Management of disposable pipet tip

The device with a tip holder conveyor and drive mechanism addresses the disruption of continuous processing by managing pipette tip disposal, allowing uninterrupted operation and efficient tip handling in instruments with robotic pipettors.

JP2025148382APending Publication Date: 2025-10-07GEN PROBE INC
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Patent Information

Application Number
JP2025111517
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2019-03-29
Filing Date
2025-07-01
Publication Date
2025-10-07

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  • Figure 2025148382000001_ABST
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Abstract

To provide a device for capturing one or more pipet tips which are released from an automatic pipetter, at a tip release place.SOLUTION: After using a disposable pipet tip by an automatic pipetter, the disposable pipet tip is released by a pipetter, and is fallen into a waste disposal container. When the waste disposable container is detached to empty it, the pipet tip is temporarily isolated in a pipet tip holding station so that the automatic pipetter operates continuously. After exchanging a waste disposable container, the pipet tip isolated by the holding station is released into the waste disposable container. Embodiments are achieved in a device for capturing one or more pipet tips released from the automatic pipetter at a tip release place.SELECTED DRAWING: Figure 6
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Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit under 35 U.S.C. §119(e) of Provisional Patent Application No. 62 / 826,599, filed March 29, 2019, the disclosure of which is incorporated herein by reference.

[0002] The present disclosure relates to handling discarded disposable pipette tips in instruments employing robotic pipettors. [Background technology]

[0003] Certain instruments, such as diagnostic and clinical analyzers, in which liquids are transferred to, from, or between different receptacles, reservoirs, or other liquid-containing containers often employ robotic pipettors to aspirate and dispense liquids. To prevent contamination of the pipettor's probe, disposable pipette tips can be removably attached to the pipettor's probe so that liquid is aspirated into the pipette tip without contacting the probe. After a pipette tip is used, it is typically discarded by releasing or ejecting it from the pipettor probe and placing it in a waste container into which the released pipette tip falls. Periodically, throughout the instrument's sustained operation, the waste container must be emptied as it fills with discarded pipette tips. Typically, the waste container is emptied by removing it from the instrument and discarding the accumulated pipette tips before replacing the instrument's waste container. However, during the time the waste container is removed from the instrument, the instrument's operation must be paused because there is no place to discard the pipette tips released from the pipettor probe. Having to pause the operation of the equipment every time a waste container needs to be emptied can have a detrimental effect on the equipment. Summary of the Invention [Means for solving the problem]

[0004] The following presents a simplified summary in order to provide a basic understanding of some aspects described herein. This summary is not an extensive overview of the claimed subject matter. It is not intended to identify key or critical elements or delineate the scope of the claimed subject matter. Its sole purpose is to present some concepts in a simplified form as a prelude to the more detailed description that is presented later.

[0005] Aspects of the present disclosure are embodied in a device for capturing one or more pipette tips released from an automated pipettor at a tip release location. The device may include a tip holder conveyor, a drive mechanism, and a tip ejector. The tip holder conveyor may include or support multiple tip holders, each configured to receive and releasably hold a single pipette tip. The drive mechanism is configured to index the tip holder conveyor to sequentially position each of one or more of the multiple tip holders at the tip release location to receive pipette tips released by the automated pipettor into each tip holder positioned at the tip release location. The tip ejector may be positioned to engage pipette tips held in each of the one or more of the multiple tip holders when the tip holder conveyor is moved relative to the tip ejector by the drive mechanism, and the tip ejector is configured to remove each pipette tip engaged by the tip ejector from its associated tip holder.

[0006] According to another aspect, multiple tip holders of a tip holder conveyor may be interconnected to form a tip holder chain.

[0007] According to another aspect, the tip holder chain may include a continuous chain guided by a continuous track.

[0008] According to another aspect, after a pipette tip is released by an automatic pipettor into a tip holder located at a tip release location, if at least one of the multiple tip holders does not receive the pipette tip released by the automatic pipettor, the drive mechanism may index the tip holder conveyor to index a subsequent tip holder to the tip release location.

[0009] According to another aspect, when there is no tip holder located at the tip release location, pipette tips released from the automated pipettor may fall into a removable waste container positioned to receive the released pipette tips. The device may further include a waste container sensor configured to detect whether the waste container is positioned to receive the released pipette tips. Detecting by the waste container sensor that the waste container is not positioned to receive the released pipette tips may cause the drive mechanism to index the tip holder conveyor to sequentially position each of the one or more tip holders at the tip release location to capture each pipette tip released while the waste container is not positioned to receive the released pipette tips. Detecting by the waste container sensor that the waste container is positioned to receive the released pipette tips may cause the drive mechanism to move the tip holder conveyor to sequentially move each of the one or more tip holders relative to the tip ejector to remove the pipette tips from the associated tip holders at the tip removal location.

[0010] According to other aspects, the device may further include a waste chute positioned below the tip release location and below the tip removal location, and the waste chute may be configured to direct pipette tips released by the automated pipettor or removed from tip holders of the tip holder conveyor into a waste container.

[0011] According to another aspect, when the waste container sensor detects that the waste container is positioned to receive a released pipette tip, the drive mechanism can be configured to move the tip holder conveyor to a standby position where no tip holder is located at the tip release location.

[0012] According to another aspect, when the tip holder conveyor moves to a standby position, each tip holder holding a pipette tip may be moved sequentially relative to a tip ejector to remove the pipette tip from the associated tip holder so that the pipette tip is not held by the tip holder conveyor when the tip holder conveyor is in the standby position.

[0013] According to another aspect, the tip holder conveyor may include a tip holder chain comprising a plurality of interconnected links, and each tip holder may be part of one of the links.

[0014] According to other aspects, the chip holder conveyor may include a detection element at each chip holder, and the device may further include a sensor for detecting each detection element passing by the sensor when the drive mechanism moves the chip holder conveyor.

[0015] According to other aspects, the tip holder conveyor may include a tip holder chain having a plurality of interconnected links, each tip holder may be part of one of the links, and each detection element may include a pin connecting one link to an adjacent link.

[0016] According to another aspect, the device may further include a controller configured to determine a position of the tip holder chain based on the number of sensing elements that have passed the sensor.

[0017] According to another aspect, the tip holder chain may include a continuous chain guided by a continuous track.

[0018] According to another aspect, the drive mechanism may include a chain drive with a motorized wheel, with a continuous chain wrapped around the motorized wheel.

[0019] According to another aspect, each tip holder may include a clip defining an opening configured to receive a pipette tip without any resistance.

[0020] According to other aspects, each clip may include opposing arms configured to hold a pipette tip therebetween and defining a lateral opening narrower than the width of a portion of the pipette tip held between the opposing arms.

[0021] According to other aspects, the tip ejector may include one or more ramps or wedges that contact a pipette tip held within the opening of the clip when the tip holder passes through the tip ejector, and the opposing arms are flexible so that when the one or more ramps contact the pipette tip, the pipette tip moves laterally, urging the opposing arms to open, enlarging the lateral opening and allowing the pipette tip to pass through the lateral opening and be removed from the tip holder.

[0022] According to another aspect, the tip holder conveyor may follow a curved path adjacent to the tip ejector.

[0023] According to other aspects, the tip ejector may include first and second laterally extending ramps or wedges, the first laterally extending ramp may be configured to engage a first portion of the pipette tip extending above the clip when the tip holder is moved relative to the tip ejector, and the second laterally extending ramp may be configured to engage a second portion of the pipette tip extending below the clip when the tip holder is moved relative to the tip ejector.

[0024] According to other aspects, the drive mechanism may be configured to move the tip holder conveyor in a first direction to sequentially position each tip holder at a tip release location, and to move the tip holder conveyor in a second direction opposite to the first direction to move the tip holder conveyor relative to the tip ejector to remove pipette tips from the associated tip holders.

[0025] According to other embodiments, at least a portion of the chip holder conveyor may follow a linear path when moving in the first and second directions.

[0026] Aspects of the present disclosure are embodied in an instrument including a pipettor, a waste container, and a pipette tip holder. The pipettor may be configured to move laterally and vertically within the instrument, and the pipettor has a mounting end adapted to receive a pipette tip in a friction fit. The waste container is movable between a first receptacle position and a second receptacle position. When the waste container is in the first receptacle position, the waste container is positioned to receive a pipette tip released from the mounting end of the pipettor at a tip release location, and when the waste container is in the second receptacle position, the waste container is not positioned to receive a pipette tip released from the mounting end of the pipettor at the tip release location. The pipette tip holder is movable between a first tip holder position and a second tip holder position. In the first tip holder position, the pipette tip holder is not positioned to receive a pipette tip released from the mounting end of the pipettor at the tip release location when the waste container is in the first receptacle position, and in the second tip holder position, the pipette tip holder is positioned to receive and hold a pipette tip released from the mounting end of the pipettor at the tip release location when the waste container is in the second receptacle position.

[0027] According to other embodiments, the pipettor can be configured for X, Y, and Z movement.

[0028] According to another aspect, the pipettor may include a probe and the attachment end may include a distal end of the probe.

[0029] According to another aspect, the instrument may further include a pipette tip holder bay and a container of pipette tips disposed within the pipette tip holder bay, the pipette tips of the container within the pipette tip holder bay being positioned and oriented to be engaged by the mounting end of the pipettor.

[0030] According to other embodiments, the pipette tip holder may be movable to a third tip holder position, different from the second tip holder position, at which the pipette tip held in the pipette tip holder is removed from the pipette tip holder.

[0031] According to other embodiments, the instrument may further include a tip ejector configured to remove the pipette tip from the pipette tip holder at the third position.

[0032] According to another aspect, the pipette tip can be laterally displaced from the pipette tip holder by a tip ejector.

[0033] According to another aspect, movement of the pipette tip holder from the first tip holder position to the second tip holder position can be in a first lateral direction, and movement of the pipette tip holder from the second tip holder position to the third tip holder position can be in a second lateral direction, the first and second lateral directions being opposite directions.

[0034] According to another aspect, the waste container may be lined with a disposable plastic bag.

[0035] According to other aspects, the device may further include a drawer configured to support the waste container and move the waste container laterally between the first and second receptacle locations.

[0036] According to other aspects, the device may further include a sensor for detecting when a waste container is present in at least one of the first and second receptacle locations.

[0037] According to another aspect, the pipette tip holders may be transported on a conveyor.

[0038] According to another aspect, the device may include a track for supporting the conveyor.

[0039] According to other aspects, the device may further include a sensor for monitoring the position of the pipette tip holder on the track.

[0040] According to another aspect, the device may further include a drip tray located below a portion of the conveyor.

[0041] According to other embodiments, the pipette tip holder can be one of a plurality of pipette tip holders.

[0042] According to another aspect, the pipette tip is released into the waste container when the pipette tip holder is not in a second tip holder position for receiving a pipette tip released from the mounting end of the pipettor at the tip release location and the waste container is in the first receptacle position.

[0043] According to another aspect, when the pipette tip holder is not in a second tip holder position for receiving a pipette tip released from the mounting end of the pipettor at the tip release location and the waste container is in the first receptacle position, the pipette tip can be released into a chute that directs the pipette tip to the waste container.

[0044] According to another aspect, the tip holder may include a clip defining an opening configured to receive the pipette tip without any resistance.

[0045] According to another aspect, the clip may include opposing arms configured to hold a pipette tip therebetween and defining a lateral opening narrower than the width of a portion of the pipette tip held between the opposing arms.

[0046] According to another aspect, the pipettor may include a tip release mechanism for releasing the pipette tip from the mounting end of the pipettor.

[0047] According to another aspect, the tip release mechanism may include a release sleeve coaxially mounted on the mounting end and configured to be axially movable relative to the mounting end.

[0048] According to other aspects, the tip release mechanism may further include a release trigger coupled to the release sleeve and configured to move the release sleeve axially relative to the mounting end to release the pipette tip from the mounting end when the pipettor moves the release trigger into contact with the release surface.

[0049] Aspects of the present disclosure are embodied in a method for capturing one or more pipette tips released from an automated pipettor. The method may include the steps of: a) repeatedly moving the pipette tip, while securing the pipette tip to the pipette, laterally to a tip release position to release the pipette tip from the pipette, thereby dropping the released pipette tip into a waste container positioned to receive the released pipette tip; b) detecting whether the waste container is no longer positioned to receive the pipette tip released from the pipette at the tip release position; and c) upon detecting that the waste container is no longer positioned to receive the pipette tip released from the pipette at the tip release position, moving the pipette tip holder from a first tip holder position where the pipette tip holder is not positioned to receive the pipette tip released from the pipette at the tip release position to a second tip holder position where the pipette tip holder is positioned to receive the pipette tip released from the pipette at the tip release position, and receiving the pipette tip released from the pipette while the pipette tip holder is in the second tip holder position.

[0050] According to other aspects, the method may further include: d) moving an additional pipette tip holder from a first tip holder position, in which the pipette tip holder is not positioned to receive a pipette tip released from a pipettor in the tip release position, while the waste container is no longer positioned to receive a pipette tip released from a pipettor in the tip release position, to a second tip holder position, in which the pipette tip holder is positioned to receive a pipette tip released from a pipettor in the tip release position; and e) receiving a pipette tip released from a pipettor having an associated pipette tip holder at the second tip holder position.

[0051] According to another embodiment, step b) is performed by a sensor for detecting the presence or absence of a waste container.

[0052] According to another aspect, the method may further include, after step c), the steps of: f) moving the pipette tip holder from the second tip holder position to a third tip holder position different from the second tip holder position upon detecting that the waste container is positioned to receive a pipette tip from the pipettor in the tip release position; and g) at the third tip holder position, removing the pipette tip from the pipette tip holder, thereby dropping the removed pipette tip into the waste container.

[0053] According to another aspect, step g) may include moving the pipette tip holder relative to a tip ejector that includes at least one ramp that engages a pipette tip held in the tip holder and laterally displaces the pipette tip from the tip holder.

[0054] According to another aspect, the tip holder chain interconnects a plurality of tip holders to form a continuous tip holder chain, and step f) may include moving the tip holder chain with a motorized drive wheel engaged with the tip holder chain.

[0055] According to another aspect, step c) may include moving the pipette tip holder in a first lateral direction, and step f) may include moving the pipette tip holder in a second lateral direction, the first and second lateral directions being opposite directions.

[0056] According to another aspect, the method may further include the step of h) monitoring the position of the pipette tip holder.

[0057] According to other aspects, the method may further include the steps of i) determining that a pipette tip holder without a pipette tip is not available, and j) interrupting operation of the pipettor when a pipette tip holder without a pipette tip is not available.

[0058] According to other aspects, releasing the pipette tip from the pipettor may include engaging the pipette tip attached to the pipettor with a tip release mechanism.

[0059] According to other aspects, the tip release mechanism may include a release sleeve coaxially mounted on the mounting end of the pipettor to which the pipette tip is attached, and engaging the pipette tip with the tip release mechanism may include axially moving the release sleeve relative to the mounting end.

[0060] According to another aspect, the tip release mechanism may further include a release trigger coupled to the release sleeve, and axially moving the release sleeve relative to the mounting end may include contacting the release surface with the release trigger.

[0061] Aspects of the present disclosure are embodied in a method for facilitating continuous processing of multiple samples in an automated system. The method may include: a) detecting that a waste container of the system is not in a pipette tip receiving position; b) isolating one or more pipette tips released from a pipettor at a pipette tip holding station of the system after step a) and while the waste container is not in the pipette tip receiving position, wherein the isolated pipette tips have previously been used to process at least a subset of the multiple samples in the system, and when the waste container is in the pipette tip receiving position, any pipette tips used to process the multiple samples and released from the pipettor may be released directly into the waste container; c) after step b), detecting that the waste container is in the pipette tip receiving position; and d) after step c), while the waste container is in the pipette tip receiving position, transferring the isolated pipette tips from the pipette tip holding station to the waste container. Processing of the multiple samples in the system is continuous between steps a) through d).

[0062] According to another aspect, the waste container is supported by a drawer that is laterally movable to and from a pipette tip receiving position.

[0063] According to another aspect, the waste container may be lined with a disposable plastic bag.

[0064] According to another embodiment, steps a) and b) include using a position sensor of the system to detect when the waste container is in or out of the pipette tip receiving position.

[0065] According to another aspect, step b) may include, for each of the one or more pipette tips, moving the pipettor into engagement with a pipette tip release surface of the holding station, thereby causing the pipettor to release the associated pipette tip from the mounting end of the pipettor.

[0066] According to another aspect, one or more pipette tips may be released to individual pipette tip holders at a first tip release location in step b), and the individual pipette tip holders are housed within the pipette tip holding station when the waste container is not at the pipette tip receiving position.

[0067] According to other embodiments, the pipette tip holder can support one or more pipette tips in an upright orientation.

[0068] According to another aspect, the individual pipette tip holders include or are supported by a loop conveyor of the pipette tip holding station.

[0069] According to another aspect, the individual pipette tip holders may be moved in a first lateral direction on the conveyor during step b) and in a second lateral direction on the conveyor in step d), the first lateral direction and the second lateral direction being opposite directions.

[0070] According to another embodiment, step d) may include laterally displacing one or more pipette tips from respective pipette tip holders.

[0071] According to another aspect, the method may further include releasing at least one pipette tip from the pipettor at a second tip release location when the waste container is in the pipette tip receiving position.

[0072] According to other embodiments, the first and second tip release locations can be the same tip release location.

[0073] According to other embodiments, the first and second tip release locations may be located above a chute for directing pipette tips into a waste container.

[0074] According to another aspect, the method may further include a step of collecting residual fluid removed from at least one of the one or more pipette tips in a tray positioned below the one or more pipette tips isolated in the holding station in step b), the tray being a component of the holding station.

[0075] According to other aspects, processing at least a subset of the plurality of samples may include reconstituting or transferring reagents for performing nucleic acid-based amplification reactions.

[0076] According to other embodiments, processing at least a subset of the plurality of samples may include forming a reaction mixture including one of the samples and at least one reagent for performing a nucleic acid-based amplification reaction.

[0077] Other features and characteristics of the subject matter of the present disclosure, as well as its method of operation, function of associated elements of construction and combination of parts, and economies of manufacture, will become more apparent from a consideration of the following description and the appended claims, taken in conjunction with the accompanying drawings, all of which form a part of this specification and in which like reference numerals indicate corresponding parts in the various views. The present specification also provides, for example, the following items: (Item 1) 1. A device for capturing one or more pipette tips released from an automated pipettor at a tip release location, said device comprising: a tip holder conveyor comprising or supporting a plurality of tip holders, each tip holder configured to receive and releasably hold a single pipette tip; a drive mechanism configured to index the tip holder conveyor to sequentially position each of one or more of the plurality of tip holders at the tip release location to receive pipette tips released by the automated pipettor into each tip holder positioned at the tip release location; a tip ejector positioned to engage pipette tips held in each of one or more of the plurality of tip holders when the tip holder conveyor is moved relative to the tip ejector by the drive mechanism, and configured to remove each pipette tip engaged by the tip ejector from its associated tip holder. (Item 2) Item 1. The device of item 1, wherein the plurality of chip holders of the chip holder conveyor are interconnected to form a chip holder chain. (Item 3) Item 3. The device of item 2, wherein the tip holder chain comprises a continuous chain guided by a continuous track. (Item 4) 4. The device according to any one of items 1 to 3, wherein, after a pipette tip is released by the automated pipettor into the tip holder located at the tip release location, if at least one of the plurality of tip holders has not received a pipette tip released by the automated pipettor, the drive mechanism indexes the tip holder conveyor to index a subsequent tip holder to the tip release location. (Item 5) When there is no tip holder located at the tip release location, pipette tips released from the automatic pipetter fall into a removable waste container positioned to receive the released pipette tip, and the device further comprises a waste container sensor configured to detect whether the waste container is positioned to receive the released pipette tip, whereby detecting by the waste container sensor that the waste container is not positioned to receive the released pipette tip causes the drive mechanism to index the tip holder conveyor to remove the one 5. The device of claim 1, wherein the device sequentially positions each of the one or more tip holders at the tip release location to capture each released pipette tip while the waste container is not positioned to receive the released pipette tip, and the device detects with the waste container sensor that the waste container is positioned to receive the released pipette tip by causing the drive mechanism to move the tip holder conveyor to sequentially move each of the one or more tip holders relative to the tip ejector to remove the pipette tip from the associated tip holder at a tip removal location. (Item 6) Item 6. The device of item 5, further comprising a waste chute positioned below the tip release location and below the tip removal location, the waste chute configured to direct pipette tips released by the automated pipettor or removed from tip holders of the tip holder conveyor into the waste container. (Item 7) Item 6. The device of item 5, wherein the drive mechanism is configured to move the tip holder conveyor to a standby position where no tip holder is located at the tip release location when the waste container sensor detects that the waste container is positioned to receive the released pipette tip. (Item 8) 8. The device of claim 7, wherein when the tip holder conveyor moves to the standby position, each tip holder holding a pipette tip is moved sequentially relative to the tip ejector to remove the pipette tip from the associated tip holder so that the pipette tip is not held by the tip holder conveyor when the tip holder conveyor is in the standby position. (Item 9) 9. The device of any one of items 1 to 8, wherein the tip holder conveyor comprises a tip holder chain comprising a plurality of interconnected links, each tip holder being part of one of the links. (Item 10) 9. The device according to any one of items 1 to 8, wherein the chip holder conveyor includes a detection element on each chip holder, and the device further includes a sensor for detecting each detection element passing by the sensor when the drive mechanism moves the chip holder conveyor. (Item 11) Item 11. The device of item 10, wherein the chip holder conveyor may include a chip holder chain comprising a plurality of interconnected links, each chip holder being part of one of the links, and each detection element comprising a pin connecting one link to an adjacent link. (Item 12) Item 12. The device of item 11, further comprising a controller configured to determine a position of the chip holder chain based on a number of detection elements that have passed the sensor. (Item 13) 13. The device of claim 11 or 12, wherein the chip holder chain comprises a continuous chain guided by a continuous track. (Item 14) Item 14. The device of item 13, wherein the drive mechanism comprises a chain drive with a motorized wheel, the continuous chain being wrapped around the motorized wheel. (Item 15) 15. The device of any one of items 1 to 14, wherein each tip holder comprises a clip defining an opening configured to receive a pipette tip without any resistance. (Item 16) Item 16. The device of item 15, wherein each clip has opposing arms configured to hold a pipette tip therebetween and defining a lateral opening narrower than the width of a portion of the pipette tip held between the opposing arms. (Item 17) Item 17. The device of item 16, wherein the tip ejector comprises one or more ramps or wedges that contact a pipette tip held in the opening of the clip when the tip holder passes through the tip ejector, and the opposing arms are flexible so that when the one or more ramps contact the pipette tip, the pipette tip moves laterally, urging the opposing arms to open and enlarging the lateral opening to allow the pipette tip to pass through the lateral opening and be removed from the tip holder. (Item 18) Item 18. The device of item 17, wherein the tip holder conveyor follows a curved path adjacent to the tip ejector. (Item 19) Item 19. The device of item 17 or 18, wherein the tip ejector comprises first and second laterally extending ramps or wedges, the first laterally extending ramp configured to engage a first portion of the pipette tip extending above the clip when the tip holder is moved relative to the tip ejector, and the second laterally extending ramp configured to engage a second portion of the pipette tip extending below the clip when the tip holder is moved relative to the tip ejector. (Item 20) 20. The device of any one of items 1 to 19, wherein the drive mechanism is configured to move the tip holder conveyor in a first direction to sequentially position each tip holder at the tip release location, and to move the tip holder conveyor in a second direction opposite to the first direction to move the tip holder conveyor relative to the tip ejector to remove the pipette tip from the associated tip holder. (Item 21) 21. The device of claim 20, wherein at least a portion of the chip holder conveyor follows a linear path when moving in the first and second directions. (Item 22) A device, a pipettor configured for lateral and longitudinal movement within the instrument, the pipettor having a mounting end adapted to receive a pipette tip in a friction fit; a waste container movable between a first receptacle position and a second receptacle position, wherein when the waste container is in the first receptacle position, the waste container is positioned to receive pipette tips released from the mounting end of the pipettor at a tip release location, and when the waste container is in the second receptacle position, the waste container is not positioned to receive pipette tips released from the mounting end of the pipettor at the tip release location; a pipette tip holder movable between a first tip holder position and a second tip holder position, wherein in the first tip holder position, the pipette tip holder is not positioned to receive pipette tips released from the mounting end of the pipettor at the tip release location when the waste container is in the first receptacle position, and wherein in the second tip holder position, the pipette tip holder is positioned to receive and hold pipette tips released from the mounting end of the pipettor at the tip release location when the waste container is in the second receptacle position. (Item 23) 1. A method for capturing one or more pipette tips released from an automated pipettor, the method comprising: a) repeatedly moving the pipettor laterally with the pipette tip secured thereto to a tip release position to release the pipette tip from the pipettor, thereby causing the released pipette tip to drop into a waste container positioned to receive the released pipette tip; b) detecting whether the waste container is no longer positioned to receive pipette tips released from the pipettor at the tip release position; c) upon detecting that the waste container is no longer positioned to receive pipette tips released from the pipettor at the tip release position, moving a pipette tip holder from a first tip holder position where the pipette tip holder is not positioned to receive pipette tips released from the pipettor at the tip release position to a second tip holder position where the pipette tip holder is positioned to receive pipette tips released from the pipettor at the tip release position, and receiving the pipette tips released from the pipettor while the pipette tip holder is in the second tip holder position. (Item 24) 1. A method for facilitating sequential processing of multiple samples in an automated system, the method comprising: a) detecting that a waste container of the system is not in a pipette tip receiving position; b) after step a), and while the waste container is not in the pipette tip receiving position, isolating one or more pipette tips released from a pipettor in a pipette tip holding station of the system, wherein the isolated pipette tips have previously been used for the processing of at least a subset of the plurality of samples in the system, and when the waste container is in the pipette tip receiving position, any pipette tips used for the processing of the plurality of samples and released from the pipettor are released directly into the waste container; c) after step b), detecting that the waste container is in the pipette tip receiving position; d) after step c) and while the waste container is in the pipette tip receiving position, transferring the isolated pipette tip from the pipette tip holding station to the waste container; A method wherein the processing of the plurality of samples in the system is continuous between steps a) to d). [Brief explanation of the drawings]

[0078] The accompanying drawings, which are incorporated in and form a part of this specification, illustrate various non-limiting embodiments of the present disclosure, in which like reference numbers indicate identical or functionally similar elements.

[0079] [Figure 1] FIG. 1 is a perspective view of an instrument in which the pipette tip holding station disclosed herein may be implemented. [Figure 2] FIG. 1 is a partial perspective view of a portion of an instrument in which a pipette tip holding station may be implemented. [Figure 3] FIG. 1 is a perspective view of the holding station together with the instrument's automated pipettor, waste container, and waste drawer. [Figure 4] FIG. 10 is a perspective view of a holding station together with a waste container and waste container sensor shown schematically. [Figure 5]FIG. 1 is a perspective view of a holding station with various components, frame elements, and cover panels omitted to reveal the internal components of the device. [Figure 6] FIG. 1 is a perspective view of a holding station with various components, frame elements, and cover panels omitted to reveal the internal components of the device. [Figure 7] FIG. 1 is a perspective view of a holding station with various components, frame elements, and cover panels omitted to reveal the internal components of the device. [Figure 8] FIG. 1 is a perspective view of a portion of a tip holder chain including two tip holder links and two connector links. [Figure 9] FIG. 10 is a perspective view of a single tip holder link and connector pin. [Figure 10] FIG. 1 is a perspective view of a single connector link and connector pin. [Figure 11] FIG. 10 is a bottom perspective view of the top frame of the detached pipette tip holding station. [Figure 12] FIG. 1 is a top perspective view of the top frame separated. [Figure 13] FIG. 10 is a partial top perspective view of a top frame and a portion of a tip holder chain. [Figure 14] FIG. 10 is a bottom perspective view of the upper track panel of the top frame separated with a portion of the tip holder chain. [Figure 15] FIG. 10 is a top perspective view of the lower track panel of the top frame separated with a portion of the tip holder chain. [Figure 16] FIG. 10 is a top perspective view of the lower track panel of the top frame separated with a portion of the tip holder chain. [Figure 17] FIG. 1 is a side view of an automated pipettor with disposable pipette tips attached. [Figure 18] FIG. 1 is a side view of an automated pipettor with disposable pipette tips released. [Figure 19] FIG. 10 is a partial top view of the holding station. [Figure 20] FIG. 1 is a top view of the holding station with various components, frame elements, and cover panels omitted to reveal the internal components of the device. [Figure 21] FIG. 10 is a partial cross-sectional view of the tip holding station showing the automated pipettor releasing a pipette tip into a tip holder link of the tip holder chain. [Figure 22] FIG. 10 is a partial perspective view of the top frame of the tip holding station showing that the tip ejector and pipette tips are held within the tip holder links of the tip holder chain. [Figure 23] 1 is a flow chart illustrating a method for facilitating sequential processing of multiple samples in an automated system. [Figure 24] FIG. 2 is a block diagram that schematically illustrates the control structure of the device. DETAILED DESCRIPTION OF THE INVENTION

[0080] While aspects of the presently disclosed subject matter may be embodied in a variety of forms, the following description and the accompanying drawings are intended to disclose only some of these forms as particular examples of the subject matter, and therefore, the presently disclosed subject matter is not intended to be limited to the forms or embodiments so described and illustrated.

[0081] Unless otherwise defined, all technical terms, notations, and other scientific or technical terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents, applications, published applications, and other publications referenced herein are incorporated by reference in their entirety. To the extent that a definition set forth in this section contradicts or conflicts with a definition set forth in a patent, application, published application, or other publication incorporated herein by reference, the definition set forth in this section shall prevail over the definition incorporated herein by reference.

[0082] As used herein, "a" or "an" means "at least one" or "one or more."

[0083] The present description may use relative spatial and / or orientation terms when describing the location and / or orientation of components, devices, locations, features, or portions thereof. Unless specifically stated or otherwise indicated by the context of the description, such terms, including but not limited to top, bottom, above, below, under, on, upper, lower, left, right, front, back, next to, adjacent, between, horizontal, vertical, diagonal, longitudinal, lateral, radial, axial, etc., are used for convenience when referring to such components, devices, locations, features, or portions thereof in the drawings, but are not intended to be limiting.

[0084] Additionally, unless otherwise specified, specific dimensions referred to in this description merely represent example implementations of devices embodying aspects of the present disclosure and are not intended to be limiting.

[0085] The use of the term "about" or similar terms applies to all numerical values ​​specified herein, whether explicitly stated or not. This term generally refers to a range of numbers that one of ordinary skill in the art would consider, in the context of this disclosure, a reasonable amount of deviation from the recited numerical value (i.e., having an equivalent function or result). For example, and without intending to be limiting, this term can be interpreted to include a deviation of ±10 percent from a given numerical value, although such deviation does not alter the resulting final function or value. Thus, in some circumstances, as understood by those skilled in the art, a value of about 1% can be interpreted as being in the range of 0.9% to 1.1%.

[0086] As used herein, the term "adjacent" or similar terms refers to being near or adjacent. Adjacent objects can be spaced apart from one another or can actually be in direct contact with one another. In some cases, adjacent objects can be joined to one another or integrally formed with one another.

[0087] As used herein, the terms "substantially" and "substantial," or similar terms, refer to a significant degree or extent. When used in conjunction with an event, circumstance, characteristic, property, or the like, these terms can refer to instances in which the event, circumstance, characteristic, or property occurs exactly, as well as instances in which the event, circumstance, characteristic, or property occurs to a close approximation, such as to account for a typical tolerance level or variability in the embodiments described herein.

[0088] As used herein, the terms "optional" and "optionally" or similar terms mean that a subsequently described component, structure, element, event, circumstance, characteristic, feature, etc. may or may not be included, or may or may not occur, and that the description includes or occurs, as the case may be, the component, structural element, event, circumstance, characteristic, feature, etc.

[0089] As used herein, the term "uninterrupted" or phrase "uninterrupted processing," or similar terms or phrases, refers to a system or equipment that performs a process that includes multiple sequential steps without pausing or stopping the process—either during or between steps—for any reason other than for a normal or predetermined pause in the process during or between steps. Non-limiting examples of normal pauses include waiting for a predetermined period of time to complete a step, waiting for equipment or materials to reach a predetermined temperature or other necessary or desired state or condition, or pausing between process steps while one or more common components required to perform the next step in the process are used to perform one or more steps in another process.

[0090] An instrument in which a pipette tip holding station as disclosed herein may be implemented is designated by reference numeral 225 in FIGS. 1 and 2 and includes an automated robotic pipettor 300. With reference to FIGS. 2 and 3, a pipette tip holding station for capturing and temporarily holding (isolating) pipette tips separated from a pipettor is designated by reference numeral 100 and may be referred to herein as a "holding station." As shown in FIGS. 2 and 3, holding station 100 is disposed below pipettor 300. A waste container 220 for receiving pipette tips discarded by pipettor 300 may be supported within a waste drawer 224 of instrument 225 (see FIGS. 1 and 3), which is configured to move laterally into or out of instrument 225. Waste container 220 may be lined with a plastic bag, which may be disposable. When drawer 224 is moved laterally into instrument 225 and in a closed position, as shown in FIG. 3, holding station 100 is disposed above waste container 220.

[0091] The instrument 225 may be a chemical or biological analyzer, such as a molecular analyzer for performing nucleic acid-based amplification reactions. Exemplary processing instruments with which the holding station 100 may be used include the analyzers described in U.S. Patent Nos. 8,731,712 and 9,732,374 and International Patent Application No. PCT / US2018 / 041472, as well as the Panther® and Panther Fusion® systems available from Hologic, Inc. (Marlborough, MA).

[0092] The pipettor 300 can be configured to move laterally and vertically, e.g., in the X, Y, and Z directions, and is used to remove liquids from and dispense liquids into containers. For example, the pipettor 300 can be used to transfer one or more reagents from one or more reagent containers to one or more reaction containers and to transfer sample material from one or more sample containers to one or more reaction containers to form a reaction mixture. The reagents can be stored in a liquid state, or they can be stored in a non-liquid state, e.g., a lyophilized state, in which case the pipettor can be used to transfer a reconstituting agent into a reagent container and then transfer the reconstituted reagent to a reaction container. The instrument 225 can include a tray or container 228 (see FIG. 2 ) that holds a plurality of pipette tips. The tray or container 228 may reside within a pipette tip holder bay (e.g., a drawer) of the instrument 225 for removably attaching to the pipettor 300 in a position and orientation that allows the pipettor 300 to selectively engage individual pipette tips.

[0093] 17 and 18, a pipettor 300 may have a probe 302 (shown only in FIG. 18) having a mounting end 314 (which may be the distal end of the probe) to which a disposable pipette tip 290 is removably attached. In one embodiment, the mounting end 314 of the pipettor 300 is configured to receive the pipette tip 290 in a friction fit when the mounting end 314 is inserted into the pipette tip 290 or when the pipette tip 290 is mounted onto the mounting end 314. Referring to FIG. 18, one embodiment of the pipette tip 290 includes a collar 292 at a first (proximal) end of the pipette tip 290, a conically tapered tip 296 at a second (distal) end of the pipette tip 290, and a barrel portion 294 between the collar 292 and the tip 296, which may be cylindrical in shape with a substantially constant diameter. Exemplary commercially available pipette tips are available from TECAN (TECAN Inc., Research Triangle Park, NC).

[0094] As shown in FIGS. 17 and 18 , the pipettor 300 includes a generally vertical pipettor arm 310 terminating in a housing 312 that couples a probe 302 to the pipettor arm 310. The housing 312 couples or connects the probe 302 to a pressure source (vacuum or positive pressure) through the arm 310. The pipettor 300 may include a tip release mechanism for releasing the pipette tip 290 from the mounting end 314 of the probe 302. In one embodiment, the tip release mechanism includes a release sleeve 304 that is coaxially mounted on the probe 302 and axially movable relative to the probe 302. The release sleeve 304 is connected to a release lever 306 that is configured to move the release sleeve 304 axially relative to the probe 302. A release trigger 308 (shown only in FIG. 17 ) is coupled to the release lever 306 within the housing 312 by a linkage (not shown).

[0095] The pipette tip 290 is frictionally secured to the probe 302 by inserting the probe 302 into an opening surrounded by a collar 292 of the pipette tip 290 supported in the pipette tray 228. When the probe 302 is inserted into the pipette tip 290, the top end of the probe 290 contacts the release sleeve 304, pushing the sleeve 304 and release lever 306 upward to the position shown in Figure 17. When the sleeve 304 and release lever 306 are pushed up, the linkage connecting the release lever 306 to the release trigger 308 causes the release trigger 308 to extend below the housing 312, as shown in Figure 17. To dispense or release the pipette tip 290 from the pipettor 300, the pipette arm 310 is lowered until the release trigger 308 contacts a release surface, which forces the release trigger 308 upward into the housing 312, thereby moving the release lever 306 and release sleeve 304 axially downward relative to the probe 302. The downward movement of the release sleeve 304 contacts the top end of the pipette tip 290, which is frictionally secured to the probe 302, thereby pushing the pipette tip 290 from the probe 302 and releasing the pipette tip 290 from the pipettor 302.

[0096] 4, one embodiment of holding station 100 includes a top frame 102, a side box frame 150, a side cover panel 160 disposed on top of the side box frame 150, an upper waste chute 152 (which may be a lower portion of the side box frame 150) connecting to a lower waste chute 162, and a waste chute cover panel 164 disposed on top of the lower waste chute 162. Holding station 100 further includes a holding compartment 166 disposed below a portion of top frame 102. As mentioned above, waste container 220 (schematically represented by a square in FIG. 4) comprises a container positioned below waste chute 162 for receiving waste items, such as pipette tips, that fall through chute 162. The waste container is typically disposable and may be lined with a plastic bag. As described above, the waste container 220 may be supported within the device 225 in a drawer 224 configured to move laterally (e.g., move forward and backward relative to the front of the device 225) between a first or closed position and a second or open position within the device 225, in which the drawer 224 is pulled out of the device 225 in a manner that allows access to the waste container 220 so that the waste container can be removed from the drawer 224 and emptied, and / or the bag lining the waste container 220 can be removed from the waste container 220 and replaced with a new empty bag.

[0097] When the waste container 220 is positioned under the waste chute 162 of the holding station 100—e.g., when the drawer is in the first or closed position—the waste container 220 is in a pipette tip receiving position relative to the pipettor 300, positioned to capture used pipette tips released by the pipettor 300. In various embodiments, the waste container sensor 222 generates a signal—described below—for the system control software to detect the presence or absence of the waste container 220 (i.e., the waste container sensor 222 detects whether the waste container 220 is in the pipette tip receiving position). Alternatively, when the waste container 220 is supported within a drawer, the waste container sensor 222 may detect whether the drawer 224 is in the open or closed position to determine whether the waste container 220 is in the pipette tip receiving position. The waste container sensor 222 may include any sensor for detecting the presence or absence of the waste container 220 and / or the position of the drawer 224, such as a proximity sensor, a contact sensor, a switch, an optical sensor, etc.

[0098] In one exemplary embodiment, holding station 100 may optionally include a printed circuit board 280 mounted to top frame 102. Circuit board 280 may include circuitry and power and logic components for controlling and providing power to holding station 100.

[0099] 5 is a perspective view of holding station 100 with top frame 102, printed circuit board 280, side cover panel 160, holding compartment 166, and waste chute cover panel 164 omitted to reveal the internal components of holding station 100. As shown in FIG. 5, holding station 100 includes a chip holder conveyor which, in the illustrated embodiment, is partially supported by lower track panel 130 and includes a chip holder chain 230 driven by a chain drive mechanism 200. Chain drive mechanism 200 is mounted to top frame 102 and includes a motor 202 connected to a drive wheel 204 operably coupled to chip holder chain 230. Motor 202 may be controlled by one or more components of printed circuit board 280, and power may be transmitted to motor 202 by the printed circuit board.

[0100] FIG. 6 is a perspective view of the holding station 100, with the top frame 102, drive mechanism 200, printed circuit board 280, side cover panel 160, lower track panel 130, and waste chute cover panel 164 omitted to reveal the internal components of the holding station 100. FIG. 7 is a perspective view of the holding station 100, with the top frame 102, drive mechanism 200, printed circuit board 280, side box frame 150, and lower track panel 130 omitted to reveal the internal components of the holding station 100. As shown in FIGS. 6 and 7 , the tip holder chain 230 can include multiple tip holder links 232 and multiple connector links 252. While each tip holder link 232 is shown holding a pipette tip 290 in FIG. 6 , depending on the state of the holding station 100, one or more or all of the tip holder links 232 may not be holding a pipette tip 290. 5 and 6 , the box frame 150 includes a lower flange 154, and a portion of the pipette tips 290 carried on the tip holder chain 230 is disposed above the lower flange 154 and behind the side cover panel 160. In one embodiment, the tip holder chain 230 is a continuous chain supported on a continuous track (described in more detail below), and a portion of the pipette tips 290 carried on the tip holder chain 230 may remain in the upper retaining compartment 166 of the drip panel 168 (see FIG. 7 ), which cooperates with the lower flange 154 of the box frame 150 to form a drip tray below the pipette tips 290 supported on the tip holder chain 230. The drip tray is positioned to capture residual liquid that may drip from the pipette tips 290 carried on the tip holder chain 230 and may direct the captured liquid toward the upper chute 152 and lower chute 162 and into the waste container 220.

[0101] 6 and 7, the tip holder chain 230 may comprise a continuous chain of multiple interconnected tip holders, each configured to receive and hold a pipette tip released from a pipettor. In one example, the tip holder comprises tip holder links 232, and in the illustrated embodiment, 22 tip holder links 232. In alternative embodiments, the tip holder chain may comprise fewer or more than 22 tip holder links 232. The tip holder chain 230 may further include multiple connector links 252 connected to or by pins with adjacent connector links 252, as described below.

[0102] In alternative embodiments, the tip holder chain may be discontinuous - or even non-chain - but may comprise a straight or curved chain or rail on which a plurality of tip holders are supported.

[0103] Features of one embodiment of tip holder chain 230 are shown in Figures 8, 9, and 10. Figure 8 is a perspective view of a portion of tip holder chain 230 including two tip holder links 232a and 232b and two connector links 252a and 252b. Figure 9 is a perspective view of a single tip holder link 232 and connector pin 249. Figure 10 is a perspective view of a single connector link 252 and connector pin 259.

[0104] 9 , each tip holder link 232 includes a holder clip defined by opposing arms 234 and 236 with a lateral opening or gap 238 defined between the distal ends of the arms 234, 236. The tip holder link 232 includes a lower lug 244 and an upper lug 246. A riser 240 extends from the opposing arms 234, 236 to the lugs 244, 246. A tip support shelf 242 is partially formed by the top surfaces of the arms 234, 236 and extends across the riser 240 and between the arms 234, 236. In one embodiment, the space partially encompassed by the arms 234, 236 and the riser 240 defines an opening configured to receive the barrel 294 of the pipette tip 290 with little or no resistance and with the collar 292 of the pipette tip 290 supported on the tip support shelf 242.

[0105] A connector pin or post 249 extends through and is preferably secured within the lower lug 244, with an upper portion 248 (upper post) extending above the lower lug 244 and a lower portion 250 (lower post) extending below the lower lug 244. A pin opening 245 in the upper lug 246 receives a connector pin of an adjacent link.

[0106] 10 , each connector link 252 includes a first lug 254 and a second lug 256, with the first lug 254 disposed above the second lug 256. A connector pin (or post) 259 extends through, and is preferably secured within, the second lug 256, with an upper portion 258 (upper post) extending above, and a lower portion 260 (lower post) extending below, the second lug 256. A pin opening 255 in the first lug 254 receives a connector pin of an adjacent link.

[0107] 8, one connector link 252a is connected to an adjacent connector link 252b by inserting a connector pin 259b of the second connector link 252b through the pin opening 255 of the first lug 254 of the first connector link 252a. One tip holder link 232a is connected to an adjacent tip holder link 232b by inserting a connector pin 249b of the second tip holder link 232b through the pin opening 245 of the top lug 246 of the first tip holder link 232a. Connector link 252b is connected to an adjacent tip holder link 232a by inserting a connector pin 249a of the adjacent tip holder link 232a through the pin opening 255 of the first lug 254 of connector link 252b.

[0108] Features of the top frame 102 are shown in Figures 11-16. Figure 11 is a bottom perspective view of the top frame 102 in isolation, and Figure 12 is a top perspective view of the top frame 102. A tip holder chain (not shown in Figures 11 or 12) is supported in a track 122 defined between an upper track panel 110 and a lower track panel 130, which form the top frame 102. A drive motor 202 of a chain drive mechanism 200 is mounted on the upper track panel 110, and a chain drive wheel 204 is disposed between the upper track panel 110 and the lower track panel 130. The chain drive wheel 204 may be rotatably supported within the top frame 102 by a bearing 214 formed in the upper track panel 110 (see Figure 13) and a bearing in the lower track panel 130. A release opening 120 is formed along one edge of the upper track panel 110. The tip ejector positioned adjacent the release opening 120 is defined by an upper tip ejector ramp or wedge 114 that is part of the upper track panel 110 and a lower tip ejector ramp or wedge 142 that is part of the lower track panel 130 .

[0109] 13 is a partial top perspective view of the top frame 102 and a portion of the tip holder chain 230. As shown in FIG. 13, the tip holder chain 230 is supported by the upper track panel 110 and the lower track panel 130, such that a portion of the tip holder chain 230 passes between the upper tip ejector ramp 114 and the lower tip ejector ramp 142.

[0110] FIG. 14 is a bottom perspective view of the separated upper track panel 110 with a portion of the tip holder chain 230. As shown in FIG. 14, the tip holder chain 230 is disposed in an upper track slot 112 formed in the upper track panel 110. Specifically, the upper posts 248 and 258 of the tip holder link 232 and the connector link 252 of the tip holder chain 230 (see FIGS. 9 and 10) each extend into the upper track slot 112. A sensor opening 116 is formed in the upper track panel 110 (see also FIG. 12) and spans a portion of the upper track slot 112. An optical sensor (not shown in FIGS. 12 or 14) may be installed in the opening 116 to detect the passage of the upper posts 248, 258 of the tip holder chain 230 as the chain 230 passes through the opening 116. In one embodiment, the sensor comprises an optical transmitter on one side of the upper track slot 112 and an optical receiver on the opposite side of the track slot 112. As the tip holder chain 230 advances around the upper track slot 112, the upper posts 248, 258 of the tip holder chain 230 pass through the opening 116 between the optical transmitter and optical receiver of the optical sensor located therein, thereby interrupting the optical beam from the transmitter to the receiver and generating a signal as each post of the tip holder chain 230 passes the sensor positioned in the opening 116. Thus, the position of the tip holder chain 230 can be monitored by a system controller—described below—by counting the number of posts that pass the sensor as well as by using the encoder count or motor count of the chain drive motor 202.

[0111] In one embodiment, one of the posts may be referred to as the "home" post, thereby identifying a particular position of the tip holder chain 230 as the "home" position. For example, the "home" post may be shorter than all other posts, but short enough so that the height of the post does not trip the optical sensor in the sensor opening 116. The system control software expects the optical sensor to be tripped after a certain number of motor steps. If it finds home, it knows that the expected number of motor steps to the next post has been exceeded, so the software continues moving the tip holder chain until the next post trips the sensor. The control software then reverses the direction of the tip holder chain by a set number of motor steps and sets that position as home.

[0112] 14, in one embodiment, the chain drive wheel 204 includes an upper wheel 206 and a lower wheel 208 connected by a connecting hub 210. A peripheral notch 213 is formed in the upper wheel 206, and a peripheral notch 212 is formed in the lower wheel 208. Upper posts 248, 258 of the tip holder chain 230 are received in the upper peripheral notch 213 of the upper wheel 206 as the chain drive wheel 204 rotates, and lower posts 250, 260 of the tip holder chain 230 are received in the lower peripheral notch 212 of the lower wheel 208 as the chain drive wheel 204 rotates (see also FIGS. 15 and 16).

[0113] 15 and 16 are top perspective views of the isolated lower track panel 130 with a portion of the chip holder chain 230. The lower track panel 130, which is secured to the bottom of the upper track panel 110, includes a lower track slot 132 around a portion of its periphery. A chain drive wheel 204 is rotatably supported on the lower track panel 130. When the lower track panel 130 is secured to the upper track panel 110, the lower track slot 132 aligns with the upper track slot 112. A lower track inner shelf 140 and a lower track outer shelf 144 are located on either side of the lower track slot 132. The chip holder chain 230 is supported within the lower track slot 132 by the lower track inner shelf 140 and the lower track outer shelf 144. More specifically, the lower portion of each tip holder link 232, forming the lower lug 244 and upper lug 246, is supported on the lower track inner shelf 140 and lower track outer shelf 144, and a lower post 250 of each connector pin 249 extends into the lower track slot 132. Similarly, although not shown in FIGS. 15 and 16 , each connector link 252 of the tip holder chain 230 is similarly supported by a second lower lug 256 that is supported on the lower track inner shelf 140 and lower track outer shelf 144, and a lower post 260 of each of the connector pins 259 extends into the lower track slot 132.

[0114] 19 and 20 , under normal operation of the instrument 225 and the pipettor 300, after a pipette tip 290 is used, the pipettor 300 moves to the tip release location 270 of the release opening 120 formed in the top frame 102. At the tip release location 270, the pipettor 300 lowers the pipette tip 290 into the release opening 120, and the pipette tip 290 is released (discharged) from the pipettor 300 and falls through the release opening 120 in the back of the side cover panel 160, through the lower waste chute 162 in the back of the waste chute cover panel 164, and into the waste container 220. During this operation, while the waste container 220 is in place or while the drawer 224 supporting the waste container is closed - as detected by the waste container sensor 222 - the tip holder chain 230 (or in an embodiment that does not include a tip holder chain, the tip holder conveyor) is in a first or standby position, in which none of the tip holder links 232 (or in an embodiment that does not include a tip holder chain, the tip holders) are positioned at the tip release location 270, and typically none of the holder links are holding a pipette tip. When the waste container 220 is removed or the drawer 224 is opened, detected by the sensor 222, a tip holder advance command is sent to the drive mechanism 200, which then advances the tip holder chain 230 in a direction "A" (clockwise in FIG. 20 ), which is transverse to the orientation of the pipette tip 290, to position the first tip holder link 232 at a second position in the tip release location 270 to capture and hold the pipette tip 290 released by the pipettor 300. If the waste container 220 is not in a position to receive the pipette tip released by the pipettor, after the pipette tip 290 is released into the first tip holder link 232, a tip holder advance command is sent to the drive mechanism 200 to index the tip holder chain 230 and position the next tip holder link 232 at the tip release location 270 to capture and hold the next pipette tip 290 released by the pipettor 300.In response to the tip holder advance command, the drive mechanism 200 continues to advance the tip holder chain 230 in direction "A", sequentially positioning the tip holder links 232 at the tip release locations 270 to capture and hold each pipette tip 290 released by the pipettor 300 while the waste container 220 was not in the pipette tip receiving position.

[0115] In an alternative embodiment, the location where a pipette tip is released into a tip holder when a waste container is not positioned to receive the released pipette tip (i.e., the second tip release location) is different from the tip release location 270 where a pipette tip is released when a waste container is positioned to receive the released pipette tip (i.e., the first tip release location). Such an embodiment necessarily requires a reconfiguration of the tip holder chain 230 (or the tip holder conveyor, in an embodiment that does not include a tip holder chain) so that tip holders 232 are sequentially positioned at the second tip release location to capture released tips when a waste container is not positioned to receive the released pipette tip.

[0116] 21 is a partial cross-sectional view of the tip holding station 100 showing the pipettor 300 releasing the pipette tip 290 into the tip holder link 232 of the tip holder chain 230. As shown in FIG. 21 , with one of the tip holder links 232 of the tip holder chain 230 positioned at the tip release location 270, the pipettor 300 lowers the pipettor tip 290 into the tip holder link 232. As the pipettor 300 continues to lower, the release trigger 308 contacts the release surface 156 at the top of the side box frame 150 of the holding station 100. This pushes the release trigger 308 upward, thereby moving the release lever 306 and release sleeve 304 downward and pushing the pipette tip 290 from the pipettor 300 into the tip holder link 232 positioned at the tip release location 270.

[0117] In the illustrated embodiment, pipettor 300 releases pipette tips at tip release location 270, regardless of whether the pipette tips are released into waste container 220 positioned to receive released pipette tips or into a tip holder of the tip holder conveyor when waste container 220 is not positioned to receive released pipette tips. In another embodiment, pipette tips released into a waste container positioned to receive released pipette tips are released at a different location than the location where pipette tips are released into tip holders of the tip holder conveyor when the waste container is not positioned to receive released pipette tips.

[0118] In one embodiment, the tip holder advance command to actuate the drive mechanism 200 can be triggered by movement of the pipettor 300 when the waste container 220 is not positioned to receive a pipette tip released by the pipettor 300. After the pipettor 300 releases a pipette tip 290 and retracts to a position away from the tip release location 270, the drive mechanism 200 is actuated to position the tip holder chain 230 to the next tip holder link 232 in the tip release location 270 and waits until the pipettor 300 releases another pipette tip 290. The release of the pipette tip 290 from the pipettor 300 may be detected by actuation of a tip ejector, such as a release sleeve 304, configured to eject the pipette tip 300 from the probe 302 (e.g., by a switch actuated by a release trigger 308 and / or a release lever 306), or the pipette tip 290 may be at least partially conductive and the pipettor 300 may be configured to detect (e.g., capacitively) the presence or absence of the pipette tip 290 on the probe 302.

[0119] In the illustrated embodiment, once a pipette tip 290 is captured and held by a tip holder link 232 of the tip holder chain 230, the chain 230 is advanced laterally relative to the orientation of the pipette tip, and the captured tip is positioned behind the side cover panel 160 and above the lower flange 154 of the side box frame 150 (see FIGS. 5 and 6 ). As the tip holder chain 230 continues to advance, some of the tip holder links 232 and the pipette tips 290 held thereby are held above the drop plate 168, as shown in FIG. 7 , and within the holding compartments 166, as shown in FIGS. 6 , 7 , and 20 . This arrangement contains any liquid that drips from the pipette tips 290 being carried by the tip holder chain 230.

[0120] When the waste container 220 is again in the pipette tip receiving position, e.g., after the waste container 220 has been replaced or the drawer 224 has been closed—as detected by the waste container sensor 222—the pipette tips 290 held in the tip holders (e.g., tip holder links 232) are transferred from the tip holding station 100 to the waste container 220. For example, the pipette tips 290 held in the tip holders are ejected, removed, or displaced from the associated tip holders at a tip removal location 165, which may be adjacent to the tip release location 270 (see FIGS. 19 and 20). In one embodiment, a tip holder reverse command causes the drive mechanism 200 to reverse the direction of the tip holder chain 230 and move it in the lateral direction “B” (counterclockwise in FIG. 20). As shown in FIGS. 11-13 and described above, the tip ejector may include an upper tip ejector ramp 114 and a lower tip ejector ramp 142. Tip ejector ramps or wedges 114 and 142 each include a sloped edge or surface, and as tip holder link 232 passes over ramps 114, 142 in a direction of increasing outward extension, as shown in FIG. 22, ramps 114 and 142 engage pipette tip 290 held by tip holder link 232, displacing or ejecting pipette tip 290 from between arms 234 and 236 (only arm 234 is visible in FIG. 22), removing the pipette tip from tip holder link 232.

[0121] As the tip holder chain 230, carrying one or more pipette tips 290, moves in direction "B" relative to the tip ejector (ramps 114, 142), each tip holder link is positioned at a third position at the tip removal location 165. As the tip holder link 232 passes the third position, each pipette tip 290 engages with the tip ejector ramps 114, 142 and is laterally displaced from between the arms 234 and 236 of the associated tip holder link 232 as the link passes the tip ejector. More specifically, as shown in the embodiment of FIG. 22 , the upper tip ejector ramp 114 engages a portion of the collar 292 of the pipette tip 290 located above the tip holder link 232, and the lower tip ejector ramp 142 engages a portion of the barrel 294 of the pipette tip 290 located below the tip holder link 232. The arms 234, 236 of the tip holder link 232 may be made from a flexible material such as polyoxymethylene (POM), available under the trade name Delrin®. POM, also known as acetal, polyacetal, and polyformaldehyde, is an engineering thermoplastic used in precision parts requiring high stiffness, low friction, and excellent dimensional stability. It is also available under trade names such as Celcon®, Ramtal, Duracon®, Kepital®, and Hostaform®, which have slightly different chemical formulas. In this manner, when the tip ejector ramps 114, 142 engage the pipette tip 290 while the tip holder link 232 moves along the track slot 112 / 132 relative to the tip ejector ramps 114, 142 and the pipette tip 290 is pushed into the gap 238 between the arms 234, 236 (see FIG. 9), the arms 234, 236 flex outward, thereby widening the gap 238 and allowing the barrel 294 of the pipette tip 290 to pass through the gap 238, thereby removing the pipette tip 290 from the tip holder 232.Alternatively, the arms 234, 236 can be made of a relatively inflexible material, such as aluminum, and the pipette tip 290 can be formed from a compressible material, such that while the tip holder link 232 moves relative to the tip ejector ramps 114, 142, the tip ejector ramps 114, 142 engage the pipette tip 290, forcing the pipette tip 290 into the gap 238 between the arms 234, 236 (see FIG. 9 ), compressing the barrel 294 of the pipette tip 290 to the width of the gap 238, thereby allowing the barrel 294 to pass through the gap 238 and removing the pipette tip 290 from the tip holder 232. As a further alternative, the pipette tip 290 can be removed by a combination of flexing of the arms 234, 236 and compression of the barrel 294 of the pipette tip 290.

[0122] In an alternative embodiment, the tip ejector is located at a position along the continuous travel path of the pipette tip holder chain 230 at a location displaced in the direction "A" from the tip release location 270. In such an arrangement, continued movement of the pipette tip holder chain 230 in the direction "A" causes the tip holders 232 to pass the tip ejector, thus removing any pipette tips being carried by the tip holder chain 230. Thus, pipette tips 290 are not removed from the tip holders 232 of the pipette tip holder chain 230 by reversing the direction of movement of the tip holder chain, but rather by continued movement in the same direction "A" as the tip holder chain moves while the pipette tip is captured in the tip holder. Because the tip removal location in such an embodiment may not be proximate to the tip release location 270, an enlarged or otherwise modified waste chute may be required to direct removed pipette tips from the tip holders 232 into the waste container 220.

[0123] In an alternative embodiment, the tip ejector can include a single ramp that engages the pipette tip 290 above or below the tip holder link 232. In a further embodiment, the tip ejector includes more than two ramps that engage the pipette tip 290 in three or more locations above and / or below the tip holder link 232.

[0124] The tip ejector may be located adjacent to the tip release location 270 and above the lower waste chute 162, thereby removing the pipette tips 290 from their respective tip holder links 232 and causing the pipette tips 290 to fall through the lower waste chute 162 into the waste container 220.

[0125] In the illustrated embodiment, the tip holder chain 230 can capture and transport up to 22 pipette tips 290 (this is a non-limiting example; the tip holder conveyor may transport fewer or more than 22 pipette tips 290). However, it is not necessary to capture a pipette tip 290 in every available tip holder link 232. When the waste container sensor 222 detects that the waste container 220 has been removed or is otherwise not in a tip-receiving position, the drive mechanism 200 advances the tip holder chain 230 in direction "A" to sequentially position each tip holder link 232 at the tip release location 270. When the waste container sensor 222 detects that the waste container 220 is again in the pipette tip receiving position, the drive mechanism 200 may reverse the direction of the tip holder chain 230 to direction "B" to remove all of the pipette tips 290 carried by the tip holder chain 230, regardless of whether the pipette tips 290 are captured by any of the tip holder links 232. On the other hand, if the waste container 220 has been absent for an extended period of time and the pipette tips 290 are captured by all of the tip holder links 232 before the waste container 220 is replaced, no tip holder advance command will be sent to the drive motor 202, the pipette tip holder conveyor (e.g., the pipette tip holder chain 230) will not move, and operation of the pipettor 300 may be suspended until the waste container 220 is returned to the pipette tip receiving position.

[0126] As mentioned above, in alternative embodiments, the tip holder chain 230 need not be a continuous chain as shown, but may be a discontinuous group of tip holders having a looped or linear arrangement of adjacently positioned tip holders, including means for automatically moving the arrangement to sequentially place each tip holder at a tip release location, or for a tip ejector to pass each tip holder sequentially to remove the pipette tip from the tip holder.

[0127] 23 is a flowchart illustrating a method 400 for facilitating sequential processing of multiple samples in an automated system. Generally, the purpose of the method and apparatus is to detect whether a waste container is positioned in a pipette tip receiving position relative to a pipette release location of a pipettor. If the waste container is not in the pipette tip receiving position, pipette tips released by the pipettor are captured and held by a pipette tip holding station, isolating them until the waste container is returned to the pipette tip receiving position. In one embodiment, the isolated pipette tips have previously been used to process at least a subset of multiple samples in the system. When the waste container is in the pipette tip receiving position, any pipette tips used to process multiple samples and released from the pipettor are released directly into the waste container. After the waste container is returned to the pipette tip receiving position, the isolated pipette tips are transferred from the pipette tip holding station to the waste container.

[0128] The method of one embodiment begins at step S402. In step S404, the pipettor 300 moves to the tip release location 270, as shown in Figures 19-21.

[0129] In step S406, it is determined whether the waste container is in place, i.e., whether the waste container is in a pipette tip receiving position. Step S406 may be performed by using sensor 222 to determine whether waste container 220 is in place to receive pipette tips 290 released by pipettor 300 and / or whether drawer 224 supporting waste container 220 is in an open or closed position.

[0130] If a waste container is determined to be in the pipette tip receiving position in step S408, the pipette tip 290 is released from the pipettor 300 and falls through the chute 162 into a waste container (eg, waste container 220).

[0131] If in step S406 it is determined that the waste container is not in a position to receive the pipette tip 290 released by the pipettor 300, then in step S410 a first tip holder of the tip holder conveyor is moved to a tip release position. If the tip holder conveyor includes a tip holder chain 230, step S410 may be performed by advancing the tip holder chain 230 to position the first tip holder link 232 at the tip release position 270 (see FIGS. 19 and 20).

[0132] In step S412, the pipette tip 290 is released into the tip holder that has been moved to the pipette tip release location. In one embodiment, step S412 may be performed by releasing the pipette tip 290 from the pipettor 300 into the first tip holder link 232.

[0133] In step S414, it is determined whether the waste container has been replaced, i.e., returned to the pipette tip receiving position. Step S414 may be performed by using sensor 222 to determine whether waste container 220 is in position to receive pipette tips 290 released by pipettor 300 and / or whether drawer 224 supporting waste container 220 is in an open or closed position.

[0134] If the waste container is determined to be at the pipette tip receiving position in step S414, then in step S416, one or more pipette tips carried by the tip holder are ejected or removed from the tip holder and allowed to fall into the waste container. The tip holder is then moved away from the tip release location. In one embodiment, step S416 is performed by moving the tip holder chain 230 relative to the tip ejector (e.g., the upper tip ejector ramp 114 and / or the lower tip ejector ramp 142), which engages and displaces the pipette tip 290 held in the tip holder link 232, which then drops the pipette tip 290 into the waste container 220.

[0135] On the other hand, if it is determined in step S414 that the waste container has not returned to the pipette tip receiving position, then in step S418 it is determined whether all tip holders on the tip holder conveyor are being used to hold pipette tips to be released by the pipettor. In one embodiment, step S418 is performed by counting the number of tip holder links 232 that have passed the tip release location 270 and the number of pipette tips 290 that have been released by the pipettor 300. The number of tip holder links 232 that have passed the tip release location 270 can be determined by a sensor located in the sensor opening 116 of the upper track panel 110 (see FIGS. 12 and 14 ).

[0136] If it is determined in step S418 that all tip holders are not being used to hold released pipette tips, the pipettor is moved to the tip release location in step S420. The next tip holder is moved to the tip release location in step S422, and the pipette tip is released by the pipettor to the tip release location of the next tip holder in step S424. Process 400 then returns to step S414.

[0137] If, in step S418, it is determined that all tip holders have been used to hold pipette tips to be released by the pipettor, and no unused tip holders remain, operation of the pipettor is suspended in step S426 because there is no means for handling additional used pipette tips. Therefore, used pipette tips cannot be discarded until the waste container is returned to the pipette tip receiving position. Therefore, process 400 returns to step S414.

[0138] Control System 24 is a block diagram that schematically illustrates a control architecture for a disposable pipette tip management system 500 for controlling the holding station 100. The exemplary control architecture may include a controller 350 that monitors, communicates with, and controls aspects of the system 500, including the drive motor 202 and link sensor 118 of the holding station 100 (which may be located in a sensor opening 116 formed in the upper track panel 110, see FIGS. 12 and 14), the pipettor 300, and the waste container sensor 222. The drive motor 202 of the holding station 100 is coupled to and controlled by the controller 350, and may also be connected to a power supply 352 that is controllable by the controller 350. The controller 350 provides power and operational control signals to the drive motor 202. The controller 350 may also receive data from the drive motor 202 in the form of rotational encoder counts from an encoder (e.g., a rotational encoder) coupled to the drive motor 202, as well as other feedback sensor signals.

[0139] Controller 350 may comprise a computer system for executing control software (which may include firmware) that effects the power, operation, control, and / or monitoring of holding station 100 and other components of system 500. Controller 350 may be implemented via one or more logic elements, such as a computer, embedded controller, programmable gate array, application-specific integrated circuit, programmable logic device, etc., and may also include or have access to data storage memory 354, which may include random access memory (RAM), read-only memory (ROM), flash memory, and other types of memory now known or later developed. Controller 350 may also include additional memory, including, for example, hard disk drives and / or magnetic tape drives, including removable storage drives, optical disk drives, USB slots, memory card interfaces, Internet memory, cloud-based memory, or any storage medium or format now known or later developed. As used herein, memory device and storage unit may include any storage medium now known or later developed for persistent and / or volatile storage of electronic data. Such data may be stored in a storage medium in a database, which may include any data structure and format now known or later developed, including, for example, a relational database, an object database, a flat file, a list, etc., or some combination thereof.

[0140] In alternative embodiments, some or all of the memory may include other similar means for allowing computer programs or other instructions to be loaded into the computer system. Such means may include, for example, removable storage units and interfaces. Examples of such may include memory sticks and memory stick interfaces, secure digital cards and interfaces, and other portable media and interfaces that allow software and data to be transferred to controller 350.

[0141] The software includes instructions stored on a non-transitory computer-readable medium that, when executed by logic elements of the controller 350, cause the control and computing hardware to perform one or more automatic or semi-automatic processes.

[0142] The computer system of controller 350 may also include a communications interface, which allows information (e.g., power, control and feedback signals, software, data, etc.) to be transferred between controller 350 and external devices. Examples of communications interfaces may include a modem, a network interface (such as an Ethernet card), a communications port, a PCMCIA slot and card, a USB port, a Firewire port, Bluetooth, or any now known or later developed interface. Information is transferred over the communications interface in the form of signals, which may be electronic, electromagnetic, optical, or other signals capable of being received by the communications interface.

[0143] The computer system of the controller 350 may also include one or more input devices, such as a touch screen, a stylus, a keyboard, a mouse or other pointing device, a microphone, a data scanner (e.g., barcode, RFID, etc.), etc. Various output devices may also be included in the computer system, including indicator lights, a display, a printer, a tactile (e.g., vibration) indicator, and an audio speaker.

[0144] As used herein, the terms “computer program medium,” “computer-readable medium,” “computer-usable medium,” and the like are used generally to refer to media such as removable storage units, hard disks installed in hard disk drives, and other means for providing software and data to controller 350.

[0145] Computer programs (also called computer control logic) are stored in one or more portions of memory 354 that are part of or accessed by controller 350. Computer programs may also be received via a communications interface. Such computer programs may include algorithms, such as algorithm 400 illustrated in FIG. 23, that, when executed, enable the computer system of controller 350 to control the operation of system 500 in accordance with embodiments disclosed herein.

[0146] In one embodiment in which aspects of the subject matter disclosed herein are implemented using software, the software may be stored on a computer program product and loaded into the computer system of controller 350 using a removable storage drive, hard drive, interface, and / or communications interface. The control logic (software), when executed by the processor of controller 350, causes the processor to perform functional aspects of the subject matter described herein via the systems, devices, apparatus, sensors, encoders, etc. described above. An operating system may perform basic tasks such as recognizing input from input devices, sending output to output devices, managing files and system resources, and managing various processes that embody computer programs running on the computer system.

[0147] Controller 350 may comprise a system 500 dedicated to holding station 100 (e.g., on printed circuit board 280, see FIG. 4 ) or a stand-alone system, or in addition to system 500, one or more components of controller 350—e.g., processor, memory, interfaces, input / output devices, etc.—may be a shared part of a global controller that controls one or more components of an instrument, such as instrument 225, or a laboratory of which system 500 is a part.

[0148] 24 , with respect to the pipette tip holding station 100, the controller 350 receives signals from and sends signals to the drive motor 202 and link sensor 118. The controller 350 may receive and send signals to the pipettor 300 and may also receive signals from the waste container sensor 222. For example, the controller 350 may send a control signal to the pipettor 300 to move to the pipette tip release location 270 and lower the pipettor arm 310 until the release trigger 308 contacts the release surface 156 (see FIG. 21 ). The controller 350 may send a signal to the pipettor 300 to move from the pipette release location 270 after the pipette tip 290 is released. The controller 350 may receive a signal from the waste container sensor 222 indicating whether the waste container 220 is in the pipette tip receiving position and / or whether the drawer 224 supporting the waste container 220 is in the open or closed position (see FIGS. 1-4). Upon receiving a signal from the waste container sensor 222 that the waste container 220 is not in the pipette tip receiving position, the controller 350 sends a signal (tip holder advance command) to the drive motor 202 to move the pipette tip holder conveyor (e.g., the pipette tip holder chain 230) to move the tip holder to the pipette tip release position. The signal from the motor 202 and / or the signal from the link sensor 118 to the controller 350 enables the controller 350 to control the drive motor 202 to appropriately position the tip holder at the tip release location. When the controller 350 receives a signal from the pipettor 300 that a pipette tip 290 has been released, the controller 350 may send a signal (tip holder advance command) to the drive motor 202 to move the next tip holder to the pipette tip release location. If the signal received by the controller 350 from the link sensor 118 indicates that all tip holders have moved to the pipette tip release location, a signal from the controller 350 to the pipettor 300 may halt operation of the pipettor 300.Upon receiving a signal from the waste container sensor 222 that the waste container 220 is in the pipette tip receiving position, the controller 350 sends a signal to the drive motor 202 (e.g., a tip holder inversion command) to move the pipette tip holder conveyor (e.g., the pipette tip holder chain 230) to a standby position. As the pipette tip holder conveyor moves toward the standby position, the tip holders that have received the pipette tips are moved by the tip ejectors, and the pipette tips transported thereby are removed from the tip holders by the tip ejectors.

[0149] Embodiment Embodiment 1. A device for capturing one or more pipette tips released from an automated pipettor at a tip release location, the device comprising:

[0150] a tip holder conveyor comprising or supporting a plurality of tip holders, each tip holder configured to receive and releasably hold a single pipette tip;

[0151] a drive mechanism configured to index the tip holder conveyor to sequentially position each of one or more of the plurality of tip holders at a tip release location to receive pipette tips released by the automated pipettor into each tip holder positioned at the tip release location;

[0152] a tip ejector positioned to engage with pipette tips held in each of one or more of the plurality of tip holders when the tip holder conveyor is moved relative to the tip ejector by a drive mechanism, and configured to remove each pipette tip engaged by the tip ejector from its associated tip holder.

[0153] Embodiment 2. A device as described in embodiment 1, wherein the plurality of chip holders of the chip holder conveyor are interconnected to form a chip holder chain.

[0154] Embodiment 3. A device as described in embodiment 2, wherein the chip holder chain comprises a continuous chain guided by a continuous track.

[0155] Embodiment 4. A device described in any one of embodiments 1 to 3, wherein after a pipette tip is released by an automatic pipetter into a tip holder located at a tip release location, if at least one of the multiple tip holders does not receive the pipette tip released by the automatic pipetter, the drive mechanism indexes the tip holder conveyor to index a subsequent tip holder to the tip release location.

[0156] Embodiment 5. A device according to any one of embodiments 1 to 4, wherein when there is no tip holder located at the tip release location, pipette tips released from the automatic pipetter fall into a removable waste container positioned to receive the released pipette tips, and the device further comprises a waste container sensor configured to detect whether the waste container is positioned to receive the released pipette tips, whereby detecting by the waste container sensor that the waste container is not positioned to receive the released pipette tips causes the drive mechanism to index the tip holder conveyor to sequentially position each of the one or more tip holders at the tip release location to capture each released pipette tip while the waste container is not positioned to receive the released pipette tips, and detecting by the waste container sensor that the waste container is positioned to receive the released pipette tips causes the drive mechanism to move the tip holder conveyor to sequentially move each of the one or more tip holders relative to the tip ejector to remove the pipette tips from the associated tip holders at the tip removal location.

[0157] Embodiment 6: The device of embodiment 5, further comprising a waste chute positioned below the tip release location and below the tip removal location, the waste chute configured to direct pipette tips released by the automated pipettor or removed from tip holders of the tip holder conveyor into a waste container.

[0158] Embodiment 7. A device as described in embodiment 5, wherein the drive mechanism is configured to move the tip holder conveyor to a waiting position in which no tip holder is located at the tip release location when the waste container sensor detects that the waste container is positioned to receive a released pipette tip.

[0159] Embodiment 8. A device as described in embodiment 7, wherein when the tip holder conveyor moves to a standby position, each tip holder holding a pipette tip is moved sequentially relative to a tip ejector to remove the pipette tip from the associated tip holder so that the pipette tip is not held by the tip holder conveyor when the tip holder conveyor is in the standby position.

[0160] Embodiment 9. A device described in any one of embodiments 1 to 8, wherein the chip holder conveyor comprises a chip holder chain comprising a plurality of interconnected links, each chip holder being part of one of the links.

[0161] Embodiment 10. A device described in any one of embodiments 1 to 8, wherein the chip holder conveyor includes a detection element in each chip holder, and the device further includes a sensor for detecting each detection element passing by the sensor when the drive mechanism moves the chip holder conveyor.

[0162] Embodiment 11. A device as described in embodiment 10, wherein the chip holder conveyor may include a chip holder chain having a plurality of interconnected links, each chip holder being part of one of the links, and each detection element having a pin connecting one link to an adjacent link.

[0163] Embodiment 12. A device as described in embodiment 11, further comprising a controller configured to determine the position of the chip holder chain based on the number of detection elements that have passed the sensor.

[0164] Embodiment 13. A device as described in embodiment 11 or 12, wherein the chip holder chain comprises a continuous chain guided by a continuous track.

[0165] Embodiment 14. A device as described in embodiment 13, wherein the drive mechanism comprises a chain drive with a motorized wheel, and a continuous chain is wrapped around the motorized wheel.

[0166] Embodiment 15. A device described in any one of embodiments 1 to 14, wherein each tip holder has a clip defining an opening configured to receive a pipette tip without resistance.

[0167] Embodiment 16: A device as described in embodiment 15, wherein each clip has opposing arms configured to hold a pipette tip therebetween and defining a lateral opening narrower than the width of a portion of the pipette tip held between the opposing arms.

[0168] Embodiment 17. A device as described in embodiment 16, wherein the tip ejector has one or more ramps or wedges that contact a pipette tip held within the opening of the clip when the tip holder passes through the tip ejector, and the opposing arms are flexible so that when the one or more ramps contact the pipette tip, the pipette tip moves laterally, urging the opposing arms to open, enlarging the lateral opening and allowing the pipette tip to pass through the lateral opening and be removed from the tip holder.

[0169] Embodiment 18. A device as described in embodiment 17, wherein the chip holder conveyor follows a curved path adjacent to the chip ejector.

[0170] Embodiment 19. A device as described in embodiment 17 or 18, wherein the tip ejector has first and second laterally extending ramps or wedges, the first laterally extending ramp configured to engage with a first portion of the pipette tip extending above the clip when the tip holder moves relative to the tip ejector, and the second laterally extending ramp configured to engage with a second portion of the pipette tip extending below the clip when the tip holder moves relative to the tip ejector.

[0171] Embodiment 20. A device described in any one of embodiments 1 to 19, wherein the drive mechanism is configured to move the tip holder conveyor in a first direction to sequentially position each tip holder at a tip release location, and to move the tip holder conveyor in a second direction opposite to the first direction to move the tip holder conveyor relative to the tip ejector to remove pipette tips from the associated tip holders.

[0172] Embodiment 21. A device as described in embodiment 20, wherein at least a portion of the chip holder conveyor follows a linear path when moving in the first and second directions.

[0173] Embodiment 22. A device, a pipettor configured for lateral and longitudinal movement within the instrument, the pipettor having a mounting end adapted to receive a pipette tip in a friction fit; a waste container movable between a first receptacle position and a second receptacle position, wherein when the waste container is in the first receptacle position, the waste container is positioned to receive pipette tips released from the mounting end of the pipettor at a tip release location, and when the waste container is in the second receptacle position, the waste container is not positioned to receive pipette tips released from the mounting end of the pipettor at the tip release location; a pipette tip holder movable between a first tip holder position and a second tip holder position, wherein in the first tip holder position, the pipette tip holder is not positioned to receive a pipette tip released from the mounting end of the pipettor at a tip release location when the waste container is in the first receptacle position, and wherein in the second tip holder position, the pipette tip holder is positioned to receive and hold a pipette tip released from the mounting end of the pipettor at the tip release location when the waste container is in the second receptacle position.

[0174] Embodiment 23. An instrument as described in embodiment 22, wherein the pipettor is configured for X, Y, and Z movement.

[0175] Embodiment 24. An instrument as described in embodiment 22 or 23, wherein the pipettor comprises a probe and the attachment end comprises the distal end of the probe.

[0176] Embodiment 25. An apparatus described in any one of embodiments 22 to 24, further comprising a pipette tip holder bay and a container of pipette tips arranged in the pipette tip holder bay, wherein the pipette tips of the container in the pipette tip holder bay are positioned and oriented so as to be engaged by the mounting end of the pipettor.

[0177] Embodiment 26. An apparatus described in any one of embodiments 22 to 25, wherein the pipette tip holder is movable to a third tip holder position different from the second tip holder position, at which the pipette tip held in the pipette tip holder is removed from the pipette tip holder.

[0178] Embodiment 27. The device of embodiment 26, further comprising a tip ejector configured to remove the pipette tip from the pipette tip holder at the third position.

[0179] Embodiment 28. An instrument as described in embodiment 27, wherein the pipette tip is displaced laterally from the pipette tip holder by a tip ejector.

[0180] Embodiment 29. An apparatus described in any one of embodiments 26 to 28, wherein movement of the pipette tip holder from the first tip holder position to the second tip holder position is in a first lateral direction, and movement of the pipette tip holder from the second tip holder position to the third tip holder position is in a second lateral direction, and the first and second lateral directions are opposite directions.

[0181] Embodiment 30. A device described in any one of embodiments 22 to 29, wherein the waste container is lined with a disposable plastic bag.

[0182] Embodiment 31. An apparatus described in any one of embodiments 22 to 30, further comprising a drawer configured to support a waste container and move the waste container laterally between the first and second receptacle positions.

[0183] Embodiment 32. An apparatus described in any one of embodiments 22 to 31, further comprising a sensor for detecting when a waste container is present in at least one of the first and second receptacle locations.

[0184] Embodiment 33. An apparatus described in any one of embodiments 22 to 32, wherein the pipette tip holders are transported by a conveyor.

[0185] Embodiment 34. The apparatus of embodiment 33, further comprising a track for supporting the conveyor.

[0186] Embodiment 35. The device described in embodiment 34, further comprising a sensor for monitoring the position of the pipette tip holder on the track.

[0187] Embodiment 36. An apparatus described in any one of embodiments 33 to 35, further comprising a drip tray positioned below a portion of the conveyor.

[0188] Embodiment 37. An apparatus described in any one of embodiments 22 to 36, wherein the pipette tip holder is one of a plurality of pipette tip holders.

[0189] Embodiment 38. An apparatus described in any one of embodiments 22 to 37, wherein the pipette tip is released into the waste container when the pipette tip holder is not in a second tip holder position for receiving a pipette tip released from the mounting end of the pipettor at the tip release location and the waste container is in the first receptacle position.

[0190] Embodiment 39. An apparatus as described in embodiment 38, wherein when the pipette tip holder is not in a second tip holder position for receiving a pipette tip released from the mounting end of the pipettor at the tip release location and the waste container is in the first receptacle position, the pipette tip is released into a chute that directs the pipette tip to the waste container.

[0191] Embodiment 40. An apparatus described in any one of embodiments 22 to 39, wherein the tip holder has a clip defining an opening configured to receive the pipette tip without any resistance.

[0192] Embodiment 41. An apparatus as described in embodiment 40, wherein the clip has opposing arms configured to hold a pipette tip therebetween and defines a lateral opening narrower than the width of a portion of the pipette tip held between the opposing arms.

[0193] Embodiment 42. An instrument described in any one of embodiments 22 to 41, wherein the pipettor includes a tip release mechanism for releasing the pipette tip from the mounting end of the pipettor.

[0194] Embodiment 43. An apparatus as described in embodiment 42, wherein the tip ejection mechanism comprises a release sleeve coaxially mounted on the mounting end and configured to be axially movable relative to the mounting end.

[0195] Embodiment 44. The device of embodiment 43, wherein the tip release mechanism further comprises a release trigger coupled to the release sleeve and configured to move the release sleeve axially relative to the mounting end when the pipettor moves the release trigger in contact with the release surface to release the pipette tip from the mounting end.

[0196] Embodiment 45. A method for capturing one or more pipette tips released from an automated pipettor, the method comprising: a) with the pipette tip secured to the pipettor, repeatedly moving the pipettor laterally to a tip release position to release the pipette tip from the pipettor, thereby dropping the released pipette tip into a waste container positioned to receive the released pipette tip; b) detecting whether the waste container is no longer positioned to receive a pipette tip released from the pipettor in the tip release position; c) upon detecting that the waste container is no longer positioned to receive pipette tips released from the pipettor in the tip release position, moving the pipette tip holder from a first tip holder position where the pipette tip holder is not positioned to receive pipette tips released from the pipettor in the tip release position to a second tip holder position where the pipette tip holder is positioned to receive pipette tips released from the pipettor in the tip release position, and receiving the pipette tips released from the pipettor while the pipette tip holder is in the second tip holder position.

[0197] Embodiment 46. d) while the waste container is no longer positioned to receive pipette tips released from the pipettor in the tip release position, moving the additional pipette tip holder from a first tip holder position where the pipette tip holder is not positioned to receive pipette tips released from the pipettor in the tip release position to a second tip holder position where the pipette tip holder is positioned to receive pipette tips released from the pipettor in the tip release position; 46. ​​The method of embodiment 45, further comprising: e) receiving a pipette tip released from a pipettor with an associated pipette tip holder at a second tip holder position.

[0198] Embodiment 47. The method of embodiment 45 or 46, wherein step b) is performed by a sensor for detecting the presence or absence of a waste container.

[0199] Embodiment 48. After step c), f) upon detecting that the waste container is positioned to receive pipette tips from the pipettor in the tip release position, moving the pipette tip holder from the second tip holder position to a third tip holder position different from the second tip holder position; 48. The method of any one of embodiments 45 to 47, further comprising: g) removing the pipette tip from the pipette tip holder at a third tip holder position, thereby dropping the removed pipette tip into a waste container.

[0200] Embodiment 49. The method of embodiment 48, wherein step g) includes moving the pipette tip holder relative to a tip ejector having at least one ramp that engages with a pipette tip held in the tip holder and laterally displaces the pipette tip from the tip holder.

[0201] Embodiment 50. A method according to any one of embodiments 45 to 49, wherein the chip holder chain interconnects a plurality of chip holders to form a continuous chip holder chain, and step f) includes moving the chip holder chain having a motorized drive wheel engaged with the chip holder chain.

[0202] Embodiment 51. A method according to any one of embodiments 48 to 50, wherein step c) may include moving the pipette tip holder in a first lateral direction, and step f) may include moving the pipette tip holder in a second lateral direction, the first and second lateral directions being opposite directions.

[0203] Embodiment 52. The method according to any one of embodiments 45 to 51, further comprising: h) monitoring the position of the pipette tip holder.

[0204] Embodiment 53. i) determining that no pipette tip holders without pipette tips are available; 53. The method according to any one of embodiments 45 to 52, further comprising: j) interrupting the operation of the pipettor when a pipette tip holder without pipette tips is not available.

[0205] Embodiment 54. The method of any one of embodiments 45 to 53, wherein releasing the pipette tip from the pipettor comprises engaging the pipette tip attached to the pipettor with a tip release mechanism.

[0206] Embodiment 55. The method of embodiment 54, wherein the tip release mechanism comprises a release sleeve coaxially mounted on the mounting end of the pipette to which the pipette tip is attached, and engaging the pipette tip with the tip release mechanism comprises moving the release sleeve axially relative to the mounting end.

[0207] Embodiment 56. The method of embodiment 55, wherein the tip release mechanism further comprises a release trigger coupled to the release sleeve, and wherein axially moving the release sleeve relative to the mounting end includes contacting the release surface with the release trigger.

[0208] Embodiment 57. A method for facilitating sequential processing of multiple samples in an automated system, the method comprising: a) detecting that a waste container of the system is not in a pipette tip receiving position; b) after step a), and while the waste container is not in the pipette tip receiving position, isolating one or more pipette tips released from the pipettor in a pipette tip holding station of the system, wherein the isolated pipette tips have previously been used for processing at least a subset of a plurality of samples in the system, and when the waste container is in the pipette tip receiving position, any pipette tips used for processing the plurality of samples and released from the pipettor are released directly into the waste container; c) after step b), detecting that the waste container is in the pipette tip receiving position; d) after step c) and while the waste container is in the pipette tip receiving position, transferring the isolated pipette tips from the pipette tip holding station to the waste container. A method wherein the processing of multiple samples in the system is continuous between steps a) to d).

[0209] Embodiment 58. The method of embodiment 57, wherein the waste container is supported by a drawer that is laterally movable to or from the pipette tip receiving position.

[0210] Embodiment 59. The method of embodiment 57 or 58, wherein the waste container is lined with a disposable plastic bag.

[0211] Embodiment 60. A method according to any one of embodiments 57 to 59, wherein steps a) and b) include using a position sensor of the system to detect when the waste container is in or is not in a pipette tip receiving position.

[0212] Embodiment 61. A method according to any one of embodiments 57 to 60, wherein step b) includes, for each of one or more pipette tips, moving the pipettor into engagement with a pipette tip release surface of the holding station, thereby causing the pipettor to release the associated pipette tip from the mounting end of the pipettor.

[0213] Embodiment 62. A method according to any one of embodiments 57 to 61, wherein one or more pipette tips are released to individual pipette tip holders at a first tip release location in step b), and the individual pipette tip holders are accommodated within a pipette tip holding station when the waste container is not at the pipette tip receiving position.

[0214] Embodiment 63. The method of embodiment 62, wherein the pipette tip holder supports one or more pipette tips in an upright orientation.

[0215] Embodiment 64. The method of embodiment 62 or 63, wherein the individual pipette tip holders include or are supported by a loop conveyor of a pipette tip holding station.

[0216] Embodiment 65. The method of embodiment 64, wherein the individual pipette tip holders are moved in a first lateral direction on the conveyor during step b) and in a second lateral direction on the conveyor in step d), the first lateral direction and the second lateral direction being opposite directions.

[0217] Embodiment 66. A method according to any one of embodiments 62 to 65, wherein step d) comprises laterally displacing one or more pipette tips from respective pipette tip holders.

[0218] Embodiment 67. The method of any one of embodiments 62 to 66, further comprising the step of releasing at least one pipette tip from the pipettor at a second tip release location when the waste container is in the pipette tip receiving position.

[0219] Embodiment 68. The method of embodiment 67, wherein the first and second tip release locations are the same tip release location.

[0220] Embodiment 69. The method of embodiment 67 or 68, wherein the first and second tip release locations are located above a chute for directing pipette tips into a waste container.

[0221] Embodiment 70. The method of any one of embodiments 57 to 69, further comprising a step of collecting residual fluid removed from at least one of the one or more pipette tips in a tray positioned below the one or more pipette tips isolated in the holding station in step b), wherein the tray is a component of the holding station.

[0222] Embodiment 71. The method of any one of embodiments 57 to 70, wherein processing at least a subset of the plurality of samples comprises reconstituting or transferring reagents for performing a nucleic acid-based amplification reaction.

[0223] Embodiment 72. The method of any one of embodiments 57 to 71, wherein processing at least a subset of the plurality of samples comprises forming a reaction mixture comprising one of the samples and at least one reagent for performing a nucleic acid-based amplification reaction.

[0224] While the subject matter of the present disclosure has been described and illustrated in considerable detail with reference to certain illustrative embodiments, including various combinations and subcombinations of features, those skilled in the art will readily appreciate other embodiments and variations and modifications thereof that are encompassed within the scope of the present disclosure. Moreover, the description of such embodiments, combinations, and subcombinations is not intended to convey that the claimed subject matter requires any features or combinations of features other than those expressly recited in the claims. Accordingly, the scope of the present disclosure is deemed to include all modifications and variations encompassed within the spirit and scope of the following appended claims.

Claims

[Claim 1] The invention as described in the drawings of this application.