HK40076921A - Systems and methods for automated preparation of biological specimens - Google Patents

Description

System and method for automatically preparing biological sample

The present application is a divisional application of an invention patent application having an application date of 2018, 3 and 9, and a chinese application number of 201880016720.3 (international application number of PCT/US 2018/021879), entitled "system and method for automatically preparing biological samples", the entire contents of which are incorporated herein by reference.

Technical Field

The present disclosure relates generally to the preparation of biological samples, and in particular to automated systems and methods for collecting biological samples from liquid sample containers and dispensing the samples onto analytical elements such as sample slides, as well as for obtaining sample aliquots for additional testing.

Background

Cytology is a branch of biology dealing with the study of cell formation, structure, and function. When used in a laboratory setting, cytologists, cytotechnologists, and other medical professionals make medical diagnoses of a patient's condition based on visual inspection of a patient's cell sample. One typical cytological technique is the "cervical smear" test, in which cells are scraped from a woman's cervix and analyzed to detect the presence of abnormal cells (precursors to cervical cancer onset). Cytological techniques have also been used to detect abnormal cells and diseases in other parts of the human body.

Cytological techniques are widely used because collecting a cell sample for analysis is generally less invasive than traditional surgical pathology procedures (e.g., biopsy) which use a dedicated biopsy needle with a spring-loaded movable probe or fixed cannula or the like to excise a solid tissue sample from a patient. Cell samples can be obtained from a patient by a variety of techniques, including, for example, scraping or swabbing an area, or aspirating bodily fluids from the chest, bladder, spinal canal, or other suitable area with a needle. The cell sample obtained is typically placed in a preservative solution, then extracted from the solution and transferred to a slide. Fixative is applied to the cell sample to ensure that the cells are fixed on the slide for subsequent staining and examination.

It is generally desirable that the cells on the slide have an appropriate spatial distribution so that individual cells can be examined. A monolayer of cells is often desirable. Thus, preparing a specimen from a liquid sample containing many (e.g., tens of thousands) of cells typically requires first separating the cells from each other by mechanical dispersion, liquid shearing, or other techniques in order to collect and deposit a thin monolayer of cells on a slide. In this way, the cytotechnologist can more easily discern whether there are any abnormal cells in the patient sample. The number of cells can also be counted to ensure that a sufficient number of cells have been evaluated.

Methods and apparatus for generating a thin monolayer of cells from a liquid sample container and transferring the thin layer to a "sample slide" for visual inspection are disclosed in U.S. Pat. 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 in a sample container is used to disperse patient cells in a preservative fluid in the sample container. A controlled vacuum is applied to the sample collector to draw the liquid through its screen filter until the desired amount and spatial distribution of cells is collected on the filter. Thereafter, the sample collector is removed from the sample container and the filter portion is pressed against the slide to transfer the collected cells onto the slide in a spatial distribution that is substantially the same as the collected spatial distribution. Devices made in accordance with the teachings of one or more of these patents are commercially successful, for example2000 processor (processing one sample slide at a time from a patient sampleSheet) and5000 processors (processing specimen slides from patient sample batches) manufactured and sold by Hologic corporation of Marlbert, mass., USA. Further reference is made to U.S. Pat. nos. 7,556,777 and 7,771,662, the disclosures of which are incorporated herein by reference in their entirety.

Once the specimen slides are prepared, the specimens can be visually inspected by a cytotechnologist, typically under magnification, with or without various illumination sources. Additionally or alternatively, an automated slide imaging system is used to assist in the cytological examination procedure. For example, an automated slide imaging system may take images of all or substantially all of the cells captured on a slide and perform a preliminary assessment of the cells using image processing techniques in order to guide a cytotechnologist to potentially the most relevant cells on the slide for review. Examples of such imaging systems are disclosed in U.S. Pat. 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 the actual specimen is examined under magnification or the magnified image of the specimen, the specimen is typically classified by cell technicians as "normal" or "abnormal," where abnormal specimens typically fall into one of the major categories defined by the Bethesda advisory system of cervical/vaginal cytology diagnosis, including low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), squamous cell carcinomas, adenocarcinomas, atypical glandular cells of unknown significance (AGUS), adenocarcinoma In Situ (AIS), and Atypical Squamous Cells (ASC). More information about the classification of cell samples is widely available.

It may be desirable to perform other types of diagnostic tests on the same patient sample, for example for Human Papilloma Virus (HPV). Based on the strong correlation between HPV and cervical cancer, it has been suggested to classify HPV DNA detection as a smear result as a hierarchical detection (triage test) of patients of ASC-US. Where a liquid-based smear has been performed, the same sample used to perform the smear analysis can conveniently be used to perform a "reflexive" HPV DNA test, thus eliminating the need for repeated visits and a second smear check. For example, if a sample is classified as ASC-US positive, an "aliquot" (e.g., 4 mL) of the liquid sample may be removed from the stored vial and sent to a molecular diagnostic laboratory for HPV DNA detection.

Importantly, laboratories performing HPV DNA testing are bored by molecular contamination, a well-known problem in molecular diagnostic laboratories. Thus, due to the risk of cross-contamination, molecular diagnostic laboratories may not accept aliquots taken from processed liquid smears because of concerns about unwanted production of HPV false positives. Therefore, it is desirable to obtain and store an aliquot of each patient sample prior to the specimen slide manufacturing procedure to retain portions of the sample from cross-contamination. For example, some methods and apparatus for obtaining aliquots of patient samples prior to a specimen slide manufacturing procedure are disclosed in U.S. Pat. nos. 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 together with making specimen slides) are disclosed in U.S. patent No. 9,335,336 and U.S. patent publication No. 2017/0052205, the disclosures of which are incorporated herein by reference in their entirety.

In addition to being used for HPV DNA detection, aliquots of liquid smear samples may also be used for DNA detection of other sexually transmitted diseases, such as Chlamydia trachomatis and Neisseria gonorrhoeae. However, false positives are a particular problem in the detection of chlamydia trachomatis and neisseria gonorrhoeae, as they may have a tremendous domestic and social impact. Thus, molecular diagnostic laboratories are less likely to accept aliquots of processed liquid smear samples. The detection of other sexually transmitted diseases need not be used only for the detection of ASC-US samples. Indeed, such tests are intended to be performed at the request of the physician in parallel with the smear test, and aliquots can be removed from the smear sample prior to processing, for example by manually pipetting aliquots in vials, thereby minimizing the risk of cross-contamination. However, this step may still not meet the stringent contamination prevention requirements of molecular diagnostic laboratories.

In addition to contamination issues, aspiration of aliquots from liquid smear samples, whether done before or after liquid smear sample processing, and whether done for HPV detection or any other sexually transmitted disease detection, increases the cost of physical labor, which involves not only pipetting aliquots into additional vials, but also labeling of vials.

There is therefore a need to provide improved apparatus and methods for obtaining aliquots from liquid-based biological samples (e.g., cervical smear samples) while minimizing the risk of cross-contamination.

Disclosure of Invention

Embodiments of the present disclosure pertain to improved automated systems and methods for processing samples (such as biological samples) contained in sample containers.

In an embodiment, an automated system for processing a sample contained in a liquid sample container includes a sample container holder configured to hold a 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 including 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 and then transfer the obtained sample to an analysis element (e.g., a slide) held by the analysis element holder, respectively, by one or both of rotation of the tool head about the first axis and translation of the tool head along the second axis. Without limitation, the working end of the sample transfer device may be configured to receive a filter thereon, the filter comprising a tubular body forming a seal with the working end of the sample transfer device, and a porous membrane end configured to allow liquid to pass therethrough while retaining cellular material on an outer surface thereof.

The system can further comprise an analysis element positioner comprising an analysis element holder, wherein the analysis element holder is configured to releasably grasp the analysis element. The analytical element positioner may be configured to automatically place the analytical element carried by the analytical element positioner into the fixative container held by the fixative container holder after the sample has been transferred to the analytical element. The system may include an analytical element (e.g., slide) loading platform located on a surface of the tool head, wherein the analytical element positioner is in operative cooperation with the tool head such that the analytical element holder automatically engages and removes an analytical element placed on the loading platform, and wherein the analytical element positioner is in operative cooperation with the tool head to automatically position the engaged analytical element proximate a working end of the sample transfer device to transfer a sample to the engaged analytical element.

The system may further comprise a sample container capping device disposed on the tool head and configured to controllably grip and release a cap of a sample container held in the sample container holder, wherein the tool head is configured to automatically position the sample container capping device in proximity to the sample container cap 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 wherein the sample container capping device is operable to cooperate 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 rotational direction and a counterclockwise rotational direction when the sample container capping device engages the sample container lid to remove the sample container lid from the sample container, and wherein the sample container holder is configured to automatically rotate in the other of the clockwise rotational direction and the counterclockwise rotational direction when the sample container capping device engages the sample container lid to mount the sample container lid onto the sample container.

The system may further include a pipette tip dispenser and a tool tip carried pipette having a pipette tip engagement member configured to releasably engage a pipette tip, wherein the tool tip is configured to automatically position a pipette tip engagement member in proximity to the pipette tip dispenser by one or both of rotation of the tool tip about a first axis and translation of the tool tip along the second axis to allow the pipette tip engagement member to engage a pipette tip held by the pipette tip dispenser. Non-limiting, 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 may be selectively translated to a position at which the tool head positions the pipette tip engagement member 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 tip positions the pipette tip engagement member to engage a pipette tip from the pipette tip dispenser and a second position within the isolation chamber. The pipette tip waste barrel may be mounted on a pipette tip dispenser carrier, wherein the pipette tip dispenser carrier is configured to selectively translate the pipette tip waste barrel to a position at which the tool tip positions the pipette tip engagement member to disengage the pipette tip into the pipette tip waste barrel. For example, a pipette tip waste bucket may be mounted on a pipette tip carrier relative to a pipette tip dispenser such that when the pipette tip waste bucket is moved into a position where a tool tip positions the pipette tip engagement member to disengage the pipette tip from the pipette tip waste bucket, the pipette tip dispenser is simultaneously translated into an isolation chamber.

In embodiments comprising a pipette, the system may further comprise a replenishment receptacle holder configured for holding a replenishment receptacle, wherein the tool head is configured to automatically position the pipette tip engagement member into a position in which a pipette tip engaged on the pipette tip is inserted into a sample receptacle held in the sample receptacle holder, and into a position in which an engaged pipette tip is inserted into a replenishment receptacle held in the replenishment receptacle holder, respectively, 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 replenishment receptacle may be an aliquot receptacle wherein, when the tool tip and pipette are operatively mated to automatically engage the pipette tip engagement member with a pipette tip from the pipette tip dispenser, an aliquot of the sample is withdrawn from the sample container held in the sample container holder using the engaged pipette tip, respectively, and the obtained sample aliquot is dispensed into the aliquot receptacle. Alternatively, and without limitation, the supplemental container may be a reagent container containing a reagent, and wherein when the tool tip and the pipette are operatively cooperative to automatically engage the pipette tip engagement member with the pipette tip of the pipette tip dispenser, an aliquot of the reagent is withdrawn from the reagent container and dispensed into a sample container contained in the sample container holder using the engaged pipette tip, respectively.

A refill container closure device may be disposed on the tool head and configured to controllably grip and release a lid of a refill container held in the 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 the first axis and translation of the tool head along the second axis, and wherein the refill container closure device is operable to cooperate with the refill container holder to remove or install a refill container lid. For example, the refill container holder may be configured to automatically rotate in one of a clockwise rotational direction and a counterclockwise rotational direction when the refill container capping device engages the refill container cap so as to remove the refill container cap from the refill container closure, and wherein the refill container holder is configured to automatically rotate in the other of the clockwise rotational direction and the counterclockwise rotational direction when the refill container capping device engages the refill container cap so as to mount the refill container cap onto the refill container. In some embodiments that include both a sample container capping device and a refill container capping device, the two capping devices may be offset from each other on the tool head such that when the sample container capping device is in a position to grip and remove a sample container lid, the refill container capping device is in a position to grip and remove a refill container lid without further rotational movement of the tool head.

The system may further comprise an analytical element loading platform located on a surface of the tool head, wherein the analytical element positioner is in operative cooperation with the tool head such that the analytical element positioner automatically engages and removes an analytical element placed on the tool head, and wherein the analytical element positioner is in operative cooperation with the tool head to automatically position the engaged analytical element proximate to the working end of the sample transfer device to transfer a sample to the engaged analytical element.

The system may further include a reader (e.g., a bar code reader or scanner) located on the tool head and configured to read sample container indicia located on any of the sample containers. The analytical element printer may be disposed in communication with the reader and configured to print analytical element indicia corresponding to the sample container indicia read by the reader onto the analytical element. The aliquot container printer may also be disposed in communication with the reader and configured to print an analytical element label corresponding to the sample container label read by the reader onto the aliquot container. In various embodiments, the reader is further configured to read indicia on other system components and consumables (such as on a carrier sheet or a filter used to obtain the sample specimen).

Embodiments of the system may include a controller for controlling operation of one or more of the tool tip, pipette, capping device, and analysis element positioner, the system further comprising a user interface operably coupled with the controller and configured for displaying system status and/or queries to a user and for receiving user input in response to the displayed system status and/or queries.

In an embodiment, an automated system for processing a sample contained in a liquid sample container includes a sample container holder for holding a sample container, an automated tool tip 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 tip, the pipette having a pipette tip engagement member configured to releasably engage a pipette tip, wherein the tool tip is configured to automatically position the pipette tip engagement member proximate the pipette tip dispenser to engage a pipette tip held by the pipette tip dispenser by one or both of rotation of the tool tip about the first axis and translation of the tool tip along the second axis, wherein the pipette tip is mounted on a pipette tip dispenser carrier configured to translate the pipette tip dispenser relative to the tool tip to selectively displace the tip dispenser to a position at which the tool tip positions the 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 tip positions the pipette tip engagement member to engage a pipette tip from the pipette tip dispenser and a second position within the isolation chamber.

In yet another embodiment, an automated system for processing a sample contained in a liquid sample container includes a sample container holder for holding a sample container, an automated tool tip 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 tip, the pipette having a pipette tip engagement member configured to releasably engage a pipette tip, wherein the tool tip is configured to automatically position the pipette tip engagement member proximate the pipette tip dispenser to engage a pipette tip held by the pipette tip dispenser by one or both of rotation of the tool tip about the first axis and translation of the tool tip along the second axis, and a supplemental container holder configured to hold a supplemental container, wherein the tool tip is configured to automatically position the pipette tip engagement member in a position in which the engaged pipette tip is inserted into a sample container held in the sample container holder and to position a position in which the engaged pipette tip is inserted into a supplemental container held in the supplemental container holder by one or both of rotation of the tool tip about the first axis and translation of the tool tip along the second axis, respectively. Without limitation, the replenishment container may be one of a reagent container and an aliquot container.

In yet another embodiment, an automated system for processing a sample contained in a liquid sample container includes a sample container holder for holding a sample container, a refill container holder configured to hold a refill 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 grip and release a cap of the sample container held in the sample container holder, and wherein the tool head is configured to automatically position the first capping device in proximity to the sample container cap 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 wherein the first capping device is in operative cooperation with the sample container holder to remove or install the sample container cap, and a second capping device disposed on the tool head and configured to controllably grip and release a cap of a refill container held in the refill container holder, and wherein the tool head is configured to automatically position the second capping device in proximity to remove or install the refill container cap 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 sample container holder may be configured to automatically rotate in one of a clockwise rotation direction and a counterclockwise rotation direction when the first closure device engages the sample container closure to remove the sample container lid from the sample container, and wherein the sample container holder is configured to automatically rotate in the other of the clockwise rotation direction and the counterclockwise rotation direction when the first closure device engages the sample container closure to mount the sample container closure onto the sample container. The refill container holder is configured to automatically rotate in one of a clockwise rotational direction and a counterclockwise rotational direction to remove the refill container lid from the refill container when the second capping device engages the refill container lid, and wherein the refill container holder is configured to automatically rotate in the other of the clockwise rotational direction and the counterclockwise rotational direction to install the refill container lid onto the refill container when the second capping device engages the refill container lid. The sample and supplemental cappers are offset from each other on the tool head such that when the sample capper is in a position to grasp and remove a sample container cap, the supplemental capper can grasp and remove a supplemental container cap without further rotational movement of the tool head. Without limitation, the replenishment container may be one of a reagent container and an aliquot container.

Other and further aspects and features of the disclosed embodiments will become apparent from a reading of the following detailed description in conjunction with the accompanying drawings.

Drawings

The foregoing and other aspects of embodiments of the present disclosure are explained in greater detail with reference to the drawings, wherein like reference numerals refer to like elements, and the description of like elements shall apply to all such embodiments when relevant, and wherein:

FIG. 1 is a right side front perspective view of an exemplary automated biological sample processing system including a sample processing cabinet, a slide printer, and an aliquot vessel printer, according to one embodiment;

FIG. 2 is a right front perspective view of the sample processing cabinet of FIG. 1 with the outer cabinet walls not shown to better show the system components located therein;

FIG. 3 is a left side front perspective view of the sample processing cabinet of FIG. 1, with exterior and partially interior walls and/or partitions not shown to better show the system components located therein;

FIGS. 4-14 are respective left, right, and front perspective views of system components of the sample processing cabinet of FIG. 1, illustrating various movements and operations performed by the system components during sample processing;

FIG. 15 is an elevational side view of the components carried by the rotary tool head within the sample processing cabinet of FIG. 1, with the tool cover not shown;

FIG. 16 is a perspective view of the bottom of the sample processing cabinet of FIG. 1 with a bottom cover plate removed to show system components; and

fig. 17 is a perspective view of the back of the sample processing cabinet of fig. 1 with a bottom cover plate removed to show system components.

Detailed Description

For illustrative purposes, the disclosed systems and methods of use shown herein and in the drawings relate to processing patient samples to produce conventional cytological specimen slides, and in connection with obtaining, it is to be understood that alternative embodiments may include 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 are to be considered within the scope of the disclosed embodiments and claims. In addition, the disclosed systems and methods may be used to process other types of liquid samples, including non-biological particles and liquids. Accordingly, it is to be understood that the disclosed and illustrated embodiments are for purposes of illustration and not limitation.

As used herein, terms such as "specimen", "specimen sample", "biological sample", "cytological specimen", "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 (aliquot)" and "aliquot sample" may be used interchangeably and should be similarly understood and interpreted. For example, but not by way of limitation, the systems and methods disclosed herein may be used to process biological samples contained in liquid sample containers to produce specimens or specimen samples, as well as aliquot or aliquots of samples. Furthermore, the term "aliquoting" should not be construed as limiting, as "aliquoting" is another way of expressing "a 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" and "patient vial," "tube," "refill container" and other arrangements may be used interchangeably and should be similarly understood and interpreted unless the context in which they are used requires a more specific meaning; for example, based on the contents of the container as stated.

The terms "automatic" and "automation" as used herein refer to the execution of a system, device, program, and/or function without the intervention of a user (e.g., a system operator), typically, but not necessarily, under the control of a programmed processor. In particular, the automated systems and methods disclosed herein advantageously reduce the number of manual steps required to prepare a biological sample, e.g., prepare a cytological specimen slide and/or obtain an aliquot of a patient sample for additional detection and/or additional sample processing (e.g., introduction of reagents into the sample prior to further processing).

Fig. 1 illustrates an exemplary automated biological sample processing system 10 that may be used to prepare cytological specimen slides and/or aliquots from a biological sample contained in a liquid sample container (e.g., obtained from a cervical smear). As will be explained in more detail below, the system 10 may be used for other types of sample processing, such as (but not limited to) for adding reagents to biological or other types of samples.

The system 10 generally includes a sample processing cabinet 11, a slide printer 13, and an aliquoting tube printer 19. In the illustrated embodiment, the major components of the system 10 are housed in (and/or attached to) a sample processing cabinet 11. As will be described in greater detail below, the slide printer 13 and the aliquot printer 15 are operatively coupled to the sample processing cabinet under the control of one or more processors disposed in the sample processing cabinet 11 via known wireless or wired communication links (not shown). For simplicity, the one or more processors are collectively referred to hereinafter as a "system controller 60" (described further below in connection with fig. 17) that controls automated movement and other operations of the components of the system 10 housed within the sample processing cabinet 11, as well as communication with the respective slide printer 13 and aliquot vial printer 19. For ease of illustration of the system 10, the components of the individual sample processing cabinets 11, slide printers 13, and aliquoting tube printers 19 are collectively referred to as a "system" 10, regardless of where particular components may be located. It should be understood that in alternative embodiments, the various components of the system 10 may be separately positioned or otherwise provided.

By way of example and not limitation, the system 10 may be configured to process sample containers, such as ThinSample bottles and e.g.Aliquoting container for vials, both of which are available from the american massaObtained from Hologic corporation of marberler, such as seine (www. Hologic. Com).

The sample processing cabinet 11 is preferably an environmentally closed housing (or "skin") to reduce possible contamination introduced 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 so as to be rotatable to open and close, 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 such that the system components housed in the sample processing cabinet 11 are visible when the front door 15 is in the closed position, but this is not necessary to practice the disclosed embodiments. Referring also briefly to fig. 16, a stabilizing foot 79, which may be made of a material that minimizes the vibratory motion of the cabinet, may be provided at each of the four corners of the bottom of the cabinet, which typically rests on a table top in a laboratory with four feet. In addition to providing greater stability, the foot 79 is preferably sized and configured to allow some clearance from the table top surface.

Slide Printer 13 can be any commercially available Slide Printer, such as the Signature Slide Printer (https:// www.printer. Com/Signature-Slide-Printer) available from Printer technology of Plymouth, minnesota, usa. The slide printer 13 is loaded with new slides and outputs the printed slides through an output slot 17 for receiving cytological specimens thereon as part of processing a corresponding patient specimen container. Specifically, the printer 13 prints indicia (e.g., a barcode) onto a portion of the slide (which is the side to which the cytological specimen is applied), where the printed indicia on the slide matches or otherwise corresponds to the indicia read on the sample container under treatment, as described in further detail below.

The aliquot vessel printer 19 is preferably the same as that taught in U.S. patent No. 9,724,948 (the' 948 patent), the disclosure of which is incorporated by reference herein in its entirety. As explained in the' 948 patent, the aliquot container printer 19 is provided with an opening 21 into which a new (unprinted) aliquot may be inserted. As explained in further detail below, the printer 19 prints indicia (e.g., a barcode) on the aliquot container that matches or otherwise corresponds to the indicia read on the sample container under processing. The printed container is then fed out of the opening 21 or otherwise may be removed from the opening 21 in other ways.

Fig. 2 and 3 depict components of the system 10 disposed within or otherwise attached to a sample processing cabinet 11, with cabinet walls removed for ease of illustration. The cabinet 11 includes a chassis 14 that may include a plurality of floors, walls and/or supports that provide the primary support structure to which the various system components are mounted/mounted.

As best seen in fig. 3, a cylindrical sample vessel holder 16 is disposed in a lower central portion of the base 14. As will be described in greater detail below, the sample container holder 16 is fixedly mounted on a rotating platform configured to rotate the sample containers 12 (shown in fig. 4) held in the sample container holder 16 about the central z-axis of the containers 12 to mix the sample to achieve a substantially uniform dispersion of cells or other particular materials contained in the sample containers 12 prior to beginning processing and also to facilitate uncapping and recapping of the containers 12 during processing. In the illustrated embodiment, the sample container holder 16 is a cylindrical container configured to snugly receive and hold the sample container 12. The sample container holder 16 has an outer wall that extends to a height less than the height of the sample container 12 such that the lid 43 on the sample container 12 held in the sample container holder 16 is fully exposed to facilitate its respective mixing, uncapping, and capping. In alternate embodiments, the sample container holder 16 may be any suitable shape for receiving a particular sample container for use with the system 10, such as a rectangular box or other shape.

As also best seen in fig. 3, an aliquot vessel holder 18 is disposed directly in front of the sample vessel holder 16 in a lower central portion of the chassis 14. As will be described in greater detail below, the aliquoting container holder 18 is fixedly mounted on a rotating platform configured to rotate an aliquoting container 20 (shown in fig. 5) held in the aliquoting container holder 18 about a central z-axis of the container 20 to facilitate uncapping and reclosing of the container 20 during sample processing. The aliquoting container holder 18 is configured to snugly receive and hold the aliquoting container 20 and has an outer wall extending to a height less than the height of the aliquoting container 20 so that the lid 45 on the aliquoting container 20 held in the aliquoting container holder 18 is fully exposed to facilitate mixing, uncapping, and capping thereof, respectively. In the illustrated embodiment, the aliquoting container holder 18 is sized and configured to hold a more tubular container than the container held by the sample container holder 16. In alternate embodiments, the aliquot vessel holder may be any suitable shape for receiving a particular aliquot vessel for use with system 10, such as a rectangular box or other shape. Also as follows, the system 10 may be used for additional sample processing steps, such as for introducing reagents into sample containers. Accordingly, it should be understood that references to the aliquot vessel holder 18 and the aliquot vessel 20 themselves are to be understood as exemplary and not limiting. For example, the terms "refill container holder" and "refill container" may be used interchangeably with aliquoting container holder and aliquoting container.

More specifically, the sample container holder 16 and aliquot container holder 18 are each mounted on (or otherwise integrally formed with) a respective lower rotatable platform (not shown) that is rotatably coupled to or near the floor of the chassis 14. The individual rotary platforms, and thus the container holders 16 and 18, can be selectively rotated in either a clockwise or counterclockwise rotational direction about the central z-axis of each holder 16 and 18. In particular, and with additional reference to fig. 16, a sample dispersal 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 within the liquid sample prior to further processing of the sample. The sample dispersion rotary drive assembly includes a sample dispersion motor (not shown) mounted adjacent a floor of the chassis 14, the sample dispersion motor having a rotary output axis that extends through the chassis floor to rotate the drive wheel 81. The drive wheel 81 in turn rotates a larger diameter drive wheel 93 via a drive belt 88. The high/low speed clutch 82 is operatively connected with 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 upwardly back through the chassis floor, thereby also rotating the sample container holder 16 to disperse the particles contained in the sample container 12 held therein at a relatively high speed prior to further processing of the sample.

With continued reference to FIG. 15, the system 10 further includes a lid drive assembly for simultaneously providing relatively low speed rotation of the sample and aliquot vessel holders 16 and 18 to remove and reinstall the respective lids 43 and 45 on the sample and aliquot vessels 12 and 20, with the vessels 12 and 20 retained in the respective sample and aliquot vessel holders 16 and 18, as described in more detail below. The lid drive assembly includes a lid motor 39 (see fig. 3) mounted in the lower compartment 28 of the cabinet 11 on or near the floor of the chassis 14. The capping motor is reversible to provide rotational movement in each of a clockwise direction and a counterclockwise direction. The capping motor 39 has a rotary output shaft that extends through the floor of the chassis 14 to rotate the drive gear 84, which in turn rotates the larger drive gear 91 via a drive belt 85. The high/low clutch 82 is operatively connected to the drive gear 91, thereby selectively engaging the drive gear 91 with the rotary platforms associated with the sample vessel holder 16 and the aliquot vessel holder 18 via a rotary shaft (not shown) extending upwardly from the drive gear 91 back through the floor of the chassis. It is noted that in the lower part of the chassis, below the respective rotary platforms of the sample container holder 16 and the aliquoting container holder 18, one or more drive gears/wheels and drive belts (not shown) are further provided in order to distribute the rotary motion of the wheels 91 to each rotary platform simultaneously. In this manner, depending on the direction of rotation of the output shaft of motor 39, actuation of the capper motor may simultaneously rotate the sample-container holder 16 and the aliquot-container holder 18 at a relatively slow speed to remove or reinstall the caps 43 and 45.

Referring to FIG. 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 pivot or rotate back and forth about an axis of rotation indicated by dashed line 33 in FIG. 7. Preferably, the tool head 30 has an arc range of at least 270 degrees of rotation about the axis of rotation, although no particular minimum amount of rotational travel is required other than that required to perform the function of a particular system embodiment. In the illustrated embodiment, the tool head is rotated at least 270 degrees about its axis of rotation 33. The load bearing shaft assembly 34 preferably includes a rotational bearing (not shown) to minimize friction between the tool head 30 and a mounting shaft (not shown) mounted on the tool head 30. A tool head rotation actuation motor 36 is attached to the load bearing shaft assembly 34, with an output shaft (not shown) of the motor 36 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 rotary motion in both a clockwise direction of rotation and a counterclockwise direction of rotation of the tool head 30.

With continued reference to fig. 4, motor 36 is housed in a block-type support housing (also referred to as item 36 in the figures) that is threadably mounted on a vertical lead screw 55 (best seen in fig. 15) disposed at the rear of chassis 14. 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 the clockwise and counterclockwise rotational directions. Specifically, rotation of the lead screw 55 in one of the clockwise and counterclockwise directions causes the motor block 36, and thus the respective load bearing shaft assembly 34 and tool head 30, to travel linearly upward relative to the chassis 14 along a vertical (or "z") translation axis indicated by dashed line 51 in fig. 4, and rotation of the lead screw 55 in the other of the clockwise and counterclockwise rotational directions causes the motor block 36, and thus the respective load bearing shaft assembly 34 and tool head 30, to travel linearly downward relative to the chassis 14 along the vertical axis 51. With this mechanical arrangement, and as further described below, the automated tool head 30 is configured to selectively controllably rotate about the axis of rotation 33 in each of a clockwise rotational direction and a counterclockwise rotational direction, and independently selectively translate up or down, respectively, along the vertical axis 51, including simultaneous rotational and translational movements. Operation of the rotary actuation motor 36 controls the rotational position of the tool head 30 about the rotational axis 33, while operation of the linear actuation motor 32 controls the vertical position of the tool head 30 along the vertical axis 51 inside the cabinet 11.

A plurality of sample processing devices (or "tools") are arranged circumferentially about the tool head 30 and are arranged 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., laterally with respect to the cabinet 11) or the y-direction (i.e., fore-aft with respect to the cabinet 11). In the illustrated embodiment, these means include: an indicia reader 31 configured to read indicia, such as a barcode, on a specimen container 12, a first capping device 42 including pneumatically controlled grippers, a grasping device configured to releasably grasp a cap 43 of the specimen container 12 being processed, a second capping device 44 including pneumatically controlled grippers, configured to releasably grasp a cap 45 of a supplemental container 20 (e.g., an aliquot tube or a vessel containing reagents), a pipette 37 (best seen in fig. 15) having a pipette tip engagement 38 extending outwardly from the tool head 30 and configured to releasably engage a pipette tip, a specimen collection and transfer device (hereinafter, "specimen transfer device") 40 having a working end extending outwardly from the tool head 30 and configured for obtaining specimen samples from the specimen containers, and a slide loading bed or "platform" 46 configured to receive a slide 50, the slide 50 to be transferred by the tool head 30 to a slide holder 57 of a slide locator assembly 56 (described in more detail below).

Each of the devices 31, 42,44, 37/38, 40 and 46 is at a different circumferential and/or angular position and orientation on the tool head 30 about the axis of rotation 33, such that each of these devices rotates with the tool head 30 as the tool head rotates about its axis of rotation 33 under the control of the rotary actuation motor 34, and moves vertically up or down within the interior of the cabinet 11 along the vertical axis 51 of the tool head under the control of the tool head translation actuation motor 32. Thus, as further described herein, rotational and/or vertical translational actuation of the tool head 30 positions each of these devices at a relative rotational and vertical position within the interior of the cabinet 11 in order 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 required and is not limiting. For example, in alternative embodiments, more or fewer devices/tools may be carried on the tool head 30. For example, only a single capping device (e.g., 42 or 44) may be used and/or the reader 31 may be provided in a location separate from the tool head 30, including not within the cabinet 11. As a further example, the slide loading platform 46 may be omitted in some embodiments, wherein the system operator loads the slides directly into a slide holder, such as or similar to the slide holder 57. Variations and permutations of these and other arrangements of devices/tools on the tool head 30 are also considered to fall within the scope of the present disclosure.

As shown in fig. 3 and 4, a pump 47 having a pump head 49 supplies pressurized air stored in a high pressure tank 71, the high pressure tank 71 providing the pressurized air to operate various pneumatic devices located in the cabinet 11 via a solenoid valve 68 and a manifold of connectors 67. A slightly elevated pressure canister 72 and a slightly negative pressure canister 73, respectively, are also provided for operation of the sample transfer device 40 (described in more detail below). For clarity, communication paths for pressurized air, such as solid and/or flexible lines connecting pump 47 to tank 71 and tank 71 to various pneumatic devices, are not shown, so as to more clearly view the system components located in cabinet 11 without being obscured by the lines. However, in fig. 2 (only) flexible conduit 23 is shown through which various pneumatic and electrical conduits are connected to tool head 30 and various devices thereon, such as, but not limited to, sealers 42,44, pipettes 37 and sample transfer devices. Bundling the various pipes and wires together with the single conduit 23 reduces the chance of the tool arm 30 snagging or dislodging a pipe or wire from the connector when it is operated. It should be noted that the length of the lines and electrical connections through the conduit 23 are long enough to allow the conduit 23 to move with the tool head 30 as the tool head 30 translates linearly along its vertical axis 51 and rotates about its axis of rotation 33.

Referring back to fig. 2 and 3, the reader 31 is configured to read identifying indicia, such as (but not limited to) a patient identification and/or medical record identifier, a date or medical facility at which the sample was obtained, etc., on any of the sample container 12, aliquoting container 20, slide 50, and/or filter 54. The reader 31 may be an optical reader or scanner, such as for reading bar codes, QR codes, machine-readable alphanumerics, and/or an optical camera that acquires an image of a tag that may 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 indicia. Examples of such alternative indicia storage techniques for slides are provided in U.S. Pat. No. 7,083,106 and U.S. patent publication No. 20070148041, which are incorporated herein by reference in their entirety. In the illustrated embodiment, the reader 31 is configured to read indicia in the form of, inter alia, bar codes. The indicia on the specimen container 12 are read by the reader 31 and transmitted via the system controller 60 (described in further detail below) into each of the slide printer 13 and the aliquoting container printer 19 to print out matching or other corresponding indicia on the respective slides 50 and/or aliquoting containers 20 to be used in the specimen processing procedure.

Referring (primarily) to fig. 2-5, a pipette tip dispenser rack or "carrier" 22 is coupled to the chassis 14 in front of the aliquoting vessel holder 16. Pipette tip dispenser carrier 22 includes a pipette tip dispenser holder 24 configured to securely seat 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 cassette. Pipette tip dispenser 26 may be removably mounted to holder 24 in any of a variety of ways. In the illustrated embodiment, pipette tip dispenser 26 is magnetically coupled to pipette tip dispenser holder 24 in a manner that ensures precise and predictable positioning of dispenser 26 relative to holder 24, and which also allows system controller 60 (described further below) to confirm through sensor circuitry that dispenser 26 is properly attached and positioned relative to holder 24. This is important to ensure that pipette tip engagement members 38 carried by tool tip 30 are able to precisely align and thereby engage pipette tips 48 held in corresponding slots of a dispenser during a sample processing procedure.

Referring briefly also to fig. 16, lateral translation of the pipette tip dispenser carrier 22 is performed by an electrically driven belt 87, the electrically driven belt 87 rotating back and forth on drive wheels 80a and 80b located below the bottom surface of the chassis 14. The drive wheels in turn rotate respective shafts (not shown) extending back through the floor of the chassis and are mechanically coupled to carrier 22 to move pipette tip holder 24 and pipette tip dispenser 26 mounted thereon laterally between a storage position, in which the pipette tip dispenser is located within isolation chamber 28 as shown in fig. 4, and a loading position, in which a slot of pipette tip holder 26 containing available pipette tips 48 is aligned with pipette tip engagement 38 on tool head 30 as shown in fig. 7. In particular, the loading position will vary depending on which well of the dispenser 26 has a pipette tip. In the storage position, the respective pipette tip holder 24 and pipette tip dispenser 26 mounted thereon are located within an isolation chamber 28 within the sample processing cabinet 11 to reduce the chance of contamination of unused tips from sample processing activities occurring in the main interior region of the cabinet 11.

As can be seen by comparing fig. 4 and 5, a faceplate 52 (fig. 4) is attached to one side of pipette tip dispenser 26 and is sized and shaped to close one of the openings through which holder 24 and dispenser 26 enter isolation chamber 28. As shown in fig. 3, pipette tip sensor 35 located in isolation chamber 28 tracks pipette tips 48 held in dispenser 26 to inform system controller 60 to precisely move pipette tip dispenser carrier 22 to a position in which tips 48 held in dispenser 26 are aligned with pipette tip engagement members 38 on tool tip 30 and also to ensure that there are enough pipette tips in dispenser 26 to perform a particular sample processing procedure. If dispenser 26 is empty or otherwise contains an insufficient amount of pipette tips 48 to perform a particular sample processing procedure volume, system 10 will pause and not perform any further sample procedures until a new pipette tip 48 has been loaded into dispenser 26.

The used pipette tip waste barrel 25 is mounted on a separate platform/holder 27 connected to the pipette tip carrier 22, wherein the pipette tip dispenser carrier is configured to selectively translate the waste barrel 25 to a position where the tool tip 30 positions the pipette tip engagement member 38 to disengage the engaged pipette tip 48 into the waste barrel 25. As with pipette tip dispenser 26 and holder 24, waste bucket 25 is preferably magnetically coupled to holder 27 to simultaneously provide stability and allow system 10 to confirm that the waste bucket is properly attached via sensing circuitry. In particular, pipette tip waste barrel holder 27 is mounted on pipette tip carrier 22 relative to pipette tip dispenser holder 24 such that when pipette tip dispenser 26 is translated into isolation chamber 28, pipette tip waste barrel 25 is simultaneously translated to a position where tool tip 30 locates pipette tip engagement member 38 to disengage engaged/used pipette tip 48 from entering waste barrel 25.

Referring also to fig. 15, the pipettor 37 is positioned on the tool tip such that the pipette tip engagement member 38 is slightly tilted relative to the pipette tip dispenser 26. Similarly, the slight inclination enables the engagement members to mate via one or both of rotational and translational movement of the tool tip 30 to thereby engage a pipette tip 48 retained in one of the slots. Pipettes 37 may be, for example and without limitation, sold by Tecan Group ltdAn Air Displacement Pipette (ADP) (www. Tecan. Com/components) comprising a spring biased engagement tip 53 (shown in fig. 15) which, when inserted into a bore of a respective pipette tip 48, releasably engages the respective pipette tip via its compression fit. Once pipette tip 48 is engaged (or mounted) on pipette tip engagement member 38, pipette 37 is configuredCausing selective aspiration of liquid from the sample container 12 into the pipette tip 48 and dispensing of aspirated liquid contained in the pipette tip 48 into the aliquoting containers 20, respectively.

In this manner, during sample processing, pipette 37 engages pipette tip 48 from pipette tip dispenser 26. The pipettor is then repositioned by the tool tip 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 as to confirm, using impedance sensing circuitry of pipette 37, that pipette tip 48 is submerged in a liquid to draw a sample, such as an aliquot from a sample container, by drawing a volume of sample into pipette tip 48 via providing a vacuum within a well of pipette tip 48. Pipettor 37 allows sample to be dispensed from pipette tip 48 by releasing the vacuum to dispense the sample aspirated into pipette tip 48 into, for example, open aliquot vessel 20. Pipette 37 is constructed and operated such that only pipette tip 48 is in contact with the sample material, such that pipette tip engagement member 38 of pipette 37 is not contaminated with the sample material. Pipette tip engagement member 38 is configured to separate pipette tip 48 into waste container 25 after use via a movable displacement sleeve that pushes tip 48 away from tip 53 of pipette tip engagement member 38.

The sample transfer device 40 is carried by the tool head 30 and is configured to collect a sample from a sample in the sample container 12 and transfer the collected sample to a slide 50. In the depicted embodiment, the sample transfer device 40 includes a cylindrical working end that extends away from the tool head 30 and is configured to form a pressure seal around its circumference with a filter 54 disposed thereon prior to beginning a sample processing procedure, as shown in fig. 4. The filter 54 comprises a hollow cylindrical body having an open proximal end and a membrane spanning its distal end with pores of a size selected to capture cells desired for a sample specimen and to pass smaller cells and non-cellular particles and liquid therethrough. Embodiments of the filter 54, as well as sample collection and transfer devices and techniques 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, the filter 54 extends away from the tool head 30 a sufficient distance to allow the filter to be inserted into the sample container 12 to collect a sample on the filter membrane without the sample liquid contacting any part of the sample transfer device 40, and only the filter contacts the sample liquid. This ensures that the sample transfer device 40 is not contaminated with sample material when collecting a sample from the 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 described in detail below.

In particular, sample transfer device 40 and system 10 are configured to insert the membrane of the filter into the specimen in the specimen container via one or both of translational and rotational movement of tool head 30, and force the specimen back and forth across the membrane to collect the specimen sample onto the membrane in a "sipping" manner, which deposits a thin layer of cells in the liquid specimen 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. Additionally or alternatively, the sample transfer device 40 and system 10 may be configured to move the membrane up and down within the sample so that the sample is collected on the membrane. Methods and devices for determining whether a sufficient amount but not too many cells have been collected on a filter membrane using the same "sip procedure" are disclosed and described in U.S. patent No. 8,119,399, incorporated above. 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 incorporated above. Referring briefly to fig. 17, the waste fluid from the sample collection procedure is discharged to a port 95 in the rear of the cabinet 11.

The sample container capping device 42 includes a movable pneumatic fork or gripper configured to grasp and hold the cap 43 of the sample container 12. As can be seen in fig. 15, the grippers are actuated via pneumatic force supplied on the actuating member 77 to alternately provide a tweezer-like radially inward gripping motion or a radially outward releasing motion. The two or more grippers are preferably arranged substantially evenly around the circumference of the sample container lid 43 and can be placed in a "capping" or "uncapping" position via one or more of translational and rotational movement of the tool head 30. With the cap 43 removed, the capper 42 grasps the cap 43 as the container holder 16 is rotated in one of a clockwise or counterclockwise direction, and the tool bit 30 is raised slightly and steadily upward to allow the cap 43 to travel upward as it is rotated on the threads (not shown) of the container 12. In the event that the cap 43 gripped by the gripper is installed back onto the container 12, the tool head 30 positions the capper 42 on the open container and moves downwardly somewhat smoothly as the holder 16 is rotated in the other of the clockwise and counterclockwise directions, while the tool head 30 descends somewhat smoothly as the container is rotated relative to the cap 43 via the holder 16 to allow the cap 43 to travel downwardly onto the container 12. The grippers for the sample container capping device 42, but also for the aliquoting container capping device 44 described below, include parallel pneumatic grippers/grippers of the 2-jaw, 3-jaw and 4-jaw series, commercially available from SMC pneumamatics.

The aliquoting container capper arrangement 44 operates in essentially the same manner as a sample container capper, including releasably gripping the aliquot container 20 cap 45 using two or more prongs or grippers, while the aliquot container holder is rotated clockwise or counter-clockwise to remove the cap 45 from the container 20 or mount the cap 45 onto the container 20, respectively. Again, the tool head 30 moves smoothly downward or upward to accommodate movement of the lid relative to the container 20 during processing. Notably, because of the low torque required to open and close the aliquoting container 20, the aliquoting container gripper is driven using direct air pressure supplied through a hose attachment 75, as shown in fig. 15.

The sample container capping device 42 and aliquoting container capping device 44 are preferably positioned and oriented on the tool head 30 such that the capping devices 42 and 44 are in place to remove the respective caps 43 and 45 without having to reposition the tool head 30.

It should be understood that in alternative embodiments, the respective cappers 42 and 44 may be rotating, in which case the capping process would include having the capper 42 grip the lid 43 and rotate while the sample holder remains stationary, such as taught in U.S. Pat. No. 9,335,336 and U.S. patent publication No. 2017/0052205.

The slide loading platform 46 is preferably located on the tool head 30 at a position that facilitates loading of slides 50 thereon by a system operator prior to a sample processing procedure, and is configured to receive and hold slides 50 while they are loaded thereon. Although the loading platform 46 in the embodiment depicted is configured to receive and hold a microscope slide as the slide 50, it should be understood that the loading platform 46 may be configured to receive and hold other types of analytical elements besides slides, depending on the type of specimen sample to be output by the system 10.

As above, the slide positioner 56 includes a slide holder 57 having a pneumatic gripper 59, the pneumatic gripper 59 being configured to grasp and remove the slide 50 from the loading platform 46 (this transfer can be seen in fig. 5), and thereafter position the slide to receive a sample specimen obtained by the sample transfer device 40. The slide positioner may also be provided with at least two degrees of freedom of movement by a slide positioner motor 63 and various articulated arms, and supported by a counterweight 64. After pressing the membrane of the filter 54 against the slide 50 to transfer the sample specimen (fig. 12), the slide positioner moves and rotates the slide 50 90 degrees and adjacent to the open container of fixative 58 disposed in the fixative container holder 61, and the slide positioner 56 is configured to grasp and move the slide 50. To this end, as shown in fig. 5, the slide positioner 56 includes a pneumatically controlled gripper 59 configured to grasp the slide 50 and thereby remove the slide 50 from the loading platform 46. The slide positioner 56 then moves the slide to a transfer position where the sample transfer device 40 can transfer the sample from the filter 54 to the slide 50, as shown in fig. 11, and then to a holding position where the analysis positioner 50 can place the slide 50 into a fixative container 58 containing a fixative to fix the sample to the slide 50. The system 10 comprises a fixative container holder 61.

Referring to fig. 17, the system 10 also includes one or more processors, which may be collectively referred to as a controller 60 located in the rear panel of the cabinet. The controller 60 is operatively coupled to and configured to communicate with and control the automated operation of the various components of the system 10, including the tool head 30, the tool head actuator 32, the pipette 37, the sample transfer device 40, the first capping device 42, the second capping device 44, the slide positioner 56, and the reader 31. The controller 60 includes a computer processor, input/output interfaces, and other electronics that support communication with and control the operation of the system components. The controller 60 has user input devices for allowing a system operator to input commands, data, etc. into the controller 60. The user input device may be a touch screen/display 62, as follows. The controller 60 also has system software for programming the controller 60 to communicate with the system 10 and control the system 10 to perform the procedures herein for preparing a sample specimen and/or aliquot from a biological or other sample contained in the sample container 12. In the illustrated embodiment, a touch screen/display 62 is attached to the chassis and preferably integrated into the cabinet housing to provide for allowing the system operator to enter instructions (e.g., if prompted by the system 10) and check the status of items performed during sample processing. The touch screen/display 62 is configured to display graphics generated by the controller 60, including information regarding the operation of the system 10, such as operating status, data, and the like. The touch screen/display 62 may be any suitable display, such as a Liquid Crystal Display (LCD), LED display, AMOLED, and the like.

An exemplary sample processing procedure will now be described with reference to fig. 1-14 in order to further illustrate and describe various elements and components of the system 10. Specifically, exemplary sample processing includes first obtaining an aliquot of a sample, and then processing the sample to create a biological sample slide. This procedure is described for purposes of illustration and not limitation, and it is understood that other types of sample processing can be performed using the disclosed and described system and variations thereof while remaining within the scope of the present disclosure. By way of example, and not limitation, each of the methods of processing a sample contained in a sample container using an automated system set forth in the appended claims should be construed as additional exemplary sample processing procedures that may be performed using the illustrated system 10.

To begin processing a given patient sample container 12, the system operator enters the same instruction, for example, via contact with a "start button" or similar symbol on the user interface 62. The system controller 60 causes the tool head 30 to assume a "home" position (if the tool head 30 is not in this position), in which 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 provide the sample vials 12, as shown in fig. 4.

Upon receiving a visual confirmation from the system controller 60 from the user interface display 62, the system operator provides the sample container 12 to the reader 31 such that the patient and/or other indicia on the sample container 12 are within the field of view of the reader 31. The reader 31 reads the indicia on the specimen container 12 and conveys it (via the controller 60) to the respective slide printer 13 and aliquoting container printer 19. The slide printer automatically prints and outputs a new (i.e., unused) slide 50, wherein indicia matching or otherwise corresponding to the indicia on the sample container 12 is printed on the slide 50. The system operator also inserts a new (i.e., unused) aliquot container 20 into the aliquot container printer, which prints indicia on the aliquot container 20 that also matches or corresponds to the indicia on the sample container 12.

In the event that additional tips 48 must be added, the pipette tip dispenser carrier 22 is moved to the loading position (fig. 2) to expose the pipette tip dispensers 26. Loading of the sample container 12, aliquot container 20, slide 50, and pipette tip dispenser 26 into the system 10 may be automated using, for example, robotics, or may be performed manually by a system operator-the latter being assumed in this example for simplicity. Specifically, the system operator then loads the (capped) sample container 12 into the sample container holder 16 and the (capped) aliquoting container 20 into the aliquoting container holder 18, both after the reader 31 reads and confirms that the individual sample and aliquoting container indicia match. The system operator loads the slide 50 onto the slide platform 46 in a face-down orientation, i.e., with the side of the slide having printed indicia and "cell spot" areas to receive the specimen sample facing down toward the platform 46. The system operator loads a new filter 54 onto the working end of the sample transfer device 40 and confirms that there is a sufficient (at least one) number of unused pipette tips 48 in the pipette tip dispenser 26 and that the pipette tip waste bucket 25 is empty. Once all consumables are loaded, the system operator closes the door 15 of the cabinet 11 and indicates through the user interface that the sample processing program can begin, assuming all system verifications are complete.

It is worth noting that the system 10 will not initiate a sample processing procedure unless the sensor 35 indicates that a sufficient number of pipette tips 48 are in the dispensers 26, even though this only means one, and that the pipette tip dispensers 26 and waste buckets 25 are properly positioned and magnetically coupled to their respective mounting platforms 24 and 27 on the pipette tip dispenser carrier 22. The sample transfer device 40 performs a "dry" test to verify the integrity of the filter 54, in particular, to confirm that the distal membrane has not been pierced (indicating that the filter 54 has been previously used) or otherwise closed or torn. It is noted that once it is confirmed that there are sufficient pipette tips 48, the pipette tip dispenser carrier is moved by the system so that the pipette tip dispensers are located in the isolation chamber 28. From that time on until the sample processing procedure is completed, no further involvement of the system operator is usually required.

As shown in fig. 4-6, at the beginning of the sample processing process, pipette tip dispenser carrier 22 moves the pipette tip dispenser to a storage position in separation chamber 28 (fig. 3), and tool head 30 is translated slightly upwardly and linearly upwardly so that slide 50 can be grasped by gripper 59 of slide holder 57. The tool head 30 is then translated linearly downward and rotated so that the reader 31 can read the indicia on the side 50 to confirm that the indicia match the indicia of the respective sample container 12 and aliquoting container 20. Assuming that the match is verified, the system 10 continues to execute an automated procedure to prepare sample samples and aliquot samples, wherein each component of the system 10 is operated and controlled by the controller 60.

As shown in fig. 6, the tool head 30 is rotated and moved vertically downward by the tool head actuator 34 to position the sample container capping device 42 over the cap 43 on the sample container 42 and the aliquoting container capping device 44 over the second cap 45 on the aliquoting container 20. In conjunction with the rotation of each container holder 156 and 18, the individual capping devices 42 and 44 remove and grasp the caps 43 and 45.

As shown in fig. 7, pipette tip dispenser carrier 22 moves to a loading position to position a pipette tip 48 contained in pipette tip dispenser 26 to be mounted on pipette tip engagement member 38 of pipette 37. As also shown in fig. 7, tool tip 30 is rotated to position pipette tip engagement member 38 to mount pipette tip 48 by pushing the pipette tip engagement member into pipette tip 48 via corresponding rotation and translation of tool tip 30.

As shown in fig. 8, pipette tip dispenser carrier 22 moves back to the storage position. Tool tip 30 rotates and vertically translates to place a pipette tip 48 on a pipette 37 into a sample in sample container 12. Pipette 37 draws a vacuum within pipette tip 48 to draw a volume of sample (aliquot) into pipette tip 48.

As shown in fig. 9, tool tip 30 is rotated and vertically translated to position pipette tip 48 in aliquoting vessel 20. The pipette 37 releases the vacuum to dispense the aliquot sample out of the pipette tip 48 and into the aliquot vessel 20. After the aliquot sample has been dispensed into the aliquot vessel 20, the tool head 30 is rotated and translated to position the aliquot vessel cover device 44 to reinstall the cover 45 onto the aliquot vessel 20 (same position as shown in fig. 6).

As shown in fig. 10, tool tip 30 is rotated and translated to position pipette tip 48 on or within waste container 25. Pipette tip engagement member 38 then separates (ejects) the used pipette tip 48 into waste container 25.

As shown in fig. 11, the tool head 30 is rotated and translated to position the filter 54 mounted on the sample transfer device 40 in a position to collect the sample in the sample container 20 onto the filter membrane according to the procedure described above, i.e., the sample is forced back and forth across the membrane via a cyclical vacuum and/or via moving the filter up and down (e.g., via moving the tool head 30 via the tool head actuator 34). This procedure allows a thin layer or monolayer of cells to be collected on the membrane.

As shown in fig. 12, the tool head 30 is rotated and translated to position the filter membrane for transfer of the specimen sample onto a slide 50 held by a holder 59 of the slide holder 57. The sample transfer device 40 and/or the slide positioner 56 are then manipulated to contact the film with the sample thereon onto the slide 50. The tool head 30 may be moved via the tool head actuator 34 to manipulate the sample transfer device 40. To provide for transfer of a 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 first contact the slide 50 at substantially a single location, forming a predetermined small pre-contact angle between the membrane and the deposition surface of the slide 50, and then gently and gradually contact the slide 50 completely. This may be accomplished by coordinated manipulation of the sample transfer device 40 and the slide positioner 56.

As shown in fig. 13, the tool head 30 moves downward and may also rotate to provide space for a slide positioner 56 to place the slide 50 with the specimen sample thereon into a fixative container 58 containing a fixative to fix the specimen sample to the slide 50. After transferring the sample specimen to the slide 50, the tool head 30 translates and/or rotates to drive the filter membrane into the pins 41 (fig. 4) to break the filter membrane to prevent reuse. As shown in fig. 13, the slide positioner 56 is actuated to place the slide 50 with the specimen sample thereon into the fixative container 58. Once the sample processing procedure is complete, the system operator may remove the specimen slide 50 from the fixative solution in the receptacle 58 or may remove the fixative receptacle, including the specimen slide 50, and replace (or place a new) fixative receptacle 58 in the holder 61 before starting a new specimen processing procedure.

The tool head 30 is rotated and moved downwardly to position the sample container capping device 42 to reinstall the cap 43 onto the sample container 12 (same position as shown in figure 4).

This completes the automated procedure of preparing the sample specimen and aliquoting the specimen. The slide 56 of the specimen sample immobilized thereon with the fixative can then be removed from the fixative container 58 and used for testing. The sample container 12 and aliquot container 20 may also be removed from the system 10 and stored as appropriate. Waste container 25 is removed from system 10 and dumped into a waste bin to dispose of used pipette tips 48. The waste container 25 may then be placed back onto the waste container platform 27.

The procedure may be repeated for more sample containers containing individual specimens, as desired.

While specific embodiments have been illustrated and described, it will be appreciated that the above description is not intended to limit the scope of these embodiments. While variations of many aspects of the embodiments disclosed herein have been disclosed and described, it is to be understood that the foregoing disclosure is for purposes of illustration and description only and that various changes and modifications may be made to the disclosed embodiments without departing from the scope of the appended claims. For example, not all of the components depicted and described in an embodiment are required, and alternative embodiments may include any suitable combination of components and may modify the general shape and relative dimensions of the components.

Claims (21)

1. A method of using an automated system for processing biological samples, the system comprising: a sample container holder; an analysis element holder; an automated tool head configured to rotate about a first axis and translate along a second axis different from the first axis; a sample container capping device disposed at a first location on the tool head; and a sample transfer device disposed at a second location on the tool head different from the first location, the method comprising:

placing a sample container in the sample container holder, the sample container comprising the biological sample suspended in a sample fluid;

positioning the sample container capping device in proximity to the sample container by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis;

operating said sample container capping device to grip a sample container cap on said sample container;

rotating one of the sample container holder and the sample container closure device relative to the other of the sample container holder and the sample container closure device in a first one of a clockwise rotational direction and a counterclockwise rotational direction, thereby removing the sample container lid from the sample container;

after removing the specimen container lid from the specimen container, positioning a working end of the sample transfer device in an interior of the specimen container by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis;

operating the sample transfer device to obtain a sample of the biological sample contained in the sample container;

after obtaining the sample, repositioning the working end of the sample transfer device proximate an analysis element held by the analysis element holder by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis; and

operating 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 of claim 1, further comprising:

after obtaining the sample specimen from the specimen container, and while the removed specimen container cap is gripped by the specimen container capping device, positioning the specimen container capping device in proximity to the specimen container by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis; and

rotating one of the sample container holder and the sample container capping device relative to the other of the sample container holder and the sample container capping device in the other of the clockwise direction of rotation and the counterclockwise direction of rotation, thereby reinstalling the sample container lid on the sample container.

3. The method of claim 1, the system further comprising a pipette tip dispenser and a pipette disposed at a third location on the tool head different from the first and second locations, the method further comprising:

positioning a pipette tip engagement member of the pipette to engage a pipette tip on the pipette tip dispenser by one or both of automatic rotation of the tool tip about the first axis and automatic translation of the tool tip along the second axis.

4. The method of claim 3, the system further comprising an aliquot vessel holder and an aliquot vessel capping device disposed at a fourth location on the tool head different from the first, second, and third locations, respectively, the method further comprising:

placing an aliquot vessel in the aliquot vessel holder;

positioning the aliquoting container capping device adjacent the aliquoting container by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis;

operating said aliquoting container capping device to clamp an aliquoting container lid on said aliquoting container; and

rotating one of the aliquot holder and the aliquot cover device relative to the other of the aliquot holder and the aliquot cover device in a first one of a clockwise rotation direction and a counterclockwise rotation direction, thereby removing the aliquot cover from the aliquot container.

5. The method of claim 4, further comprising:

positioning the pipette tip engagement member of the pipette by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis while the removed sample vessel lid is gripped by the sample vessel capping device and the removed aliquot vessel lid is gripped by the aliquot vessel capping device, thereby positioning the engaged pipette tip within the interior of the sample vessel;

operating the pipette to obtain an aliquot of sample fluid from the sample container within the engaged pipette tip;

repositioning the pipette tip engagement by one or both of automatic rotation of the tool tip about the first axis and automatic translation of the tool tip along the second axis after obtaining an aliquot of the sample fluid, thereby repositioning the engaged pipette tip within an interior of the aliquot vessel; and

operating the pipette to dispense an aliquot of the sample fluid into the aliquot vessel.

6. The method of claim 5, further comprising:

after dispensing an aliquot of the sample fluid into the aliquot vessel, and while the removed aliquot vessel lid is gripped by the aliquot vessel capping device, positioning the aliquot vessel capping device proximate to the aliquot vessel by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis, and

rotating one of the aliquot vessel holder and the aliquot vessel closing device relative to the other of the aliquot vessel holder and the aliquot vessel closing device in the other of the clockwise direction of rotation and the counterclockwise direction of rotation to remount the aliquot vessel lid on the aliquot vessel.

7. The method of claim 4, wherein the first location on the tool head is angularly spaced from the second location about the first axis, and wherein the fourth location on the tool head is aligned with the first location along the second axis.

8. The method of claim 3, wherein the pipette tip dispenser is mounted on an automated pipette tip dispenser carrier, the method further comprising:

translating the pipette tip dispenser carrier thereby translating the pipette tip dispenser relative to the tool tip such that the pipette tip in the pipette tip dispenser is positioned at a location where the tool tip positions the pipette tip engagement member to engage the pipette tip; and

after the pipette tip engagement member engages the pipette tip, translating the pipette tip dispenser carrier, thereby translating the pipette tip dispenser relative to the tool tip such that the pipette tip dispenser is positioned within a chamber that is substantially environmentally isolated from the tool tip.

9. The method of claim 8, the system further comprising a pipette tip waste container mounted on the pipette tip dispenser carrier, the method further comprising:

translating the pipette tip dispenser carrier to thereby translate the pipette tip waste container to a location proximate to the pipette tip engagement member;

positioning the pipette tip engagement member by one or both of automatic rotation of the tool tip about the first axis and automatic translation of the tool tip along the second axis, thereby positioning the engaged pipette tip above the pipette tip waste container, and

operating the pipette to release the engaged pipette tip from the pipette tip engagement member into the pipette tip waste container,

wherein 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 a position where the tool tip positions the pipette tip engagement member to release the pipette tip into the pipette tip waste container, the pipette tip dispenser is simultaneously translated into the chamber.

10. The method of claim 1, wherein the analysis element comprises a slide and the analysis element holder comprises a controllable gripper that engages the slide, the method further comprising:

automatically repositioning the controllable gripper above an output receptacle containing a fixative after transferring the specimen sample to the slide, an

Operating the controllable gripper to release the slide into the output receptacle.

11. A method of using an automated system for processing biological samples, the system comprising: a sample container holder; a slide holder; an automated tool head configured to rotate about a first axis and translate along a second axis different from the first axis; a sample container capping device disposed at a first circumferential location on the tool head; and a sample transfer device disposed on the tool head at a second circumferential location angularly spaced about the first axis from the first circumferential location, the method comprising:

placing a sample container in the sample container holder, the sample container comprising the biological sample suspended in a sample fluid;

positioning the sample container capping device in proximity to the sample container by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis;

operating said sample container capping device to grip a sample container cap on said sample container;

rotating one of the sample container holder and the sample container closure device relative to the other of the sample container holder and the sample container closure device in a first one of a clockwise rotational direction and a counterclockwise rotational direction, thereby removing the sample container lid from the sample container;

after removing the sample container lid from the sample container, positioning a working end of the sample transfer device in an interior of the sample container by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis;

operating the sample transfer device to obtain a sample of the biological sample contained in the sample container;

after obtaining the sample specimen from the specimen container, and while the removed specimen container cap is gripped by the specimen container capping device, positioning the specimen container capping device in proximity to the specimen container by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis; and

rotating one of the sample container holder and the sample container capping device relative to the other of the sample container holder and the sample container capping device in the other of the clockwise direction of rotation and the counterclockwise direction of rotation, thereby reinstalling the sample container lid on the sample container.

12. The method of claim 11, the slide holder including a controllable gripper that engages a slide, the method further comprising:

automatically repositioning the controllable gripper above an output receptacle containing a fixative after transferring the sample specimen to the slide, an

Operating the controllable gripper to release the slide into the output receptacle.

13. The method of claim 11, the sample transfer device comprising a filter membrane, the method further comprising:

verifying the integrity of the filter membrane prior to positioning the working end of the sample transfer device into the sample container.

14. The method of claim 13, further comprising:

after transferring the sample specimen to a slide, the working end of the sample transfer device with the filter membrane thereon is pressed onto an object to break the integrity of the filter membrane.

15. The method of claim 11, the system further comprising a reader carried on the tool head, the method further comprising:

reading patient indicia on a slide using the reader;

reading patient indicia on the sample container using the reader;

verifying that the patient indicia on the slide corresponds to the patient indicia on the sample container.

16. A method of using an automated system for processing biological samples, the system comprising: a sample container holder; an aliquoting container holder; a pipette tip dispenser; an automated tool head configured to rotate about a first axis and translate along a second axis different from the first axis; a sample container capping device disposed at a first location on the tool head; aliquoting container capping means provided at a second position on the tool head different from the first position; and a pipette disposed at a third location on the tool head different from the first location and the second location, the method comprising:

placing a sample container in the sample container holder, the sample container comprising the biological sample suspended in a sample fluid;

placing an aliquot vessel in the aliquot vessel holder;

positioning the sample container capping device adjacent the sample container by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis;

operating said sample container capping apparatus to clamp a sample container cap on said sample container;

rotating one of the sample container holder and the sample container closure device relative to the other of the sample container holder and the sample container closure device in a first one of a clockwise rotational direction and a counterclockwise rotational direction, thereby removing the sample container lid from the sample container;

positioning a pipette tip engagement member of the pipette by one or both of automatic rotation of the tool tip about the first axis and automatic translation of the tool tip along the second axis so as to engage a pipette tip from the pipette tip dispenser;

after removing the sample vessel cover from the sample vessel and engaging the pipette tip onto the pipette tip engagement member, positioning the aliquoting vessel capping device in proximity to the aliquoting vessel by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis;

operating the aliquoting container capping device to clamp an aliquoting container cap on the aliquoting container; and

rotating one of the aliquot holder and the aliquot cover device relative to the other of the aliquot holder and the aliquot cover device in a first one of a clockwise rotation direction and a counterclockwise rotation direction, thereby removing the aliquot cover from the aliquot container;

positioning the pipette tip engagement member of the pipette by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis while the removed sample vessel cover is gripped by the sample vessel capping device and the removed aliquot vessel cover is gripped by the aliquot vessel capping device, thereby positioning the engaged pipette tip within the interior of the sample vessel;

operating the pipette to obtain an aliquot of sample fluid from the sample container within the engaged pipette tip;

repositioning the pipette tip engagement by one or both of automatic rotation of the tool tip about the first axis and automatic translation of the tool tip along the second axis after obtaining an aliquot of the sample fluid, thereby repositioning the engaged pipette tip within an interior of the aliquot vessel; and

operating the pipette to dispense an aliquot of the sample fluid into the aliquot vessel.

17. The method of claim 16, further comprising:

after obtaining an aliquot of the sample fluid from the sample container, and while the removed sample container cap is gripped by the sample container capping device, positioning the sample container capping device in proximity to the sample container by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis; and

rotating one of the sample container holder and the sample container capping device relative to the other of the sample container holder and the sample container capping device in the other of the clockwise direction of rotation and the counterclockwise direction of rotation, thereby reinstalling the sample container lid on the sample container.

18. The method of claim 16, further comprising:

after dispensing an aliquot of the sample fluid into the aliquot vessel, and while the removed aliquot vessel lid is gripped by the aliquot vessel capping device, positioning the aliquot vessel capping device proximate to the aliquot vessel by one or both of automatic rotation of the tool head about the first axis and automatic translation of the tool head along the second axis, and

rotating one of the aliquot holder and the aliquot cover device relative to the other of the aliquot holder and the aliquot cover device in the other of the clockwise direction of rotation and the counterclockwise direction of rotation to reattach the aliquot cover to the aliquot container.

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

20. The method of claim 16, wherein the pipette tip dispenser is mounted on an automated pipette tip dispenser carrier, the method further comprising:

translating the pipette tip dispenser carrier thereby translating the pipette tip dispenser relative to the tool tip such that the pipette tip in the pipette tip dispenser is positioned at a location where the tool tip positions the pipette tip engagement member to engage the pipette tip; and

after the pipette tip engagement member engages the pipette tip, translating the pipette tip dispenser carrier, thereby translating the pipette tip dispenser relative to the tool tip such that the pipette tip dispenser is positioned within a chamber that is substantially environmentally isolated from the tool tip.

21. The method of claim 20, the system further comprising a pipette tip waste container mounted on the pipette tip dispenser carrier, the method further comprising:

translating the pipette tip dispenser carrier to thereby translate the pipette tip waste container to a position proximate to the pipette tip engagement member;

positioning the pipette tip engagement member by one or both of automatic rotation of the tool tip about the first axis and automatic translation of the tool tip along the second axis, thereby positioning the engaged pipette tip above the pipette tip waste container, and

operating the pipette to release the engaged pipette tip from the pipette tip engagement member into the pipette tip waste container,

wherein the pipette tip waste container is mounted on the pipette tip dispenser carrier relative to the pipette tip dispenser such that the pipette tip dispenser is simultaneously translated into the chamber when the pipette tip waste container is translated to a position where the tool tip positions the pipette tip engagement member to release the pipette tip into the pipette tip waste container.