Disposable Pipette Tip Management

Abstract

After disposable pipette tips are used by an automated pipette, they are released by the pipette and fall into a waste container. When the waste container is removed for emptying, the pipette tips are temporarily isolated in a pipette tip holding station so that the automated pipette can operate without interruption. After the waste container is replaced, the isolated pipette tips are released by the holding station into the waste container.

Description

[0001] Cross - reference to related applications

[0002] This application claims the benefit under 35 U.S.C. § 119(e) of the filing date of provisional patent application serial number 62 / 826,599, filed on March 29, 2019, the disclosure of which is incorporated herein by reference. Technical Field

[0003] The present disclosure relates to the handling of discarded disposable pipette tips within an instrument employing a robotic pipette. Background Art

[0004] Certain instruments, such as diagnostic and clinical analyzers in which liquids are transferred to different receptacles, reservoirs, or other liquid-containing containers, from which they are transferred, or between which they are transferred, typically employ a robotic pipette to aspirate and dispense liquids. To prevent contamination of the pipette probe, a disposable pipette tip can be removably attached to the pipette probe such that liquid is aspirated into the pipette tip without contacting the probe. After the pipette tip has been used, it is typically discarded by releasing or ejecting it from the pipette probe above a waste container, and the released pipette tip falls into the waste container. During the continuous operation of the instrument, the waste container must be emptied periodically because it becomes filled with discarded pipette tips. Typically, the waste container is emptied by removing it from the instrument and disposing of the accumulated pipette tips before replacing the waste container into the instrument. However, during the removal of the waste container from the instrument, the operation of the instrument must be paused because there is no place to discard the pipette tips released from the pipette probe. The operation of the instrument must be paused every time the waste container must be emptied, which has a negative impact on the throughput of the instrument. Summary of the Invention

[0005] A simplified summary is presented below 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 neither intended to identify key or critical elements of the claimed subject matter nor to delineate its scope. Its sole purpose is to present some concepts in a simplified form as a prelude to the more detailed description presented later.

[0006] Aspects of the present disclosure are embodied in an apparatus for capturing one or more pipette tips released from an automated pipette at a tip release position. The apparatus may include a tip holder transporter, a drive mechanism, and a tip ejector. The tip holder transporter may include or support a plurality of tip holders, where each tip holder may be configured to receive and releasably hold a single pipette tip. The drive mechanism is configured to rotate the tip holder transporter to sequentially place each of one or more of the plurality of tip holders in the tip release position to receive the pipette tips released by the automated pipette into each tip holder placed at the tip release position. The tip ejector may be positioned to engage the pipette tips held in each of one or more of the plurality of tip holders when the tip holder transporter is moved relative to the tip ejector by the drive mechanism, where the tip pusher is configured to remove each pipette tip engaged from the associated tip holder.

[0007] In accordance with other aspects, the plurality of tip holders of the tip holder transporter may be interconnected to form a tip holder chain.

[0008] In accordance with other aspects, the tip holder chain may include a continuous chain guided by a continuous track.

[0009] In accordance with other aspects, after the pipette tip is released by the automated pipette into the tip holder located at the tip release position, if at least one of the plurality of tip holders has not received the pipette tip released by the automated pipette, the drive mechanism may rotate the tip holder transporter to rotate a subsequent tip holder to the tip release position.

[0010] In accordance with other aspects, when there is no tip holder at the tip release position, the pipette tip released from the automated pipette may fall into a removable waste container positioned to receive the released pipette tip. The apparatus may also include a waste container sensor configured to detect whether the waste container is positioned to receive the released pipette tip. Detection by the waste container sensor that the waste container is not positioned to receive the released pipette tip may cause the drive mechanism to rotate the tip holder transporter to sequentially position each of one or more tip holders at the tip release position to capture each pipette tip released when the waste container is not positioned to receive the released pipette tip. Detection by the waste container sensor that the waste container is positioned to receive the released pipette tip may cause the drive mechanism to move the tip holder transporter to sequentially move each of one or more tip holders relative to the tip pusher to remove the pipette tip from the associated tip holder at the tip removal position.

[0011] In other aspects, the apparatus may further include a waste chute located below the tip release position and below the tip removal position, and the waste chute may be configured to direct a pipette tip released by an automated pipette or a pipette tip removed from a tip holder of the tip holder transporter into a waste container.

[0012] In other aspects, the drive mechanism may be configured to move the tip holder transporter to a standby position when a waste container sensor detects that the waste container is positioned to receive a released pipette tip, and in the standby position, no tip holder is located at the tip release position.

[0013] In other aspects, when the tip holder transporter is moved to the standby position, each tip holder holding a pipette tip may be moved sequentially relative to the tip ejector to remove the pipette tip from the associated tip holder, such that when the tip holder transporter is in the standby position, the tip holder transporter does not hold a pipette tip.

[0014] In other aspects, the tip holder transporter may include a tip holder chain including a plurality of interconnected links, and each tip holder may be part of one of the links.

[0015] In other aspects, the tip holder transporter may include a detection element at each tip holder, and the apparatus may further include a sensor for detecting each detection element passing through the sensor when the drive mechanism moves the tip holder transporter.

[0016] In other aspects, the tip holder transporter may include a tip holder chain including 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.

[0017] In other aspects, the apparatus may further include a controller configured to determine the position of the tip holder chain based on the number of detection elements that have passed through the sensor.

[0018] In other aspects, the tip holder chain may include a continuous chain guided by a continuous track.

[0019] In other aspects, the drive mechanism may include a chain drive including a motorized wheel, and the continuous chain is towed around the motorized wheel.

[0020] In other aspects, each tip holder may include a clip defining an opening configured to receive a pipette tip without any resistance.

[0021] According to other aspects, each clip may include opposing arms configured to hold a pipette tip therebetween and defining a lateral opening that is smaller than a width of a portion of the pipette tip held between the opposing arms.

[0022] According to other aspects, the tip ejector may include one or more ramps or wedges that contact a pipette tip held in the opening of the clip as the tip holder passes over the tip ejector, and the opposing arms are flexible such that the one or more ramps contact the pipette tip, causing the pipette tip to move laterally and push the opposing arms apart to widen the lateral opening and allow the pipette tip to pass through the lateral opening and be removed from the tip holder.

[0023] According to other aspects, the tip holder conveyor may follow a curved path adjacent to the tip ejector.

[0024] 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 a pipette tip extending over the clip as the tip holder moves relative to the tip ejector, and the second laterally extending ramp may be configured to engage a second portion of the pipette tip extending under the clip as the tip holder moves relative to the tip ejector.

[0025] 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 position, and may be configured to move the tip holder conveyor in a second direction opposite the first direction to move the tip holder conveyor relative to the tip ejector to remove a pipette tip from an associated tip holder.

[0026] According to other aspects, at least a portion of the tip holder conveyor may follow a linear path when moved in the first and second directions.

[0027] Aspects of the present disclosure are embodied in an instrument including a pipette, a waste container, and a pipette tip holder. The pipette may be configured to move horizontally and vertically within the instrument, and the pipette 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. The waste container is positioned to receive a pipette tip released from the mounting end of the pipette at a tip release position when the waste container is in the first receptacle position, and the waste container is not positioned to receive a pipette tip released from the mounting end of the pipette at the tip release position when the waste container is in the second receptacle position. 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 pipette at the tip release position when the waste container is in the first receptacle position. In the second tip holder position, the pipette tip holder is positioned to receive a pipette tip released from the mounting end of the pipette at the tip release position when the waste container is in the second receptacle position.

[0028] In accordance with other aspects, the pipette may be configured for X, Y, and Z movement.

[0029] In accordance with other aspects, the pipette may include a probe, and the mounting end may include the distal end of the probe.

[0030] In accordance with other aspects, the instrument may further include a pipette tip holder compartment and a container of pipette tips disposed within the pipette tip holder compartment, and the pipette tips in the container within the pipette tip holder compartment are positioned and oriented to be engaged by the mounting end of the pipette.

[0031] In accordance with other aspects, the pipette tip holder may be moved to a third tip holder position different from the second tip holder position, at which a pipette tip held in the pipette tip holder is removed from the pipette tip holder.

[0032] In accordance with other aspects, the instrument may further include a tip ejector configured to remove a pipette tip from the pipette tip holder at a third position.

[0033] In accordance with other aspects, the pipette tip may be laterally displaced from the pipette tip holder by the tip ejector.

[0034] In accordance with other aspects, the movement of the pipette tip holder from the first tip holder position to the second tip holder position may be in a first lateral direction, and the movement of the pipette tip holder from the second tip holder position to the third tip holder position may be in a second lateral direction, where the first lateral direction and the second lateral direction are opposite directions.

[0035] In other aspects, the waste container can be lined with a disposable plastic bag.

[0036] In other aspects, the instrument can further include a drawer that supports the waste container and is configured to laterally move the waste container between a first and a second seating position.

[0037] In other aspects, the instrument can further include a sensor for sensing when the waste container is in at least one of the first and second seating positions.

[0038] In other aspects, the pipette tip holder can be carried on a conveyor.

[0039] In other aspects, the device can include a track for supporting the conveyor.

[0040] In other aspects, the device can further include a sensor for monitoring the position of the pipette tip holder on the track.

[0041] In other aspects, the device can further include a drip tray located below a portion of the conveyor.

[0042] In other aspects, the pipette tip holder can be one of a plurality of pipette tip holders.

[0043] In other aspects, when the pipette tip holder is not in the second tip holder position to receive the pipette tip released from the mounting end of the pipette at the tip release position and the waste container is in the first seating position, the pipette tip is released into the waste container.

[0044] In other aspects, when the pipette tip holder is not in the second tip holder position to receive the pipette tip released from the mounting end of the pipette at the tip release position and the waste container is in the first seating position, the pipette tip can be released into a chute that directs the pipette tip into the waste container.

[0045] In other aspects, the tip holder can include a clip defining an opening configured to receive the pipette tip without any resistance.

[0046] In other aspects, the clip can include opposing arms configured to hold the pipette tip therebetween and defining a lateral opening that is smaller than the width of a portion of the pipette tip held between the opposing arms.

[0047] In other aspects, the pipette can include a tip release mechanism for releasing the pipette tip from the mounting end of the pipette.

[0048] In accordance with other aspects, the tip release mechanism can include a release sleeve that is coaxially mounted above the mounting end and configured to be axially movable relative to the mounting end.

[0049] In accordance with other aspects, the tip release mechanism can further include a release trigger that is coupled to the release sleeve and configured to axially move the release sleeve relative to the mounting end to release the pipette tip from the mounting end when the pipette moves the release trigger into contact with a release surface.

[0050] Aspects of the present disclosure are embodied in a method for capturing one or more pipette tips released from an automated pipette. The method can include the steps of: a) repeatedly laterally moving a pipette with a pipette tip secured thereto to a tip release position and releasing the pipette tip from the pipette, whereby the released pipette tip falls 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 pipette at the tip release position; and c) moving a pipette tip holder from a first tip holder position to a second tip holder position when it is detected that the waste container is no longer positioned to receive a pipette tip released from the pipette at the tip release position, wherein in the first tip holder position, the pipette tip holder is not positioned to receive a pipette tip released from the pipette at the tip release position, and in the second tip holder position, the pipette tip holder is positioned to receive a pipette tip released from the pipette at the tip release position; and receiving the pipette tip released from the pipette with the pipette tip holder in the second tip holder position.

[0051] In accordance with other aspects, the method can further include the steps of: d) moving an additional pipette tip holder from the first tip holder position to the second tip holder position when the waste container is no longer positioned to receive a pipette tip released from the pipette at the tip release position, wherein in the first tip holder position, the pipette tip holder is not positioned to receive a pipette tip released from the pipette at the tip release position, and in the second tip holder position, the pipette tip holder is positioned to receive a pipette tip released from the pipette at the tip release position, and e) receiving the pipette tip released from the pipette with the associated pipette tip holder in the second tip holder position.

[0052] In accordance with other aspects, step b) is performed with a sensor that detects the presence or absence of the waste container.

[0053] According to other aspects, the method may further include the following steps after step c): f) when it is detected that the waste container is positioned to receive a pipette tip from the pipette at the tip release position, moving the pipette tip from the second tip holder position to a third tip holder position different from the second tip holder position, and g) at the third tip holder position, removing the pipette tip from the pipette tip holder, whereby the removed pipette tip falls into the waste container.

[0054] According to other aspects, step g) may include moving the pipette tip holder relative to a tip ejector, the tip ejector including at least one inclined surface that engages the pipette tip held in the tip holder and laterally moves the pipette tip out of the tip holder.

[0055] According to other aspects, a plurality of tip holders are interconnected to form a continuous chain of tip holders, and step f) may include moving the chain of tip holders with a motor-driven wheel that engages the tip holder link.

[0056] According to other aspects, 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, wherein the first and second lateral directions are opposite directions.

[0057] According to other aspects, the method may further include the following step: h) monitoring the position of the pipette tip holder.

[0058] According to other aspects, the method may further include the following steps: i) determining that no pipette tip holder without a pipette tip is available, and j) interrupting the operation of the pipette when no pipette tip holder without a pipette tip is available.

[0059] According to other aspects, releasing the pipette tip from the pipette may include engaging the pipette tip attached to the pipette with a tip release mechanism.

[0060] According to other aspects, the tip release mechanism may include a release sleeve coaxially mounted above the mounting end of the pipette, 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.

[0061] According to other aspects, 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 bringing a release surface into contact with the release trigger.

[0062] Aspects of the present invention are embodied in a method for facilitating the uninterrupted processing of multiple samples in an automated system. The method can include the following steps: a) detecting that the waste container of the system is not in the 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 pipette in a pipette tip holding station of the system, where the isolated pipette tips have previously been used to process at least a subset of the multiple samples in the system, and where any pipette tips used to process the multiple samples and released from the pipette while the waste container is in the pipette tip receiving position can 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) 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. The processing of the multiple samples in the system during steps a) to d) is uninterrupted.

[0063] According to other aspects, the waste container is supported by a drawer that can move laterally towards or away from the pipette tip receiving position.

[0064] According to other aspects, the waste container can be lined with a disposable plastic bag.

[0065] According to other aspects, steps a) and b) include using a position sensor of the system to detect when the waste container is or is not in the pipette tip receiving position.

[0066] According to other aspects, step b) can include, for each of the one or more pipette tips, moving the pipette to engage with a pipette tip release surface of the holding station, such that the pipette releases the associated pipette tip from the mounting end of the pipette.

[0067] According to other aspects, in step b), the one or more pipette tips can be released into a separate pipette tip holder at a first tip release position, where the separate pipette tip holder is contained within the pipette tip holding station when the waste container is not in the pipette tip receiving position.

[0068] According to other aspects, the pipette tip holder can support the one or more pipette tips in an upright orientation.

[0069] According to other aspects, the separate pipette tip holder includes or is supported by an annular conveyor of the pipette tip holding station.

[0070] According to other aspects, a separate pipette tip holder can be moved on the conveyor in a first lateral direction during step b), and in a second lateral direction on the conveyor in step d), where the first lateral direction and the second lateral direction are opposite directions.

[0071] According to other aspects, step d) can include laterally displacing one or more pipette tips from a separate pipette tip holder.

[0072] According to other aspects, the method can further include the step of releasing at least one pipette tip from the pipette at a second tip release position when the waste container is in the pipette tip receiving position.

[0073] According to other aspects, the first and second tip release positions can be the same tip release position.

[0074] According to other aspects, the first and second tip release positions can be located above a chute for guiding the pipette tip to the waste container.

[0075] According to other aspects, the method can further include the step of collecting residual fluid discharged from at least one of the one or more pipette tips in a tray disposed below the one or more pipette tips isolated at the holding station in step b), where the tray is a component of the holding station.

[0076] According to other aspects, the processing of at least one subset of a plurality of samples can include reconstituting or transferring reagents for performing a nucleic acid-based amplification reaction.

[0077] According to other aspects, the processing of at least one subset of a plurality of samples can include forming a reaction mixture that includes one of the samples and at least one reagent for performing a nucleic acid-based amplification reaction.

[0078] When considering the following description and the appended claims in light of the accompanying drawings, other features and characteristics of the subject matter of the present disclosure, as well as the operating methods, functions of the related elements of the structure, combinations of components, and economies of manufacture, will become more apparent, all of which form a part of this specification, where like reference numerals represent corresponding components in the various drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0079] The accompanying drawings, which are incorporated herein and form a part of the specification, illustrate various embodiments of the subject matter of the present disclosure. In the drawings, like reference numerals indicate identical or functionally similar elements.

[0080] Figure 1 is a perspective view of an apparatus in which a pipette tip holding station as disclosed herein can be implemented.

[0081] Figure 2Partial perspective view of a part of the instrument where a pipette tip holder station can be implemented.

[0082] Figure 3 Perspective view of the holder station of the instrument together with an automated pipette, a waste container, and a waste drawer.

[0083] Figure 4 Perspective view of the holder station schematically shown together with a waste container and a waste container sensor.

[0084] Figure 5 Perspective view of the holder station with various components, frame elements, and cover plates omitted to reveal the internal components of the device.

[0085] Figure 6 Perspective view of the holder station with various components, frame elements, and cover plates omitted to reveal the internal components of the device.

[0086] Figure 7 Perspective view of the holder station with various components, frame elements, and cover plates omitted to reveal the internal components of the device.

[0087] Figure 8 Perspective view of a part of a tip holder chain including two tip holder links and two connector links.

[0088] Figure 9 Perspective view of a single tip holder link and a connector pin.

[0089] Figure 10 Perspective view of a single connector link and a connector pin.

[0090] Figure 11 Bottom perspective view of the top frame of the pipette tip holder station in isolation.

[0091] Figure 12 Top perspective view of the top frame in isolation.

[0092] Figure 13 Partial top perspective view of the top frame and a part of the tip holder chain.

[0093] Figure 14 Bottom perspective view of the upper track panel of the top frame in isolation with a part of the tip holder chain.

[0094] Figure 15 Top perspective view of the lower track panel of the top frame in isolation with a part of the tip holder chain.

[0095] Figure 16 Top perspective view of the lower track panel of the top frame in isolation with a part of the tip holder chain.

[0096] Figure 17 A side view of an automated pipette with a disposable pipette tip attached thereto.

[0097] Figure 18 A side view of an automated pipette from which a disposable pipette tip is released.

[0098] Figure 19 A partial top view of a holding station.

[0099] Figure 20 A top view of a holding station in which various components, frame elements, and cover plates are omitted to reveal the internal components of the device.

[0100] Figure 21 A partial cross-sectional view of a tip holding station showing an automated pipette releasing a pipette tip into a tip holder link of a tip holder chain.

[0101] Figure 22 A partial perspective view of the top frame of a tip holding station showing a tip ejector and a pipette tip held in a tip holder link of a tip holder chain.

[0102] Figure 23 A flowchart showing a method for facilitating uninterrupted processing of multiple samples in an automated system.

[0103] Figure 24 A block diagram schematically showing the control architecture of a device. DETAILED DESCRIPTION

[0104] Although aspects of the subject matter of this disclosure may be implemented in various forms, the following description and drawings are only intended to disclose some of these forms as specific examples of the subject matter. Accordingly, the subject matter of this disclosure is not intended to be limited to the forms or embodiments so described and illustrated.

[0105] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this technology belongs. All patent cases, applications, published applications, and other publications mentioned herein are incorporated by reference in their entirety. If the definitions given in this section are contrary to or inconsistent with the definitions given in patent cases, applications, published applications, and other publications incorporated by reference herein, the definitions given in this section shall prevail over the definitions incorporated by reference herein.

[0106] Unless otherwise indicated or the context otherwise implies, as used herein, "a / an" means "at least one" or "one or more".

[0107] This specification may describe the location and / or orientation of components, devices, locations, features, or portions thereof using relative space and / or orientation terms. Unless explicitly stated or otherwise specified by the context of this specification, such terms (including, but not limited to, top, bottom, above, below, underneath, on top, upper, lower, left, right, front, rear, adjacent, adjoining, between, horizontal, vertical, diagonal, longitudinal, transverse, radial, axial, etc.) are used to conveniently refer to such components, devices, locations, features, or portions thereof in the accompanying drawings and are not intended to be limiting.

[0108] In addition, unless otherwise specified, any specific dimensions mentioned in this specification only represent exemplary embodiments of the devices for implementing various aspects of the present disclosure and are not intended to be limiting.

[0109] The use of the term "about" or similar terms applies to all numerical values specified herein, whether or not precisely indicated. This term generally refers to a range of numbers that would be considered by a person of ordinary skill in the art to be a reasonable deviation from the recited numerical value (i.e., having an equivalent function or result) in the context of the present disclosure. By way of example, and not limitation, this term may be interpreted to include a deviation of ±10% of the given numerical value, provided that such deviation does not change the ultimate function or result of the numerical value. Thus, in some cases, as would be understood by a person of ordinary skill in the art, a value of about 1% may be interpreted as being in the range of 0.9% to 1.1%.

[0110] As used herein, the term "adjacent" or similar terms refer to being close or adjoining. Adjacent objects may be separated from each other or may be in physical or direct contact with each other. In some cases, adjacent objects may be coupled to each other or may be integrally formed with each other.

[0111] As used herein, the terms "substantially" and "essentially" or similar terms refer to a considerable degree or extent. When used in conjunction with, for example, an event, situation, characteristic, or property, these terms may refer to instances where the event, situation, characteristic, or property occurs precisely, as well as instances where the event, situation, characteristic, or property occurs nearly, such as considering the typical tolerance levels or variability of the embodiments described herein.

[0112] As used herein, the terms "optional" and "optionally" or similar terms mean that the subsequently described components, structures, elements, events, situations, characteristics, or properties, etc. may or may not be included or occur, and the description includes instances where the components, structures, elements, events, situations, characteristics, or properties, etc. are included or occur and instances where they are not included or do not occur.

[0113] As used herein, the term "continuous" or the phrase "continuous processing" or similar terms or phrases refer to a system or apparatus that performs a process involving multiple sequentially executed steps without pausing or stopping the process—either during a step or between steps—for any reason other than normal or prescribed pauses during a step or during the process between one step and the next. Non-limiting examples of normal pauses include waiting for a prescribed period of time to complete a step, waiting for a device or material to reach a prescribed temperature and other required or desired states or conditions, or pausing between process steps when one or more shared components used to perform the next step in the process are used to perform one or more steps of another process.

[0114] An apparatus in which a pipette tip holding station as disclosed herein can be implemented is indicated by Figure 1 and Figure 2 the reference numeral 225 in the figures, and includes an automated robotic pipette 300. Referring to Figure 2 and Figure 3 , a pipette tip holding station for capturing and temporarily holding (isolating) a pipette tip separated from the pipette is represented by the reference numeral 100 and may be referred to herein as the "holding station". As Figure 2 and Figure 3 shown, the holding station 100 is disposed below the pipette 300. A waste container 220 for receiving pipette tips discarded by the pipette 300 may be supported in a waste drawer 224 of the apparatus 225 (see Figure 1 and Figure 3 ), the waste drawer 224 being configured to move laterally in and out of the apparatus 225. The waste container 220 may be lined with a plastic bag, which may be disposable. When the drawer 224 is in the closed position and moved laterally into the apparatus 225, the holding station 100 is disposed above the waste container 220, as Figure 3 shown.

[0115] The apparatus 225 may be a chemical or biological analyzer, such as a molecular analyzer for performing nucleic acid-based amplification reactions. Exemplary processing apparatuses that may be used with the holding station 100 include the analyzers described in U.S. Patent Nos. 8,731,712 and 9,732,374 and International Patent Application No. PCT / US2018 / 041472, and the and Panther systems available from Hologic, Inc. (Marlborough, MA).

[0116] The pipettor 300 can be configured to move horizontally and vertically, e.g., in the X, Y, and Z directions, and is used to withdraw liquid from a container and dispense the liquid into a container. 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 seats, and to transfer sample material from one or more sample containers to one or more reaction seats to form a reaction mixture. The reagent can be stored in a liquid state, or the reagent can be stored in a non-liquid state, such as a lyophilized state, in which case the pipettor can be used to transfer a reconstitution agent into the reagent container and subsequently transfer the reconstituted reagent into the reaction container. The instrument 225 can include a tray or container 228 that holds a plurality of pipette tips (see Figure 2 ). The tray or container 228 can be located within a pipette tip holder compartment (e.g., a drawer) of the instrument 225 in a position and orientation such that the pipettor 300 can selectively engage an individual pipette tip to removably attach to the pipettor 300.

[0117] As Figure 17 and Figure 18 shown, the pipettor 300 can have a probe 302 (shown only in Figure 18 ), which has a mounting end 314 (which can be the distal end of the probe), and a disposable pipette tip 290 is removably attached to the mounting end 314. 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 the pipette tip 290 is mounted onto the mounting end 314. Referring to Figure 18 , an embodiment of the pipette tip 290 includes a collar 292 at the first (proximal) end of the pipette tip 290, a conical tapered tip 296 at the second (distal) end of the pipette tip 290, and a barrel section 294 between the collar 292 and the tip 296, and the barrel section 294 can be cylindrical in shape with a generally constant diameter. Exemplary commercially available pipette tips are available from TECAN (TECAN Inc., Research Triangle Park, NC).

[0118] As Figure 17 and Figure 18As shown, 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) via the arm 310. The pipettor 300 may include a tip release mechanism for releasing a 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 above the probe 302 and is axially movable relative to the probe 302. The release sleeve 304 is connected to a release lever 306 configured to axially move the release sleeve 304 relative to the probe 302. A release trigger 308 (shown only in Figure 17 is coupled to the release lever 306 via a linkage (not shown) within the housing 312.

[0119] The pipette tip 290 is frictionally fixed to the probe 302 by inserting the probe 302 into an opening surrounded by a collar 292 of the pipette tip 290 supported in a pipettor tray 228. When the probe 302 is inserted into the pipette tip 290, the tip of the probe 290 contacts the release sleeve 304, thereby pushing the sleeve 304 and the release lever 306 upward to the Figure 17 position shown. When the sleeve 304 and the release lever 306 are pushed upward, the linkage coupling the release lever 306 to the release trigger 308 causes the release trigger 308 to extend below the housing 312, as Figure 17 shown. To eject or release the pipette tip 290 from the pipettor 300, the pipettor arm 310 is lowered until the release trigger 308 contacts a release surface that pushes the release trigger 308 upward into the housing 312, thereby axially moving the release lever 306 and the release sleeve 304 downward relative to the probe 302. The downward movement of the release sleeve 304 contacts the tip of the pipette tip 290 frictionally fixed to the probe 302, thereby forcing the pipette tip 290 off the probe 302 to release the pipette tip 290 from the pipettor 302.

[0120] As Figure 4 shown, an embodiment of the holding station 100 includes a top frame 102, side cabinet frames 150, side cover plates 160 disposed above the side cabinet frames 150, an upper waste chute 152 connected to a lower waste chute 162 (which may be a lower portion of the side cabinet frame 150), and a waste chute cover plate 164 disposed above the lower waste chute 162. The holding station 100 also includes a holding compartment 166 disposed below a portion of the top frame 102. As described above, by Figure 4The waste container 220 schematically shown in the box therein includes being located below the waste chute 162 to receive waste items such as pipette tips that fall through the chute 162. The waste container may be lined with a bag, typically disposable and plastic. As described above, the waste container 220 may be supported within an instrument 225 in a drawer 224, and the drawer 224 is configured to move laterally (e.g., back-and-forth movement relative to the front of the instrument 225) between a first or closed position and a second or open position within the instrument 225. In the second or open position, the drawer 224 is pulled out from the instrument 225 in a manner that enables access to the waste container 220, such that the waste container can be removed from the drawer 224 and emptied, and / or the waste container 220 lined with a bag can be removed from the waste container 220 and replaced with a new empty bag.

[0121] When the waste container 220 is located below the waste chute 162 of the holding station 100 - for example, when the drawer is in the first or closed position - the waste container 220 is in the pipette tip receiving position relative to the pipette 300 because it is positioned to capture the used pipette tips released by the pipette 300. In various embodiments, the waste container sensor 222 generates a signal for the system control software - as described below - 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, if the waste container 220 is supported within a drawer, the waste container sensor 222 may detect whether the drawer 224 is in the open position or the 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.

[0122] In an exemplary embodiment, the holding station 100 may optionally include a printed circuit board 280 attached to the top frame 102. The circuit board 280 may include circuits for controlling the holding station 100 and providing power thereto, as well as power and logic components.

[0123] Figure 5 is a perspective view of the holding station 100, where the top frame 102, the printed circuit board 280, the side cover plates 160, the holding compartment 166, and the waste chute cover plate 164 are omitted to reveal the internal components of the holding station 100. As Figure 5As shown, the holding station 100 includes a tip holder conveyor which, in the illustrated embodiment, includes a tip holder chain 230 that is partially supported on a lower track panel 130 and driven by a chain drive mechanism 200. The chain drive mechanism 200 includes a motor 202 mounted on a top frame 102 and connected to a drive wheel 204, and the drive wheel 204 is operatively coupled to the tip holder chain 230. The motor 202 can be controlled by one or more components of a printed circuit board 280 and power can be transmitted to the motor 202 through one or more components of the printed circuit board 280.

[0124] Figure 6 is a perspective view of the holding station 100 in which the top frame 102, the drive mechanism 200, the printed circuit board 280, the side cover plate 160, the lower track panel 130, and the waste chute cover plate 164 are omitted to reveal the internal components of the holding station 100. Figure 7 is a perspective view of the holding station 100 in which the top frame 102, the drive mechanism 200, the printed circuit board 280, the side box frame 150, and the lower track panel 130 are omitted to reveal the internal components of the holding station 100. As Figure 6 and Figure 7 shown, the tip holder chain 230 can include a plurality of tip holder chain links 232 and a plurality of connector chain links 252. In Figure 6 , each tip holder chain link 232 is shown holding a pipette tip 290. However, depending on the state of the holding station 100, one or more tip holder chain links 232 or all of the tip holder chain links 232 may not hold a pipette tip 290. As Figure 5 and Figure 6 shown, 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 plate 160. In one embodiment, the tip holder chain 230 is a continuous chain supported on a continuous track (as will be described in more detail below), and a portion of the pipette tips 290 carried on the tip holder chain 230 can be located in a holding compartment 166 above a drip plate 168 (see Figure 7 ), and the drip plate 168 mates with the lower flange 154 of the box frame 150 to form a drip tray below the pipette tips 290 carried on the tip holder chain 230. The drip tray is positioned to capture any residual liquid that may fall from the pipette tips 290 carried on the tip holder chain 230 and can direct the captured liquid upwardly into a chute 152 and a lower chute 162 and into a waste container 220.

[0125] As Figure 6 and Figure 7As shown, the tip holder chain 230 can include a continuous chain of a plurality of interconnected tip holders, each tip holder being configured to receive and hold a pipette tip released from a pipette. In an example, the tip holder includes tip holder links 232, twenty-two tip holder links 232 in the illustrated embodiment. In alternative embodiments, the tip holder chain may include fewer or more than twenty-two tip holder links 232. The tip holder chain 230 may also include a plurality of connector links 252, which are connected to adjacent connector links 252 or adjacent tip holder links 232 by pins, as described below.

[0126] In alternative embodiments, the tip holder chain is not continuous—or, necessarily, even a chain—but may also include a straight or curved chain or rail having a plurality of tip holders supported thereon.

[0127] In Figure 8 、 Figure 9 and Figure 10 illustrate features of an embodiment of the tip holder chain 230. Figure 8 is a perspective view of a portion of the 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 a connector pin 249. Figure 10 is a perspective view of a single connector link 252 and a connector pin 259.

[0128] Referring Figure 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 242 is partially formed by the top surfaces of the arms 234, 236 and extends across the riser 240 between the arms 234, 236. In one embodiment, the space partially surrounded 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, where the collar 292 of the pipette tip 290 is supported on the tip support 242.

[0129] A connecting pin or post 249 extends through and is preferably fixed 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 the connector pin of an adjacent link.

[0130] Reference Figure 10 , each connector link 252 includes a first lug 254 and a second lug 256, wherein the first lug 254 is disposed above the second lug 256. A connecting pin or post 259 extends through the second lug 256 and is preferably fixed therein, wherein an upper portion 258 (upper post) extends above the second lug 256 and a lower portion 260 (lower post) extends below the second lug 256. A pin opening 255 in the first lug 254 receives the connector pin of an adjacent link.

[0131] As Figure 8 shown, one connector link 252a is connected to an adjacent connector link 252b by inserting the connector pin 259b of the second connector link 252b through the pin opening 255 in 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 the connector pin 249b of the second tip holder link 232b through the pin opening 245 in the upper lug 246 of the first tip holder link 232a. The connector link 252b is connected to an adjacent tip holder link 232a by inserting the connector pin 249a of the adjacent tip holder link 232a through the pin opening 255 in the first lug 254 of the connector link 252b.

[0132] In Figures 11 to 16 is shown the features of the top frame 102. 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. The tip holder chain ( Figure 11 or Figure 12 not shown in) is supported in the track 122 defined between the upper track panel 110 and the lower track panel 130 forming the top frame 102. The drive motor 202 of the chain drive mechanism 200 is mounted on the top of the upper track panel 110, and the chain drive wheel 204 is disposed between the upper track panel 110 and the lower track panel 130. The chain drive wheel 204 can be rotatably supported in the upper frame 102 by bearings 214 (see Figure 13 ) formed in the upper track panel 110 and bearings in the lower track panel 130. A release opening 120 is formed along one edge of the upper track panel 110. The tip ejector adjacent to the release opening 120 is defined by an upper tip ejector ramp or wedge 114 which is part of the upper track panel 110 and a lower tip ejector ramp or wedge 142 which is part of the lower track panel 130.

[0133] Figure 13Partial top perspective view of a portion of the top frame 102 and the tip holder chain 230. As Figure 13 shown, the tip holder chain 230 is supported by an upper track panel 110 and a lower track panel 130 such that a portion of the tip holder chain 230 passes between an upper tip ejector ramp 114 and a lower tip ejector ramp 142.

[0134] Figure 14 Bottom perspective view of the upper track panel 110 in isolation with a portion of the tip holder chain 230. As Figure 14 shown, 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 links 232 and the connector links 252 of the tip holder chain 230 (see Figure 9 and Figure 10 ) extend into the upper track slot 112, respectively. A sensor opening 116 is formed in the upper track panel 110 (see also Figure 12 ) and spans a portion of the upper track slot 112. An optical sensor ( Figure 12 or Figure 14 , not shown) may be mounted 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 includes an optical emitter located on one side of the upper track slot 112 and an optical receiver located 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 emitter and the receiver of the optical sensor disposed therein, thereby interrupting the light beam from the emitter to the receiver and generating a signal as each post of the tip holder chain 230 passes through the sensor located in the opening 116. Thus, the position of the tip holder chain 230 can be monitored by a system controller, as described below, by counting the number of posts that have passed through the sensor and by using an encoder count or motor count of the chain drive motor 202.

[0135] In one embodiment, one of the posts can be designated as the "home" post, thereby identifying a specific position of the tip holder chain 230 as the "home" position. For example, the "home" post can be shorter than all the other posts and short enough such that the post height does not trip the optical sensor within the sensor opening 116. The system control software expects to see the optical sensor trip after a certain number of motor steps. In the case of finding home, it sees that it has exceeded the expected number of motor steps to the next post, so the software continues to move 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 certain number of motor steps to set that position as home.

[0136] Also as Figure 14 shown, in one embodiment, the chain drive wheel 204 includes an upper wheel 206 and a lower wheel 208 connected by a connecting hub 210. Peripheral notches 213 are formed in the upper wheel 206, and peripheral notches 212 are formed in the lower wheel 208. When the chain drive wheel 204 rotates, the upper posts 248, 258 of the tip holder chain 230 are received in the upper peripheral notches 213 of the upper wheel 206, and when the chain drive wheel 204 rotates, the lower posts 250, 260 of the tip holder chain 230 are received in the lower peripheral notches 212 of the lower wheel 208 (also see Figure 15 and Figure 16 ).

[0137] Figure 15 and Figure 16 is a top perspective view of the lower track panel 130 in isolation with a portion of the tip holder chain 230. The lower track panel 130, which is fixed to the bottom of the upper track panel 110, includes lower track slots 132 around a portion of its perimeter. The chain drive wheel 204 is rotatably supported on the lower track panel 130. When the lower track panel 130 is fixed to the upper track panel 110, the lower track slots 132 are aligned with the upper track slots 112. A lower track inner frame 140 and a lower track outer frame 144 are disposed on opposite sides of the lower track slots 132. The tip holder chain 230 is supported on the lower track inner frame 140 and the lower track outer frame 144 within the lower track slots 132. More specifically, the lower portion of each tip holder chain link 232 forming lower and upper lugs 244, 246 is supported on the lower track inner frame 140 and the lower track outer frame 144 and on the lower posts 250 of each connector pin 249 extending into the lower track slots 132. Similarly, although not shown in Figure 15 and Figure 16 each connector link 252 of the tip holder chain 230 is similarly supported by a second lower lug 256 on the lower track inner frame 140 and the lower track outer frame 144 and on the lower posts 260 of each of the connector pins 259 extending into the lower track slots 132.

[0138] During normal operation of the instrument 225 and the pipette 300, after the pipette tip 290 has been used, the pipette 300 moves to the tip release position 270 at the release opening 120 formed in the top frame 102, as Figure 19 and Figure 20 shown. The pipette 300 lowers the pipette tip 290 into the release opening 120 at the tip release position 270, and the pipette tip 290 is released (ejected) from the pipette 300 to drop through the release opening 120 behind the side cover plate 160, through the lower waste chute 162 behind the waste chute cover plate 164 and into the waste container 220. During this operation, when the waste container 220 is in place or the drawer 224 supporting the waste container is closed - as detected by the waste container sensor 222 - the tip holder chain 230 (or the tip holder conveyor in embodiments not including a tip holder chain) is held in a first or standby position in which none of the tip holder links 232 (or the tip holder in embodiments not including a tip holder chain) is located at the tip release position 270, and, typically, no holder link holds a pipette tip. When the waste container 220 is removed or the drawer 224 is opened, as 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 the direction "A" ( Figure 20 the clockwise direction in) which is transverse to the orientation of the pipette tip 290, to place the first tip holder link 232 in a second position at the tip release position 270 to capture and hold the pipette tip 290 released by the pipette 300. As long as the waste container 220 is not in a position to receive the pipette tip released by the pipette, after the pipette tip 290 has been released into the first tip holder link 232, a tip holder advance command will be sent to the drive mechanism 200 to index the tip holder chain 230 to place the next tip holder link 232 at the tip release position 270 to capture and hold the next pipette tip 290 released by the pipette 300. The drive mechanism 200 continues to advance the tip holder chain 230 in the direction "A" in response to the tip holder advance command, thereby sequentially placing the tip holder links 232 at the tip release position 270 to capture and hold each pipette tip 290 released by the pipette 300 when the waste container 220 is not in the pipette tip receiving position.

[0139] In an alternative embodiment, the position at which the pipette tip is released into the tip holder (i.e., the second tip release position) when the waste container is not positioned to receive the released pipette tip is different from the tip release position 270 (i.e., the first tip release position) at which the pipette tip is released when the waste container is positioned to receive the released pipette tip. Such an embodiment would necessarily require reconfiguring the tip holder chain 230 (or the tip holder transporter in embodiments that do not include a tip holder chain) such that the tip holder 232 is placed sequentially at the second tip release position to capture the released tip when the waste container is not positioned to receive the released pipette tip.

[0140] Figure 21 is a partial cross-sectional view of the holding station 100, which shows the pipette 300 releasing the pipette tip 290 into the tip holder link 232 of the tip holder chain 230. As Figure 21 shown, with one of the tip holder links 232 of the tip holder chain 230 positioned at the tip release position 270, the pipette 300 lowers the pipette tip 290 into the tip holder link 232. As the pipette 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 causes the release trigger 308 to be pushed upward, thereby causing the release lever 306 and the release sleeve 304 to move downward to push the pipette tip 290 away from the pipette 300 and into the tip holder link 232 located at the tip release position 270.

[0141] In the illustrated embodiment, the pipette 300 releases the pipette tip at the tip release position 270 regardless of whether the pipette tip is released into the waste container 220 positioned to receive the released pipette tip or into the tip holder of the tip holder transporter when the waste container 220 is not positioned to receive the released pipette tip. In another embodiment, the pipette tip released into the waste container positioned to receive the released pipette tip is released at a position different from the position at which the pipette tip is released into the tip holder of the tip holder transporter when the waste container is not positioned to receive the released pipette tip.

[0142] In one embodiment, when the waste container 220 is not positioned to receive the pipette tip released by the pipette 300, a tip holder advancement command for activating the drive mechanism 200 can be triggered by the movement of the pipette 300. After the pipette 300 has released the pipette tip 290 and retracted to a position away from the tip release position 270, the drive mechanism 200 will be activated to advance the tip holder chain 230 to position the next tip holder link 232 at the tip release position 270 to await the release of another pipette tip 290 by the pipette 300. The release of the pipette tip 290 from the pipette 300 can be detected by the activation of a tip ejector, such as the release sleeve 304, which is configured to eject the pipette tip 300 from the probe 302 (e.g., by a switch activated by the release trigger 308 and / or the release lever 306), or the pipette tip 290 can be at least partially conductive and the pipette 300 can be configured to (e.g., capacitively) detect the presence or absence of the pipette tip 290 on the probe 302.

[0143] In the illustrated embodiment, when the pipette tip 290 is captured and held by the tip holder link 232 of the tip holder chain 230, the orientation of the tip holder chain 230 relative to the pipette tip is advanced laterally, with the captured tip disposed behind the side cover plate 160 and above the lower flange 154 of the side cabinet frame 150 (see Figure 5 and Figure 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 retained within the holding compartment 166, as Figure 6 , Figure 7 and Figure 20 shown, above the drip plate 168, as Figure 7 shown. This arrangement contains any liquid dripping from the pipette tips 290 carried on the tip holder chain 230.

[0144] When the waste container 220 is again in the pipette tip receiving position, e.g., after replacing the waste container 220 or closing the drawer 224 - as detected by the waste container sensor 222 - the pipette tip 290 held in the tip holder (e.g., tip holder link 232) is transferred from the tip holding station 100 to the waste container 220. For example, the pipette tip 290 held in the tip holder is pushed out, removed, or displaced from the associated tip holder at a tip removal position 165 that may be adjacent to the tip release position 270 (see Figure 19 and Figure 20 ). In one embodiment, a tip holder reverse command causes the drive mechanism 200 to reverse the direction of the tip holder chain 230 to move laterally in "B" ( Figure 20move counterclockwise) upward. As Figures 11 to 13 shown and as described above, the tip ejector can include an upper tip ejector ramp 114 and a lower tip ejector ramp 142. The ejector ramps or wedges 114 and 142 each include an inclined edge or surface, and as the tip holder link 232 passes over the ramps 114, 142 in an increasing outwardly extending direction, as Figure 22 shown, the ramps 114 and 142 engage the pipette tip 290 held in the tip holder link 232 and displace or eject the pipette tip 290 from between the arms 234 and 236 ( Figure 22 only arm 234 is visible in), to remove the pipette tip from the tip holder link 232.

[0145] As the tip holder chain 230 carrying one or more pipette tips 290 moves relative to the tip ejector (ramps 114, 142) in direction “B”, at the tip removal position 165, each tip holder link is placed in a third position. As the tip holder link 232 passes through the third position, each pipette tip 290 engages the tip ejector ramps 114, 142 and laterally displaces from between the arms 234 and 236 of the associated tip holder link 232 as the link passes over the tip ejector. More specifically, as Figure 22 shown in the embodiment of, 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 can be made of a flexible material, such as polyoxymethylene (POM), which can be obtained under the trade name purchased. POM, also known as acetal, polyacetal, and polyformaldehyde, is an engineering thermoplastic used in precision parts that require high stiffness, low friction, and excellent dimensional stability. Slightly different formulations can also be used to Ramtal, and purchased under the trade name. In this way, as the tip holder link 232 moves along the track slots 112 / 132 relative to the tip ejector ramps 114, 142 and forces the pipette tip 290 into the gap 238 between the arms 234, 236, the tip ejector ramps 114, 142 engage the pipette tip 290 (see Figure 9), the arms 234, 236 bend outwardly, thereby expanding the gap 238 such that the barrel 294 of the pipette tip 290 can pass through the gap 238 and the pipette tip 290 can be removed from the tip holder 232. Alternatively, the arms 234, 236 can be made of a relatively non-flexible material, such as aluminum, and the pipette tip 290 can be formed of a compressible material such that as the tip holder link 232 moves relative to the tip ejector ramps 114, 142 and forces the pipette tip 290 into the gap 238 between the arms 234, 236, the tip ejector ramps 114, 142 engage the pipette tip 290 (see Figure 9 ), the barrel 294 of the pipette tip 290 is compressed to the width of the gap 238 such that the barrel 294 can pass through the gap 238 and the pipette tip 290 can be removed from the tip holder 232. As another alternative, the pipette tip 290 can be removed by a combination of flexion of the arms 234, 236 and compression of the barrel 294 of the pipette tip 290.

[0146] In an alternative embodiment, at a position displaced in the direction "A" from the tip release position 270, the tip ejector is located at a position along the continuous travel path of the pipette tip holder chain 230. In such an arrangement, continued movement of the pipette tip holder chain 230 in the direction "A" causes the tip holder 232 to pass over the tip ejector, thereby removing any pipette tips carried by the pipette tip holder chain 230. Thus, instead of reversing the direction of movement of the tip holder chain to remove the pipette tip 290 from the tip holder 232 of the pipette tip holder chain 230, it is removed by continuing to move in the same direction "A" of the pipette tip holder chain while the pipette tip is captured in the tip holder. Since the tip removal position in such embodiments may not be adjacent to the tip release position 270, an enlarged or otherwise modified waste chute may be required to direct the pipette tip removed from the tip holder 232 into the waste container 220.

[0147] 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 at three or more positions above and / or below the tip holder link 232.

[0148] The tip ejector can be located adjacent to the tip release position 270 and above the lower waste chute 162 such that when the pipette tip 290 is removed from its corresponding tip holder link 232, the pipette tip 290 will fall through the lower waste chute 162 into the waste container 220.

[0149] In the illustrated embodiment, the tip holder chain 230 can capture and carry up to 22 pipette tips 290 (this is a non-limiting example; the tip holder conveyor can carry more or fewer than 22 pipette tips 290). However, it is not necessary for the pipette tips 290 to be captured in each 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 the tip receiving position, the tip holder chain 230 will be advanced by the drive mechanism 200 in the direction "A" to sequentially place each tip holder link 232 at the tip release position 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 can reverse the direction of the tip holder chain 230 in the direction "B", regardless of whether the pipette tips 290 have been captured in each tip holder link 232, to remove all of the pipette tips 290 carried by the tip holder chain 230. On the other hand, if the waste container 220 is absent for an extended period of time and the pipette tips 290 are captured in 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 to move the pipette tip holder conveyor (e.g., the tip holder chain 230), and the operation of the pipette 300 can be interrupted until the waste container 220 is returned to the pipette tip receiving position.

[0150] As described above, in an alternative embodiment, the tip holder chain 230 need not be a continuous chain as shown, but can be a discontinuous group of tip holders with an adjacent positioning having a circular or linear arrangement, which includes means for automatically moving the arrangement to sequentially place each tip holder in the tip release position or to pass each tip holder sequentially past a tip ejector to remove the pipette tip from the tip holder.

[0151] Figure 23is a flowchart showing a method 400 for facilitating the uninterrupted processing of multiple samples in an automated system. Generally, the goal of the method and apparatus is to detect whether a waste container is located in the pipette tip release position relative to the pipette release position of a pipette, and if the waste container is not in the pipette tip receiving position, the pipette tip released by the pipette is captured and retained by a pipette tip holding station to isolate it until the waste container returns to the pipette tip receiving position. In one embodiment, the isolated pipette tip has previously been used to process at least a subset of the multiple samples in the system, and any pipette tip used to process the multiple samples and released from the pipette when the waste container is in the pipette tip receiving position is released directly into the waste container. After the waste container returns to the pipette tip receiving position, the isolated pipette tip is transferred from the pipette tip holding station to the waste container.

[0152] The method of the embodiment begins at step S402. At step S404, the pipette 300 moves to the tip release position 270, as Figures 19 to 21 shown.

[0153] At step S406, it is determined whether the waste container is in place - that is, whether the waste container is in the pipette tip receiving position. Step S406 can be performed by using a sensor 222 to determine whether the waste container 220 is in place to receive the pipette tip 290 released by the pipette 300 and / or whether the drawer 224 supporting the waste container 220 is in the open position or the closed position.

[0154] At step S408, if the waste container is determined to be in the pipette tip receiving position, the pipette tip 290 is released from the pipette 300 and falls through the chute 162 and into the waste container (e.g., waste container 220).

[0155] If at step S406 it is determined that the waste container is not in the position for receiving the pipette tip 290 released by the pipette 300, then at step S410 the first tip holder of the tip holder conveyor is moved to the tip release position. In the case where the tip holder conveyor includes a tip holder chain 230, step S410 can be performed by advancing the tip holder chain 230 to place the first tip holder link 232 at the tip release position 270 (see Figure 19 and Figure 20 ).

[0156] At step S412, the pipette tip 290 is released into the tip holder, which moves to the pipette tip release position. In one embodiment, step S412 can be performed by releasing the pipette tip 290 from the pipette 300 into the first tip holder link 232.

[0157] In step S414, it is determined whether the waste container has been replaced, i.e., whether it has been returned to the pipette tip receiving position. Step S414 can be determined by using sensor 222 to determine whether the waste container 220 is in place to receive the pipette tip 290 released by the pipette 300 and / or whether the drawer 224 supporting the waste container 220 is in the open or closed position.

[0158] If it is determined in step S414 that the waste container is in the pipette tip receiving position, one or more pipette tips carried in the tip holder are pushed out or removed from the tip holder and are allowed to fall into the waste container in step S416. Then, the tip holder is moved away from the tip release position. In one embodiment, step S416 is performed by moving the tip holder chain 230 relative to the tip ejector (e.g., upper and / or lower tip ejector ramps 114, 142), and the tip ejector engages the pipette tip held in the tip holder link 232 to displace the pipette tip 290, and the pipette tip 290 then falls into the waste container 220.

[0159] On the other hand, if it is determined in step S414 that the waste container has not been returned to the pipette tip receiving position, then in step S418, it is determined whether all the tip holders of the tip holder conveyor have been used to hold the pipette tips released by the pipette. In one embodiment, step S418 is performed by counting the number of tip holder links 232 that have passed through the tip release position 270 and the number of pipette tips 290 that have been released by the pipette 300. The number of tip holder links 232 that have passed through the tip release position 270 can be determined by a sensor disposed in the sensor opening 116 of the upper track panel 110 (see Figure 12 and Figure 14 ).

[0160] If it is determined in step S418 that not all the tip holders have been used to hold the released pipette tips, then in step S420, the pipette is moved to the tip release position. In step S422, the next tip holder is moved to the tip release position, and in step S424, the pipette tip is released by the pipette into the next tip holder at the tip release position. The process 400 then returns to step S414.

[0161] If it is determined in step S418 that all the tip holders have been used to hold the pipette tips released by the pipettor and there are no remaining unused tip holders, the operation of the pipettor is interrupted in step S426 because there is no means for handling additional used pipette tips. Thus, the used pipette tips cannot be discarded until the waste container is returned to the pipette tip receiving position. Accordingly, process 400 returns to step S414.

[0162] Control system

[0163] Figure 24 is a block diagram schematically showing a control architecture of a disposable pipette tip management system 500 for controlling a holding station 100. An exemplary control architecture can include a controller 350 that monitors, communicates with, and controls various aspects of system 500, including a drive motor 202 of the holding station 100 and a link sensor 118 (which can be disposed in a sensor opening 116 formed in the upper track panel 110, see Figure 12 and Figure 14 ), a pipettor 300, and a waste container sensor 222. The drive motor 202 of the holding station 100 is coupled to and controlled by the controller 350, which can also be connected to a power supply 352 that can be controlled by the controller 350. The controller 350 provides power and operation control signals to the drive motor 202. The controller 350 can also receive data from the drive motor 202 in the form of rotary encoder counts from an encoder (e.g., a placement encoder) coupled to the drive motor 202, as well as other feedback sensor signals.

[0164] The controller 350 may include a computer system for executing control software (which may include firmware) that affects the power, operation, control, and / or monitoring of the holding station 100 and other components of the system 500. The controller 350 may be implemented by one or more logic elements such as a computer, an embedded controller, a programmable gate array, an application specific integrated circuit, a programmable logic device, etc., and may include or access a 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. The controller 350 may also include additional memory, including for example a hard disk drive and / or a removable storage drive, representing a tape drive, a compact disc drive, a USB slot, a memory card interface, an Internet memory, a cloud-based memory, or any storage medium or format now known or later developed. The storage devices and storage units used herein may include any storage medium for the persistent and / or volatile storage of electronic data now known or later developed. Such data may be stored in a database in the storage medium, 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.

[0165] In an alternative embodiment, some or all of the memory may include other similar devices for allowing a computer program or other instructions to be loaded into the computer system. Such devices may include for example a removable storage unit and interface. Examples of such may include a memory stick and memory stick interface, a secure digital card and interface, and other portable media and interfaces that allow software and data to be transferred to the controller 350.

[0166] The software contains instructions stored on a non-transitory computer-readable medium that, when executed by the logic elements of the controller 350, cause the control and computing hardware to perform one or more automated or semi-automated processes.

[0167] The computer system of the controller 350 may also include a communication interface that allows information (such as power, control, and feedback signals, software, data, etc.) to be transmitted between the controller 350 and networked external devices and / or an external network. Examples of communication interfaces may include a modem, a network interface (such as an Ethernet card), a communication port, a PCMCIA slot and card, a USB port, a FireWire port, Bluetooth, or any interface now known or later developed. The information transmitted via the communication interface is in the form of signals, which may be electronic, electromagnetic, optical, or other signals that can be received by the communication interface.

[0168] The computer system of controller 350 may also include one or more input devices, such as a touch screen, stylus, keyboard, mouse or other pointing device, microphone, data scanner (e.g., bar code, RFID, etc.), and so on. The computer system may also include various output devices, including indicator lights, displays, printers, tactile (e.g., vibration) indicators, and audio speakers.

[0169] As used herein, terms such as "computer program medium", "computer-readable medium", "computer-usable medium" are used to generally refer to media such as removable storage units, hard disks installed in hard disk drives, and other devices for providing software and data to controller 350.

[0170] The computer program (also referred to as computer control logic) is stored in one or more portions of memory 354, which is part of or accessible by controller 350. A computer program may also be received via the communication interface. Such a computer program may include algorithms, such as Figure 23 algorithm 400 shown in

[0171] When software is used to implement aspects of the subject matter disclosed herein in an embodiment, the software may be stored in a computer program product and loaded into the computer system of controller 350 using a removable storage drive, hard disk drive, interface, and / or communication interface. The control logic (software), when executed by a processor of controller 350, causes the processor to perform the functional aspects as described herein via the above-described systems, devices, equipment, sensors, encoders, etc. The 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 of computer programs running on the computer system.

[0172] Controller 350 may include a stand-alone system dedicated to system 500 or holding station 100 (e.g., in printed circuit board 280, see Figure 4 )), or one or more components of controller 350 - e.g., processor, memory, interface, input / output devices, etc. - may be a shared portion of a global controller of one or more components of a controller device, such as device 225, or in addition to system 500, the laboratory of which system 500 is a part.

[0173] As Figure 24Schematically shown, with respect to the pipette tip holder station 100, the controller 350 receives signals from the drive motor 202 and the link sensor 118 and sends signals to the drive motor 202. The controller 350 can also receive signals from the pipette 300 and send signals to the pipette 300, and can receive signals from the waste container sensor 222. For example, the controller 350 can send a control signal to the pipette 300 to move to the pipette tip release position 270 and lower the pipette arm 310 until the release trigger 308 contacts the release surface 156 (see Figure 21 ). After the pipette tip 290 is released, the controller 350 can send a signal to the pipette 300 to move from the pipette release position 270. The controller 350 can receive a signal from the waste container sensor 222 that indicates whether the waste container 220 is in the pipette tip receiving position and / or indicates whether the drawer 224 supporting the waste container 220 is in the open position or the closed position. (See Figures 1 to 4 ). When 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 will send 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. Signals from the motor 202 and / or signals from the link sensor 118 to the controller 350 allow the controller 350 to control the drive motor 202 to properly position the tip holder at the tip release position. When the controller 350 receives a signal from the pipette 300 that the pipette tip 290 has been released, the controller 350 can send a signal (tip holder advance command) to the drive motor 202 to move the next tip holder to the position at the pipette tip release position. If the signal received by the controller 350 from the link sensor 118 indicates that all tip holders have been moved to the pipette tip release position, the signal from the controller 350 to the pipette 300 can interrupt the operation of the pipette 300. When receiving a signal from the waste container sensor 222 that the waste container 220 is in the pipette tip receiving position, the controller 350 will send a signal to the drive motor 202 (e.g., tip holder reverse command) to move the pipette tip holder conveyor (e.g., the pipette tip holder chain 230) to the standby position. As the pipette tip holder conveyor moves towards the standby position, the tip holder that has received the pipette tip is moved by the tip ejector, and the pipette tip carried by it is removed from the tip holder by the tip ejector.

[0174] Embodiment

[0175] Example 1. A device for capturing one or more pipette tips released from an automated pipette at a tip release position, the device comprising:

[0176] A tip holder transporter including or supporting a plurality of tip holders, each tip holder configured to receive and releasably hold a single pipette tip;

[0177] A drive mechanism configured to rotate the tip holder transporter to sequentially place each of one or more of the plurality of tip holders in the tip release position to receive a pipette tip released by the automated pipette into each tip holder placed in the tip release position; and

[0178] A tip ejector positioned to engage a pipette tip held in each of one or more of the plurality of tip holders when the tip holder transporter is moved relative to the tip ejector by the drive mechanism, the tip ejector configured to remove each pipette tip engaged from an associated tip holder.

[0179] Example 2. The device according to Example 1, wherein the plurality of tip holders of the tip holder transporter are interconnected to form a tip holder chain.

[0180] Example 3. The device according to Example 2, wherein the tip holder chain includes a continuous chain guided by a continuous track.

[0181] Example 4. The device according to any one of Examples 1 to 3, wherein, after the automated pipette releases a pipette tip into the tip holder located at the tip release position, if at least one of the plurality of tip holders has not received a pipette tip released by the automated pipette, the drive mechanism rotates the tip holder transporter to rotate a subsequent tip holder to the tip release position.

[0182] Example 5. The device according to any one of Examples 1 to 4, wherein when there is no tip holder at the tip release position, the pipette tip released from the automated pipette will fall into a removable waste container positioned to receive the released pipette tip, and wherein the device further includes a waste container sensor configured to detect whether the waste container is positioned to receive the released pipette tip, whereby detection by the waste container sensor that the waste container is not positioned to receive the released pipette tip causes the drive mechanism to rotate the tip holder conveyor to position each of the one or more tip holders in sequence at the tip release position to capture each pipette tip released when the waste container is not positioned to receive the released pipette tip, and detection by the waste container sensor that the waste container is positioned to receive the released pipette tip causes the drive mechanism to move the tip holder conveyor to move each of the one or more tip holders in sequence relative to the tip ejector to remove the pipette tip from the associated tip holder at the tip removal position.

[0183] Example 6. The device according to Example 5, further including a waste chute located below the tip release position and below the tip removal position, wherein the waste chute is configured to direct the pipette tip released by the automated pipette or the pipette tip removed from the tip holder of the tip holder conveyor into the waste container.

[0184] Example 7. The device according to Example 5, wherein the drive mechanism is configured to move the tip holder conveyor to a standby position when the waste container sensor detects that the waste container is positioned to receive the released pipette tip, at which standby position no tip holder is at the tip release position.

[0185] Example 8. The device according to Example 7, wherein when the tip holder conveyor moves to the standby position, each tip holder holding a pipette tip moves in sequence relative to the tip ejector to remove the pipette tip from the associated tip holder such that when the tip holder conveyor is in the standby position, the tip holder conveyor does not hold a pipette tip.

[0186] Example 9. The device according to any one of Examples 1 to 8, wherein the tip holder conveyor includes a tip holder chain including a plurality of interconnected links, and wherein each tip holder is part of one of the links.

[0187] Example 10. The device according to any one of Examples 1 to 8, wherein the tip holder transporter includes a detection element at each tip holder, and the device further includes a sensor for detecting each detection element of the sensor as the drive mechanism moves the tip holder transporter.

[0188] Example 11. The device according to Example 10, wherein the tip holder transporter includes a tip holder chain, which includes a plurality of interconnected links, and each tip holder is part of one of the links, and each detection element includes a pin connecting one link to an adjacent link.

[0189] Example 12. The device according to Example 11, further comprising a controller configured to determine the position of the tip holder chain based on the number of detection elements that have passed through the sensor.

[0190] Example 13. The device according to Example 11 or 12, wherein the tip holder chain includes a continuous chain guided by a continuous track.

[0191] Example 14. The device according to Example 13, wherein the drive mechanism includes a chain drive including a motorized wheel, and the continuous chain is towed around the motorized wheel.

[0192] Example 15. The device according to any one of Examples 1 to 14, wherein each tip holder includes a clip defining an opening configured to receive a pipette tip without any resistance.

[0193] Example 16. The device according to Example 15, wherein each clip includes opposing arms configured to hold a pipette tip therebetween and defining a lateral opening that is smaller than the width of a portion of the pipette tip held between the opposing arms.

[0194] Example 17. The device according to Example 16, wherein the tip ejector includes one or more inclined surfaces that contact the pipette tip held in the opening of the clip as the tip holder passes by the tip ejector, and wherein the opposing arms are flexible such that the one or more inclined surfaces contact the pipette tip, the pipette tip moves laterally and pushes the opposing arms apart to widen the lateral opening and allow the pipette tip to pass through the lateral opening and be removed from the tip holder.

[0195] Example 18. The device according to Example 17, wherein the tip holder transporter follows a curved path adjacent to the tip ejector.

[0196] Example 19. The apparatus according to Example 17 or 18, wherein the tip ejector includes first and second laterally extending ramps, wherein the first laterally extending ramp is configured to engage a first portion of the pipette tip extending over the clip as the tip holder moves relative to the tip ejector, and the second laterally extending ramp is configured to engage a second portion of the pipette tip extending under the clip as the tip holder moves relative to the tip ejector.

[0197] Example 20. The apparatus according to any one of Examples 1 to 19, wherein the drive mechanism is configured to move the tip holder transporter in a first direction to sequentially place each tip holder at the tip release position, and is configured to move the tip holder transporter in a second direction opposite to the first direction to move the tip holder transporter relative to the tip ejector to remove the pipette tip from the associated tip holder.

[0198] Example 21. The apparatus according to Example 20, wherein at least a portion of the tip holder transporter follows a linear path when moved in the first and second directions.

[0199] Example 22. An instrument, comprising:

[0200] A pipette configured to move laterally and vertically within the instrument, the pipette having a mounting end adapted to receive a pipette tip in a friction fit;

[0201] A waste container movable between a first receptacle position and a second receptacle position, wherein the waste container is positioned to receive a pipette tip released from the mounting end of the pipette at the tip release position when the waste container is in the first receptacle position, and wherein the waste container is not positioned to receive a pipette tip released from the mounting end of the pipette at the tip release position when the waste container is in the second receptacle position; and

[0202] 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 pipette at the tip release position 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 a pipette tip released from the mounting end of the pipette at the tip release position when the waste container is in the second receptacle position.

[0203] Example 23. The instrument according to Example 22, wherein the pipette is configured for X, Y, and Z movement.

[0204] Example 24. The instrument according to Example 22 or 23, wherein the pipette includes a probe, and wherein the mounting end includes the distal end of the probe.

[0205] Example 25. The instrument according to any one of Examples 22 to 24, further comprising a pipette tip holder compartment and a container for pipette tips disposed within the pipette tip holder compartment, wherein within the pipette tip holder compartment the pipette tips in the container are positioned and oriented to be engaged by the mounting end of the pipette.

[0206] Example 26. The instrument according to any one of Examples 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 position the pipette tip held in the pipette tip holder is removed from the pipette tip holder.

[0207] Example 27. The instrument according to Example 26, further comprising a tip ejector configured to remove the pipette tip from the pipette tip holder at the third position.

[0208] Example 28. The instrument according to Example 27, wherein the pipette tip is laterally displaced from the pipette tip holder by the tip ejector.

[0209] Example 29. The instrument according to any one of Examples 26 to 28, wherein the 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 the movement of the pipette tip holder from the second tip holder position to the third tip holder position is in a second lateral direction, the first lateral direction and the second lateral direction being opposite directions.

[0210] Example 30. The instrument according to any one of Examples 22 to 29, wherein the waste container is lined with a disposable plastic bag.

[0211] Example 31. The instrument according to any one of Examples 22 to 30, further comprising a drawer that supports the waste container, wherein the drawer is configured to laterally move the waste container between the first and second seat positions.

[0212] Example 32. The apparatus according to any one of Examples 22 to 31, further comprising a sensor for sensing when the waste container is in at least one of the first and second receptacle positions.

[0213] Example 33. The apparatus according to any one of Examples 22 to 32, wherein the pipette tip holder is carried on a conveyor.

[0214] Example 34. The apparatus according to Example 33, further comprising a track for supporting the conveyor.

[0215] Example 35. The apparatus according to Example 34, further comprising a sensor for monitoring the position of the pipette tip holder on the track.

[0216] Example 36. The apparatus according to any one of Examples 33 to 35, further comprising a drip tray located below a portion of the conveyor.

[0217] Example 37. The apparatus according to any one of Examples 22 to 36, wherein the pipette tip holder is one of a plurality of pipette tip holders.

[0218] Example 38. The apparatus according to any one of Examples 22 to 37, wherein when the pipette tip holder is not in the second tip holder position to receive the pipette tip released from the mounting end of the pipette at the tip release position and the waste container is in the first receptacle position, the pipette tip is released into the waste container.

[0219] Example 39. The apparatus according to Example 38, wherein when the pipette tip holder is not in the second tip holder position to receive the pipette tip released from the mounting end of the pipette at the tip release position and the waste container is in the first receptacle position, the pipette tip can be released into a chute that guides the pipette tip into the waste container.

[0220] Example 40. The apparatus according to any one of Examples 22 to 39, wherein each tip holder includes a clip defining an opening configured to receive a pipette tip without any resistance.

[0221] Example 41. The apparatus according to Example 40, wherein the clip includes opposing arms configured to hold a pipette tip therebetween and defining a lateral opening that is smaller than the width of a portion of the pipette tip held between the opposing arms.

[0222] Example 42. The instrument according to any one of Examples 22 to 41, wherein the pipette includes a tip release mechanism for releasing the pipette tip from the mounting end of the pipette.

[0223] Example 43. The instrument according to Example 42, wherein the tip release mechanism includes a release sleeve coaxially mounted above the mounting end and configured to be axially movable relative to the mounting end.

[0224] Example 44. The instrument according to Example 43, wherein the tip release mechanism further includes a release trigger coupled to the release sleeve and configured to axially move the release sleeve relative to the mounting end to release the pipette tip from the mounting end when the pipette moves the release trigger into contact with a release surface.

[0225] Example 45. A method for capturing one or more pipette tips released from an automated pipette, the method comprising:

[0226] a) repeatedly laterally moving the pipette with the pipette tip fixed thereto to a tip release position and releasing the pipette tip from the pipette, whereby the released pipette tip falls into a waste container positioned to receive the released pipette tip;

[0227] 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

[0228] c) when it is detected 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, in which 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, in which 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 with the pipette tip holder in the second tip holder position.

[0229] Example 46. The method according to Example 45, further comprising:

[0230] d) When the waste container is no longer positioned to receive a pipette tip released from the pipette at the tip release position, move an additional pipette tip holder from the first tip holder position to the 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 pipette at the tip release position, and in the second tip holder position, the pipette tip holder is positioned to receive a pipette tip released from the pipette at the tip release position, and

[0231] e) Receive the pipette tip released from the pipette with an associated pipette tip holder in the second tip holder position.

[0232] Example 47. The method according to Example 45 or 46, wherein step b) is performed with a sensor that detects the presence or absence of the waste container.

[0233] Example 48. The method according to any one of Examples 45 to 47, further comprising, after step c):

[0234] f) When it is detected that the waste container is positioned to receive a pipette tip from the pipette at the tip release position, move the pipette tip from the second tip holder position to a third tip holder position different from the second tip holder position; and

[0235] g) At the third tip holder position, remove the pipette tip from the pipette tip holder, whereby the removed pipette tip falls into the waste container.

[0236] Example 49. The method according to Example 48, wherein step g) includes moving the pipette tip holder relative to a tip ejector, the tip ejector including at least one inclined surface that engages the pipette tip held in the tip holder and laterally displaces the pipette tip out of the tip holder.

[0237] Example 50. The method according to any one of Examples 45 to 49, wherein a plurality of tip holders are interconnected to form a continuous chain of tip holders, and step f) includes moving the chain of tip holders with a motor-driven wheel that engages the chain of tip holders.

[0238] Example 51. The method according to any one of Examples 48 to 50, wherein step c) includes moving the pipette tip holder in a first lateral direction, and step f) includes moving the pipette tip holder in a second lateral direction, wherein the first and second laterals are opposite directions.

[0239] Example 52. The method according to any one of Examples 45 to 51, further comprising:

[0240] h) Monitoring the position of the pipette tip holder.

[0241] Example 53. The method according to any one of Examples 45 to 52, further comprising:

[0242] i) Determining that no pipette tip holder without a pipette tip is available; and

[0243] j) Interrupting the operation of the pipette when no pipette tip holder without a pipette tip is available.

[0244] Example 54. The method according to any one of Examples 45 to 53, wherein releasing the pipette tip from the pipette comprises engaging the pipette tip attached to the pipette with a tip release mechanism.

[0245] Example 55. The method according to Example 54, wherein the tip release mechanism comprises a release sleeve coaxially mounted above the mounting end of the pipette, the pipette tip being attached to the mounting end, and wherein engaging the pipette tip with the tip release mechanism comprises axially moving the release sleeve relative to the mounting end.

[0246] Example 56. The method according to Example 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 comprises bringing a release surface into contact with the release trigger.

[0247] Example 57. A method for facilitating uninterrupted processing of a plurality of samples in an automated system, the method comprising the steps of:

[0248] a) Detecting that the waste container of the system is not in the pipette tip receiving position;

[0249] b) After step a) and when the waste container is not in the pipette tip receiving position, isolating one or more pipette tips released from the pipette in a pipette tip holding station of the system, the isolated pipette tips having previously been used to process at least a subset of the plurality of samples in the system, wherein any pipette tip used to process the plurality of samples and released from the pipette when the waste container is in the pipette tip receiving position is released directly into the waste container;

[0250] c) After step b), detecting that the waste container is in the pipette tip receiving position; and

[0251] d) After step c) and when the waste container is in the pipette tip receiving position, transfer the isolated pipette tip from the pipette tip holding station to the waste container.

[0252] Wherein the processing of the plurality of samples in the system during steps a) to d) is uninterrupted.

[0253] Example 58. The method according to Example 57, wherein the waste container is supported by a drawer that is movable laterally towards or away from the pipette tip receiving position.

[0254] Example 59. The method according to Example 57 or 58, wherein the waste container is lined with a disposable plastic bag.

[0255] Example 60. The method according to any one of Examples 57 to 59, wherein steps a) and b) include using a position sensor of the system to detect when the waste container is or is not in the pipette tip receiving position.

[0256] Example 61. The method according to any one of Examples 57 to 60, wherein step b) includes, for each of the one or more pipette tips, moving the pipette to engage with the pipette tip release surface of the holding station, such that the pipette releases the associated pipette tip from the mounting end of the pipette.

[0257] Example 62. The method according to any one of Examples 57 to 61, wherein in step b), the one or more pipette tips are released into a separate pipette tip holder at a first tip release position, and when the waste container is not in the pipette tip receiving position, the separate pipette tip holder is contained within the pipette tip holding station.

[0258] Example 63. The method according to Example 62, wherein the pipette tip holder supports the one or more pipette tips in an upright orientation.

[0259] Example 64. The method according to Example 62 or 63, wherein the separate pipette tip holder includes or is supported by an annular conveyor of the pipette tip holding station.

[0260] Example 65. The method according to Example 64, wherein the separate pipette tip holder moves in a first lateral direction on the conveyor during step b), and in a second lateral direction on the conveyor during step d), the first lateral and the second lateral being opposite directions.

[0261] Example 66. The method according to any one of Examples 62 to 65, wherein step d) comprises laterally displacing the one or more pipette tips from the separate pipette tip holders.

[0262] Example 67. The method according to any one of Examples 62 to 66, further comprising the step of releasing at least one pipette tip from the pipette at a second tip release position when the waste container is in the pipette tip receiving position.

[0263] Example 68. The method according to Example 67, wherein the first and second tip release positions are the same tip release position.

[0264] Example 69. The method according to Example 67 or 68, wherein the first and second tip release positions are located above a chute for guiding the pipette tip to the waste container.

[0265] Example 70. The method according to any one of Examples 57 to 69, further comprising the step of collecting residual fluid discharged from at least one of the one or more pipette tips in a tray disposed below the one or more pipette tips isolated in the holding station in step b), the tray being a component of the holding station.

[0266] Example 71. The method according to any one of Examples 57 to 70, wherein the processing of at least one subset of the plurality of samples comprises reconstituting or transferring reagents for performing a nucleic acid-based amplification reaction.

[0267] Example 72. The method according to any one of Examples 57 to 71, wherein the processing of at least one 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.

[0268] Although 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 sub-combinations of features, those skilled in the art will readily appreciate other embodiments and variations and modifications encompassed within the scope of the present disclosure. Additionally, the description of such embodiments, combinations, and sub-combinations is not intended to convey that the claimed subject matter requires features or combinations of features other than those expressly recited in the claims. Accordingly, the scope of the present disclosure is intended to embrace all modifications and variations that fall within the spirit and scope of the appended claims.

Claims

1. An apparatus, the apparatus comprising: An automated pipette positioned at a tip release position; A removable waste container; A tip holder transporter including or supporting a plurality of tip holders, each tip holder configured to receive and releasably hold a single pipette tip, wherein when there is no tip holder at the tip release position, a pipette tip released from the automated pipette will fall into the removable waste container positioned to receive the released pipette tip; A drive mechanism configured to index the tip holder transporter to sequentially place each of one or more of the plurality of tip holders in the tip release position to receive a pipette tip released by the automated pipette into each tip holder placed at the tip release position; A tip ejector positioned to engage a pipette tip held in each of one or more of the plurality of tip holders when the tip holder transporter is moved by the drive mechanism relative to the tip ejector, the tip ejector configured to remove each pipette tip engaged from an associated tip holder; And A waste container sensor configured to detect whether the waste container is positioned to receive the released pipette tip, whereby detection 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 transporter to sequentially position each of the one or more tip holders at the tip release position to capture each pipette tip released when the waste container is not positioned to receive the released pipette tip, and detection by the waste container sensor that the waste container is positioned to receive the released pipette tip causes the drive mechanism to move the tip holder transporter 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 position.

2. The apparatus according to claim 1, wherein the plurality of tip holders of the tip holder transporter are interconnected to form a tip holder chain.

3. The apparatus according to claim 2, wherein the tip holder chain comprises a continuous chain guided by a continuous track.

4. The apparatus according to claim 1, wherein, After the automated pipette releases a pipette tip into the tip holder at the tip release position, if at least one of the plurality of tip holders has not received the pipette tip released by the automated pipette, the drive mechanism indexes the tip holder transporter to index a subsequent tip holder to the tip release position.

5. The apparatus according to claim 4, further comprising a waste chute located below the tip release position and below the tip removal position, wherein the waste chute is configured to direct a pipette tip released by the automated pipette or a pipette tip removed from the tip holder of the tip holder conveyor to the waste container.

6. The apparatus according to claim 4, wherein the drive mechanism is configured to move the tip holder conveyor to a standby position when the waste container sensor detects that the waste container is positioned to receive the released pipette tip, and in the standby position, no tip holder is located at the tip release position.

7. The apparatus according to claim 6, wherein when the tip holder conveyor is moved to the standby position, each tip holder holding a pipette tip moves sequentially relative to the tip ejector to remove the pipette tip from the associated tip holder, such that when the tip holder conveyor is in the standby position, the tip holder conveyor does not hold a pipette tip.

8. The apparatus according to claim 1, wherein the tip holder conveyor comprises a tip holder chain, which comprises a plurality of interconnected links, and wherein each tip holder is part of one of the links.

9. The apparatus according to claim 1, wherein the tip holder conveyor comprises a detection element at each tip holder, and the apparatus further comprises a sensor for detecting each detection element passing through the sensor when the drive mechanism moves the tip holder conveyor.

10. The apparatus according to claim 9, wherein the tip holder conveyor comprises a tip holder chain, which comprises a plurality of interconnected links, and each tip holder is part of one of the links, and each detection element comprises a pin connecting one link to an adjacent link.

11. The apparatus according to claim 10, further comprising a controller configured to determine the position of the tip holder chain based on the number of detection elements that have passed through the sensor.

12. The apparatus according to claim 10 or 11, wherein the tip holder chain comprises a continuous chain guided by a continuous track.

13. The apparatus according to claim 12, wherein the drive mechanism comprises a chain drive, which comprises a motorized wheel, and the continuous chain is pulled around the motorized wheel.

14. The apparatus according to claim 1, wherein each tip holder comprises a clip defining an opening configured to receive a pipette tip without any resistance.

15. The apparatus according to claim 14, wherein each clip comprises opposing arms configured to hold a pipette tip therebetween and defining a lateral opening that is smaller than the width of a portion of the pipette tip held between the opposing arms.

16. The instrument according to claim 15, wherein the tip ejector includes one or more inclined surfaces that contact a pipette tip held in the opening of the clip as the tip holder passes over the tip ejector, and wherein the opposing arms are flexible such that the one or more inclined surfaces contact the pipette tip, the pipette tip moves laterally and pushes the opposing arms apart to widen the lateral opening and allow the pipette tip to pass through the lateral opening and be removed from the tip holder.

17. The instrument according to claim 16, wherein the tip holder conveyor follows a curved path adjacent to the tip ejector.

18. The instrument according to claim 16 or 17, wherein the tip ejector includes a first laterally extending inclined surface and a second laterally extending inclined surface, wherein the first laterally extending inclined surface is configured to engage a first portion of the pipette tip extending over the clip as the tip holder moves relative to the tip ejector, and the second laterally extending inclined surface is configured to engage a second portion of the pipette tip extending under the clip as the tip holder moves relative to the tip ejector.

19. The instrument according to claim 1, wherein the drive mechanism is configured to move the tip holder conveyor in a first direction to sequentially place each tip holder at the tip release position, and is configured 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.

20. The instrument according to claim 19, wherein at least a portion of the tip holder conveyor follows a linear path when moved in the first and second directions.

21. An instrument comprising: a pipette configured to move laterally and vertically within the instrument, the pipette having a mounting end adapted to receive a pipette tip in a friction fit; a waste container movable between a first seating position and a second seating position, wherein the waste container is positioned to receive a pipette tip released from the mounting end of the pipette at the tip release position when the waste container is in the first seating position, and wherein the waste container is not positioned to receive a pipette tip released from the mounting end of the pipette at the tip release position when the waste container is in the second seating position; and A pipette tip holder movable between a first tip holder position, a second tip holder position, and a third tip holder position different from the 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 pipette at the tip release position when the waste container is in the first receptacle position, 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 pipette at the tip release position when the waste container is in the second receptacle position, and wherein at the third tip holder position, the pipette tip held in the pipette tip holder is removed from the pipette tip holder.

22. The apparatus according to claim 21, wherein the pipette is configured for X, Y, and Z movement.

23. The apparatus according to claim 21, wherein the pipette includes a probe, and wherein the mounting end includes the distal end of the probe.

24. The apparatus according to claim 21, further comprising a pipette tip holder compartment and a container for pipette tips disposed within the pipette tip holder compartment, wherein the pipette tips in the container within the pipette tip holder compartment are positioned and oriented to be engaged by the mounting end of the pipette.

25. The apparatus according to claim 21, further comprising a tip ejector configured to remove the pipette tip from the pipette tip holder at the third tip holder position.

26. The apparatus according to claim 25, wherein the pipette tip is laterally displaced from the pipette tip holder by the tip ejector.

27. The apparatus according to claim 21, wherein the 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 the movement of the pipette tip holder from the second tip holder position to the third tip holder position is in a second lateral direction, the first lateral direction and the second lateral direction being opposite directions.

28. The apparatus according to claim 21, wherein the waste container is lined with a disposable plastic bag.

29. The apparatus according to claim 21, further comprising a drawer that supports the waste container, wherein the drawer is configured to laterally move the waste container between the first receptacle position and the second receptacle position.

30. The apparatus according to claim 21, further comprising a sensor for sensing when the waste container is in at least one of the first receptacle position and the second receptacle position.

31. The apparatus according to claim 21, wherein the pipette tip holder is carried on a conveyor.

32. The apparatus according to claim 31, further comprising tracks for supporting the conveyor.

33. The apparatus according to claim 32, further comprising a sensor for monitoring the position of the pipette tip holder on the track.

34. The apparatus according to any one of claims 31 to 33, further comprising a drip tray located below a part of the conveyor.

35. The apparatus according to claim 21, wherein the pipette tip holder is one of a plurality of pipette tip holders.

36. The apparatus according to claim 21, wherein when the pipette tip holder is not in the second tip holder position to receive the pipette tip released from the mounting end of the pipette at the tip release position and the waste container is in the first receptacle position, the pipette tip is released into the waste container.

37. The apparatus according to claim 36, wherein when the pipette tip holder is not in the second tip holder position to receive the pipette tip released from the mounting end of the pipette at the tip release position and the waste container is in the first receptacle position, the pipette tip is released into a chute that guides the pipette tip to the waste container.

38. The apparatus according to claim 21, wherein the tip holder comprises a clip defining an opening configured to receive a pipette tip without any resistance.

39. The apparatus according to claim 38, wherein the clip comprises opposing arms configured to hold a pipette tip therebetween and defining a lateral opening that is smaller than the width of a portion of the pipette tip held between the opposing arms.

40. The apparatus according to claim 21, wherein the pipette comprises a tip release mechanism for releasing the pipette tip from the mounting end of the pipette.

41. The apparatus according to claim 40, wherein the tip release mechanism comprises a release sleeve coaxially mounted above the mounting end and configured to be axially movable relative to the mounting end.

42. The apparatus according to claim 41, wherein the tip release mechanism further comprises a release trigger coupled to the release sleeve and configured to axially move the release sleeve relative to the mounting end to release the pipette tip from the mounting end when the pipette moves the release trigger into contact with a release surface.

43. A method for capturing one or more pipette tips released from an automated pipette, the method comprising: a) repeatedly laterally moving the pipette with a pipette tip fixed thereto to a tip release position and releasing the pipette tip from the pipette, whereby the released pipette tip falls 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 pipette at the tip release position; and c) When it is detected that the waste container is no longer positioned to receive a pipette tip released from the pipette at the tip release position, move the pipette tip holder from a first tip holder position to 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 pipette at the tip release position. In the second tip holder position, the pipette tip holder is positioned to receive a pipette tip released from the pipette at the tip release position; and receive, with the pipette tip holder in the second tip holder position, a pipette tip released from the pipette.

44. The method according to claim 43, further comprising: d) When the waste container is no longer positioned to receive a pipette tip released from the pipette at the tip release position, move an additional pipette tip holder from the first tip holder position to the 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 pipette at the tip release position. In the second tip holder position, the pipette tip holder is positioned to receive a pipette tip released from the pipette at the tip release position, and e) receive, with the associated pipette tip holder in the second tip holder position, the pipette tip released from the pipette.

45. The method according to claim 43, wherein step b) is performed by a sensor that detects the presence or absence of the waste container.

46. The method according to any one of claims 43 to 45, further comprising, After step c): f) When it is detected that the waste container is positioned to receive a pipette tip from the pipette at the tip release position, move the pipette tip holder from the second tip holder position to a third tip holder position different from the second tip holder position; and g) at the third tip holder position, remove the pipette tip from the pipette tip holder, whereby the removed pipette tip falls into the waste container.

47. The method according to claim 46, wherein step g) includes moving the pipette tip holder relative to a tip ejector, the tip ejector including at least one inclined surface that engages the pipette tip held in the pipette tip holder and laterally moves the pipette tip out of the tip holder.

48. The method according to claim 43, wherein a plurality of tip holders are interconnected to form a continuous tip holder chain, and step f) includes moving the tip holder chain with a motor-driven wheel that engages the tip holder chain.

49. The method according to claim 46, wherein step c) includes moving the pipette tip holder in a first lateral direction, and step f) includes moving the pipette tip holder in a second lateral direction, wherein the first lateral direction and the second lateral direction are opposite directions.

50. The method according to claim 43, further comprising: h) Monitoring the position of the pipette tip holder.

51. The method according to claim 43, further comprising: i) Determining that no pipette tip holder without a pipette tip is available; and j) Interrupting the operation of the pipette when no pipette tip holder without a pipette tip is available.

52. The method according to claim 43, wherein releasing the pipette tip from the pipette comprises engaging the pipette tip attached to the pipette with a tip release mechanism.

53. The method according to claim 52, wherein the tip release mechanism comprises a release sleeve coaxially mounted above the mounting end of the pipette, to which the pipette tip is attached, and wherein engaging the pipette tip with the tip release mechanism comprises axially moving the release sleeve relative to the mounting end.

54. The method according to claim 53, 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 comprises bringing a release surface into contact with the release trigger.

55. A method for facilitating uninterrupted processing of a plurality of samples in an automated system, the method comprising the steps of: a) Detecting that a waste container of the system is not in a pipette tip receiving position; b) After step a) and when the waste container is not in the pipette tip receiving position, isolating one or more pipette tips released from the pipette in a pipette tip holding station of the system, the isolated pipette tips having previously been used to process at least a subset of the plurality of samples in the system, wherein any pipette tips used to process the plurality of samples and released from the pipette when the waste container is in the pipette tip receiving position are 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) and when 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, wherein the processing of the plurality of samples in the system during steps a) to d) is uninterrupted.

56. The method according to claim 55, wherein the waste container is supported by a drawer movable laterally towards or away from the pipette tip receiving position.

57. The method according to claim 55, wherein the waste container is lined with a disposable plastic bag.

58. The method according to claim 55, wherein steps a) and b) comprise using a position sensor of the system to detect when the waste container is or is not in the pipette tip receiving position.

59. The method according to claim 55, wherein step b) comprises, for each of the one or more pipette tips, moving the pipette to engage with the pipette tip release surface of the holding station, such that the pipette releases the associated pipette tip from the mounting end of the pipette.

60. The method according to claim 55, wherein in step b), the one or more pipette tips are released into separate pipette tip holders at a first tip release position, and when the waste container is not in the pipette tip receiving position, the separate pipette tip holders are contained within the pipette tip holding station.

61. The method according to claim 60, wherein the pipette tip holders support the one or more pipette tips in an upright orientation.

62. The method according to claim 60 or 61, wherein the separate pipette tip holders comprise or are supported by a ring conveyor of the pipette tip holding station.

63. The method according to claim 62, wherein the separate pipette tip holders move in a first lateral direction on the conveyor during step b), and move in a second lateral direction on the conveyor in step d), the first lateral direction and the second lateral direction being opposite directions.

64. The method according to claim 60, wherein step d) comprises laterally displacing the one or more pipette tips from the separate pipette tip holders.

65. The method according to claim 60, further comprising the step of releasing at least one pipette tip from the pipette at a second tip release position when the waste container is in the pipette tip receiving position.

66. The method according to claim 65, wherein the first tip release position and the second tip release position are the same tip release position.

67. The method according to claim 65 or 66, wherein the first tip release position and the second tip release position are located above a chute for guiding the pipette tip to the waste container.

68. The method according to claim 55, further comprising the steps of: Collect the residual fluid discharged from at least one of the one or more pipette tips in a tray disposed below the one or more pipette tips isolated in the holding station in step b), the tray being a component of the holding station.

69. The method according to claim 55, wherein the processing of at least one subset of the plurality of samples comprises reconstituting or transferring reagents for performing a nucleic acid-based amplification reaction.

70. The method according to claim 55, wherein the processing of at least one subset of the plurality of samples comprises forming a reaction mixture, which comprises one of the samples and at least one reagent for performing a nucleic acid-based amplification reaction.

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