 are positioned at a height sufficient to carry the slide basket 210G to the dewatering station 1130, either by gripping or engaging with the slide basket, for example, by the end effectors (e.g., two spaced-apart arms, forks, or blades) of the robotic mechanism 1140, for example, by gripping both sides of the slide basket. The robotic mechanism raises and lowers the slide rack into or from the dewatering tank to increase agitation and accelerate the dewatering process. The slide basket can then be raised and transferred to subsequent tanks. As an example, the slide basket may be held in tank 1133 of 100 percent ethanol for 30 seconds, in tank 1134 of 100 percent ethanol for 1 minute, and in tank 1136 of xylene for 2 minutes. Following the dewatering protocol, program instructions may instruct the robotic mechanism 1140 to transfer the slide basket to the dripping platform 1139 on the processing platform 1101.From the dispensing platform 1139, program instructions may further instruct the robotic mechanism to transfer the slide basket to the outlet opening 125 of the core module 110.

[0091] Certain reagents, when printed on a slide, may not be compatible with dehydration processes requiring alcohol and / or xylene. Examples may include certain chromogens or fluorescent reagents. For samples treated with reagents that may not be compatible with dehydration processes requiring alcohol and / or xylene, the processor 136 may instruct the robotic mechanism 1140 to transfer the slide basket containing the slides with such treated samples to the storage tank 1135 of the dehydration station 1130. The storage tank 1135 may contain aqueous buffer solution. After any time in the storage tank 1135, the slide basket containing the slides may be transferred by the robotic mechanism 1140 to the dispensing platform 1139.

[0092] Reagents in other tanks stored in the core module 110, along with tanks 1133, 1134, 1136, and 1135, may be connected to the supply and waste tanks below the processing platform 1101 via piping (e.g., conduits and valves). Reagents may be periodically replaced based on processing commands from the processor 136 by draining the reagents into the waste tank and then refilling the drained tank with new reagents. The determination of when a tank's reagent should be replaced may be made, for example, by measuring the density (volumetric weight) of the reagent present in the tank and comparing this density to the density of the same reagent in a new or unused state, or to a predetermined acceptable density that may differ from the density of the reagent in a new or unused state (e.g., the density of the reagent at the time of use, but still acceptable for use in performing the desired function). Each tank in the core module 110 and the staining module 120 may house a liquid density monitor that provides the processor 136 with a measured value of the reagent in that tank. If the density difference between the measured density and the new or predetermined density exceeds a selected value stored in memory 137, the processor 136 may instruct the replacement of the reagent in the tank. Another method for determining when the reagent in the tank should be replaced may be based on the reagent's conductivity. The concentration of salts in the reagent changes with use, which can cause a change in the conductivity of the reagent being measured. Each tank in the core module 110 and the staining module 120 may house a liquid density monitor that provides the processor 136 with a density measurement of the reagent in the tank. If the measured conductivity exceeds a predetermined value stored in memory 137, the processor 136 may instruct the replacement of the reagent in the tank. A further method for determining when the reagent in the tank should be replaced may be based on the reagent's color. Typically, a new or unused reagent may have an absorbance value (initial value) or may be colored with a dye to provide an initial value stored in memory 137. The processor 136 may instruct the reagent in the tank to be periodically screened for its absorbance. When the absorbance value of the reagent deviates by a predetermined percentage, the processor 136 may issue a command to replace the reagent in the tank.Further methods for determining when reagents in a tank should be replaced may involve the use of a hydrometer or a device that floats with the reagent based on buoyancy. The hydrometer or floating device in the tank may be connected to a sensor that is in communication with the processor 136. When the reagent becomes contaminated, its density or other properties change, and the hydrometer or floating device activates a sensor to initiate the replacement of the reagent in the tank or transmits other information to the processor 136. Each of the supply tanks and waste tanks below the processing platform 1101 may house a liquid level sensor that is in communication with the processor 136. The liquid levels in the supply tanks and waste tanks may be displayed on the screen of the display 135 so that the operator can visually check the liquid levels. When a supply tank is empty or nearly empty, the processor 136 may send an alert (e.g., an alert on the display 135 or an alarm) to the operator so that the supply tank may be replaced. Similarly, when the waste tank is full or nearly full, the processor 136 may send an alert (an alert on the display 135, or an alarm) to the operator so that the waste tank may be replaced.

[0093] Before the slide basket containing the processed (stained / printed) slides is ejected from the exit opening 125, glass or film coverslips may be fitted onto the individual slides (e.g., one or more slides) in the slide basket. Depending on the reagents printed on the sample on the slide, some slides are suitable for glass coverslips, while others are suitable for film coverslips. Figure 2 shows the glass coverslip station 1230A and the film coverslip station 1230B in the staining module 120. Typically, samples on slides printed with chromogen or fluorescent reagents may not be compatible with film coverslips. Based on the processing the samples on the slides in the slide basket undergo at the print station 1270, instructions from the processor 136 may instruct the robotic mechanism 1140 to transfer the slide basket to either the glass coverslip station 1230A or the film coverslip station 1230B. Typically, the glass coverslip station 1230A is similar to, or may have similar features to, the Tissue-Tek Film registered trademark automated glass coverslip dispenser commercially available from Sakura Finetek USA, Inc. Typically, the film coverslip station 1230B is similar to, or may have similar features to, the Tissue-Tek Film registered trademark coverslip dispenser commercially available from Sakura Finetek USA, Inc. The Tissue-Tek Film registered trademark Glass™ automated coverslip dispenser and the Tissue-Tek registered trademark Automated Coverslipper each receive a slide basket and process slides individually in an automated process.

[0094] Following dewatering or storage processing at the dewatering station 1130 and optionally coverslip mounting at the coverslip station 1230A or coverslip station 1230B, a command from the processor 136 may instruct the robot controller 1140 to transfer the slide basket to the outlet opening 125 of the core module 110. Within the outlet opening 125, a conveyor 1103, such as a belt conveyor system, may be present in the processing platform 1101 and a portion of the shelf section 112. Conveyor 1103 may be similar to conveyor 1102A or conveyor 1102B associated with the inlet opening 115 and inlet opening 114, respectively. A command from the processor 136 may instruct the robot controller 1140 to place the slide basket onto conveyor 1103, and additional commands may instruct conveyor 1103 to carry the slide basket from the shelf section 112. Alternatively, the operation of the conveyor 1103 can be initiated by a sensor that detects the presence of an object (e.g., a slide basket) on it and moves the conveyor belt accordingly.

[0095] Figure 31 shows a front view of a reagent cartridge 1279A that may be used in the printer of the humidifier rack assembly of Figure 11. In Figure 31, the side of the reagent cartridge 1279A is cut out to reveal the contents of the cartridge. The reagent cartridge 1279A includes a body 22791 made of plastic material. The body 22791 may have an identifier 12792 on its side. The identifier 12792 may provide an expiration date and / or other data, along with identification information of the reagent in the reagent cartridge 1279A. The identifier 12792 may be, for example, a barcode that can be read by a reader of the processing assembly 100. The body 22791 defines a container with volume. Distributed within the volume of the body 22791 is a bag 22792 made of plastic or non-metallic material, into which the reagent can be filled through a spout 22793, and the spout is also made of plastic material. An outlet 22796 (e.g., a plastic or non-metallic spout) at the bottom of the bag 22792 within the volume of the body 22791 is a regulator 22794, also made of plastic or non-metallic material, which can act to regulate the flow of reagent from the bag 22792 to the printhead 12798. Also within the volume of the body 22791 between the regulator 22794 and the printhead 12798 is a filter 22795, also made of plastic or non-metallic material. The reagent cartridge 1279A serves as a contact fluid path for the reagent in the bag 22792, minimizing metal exposure. Possible metal sources may be limited to the nozzles and resistors of the printhead, but there are no metal sources such as metal springs that are typically associated with inkjet cartridges. At least a non-metallic or non-metallic fluid path to the printhead avoids problems related to reagents that can react with metals (e.g., reagents containing hydrogen peroxide).

[0096] The following numbered sections summarize some aspects of the present invention. 1. An exposure station that can be operated to expose the sample on the slide, A print station capable of applying reagents to exposed samples through thermal inkjet processing, A robotic transfer mechanism that moves slides from the exposure station to the print station, A processing unit assembly comprising the following: 2. A processor that includes non-temporary machine-readable instructions that, at runtime, instruct the processor to apply reagent from the reagent cartridge of the print station to a portion of the sample on the slide. The processing unit assembly of Section 1 further comprises the following. 3. An imaging device capable of capturing an image of the sample prior to the application of the reagent to the specified sample. It further comprises, During execution, the processor includes non-temporary, machine-readable instructions that cause the processor to determine the target position on the sample based on the captured image for the application of reagent from the reagent cartridge. Processor assembly in Section 2. 4. A processor assembly according to Section 2 or 3, wherein reagent cartridges are placed in a printer at a print station, and further comprises a storage station operable to store multiple reagent cartridges, wherein, prior to instructions for dispensing reagents from the reagent cartridges, the cartridges are automatically retrieved from the storage station and coupled to the printer by command. 5. Any processor assembly in the preceding clause, wherein the print station comprises a humidifier housing and the processor includes a non-temporary machine-readable instruction that causes the slide to be removed from the humidifier housing and transferred to the printer at runtime. 6. Any processor assembly from the preceding clauses, wherein the exposure station comprises a first exposure station operable to bake and dewax a sample, and a second exposure station operable to use pressure to expose the antigenic site of the sample, and the processor includes non-transient machine-readable instructions to transport the slide to an antigen retrieval station during execution and to a print station after the antigen retrieval process. 7. Any processor assembly from the preceding clauses, further comprising a dehydration station, wherein the processor includes non-temporary machine-readable instructions to transport the slide to the dehydration station at runtime after the reagent has been applied at the print station. 8. A processing assembly from any of the preceding sections, wherein the exposure station comprises a baking station and a dewaxing station. 9. Any processing assembly from the preceding section, further comprising an identification station having a sensor that identifies label information on a slide or is operable to identify label information on a slide and capture an image of a sample on the slide. 10. A processor assembly as described in Section 9, further comprising a sorting station operable to store multiple slide baskets, wherein the processor includes non-temporary machine-readable instructions that cause the sorting station to sort slides into one of the multiple slide baskets based on the label information of the slides at runtime. 11. The processing unit assembly from Section 10, which classifies slides according to instructions based on the reagents applied to them. 12. Any processor assembly in any of the preceding clauses, wherein, in an exposure station, slides are provided in a slide basket that is operable to store multiple slides, and the processor assembly further comprises a processor including a non-temporary machine-readable instruction that causes the slides to be removed from the basket for a print operation at a print station at runtime. 13. A processor assembly from Sections 3 to 12, in which the reagent cartridge is coupled to the printer via magnetic attraction. 14. Any processing assembly from Sections 4 to 13, wherein the print station comprises multiple slide platens, each of which is operable to house a slide, and a printer is coupled at the print position to a slide carrier linear rail so that a reagent can be applied to a sample on a slide using each of the multiple slide platens. 15. The processor assembly from Section 14, wherein the printer is slidably coupled to a rail, and executable instructions from the processor move the printer individually to a position for applying reagent to a sample on a slide in each of several slide platens. 16. A processor assembly according to Section 14 or 15, wherein each of the multiple slide platens is operable to automatically move between a print position and a position comprising a humidifier housing. 17. A processor assembly from Sections 12 to 16, which houses multiple reagent cartridges and allows the printer to operate to dispense reagents individually from each of the multiple reagent cartridges. 18. Any of the processors described in Sections 12 to 17, further comprising a sensor coupled to a printer, the sensor being operable to capture an image of a sample on a slide when the slide platen is in the print position. 19. Any processing assembly from Sections 2 to 18, further comprising a service station comprising a spitoon and a wiping ribbon, wherein the wiping ribbon is disposed between a supply roller and a take-up roller, and one of the print head of an ink cartridge and the wiping ribbon is operable to move relative to the other to perform a wiping operation on the print head. 20. A body defining a container having volume, A non-metallic bag in a container that can be operated to store reagents, A print head at the bottom of the body, which is connected to the bag's exit, A reagent cartridge equipped with [a certain feature]. 21. The reagent cartridge of Section 20, further comprising a container regulator, wherein the regulator is coupled to the outlet of the bag so as to be positioned between the outlet of the bag and the print head. 22. A reagent cartridge according to Section 20 or 21, wherein the body has a side that is operable to be coupled to a printer, and the side contains material that is coupled to the printer by magnetic attraction. 23. A reagent cartridge according to any of sections 20-22, in which the bottom of the body contains a material that is bonded to the cap by magnetic attraction. 24. A reagent cartridge from Section 23, with a magnet at the bottom of the body. 25. Exposing the sample on the slide in the processing assembly, The robotic transfer of the slides from the processing unit assembly to the print station, The reagent is applied to the exposed sample on the print station using thermal inkjet printing, A method of including. 26. The method of Section 25, wherein exposure of the sample on the slides involves placing the basket containing the slides on at least one of the baking station and the dewaxing station. 27. The method of Section 25 or 26, wherein exposure includes exposing the antigenic site of the sample. 28. The method of Section 27, wherein exposure of the antigen site of the sample includes placing the slide in an antigen retrieval solution under high temperature and high pressure. 29. Any method from Sections 25 to 28, wherein the robotic transport of slides includes the robotic transport of a basket containing slides, and the basket has a volume for storing multiple slides. 30. The method of Section 29, which includes removing the slide from the basket prior to applying the reagent to the exposed sample. 31. The method of Section 30, which includes placing the slide in the humidifier housing prior to applying the reagent to the exposed sample. 32. The method of Section 30 or 31, which includes washing the slide with an aqueous solution prior to and / or after applying the reagent to the exposed sample. 33. The method of Section 32, which includes the method of removing at least a portion of the cleaning solution after cleaning the slide with an aqueous solution. 34. Any method from Sections 30 to 34, which includes a method of capturing an image of the sample with the slide in the print position of the print station after the reagent has been applied to the exposed sample. 35. Any method from Sections 25 to 34, further comprising dehydrating the sample after applying the reagent to the exposed sample. 36. Any method from Sections 25 to 35, which includes a method for detecting information from slides prior to the robotic transport of slides to a print station. 37. Information detection, The system captures at least one first image of the sample on the slide prior to its exposure, and captures a second image of the sample on the slide after its exposure. The position of at least a portion of the sample is determined based on the first image or the second image, or a comparison between the first and second images. The method described in Section 36, which includes [the above]. 38. The method of Section 37, wherein the sample is exposed to the staining agent prior to capturing the second image of the sample on the slide. 39. The method of Section 37 or 38, wherein the application of the reagent includes selective application of the reagent to a specific location on a portion of the sample. 40. Any method from Sections 25 to 39, which includes obtaining a reagent cartridge containing the reagent from a storage station and connecting the reagent container to a printer at a print station, prior to applying the reagent to the sample. 41. Any method described in Sections 25 to 40, wherein the application of reagents includes the application of two or more reagents. 42. The application of reagents to exposed samples, Apply the first reagent, After applying the first reagent, wash the sample on the slide, After washing the sample on the slide, apply the second reagent, The method described in Section 41, which includes [the above]. 43. Any method from Sections 25 to 42 for detecting sample information after applying a reagent to an exposed sample. 44. The method of Section 43, wherein the detection of information includes detecting identification information and / or detecting an image of a sample on a slide. 45. Any method from Sections 25 to 44, which includes detecting identification information from a label or label area on a slide prior to the exposure of the sample on the slide, and classifying the sample into one of several slide baskets based on the identification information. 46. ​​One of the methods described in Sections 25 to 45, wherein, prior to the application of reagents to the exposed sample at the print station, the reagent cartridge containing the reagents is robotically transferred from the storage station to the print station. 47. The method of Section 46, wherein the reagent cartridge has a cap that covers the print head, and the method includes removing the cap prior to transferring the reagent cartridge to the print station. 48. The method of Section 47, which involves overcoming magnetic attraction between the cap and the printhead when removing the cap. 49. Prior to and / or after the transfer of reagent cartridges to the print station, the reagent cartridges are robotically transferred to the service station. The service provided to the reagent cartridge at the service station includes activating the reagent ejection from the printhead of the reagent cartridge, and, after activating the ejection, exposing the printhead to the ribbon wiping operation. Any method described in sections 44-48, which includes the above.

[0097] The algorithms, instructions, and representations presented herein for the operation of processor 136 and / or processing assembly 100 are not inherently related to any particular computer or other device. Various general-purpose systems may be used with the programs taught herein, or it may be advantageous to construct relatively specialized devices to implement the methods described herein. In addition, the present invention is not described in terms of any particular programming language. It will be recognized that a variety of programming languages ​​may be used to implement the teachings of the invention described herein.

[0098] Computer-readable media include any mechanism for storing information in a form that can be read by a computer. For example, computer-readable media include read-only memory ("ROM"), random-access memory ("RAM"), magnetic disk storage media, optical storage media, flash memory devices, or other types of machine-accessible storage media.

[0099] Any reference throughout this specification to “one embodiment,” “an embodiment,” or “one or more embodiments” should be understood to mean, for example, that certain features may be included in the practice of the invention. Similarly, it should be understood that, in the description, various features may sometimes be summarized in a single embodiment, figure, or description, for the purpose of simplifying the disclosure and aiding in the understanding of various embodiments of the invention. However, this method of disclosure should not be interpreted as reflecting an intention that the invention requires more features than those expressed in each claim. Rather, as reflected in the following claims, embodiments of the invention may exist with fewer features than all the features of the disclosed single embodiment combined. Thus, it is clear that the claims following the “Detailed Description” are incorporated into that “Detailed Description,” and each claim stands independently as a separate embodiment of the invention.

[0100] The above specification describes the invention in terms of specific embodiments. However, it will be apparent that various modifications and changes can be made without departing from the broad spirit and scope of the invention presented in the appended claims. For example, the reagent cartridges disclosed herein (e.g., reagent cartridge 408) may contain a solvent or water instead of a reagent and be used for purposes other than staining a sample on the slide below, for example. Therefore, the specification and drawings are to be considered illustrative and not limiting. [Explanation of Symbols]

[0101] 100 Processing Assembly 105 Sorting Station 110 Core Modules 115 Inlet opening 120 staining modules 125 Lead-out opening 135 Interfaces 136 processors 137 memory 210A, B, C, D, E Slide Basket 300 equipment 301 Bracket Screen 303 304 Support 306 Daibu 310 Tray 320 belt 324 trucks 325A,B Roller 1101 Processing Platform 1102 Conveyor System 1102A,B Conveyor 1103 Conveyor 1110 Baking and Dewaxing Station 1120, 1121 Slide Identification Station 1130 Dehydration Station 1133, 1134, 1136 tanks 1135 Storage Tank 1139 Droplet Platform 1140 Robot Mechanism 1141 Robot Controller 1145, 1146 rails 1201 Processing Platform 1230A Glass Cover Slip Installation Station 1230B Film Cover Slip Installation Station 1240 Antigen Retrieval Station 1250 Reagent Storage Cabinet 12502 Optical Array 1252 Carousel 12521 Inner Carousel 12522 Outer Carousel 12523 Opening 1255 Robot Mechanism 12551 Controller or Processor 12552 End Effector 1270 Print Station 1272 Humidifier Rack Assembly 12725A,B,C,D,E Slide Carrier Linear Rail 12727A Bracket 12728A Slide Platen 12729A Humidifier Housing 1275A, B, C, D, E Ink Cartridge Rail 1276A Printer 12761 Sensor 12764 Electronic contact or pin 12765 Magnet 12766 Matching pins 1279A Reagent Cartridge 12791 Divot 12792 Identifier 12798 Printhead 12799 Magnet 1280A Reagent Cartridge 12807 Spacer 1281A Reagent Cartridge 1290 Service Station 12902 Rail 12903, 12904 Pulley support 12905, 12906 belt 12907, 12908 Carriage 12912 Wiping Station 129122 Feeding roller 129123 Winding roller 129124 Ribbon 129125 Contact Roller 129126, 129127 Tension Roller 12916 Magnet 12917 Matching pin 1295 Cap Opening Station Area 12952 12953 Solenoid 1310 Cap 13102 Plastic Housing 13104 Plate 13105 Container 13106 Matching pin 22791 Body 22792 Bag 22793 Spout 22794 Regulator 22795 filter

Claims

1. A step of exposing the sample on the slide within the processing unit assembly, A step of robotically transferring the slide to the print station of the processing unit assembly, A method comprising the step of applying a reagent to an exposed sample by a thermal inkjet printing process at the print station.

2. The method according to claim 1, wherein the step of exposing the sample on the slide includes the step of placing a basket containing the slide in at least one of a baking station and a dewaxing station.

3. The method according to claim 1 or claim 2, wherein the step of exposing the sample includes the step of exposing the antigenic portion of the sample.

4. The method according to claim 3, wherein the step of exposing the antigenic site of the sample includes the step of placing the slide in an antigen retrieval solution under high temperature and high pressure.

5. The method according to claim 1, wherein the step of robotically transporting the slides includes the step of robotically transporting a basket containing the slides, and the basket has a volume capable of accommodating a plurality of slides.

6. The method according to claim 5, further comprising removing the slide from the basket before applying the reagent to the exposed sample.

7. The method according to claim 3, further comprising placing the slide inside the humidifier housing before applying the reagent to the exposed sample.

8. The method according to claim 6 or 7, comprising washing the slide with an aqueous solution before and / or after applying the reagent to the exposed sample.

9. The method according to claim 8, comprising washing the slide with an aqueous solution and then removing at least a portion of the washing aqueous solution.

10. The method according to claim 1, comprising applying a reagent to an exposed sample and then acquiring an image of the sample while the slide is in the print position within the print station.

11. The method according to claim 1, further comprising applying a reagent to an exposed sample and then dehydrating the sample.

12. The method according to claim 1, further comprising detecting information from the slide before applying the reagent to the exposed sample at the print station.

13. Detecting the aforementioned information means At least one of the following: obtaining a first image of the specimen on the slide before exposing the sample on the slide, and obtaining a second image of the specimen on the slide after exposing the sample on the slide, The method according to claim 12, comprising determining the position of at least a portion of the sample based on the first image or the second image, or a comparison between the first image and the second image.

14. The method according to claim 13, wherein the sample is exposed to a staining agent before acquiring the second image of the sample on the slide.

15. The method according to claim 13, wherein the application of the reagent includes selectively applying the reagent to a portion of the sample.

16. The method according to claim 1, further comprising the steps of removing a reagent cartridge containing a reagent from a storage station and connecting the reagent cartridge to a printer in the print station before applying the reagent to the sample.

17. The method according to claim 1, wherein the step of applying a reagent includes the step of applying a plurality of reagents.

18. The process of applying reagents to the exposed sample is The process involves applying the first reagent, After applying the first reagent, the step of washing the sample on the slide, The method according to claim 17, further comprising the step of washing the sample on the slide and then applying a second reagent.

19. The method according to claim 1, comprising applying a reagent to an exposed sample and then detecting information about the sample.

20. Detecting information from the aforementioned sample is The method according to claim 19, comprising the steps of detecting identification information and / or detecting an image of the sample on the slide.

21. The method according to claim 1, comprising detecting identification information from a label or label area on the slide before exposing the sample on the slide, and classifying the sample into one of a plurality of slide baskets based on the identification information.

22. The method according to claim 1, further comprising robotically transferring a reagent cartridge containing a reagent from a storage station to a print station before applying the reagent to an exposed sample at the print station.

23. The method according to claim 22, wherein the reagent cartridge has a cap that covers the print head, and the method includes removing the cap before transferring the reagent cartridge to the print station.

24. The method according to claim 23, wherein removing the cap includes overcoming the magnetic attraction between the cap and the print head.

25. A step of robotically transporting the reagent cartridge to the service station before and / or after transporting it to the print station, The method according to claim 23 or claim 24, comprising the steps of servicing the reagent cartridge at the service station, the steps of discharging the reagent from the print head of the reagent cartridge, and wiping the print head with a ribbon after the reagent has been discharged.

Images