Systems and methods for automated preparation of biological samples

Abstract

An automated system for processing a sample contained in a fluid sample container includes: an automated tool head configured to rotate about a first axis and translate along a second axis different from the first axis; an analytical element positioner having an analytical element holder configured to releasably grasp an analytical element; and a sample transfer device carried by the tool head, wherein the tool head is configured to automatically position the working end of the sample transfer device by one or both of rotation of the tool head about the first axis and translation of the tool head along the second axis to obtain a sample from the sample container held in the sample container holder and transfer the obtained sample to an analytical element held by the analytical element holder.

Description

[0001] This application is a divisional application of Chinese Patent Application No. 201880016720.3 (International Application No. PCT / US2018 / 021879) filed on March 9, 2018, entitled "System and Method for Automated Preparation of Biological Samples", the entire contents of which are incorporated herein by reference. Technical Field

[0002] This disclosure relates primarily to the preparation of biological samples, and more specifically, to automated systems and methods for collecting biological samples from liquid sample containers and distributing the samples onto analytical elements such as sample slides, as well as automated systems and methods for obtaining sample aliquots for additional testing. Background Technology

[0003] Cytology is a branch of biology that studies the formation, structure, and function of cells. When applied in a laboratory setting, cytologists, cell technicians, and other medical professionals make medical diagnoses based on visual examination of a patient's cell samples. A typical cytological technique is the Pap smear, in which cells are scraped from a woman's cervix and analyzed to detect the presence of abnormal cells (precursors to cervical cancer). Cytological techniques are also used to detect abnormal cells and diseases in other parts of the body.

[0004] Cytological techniques are widely used because collecting cell samples for analysis is generally less invasive than traditional surgical pathology procedures such as biopsies, which involve removing a solid tissue sample from a patient using a specialized biopsy needle equipped with a spring-loaded movable probe or a fixed cannula. Cell samples can be obtained from a patient using various techniques, including, for example, scraping or wiping an area, or aspirating fluid from the pleural cavity, bladder, spinal canal, or other suitable area using a needle. The obtained cell samples are typically placed in a preservative solution, then extracted from the solution and transferred to a glass slide. A fixative is applied to the cell sample to ensure the cells are fixed on the slide for subsequent staining and examination.

[0005] Generally, it is desirable for cells on a slide to have an appropriate spatial distribution so that individual cells can be examined. A monolayer of cells is typically desired. Therefore, preparing a sample from a liquid sample containing many (e.g., tens of thousands) cells usually requires first separating the cells from each other using mechanical dispersion, liquid shearing, or other techniques to collect and deposit a thin monolayer of cells onto a slide. In this way, cell technicians can more easily identify the presence of any abnormal cells in the patient sample. It is also possible to count the cells to ensure that a sufficient number of cells have been evaluated.

[0006] Methods and apparatus for generating a thin monolayer of cells from a liquid sample container and transferring that thin layer to a “sample slide” suitable for visual examination are disclosed in U.S. Patent Nos. 5,143,627, 5,240,606, 5,269,918, 5,282,978, 6,562,299, 6,572,824, and 7,579,190, the contents of which are incorporated herein by reference in their entirety. According to one method disclosed in these patents, a rotating sample collector disposed within a sample container is used to disperse patient cells in a preservative liquid within the sample container. A controlled vacuum is applied to the sample collector to aspirate the liquid through its filter until a desired amount and spatial distribution of cells are collected on the filter. The sample collector is then removed from the sample container, and a portion of the filter is pressed against a slide to transfer the collected cells onto the slide in a spatial distribution substantially identical to the collected spatial distribution. Devices manufactured according to the teachings of one or more of these patents have been commercially successful, for example... 2000 processor (processes one sample slide at a time from the patient sample) and The 5000 processor (for processing sample slides from patient sample batches) is manufactured and marketed by Hologic, Inc., located in Marlborough, Massachusetts, USA. Further reference is made to U.S. Patent Nos. 7,556,777 and 7,771,662, the disclosures of which are incorporated herein by reference in their entirety.

[0007] Once the sample slides are prepared, cell technicians can visually examine the samples, typically under magnification and with or without various lighting sources. Alternatively, automated slide imaging systems can be used to assist in the cytological examination procedure. For example, an automated slide imaging system can acquire images of all or substantially all cells captured on the slide and use image processing techniques to perform a preliminary assessment of the cells, guiding the cell technician to the potentially most relevant cells on the slide for closer examination. Examples of such imaging systems are disclosed in U.S. Patent Nos. 7,587,078, 6,665,060, 7,006,674, and 7,590,492, the entire contents of which are incorporated herein by reference. Whether examining actual samples at magnification or magnified images of samples, samples are typically classified by cytologists as "normal" or "abnormal." Abnormal samples usually fall into one of the main categories defined by the Bethesda Notification System for Cervical / Vaginal Cytology Diagnosis. These categories include Low-grade squamous intraepithelial lesion (LSIL), High-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma, adenocarcinoma, atypical glandular cells of unknown significance (AGUS), adenocarcinoma in situ (AIS), and atypical squamous cells (ASC). More information on cell sample classification is widely available.

[0008] It may be desirable to perform other types of diagnostic tests on the same patient sample, such as for human papillomavirus (HPV). Given the strong correlation between HPV and cervical cancer, it has been suggested that HPV DNA testing be used as a triage test for patients with Pap smear results classified as ASC-US. In cases where a liquid-based Pap smear has already been performed, the same sample used for the smear analysis can be conveniently used to perform a reflexive HPV DNA test, thus eliminating the need for repeat visits and a second Pap smear. For example, if the sample is classified as ASC-US positive, an aliquot (e.g., 4 mL) of the liquid sample can be removed from the storage vial and sent to a molecular diagnostic laboratory for HPV DNA testing.

[0009] Importantly, laboratories performing HPV DNA testing are wary of molecular contamination, a well-known problem in molecular diagnostics labs. Therefore, due to the risk of cross-contamination, molecular diagnostics labs may refuse aliquots from their own processed liquid smears for fear of unnecessarily generating false HPV positives. Thus, it is desirable to obtain and store aliquots of each patient's sample before the sample slide fabrication process to preserve portions of the sample from cross-contamination. For example, methods and apparatus for obtaining aliquots of patient samples before the sample slide fabrication process are disclosed in U.S. Patents 7,674,434 and 8,137,289, the disclosures of which are incorporated herein by reference in their entirety. Additional examples of obtaining sample aliquots in general (but not necessarily in conjunction with sample slide fabrication) are disclosed in U.S. Patents 9,335,336 and U.S. Patent Publication 2017 / 0052205, the disclosures of which are incorporated herein by reference in their entirety.

[0010] Besides HPV DNA testing, aliquots of liquid smear samples can also be used for DNA testing of other sexually transmitted infections (STIs), such as Chlamydia trachomatis and Neisseria gonorrhoeae. However, false positives are a particular concern when testing for Chlamydia trachomatis and Neisseria gonorrhoeae, as they can have significant family and social consequences. Therefore, molecular diagnostic laboratories are less inclined to accept aliquots of pre-processed liquid smear samples. Testing for other STIs does not need to be limited to ASC-US samples. In practice, such tests are intended to be performed in parallel with smear testing upon a physician's request, by removing aliquots from the smear sample before processing, for example, by manually aspirating the aliquots from the vial, thereby minimizing the risk of cross-contamination. However, this step may still not meet the stringent contamination prevention requirements of molecular diagnostic laboratories.

[0011] In addition to contamination issues, aliquoting liquid smear samples, whether done before or after liquid smear sample processing, and regardless of whether it is for HPV testing or testing for any other sexually transmitted disease, increases the physical labor cost. This involves not only transferring the aliquots into additional vials, but also labeling the vials.

[0012] Therefore, there is a need for improved equipment and methods to obtain aliquots from liquid-based biological samples (e.g., cervical smear samples) while minimizing the risk of cross-contamination. Summary of the Invention

[0013] Embodiments of this disclosure relate to improved automated systems and methods for processing samples (such as biological samples) contained in sample containers.

[0014] In one embodiment, an automated system for processing a sample contained in a liquid sample container includes a sample container holder configured to hold the sample container, and an automated tool head configured to rotate about a first axis and translate along a second axis different from the first axis. The system further includes a sample transfer device carried by the tool head, wherein the tool head is configured to automatically position a working end of the sample transfer device to obtain a sample from the sample container held in the sample container holder by one or both of rotation of the tool head about the first axis and translation of the tool head along the second axis, and then transfer the obtained sample to an analytical element (such as a glass slide) held by an analytical element holder. Without limitation, the working end of the sample transfer device may be configured to receive a filter thereon, the filter including a tubular body that forms a seal with the working end of the sample transfer device, and a porous membrane end configured to allow liquid to pass through it while retaining cellular material on its outer surface.

[0015] The system may further include an analytical element positioner comprising an analytical element holder configured to releasably grasp an analytical element. The analytical element positioner may be configured to automatically place the analytical element carried by the positioner into a fixative container held by a fixative container holder after the sample has been transferred onto the analytical element. The system may include an analytical element (e.g., a slide) loading platform located on a surface of a tool head, wherein the analytical element positioner operatively cooperates with the tool head to automatically engage and remove analytical elements placed on the loading platform, and wherein the analytical element positioner operatively cooperates with the tool head to automatically position the engaged analytical element near the working end of a sample transfer device to transfer the sample onto the engaged analytical element.

[0016] The system may further include a sample container capping device disposed on a tool head and configured to controllably clamp and release the cap of a sample container held in a sample container holder, wherein the tool head is configured to automatically position the sample container capping device near the sample container cap by one or both of rotation of the tool head about a first axis and translation of the tool head along a second axis, and wherein the sample container capping device operatively cooperates with the sample container holder to remove or install the sample container cap. Without limitation, the sample container holder may be configured to automatically rotate in one of a clockwise and counterclockwise rotational direction when the sample container capping device engages the sample container cap to remove the sample container cap from the sample container, and wherein the sample container holder is configured to automatically rotate in the other of a clockwise and counterclockwise rotational direction when the sample container capping device engages the sample container cap to install the sample container cap onto the sample container.

[0017] The system may further include a pipette tip dispenser and a pipette carried by a tool head, the pipette having a pipette tip engagement component configured to releasably engage a pipette tip, wherein the tool head is configured to automatically position the pipette tip engagement component near the pipette tip dispenser by one or both of rotation of the tool head about a first axis and translation of the tool head along a second axis, allowing the pipette tip engagement component to engage a pipette tip held by the pipette tip dispenser. Notably, the pipette tip dispenser may be mounted on a pipette tip dispenser carrier configured to translate the pipette tip dispenser relative to the tool head, such that the pipette tip dispenser can be selectively translated to a position where the tool head positions the pipette tip engagement component to engage a pipette tip from the pipette tip dispenser. The system may further include a pipette tip dispenser isolation chamber, wherein the pipette tip dispenser carrier is configured to selectively translate the pipette tip dispenser between a position where the tool head positions the pipette tip engagement to engage a pipette tip from the pipette tip dispenser and a second position within the isolation chamber. A pipette tip waste container may be mounted on the pipette tip dispenser carrier, wherein the pipette tip dispenser carrier is configured to selectively translate the pipette tip waste container to a position where the tool head positions the pipette tip engagement to disengage a pipette tip into the pipette tip waste container. For example, the pipette tip waste container may be mounted on the pipette tip carrier relative to the pipette tip dispenser such that when the pipette tip waste container moves to the position where the tool head positions the pipette tip engagement to disengage a pipette tip into the pipette tip waste container, the pipette tip dispenser is simultaneously translated into the isolation chamber.

[0018] In embodiments including a pipette, the system may further include a replenishment container holder configured to hold a replenishment container, wherein the tool head is configured to automatically position a pipette tip engagement member to a position in which a pipette tip engaged with a pipette tip is inserted into a sample container held in a sample container holder, and to a position in which an engaged pipette tip is inserted into a replenishment container held in a replenishment container holder, by one or both of rotation of the tool head about a first axis and translation of the tool head along a second axis. The replenishment container may be a dispensing container, wherein when the tool head and the pipette are operatively engaged to automatically engage a pipette tip from a pipette tip dispenser, aliquots of sample are drawn from the sample container held in the sample container holder using the engaged pipette tip, and the obtained aliquots are dispensed into the dispensing container. Alternatively, and without limitation, the replenishment container may be a reagent container containing reagents, wherein when the tool tip and the pipette are operably coordinated to automatically engage the pipette tip of the pipette tip dispenser, aliquots of reagents are taken from the reagent container using the engaged pipette tip, and the aliquots are dispensed into the sample container contained in the sample container holder.

[0019] A refill container capping device may be disposed on a tool head and configured to controllably clamp and release the cap of a refill container held in a refill container holder, wherein the tool head is configured to automatically position the refill container by one or both of rotation of the tool head about a first axis and translation of the tool head along a second axis, and wherein the refill container capping device and the refill container holder are operatively cooperate to remove or install the refill container cap. For example, the refill container holder may be configured to automatically rotate in one of a clockwise and counterclockwise rotational direction when the refill container capping device engages the refill container cap in order to remove the refill container cap from the refill container, and wherein the refill container holder is configured to automatically rotate in the other of a clockwise and counterclockwise rotational direction when the refill container capping device engages the refill container cap in order to install the refill container cap onto the refill container. In some embodiments that include both a sample container capping device and a replenishment container capping device, the two capping devices are offset from each other on the tool head such that when the sample container capping device is in the position of clamping and removing the sample container cap, the replenishment container capping device is in the position of clamping and removing the replenishment container cap without further rotational movement of the tool head.

[0020] The system may further include an analytical element loading platform located on the surface of the tool head, wherein an analytical element locator is operatively cooperated with the tool head to automatically engage and remove analytical elements placed on the tool head, and wherein the analytical element locator is operatively cooperated with the tool head to automatically position the engaged analytical element near the working end of the sample transfer device to transfer the sample onto the engaged analytical element.

[0021] The system may further include a reader (such as a barcode reader or scanner) located on the tool head and configured to read sample container markings located on any sample container. An analytical element printer may be configured to communicate with the reader and to print analytical element markings corresponding to the sample container markings read by the reader onto the analytical element. A dispensing container printer may also be configured to communicate with the reader and to print analytical element markings corresponding to the sample container markings read by the reader onto the dispensing containers. In various embodiments, the reader is further configured to read markings on other system components and consumables (such as carrier chips or filters used to obtain sample samples).

[0022] Embodiments of the system may include a controller for controlling the operation of one or more of a tool tip, pipette, capping device, and analytical element positioner. The system further includes a user interface operatively coupled to the controller and configured to display system status and / or queries to a user, and to receive user input in response to the displayed system status and / or queries.

[0023] In one embodiment, an automated system for handling samples contained in a liquid sample container includes a sample container holder for holding the sample container, an automated tool head configured to rotate about a first axis and translate along a second axis different from the first axis, a pipette tip dispenser, a pipette carried by the tool head, and a pipette tip engagement configured to releasably engage a pipette tip, wherein the tool head is configured to automatically position the pipette tip engagement near the pipette tip dispenser to engage the pipette tip by one or both of rotation of the tool head about the first axis and translation of the tool head along the second axis. A pipette tip held by a tip dispenser, wherein the pipette tip is mounted on a pipette tip dispenser carrier configured to translate the pipette tip dispenser relative to a tool head such that the pipette tip dispenser is selectively displaced to a position in which the tool head positions a pipette tip engagement member to engage a pipette tip from the pipette tip dispenser; and a pipette tip dispenser isolation chamber, wherein the pipette tip dispenser carrier is configured to selectively translate the pipette tip dispenser between a position in which the tool head positions the pipette tip engagement member to engage a pipette tip from the pipette tip dispenser and a second position within the isolation chamber.

[0024] In yet another embodiment, an automated system for processing samples contained in a liquid sample container includes a sample container holder for holding the sample container, an automated tool head configured to rotate about a first axis and translate along a second axis different from the first axis, a pipette tip dispenser, a pipette carried by the tool head, and the pipette having a pipette tip engagement configured to releasably engage a pipette tip, wherein the tool head is configured to engage the pipette tip by one or both of rotation of the tool head about the first axis and translation of the tool head along the second axis. The connector is automatically positioned near the pipette tip dispenser to engage a pipette tip held by the pipette tip dispenser and a replenishment container holder configured to hold a replenishment container. The tool head is configured to automatically position the pipette tip connector, with the engaged pipette tip inserted into the sample container held in the sample container holder and the engaged pipette tip inserted into the replenishment container held in the replenishment container holder, respectively, by one or both of rotation of the tool head about a first axis and translation of the tool head along a second axis. The replenishment container can be either a reagent container or an aliquot container.

[0025] In yet another embodiment, an automated system for handling a sample contained in a liquid sample container includes a sample container holder for holding the sample container, a replenishment container holder configured to hold a replenishment container, an automated tool head configured to rotate about a first axis and translate along a second axis different from the first axis, a first capping device disposed on the tool head and configured to controllably clamp and release a cap of the sample container held in the sample container holder, and wherein the tool head is configured to, by one or both of rotation of the tool head about the first axis and translation of the tool head along the second axis, hold the first sample container in the sample container holder. A capping device is automatically positioned near the sample container cap, and wherein the first capping device operatively cooperates with a sample container holder to remove or install the sample container cap, and a second capping device is disposed on a tool head and configured to controllably clamp and release the cap of a supplementary container held in a supplementary container holder, wherein the tool head is configured to automatically position the second capping device near the supplementary container cap by one or both of rotation of the tool head about a first axis and translation of the tool head along the second axis, and wherein the second capping device operatively cooperates with the supplementary container holder to remove or install the supplementary container cap. The sample container holder may be configured to automatically rotate in one of a clockwise and counterclockwise rotation direction when the first capping device engages the sample container cap to remove the sample container cap from the sample container, and wherein the sample container holder is configured to automatically rotate in the other of a clockwise and counterclockwise rotation direction when the first capping device engages the sample container cap to install the sample container cap onto the sample container. The replenishment container holder is configured to automatically rotate in one of a clockwise or counterclockwise direction when the second capping device engages the replenishment container cap, to remove the replenishment container cap from the replenishment container. The replenishment container holder is also configured to automatically rotate in the other of a clockwise or counterclockwise direction when the second capping device engages the replenishment container cap, to attach the replenishment container cap to the replenishment container. The sample capping device and the replenishment capping device are offset from each other on the tool head, such that when the sample capping device is in the position for gripping and removing the sample container cap, the replenishment capping device can grip and remove the replenishment container cap without further rotational movement of the tool head. In any unrestricted case, the replenishment container can be either a reagent container or an aliquot container.

[0026] Other and further variations and features of the disclosed embodiments will become clearer from reading the following embodiments together with the accompanying drawings. Attached Figure Description

[0027] The above and other embodiments of the present disclosure are described in more detail with reference to the accompanying drawings, wherein similar reference numerals refer to similar elements, and the description of similar elements should apply to all described embodiments where applicable, and in the figures:

[0028] Figure 1 This is a right-side front perspective view of an exemplary automated biological sample processing system according to one embodiment, which includes a sample processing cabinet, a slide printer, and a dispensing container printer.

[0029] Figure 2 for Figure 1 Right front perspective view of the sample processing cabinet, where the outer cabinet wall is not shown to better show the system components located therein;

[0030] Figure 3 for Figure 1 The left front perspective view of the sample processing cabinet, where the external and some internal walls and / or partitions are not shown in order to better show the system components located therein;

[0031] Figures 4 to 14 for Figure 1 The corresponding left, right, and front perspective views of the system components of the sample processing cabinet show the various movements and operations performed by the system components during sample processing;

[0032] Figure 15 For the reason Figure 1 Elevation side view of the components carried by the rotating tool head inside the sample processing cabinet, wherein the tool cover is not shown;

[0033] Figure 16 for Figure 1 A perspective view of the bottom of the sample processing cabinet, with the bottom cover removed to reveal system components; and

[0034] Figure 17 for Figure 1 A perspective view of the rear of the sample processing cabinet, with the bottom cover removed to reveal the system components. Detailed Implementation

[0035] For illustrative purposes, the systems and methods of use disclosed herein and in the accompanying drawings relate to processing patient samples to produce conventional cytological sample slides. Along with this, it is understood that alternative embodiments may include the preparation of different types of biological samples presented on different types of analytical elements (i.e., other than cytology, and not on slides), all of which should be considered within the scope of the disclosed embodiments and claims. Furthermore, the disclosed systems and methods can be used to process other types of liquid samples, including non-biological particles and liquids. Therefore, it should be understood that the disclosed and illustrated embodiments are for illustrative purposes and not for limitation.

[0036] As used herein, terms such as “specimen,” “specimen sample,” “biological sample,” “cytological sample,” “cellular sample,” and “biological sample” are used interchangeably and should be understood and interpreted similarly unless the context in which they are used requires a more specific meaning. Furthermore, terms such as “aliquot” and “aliquot sample” are used interchangeably and should be understood and interpreted similarly. For example, but not limited to, the systems and methods disclosed herein can be used to process biological samples contained in liquid sample containers to produce a sample or aliquot, as well as an aliquot or aliquot sample. Moreover, the term “aliquot” should not be construed as restrictive, as “aliquot” is another way of expressing “liquid sample” or “a portion of a liquid sample.” In other words, obtaining an aliquot or aliquot sample of a biological sample means obtaining a portion of the original sample and storing it in a separate container for subsequent evaluation. Furthermore, terms such as “sample container,” “liquid sample container,” “patient container,” “sample vial,” “patient bottle,” “tube,” “replenishment container,” and other arrangements are used interchangeably and should be understood and interpreted similarly, unless the context in which they are used requires a more specific meaning, such as based on the contents of the container as stated.

[0037] As used herein, the terms “automatic” and “automated” refer to the execution of systems, devices, programs, and / or functions, typically but not necessarily under the control of a programmed processor, without user (e.g., system operator) intervention. In particular, the automated systems and methods disclosed herein advantageously reduce the number of manual steps required to prepare biological samples, such as preparing cell sample slides and / or obtaining aliquots of patient samples for additional testing and / or additional sample processing (e.g., introducing reagents into the sample prior to further processing).

[0038] Figure 1 An exemplary automated biological sample processing system 10 is shown, which can be used to prepare cell sample slides and / or aliquots from biological samples (e.g., obtained from cervical smears) contained in a liquid sample container. As will be explained in more detail below, system 10 can be used for other types of sample processing, such as (but not limited to) adding reagents to biological or other types of samples.

[0039] System 10 typically includes a sample processing cabinet 11, a slide printer 13, and a tube sizing printer 19. In the illustrated embodiment, the main components of system 10 are housed in (and / or attached to) the sample processing cabinet 11. As will be detailed below, the slide printer 13 and the tube sizing printer 15 are operatively coupled to the sample processing cabinet 11 via a known wireless or wired communication link (not shown) under the control of one or more processors located in the sample processing cabinet 11. For simplicity, the one or more processors are collectively referred to below as "system controller 60" (hereinafter referred to in conjunction with...). Figure 17 (Further description) It controls the automated movement and other operations of the components of system 10 housed within sample processing cabinet 11, as well as communication with the corresponding slide printer 13 and aliquot printer 19. For ease of illustration, the individual components of sample processing cabinet 11, slide printer 13, and aliquot printer 19 are collectively referred to as "system" 10, without regard to where any particular component may be placed. It should be understood that, in alternative embodiments, the various components of system 10 may be individually housed or otherwise arranged.

[0040] For example, and not limited to, system 10 can be configured to process sample containers, such as Thin Sample vials and, for example Both the vials and the aliquot containers are available from Hologic, Marlborough, Massachusetts, USA (www.hologic.com).

[0041] The sample processing cabinet 11 is preferably an environmentally enclosed housing (or "skin") to reduce potential contamination from the surrounding environment. In the illustrated embodiment, the sample processing cabinet 11 is provided with an openable front door 15 to provide access to the system components therein. The door 15 is hinged to open and close in a rotary manner and is provided with a handle 29. In an alternative embodiment, the door 15 may be a slide door, such as a side slide, to open and close. In the illustrated embodiment, the front door 15 has a transparent or translucent panel, allowing the system components housed in the sample processing cabinet 11 to be visible when the front door 15 is in the closed position, but this is not necessary for practicing the disclosed embodiments. Also briefly referenced... Figure 16 Stabilizing feet 79, made of a material that minimizes vibration and movement of the cabinet, can be installed at each of the four corners of the bottom of the cabinet, which is typically placed on a desktop in a laboratory with four feet. In addition to providing better stability, the size and construction of the feet 79 allow for a certain gap between them and the desktop surface.

[0042] The slide printer 13 can be any commercially available slide printer, such as the Signature SlidePrinter (https: / / www.primera.com / signature-slide-printer) available from Primera Technologies, Inc., Plymouth, Minnesota, USA. The slide printer 13 loads new slides and outputs printed slides through output slot 17, on which cell samples are received as part of the processing of the corresponding patient sample container. Specifically, the printer 13 prints markings (e.g., barcodes) onto a portion of the slide (the side on which the cell sample is applied), wherein the printed markings on the slide match or otherwise correspond to markings read on the sample container being processed, as further detailed below.

[0043] The dividing container printer 19 is preferably identical to that taught in U.S. Patent No. 9,724,948 ('948 Patent), the disclosure of which is incorporated herein by reference in its entirety. As explained in the '948 Patent, the dividing container printer 19 is provided with an opening 21 into which a new (unprinted) dividing portion can be inserted. As explained in further detail below, the printer 19 prints a mark (e.g., a barcode) on the dividing container that matches or otherwise corresponds to a mark read from a sample container being processed. The printed container is then ejected from the opening 21 or otherwise removed from the opening 21.

[0044] Figure 2 and Figure 3 The components of system 10, which are housed or otherwise attached to sample processing cabinet 11, are depicted, with the cabinet walls removed for ease of illustration. Cabinet 11 includes a chassis 14, which may include multiple floors, walls, and / or supports providing a primary support structure to which various system components are mounted / attached.

[0045] As in Figure 3 Most clearly, the cylindrical sample container holder 16 is arranged in the lower central portion of the base 14. As will be described in more detail below, the sample container holder 16 is fixedly mounted on a rotating platform, which is configured to hold the sample container 12 (…) within the sample container holder 16. Figure 4The sample container 12 (as shown) rotates about its central z-axis to mix the sample, achieving a substantially uniform dispersion of cells or other specific materials contained within it before processing begins, and also facilitating opening and resealing of the container 12 during processing. In the illustrated embodiment, the sample container holder 16 is a cylindrical container configured to tightly contain and hold the sample container 12. The sample container holder 16 has an outer wall extending to a height less than that of the sample container 12, such that the cap 43 on the sample container 12 held within the sample container holder 16 is fully exposed to facilitate its separate mixing, opening, and resealing. In alternative embodiments, the sample container holder 16 can be any suitable shape for receiving a specific sample container used with the system 10, such as a rectangular box or other shape.

[0046] Similarly, Figure 3 Most clearly, the aliquot container holder 18 is positioned in the lower central portion of the chassis 14 directly in front of the sample container holder 16. As will be described in more detail below, the aliquot container holder 18 is fixedly mounted on a rotating platform configured to hold the aliquot containers 20 ( ) within the aliquot container holder 18. Figure 5 The sample container 10 (as shown) rotates about the central z-axis of the container 20 to facilitate opening and resealing of the container 20 during sample processing. The aliquot container holder 18 is configured to tightly accommodate and hold the aliquot container 20 and has an outer wall extending to a height less than that of the aliquot container 20, such that the cap 45 of the aliquot container 20 held in the aliquot container holder 18 is fully exposed for easy mixing, opening, and resealing. In the illustrated embodiment, the aliquot container holder 18 is sized and configured to hold a more tubular container than the container held by the sample container holder 16. In alternative embodiments, the aliquot container holder can be any suitable shape for accommodating a particular aliquot container used with system 10, such as a rectangular box or other shape. System 10 can also be used for additional sample processing steps, such as for introducing reagents into the sample container. Therefore, it should be understood that references to the aliquot container holder 18 and the aliquot container 20 themselves should be construed as exemplary and not limiting. For example, the terms “replenishment container holder” and “replenishment container” can be used interchangeably with “dividing container holder” and “dividing container”.

[0047] More specifically, the sample container holder 16 and the equal-division container holder 18 are each mounted on a separate, rotatable lower platform (not shown) (or otherwise integrally formed), which are rotatably coupled to or near the base plate of the chassis 14. The individual rotating platforms, and thus the container holders 16 and 18, can be selectively rotated about the central z-axis of each holder 16 and 18 in a clockwise or counterclockwise direction. Specifically, and further reference... Figure 16A sample dispersion drive assembly is provided for performing relatively high-speed mixing of the contents of the sample container 12 held in the sample container holder 16, in order to disperse cells and / or other particulate matter suspended in the liquid sample prior to further sample processing. The sample dispersion rotary drive assembly includes a sample dispersion motor (not shown) mounted near a base plate of the chassis 14, having a rotary output shaft extending through the chassis base plate to rotate a drive wheel 81. The drive wheel 81, in turn, rotates a larger diameter drive wheel 93 via a drive belt 88. A high / low speed clutch 82 is operatively connected to the drive wheel 93 to selectively engage the drive wheel 93 with a corresponding rotary platform associated with the sample container holder 16 via a rotary drive shaft (not shown) extending upward and backward through the chassis base plate, thereby also rotating the sample container holder 16 to disperse the particles contained in the sample container 12 held therein at relatively high speed prior to further sample processing.

[0048] Continue to refer to Figure 15 System 10 also includes a cap drive assembly for simultaneously providing relatively low-speed rotation of the sample and aliquot container holders 16 and 18 to remove and reinstall corresponding caps 43 and 45 on the sample and aliquot containers 12 and 20, which are held in their respective sample and aliquot container holders 16 and 18, as described in more detail below. The cap drive assembly includes a capping motor 39 mounted in or near the bottom plate of chassis 14 in the lower compartment 28 of cabinet 11. Figure 3 The capping motor is reversible to provide rotational motion in both clockwise and counterclockwise directions. The capping motor 39 has a rotary output shaft extending through the base plate of the chassis 14 to rotate a drive gear 84, which in turn rotates a larger drive gear 91 via a drive belt 85. A high / low speed clutch 82 is operatively connected to the drive gear 91, thereby selectively engaging the drive gear 91 with the rotating platforms associated with the sample container holder 16 and the dividing container holder 18 via a rotary shaft (not shown) extending upwards and backwards from the drive gear 91 through the chassis base plate. Note that in the lower part of the chassis, below the respective rotating platforms of the sample container holder 16 and the dividing container holder 18, one or more drive gears / wheels and drive belts (not shown) are further provided to simultaneously distribute the rotational motion of the wheel 91 to each rotating platform. In this way, depending on the rotation direction of the output shaft of motor 39, the capping motor can be actuated to rotate the sample container holder 16 and the equalizing container holder 18 at a relatively low speed to remove or reinstall caps 43 and 45.

[0049] refer to Figure 4 The system 10 includes an automated tool head 30 rotatably mounted on a load-bearing shaft assembly 34, such that the tool head 30 is configured to surround... Figure 7The axis of rotation, indicated by the dashed line 33, pivots or rotates back and forth. Preferably, the tool head 30 has an arc range of at least 270 degrees of rotation about the axis of rotation, although no specific minimum rotational stroke is required except as necessary for performing the functions of a particular system embodiment. In the illustrated embodiment, the tool head rotates at least 270 degrees about its axis of rotation 33. The load-bearing shaft assembly 34 preferably includes a rotary bearing (not shown) to minimize friction between the tool head 30 and the mounting shaft (not shown) mounted on the tool head 30. A tool head rotary actuator motor 36 is attached to the load-bearing shaft assembly 34, wherein the output shaft (not shown) of the motor 36 is operatively coupled to the shaft via a drive belt 74 to rotate the tool head 30. The rotary actuator motor 36 is reversible to selectively provide rotational movement of the tool head 30 in both clockwise and counterclockwise directions.

[0050] Continue to refer to Figure 4 The motor 36 is housed in a block-shaped support housing (also referred to as object 36 in the figure), which is threadedly mounted on a vertical lead screw 55 disposed at the rear of the chassis 14. Figure 15 (Most clearly visible in the center). The lead screw 55 is actuated by a tool head linear actuation motor 32 mounted on the rear wall (near the top) of the chassis 14. The tool head linear actuation motor 32 is reversible to selectively provide rotational movement of the lead screw 55 in both clockwise and counterclockwise directions. Specifically, rotation of the lead screw 55 in one of the clockwise or counterclockwise directions causes the motor block 36, and thus the corresponding load-bearing shaft assembly 34 and the tool head 30, to rotate along... Figure 4 The vertical (or "z") translation axis, indicated by the dashed line 51, travels linearly upward relative to the chassis 14, and the rotation of the lead screw 55 in either the clockwise or counterclockwise direction causes the motor block 36, and consequently the corresponding load-bearing shaft assembly 34 and tool head 30, to travel linearly downward relative to the chassis 14 along the vertical axis 51. Using this mechanical arrangement, and as further described below, the automated tool head 30 is configured to selectively and controllably rotate about the rotation axis 33 in each of the clockwise and counterclockwise directions, and independently and selectively translate upward or downward along the vertical axis 51, including simultaneous rotational and translational movements. The operation of the rotary actuation motor 36 controls the rotational position of the tool head 30 about the rotation axis 33, while the operation of the linear actuation motor 32 controls the vertical position of the tool head 30 within the cabinet 11 along the vertical axis 51.

[0051] Multiple sample processing devices (or "tools") are arranged circumferentially around a tool head 30 and are configured such that the individual functions performed by each device can be achieved via one or both of rotation of the tool head about its axis of rotation 33 and translation of the tool head 30 along its vertical translation axis 51, without requiring movement of the tool head 30 in the x-direction (i.e., lateral relative to the cabinet 11) or y-direction (i.e., longitudinal relative to the cabinet 11). In the illustrated embodiment, these devices include: a tag reader 31 configured to read tags such as barcodes on sample containers 12; a first capping device 42 including a pneumatically controlled gripper with a gripping device configured to releasably grip the cap 43 of the sample container 12 being processed; a second capping device 44 including a pneumatically controlled gripper configured to releasably grip the cap 45 of a replenishment container 20 (e.g., an aliquot tube or a reagent-containing vessel); and a pipette 37 (in... Figure 15 As can be seen most clearly in the image, it has a pipette tip engagement 38 extending outward from the tool head 30 and configured to releasably engage a pipette tip, a sample collection and transfer device (hereinafter, "sample transfer device") 40 having a working end extending outward from the tool head 30 and configured to obtain a sample from a sample container, and a slide loading bed or "platform" 46 configured to receive a slide 50, which will be transferred from the tool head 30 to a slide holder 57 of the slide positioner assembly 56 (described in more detail below).

[0052] Each of devices 31, 42, 44, 37 / 38, 40, and 46 is positioned and oriented on the tool head 30 about a rotation axis 33 in different circumferential and / or angular positions and orientations, such that each of these devices rotates with the tool head 30 as the tool head rotates about its rotation axis 33 under the control of a rotary actuator motor 34, and moves vertically upward or downward along the vertical axis 51 of the tool head within the cabinet 11 under the control of a tool head translation actuator motor 32. Thus, as further described herein, rotational and / or vertical translation actuation of the tool head 30 positions each of these devices in a relative rotational and vertical position within the cabinet 11 to perform their respective functions. It should be understood that each particular device or tool disposed on the tool head 30 in the illustrated embodiment is not necessary or limiting. For example, in alternative embodiments, more or fewer devices / tools may be carried on the tool head 30. For example, a single capping device (e.g., 42 or 44) may be used and / or the reader 31 may be located separately from the tool head 30 (including not within the cabinet 11). As a further example, in some embodiments the slide loading platform 46 may be omitted, where the system operator loads slides directly into a slide holder such as or similar to a slide holder 57. Variations and substitutions of these and other arrangements of the devices / tools on the tool head 30 are also considered to fall within the scope of this disclosure.

[0053] like Figure 3 and Figure 4 As shown, a pump 47 with a pump head 49 supplies pressurized air stored in a high-pressure tank 71. The high-pressure tank 71 provides pressurized air to operate various pneumatic devices located in cabinet 11 via a manifold operated through a solenoid valve 68 and a connector 67. A slightly elevated pressure tank 72 and a slightly negative pressure tank 73 are also provided for the operation of the sample transfer device 40 (described in more detail below). For clarity, the communication paths for pressurized air, such as the solid and / or flexible lines connecting the pump 47 to tank 71 and the tank 71 to the various pneumatic devices, are not shown to provide a clearer view of the system components located in cabinet 11 without obstruction by the lines. However, in Figure 2 The flexible conduit 23 is shown (only) through which various pneumatic and electrical conduits are connected to the tool head 30 and various devices thereon, such as (but not limited to) cappers 42, 44, pipettes 37, and sample transfer devices. Bundling various tubing and wires together via a single conduit 23 reduces the chance of the tool arm 30 detaching from the connector or moving the tubing or wire during operation. It should be noted that the length of the tubing and electrical connections through conduit 23 is sufficient to allow conduit 23 to move with the tool head 30 as it translates linearly along its vertical axis 51 and rotates about its axis of rotation 33.

[0054] Refer back Figure 2 and Figure 3 The reader 31 is configured to read identification marks on any of the sample container 12, the dividing container 20, the slide 50, and / or the filter 54, such as (but not limited to) patient identification and / or medical record identifiers, the date the sample was obtained, or the medical institution, etc. The reader 31 may be an optical reader or scanner, such as one used to read barcodes, QR codes, machine-readable alphanumeric characters, and / or an optical camera that acquires an image of a tag, which can then be read and / or identified using optical character recognition (OCR) software or an electronic reader configured to read NFC chips, RFID, or other electronic tags, or other readers configured to read readable marks. Examples of such alternative mark storage technologies for slides are provided in U.S. Patent No. 7,083,106 and U.S. Patent Publication No. 20070148041, the entire contents of which are incorporated herein by reference. In the illustrated embodiment, the reader 31 is configured to read marks, particularly in the form of barcodes. The markings on the sample container 12 are read by the reader 31 and transmitted via the system controller 60 (described in further detail below) to each of the slide printer 13 and the aliquot container printer 19 to print matching or other corresponding markings on the appropriate slides 50 and / or aliquot containers 20 to be used in the sample processing procedure.

[0055] (Main) Reference Figures 2 to 5 A pipette tip dispenser stand or "carrier" 22 is coupled to the chassis 14 in front of the dispensing container holder 16. The pipette tip dispenser carrier 22 includes a pipette tip dispenser holder 24 configured to securely hold a pipette tip dispenser 26 thereon. The pipette tip dispenser is configured to hold a plurality of pipette tips 48, for example, eight pipette tips in the illustrated embodiment, wherein the dispenser may be supplied in the form of a pipette tip cartridge. The pipette tip dispenser 26 may be removably mounted to the holder 24 in any of a variety of ways. In the illustrated embodiment, the pipette tip dispenser 26 is magnetically coupled to the pipette tip dispenser holder 24 in a manner that ensures accurate and predictable positioning of the dispenser 26 relative to the holder 24, and also allows the system controller 60 (described further below) to confirm, via sensor circuitry, that the dispenser 26 is properly attached and positioned relative to the holder 24. This is important to ensure that the pipette tip engagement 38 carried by the tool head 30 can be precisely aligned during sample processing and thus engage the pipette tip 48 held in the corresponding slot of the dispenser.

[0056] Also, a brief reference Figure 16The lateral translation of the pipette tip dispenser carrier 22 is performed by an electric drive belt 87, which rotates back and forth on drive wheels 80a and 80b located below the bottom surface of the chassis 14. The drive wheels then rotate back along corresponding axles (not shown) on the chassis base plate and are mechanically coupled to the carrier 22 to laterally move the pipette tip holder 24 and the pipette tip dispenser 26 mounted thereon between a storage position and a loading position. In the storage position, the pipette tip dispenser... Figure 4 The pipette tip holder 26, located within the isolation chamber 28, is aligned with the pipette tip engagement 38 on the tool head 30 in the loading position, as shown. Figure 7 As shown in the diagram. In particular, the loading position will vary depending on which slot of dispenser 26 has a pipette tip. In the storage position, the corresponding pipette tip holder 24 and the pipette tip dispenser 26 mounted thereon are located in an isolation chamber 28 within the sample processing cabinet 11 to reduce the chance of unused tips being contaminated by sample processing activities occurring in the main internal area of ​​the cabinet 11.

[0057] By comparison Figure 4 and Figure 5 It can be seen that panel 52 ( Figure 4 It is attached to one side of the pipette tip dispenser 26, and its size and shape are configured to close the retainer 24 and the dispenser 26 through one of the openings into the isolation chamber 28. Figure 3 As shown, the pipette tip sensor 35, located in the isolation chamber 28, tracks the pipette tips 48 held in the dispenser 26 to notify the system controller 60 to precisely move the pipette tip dispenser carrier 22 to a position where the tips 48 held in the dispenser 26 are aligned with the pipette tip engagement 38 on the tool tip 30, and also to ensure that there are sufficient pipette tips in the dispenser 26 to perform a specific sample processing procedure. If the dispenser 26 is empty or otherwise contains insufficient amounts of pipette tips 48 to perform a specific sample processing procedure, the system 10 will pause and not perform any further sample processing until new pipette tips 48 have been loaded into the dispenser 26.

[0058] Used pipette tip waste container 25 is mounted on a separate platform / retainer 27 connected to a pipette tip carrier 22, wherein the pipette tip dispenser carrier is configured to selectively translate the waste container 25 to the position where the tool head 30 positions the pipette tip engagement 38, so that the engaged pipette tip 48 disengages into the waste container 25. Like the pipette tip dispenser 26 and retainer 24, the waste container 25 is preferably magnetically coupled to the retainer 27 to provide both stability and allow the system 10 to confirm proper attachment of the waste container via sensing circuitry. In particular, the pipette tip waste container holder 27 is mounted on the pipette tip carrier 22 relative to the pipette tip dispenser holder 24, such that when the pipette tip dispenser 26 is moved into the isolation chamber 28, the pipette tip waste container 25 is simultaneously moved to the position of the tool head 30 positioning the pipette tip engagement 38, so that the engaged / used pipette tip 48 is disengaged from the waste container 25.

[0059] Also refer to Figure 15 The pipette 37 is disposed on the tool head such that the pipette tip engagement 38 is slightly tilted relative to the pipette tip dispenser 26. Similarly, this slight tilt allows the engagement to mate via one or both of the rotational and translational movements of the tool head 30 to engage the pipette tip 48 held in one of the slots. The pipette 37 may be, for example, but not limited to, those sold by Tecan Group Ltd. Air displacement pipette (ADP) (www.tecan.com / components), which includes a spring-biased engagement end 53 ( Figure 15 As shown in the diagram, the engagement end 53 releasably engages the corresponding pipette tip 48 via its compression fit when inserted into the orifice of the corresponding pipette tip 48. Once the pipette tip 48 is engaged (or mounted) on the pipette tip engagement 38, the pipette 37 is configured to selectively aspirate liquid from the sample container 12 into the pipette tip 48 and dispense the aspirated liquid contained in the pipette tip 48 into the dispensing containers 20.

[0060] In this manner, during sample processing, pipette 37 engages pipette tip 48 from pipette tip dispenser 26. The pipette is then repositioned by tool head 30 to position the engaged tip in an open container (e.g., open sample container 12). In a known manner, pipette tip 48 is made of a conductive material (e.g., a conductive polymer) so that impedance sensing circuitry of pipette 37 can confirm that pipette tip 48 is immersed in a liquid to aspirate a volume of sample, such as an aliquot from a sample container, by providing a vacuum within the orifice of pipette tip 48. Pipette 37 then releases the vacuum to allow sample dispensing from pipette tip 48 into, for example, an open aliquot container 20. The pipette 37 is constructed and operated such that only the pipette tip 48 comes into contact with the sample material, preventing the pipette tip assembly 38 of the pipette 37 from being contaminated by the sample material. The pipette tip assembly 38 is configured to separate the pipette tip 48 into the waste container 25 after use via a movable displacement sleeve that pushes the tip 48 away from the end 53 of the pipette tip assembly 38.

[0061] The sample transfer device 40 is carried by the tool head 30 and configured to collect sample samples from the sample container 12 and transfer the collected sample samples to the slide 50. In the described embodiment, the sample transfer device 40 includes a cylindrical working end that extends from the tool head 30 and is configured to form a pressure seal around its circumference using a filter 54 disposed thereon before initiating the sample processing procedure. Figure 4 As shown. Filter 54 comprises a hollow cylindrical body having an open proximal end and a membrane spanning its distal end, the membrane having pores of a selected size to capture cells desired for use in the sample and allow smaller cellular and non-cellular particles and liquids to pass through. Filter 54, along with sample collection and transfer devices and embodiments of the technology suitable for use with the illustrated system 10, are disclosed and further described in U.S. Application No. 8,119,399, U.S. Application Publication No. 20050100483, and U.S. Application Publication No. 20080145887. When mounted on the working end of the sample transfer device 40, filter 54 extends a sufficient distance away from tool head 30 to allow the filter to be inserted into sample container 12 to collect the sample on the filter membrane without allowing sample liquid to come into contact with any part of sample transfer device 40; only the filter contacts the sample liquid. This ensures that sample transfer device 40 is not contaminated by sample material when collecting sample from sample container 12. Once the sample transfer device 40 has collected the sample onto the sample collector 54, the sample transfer device 40 is then manipulated to transfer the sample from the filter 54 to the slide 50, as detailed below.

[0062] In particular, the sample transfer device 40 and system 10 are configured to insert the filter membrane into the sample in the sample container via one or both of the translational and rotational movements of the tool head 30, and to force the sample back and forth through the membrane to collect the sample onto the membrane in a "sipping" manner, which deposits a thin layer of cells from the liquid sample onto the outer surface of the membrane. The sample transfer device 40 may be configured to circulate a vacuum (and pressure) within the working end of the sample transfer device to force the sample back and forth through the membrane. Alternatively or additionally, the sample transfer device 40 and system 10 may be configured to move the membrane up and down within the sample to collect the sample onto the membrane. A method and apparatus for determining whether a sufficient number, but not excessive number, of cells have been collected onto the filter membrane using the same "sipping procedure" is disclosed and described in the foregoing U.S. Patent No. 8,119,399. Further details of the general sample collection process and the design and operation of the sample transfer device 40 (and filter 54) are found in U.S. Patent No. 8,137,642, the disclosure of which is incorporated herein by reference in its entirety, as well as several other patents combined above. Brief Reference Figure 17 Waste liquid from the sample collection process is discharged to port 95 at the back of cabinet 11.

[0063] The sample container sealing device 42 includes a movable pneumatic fork or gripper configured to grasp and hold the lid 43 of the sample container 12. Figure 15 As can be seen, pneumatically actuated grippers supplied on actuator 77 alternately provide tweezer-like radially inward grasping motion or radially outward release motion. Two or more grippers are preferably arranged substantially evenly around the circumference of sample container cap 43 and can be positioned in a “capped” or “uncapped” position via one or more translational and rotational movements of tool head 30. When cap 43 is removed, capping device 42 grips cap 43 as container holder 16 rotates in one of a clockwise or counterclockwise direction, and tool head 30 rises slightly and steadily upward to allow cap 43 to travel upward as it rotates on the threads (not shown) of container 12. In the case of reattaching the cap 43 held by the gripper to the container 12, the tool head 30 positions the capper 42 on the open container and moves slightly and smoothly downward as the retainer 16 rotates in either a clockwise or counterclockwise direction, while the tool head 30 descends slightly and smoothly as the container rotates relative to the cap 43 via the retainer 16, allowing the cap 43 to travel downward onto the container 12. The grippers used for the sample container capping device 42, and also for the aliquot container capping device 44 described below, include parallel pneumatic grippers / 2-jaw, 3-jaw, and 4-jaw series available from SMCPneumatics.com.

[0064] The aliquot container capping device 44 operates essentially in the same manner as the sample container capping device, including releasably clamping the cap 45 of the aliquot container 20 using two or more forks or grippers while the aliquot container holder rotates clockwise or counterclockwise to remove the cap 45 from or install it onto the container 20, respectively. Again, the tool head 30 moves smoothly downward or upward to accommodate the movement of the cap relative to the container 20 during processing. It is noteworthy that because opening and sealing the aliquot container 20 requires relatively small torque, as... Figure 15 As shown, the equal container holder is driven using direct air pressure supplied via hose attachment 75.

[0065] The sample container capping device 42 and the equalizing container capping device 44 are preferably positioned and oriented on the tool head 30 such that the capping devices 42 and 44 are in the proper position to remove the corresponding caps 43 and 45 without repositioning the tool head 30.

[0066] It should be understood that, in alternative embodiments, the corresponding cappers 42 and 44 may be rotatable, in which case the capping process would involve clamping and rotating the cap 43 with the capper 42 while the sample holder remains fixed, as taught in U.S. Patent Nos. 9,335,336 and 2017 / 0052205.

[0067] The slide loading platform 46 is preferably located on the tool head 30 at a position convenient for the system operator to load the slide 50 prior to the sample processing procedure, and is configured to accommodate and hold the slide when it is loaded. Although the loading platform 46 in this described embodiment is configured to accommodate and hold a microscope slide as slide 50, it should be understood that, depending on the type of sample to be output by the system 10, the loading platform 46 may be configured to accommodate and hold other types of analytical elements besides slides.

[0068] As described above, the slide positioner 56 includes a slide holder 57 with a pneumatic gripper 59 configured to grip and remove slide pieces 50 from the loading platform 46. Figure 5 This transfer can be observed), and the slide is then positioned to receive the sample obtained by the sample transfer device 40. The slide positioner can also be provided with at least two degrees of freedom of movement by the slide positioner motor 63 and various hinged arms, and is supported by the counterweight 64. The membrane of the filter 54 is pressed against the slide 50 to transfer the sample ( Figure 12 Afterwards, the slide positioner moves and rotates the slide 50 by 90 degrees and approaches the open container of the fixative 58 placed in the fixative container holder 61. The slide positioner 56 is configured to grasp and move the slide 50. For this purpose, as... Figure 5As shown, the slide positioner 56 includes a pneumatically controlled gripper 59 configured to grasp the slide piece 50 and thereby remove it from the loading platform 46. The slide positioner 56 then moves the slide piece to a transfer position where the sample transfer device 40 can transfer a sample from the filter 54 to the slide 50, as... Figure 11 As shown, the sample is then moved to a fixed position where the analyzer 50 can place the slide 50 into a fixative container 58 containing fixative to fix the sample onto the slide 50. The system 10 includes a fixative container holder 61.

[0069] refer to Figure 17 System 10 also includes one or more processors, collectively referred to as controller 60 located in the rear panel of the cabinet. Controller 60 is operatively coupled to and configured to communicate with and control the automated operation of various components of system 10, including tool head 30, tool head actuator 32, pipette 37, sample transfer device 40, first capping device 42, second capping device 44, slide positioner 56, and reader 31. Controller 60 includes a computer processor, input / output interface, and other electronics that support communication with and control the operation of system components. Controller 60 has a user input device for allowing a system operator to input commands, data, etc., into controller 60. The user input device may be a touch screen / display 62, as described below. Controller 60 also has system software for programming controller 60 to communicate with and control system 10 to perform procedures, as described herein, for preparing sample samples and / or aliquots from biological or other samples contained in sample container 12. In the illustrated embodiment, the touchscreen / display 62 is attached to the chassis and preferably integrated into the cabinet housing to allow the system operator to input commands (e.g., if prompted by system 10) and check the status of items performed during sample handling. The touchscreen / display 62 is configured to display graphics generated by the controller 60, including information about the operation of system 10, such as operating status, data, etc. The touchscreen / display 62 can be any suitable display, such as a liquid crystal display (LCD), an LED display, AMOLED, etc.

[0070] Now refer to Figures 1 to 14An exemplary sample processing procedure is described to further illustrate and describe various elements and components of system 10. Specifically, the exemplary sample processing includes first obtaining aliquots of the sample and then processing the sample to create a biological sample slide. This procedure is described for illustrative purposes and not for limitation, and it should be understood that other types of sample processing can be performed using the disclosed and described system and its variations, while still remaining within the scope of this disclosure. By way of example and not limitation, each method of processing samples contained in a sample container using an automated system as set forth in the appended claims should be considered as an additional exemplary sample processing procedure that can be performed using the illustrated system 10.

[0071] To begin processing a given patient sample container 12, the system operator enters the same command, for example, via a "Start" button or similar symbol on the user interface 62. The system controller 60 positions the tool head 30 in a "start" position (if the tool head 30 is not already in this position), where the tool head 30 is positioned and rotated within the cabinet 11 to position the reader 31 in a convenient location for the system operator to present the sample vial 12, such as... Figure 4 As shown.

[0072] After receiving visual confirmation from the system controller 60 on the user interface display 62, the system operator provides the sample container 12 to the reader 31, ensuring that the patient and / or other markings on the sample container 12 are within the reader 31's field of view. The reader 31 reads the markings on the sample container 12 and transmits them (via the controller 60) to the corresponding slide printer 13 and aliquot container printer 19. The slide printer automatically prints and outputs new (i.e., unused) slides 50, on which markings matching or otherwise corresponding to the markings on the sample container 12 are printed. The system operator also inserts new (i.e., unused) aliquot containers 20 into the aliquot container printer, which prints markings on the aliquot containers 20 that also match or correspond to the markings on the sample container 12.

[0073] If an additional pipette tip 48 must be added, the pipette tip dispenser carrier 22 moves to the loading position. Figure 2The sample container 12, aliquot container 20, slide 50, and pipette tip dispenser 26 are exposed. The loading of the sample container 12, aliquot container 20, slide 50, and pipette tip dispenser 26 into system 10 can be automated using a robot, or it can be performed manually by the system operator – the latter is assumed for simplicity in this example. Specifically, the system operator then loads the (capped) sample container 12 into sample container holder 16 and the (capped) aliquot container 20 into aliquot container holder 18, both after the reader 31 has read and confirmed that the individual sample and aliquot container markings match. The system operator loads the slide 50 onto slide platform 46 with the face-down orientation, i.e., the side of the slide with the printed markings and "cell point" area to receive the sample is facing down towards platform 46. The system operator loads the new filter 54 onto the working end of the sample transfer device 40, confirms that there are at least one sufficient number of unused pipette tips 48 in the pipette tip dispenser 26, and confirms that the pipette tip waste container 25 is empty. Once all consumables are loaded, the system operator closes the door 15 of the cabinet 11 and indicates via the user interface that the sample processing procedure can begin, assuming all system validations are complete.

[0074] It is worth noting that system 10 will not initiate the sample processing procedure unless sensor 35 indicates that a sufficient number of pipette tips 48 are in dispenser 26, even if this means only one, and that pipette tip dispenser 26 and waste container 25 are properly positioned and magnetically coupled to their respective mounting platforms 24 and 27 on pipette tip dispenser carrier 22. Sample transfer device 40 performs a “dry” test to verify the integrity of filter 54, specifically to confirm that the distal membrane has not been punctured (indicating that filter 54 has been previously used) or otherwise blocked or torn. It is worth noting that once sufficient pipette tips 48 are confirmed to be present, the pipette tip dispenser carrier is moved by the system so that the pipette tip dispenser is located in isolation chamber 28. From that point until the sample processing procedure is completed, no further system operator intervention is typically required.

[0075] like Figures 4 to 6 As shown, at the start of the sample processing, the pipette tip dispenser carrier 22 moves the pipette tip dispenser to its storage location in the separation chamber 28. Figure 3The tool head 30 is then slightly turned upwards and linearly translated upwards, allowing the slide 50 to be gripped by the holder 59 of the slide holder 57. The tool head 30 then linearly translates downwards and rotates, allowing the reader 31 to read the markings on the side 50 to confirm that the markings match the markings on the corresponding sample container 12 and aliquot container 20. Assuming the match is verified, the system 10 continues with an automated procedure to prepare the sample and aliquots, wherein each component of the system 10 is operated and controlled by the controller 60.

[0076] like Figure 6 As shown, the tool head 30 is rotated and moved vertically downward by the tool head actuator 34 to position the sample container capping device 42 above the cap 43 on the sample container 42 and above the second cap 45 on the dividing container capping device 44 on the dividing container 20. In coordination with the rotation of the respective container holders 156 and 18, the individual capping devices 42 and 44 remove and hold the caps 43 and 45.

[0077] like Figure 7 As shown, the pipette tip dispenser carrier 22 moves to the loading position to position the pipette tip 48 contained in the pipette tip dispenser 26 onto the pipette tip coupling 38 of the pipette 37. Similarly, as... Figure 7 As shown, the tool head 30 rotates to position the pipette tip engagement 38, and the pipette tip 48 is installed by pushing the pipette tip engagement into the pipette tip 48 via the corresponding rotation and translation of the tool head 30.

[0078] like Figure 8 As shown, the pipette tip dispenser carrier 22 is moved back to the storage position. The tool head 30 rotates and moves vertically to place the pipette tip 48 on the pipette 37 into the sample in the sample container 12. The pipette 37 is evacuated inside the pipette tip 48 to draw a certain volume of sample (amplified sample) into the pipette tip 48.

[0079] like Figure 9 As shown, the tool head 30 rotates and translates vertically to position the pipette tip 48 in the aliquot container 20. The pipette 37 releases the vacuum to dispense the aliquot sample from the pipette tip 48 and into the aliquot container 20. After the aliquot sample has been dispensed into the aliquot container 20, the tool head 30 is rotated and translated to position the aliquot container capping device 44 to reinstall the cap 45 onto the aliquot container 20 (with...). Figure 6 (The same location shown).

[0080] like Figure 10 As shown, the tool head 30 is rotated and translated to position the pipette tip 48 above or inside the waste container 25. The pipette tip engagement 38 then detaches (discharges) the used pipette tip 48 into the waste container 25.

[0081] like Figure 11 As shown, the tool head 30 is rotated and translated to position the filter 54 mounted on the sample transfer device 40 in place to collect the sample from the sample container 20 onto the filter membrane according to the procedure described above. That is, the sample is forced back and forth through the membrane by a cyclic vacuum and / or by moving the filter up and down (e.g., by moving the tool head 30 via the tool head actuator 34). This procedure allows for the collection of thin or monolayer cells onto the membrane.

[0082] like Figure 12 As shown, the tool head 30 is rotated and translated to position the filter membrane to transfer the sample onto the slide 50 held by the gripper 59 of the slide holding device 57. The sample transfer device 40 and / or the slide positioner 56 are then manipulated to bring the membrane with the sample onto the slide 50. The tool head 30 can be moved via the tool head actuator 34 to manipulate the sample transfer device 40. To provide transfer of the sample (e.g., a thin layer of cells) to the slide 50 without disturbing its spatial distribution, it is desirable that the membrane of the filter 54 initially contacts the slide 50 at approximately a single location, forming a predetermined small pre-contact angle between the membrane and the deposition surface of the slide 50, and then gradually and smoothly make full contact with the slide 50. This can be accomplished by coordinating the manipulation of the sample transfer device 40 and the slide positioner 56.

[0083] like Figure 13 As shown, the tool head 30 moves downward and can also rotate to provide space for the slide positioner 56 to place the slide 50 with the sample on it into the fixative container 58 containing the fixative, thereby securing the sample onto the slide 50. After transferring the sample to the slide 50, the tool head 30 translates and / or rotates to drive the filter membrane to the pin 41 (…). Figure 4 This involves damaging the filter membrane to prevent reuse. For example... Figure 13 As shown, the actuated slide positioner 56 places the slide 50 with the sample on it into the fixative container 58. Once the sample processing is complete, the system operator can remove the sample slide 50 from the fixative solution in container 58 or remove the fixative container, including the sample slide 50, and replace (or place a new) fixative container 58 in the holder 61 before starting a new sample processing procedure.

[0084] The tool head 30 rotates and moves downward to position the sample container capping device 42 so that the cap 43 can be reinstalled onto the sample container 12 (with...). Figure 4 (The same location shown).

[0085] This completes the automated process for preparing and aliquoting samples. The sample slides 56, fixed with a fixative, can then be removed from the fixative container 58 and used for analysis. Sample containers 12 and aliquot containers 20 can also be removed from system 10 and properly stored. Waste container 25 is removed from system 10 and emptied into the waste bin to dispose of used pipette tips 48. Waste container 25 can then be returned to the waste container platform 27.

[0086] The procedure can be repeated as needed for more sample containers containing individual samples.

[0087] While specific embodiments have been shown and described, it should be understood that the above description is not intended to limit the scope of these embodiments. Although many variations of the embodiments disclosed herein have been disclosed and described, it should be understood that the foregoing disclosure is for illustrative purposes only, and various changes and modifications can be made to the disclosed embodiments without departing from the scope of the appended claims. For example, not all components depicted and described in the embodiments are essential, and alternative embodiments may include any suitable combination of components, and the general shape and relative dimensions of the components may be modified.

Claims

1. A method using an automated system for processing biological samples, the system comprising: Sample container holder; Analyze the component holder; An automated tool head is configured to rotate about a first axis and translate along a second axis different from the first axis. A sample container sealing device is located at a first position on the tool head; And a sample transfer device, disposed at a second position on the tool head different from the first position, the method comprising: The sample container is placed in the sample container holder, the sample container containing the biological sample suspended in a sample fluid; The sample container capping device is positioned near the sample container by one or both of the automatic rotation of the tool head around the first axis and the automatic translation of the tool head along the second axis. Operate the sample container sealing device to clamp the sample container cap on the sample container; One of the sample container holder and the sample container capping device is rotated relative to the other of the sample container holder and the sample container capping device in a first direction between a clockwise rotation direction and a counterclockwise rotation direction, thereby removing the sample container cap from the sample container; After the sample container cap is removed from the sample container, the working end of the sample transfer device is positioned inside the sample container by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis. The sample transfer device has a filter comprising a tubular body and a porous membrane end. The tubular body forms a seal with the working end of the sample transfer device, and the porous membrane end is configured to allow liquid to pass through it while retaining the sample on the outer surface of the porous membrane end. Operate the sample transfer device to obtain a sample of the biological sample contained in the sample container on the outer surface of the end of the porous membrane; After obtaining the sample, the working end of the sample transfer device is repositioned near the analytical element held by the analytical element holder by one or both of the automatic rotation of the tool head around the first axis and the automatic translation of the tool head along the second axis; and Operate the sample transfer device to cooperate with the analytical element holder to transfer the sample from the sample transfer device to the analytical element.

2. The method according to claim 1, further comprising: After the sample is obtained from the sample container, and when the removed sample container cap is held by the sample container capping device, the sample container capping device is positioned near the sample container by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis. as well as One of the sample container holder and the sample container capping device is rotated relative to the other of the sample container holder and the sample container capping device in the opposite direction of clockwise and counterclockwise rotation, thereby reinstalling the sample container cap onto the sample container.

3. The method according to claim 1, further comprising a pipette tip dispenser and a pipette, the pipette being disposed at a third position on the tool head different from the first position and the second position, the method further comprising: The pipette tip assembly of the pipette is positioned to engage with the pipette tip on the pipette tip dispenser by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis.

4. The method according to claim 3, further comprising a container divider holder and a container divider capping device, the container divider capping device being disposed at a fourth position on the tool head, different from the first position, the second position, and the third position, and the method further comprising: Place the equal-dividing container in the equal-dividing container holder; The equal-dividing container sealing device is positioned near the equal-dividing container by one or both of the automatic rotation of the tool head around the first axis and the automatic translation of the tool head along the second axis. Operate the equal-dividing container sealing device to clamp the equal-dividing container lid on the equal-dividing container; and The equal container holder and the equal container capping device are rotated relative to the other in a first direction between clockwise and counterclockwise rotation, thereby removing the equal container cap from the equal container.

5. The method according to claim 4, further comprising: When the removed sample container cap is held by the sample container capping device and the removed aliquot container cap is held by the aliquot container capping device, the pipette tip engagement of the pipette is positioned by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis, thereby positioning the engaged pipette tip inside the sample container. Operate the pipette to obtain an equal aliquot of sample fluid from the sample container within the engaged pipette tip; After obtaining equal portions of the sample fluid, the pipette tip assembly is repositioned by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis, thereby repositioning the engaged pipette tip inside the dispensing container. as well as Operate the pipette to dispense equal portions of the sample fluid into the dispensing containers.

6. The method according to claim 5, further comprising: After the sample fluid is equally distributed into the equalizing containers, and while the removed equalizing container caps are held by the equalizing container capping device, the equalizing container capping device is positioned near the equalizing containers by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis. Rotate one of the equal-dividing container holder and the equal-dividing container capping device relative to the other of the equal-dividing container holder and the equal-dividing container capping device in the opposite direction of clockwise and counterclockwise rotation, thereby reinstalling the equal-dividing container cap onto the equal-dividing container.

7. The method according to claim 4, wherein, The first position on the tool head is angularly spaced from the second position around the first axis, and the fourth position on the tool head is aligned with the first position along the second axis.

8. The method according to claim 3, wherein, The pipette tip dispenser is mounted on an automated pipette tip dispenser carrier, and the method further includes: The pipette tip dispenser carrier is translated such that the pipette tip dispenser is translated relative to the tool head, such that the pipette tip in the pipette tip dispenser is positioned at the location where the tool head positions the pipette tip coupling to engage the pipette tip; and After the pipette tip engagement is performed, the pipette tip dispenser carrier is translated, thereby translating the pipette tip dispenser relative to the tool tip, so that the pipette tip dispenser is positioned in a room that is substantially isolated from the tool tip in the environment.

9. The method of claim 8, further comprising a pipette tip waste container mounted on the pipette tip dispenser carrier, the method further comprising: The pipette tip dispenser carrier is translated to move the pipette tip waste container to a position near the pipette tip assembly; The pipette tip assembly is positioned by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis, thereby positioning the engaged pipette tip above the pipette tip waste container. Operate the pipette to release the engaged pipette tip from the pipette tip connector into the pipette tip waste container. The pipette tip waste container is mounted on the pipette tip dispenser carrier relative to the pipette tip dispenser, such that when the pipette tip waste container is translated to the position where the tool head positions the pipette tip assembly to release the pipette tip into the pipette tip waste container, the pipette tip dispenser simultaneously translates into the chamber.

10. The method according to claim 1, wherein, The analytical element includes a glass slide, and the analytical element holder includes a controllable clamp that engages the glass slide; the method further includes: After the sample is transferred to the slide, the controllable holder is automatically repositioned above the output container containing the fixative. Operate the controllable gripper to release the glass slide into the output container.

11. A method using an automated system for processing biological samples, the system comprising: Sample container holder; Slide holder, for attaching glass slides; An automated tool head is configured to rotate about a first axis and translate along a second axis different from the first axis. A sample container sealing device is disposed at a first circumferential position on the tool head; and a sample transfer device is disposed at a second circumferential position on the tool head, which is angularly spaced from the first circumferential position around the first axis. The method includes: The sample container is placed in the sample container holder, the sample container containing the biological sample suspended in a sample fluid; The sample container capping device is positioned near the sample container by one or both of the automatic rotation of the tool head around the first axis and the automatic translation of the tool head along the second axis. Operate the sample container sealing device to clamp the sample container cap on the sample container; One of the sample container holder and the sample container capping device is rotated relative to the other of the sample container holder and the sample container capping device in a first direction between a clockwise rotation direction and a counterclockwise rotation direction, thereby removing the sample container cap from the sample container; After the sample container cap is removed from the sample container, the working end of the sample transfer device is positioned inside the sample container by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis. The sample transfer device has a filter comprising a tubular body and a porous membrane end. The tubular body forms a seal with the working end of the sample transfer device, and the porous membrane end is configured to allow liquid to pass through it while retaining the sample on the outer surface of the porous membrane end. Operate the sample transfer device to obtain a sample of the biological sample contained in the sample container on the outer surface of the end of the porous membrane; The sample is transferred from the sample transfer device to the glass slide; After the sample is obtained from the sample container, and while the removed sample container cap is held by the sample container capping device, the sample container capping device is positioned near the sample container by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis; and One of the sample container holder and the sample container capping device is rotated relative to the other of the sample container holder and the sample container capping device in the opposite direction of clockwise and counterclockwise rotation, thereby reinstalling the sample container cap onto the sample container.

12. The method of claim 11, wherein the slide holder comprises a controllable clamp for engaging the slide, and the method further comprises: After the sample is transferred to the slide, the controllable holder is automatically repositioned above the output container containing the fixative. Operate the controllable gripper to release the glass slide into the output container.

13. The method according to claim 11, further comprising: Verify the integrity of the filter membrane before positioning the working end of the sample transfer device into the sample container.

14. The method according to claim 13, further comprising: After the sample is transferred to a glass slide, the working end of the sample transfer device with the filter is pressed against the object to disrupt the integrity of the filter membrane.

15. The method of claim 11, further comprising a reader carried on the tool head, the method further comprising: Use the reader to read the patient markings on the slide; Use the reader to read the patient label on the sample container; Verify that the patient marking on the slide corresponds to the patient marking on the sample container.

16. A method using an automated system for processing biological samples, the system comprising: Sample container holder; Equal-division container holder; A pipette tip dispenser, mounted on an automated pipette tip dispenser carrier; An automated tool head is configured to rotate about a first axis and translate along a second axis different from the first axis. A sample container sealing device is disposed at a first position on the tool head; a dividing container sealing device is disposed at a second position on the tool head, different from the first position. The method includes: and a pipette, disposed at a third position on the tool head, different from the first and second positions; The sample container is placed in the sample container holder, the sample container containing the biological sample suspended in a sample fluid; Place the equal-dividing container in the equal-dividing container holder; The sample container capping device is positioned near the sample container by one or both of the automatic rotation of the tool head around the first axis and the automatic translation of the tool head along the second axis. Operate the sample container sealing device to clamp the sample container cap on the sample container; One of the sample container holder and the sample container capping device is rotated relative to the other of the sample container holder and the sample container capping device in a first direction between a clockwise rotation direction and a counterclockwise rotation direction, thereby removing the sample container cap from the sample container; The pipette tip dispenser carrier is translated such that the pipette tip dispenser is translated relative to the tool head, such that the pipette tip in the pipette tip dispenser is positioned at the location where the tool head positions the pipette tip coupling to engage the pipette tip; and The pipette tip engagement of the pipette is positioned by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis, so as to engage the pipette tip from the pipette tip dispenser. After the pipette tip engagement is performed, the pipette tip dispenser carrier is translated, thereby translating the pipette tip dispenser relative to the tool tip, so that the pipette tip dispenser is positioned in a room that is substantially isolated from the tool tip in the environment. After removing the sample container cap from the sample container and engaging the pipette tip to the pipette tip engagement, the dispensing container capping device is positioned near the dispensing container by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis. Operate the equal-dividing container sealing device to clamp the equal-dividing container lid on the equal-dividing container; and One of the equal-dividing container holder and the equal-dividing container capping device is rotated relative to the other of the equal-dividing container holder and the equal-dividing container capping device in a first direction between a clockwise rotation direction and a counterclockwise rotation direction, thereby removing the equal-dividing container cap from the equal-dividing container; When the removed sample container cap is held by the sample container capping device and the removed aliquot container cap is held by the aliquot container capping device, the pipette tip engagement of the pipette is positioned by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis, thereby positioning the engaged pipette tip inside the sample container. Operate the pipette to obtain an equal aliquot of sample fluid from the sample container within the engaged pipette tip; After obtaining equal portions of the sample fluid, the pipette tip assembly is repositioned by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis, thereby repositioning the engaged pipette tip inside the dispensing container; and Operate the pipette to dispense equal portions of the sample fluid into the dispensing containers.

17. The method according to claim 16, further comprising: After the sample fluid is divided into equal portions from the sample container, and when the removed sample container cap is held by the sample container capping device, the sample container capping device is positioned near the sample container by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis. as well as One of the sample container holder and the sample container capping device is rotated relative to the other of the sample container holder and the sample container capping device in the opposite direction of clockwise and counterclockwise rotation, thereby reinstalling the sample container cap onto the sample container.

18. The method according to claim 16, further comprising: After the sample fluid is equally distributed into the equalizing containers, and while the removed equalizing container caps are held by the equalizing container capping device, the equalizing container capping device is positioned near the equalizing containers by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis. One of the equal-dividing container holder and the equal-dividing container capping device is rotated relative to the other of the equal-dividing container holder and the equal-dividing container capping device in the opposite direction of clockwise and counterclockwise rotation, thereby reinstalling the equal-dividing container cap onto the equal-dividing container.

19. The method of claim 16, wherein, The first position on the tool head is angularly spaced from the third position around the first axis, and wherein the second position on the tool head is aligned with the first position along the second axis of the tool head.

20. The method of claim 16, further comprising a pipette tip waste container mounted on the pipette tip dispenser carrier, the method further comprising: The pipette tip dispenser carrier is translated to move the pipette tip waste container to a position near the pipette tip assembly; The pipette tip assembly is positioned by one or both of the automatic rotation of the tool head about the first axis and the automatic translation of the tool head along the second axis, thereby positioning the engaged pipette tip above the pipette tip waste container. Operate the pipette to release the engaged pipette tip from the pipette tip connector into the pipette tip waste container. The pipette tip waste container is mounted on the pipette tip dispenser carrier relative to the pipette tip dispenser, such that when the pipette tip waste container is translated to the position where the tool head positions the pipette tip assembly to release the pipette tip into the pipette tip waste container, the pipette tip dispenser simultaneously translates into the chamber.

Images