Liquid handling device and pipette head for aspirating and / or dispensing liquid and method thereof

JP2022518066A5Active Publication Date: 2025-08-01FORMULATRIX INT HLDG LTD
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Patent Information

Application Number
JP2021543452
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2019-01-28
Filing Date
2019-12-31
Publication Date
2025-08-01
Estimated Expiration
2039-12-31

AI Technical Summary

Technical Problem

Conventional liquid handling instruments require powerful actuators and heavy mechanical structures due to high friction from compressible rubber O-rings, leading to maintenance needs and inefficiencies in pipette tip insertion, especially in multi-channel systems.

Method used

The implementation of a multi-channel liquid handling device with zero insertion force pipette tip and plunger gripping mechanisms, utilizing a pipette head with integrated motors and timing belts to manage pipette tips and plungers without the need for a sealed boundary, ensuring a reliable hermetic seal and reducing maintenance.

Benefits of technology

This solution provides a robust, contamination-free, and efficient liquid handling system that minimizes mechanical stress, reduces downtime, and enhances operational throughput by eliminating the need for periodic maintenance of sealing interfaces.

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Abstract

A liquid handling device and pipette head for aspirating and / or dispensing liquid and a method thereof are disclosed. Specifically, an automated liquid handling device is provided for aspirating and / or dispensing liquid from a source medium to a destination medium using at least one pipette head and a positive displacement pipette tip, the positive displacement pipette tip including a pipette tip and a pipette plunger. The pipette head of the liquid handling device includes a plate, a threaded rod, a motor, a timing (or drive) belt, and a custom timing pulley / nut. The pipette head further includes an arrangement of a pipette plunger gripping mechanism and a pipette tip gripping mechanism featuring a zero-insertion-force gripping mechanism.
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Description

Technical Field

[0001] Cross - reference to Related Applications The subject matter of the present disclosure is related to U.S. Provisional Patent Application No. 62 / 797,687, titled "Liquid Handling Apparatus and Pipette Head and Method for Aspirating and / or Dispensing Liquids", filed on January 28, 2019, the entire disclosure of which is incorporated herein by reference.

[0002] The subject matter of the present disclosure generally relates to liquid handling methods and more particularly to liquid handling apparatus and pipette heads for aspirating and / or dispensing liquids and methods therefor.

Background Art

[0003] Automated liquid handling apparatus includes robots used to transfer specific amounts of liquid, such as reagents or samples, between specified containers. Liquid handling apparatus is useful in a variety of applications, including cell biology, genomics, forensics, and drug research. The apparatus helps people in repetitive tasks of transferring liquids over a wide range of volumes to improve the speed and efficiency of operation and the accuracy and precision of the volume delivered. Advantages of automating the liquid handling process include improving throughput and efficiency of operation and eliminating human error.

[0004] In conventional liquid handling equipment, there is usually a sealed boundary between the equipment and each pipette tip. This sealed boundary is typically a compressible rubber O-ring, requiring periodic maintenance and / or replacement throughout the equipment's lifespan. Compressible rubber O-rings also have the disadvantage of high friction during pipette tip insertion, ultimately requiring (1) a powerful actuator to achieve the required downward force and (2) a strong / heavy mechanical structure to handle the high friction from multiple O-rings and implement a reliable sealed boundary for multiple pipette tips (e.g., 96 pipette tips used in a 96-well sample plate). For example, in conventional liquid handling equipment, one pipette tip requires an insertion force of approximately 100 grams, and therefore the actuator for that tip must provide a downward force of approximately 100 grams. Thus, in a multi-channel liquid handling device for processing, for example, 96 pipette tips, the actuator must be capable of a downward force of approximately 9.5 kilograms. Therefore, a powerful actuator is required, along with a strong / heavy mechanical support structure capable of handling high forces. [Overview of the project]

[0005] The subject of the present invention describes apparatus and methods for aspirating and / or dispensing liquids using pipette tips. In one embodiment, the liquid processing apparatus includes an apparatus housing having an apparatus deck, a pipette head on the apparatus deck, and a removable tray, wherein the apparatus deck has a removable tray that holds the removable tray.

[0006] The removable tray includes a handle. The removable tray holds one or more microplates and one or more tip caddies on top of the microplates. The removable tray has a unique identification number configured to be scanned or read. The unique identification number is a 2D barcode or a radio frequency identification tag.

[0007] Furthermore, the equipment includes robotic components and a controller. For example, the robotic components can control the movement of the pipette head relative to the equipment deck, and the controller can execute programmed instructions.

[0008] The instrument further includes one or more volumetric pipette tips, and the pipette head is a multi-channel pipette head integrated with a multi-position stage for operating one or more volumetric pipettes.

[0009] The pipette head further includes a plurality of plates stacked and arranged for four screw threads, and one or more motors for driving one or more timing belts, each of which is supported by the plurality of plates, and an upper heating mounting plate.

[0010] The plates are substantially rectangular, and the four threaded rods are arranged in a substantially rectangular shape corresponding to the four corners of the plates. In one embodiment, the plates are eight plates arranged sequentially from bottom to top along the four threaded rods.

[0011] The lower plate is fixed to the lower ends of the four threaded rods, the upper plate is fixed on top of the four threaded rods, and the remaining plate is positioned between the upper and lower plates and is movable along the four threaded rods.

[0012] In one embodiment, the lower plate is a pipette tip collet holder plate on which one or more volumetric pipette tips are attached. The instrument further includes one or more pipette tip gripping mechanisms. One of the one or more motors is a gripping tip motor, and one or more timing belts are gripping tip timing belts, and the gripping tip motor and gripping tip timing belts are configured to move one or more of a plurality of plates away from or toward the lower plate.

[0013] In another embodiment, one or more volumetric pipette tips include a pipette tip having a boundary and a pipette tip body, the boundary having an inner wall and a receptacle, the pipette tip body having a fluid channel along the length of the pipette tip body, the fluid channel having an opening at the distal end of the fluid channel, and a pipette plunger disposed along the inside of the pipette tip, the pipette plunger having a plunger tip having a plunger upper, a plunger center and a distal tip, and the receptacle configured to receive the plunger center. In one embodiment, the fluid channel is configured to receive the distal tip of the plunger tip, and one or more pipette tip gripping mechanisms are zero insertion force pipette gripping mechanisms.

[0014] In another embodiment, one or more pipette plunger gripping mechanisms are provided in the center of the pipette head, and each of the one or more pipette plunger mechanisms is coupled to the respective plunger of the respective volumetric pipette tip.

[0015] The device further includes a set of zero-insertion-force pipette plunger gripping mechanisms. In one embodiment, one of one or more motors is used to control the set of zero-insertion-force pipette plunger mechanisms. Another one of one or more motors is a gripping plunger motor, and one of one or more timing belts is a gripping plunger timing belt, and the gripping plunger motor and gripping plunger timing belt are configured to move one or more of a plurality of plates away from or toward the lower plate.

[0016] The apparatus further includes a pipette plunger. In one embodiment, one of one or more motors is used to control the pipette plunger. One or more motors is a metering plunger motor, and one or more timing belts is a metering plunger timing belt, and the metering plunger motor and metering plunger timing belts are configured to move one or more of a plurality of plates away from or toward the lower plate.

[0017] The device further includes one or more pipette plunger gripping mechanisms, which are zero insertion force pipette plunger gripping mechanisms. In one embodiment, each of the one or more zero insertion force pipette plunger gripping mechanisms includes a plunger collet and a pipette plunger fixing mechanism, the plunger collet including a shaft portion and a collet chuck portion for fitting around the top of the plunger of the pipette plunger. Furthermore, the collet chuck portion is a segment band or sleeve for fitting around the top of the plunger of the pipette plunger.

[0018] This subject further describes a method for aspirating and / or dispensing liquids. In one embodiment, the method is a step of providing a liquid processing apparatus, the liquid processing apparatus comprising an apparatus housing having an apparatus deck, a pipette head on the apparatus deck, and a removable tray, the apparatus deck holding the removable tray, the pipette head having an arrangement of one or more volumetric pipette tips for aspirating and dispensing liquids, the pipette head comprising one or more pipette tip gripping mechanisms and one or more pipette plunger gripping mechanisms, each of the one or more volumetric pipette tips comprising a pipette tip and a corresponding pipette plunger, the step of gripping one or more pipette plungers with one or more pipette plunger gripping mechanisms, the step of gripping one or more pipette tips with one or more pipette tip gripping mechanisms, and the step of performing an aspiration and / or dispensing operation using the pipette head.

[0019] Since the subject matter of this disclosure has been described in general terms, we will now refer to the attached drawings, which are not necessarily drawn to scale. [Brief explanation of the drawing]

[0020] [Figure 1] Various schematic perspective views of the multichannel liquid handling apparatus of this disclosure are drawn, including a pipette head that includes the arrangement of a volumetric pipette tip for aspirating and / or dispensing liquid. [Figure 2] Various schematic perspective views of the multichannel liquid handling apparatus of this disclosure are drawn, including a pipette head that includes the arrangement of a volumetric pipette tip for aspirating and / or dispensing liquid. [Figure 3] Various schematic perspective views of the multichannel liquid handling apparatus of this disclosure are drawn, including a pipette head that includes the arrangement of a volumetric pipette tip for aspirating and / or dispensing liquid. [Figure 4] Various schematic perspective views of the multichannel liquid handling apparatus of this disclosure are drawn, including a pipette head that includes the arrangement of a volumetric pipette tip for aspirating and / or dispensing liquid. [Figure 5] Various schematic perspective views of the multichannel liquid handling apparatus of this disclosure are drawn, including a pipette head that includes the arrangement of a volumetric pipette tip for aspirating and / or dispensing liquid. [Figure 6] Various schematic perspective views of the pipette head of this disclosure, including the arrangement of a volumetric pipette tip for aspirating and / or dispensing liquid, are drawn. [Figure 7] Various schematic perspective views of the pipette head of this disclosure, including the arrangement of a volumetric pipette tip for aspirating and / or dispensing liquid, are drawn. [Figure 8] Various schematic perspective views of the pipette head of this disclosure, including the arrangement of a volumetric pipette tip for aspirating and / or dispensing liquid, are drawn. [Figure 9] A front view of the pipette head of this disclosure is drawn, including the arrangement of a volumetric pipette tip for aspirating and / or dispensing liquid. [Figure 10]Draw a rear view of the pipette head of the present disclosure including an arrangement of a positive displacement pipette tip for aspirating and / or dispensing a liquid. [Figure 11] Draw a side view of the pipette head of the present disclosure including an arrangement of a positive displacement pipette tip for aspirating and / or dispensing a liquid. [Figure 12] Draw another side view of the pipette head of the present disclosure including an arrangement of a positive displacement pipette tip for aspirating and / or dispensing a liquid. [Figure 13] Draw a top view of the pipette head of the present disclosure including an arrangement of a positive displacement pipette tip for aspirating and / or dispensing a liquid. [Figure 14] Draw a bottom view of the pipette head of the present disclosure including an arrangement of a positive displacement pipette tip for aspirating and / or dispensing a liquid. [Figure 15] Draw a cross-sectional view of the pipette tip of the present disclosure including an arrangement of a positive displacement pipette tip for aspirating and / or dispensing a liquid. [Figures 16A-16B] Draw a schematic perspective view of an example of a positive displacement pipette and a pipette plunger of the pipette head of the present disclosure. [Figure 17] Draw a cross-sectional view of an example of a positive displacement pipette and a pipette plunger shown in FIGS. 16A and 16B. [Figure 18] Draw a cross-sectional view of the upper part of the positive displacement pipette tip of the present disclosure. [Figures 19A-19B] Draw a side view and a cross-sectional view of each of the pipette tips of the positive displacement pipette tip. [Figure 20] Draw a detailed side view of the distal tip of the pipette plunger with respect to the distal tip of the pipette tip. [Figure 21] Draw a schematic perspective view of an example of a pipette tip collet for use with a positive displacement pipette tip. <00001​​​​​​Figures 23A and 23B show schematic perspective views of the collet chuck portion of the plunger collet. [Figure 24B] Figures 23A and 23B show cross-sectional views of the pipette plunger relative to the plunger collet. [Figures 25A-25B] An example of a pipette plunger gripping mechanism and the process for gripping the pipette plunger of the pipette head of this disclosure are shown. [Figure 26] A flow diagram is drawn illustrating an example of a method using the pipette head of this disclosure, including the arrangement of a volumetric pipette tip for aspirating and / or dispensing a liquid. [Modes for carrying out the invention]

[0021] The subject matter of this disclosure is described in more detail hereafter with reference to the accompanying drawings, and some, though not all, embodiments of the subject matter of this disclosure are shown. Similar reference numerals refer to similar elements throughout. The subject matter of this disclosure is embodied in many different forms and should not be construed as being limited to the embodiments described herein, but rather these embodiments are provided to satisfy the legal requirements to which this disclosure is applicable. In fact, many modifications and other embodiments of the subject matter of this disclosure described herein will be conceivable to those skilled in the art who have benefited from the teachings shown in the foregoing description and accompanying drawings. Therefore, it should be understood that the subject matter of this disclosure should not be limited to the specific embodiments disclosed, and modifications and other embodiments are intended to be included within the scope of the accompanying claims.

[0022] In some embodiments, the subject matter of the present disclosure provides liquid processing equipment, pipette heads and methods for aspirating and / or dispensing liquids. For example, an automated liquid processing equipment is provided for aspirating and / or dispensing a liquid from a source medium to a target medium by using at least one pipette head and a volumetric pipette tip, the volumetric pipette tip comprising a pipette tip and a pipette plunger.

[0023] In some embodiments, the automated liquid handling equipment of the present disclosure is a multi-channel liquid handling equipment for aspirating and / or dispensing liquids. In one example, the multi-channel liquid handling equipment is an 8-channel liquid handling equipment that operates, for example, 8 pipette tips associated with an 8-well sample plate. In another example, the multi-channel liquid handling equipment is a 96-channel liquid handling equipment that operates, for example, 96 pipette tips associated with a 96-well sample plate.

[0024] In some embodiments, the automated liquid handling equipment of the present disclosure is a zero-insertion-force system that provides a mechanism for inserting a volumetric pipette tip using zero insertion force, since it does not require a sealing boundary between the equipment and the pipette tip. For example, the automated liquid handling equipment provides (1) one or more zero-insertion-force pipette tip gripping mechanisms and (2) one or more zero-insertion-force pipette plunger gripping mechanisms. Furthermore, each gripping mechanism provides a reliable zero-insertion-force hermetic seal that requires substantially no periodic maintenance and / or replacement, thereby ensuring a robust pipette system.

[0025] In some embodiments, the automated liquid handling equipment of this disclosure includes certain features that protect against contamination. For example, conventional liquid handling equipment has a shared air column between all pipette tip boundaries, which is a common source of contamination that may carry over to the next workflow. In contrast, the automated liquid handling equipment of this disclosure does not include a shared air column between pipette tips and is therefore free from this potential source of contamination.

[0026] Various schematic perspective views of the multichannel liquid processing apparatus 100 of this disclosure, including a pipette head 110 with arrangement of volumetric pipette tips for aspirating and / or dispensing liquids, are shown hereby with reference to Figures 1 to 5. For example, of the multichannel liquid processing apparatus 100 of this disclosure, Figure 1 shows a schematic perspective view, Figure 2 shows a front view, Figure 3 shows a rear view, Figure 4 shows one side view, and Figure 5 shows an opposite side view.

[0027] The multi-channel liquid processing equipment 100 of this disclosure is a robot-based automated liquid processing equipment. The multi-channel liquid processing equipment 100 includes, for example, an equipment housing 180 and an equipment deck 182. The equipment deck 182 is, for example, one or two rails on each side. The multi-channel liquid processing equipment 100 and the equipment deck 182 are designed to hold a removable tray. For example, a removable tray 183 is mounted on the equipment deck 182. The removable tray 183 includes a handle 184 for easy transport.

[0028] The removable tray 183 includes multiple microplate or laboratory equipment positions for holding, for example, one or more microplates 185. One or more tip caddies 186 to be processed are located on a particular microplate 185. The tip caddies 186 are consumable trays or boxes for holding / packing arrangements of multiple pipette tips 150. The multi-channel liquid handling instrument 100 includes pipette heads 110 positioned on an instrument deck 182 for aspirating liquids from liquids and / or dispensing liquids. The pipette heads 110 are equipped with arrangements of multiple pipette tips 150.

[0029] The multi-channel liquid processing apparatus 100 also includes a robotic apparatus 188 and a controller 190. The robotic apparatus 188 is any robotic apparatus capable of precisely controlling the movement of the pipette head 110 relative to the apparatus deck 182. The controller 190 is any standard controller or microprocessor device capable of executing programmed instructions.

[0030] The mechanisms of the multi-channel liquid processing apparatus 100 of this disclosure include, but are not limited to, removable trays / decks, fully automatic deck / tray calibration, fully automatic probes for calibrating multiple plate arrangements, cameras for scanning multiple microplate positions, tip caddy positions, deck / tray IDs and verifying tip availability of caddies, head collision detection, and the like.

[0031] In the multi-channel liquid processing apparatus 100 of this disclosure, the removable tray 183 has a unique ID number using a two-dimensional barcode that is scanned / read using, for example, a camera (not shown) on the pipette head 110. In another example, the removable tray 183 has a unique radio frequency identification (RFID) tag that is scanned / read using an RFID reader (not shown) on the pipette head 110. During operation, each time the multi-channel liquid processing apparatus 100 is used, the user places a removable tray 183 containing a specific set of microplates 185 in the instrument deck 182 and then performs a specific protocol. Upon completion, the user then removes their removable tray 183. The next user then places the next removable tray 183 containing the next set of microplates 185 in the instrument deck 182 and then performs a different protocol.

[0032] Therefore, the benefit of the multi-channel liquid processing equipment 100 of this disclosure is that, due to the presence of removable trays 183, the equipment can be easily and quickly shared among multiple users, with each user having their own tray containing a specific set of microplates 185 and a specific protocol to perform. This shared equipment approach achieves the maximum uptime of the multi-channel liquid processing equipment 100, which is a slow and cumbersome process that causes downtime compared to conventional equipment where the entire set of microplates must be switched from one user to the next from a non-removable deck.

[0033] The multi-channel liquid handling device 100 and / or pipette head 110 features volumetric pipette tips. Each volumetric pipette tip includes a pipette tip and a pipette plunger designed to aspirate and / or dispense a precise volume of liquid. For example, each volumetric pipette tip includes a minimum amount of space between the pipette tip and the pipette plunger, thereby optimizing the accuracy of the volume of liquid aspirated and / or dispensed. Furthermore, the pipette head 110 provides a zero insertion force gripping mechanism for both the pipette tip and the pipette plunger of each volumetric pipette tip.

[0034] The pipette head 110 is a multi-channel pipette head, such as an 8-channel or 96-channel pipette head, integrated with a multi-position stage for operating one or more volumetric pipette tips 150. For example, the pipette head 110 handles single-tip, 1-8 tips (in one column), 1-12 tips (in one row), 96 tips, and / or cluster / group tip configurations of two or more tips. Further details of examples of volumetric pipette tips 150 are shown and described below with reference to Figures 16A to 1620.

[0035] Referring here to Figures 6 to 15, Figures 6, 7, and 8 are various schematic perspective views of an example of a pipette head 110 including the arrangement of a volumetric pipette tip 150 for aspirating and / or dispensing liquid. Furthermore, Figures 9, 10, 11, 12, 13, and 14 show a front view, rear view, side view, another side view, top view, and bottom view of the pipette head 110, respectively. Furthermore, Figure 15 shows a cross-sectional view of the pipette head 110 cut along line AA in Figure 6.

[0036] Referring further to Figures 6 to 15, the pipette head 110, in combination with various other support members and / or components, includes, for example, multiple plates 112 stacked on top of four threaded rods (or main threads) 114, three motors 116 (e.g., 116a, 116b, 116c) that drive three respective timing (or drive) belts 118 (e.g., 118a, 118b, 118c), and an upper heating mounting plate 113. For example, the pipette head 110 may include, but is not limited to, any type of light source (e.g., LEDs), a camera, a heater, a printed circuit board (PCB), thermal management devices (e.g., a fan, a heat sink), any type of sensor, any type of actuator, and so on. Furthermore, the pipette head 110 includes a wide variety of components, including, but is not limited to, handles, plates, panels, bars, rods, shafts, brackets, blocks, spacers, hubs, collars, clamps, bushings, bearings, pins, dowels, cams, aligners, screws, nuts, bolts, washers, springs, clips, any type of mechanical connector, any type of electrical connector, and many other components.

[0037] The four threaded rods 114 are arranged in a substantially rectangular shape, corresponding substantially to the four corners of the rectangular plate 112. In one example, the pipette head 110 contains eight plates 112 (112a, 112b, 112c, 112d, 112e, 112f, 112g, 112h). Furthermore, the eight plates 112a, 112b, 112c, 112d, 112e, 112f, 112g, 112h are arranged sequentially from bottom to top along the four threaded rods 114. For example, plate 112a (hereinafter referred to as the lower plate 112a) is fixed to the lower end of the four threaded rods 114, while plate 112h (hereinafter referred to as the upper plate 112h) is fixed to the upper end of the four threaded rods 114. The lower plate 112a serves as a pipette tip collet holder plate to which a volumetric pipette tip 150 is attached.

[0038] The remaining plates 112b, 112c, 112d, 112e, 112f, and 112g are arranged in pairs and then motor-driven up or down along four threaded rods 114 to perform specific functions. In one example, a motor 116a (hereinafter referred to as the gripping tip motor 116a) is used to precisely control a set of zero-insertion-force pipette tip gripping mechanisms 130 (see Figure 22) of the pipette head 110. The gripping tip motor 116a is supported by plates 112b and 112c. The gripping tip motor 116a drives a timing (or drive) belt 118a (hereinafter referred to as the gripping tip timing belt 118a). For example, threaded timing belt pulleys / nuts (not shown) are attached to each of the four threaded rods 114. Thus, the gripping tip timing belt 118a is positioned on four timing belt pulleys and motor-driven pulleys (not shown). When the gripping tip motor 116a is operated, plates 112b and 112c (along with any parts attached thereto) move up and down together on four screw rods 114 by the rotational movement of a screw timing belt pulley / nut. That is, plates 112b and 112c move together away from or toward the lower plate 112a to which the positive displacement pipette tip 150 is attached.

[0039] In another example, a motor 116b (hereinafter referred to as the gripping plunger motor 116b) is used to precisely control the zero insertion force pipette plunger gripping mechanism 140 of the pipette head 110. The gripping plunger motor 116b is supported by plates 112d and 112e. The gripping plunger motor 116b drives a timing (or drive) belt 118b (hereinafter referred to as the gripping plunger timing belt 118b). For example, a screw timing belt pulley / nut (not shown) is attached to each of the four screw rods 114. Thus, the gripping plunger timing belt 118b is positioned on the four timing belt pulleys and a motor drive pulley (not shown). When the gripping plunger motor 116b is operated, plates 112d and 112e (along with any parts attached thereto) move up and down together on the four screw rods 114 by the rotational movement of the screw timing belt pulley / nut. In other words, plates 112d and 112e move together away from or toward the lower plate 112a to which the volumetric pipette plunger 150 is attached.

[0040] In yet another example, a motor 116c (hereinafter referred to as the metering plunger motor 116c) is used to control the pipette plunger of a pipette head 110 for accurately aspirating and / or dispensing liquid. The metering plunger motor 116c is supported by plates 112f and 112g. The metering plunger motor 116c drives a timing (or drive) belt 118c (hereinafter referred to as the metering plunger timing belt 118c). For example, a screw timing belt pulley / nut (not shown) is attached to each of the four screw rods 114. Thus, the metering plunger timing belt 118c is positioned on the four timing belt pulleys and a motor drive pulley (not shown). When the metering plunger motor 116c is operated, plates 112f and 112g (along with any parts attached thereto) move up and down together on the four screw rods 114 by the rotational movement of the screw timing belt pulley / nut. In other words, plates 112f and 112g move together, either away from or toward the lower plate 112a to which the volumetric pipette plunger 150 is attached.

[0041] In all cases, the screw timing belt pulley / nut (not shown) is a custom part with a dual function. In its first function, the screw timing belt pulley / nut acts as a pulley for the movement of the timing (or drive) belt 118. In its second function, the screw timing belt pulley / nut acts as a nut for the screw rod 114. Thus, when the timing (or drive) belt 118 rotates the screw timing belt pulley / nut, the screw timing belt pulley / nut moves up and down the screw rod 114, depending on the direction of rotation.

[0042] Furthermore, one or more pipette tip gripping mechanisms 130 (see Figure 22) are provided in relation to the lower plate 112a located below the pipette head 110. That is, one pipette tip gripping mechanism 130 is provided in relation to each of the volumetric pipette tips 150. For example, in an 8-channel liquid processing machine 100, eight pipette tip gripping mechanisms 130 are provided. In another example, in a 96-channel liquid processing machine 100, ninety-six pipette tip gripping mechanisms 130 are provided. Each of the pipette tip gripping mechanisms 130 is used to couple (or grasp) the boundary 210 (see Figure 22) of each volumetric pipette tip 150 so that the pipette head 110 can capture and / or release the volumetric pipette tip 150. Furthermore, each of the pipette tip gripping mechanisms 130 is a zero-insertion force mechanism. Further details of examples of pipette tip gripping mechanisms 130 are shown and described below with reference to Figure 22.

[0043] Furthermore, one or more pipette plunger gripping mechanisms 140 (see Figures 23A to 25B) are provided in the center of the pipette head 110. That is, one pipette plunger gripping mechanism 140 is provided in association with each of the volumetric pipette tips 150. For example, in an 8-channel liquid processing machine 100, eight pipette plunger gripping mechanisms 140 are provided. In another example, in a 96-channel liquid processing machine 100, ninety-six pipette plunger gripping mechanisms 140 are provided. Each of the pipette plunger gripping mechanisms 140 is used to couple (grip) the plunger 160 (see Figures 16B, 17, and 18) of its respective volumetric pipette tip 150 so that the pipette head 110 can actuate the plunger 160 to aspirate and / or dispense liquid. Furthermore, each of the pipette plunger gripping mechanisms 140 is a zero insertion force mechanism.

[0044] Referring further to Figures 6 to 15, the pipette head 110 of the multi-channel liquid processing device 100 of the present disclosure is used to drive the metering operation (e.g., aspiration / distribution operation) of the pipette tip gripping mechanism 130, the pipette plunger gripping mechanism 140, and the volumetric pipette tip 150. Furthermore, the multi-channel liquid processing device 100 of the present disclosure is characterized by (1) a zero-insertion-force pipette tip gripping mechanism 130 and (2) a zero-insertion-force pipette plunger gripping mechanism 140.

[0045] Various illustrations of examples of the volumetric pipette tip 150 and pipette plunger 160 of this disclosure for aspirating and / or distributing liquids into liquid processing equipment and / or systems refer hereto to Figures 16A, 16B, 17, and 18. For example, Figure 16A shows a schematic perspective view of an example volumetric pipette tip 150. Figure 16B shows a schematic perspective view of an example pipette plunger 160. Furthermore, Figure 17 shows a cross-sectional view of the volumetric pipette tip 150 and the pipette plunger 160 positioned relative to the volumetric pipette tip 150.

[0046] The volumetric pipette tip 150 includes a boundary 210 and a pipette tip body 212. The boundary 210 is, for example, an open barrel type structure connected to the pipette tip body 212. Thus, the boundary 210 has an inner wall 220. The boundary 210 of the volumetric pipette tip 150 is fitted to, for example, the connecting component of the pipette head 110 (Figures 21 and 22). The fluid channel 214 extends along the length of the pipette tip body 212. There is an opening 216 (see Figure 20) at the distal end of the fluid channel 214 through which the fluid is aspirated and / or distributed. Furthermore, the distal end of the pipette tip body 212 connected to the opening 216 has a tapered tip 218 (see Figure 20). Furthermore, the receptacle (or cavity) 222 is provided at the lower part of the boundary 210 of the volumetric pipette tip 150. The volumetric pipette tip 150 is formed of, for example, polymer. Further details of an example of a volumetric pipette tip 150 are shown and described below with reference to Figures 19A and 19B.

[0047] The pipette plunger 160 is positioned along the inside of the volumetric pipette tip 150. The pipette plunger 160 includes a plunger tip 236, which includes a plunger upper section 232, a plunger center section 234, and a distal tip section 238. The plunger upper section 232 fits, for example, to the connecting component of the pipette head 110 (see Figures 23A to 24B). Furthermore, the plunger center section 234 fits to the plunger stop receptacle (or cavity) 222 of the boundary section 210 of the volumetric pipette tip 150, where the plunger stop receptacle (or cavity) 222 is designed to receive the plunger center section 234 of the pipette plunger 160. The plunger center section 234 functions as the “stop” mechanism of the pipette plunger 160. The plunger tip 236 and the distal tip 238 of the pipette plunger 160 are fitted into the fluid channel 214 of the pipette tip body 212 of the volumetric pipette tip 150. Furthermore, the distal tip 238 of the plunger tip 236 is designed to connect and seal with the opening 216 and the tapered tip 218 at the distal end of the fluid channel 214 of the volumetric pipette tip 150.

[0048] Furthermore, Figure 18 shows a cross-sectional view of the top of the volumetric pipette tip 150 of the present disclosure shown in Figure 17. For example, Figure 18 shows a cross-sectional view of the top of the volumetric pipette tip 150 and the pipette plunger 160 of the volumetric pipette tip 150. In this figure, other mechanisms of the volumetric pipette tip 150 and the pipette plunger 160 are depicted. For example, the volumetric pipette tip 150 further includes a set of vertical inner wall mechanisms 224 along the inner wall 220 of the boundary 210. In one example, the volumetric pipette tip 150 includes eight vertical inner wall mechanisms 224. Each of the vertical inner wall mechanisms 224 is a raised or protruding vertical line mechanism formed along the inner wall 220 of the boundary 210.

[0049] A set of vertical inner wall mechanisms 224 is provided to assist in gripping or connecting the boundary portion 210 of a positive displacement pipette tip 150 to a connecting component (Figures 21 and 22) of a liquid handling device (not shown). For example, the set of vertical inner wall mechanisms 224 may assist in increasing the frictional force required to hold the positive displacement pipette tip 150 in place, while reducing a predetermined force required to hold the positive displacement pipette tip 150 in place.

[0050] Referring further to Figure 18, the pipette plunger 160 also includes a set of vertical wall mechanisms 233 along the outer wall of the upper plunger 232. In one example, the pipette plunger 160 includes eight vertical wall mechanisms 233. Each of the vertical wall mechanisms 233 is a raised or protruding vertical line mechanism formed along the outer wall of the upper plunger 232.

[0051] A set of vertical wall mechanisms 233 is provided to assist in gripping or connecting the plunger top 232 of the pipette plunger 160 to a connecting component (see Figures 23A to 25B) of a liquid handling device (not shown). For example, the set of vertical wall mechanisms 233 may help by increasing the frictional force that holds the pipette plunger 160 in place, while potentially reducing a given force required to hold the pipette plunger 160 in place.

[0052] The side view and cross-sectional view of the volumetric pipette tip 150 of this disclosure are shown below with reference to Figures 19A and 19B. For example, Figure 19B is a cross-sectional view taken along line AA of Figure 19A.

[0053] A cross-sectional view of the distal tip 238 of the pipette plunger 160 relative to the distal end of the pipette tip body 212 of the volumetric pipette tip 150 is shown in Figure 20 thereafter. The rounded portion 240 of the distal tip 238 of the pipette plunger 160 is designed to connect to the opening 216 and tapered tip 218 at the distal end of the fluid channel 214 of the volumetric pipette tip 150. For example, the distal tip 238 has a tapered sidewall corresponding to the tapered tip 218 of the fluid channel 214. Furthermore, the outer upper end 242 of the distal tip 238 of the plunger tip 236 is sized to slide smoothly against and along the wall of the fluid channel 214 of the pipette tip body 212. The outer upper end 242 of the distal tip 238 of the plunger tip 236 provides a "sealing" ring mechanism for the pipette plunger 160, which maintains reliability for many mixing cycles before eventually wearing out and leaking.

[0054] When the distal tip 238 and rounded portion 240 of the pipette plunger 160 seal the opening 216 and tapered tip 218 at the distal end of the fluid channel 214 of the volumetric pipette tip 150, only a very small space exists between the tapered tip 218 of the fluid channel 214 and the tapered sidewall of the distal tip 238 of the pipette plunger 160. In one example, the aspirated fluid 252 is trapped within this small space. A beneficial feature of the volumetric pipette tip 150 is that the design of the distal tip 238 of the pipette plunger 160 minimizes the size of this space. As a result, the aspirated and / or dispensed liquid volume is precisely maintained. Furthermore, the volumetric pipette tip 150 can be used in virtually any liquid class range.

[0055] Figure 20 shows an example of a volumetric pipette tip 150 in use. In one example, Figure 20 shows the pipette plunger 160 being withdrawn and the aspirating fluid 252 being drawn into the fluid channel 214 of the pipette tip body 212 of the volumetric pipette tip 150. In another example, Figure 20 shows the pipette plunger 160 being pushed and the dispensing fluid 252 being pushed out from the fluid channel 214 of the pipette tip body 212 of the volumetric pipette tip 150.

[0056] In standard air-displaced pipette tips, factors such as temperature, atmospheric pressure, specific gravity, and solution viscosity affect the performance of the air-displaced pipette tip. In contrast, volumetric pipettes are used for accurately pipetting highly viscous, volatile, high or low temperature, or corrosive samples. The volumetric pipette tip 150 and pipette plunger 160 of this disclosure are examples of volumetric pipettes.

[0057] A schematic perspective view of an example of a pipette tip collet 300 for use with the volumetric pipette tip 150 of the present disclosure is shown in Figure 21 thereafter. The pipette tip collet 300 includes, for example, an upper ring plate 310 and a collet chuck portion 312 that fits inside the boundary portion 210 of the volumetric pipette tip 150. Furthermore, the collet chuck portion 312 of the pipette tip collet 300 has a sawtooth mechanism 314 to increase friction against the boundary portion 210 of the volumetric pipette tip 150, as shown, for example, in Figure 22.

[0058] Referring here to Figure 22, the pipette tip collet 300 is a characteristic component of the pipette tip gripping mechanism 130. Furthermore, Figure 22 shows a perspective view of the volumetric pipette tip 150 relative to the pipette tip collet 300 shown in Figure 21. Generally, a “collet” is a segment band or sleeve that can be expanded and / or contracted. The collet chuck portion 312 of the pipette tip collet 300 is designed to grip onto any member surrounding the chuck. For example, the collet chuck portion 312 of the pipette tip collet 300 is a segment band or sleeve that fits inside the boundary portion 210 of the volumetric pipette tip 150. The collet chuck portion 312 of the pipette tip collet 300 is designed to expand and secure to the inner wall 220 of the boundary portion 210 of the volumetric pipette tip 150. In other words, when in a fixed position, the collet chuck portion 312 (or gripping chuck) grips the boundary portion 210 of the positive displacement pipette tip 150 that surrounds the collet chuck portion 312. Furthermore, the set of vertical inner wall mechanism 224 of the boundary portion 210 of the positive displacement pipette tip 150 and / or the sawtooth mechanism 314 of the pipette tip collet 300 is used to assist in gripping or connecting the boundary portion 210 of the positive displacement pipette tip 150 to the collet chuck portion 312 of the pipette tip collet 300.

[0059] The pipette tip gripping mechanism 130 is a zero-insertion-force pipette tip gripping mechanism. The pipette tip gripping mechanism 130 includes a pipette tip collet 300 and a pipette tip fixing mechanism 350. The pipette tip fixing mechanism 350 includes, for example, an upper ring plate 352 and a hollow sleeve portion 354 that fits inside the collet chuck portion 312 of the pipette tip collet 300. For example, when the hollow sleeve portion 354 fits inside the collet chuck portion 312 of the pipette tip collet 300, the collet chuck portion 312 expands into the inner wall 220 of the boundary portion 210 of the volumetric pipette tip 150. In contrast, when the hollow sleeve portion 354 is withdrawn from the collet chuck portion 312 of the pipette tip collet 300, the collet chuck portion 312 retracts and loosens relative to the boundary portion 210 of the volumetric pipette tip 150.

[0060] With regard to utilizing multiple pipette tip gripping mechanisms 130 of the pipette head 110, the pipette head 110 includes a specific floating mechanism (not shown) with or without a spring to avoid problems of excessive constraints in operating the multiple pipette tip gripping mechanisms 130. Furthermore, the pipette head 110 includes a specific self-centering alignment mechanism for each of the pipette tip gripping mechanisms 130, which is long-lasting and easy to assemble.

[0061] Referring here to Figures 23A and 23B, Figure 23A is a side view of the plunger collet 400, while Figure 23B is a cross-sectional view of the plunger collet 400 cut along line AA in Figure 23A. The plunger collet 400 is intended for use with the pipette plunger 160 of the volumetric pipette tip 150 of the present disclosure. The plunger collet 400 includes, for example, a shaft portion 410 and a collet chuck portion 412 for fitting around the upper plunger portion 232 of the pipette plunger 160. Furthermore, Figure 24A shows a schematic perspective view of the collet chuck portion 412 of the pipette plunger 160, and Figure 24B is a cross-sectional view of the pipette plunger 160 relative to the collet chuck portion 412 of the plunger collet 400.

[0062] The collet chuck portion 412 of the plunger collet 400 is designed to grip around any member inside the chuck. For example, the collet chuck portion 412 of the plunger collet 400 is a segment band or sleeve that fits around the plunger top 232 of the pipette plunger 160. The collet chuck portion 412 of the plunger collet 400 is designed to fix to the outer wall of the plunger top 232 of the pipette plunger 160 (see Figure 24B). That is, when in the fixed position, the collet chuck portion 412 (or gripping chuck) grips the plunger top 232 of the pipette plunger 160 inside the collet chuck portion 412. Furthermore, a set of vertical outer wall mechanisms 233 of the plunger top 232 of the pipette plunger 160 is used to assist in gripping or connecting the plunger top 232 to the collet chuck portion 412 of the plunger collet 400.

[0063] Referring here to Figures 25A and 25B, the plunger collet 400 is a characteristic component of the pipette plunger gripping mechanism 140. The pipette plunger gripping mechanism 140 is a zero-insertion-force pipette plunger gripping mechanism. The pipette plunger gripping mechanism 140 includes the plunger collet 400 and the pipette plunger fixing mechanism 450. The pipette plunger fixing mechanism 450 includes a hollow sleeve portion 454 that fits around the plunger collet 400, including, for example, an upper ring plate 452 and a collet chuck portion 412. For example, when the hollow sleeve portion 454 slides downward around the collet chuck portion 412 of the plunger collet 400, the collet chuck portion 412 closes (gripping) against the plunger upper portion 232 of the pipette plunger 160. In contrast, when the hollow sleeve portion 454 is withdrawn from the collet chuck portion 412 of the plunger collet 400, the collet chuck portion 412 releases the upper plunger portion 232 of the pipette plunger 160.

[0064] Figures 25A and 25B show a pair of pipette plunger gripping mechanisms 140, which are installed on two plates (456A and 456B) and have two springs 458 between the two plates (456A and 456B). For example, the upper plate 456A is fixed, while each spring 458 provides spring force to the corresponding pipette plunger fixing mechanism 450 that passes through the lower plate 456B in a sliding (floating) manner. Furthermore, the upper end of the plunger collet 400 is fixed to the upper plate 456A. ​​Thus, the plunger collet 400 is fixed to the upper plate 456A, while the pipette plunger fixing mechanism 450 and the lower plate 456B are movable relative to the upper plate 456A. ​​Thus, the pipette plunger fixing mechanism 450 is movable relative to the plunger collet 400.

[0065] For example, Figure 25A shows the pipette plunger gripping mechanism 140 in a non-gripping state. In Figure 25A, the lower plate 456B is pulled upward toward the upper plate 456A, while compressing the two springs 458. In this state, the hollow sleeve portion 454 of the pipette plunger fixing mechanism 450 is pulled up and separated from the collet chuck portion 412 of the plunger collet 400, allowing the plunger collet 400 to open and expand. In this state, the pipette plunger 160 is placed in the plunger collet 400 and removed from it.

[0066] In contrast, Figure 25B shows the pipette plunger gripping mechanism 140 in the gripping state. In Figure 25B, the spring force of the two springs 458 pushes the lower plate 456B and the pipette plunger fixing mechanism 450 away from the upper plate 456A. ​​In this state, the hollow sleeve portion 454 pushes down around the collet chuck portion 412 of the plunger collet 400, closing or retracting the plunger collet 400. In this state, the plunger collet 400 is gripped on the pipette plunger.

[0067] The pipette plunger gripping mechanism 140 uses a spring 458 to independently set a fixed preload, and each pipette plunger gripping mechanism 140 can handle plunger dimensions that change independently and arbitrarily from one pipette plunger 160 to the next.

[0068] During operation of the volumetric pipette tip 150 of the pipette head 110 of the multichannel liquid handling apparatus 100 of the present disclosure, the volumetric pipette tip 150 is fixed, while the pipette plunger 160 is operated relative to the volumetric pipette tip 150 to aspirate and / or dispense liquid. The benefit of the volumetric pipette tip 150 of the present disclosure is that the volumetric pipette tip 150 is designed to be operated through a pipette tip gripping mechanism 130. In one example, the pipette tip gripping mechanism 130 for the volumetric pipette tip 150 features a pipette tip collet 300, as shown, for example, in Figures 21 and 22. Similarly, the pipette plunger 160 is designed to be operated by a pipette plunger gripping mechanism 140. In one example, the pipette plunger gripping mechanism 140 for the volumetric pipette tip 150 features a plunger collet 400, as shown, for example, in Figures 23A to 25B.

[0069] A flow diagram of an example of Method 500 using the pipette head 110 of this disclosure, including the arrangement of a volumetric pipette tip 130 for aspirating and / or dispensing liquid, is shown here with reference to Figure 26. Method 500 is performed under the control of a multi-channel liquid processing unit 100 shown in Figures 1 to 5. Method 500 includes, but is not limited to, the following steps:

[0070] In step 510, a pipette head is provided that includes the arrangement of a volumetric pipette tip for aspirating and dispensing liquid. For example, a pipette head 110 including the arrangement of a volumetric pipette tip 150 for aspirating and dispensing liquid is provided, for example, in the multichannel liquid processing equipment 100 shown in Figures 1 to 5. The pipette head 110 is shown, for example, in Figures 6 to 15.

[0071] In step 515, the pipette plunger is grasped using the pipette plunger gripping mechanism. For example, the pipette plunger 160 is grasped using the pipette plunger gripping mechanism 140 of the pipette head 110, as shown in Figures 25A and 25B.

[0072] In step 520, the pipette tip is grasped onto the pipette head using a pipette tip gripping mechanism. For example, a volumetric pipette tip 150 is grasped using the pipette tip gripping mechanism 130 of the pipette head 110, as shown in Figure 22, for example.

[0073] In step 525, the liquid aspiration / distribution operation is performed using a pipette tip head that includes the arrangement of a volumetric pipette tip. For example, the liquid aspiration and / or distribution operation is performed using a pipette head 110 that includes the arrangement of a volumetric pipette tip 150.

[0074] In accordance with long-standing patent law practice, the terms “a,” “an,” and “the” refer to “one or more” when used in this application, including the claims. Therefore, for example, a reference to “one subject matter” includes multiple subject matters, unless the context clearly indicates otherwise (e.g., multiple subject matters).

[0075] Throughout this specification and the claims, the terms “comprise,” “comprises,” and “comprising” are used in a non-exclusive sense unless the context requires otherwise. Similarly, the term “includes” and its grammatical variations are intended to be non-restrictive, and the listing of items in the list does not exclude other similar items that may be substituted for or added to the listed items.

[0076] For the purposes of this specification and the attached claims, unless otherwise specified, all numbers expressing quantities, sizes, dimensions, ratios, shapes, formulations, parameters, percentages, amounts, characteristics, and other numerical values ​​used herein and in the claims should be understood to be modified in all cases by the term "about," even if the term "about" does not explicitly appear in the value, quantity, or range. Therefore, unless otherwise indicated, the numerical parameters described in the following specification and attached claims are not exact, nor do they need to be exact, but are approximate and / or more or less than desired, and reflect tolerances, conversion factors, rounding, measurement errors, and other factors known to those skilled in the art, depending on the desired characteristics to be obtained by the subject matter of this disclosure. For example, the term "about" when referring to a value means that, in some embodiments, it includes variations of ±100%, ±50%, ±20%, ±10%, ±5%, ±1%, ±0.5%, and ±0.1% from a particular amount, such variations being appropriate for performing the disclosed method or using the disclosed composition.

[0077] Furthermore, the term "approximately," when used in relation to one or more numbers or numerical ranges, should be understood to refer to all such numbers, including all numbers in the range, and to modify that range by extending above and below the boundaries of the stated numerical values. A numerical range description by endpoint includes all integers (for example, a description of 1 to 5 includes 1, 2, 3, 4, 5 and their fractions, e.g., 1.5, 2.25, 3.75, 4.1, etc.) and any range within that range.

[0078] Although the aforementioned subject matter has been described in some detail with illustrations and examples for the purpose of clarity of understanding, it will be understood by those skilled in the art that certain variations and modifications are carried out within the scope of the attached claims.

Claims

1. A multi-channel liquid processing device (100), comprising: An equipment deck (182) having a plurality of rails; A removable tray (183) removably supported on the equipment deck (182) and holding three or more microplates (185); A chip caddy (186) on one of the three or more microplates (185) for holding an array of a plurality of volumetric pipette tips (150); A pipette head (110) above the equipment deck (182); The removable tray (183) has a two-dimensional barcode containing a unique ID number, and the pipette head (110) has a camera for scanning the two-dimensional barcode; The pipette head (110) is a multi-channel pipette head integrated with a multi-position stage for operating the one or more volumetric pipette tips (150) disposed on the pipette head (110); The multi-channel liquid processing device (100) further comprises: A robotic device configured to control the operation of the pipette head (110) with respect to the equipment deck (182), the removable tray (183), and the three or more microplates (185); A controller (190) configured to execute a protocol corresponding to the removable tray (183) in combination with the three or more microplates of the removable tray (183). A multi-channel liquid processing device (100).

2. The multi-channel liquid processing device according to claim 1, wherein the removable tray (183) includes a handle (184).

3. The multi-channel liquid processing device according to claim 1, wherein the chip caddy (186) is used together with a microplate (185) not covered by the chip caddy (186).

4. The pipette head (110) is a plurality of plates (112) stacked along four lead screws (114), and the four lead screws (114) penetrate through the stacked plurality of plates (112). A plurality of plates (112); One or more timing belts (118) attached to the four lead screws (114); comprising one or more motors (116) for driving each of the one or more timing belts (118); each of the one or more motors (116) is attached to one or more of the plurality of plates (112), and by driving the one or more timing belts (118), the plurality of plates (112) start to move within the pipette head (110), the liquid processing apparatus according to claim 1.

5. The plurality of plates (112) are rectangular, the four threaded rods (114) are respectively arranged at four corners of the plurality of plates (112), the liquid processing apparatus according to claim 4.

6. The plurality of plates (112) include a lower plate (112a), an upper plate (112h) disposed on the upper side of the lower plate (112a), and the remaining plates (112b to 112g) disposed between the lower plate (112a) and the upper plate (112h), the lower plate (112a) is fixed to the lower ends of the four threaded rods (114), the upper plate (112h) is fixed to the upper ends of the four threaded rods (114), the remaining plates (112b to 112g) are arranged in pairs between the upper plate (112a) and the lower plate (112h) and are movable along the four threaded rods (114), the liquid processing apparatus according to claim 5.

7. The lower plate (112a) is a pipette tip collet holder plate to which the one or more positive displacement pipette tips (150) are attached, the liquid processing apparatus according to claim 6.

8. The liquid processing apparatus according to claim 6, comprising one or more pipette tip gripping mechanisms (130) that couple to a boundary portion (210) of the positive displacement pipette tip (150) such that the pipette head (110) captures or releases the one or more positive displacement pipette tips (150).

9. The one or more motors (116) are gripping tip motors, the one or more timing belts (118) are gripping tip timing belts, The holding chip motor and the holding chip timing belt are configured to move one or more of the plurality of plates (112) in a direction away from the lower plate (112a) or in a direction toward the lower plate (112a). The liquid processing apparatus according to claim 8.

10. The one or more positive displacement pipette tips (150) include a pipette tip and a pipette plunger (160). The pipette tip has a boundary portion (210) and a pipette tip body (212). The boundary portion (210) has an inner wall (220) and a receptacle (222). The pipette tip body (212) has a fluid channel (214) along the length of the pipette tip body (212). The fluid channel (214) has an opening (216) at the distal end of the fluid channel (214). The pipette plunger (160) is disposed along the inside of the pipette tip. has a plunger tip (236) having a plunger upper portion (232), a plunger central portion (234), and a distal tip portion (238). The receptacle (222) is configured to receive the plunger central portion (234). The fluid channel (214) is configured to receive the distal tip portion (238). The one or more pipette tip holding mechanisms (130) are zero insertion force pipette holding mechanisms. The liquid processing apparatus according to claim 5.

11. One or more pipette plunger holding mechanisms (140) are provided at the central portion of the pipette head (110). Each of the one or more pipette plunger holding mechanisms (140) is coupled to the respective pipette plunger (160) of each of the one or more positive displacement pipette tips (150). The liquid processing apparatus according to claim 10.

12. Further, it includes a set of zero insertion force pipette plunger holding mechanisms. One of the one or more motors (116) is used to control the set of zero insertion force pipette plunger holding mechanisms. The liquid processing apparatus according to claim 10.

13. One of the one or more motors (116) is a holding plunger motor. One of the one or more timing belts (118) is a holding plunger timing belt. The gripping plunger motor and the gripping plunger timing belt are configured to move one or more of the plurality of plates (112) in a direction away from the lower plate (112h) or in a direction toward the lower plate (112h). The liquid processing apparatus according to claim 12.

14. Further comprising a pipette plunger (160), One or more of the motors (116) are used to control the pipette plunger (160). The liquid processing apparatus according to claim 6.

15. One of the one or more motors (116) is a metering plunger motor, One of the one or more timing belts (118) is a metering plunger timing belt, The metering plunger motor and the metering plunger timing belt are configured to move one or more of the plurality of plates (112) in a direction away from the lower plate (112a) or in a direction toward the lower plate (112a). The liquid processing apparatus according to claim 14.

16. The one or more pipette plunger gripping mechanisms (140) are one or more zero insertion force pipette plunger gripping mechanisms. The liquid processing apparatus according to claim 11.

17. Each of the one or more zero insertion force pipette plunger gripping mechanisms includes a plunger collet (400) and a pipette plunger fixing mechanism (450), The plunger collet (400) includes a shaft portion and a collet chuck portion for fitting around the upper plunger portion (232) of the pipette plunger (160). The liquid processing apparatus according to claim 16.

18. The collet chuck portion is a segment band or sleeve for fitting around the upper plunger portion (232) of the pipette plunger (160). The liquid processing apparatus according to claim 17.

19. A method of aspirating and dispensing liquid, (a) providing a liquid processing apparatus having an apparatus housing with an apparatus deck (182), a pipette head (110) disposed above the apparatus deck (182), and a tray (183) removable from the apparatus deck (182) configured to hold three or more microplates (185), The removable tray (183) has a unique ID, The machine deck (182) holds the removable tray (183), The pipette head (110) has an arrangement of one or more positive displacement pipette tips (150) for aspirating and dispensing liquid, The pipette head (110) includes a camera capable of scanning the unique ID and verifying the presence or absence of the one or more pipette tips (150), The pipette head (110) includes one or more pipette tip gripping mechanisms (130) and one or more pipette plunger gripping mechanisms (140), Each of the one or more positive displacement pipette tips (150) includes a pipette tip and a pipette plunger corresponding to the pipette tip, The method of aspirating and dispensing the liquid further comprises, (b) scanning the unique ID with the camera and verifying the presence or absence of the one or more positive displacement pipette tips (150); (c) gripping one or more pipette plungers with the one or more pipette plunger gripping mechanisms (140); (d) based on the scan, gripping one or more available positive displacement pipette tips with the one or more pipette tip gripping mechanisms (130); (e) performing an aspiration operation and / or a dispensing operation using the pipette head; (f) executing a protocol corresponding to the removable tray (183) in combination with the three or more microplates of the removable tray (183).