Fluid delivery system

Abstract

The present invention relates to a fluid delivery system for an automated slide processing device, wherein the automated slide processing device is used to process one or more tissue samples set on a slide, wherein the slide processing device includes a plurality of slide processing modules, the plurality of slide processing modules are arranged to receive slides in the slide, and the fluid delivery system includes a fluid dispensing robot, the fluid dispensing robot is configured by a controller to dispense a plurality of reagents to the slides in the slides received in the slide processing modules to separately process the one or more tissue samples.

Description

Technical Field

[0001] The present invention relates to a fluid delivery system for an automated slide processing device, wherein the automated slide processing device is used to process one or more tissue samples set on a slide, wherein the slide processing device includes a plurality of slide processing modules, and the plurality of slide processing modules are arranged to receive slides in the slide.

[0002] The present invention particularly, but not exclusively, relates to a fluid dispensing robot, which is configured by a controller to dispense a plurality of reagents to the slide received in the slide processing module to process the one or more tissue samples. The fluid dispensing robot comprises a fluid dispensing head having one or more probes, the one or more probes having a body, the body having one or more channels, the one or more channels being arranged to receive the reagents in the reagents to be dispensed. The fluid dispensing robot is configured to select one of the probes and / or one of the channels for a selected one of the reagents, and to dispense the selected one of the reagents to the slide received in the slide processing module. Background Art

[0003] In some applications, existing tissue sample processing methods include many steps that are performed manually. For example, in immunological applications, such as in situ hybridization (ISH) and immunohistochemistry (IHC), some steps (including baking the sample onto a slide, dewaxing, and epitope retrieval) are manually performed by an operator to process the tissue sample before the tissue sample can be used in a staining device to stain the tissue sample according to a predetermined staining protocol.

[0004] Immunohistochemical staining and in situ nucleic acid analysis are means for histological diagnosis and tissue morphological studies. Immunohistochemical staining relies on the specific binding affinity of antibodies to epitopes in tissue samples, as well as the increasing availability of antibodies that specifically bind to unique epitopes that are only present in certain types of diseased cell tissues. Immunohistochemical staining involves a series of processing steps on tissue samples (usually sections) mounted on glass slides to highlight certain morphological indicators of disease states through selective staining.

[0005] Typical processing steps include: pretreatment of tissue samples to reduce nonspecific binding; antibody treatment and incubation; enzyme-labeled secondary antibody treatment and incubation; substrate reacts with enzyme to produce a fluorophore or chromophore that highlights the area of ​​the tissue sample with the epitope that binds to the antibody; counterstaining, etc. Between each processing step, the tissue sample must be rinsed to remove unreacted residual reagents from the previous step. Most processing steps involve an incubation period that is typically performed at ambient temperatures of about 25°C to up to about 40°C, while cell conditioning steps are typically performed at slightly higher temperatures (e.g., 90°C to 100°C). In situ DNA analysis relies on the specific binding affinity of the probe (DNA binding protein) to a unique nucleotide sequence in a cell or tissue sample, and similarly involves a series of process steps performed under a variety of reagents and process temperature requirements. Some specific reactions involve temperatures as high as 120°C to 130°C.

[0006] With reference to the above examples, tissue samples are stored in formalin and presented on microscope slides with a paraffin layer protecting the sample. Therefore, before the processing in the form of dyeing the sample can be performed, the operator is required to perform a processing in the form of dewaxing on the slide by at least heating and / or using a large amount of fluid reagents. For example, dewaxing is usually achieved by the operator manually immersing the slide in a dewaxing solution (e.g., a dewaxing reagent) to prepare the sample for dyeing. In addition, the sample can be further processed by manually immersing the slide in another reagent (such as alcohol) to dehydrate the sample before dyeing. In any case, the dewaxed sample on the slide is usually loaded into a dyeing device by the operator for dyeing, and then retrieved by the operator after the dyeing process is completed for observation by, for example, a pathologist.

[0007] Attempts have been made to automatically process tissue samples disposed on slides for immunological applications using, for example, automated tissue sample staining equipment. In existing examples, automated staining equipment processes tissue samples using reagents for processing samples before staining the samples on the slide. The processing of the sample is automatically performed by one or more robots, which are configured to distribute a variety of specified reagents to the slide in a predetermined order according to a staining scheme. In addition, the robot can be configured to distribute reagents (such as dewaxing solutions and alcohol) to process the samples on the slide before and after staining. However, the reagent currently distributed by one of the robots must be cleared from the robot before other reagents can be distributed, resulting in delays, waste of reagents, and inefficient use of the automated staining equipment. Summary of the invention

[0008] According to one aspect of the present invention, there is provided a fluid delivery system for an automated slide processing device, the automated slide processing device being used to process one or more tissue samples disposed on a slide, the device comprising a plurality of slide processing modules arranged to receive slides in the slide, the fluid delivery system comprising:

[0009] a fluid dispensing robot configured by a controller to dispense a plurality of reagents to the slides received in the slide processing module to process the one or more tissue samples, respectively, wherein:

[0010] The fluid dispensing robot comprises:

[0011] a fluid dispensing head having one or more probes extending therefrom, each of the probes having a body having one or more channels arranged to receive one of the reagents to be dispensed, wherein each of the reagents to be dispensed is pumped from a plurality of corresponding reagent containers by a pumping device configured by the controller, wherein:

[0012] The fluid dispensing robot is configured to select one of the probes and / or one of the channels for a selected one of the reagents and dispense the selected one of the reagents to the slide among the slides received in the slide processing module.

[0013] In a preferred embodiment, the fluid dispensing robot is configured by the controller to dispense a plurality of reagents including high value reagents and bulk fluid reagents to the slides received in the slide processing module. The reagents include bulk fluid reagents such as oxalic acid, sulfuric acid, potassium permanganate, alcohol, dewaxing agent, hematoxylin, peroxide, citric acid, EDTA, bluing agent, deionized water and BOND TM Washing solutions; and high-value reagents such as chromogens, ISH probes, fluorophores, IHC probes, antibodies, PCR reagents.

[0014] Preferably, the fluid delivery system includes one or more washing robots configured by the controller to dispense bulk washing reagents, such as deionized water and BOND TM Detergent.

[0015] Ideally, the fluid dispensing robot can be configured by the controller to use a drive device to move the fluid dispensing head having the one or more probes in the x-axis, y-axis and z-axis to position the selected probe relative to one of the slide processing modules in an appropriate position to dispense the selected one of the reagents. Here, the drive device includes: an x-axis drive, which is configured by the controller to move the fluid dispensing head in the x-axis; a y-axis drive, which is configured by the controller to move the fluid dispensing head in the y-axis; and a z-axis drive, which is configured by the controller to move the fluid dispensing head in the z-axis. In addition, the fluid dispensing robot can be configured by the controller to use the drive device to rotate the fluid dispensing head in the θ axis. Here, the drive device includes a θ axis drive, which is configured by the controller to move the fluid dispensing head in the θ axis. For example, the drive is an actuator such as a solenoid or pneumatic actuator, a motor, a stepper, etc. Alternatively, the fluid dispensing robot may be part of a single dispensing robot for XY movement and positioning.

[0016] In one embodiment, the fluid dispensing head includes a cylinder that allows each of the probes to be spaced substantially around the periphery of the cylinder and arranged to rotate on the θ axis. For example, the fluid dispensing head has ten probes extending therefrom that are spaced circumferentially around the cylinder. The fluid dispensing robot is configured to select one of the probes for a selected one of the reagents, then rotate the cylinder and move on the x-axis, the y-axis, and the z-axis as needed to position the selected probe relative to the slide processing module in a desired position to dispense the selected reagent to the slide located therein.

[0017] In another embodiment, the fluid dispensing head also includes a plurality of z-axis actuators, each of which is configured by the controller to independently move a corresponding one of the probes on the z-axis. In this case, for example, the fluid dispensing robot is also configured to select one of the probes for a selected one of the reagents, and then rotate the cylinder and / or move the fluid dispensing head on the x-axis and the y-axis. Alternatively, a fixed head rotary actuator can be utilized to engage the probe in the Z direction. Then, the actuator moves the selected probe on the z-axis to position the selected probe relative to the slide processing module in a desired position to distribute the selected reagent to the slide disposed therein.

[0018] In addition, each of the probes may include a nozzle disposed at the distal end of the probe to distribute the reagent. The nozzle of each of the probes is usually arranged to be connected to the cover member of the one in the slide processing module, and is basically sealed with the inlet port of the cover member when the reagent is being distributed. In addition, the fluid dispensing robot is configured to use the drive device to push the nozzle of the probe toward the inlet port of the one in the slide processing module on the z-axis to maintain the seal with the inlet port when the one in the reagent is being distributed. For example, the above-mentioned z-axis actuator is configured to push the nozzle of the probe toward the inlet port of the slide processing module. The cover member is described in the international publication number WO2014 / 066950 with the earliest priority date of November 1, 2012, which is called "Slide Staining Assembly and Cover Member", and its content is hereby incorporated by reference into this paper.

[0019] In one embodiment, the pumping device comprises a plurality of pumps, each of the pumps being associated with each of the plurality of reagents for pumping the reagents to each of the channels and / or each of the probes through a plurality of corresponding reagent lines.

[0020] In one embodiment, the fluid delivery system further comprises a washing station for washing the one or more probes when the one or more probes are inserted into their washing drums or tanks. The washing station can be positioned at any location, including adjacent to the fluid dispensing robot or integral with the fluid dispensing robot. In one example, the washing fluid is supplied to the washing station by a selected one of the probes.

[0021] According to another aspect of the present invention, there is provided a method for delivering a fluid for processing one or more tissue samples disposed on a slide, wherein slides in the slide are received in a plurality of slide processing modules, and a plurality of reagents are dispensed by at least one fluid dispensing robot to the slides in the slides received in the slide processing modules to respectively process the one or more tissue samples, the method comprising:

[0022] pumping the reagents to be dispensed from a plurality of corresponding reagent containers to one or more probes extending from a fluid dispensing head of the fluid dispensing robot, each of the probes having a body having one or more channels arranged to receive one of the reagents to be dispensed;

[0023] selecting one of the probes and / or one of the channels for a selected one of the reagents; and

[0024] The selected one of the reagents is dispensed to the slide among the slides received in the slide processing module.

[0025] According to another aspect of the present invention, a computer program code is provided, which, when executed by a controller, implements the above method.

[0026] According to another aspect of the present invention, there is provided a tangible computer medium comprising the above computer program code.

[0027] According to yet another aspect of the present invention, a data file including the above program code is provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0029] Figure 1 is a perspective view of an automated slide handling apparatus having a fluid delivery system according to an embodiment of the present invention;

[0030] Figure 2 According to an embodiment of the present invention Figure 1 A perspective view of an automated slide handling apparatus holding a plurality of slide handling modules, one of which is in an open configuration;

[0031] Figure 3 is a perspective view of a fluid dispensing head of a fluid dispensing robot according to an embodiment of the present invention;

[0032] Figure 3a yes Figure 3 A cross-sectional view of a fluid dispensing head;

[0033] Figure 4 is a top view of a slide transport robot and a fluid dispensing robot according to an embodiment of the present invention;

[0034] Figure 5 is a perspective view of a fluid dispensing head of a fluid dispensing robot according to an embodiment of the present invention;

[0035] Figure 5a yes Figure 5 A simplified view of a fluid dispensing head of , showing a probe selector and a probe collar;

[0036] Figure 5b yes Figure 5 and 5a A simplified view of a fluid dispensing head;

[0037] Figure 5c Shown for use Figure 5bThe theta-axis drive for the rotation of the cylinder shown;

[0038] Figure 6 is a perspective view of a probe having multiple channels according to another embodiment of the present invention;

[0039] Figure 7a and Figure 7b is an enlarged view showing a washing robot 15 according to an embodiment of the present invention;

[0040] Figure 8 is a perspective view of a slide handling module;

[0041] Fig. 9 is a perspective view of a fluid dispensing robot according to another embodiment of the present invention;

[0042] Fig.10 is a perspective view of an actuator of a fluid dispensing robot according to an embodiment of the present invention;

[0043] Fig.11 is a perspective view of a plurality of z-axis actuators configured to move a plurality of corresponding probes according to an embodiment of the present invention;

[0044] Fig.12 is a perspective view of a fluid dispensing head also having multiple z-axis actuators according to another embodiment of the present invention;

[0045] Fig.13 is a perspective view of a fluid dispensing head according to another embodiment of the present invention;

[0046] Fig.14 is a perspective view of a probe holder of a fluid dispensing head according to an embodiment of the present invention;

[0047] Fig.15 is a side view of a wafer transport robot according to an embodiment of the present invention;

[0048] Fig.16 is a perspective view of a slide transport robot according to an embodiment of the present invention;

[0049] Fig.17 is a cross-sectional view of a fluid dispensing head of a fluid dispensing robot according to an embodiment of the present invention; and

[0050] Fig.18 is a flow chart of a method of dispensing reagents to process a tissue sample disposed on a slide according to an embodiment of the present invention. DETAILED DESCRIPTION

[0051] Figure 1A fluid delivery system 10 is shown for an automated slide processing apparatus 12 for processing tissue samples disposed on slides 13. The slide processing apparatus 12 includes a plurality of slide processing modules 14 arranged to receive the slides 13, and includes at least one slide transport robot 18 in the form of a truss robot configured by a controller (not shown) to move the slides 13 to and from the slide processing modules 14. The fluid delivery system 10 includes a fluid dispensing robot 16 configured by a controller to dispense a plurality of reagents to the slides 13 received in the slide processing modules 14 to process the tissue samples on the slides 13.

[0052] exist Figure 1 In the illustrated embodiment, the fluid delivery system 10 includes: one fluid dispensing robot 16, which is configured by a controller to dispense reagents to the slides 13 in the slide processing module 14; and two washing robots 15, which are configured by a controller to dispense a plurality of lower value reagents stored in reagent containers to the slides 13 received in the slide processing module 14. As described above, the lower value reagents are typically washing reagents, such as deionized water and BOND TM Detergent.

[0053] It will be appreciated by those skilled in the art that in some cases, in order to process the tissue sample on the slide 13, higher or lower value (e.g., bulk) reagents are dispensed to the slide in a specified combination and order. It will also be appreciated that the apparatus 12 may include two or more fluid dispensing robots 16, such that one robot may be dedicated to (or primarily used for) dispensing high value reagents, while another robot may be used to dispense lower value or bulk fluid reagents. Bulk fluid reagents include, for example, oxalic acid, sulfuric acid, potassium permanganate, alcohol, dewaxing agents, hematoxylin, peroxide, citric acid, EDTA, deionized water, and BOND for processing tissue samples disposed thereon. TM Detergent.

[0054] In the embodiment shown, Figure 1 The two washing robots 15 shown are arranged on the apparatus 12 to distribute washing reagents to the two rows of the slide processing modules 14. In addition, the slide transport robot 18 is configured to move the slides 13 to and from the slide processing modules 14 without interfering with the washing robots 15, because the slide transport robot 18 can move the slides 13 above the washing robots 15 in the z direction. Figure 1As shown, the x-axis is along the length of the device 12, the y-axis is along the width of the device 12, and the z-axis corresponds to the height of the device 12. As described above, however, it should also be understood that other configurations of the washing robot 15 are contemplated, such as the device 12 including a washing robot 15 configured to move relative to the device 12 in the x-axis, y-axis, and z-axis.

[0055] As described, the slide transport robot 18 is configured by a controller to move in the x-axis, y-axis, and z-axis to move the slide 13 into and out of the slide processing module 14 so that the sample set on the slide 13 can be processed with a reagent in the slide processing module 14. The slide transport robot 18 is a truss robot and is combined with a fluid dispensing robot 16. The fluid dispensing robot 16 (hereinafter referred to as the FT robot 16) is configured by a controller to dispense a plurality of reagents stored in reagent containers to the slide 13 in the slide processing module 14. Examples of high-value reagents include chromogens and antibodies, and examples of bulk fluid reagents include oxalic acid, sulfuric acid, potassium permanganate, alcohol, dewaxing agent, hematoxylin, peroxide, citric acid, and EDTA.

[0056] Figure 1 The washing robot 15 is shown configured to move along the track 22 in the x-axis to position the slide 13 in the slide processing module 14 where the washing reagent will be dispensed. Once positioned, the washing robot 15 moves in the z and θ directions to dispense the washing reagent (such as deionized water and BOND TM Washing solution) is dispensed onto slide 13. Figure 7a and Figure 7b 2 is an enlarged view showing a washing robot 15 that can move along a track 22 to position a designated slide processing module 14 for washing. Once properly positioned along the x-axis, the washing robot 15 moves a washing probe in the z-axis (and, if necessary, about the θ-axis) to couple with an inlet port 32 in a cover member 24 covering the slide 13 to wash the slide 13 with, for example, deionized water or BOND. TM Wash the samples with washing solution.

[0057] Figure 3 , Figure 3a , Figure 4 , Figure 5 , Figure 5a , Figure 5b and Figure 5c In more detail Figure 1 The FT robot 16 of the embodiment of the present invention, wherein the FT robot 16 has a fluid dispensing head 17. In addition, Fig.17 Another embodiment of the FT robot 16 is shown in more detail in FIG.

[0058] Figure 2An embodiment of a fluid delivery system 10 having a carrier transport robot 18 is shown, which is configured to move along an x-axis track 29 and a y-axis track 31 to move a carrier 13 to a designated carrier processing module 14. In some embodiments, a processing module actuator is disposed on the dispensing head 17 of the FT robot 16 and is operable to move the carrier processing module 14 between an open and closed configuration (or, if the carrier processing device 14 is biased to a closed configuration, only from a closed configuration to an open configuration). The processing module actuator may be permanently positioned relative to the dispensing head 17 or may be retracted relative to the dispensing head 17 under the control of a controller. In one embodiment, the processing module actuator is a u-shaped member or hook 52 that is operable to engage an opening mechanism on the carrier processing module 14, thereby causing it to pivot to an open configuration (as shown at 14a). Once the carrier processing module 14 is in the open configuration, the carrier transport robot 18 is able to pick up or place a carrier 13 within the carrier processing module 14. In another embodiment, the processing module actuator is a finger member operable to engage an opening mechanism on the slide processing module 14. The finger member may also open and close the slide processing module 14 in an uncontrolled state (i.e., without the fluid dispensing robot 16 knowing where the opening mechanism is) because the finger member may just move toward the opening mechanism and open or close the slide processing module 14 without knowing the position of the slide processing module 14 on the x-axis.

[0059] Reference now Figure 3 and Figure 3a The fluid dispensing head 17 has a plurality of probes 19 extending therefrom in the z-axis for dispensing reagents. The probes 19 each have an elongated body having a channel 21 (eg, Figure 6 ), the channel 21 is arranged to receive one of the reagents to be dispensed. The probes 19 can be arranged in groups around the cylinder 25, for example, hazardous reagent probes in one group and non-hazardous reagent probes in one group, for ease of washing. In some embodiments, the fluid dispensing head 17 has an additional high-value fluid transfer probe 39 (hereinafter referred to as HV probe 39), which can be operated separately from the probe 19 around the cylinder 25. Ideally, the HV probe 39 is placed close to the front of the fluid dispensing head 17 for ease of maintenance and replacement, and can be self-aligning.

[0060] As discussed above, the fluid dispensing head 17 may include an integrated wafer transport device 20. However, it is desirable to arrange the fluid dispensing head 17 to remain within the width of the carriage along the tracks 29, 31 to minimize dead space within the wafer handling device 12. Reagents are pumped from a plurality of corresponding reagent containers (not shown) by a pumping device (not shown) configured by a controller (not shown). In one example, the device 12 includes a plurality of pumping devices, each of which is associated with each of a plurality of reagents, for pumping reagents from reagent containers to an output nozzle of a probe 19 of the FT robot 16. Figure 3 and Figure 4 In , each probe 19 has a single channel 21 associated with a corresponding reagent. Figure 6 In the embodiment, one probe 19 of the fluid dispensing head 17 has a plurality of channels 21 extending therethrough. Here, each channel 21 is arranged to receive a reagent to be dispensed. In this embodiment, the FTP robot 16 selects one of the channels 21 for a selected one of the reagents to be pumped and dispensed. In this case, only one probe 19 needs to be positioned in an appropriate position relative to the slide processing module 14 to dispense each of the reagents connected to the channel 21 to the slide 13 received therein. However, it should be understood by those skilled in the art that the device 12 may employ multiple probes each having multiple channels for dispensing multiple reagents. Thus, in one embodiment, a single fluid dispensing head 17 having, for example, fifteen probes 19 can dispense twenty or more reagents by merging multiple channels 21 into the total number of probes 19. It should be understood that many probe / channel combinations are contemplated for the fluid dispensing head 17, and all combinations are within the scope of the present invention.

[0061] Referring back to the embodiment in which each probe 19 has a single channel 21 for dispensing reagents, a plurality of pumping devices are configured to pump reagents from respective reagent containers to respective output nozzles of the probe 19. To dispense the reagents, the apparatus 12 includes a plurality of reagent lines 23 associated with each of the reagents, the reagent lines 23 extending from each of the reagent containers through respective pumps to the probe 19. That is, the apparatus 12 typically includes a dedicated pumping device (e.g., a pump) for each reagent and a dedicated reagent line 23 extending from each reagent container through each pump to the FT robot 16. Thus, in an example in which ten reagents are stored in ten different reagent containers and there is one FT robot 16, ten dedicated reagent lines 23 extend from each of the ten containers through ten in-line pumps to the FT robot 16. For example, there are dedicated reagent lines 23 for dewaxing solution, alcohol, ER1, ER2, hematoxylin, peroxide, enzyme cleaning solution, H2SO4 cleaning solution, KMnO4 cleaning solution, and oxalic acid cleaning solution.

[0062] Figure 41 is a top view of a slide transport robot 18 showing reagent lines 23 feeding into a probe 19 in a fluid dispensing head 17 in the FT robot 16. The reagent lines 23 are supplied from reagent containers (not shown) and using the probe. In one embodiment, the reagent lines 23 are made of non-reactive plastic or polymer materials, although they may be ideally coated on the outside to minimize friction and ultimately minimize damage caused by frequent contact with other reagent lines 23 and components in the fluid dispensing head 17. One or more reagent lines 23 may also include a rotary valve to direct the inflow and outflow of fluids.

[0063] In any case, the FT robot 16 is configured by the controller to select one of the probes 19 for the selected one (or more, in the case of a multi-channel probe) of the reagent to be dispensed. The FT robot 16 selects a probe 19 from the plurality of probes 19 and positions the selected probe 19 in an appropriate position relative to the designated slide processing module 14 so that the selected reagent can be dispensed. That is, the FT robot 16 is configured by the controller to move the fluid dispensing head 17 having the probe 19 in the x-axis, y-axis and / or z-axis using suitable drive means (e.g., x-axis, y-axis and z-axis actuators) to position the selected probe 19 in a desired position relative to the slide processing module 14 to dispense the selected reagent. In addition or alternatively, the FT robot 16 is configured by the controller to rotationally move the fluid dispensing head 17 around the θ-axis using a suitable θ-axis drive. In this embodiment, the FT robot 16 selects the probe 19 by rotating the cylinder 25 of the fluid dispensing head 17 so that the probes 19 are substantially spaced apart around the θ-axis around its periphery. For example, the θ-axis drive drives the shaft to rotate the cylinder 25 so that the selected probe 19 is located above the designated slide processing module 14. The FTP robot 16 then lowers the selected probe 19 in the z-direction to engage the designated slide processing module 14. The FT robot 16 is then configured to dispense the selected one of the reagents to the slide 13 received in the designated slide processing module 14.

[0064] refer to Figure 5 and Figure 5aIn the illustrated embodiment, the barrel 25 has seven probes 19 extending therefrom and spaced circumferentially about the barrel 25. The FT robot 16 is configured to select one of the probes 19A for a selected one of the reagents and rotate the barrel 25 so as to position the selected probe 19A to align with a z-axis actuator 26 configured to move in the direction of arrow A (i.e., in the z-axis). After the fluid dispensing head is moved in the x-axis (and in some other embodiments, the y-axis) to force the selected probe 19A to a desired position relative to a designated slide processing module 14 to dispense the selected reagent to a slide located therein, the z-axis actuator 26 (e.g., a lead screw and nut) depresses the selected probe 19A, for example, by engaging a probe selector 49 with a probe collar 47. Ideally, the z-axis actuator 26 and the θ-axis drive 37 operate in a ratio in the range of 1:1 to 10:1, preferably in the range of about 2:1:6:1, and more preferably about 3:1.

[0065] In more detail, each probe 19 includes a nozzle disposed at the distal end of the probe 19 to dispense one or more reagents. The nozzle of each probe 19 is arranged to be in contact with a cover member 24 (at the Figure 8 ) is coupled (with the top cover of the module removed for clarity) and substantially sealingly mates with the inlet port 32 of the cover member 24 when the selected reagent is being dispensed. Figure 5 and Figure 5a In an embodiment of the present invention, the FT robot 16 is configured to use the z-axis actuator 26 to push the nozzle of the selected probe 19A in the z-axis toward the inlet port 32 of the slide processing module 14 while rotating the dispensing reagent to maintain a seal with the inlet port 32. Ideally, a single one of the nozzles of the probes 19, 39 is removable for maintenance or replacement without destroying or moving the other dispensing tips or the probes to which they are attached. Similarly, it is desirable that the core mechanism of the actuator of the fluid dispensing head 17 can be removed without moving the probes 19, 39 or the dispensing tips.

[0066] In some embodiments, at least one probe 19 may be configured to remove material (such as liquid or tissue debris) from the slide 13 in the slide processing module 14. This may involve applying negative pressure (suction or vacuum) to the slide through a channel 21 in the probe. In some embodiments, such a probe may be configured for bidirectional fluid delivery, for example, using a rotary valve in a reagent line 23, so that fluid and / or debris can be removed and the slide processing module 14 can be emptied, and fluid can also be allowed to enter the module 14. This feature can be used to stir the fluid on the slide 13 and can be achieved by applying a series of fluid emptying and dispensing actions to the slide processing module 14 by a controller. In some embodiments, one or more probes 19, 39 may also be configured to remove fluid from a mixing bottle (not shown) and / or extract one or more fluid aliquots from the mixing bottle and deliver them to one or more slide processing modules.

[0067] The cover member 24 is described in International Publication No. WO 2014 / 066950, entitled “Slide Staining Assembly and Cover Member,” having an earliest priority date of November 1, 2012, the contents of which are hereby incorporated herein by reference.

[0068] In addition, the inlet port 32 of the cover member 24 may have a chamfer (not shown), such as a 45-degree or 60-degree chamfer, to guide and seal the nozzle of the probe 19. In addition, in one embodiment, the diameter of the probe 19 of the FT robot 16 is smaller than the diameter of the probe of the washing robot 15 configured to dispense washing reagents. Therefore, the smaller diameter tip of the probe 19 of the FT robot 16 is received deeper into the chamfered inlet port 32.

[0069] For example, while utilizing a force of 4N to 20N to dispense reagent, the z-axis actuator 26 pushes the nozzle of the probe 19 on the z-axis toward the inlet port 32 of the slide processing module 14. In other embodiments, the force may be greater depending on the application. The z-axis actuator 26 uses a stepper motor to push the nozzle toward the inlet port 32 using a force of, for example, 4N on the probe 19 in a constant torque mode. Alternatively, the z-axis actuator 26 may be a pneumatic actuator, wherein the coupling force is regulated by air pressure and is constant throughout the stroke. In addition, for example, spring actuation and solenoid actuation may be used to provide the necessary force to seal the nozzle of the probe 19 with the inlet port 32 of the cover member. In the case of solenoid activation, a latch solenoid may be used to latch the probe 19 in the retracted position. In addition, a servo motor actuation providing improved torque control is also contemplated.

[0070] In addition, after the reagent has been dispensed, the z-axis actuator 26 provides a powered return stroke in the z-axis away from the inlet port 32 of the slide handling module 14 to the selected probe 19. Figure 5 and Figure 5a As can be seen in the figure, when each of the probes 19 completes the reagent dispensing, the probes can be spring loaded and biased to return to the retracted position (i.e., non-selected). Therefore, when the z-axis actuator 26 is powered off, the probes 19 can be held or biased in the retracted position. In addition, the power return minimizes the chance of spring jamming and reduces the maximum spring force required.

[0071] Figure 5b and Figure 5c A simplified version of the fluid dispensing head 17 is shown showing the barrel 25 with the probe 19. Figure 5c , the theta-axis drive 37 rotates the cylinder 25 to position the selected probe 19 over the inlet port 32 of the designated cover device 24. This also positions the probe selector 49 between a pair of probe collars 47 and 48 on the probe 10. Once positioned, the z-axis actuator 26 (e.g., in the form of a driven lead screw) moves the probe downward by engaging the probe selector 49 with the probe collar 47, and moves the probe upward by engaging the probe selector 49 with the probe collar 48.

[0072] It will be appreciated that the probe selector may be provided in any shape or configuration that facilitates engagement of the probe collar. Additional probe collars may be provided, such as a probe collar positioned adjacent an engagement region of the probe selector, to facilitate movement of the probe.

[0073] exist Fig. 9 In the illustrated embodiment, the FT robot 16 is configured to move along a rack 28 in the z-axis to position the selected probe 19 at a designated slide processing module 14 to dispense the selected reagent to the slide 13 received in the designated slide processing module 14. The rack 28 is provided by a pinion 30 (at Fig.10 14. The fluid dispensing head 17 is driven to lower and raise the probes 19 in the z-axis. In this embodiment, the fluid dispensing head 17 has the probes 19 extending therefrom in a spaced manner in the z-axis so that when a selected one of the probes is pushed in the z-axis toward the inlet port 32 of the slide processing module 14, the non-selected probes do not interfere with the selected probes. Here, in order to help provide a gap for each of the spaced probes 19 to avoid interference, the inlet port 32 extends from the cover member 24.

[0074] The automated slide handling apparatus 12 also includes a wash station 35 for washing the probes 19 when the probes 19 are inserted into their wash drums or tanks. In one embodiment, the probes 19 are manually removed and washed in the wash drums of the wash station 35. In another embodiment, the FT robot 16 is a truss robot that moves in the x-axis, y-axis, and z-axis and is configured to insert each or all of the probes 19 into the wash drums.

[0075] Figures 11 to 13 An embodiment of a fluid dispensing head 17 is shown having probes 19 extending therefrom and a plurality of z-axis actuators 26 for depressing selected probes 19 . Fig. 9 A plurality of the above-mentioned z-axis actuators 26 are shown, each z-actuator 26 being configured to move a dedicated one of the probes 19 in the z-axis. Figure 5 and 5a Compared with the embodiment of the present invention, for non-selected probes, a smaller gap is required above the cover member 24 because the selected probe 19 can be pressed down by the corresponding actuator. In addition, the movement of the probe 19 is spring-loaded by a spring associated with each probe 19, which is held between the upper plate 27 and the lower plate 33. The lower plate 33 holds the probe 19 and is driven upward for retracting the probe 19. The top plate is optional, and the top plate can be raised to remove the spring tension when retracting the probe 19, and the top plate can be lowered to apply the spring tension before selecting the probe. In one example, the actuator 26 is a solenoid actuator that retracts to release and cancel the selection of the probe. In another example, a pull-type solenoid is used with an internal return spring. This embodiment has the advantage of being able to drop all probes 19 into the washing station 35 for simultaneous washing. Fig.12 An embodiment is shown in which the plurality of z-axis actuators 26 are pneumatic actuators, which may include pneumatic cylinders housed within a housing. Fig.13 An embodiment is shown in which four z-axis actuators 26 are provided on the fluid dispensing head 17. Here, there are twelve probes 19 with corresponding reagent lines 23 extending therefrom. Each of the four z-axis actuators 26 has three dedicated probes 19 that can be selected individually or as a group for reagent dispensing. In this way, the clearance requirements for non-selected probes 19 are minimized.

[0076] For example, the probe 19 can also be removed from the fluid dispensing head 17 for replacement. To this end, in one embodiment, a probe holder 34 is provided on the fluid dispensing head 17, such as Fig.14 The probe holder 34 includes an upper portion 36 having an upper slot 38 and a lower portion 40 having a lower slot 42 . Fig.14 The probe holder 34 is shown in a locked position with the probe captured therein. When the upper portion 36 is rotated relative to the lower portion 40 until the upper slot 38 and the lower slot 42 are aligned, the probe is released and can be removed from the fluid dispensing head 17. The probe holder 34 also includes a return spring 44 and a clamp 46 that bias the probe holder 34 to the locked position.

[0077] Re-reference Figure 1 and Figure 2In use, the slide transport robot 18 moves linearly in the x-direction along the track 31 and in the y-direction along any one of the tracks 29, depending on which is closest to the target slide processing module 14, and or which is less likely to interfere with the operation of the washing robot 15, as determined by the controller. Movement of the slide transport robot 18 along these guide rails enables the slide transport robot 18 to move a slide with a sample thereon to the slide processing module 14. The slide transport robot 18 includes a slide transport device 20 disposed on the slide transport robot 18, and the slide transport device 20 is configured by the controller to releasably hold the slide 13 so that the slide can be moved into and out of the slide processing module 14. For example, the slide transport device 20 may be as follows Figure 3 A suction cup 20 is shown, which is arranged to releasably hold the carrier 13 when the carrier 13 is to be moved to the carrier processing module 14, and to release the carrier 13 to be positioned in the carrier processing module 14. Figure 3 and Figure 4 Also shown is a reader 50 configured to read an identifier (such as a barcode or QR code) on the slide 13 to track the sample being processed by the slide processing device 12. Ideally, the reader 50 is angled to obtain an image of the identifier on the slide 13 or emit and detect light for reading the identifier on the slide 13. In some embodiments, a liquid level sensor, such as an ultrasonic liquid level sensor, may also be mounted on the slide transport robot 18.

[0078] The slide transport robot 18 may also include means for facilitating disengagement of the slide after placement in the slide handling module or at other points where disengagement of the slide is desired. Suitable means include providing Fig.15 The concave portion AAA in the suction cup 20 surrounds a portion of the carrier 13 and engages the carrier 13 after the carrier 13 is released at the desired position. In the case where the carrier 13 is attached or stuck to the bottom of a module (such as the carrier processing module 14) when the suction cup 20 engages with the carrier 13 and attempts to move the carrier 13, the carrier engaging portion (such as Fig.15 The U-shaped concave portion AAA in the support carrier conveying robot 18 assists in lifting the carrier 13. In addition, the suction cup 20 can be moved on the track R alone and has a tension arrangement S to assist in the movement, such as Fig.16 As shown. The tension arrangement reduces the force when lifting and releasing a stuck slide when it is desired to transport the slide. Thus, in the event that the slide is attached when it is desired to transport the slide, the U-shaped recess AAA will engage the slide and facilitate its release. In addition, the U-shaped recess AAA is shaped to provide additional clearance for an overhanging slide label. Fig.17 A cross-sectional view of an embodiment of a fluid dispensing head 17 of the FT robot 16 is shown.

[0079] The FT robot 16 then dispenses one or more selected reagents to the slides 13 in the slide processing module 14. High-value reagents may be dispensed to the slides 13 in a designated slide processing module 14 to process those samples disposed on the slides. Additionally / alternatively, the FT robot 16 may dispense bulk fluid reagents to the slides 13 in a designated slide processing module 14 to quickly rinse or wash the samples, for example, when a wash robot 15 is not available. In some embodiments, the use of the FT robot 16 to dispense wash reagents may eliminate the wash robot 15 from the slide processing apparatus 12, which may reduce production costs, although possibly at the expense of throughput.

[0080] It can be seen that the slide transport robot 18 and the FT robot 16 are away from the washing robot 15 on the z-axis so that they can be independently operated and controlled by the controller. It should be understood that the controller of the automated slide processing device 12 - as well as the slide transport robot 18, the washing robot 15 and the FTP robot 16 - can be implemented away from the device 12 or can be implemented locally relative to the device 12. In any case, it should also be understood that the controller includes several modules (the several modules are implemented by a processor and a memory for storing instructions for the modules) for providing instructions to the slide transport robot 18 to control its movement, and providing instructions to the washing robot 15 and the FT robot 16 to control the reagent distribution. It should be understood by those skilled in the art that the memory includes instructions for configuring the controller to distribute bulk fluid reagents and high-value reagents in a predetermined order to process tissue samples on the slide 13.

[0081] In one example, the tissue sample is stained according to a predetermined staining scheme for in situ hybridization (ISH) and immunohistochemistry (IHC) applications stored in the memory. In this way, the washing robot 15 and the FT robot 16 are configured by the controller to independently dispense reagents in a predetermined order for each of the slide processing modules 14 to process (e.g., stain) the tissue sample on each of the slides 13 disposed in the module 14. For example, the tissue sample is first processed by the FT robot 16 with bulk reagents (such as alcohol and dewaxing agent), and then the tissue sample is processed by the FT robot 16 with chromogen.

[0082] Reference now Fig.18, shows an overview of a method 100 for delivering a fluid for processing one or more tissue samples disposed on a slide, wherein slides in the slide are received in a plurality of slide processing modules, and a plurality of fluid reagents are dispensed by at least one fluid dispensing robot to the slides received in the slide processing modules to process the tissue samples on the slides. The method 100 includes: step 102: pumping the reagents to be dispensed from a plurality of corresponding reagent containers to one or more probes extending from a fluid dispensing head of the fluid dispensing robot, each of the probes having a body, the body having one or more channels, the one or more channels being arranged to receive one of the reagents to be dispensed; step 104: selecting one of the probes and / or one of the channels for the selected one of the reagents; and step 106: dispensing the selected one of the reagents to the slides in the slides received in the slide processing modules to process the one or more tissue samples disposed on the slides.

[0083] Other aspects of the method will be apparent from the above description of the fluid delivery system 10. Those skilled in the art will also appreciate that the method may be embodied in program code. The program code may be provided in a variety of ways, such as on a tangible computer readable medium such as a disk or memory.

[0084] It will be appreciated that various changes, additions and / or modifications may be made to the previously described parts without departing from the scope of the invention, and as those skilled in the art will appreciate, in view of the above teachings, the invention may be implemented in software, firmware and / or hardware in a variety of ways.

[0085] This specification includes discussions of documents, acts, materials, devices, articles of manufacture etc. solely for the purpose of providing a context for the present invention. It is not suggested or represented that any of these matters formed part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim of this application.

[0086] When the terms “comprise”, “includes”, “comprised”, and “comprising” are used in this specification (including the claims), they should be interpreted as specifying the presence of one or more features, but not excluding the presence or addition of other features in various embodiments of the invention.

Claims

1. A fluid delivery system for an automated slide processing device, the automated slide processing device being used to process one or more tissue samples disposed on a slide, the device comprising a plurality of slide processing modules arranged to receive slides in the slide, the fluid delivery system comprising: a fluid dispensing robot configured by a controller to dispense a plurality of reagents to the slides received in the slide processing module to process the one or more tissue samples, respectively, wherein: The fluid dispensing robot comprises: a fluid dispensing head having a plurality of probes extending therefrom, each of the probes having a body having a plurality of channels arranged to receive each of the reagents to be dispensed, wherein each of the reagents to be dispensed is pumped from a plurality of corresponding reagent containers by a pumping device configured by the controller, wherein: The fluid dispensing robot is configured to select one of the probes and / or one of the channels for a selected one of the reagents and dispense the selected one of the reagents to the slide among the slides received in the slide processing module; wherein the fluid dispensing robot is configured by the controller to utilize a drive device to move the fluid dispensing head having the probes in the x-axis, the y-axis, and the z-axis to position the selected one of the probes relative to the slide received in the slide processing module in an appropriate position to dispense the selected one of the reagents; wherein the fluid dispensing robot is configured by the controller to utilize the driving device to rotationally move the fluid dispensing head about the θ axis; and Wherein the fluid dispensing robot comprises a cylinder such that each of the probes are spaced substantially around a periphery of the cylinder and are arranged to rotate about the theta axis of the fluid dispensing head.

2. The system of claim 1, wherein the drive means comprises: an x-axis driver, the x-axis driver being configured by the controller to move the fluid dispensing head on the x-axis; a y-axis driver, the y-axis driver being configured by the controller to move the fluid dispensing head on the y-axis; and a z-axis driver, the z-axis driver being configured by the controller to move the fluid dispensing head on the z-axis.

3. The system of claim 2, wherein the drive device comprises a theta-axis drive configured by the controller to move the fluid dispensing head about the theta-axis.

4. The system of claim 2, wherein the dispensing head comprises a plurality of z-axis actuators, each of the plurality of z-axis actuators being configured by the controller to independently move a corresponding one of the probes in the z-axis.

5. The system of claim 2, wherein each of the probes includes a nozzle disposed at a distal end of the probe to dispense the one of the reagents.

6. A system as described in claim 5, wherein the nozzle of each of the probes is arranged to be connected to the cover member of the one of the slide processing modules and to substantially sealably cooperate with the inlet port of the cover member when the reagent is being dispensed.

7. A system as described in claim 6, wherein the fluid dispensing robot is configured to use the drive device to push the nozzle of the probe on the z-axis toward the inlet port of the one of the slide processing modules while dispensing the one of the reagents to maintain a seal with the inlet port.

8. A system as described in claim 1, wherein the pumping device includes a plurality of pumps, each of the pumps being associated with each of the plurality of reagents, for pumping the reagents to each of the channels and / or each of the probes through a plurality of corresponding reagent lines.

9. The system of claim 1, wherein the fluid delivery system further comprises a washing station for washing the one or more probes while the probes are inserted into their wash tubs.

10. The system of claim 1 wherein the fluid dispensing head further comprises a high-value fluid transfer probe configured to dispense high-value fluid and operate separately from the plurality of probes, and wherein the high-value fluid transfer probe is positioned proximate a front portion of the fluid dispensing head.

11. A method for delivering a fluid for processing one or more tissue samples disposed on a slide, wherein slides in the slides are received in a plurality of slide processing modules, and a plurality of reagents are dispensed by at least one fluid dispensing robot to the slides in the slides received in the slide processing modules to respectively process the one or more tissue samples, the method comprising: pumping reagents to be dispensed from a plurality of corresponding reagent containers to a plurality of probes extending from a fluid dispensing head of the fluid dispensing robot, each of the probes having a body having a plurality of channels arranged to receive each of the reagents to be dispensed; selecting one of the probes and / or one of the channels for a selected one of the reagents; using a drive device to move the fluid dispensing head having the probes in x-, y-, and z-axes to position the selected one of the probes relative to the slide received in the slide processing module; rotatably moving the fluid dispensing head about a theta axis, wherein the fluid dispensing robot includes a cylinder having each of the probes spaced substantially about a periphery of the cylinder and arranged to rotate about the theta axis of the fluid dispensing head; as well as The selected one of the reagents is dispensed to the slide among the slides received in the slide processing module.

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