Liquid treatment instrument and liquid treatment head and method for suction and / or dispensing of

Abstract

A liquid treatment instrument and pipette head and method for aspirating and / or dispensing a liquid are disclosed. Namely, an automated liquid handling instrument is provided for aspirating and / or dispensing liquid from a source medium to a target medium using at least one pipette tip and by using a positive displacement pipette tip, where the positive displacement pipette tip includes a pipette tip and a pipette plunger. A pipette head of a liquid treatment instrument includes an arrangement of a plate, a threaded rod, a motor, a timing (or drive) belt, and a customized timing pulley / nut. The pipette tip further comprises an arrangement of a pipette plunger clamping mechanism and a pipette tip clamping mechanism, the pipette plunger clamping mechanism and the pipette tip clamping mechanism being characterized as zero insertion force clamping mechanisms.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] The subject matter of the present disclosure is related to U.S. Provisional Patent Application No. 62 / 797,687, entitled “Instruments and Methods for Aspirating and / or Dispensing Liquids,” filed on January 28, 2019; the entire disclosure of which is incorporated herein by reference. Technical Field

[0003] The presently disclosed subject matter relates generally to liquid handling methods, and more particularly to a liquid handling instrument and pipette head and method for aspirating and / or dispensing liquids. Background Art

[0004] Automated liquid handling instruments include robots for transferring specific amounts of liquids (such as reagents or samples, etc.) between designated containers. Liquid handling instruments can be used in a variety of applications, including cell biology, genomics, forensics, and pharmaceutical research. Instruments assist humans in repetitive tasks: transferring a wide range of volumes of liquids to improve the speed and efficiency of operations, as well as the precision and accuracy of the delivered volumes. The advantages of automating the liquid handling process include increasing the throughput and efficiency of operations and eliminating human error.

[0005] In conventional liquid handling instruments, there is usually a sealing interface between the instrument and each pipette tip in the pipette tip. The sealing interface is usually a compressible rubber O-ring, which needs to be regularly maintained and / or replaced during the service life of the instrument. The compressible rubber O-ring also has the disadvantage of high friction during the pipette tip insertion process, which ultimately requires: (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 so as to implement a reliable sealing interface for multiple pipette tips (for example, 96 pipette tips used with 96 hole sample plates). For example, in conventional liquid handling instruments, a pipette tip may require an insertion force of about 100 grams, and therefore the actuator for the tip must provide a downward force of about 100 grams. Therefore, in a multichannel liquid handling instrument for processing, for example, 96 pipette tips, the actuator must be able to withstand a downward force of about 9.5 kilograms. Therefore, there is a need for powerful actuators with strong / heavy mechanical support structures that can handle the high forces. Summary of the invention

[0006] The present subject matter describes an instrument and method for aspirating and / or dispensing liquids using a pipette tip. In one embodiment, a liquid handling instrument may include: an instrument housing with an instrument platform; a pipette head located above the instrument platform; and a removable tray, the instrument platform supporting the removable tray.

[0007] The removable tray may include a handle. The removable tray may support one or more microplates, and a tip caddy on top of the one or more microplates. The removable tray may have a unique identification number adapted to be scanned or read. The unique identification number may include a two-dimensional (2D) barcode or a radio frequency identification tag.

[0008] A robotics instrument and a controller may also be included in the instrument. For example, the robotics instrument can control the movement of the pipetting head relative to the instrument platform, and the controller can execute program instructions.

[0009] The instrument may further include one or more positive displacement pipette tips, and the pipetting head may be a multi-channel pipetting head integrated with a multi-positioning stage for manipulating the one or more positive displacement pipette tips.

[0010] The pipetting head may further include: a plurality of plates arranged in a stack relative to the four threaded rods; one or more motors driving one or more respective timing belts, the one or more motors supported by the plurality of plates; and a topheat mounting plate.

[0011] The plurality of plates may be substantially rectangular, and the four threaded rods may be arranged in a substantially rectangular configuration relative to the four corners of the plurality of plates. In one embodiment, the plurality of plates may be eight plates arranged sequentially from bottom to top along the four threaded rods.

[0012] The bottom plate may be held fixed at the bottom ends of the four threaded rods, the top plate may be held fixed at the tops of the four threaded rods, and the remaining plates may be arranged between the top plate and the bottom plate and be movable along the four threaded rods.

[0013] In one embodiment, the base plate can be a pipette tip chuck holder plate to which one or more positive displacement pipette tips can be mounted. The instrument can further include one or more pipette tip clamping mechanisms. One of the one or more motors can be a clamping tip motor, one or more of the timing belts can be a clamping tip timing belt, and the clamping tip motor and the clamping tip timing belt can be adapted to move one or more of the multiple plates away from or toward the base plate.

[0014] In another embodiment, one or more positive displacement pipette tips may include: a pipette tip and a pipette plunger. The pipette tip has an interface portion and a pipette tip body, the interface portion may have an inner wall and a receptacle, the pipette tip body may have a fluid channel along the length of the pipette tip body, and the fluid channel may have an opening at the distal end of the fluid channel; the pipette plunger may be positioned along the interior of the pipette tip, the pipette plunger may have a plunger top, a plunger centering portion, and a plunger tip having a distal suction head, wherein the receptacle may be adapted to receive the plunger centering portion. In one embodiment, the fluid channel may be adapted to receive the distal suction head of the plunger tip, and one or more pipette tip clamping mechanisms may be zero insertion force pipette clamping mechanisms.

[0015] In another embodiment, one or more pipette plunger clamping mechanisms can be disposed in a central portion of the pipette head, and each of the one or more pipette plunger mechanisms can be coupled to the plunger of each positive displacement pipette tip in a respective positive displacement pipette tip.

[0016] The instrument may further include a grouped zero insertion force pipette plunger clamping mechanism. In one embodiment, one of the one or more motors can be used to control the grouped zero insertion force pipette plunger mechanism. Moreover, one of the one or more motors can be a clamping plunger motor, one of the one or more timing belts can be a clamping plunger timing belt, and the clamping plunger motor and the clamping plunger timing belt can be adapted to move one or more of the multiple plates away from or toward the base plate.

[0017] The instrument may further include a pipette plunger. In one embodiment, one of the one or more motors may be used to control the pipette plunger. The one or more motors may be metering plunger motors, and the one or more timing belts may be metering plunger timing belts, and the metering plunger motor and metering plunger timing belt may be adapted to move one or more of the plurality of plates away from or toward the base plate.

[0018] The instrument may further include one or more pipette plunger clamping mechanisms, which are zero insertion force pipette plunger clamping mechanisms. In one embodiment, each of the one or more zero insertion force pipette plunger clamping mechanisms may include a plunger collet and a pipette plunger locking mechanism, and the plunger collet may include a shaft portion and a collet chuck portion for mounting around the upper portion of the plunger of the pipette plunger. Further, the collet chuck portion may be a segmented band or sleeve for mounting around the upper portion of the plunger of the pipette plunger.

[0019] The present subject matter further describes a method for aspirating and / or dispensing liquids. In one embodiment, the method may include the following steps: providing a liquid handling instrument, the liquid handling instrument including an instrument housing with an instrument platform, a pipette head above the instrument platform, and a removable tray, the instrument platform supporting the removable tray, the pipette head having an arrangement of one or more positive displacement pipette tips for aspirating and dispensing liquids, wherein the pipette head includes one or more pipette tip clamping mechanisms and one or more pipette plunger clamping mechanisms, and wherein each of the one or more positive displacement pipette tips includes a pipette tip and a corresponding pipette plunger; clamping one or more pipette plungers by one or more pipette plunger clamping mechanisms; clamping one or more pipette tips by one or more pipette tip clamping mechanisms; and using the pipette head to perform aspiration and / or dispensing operations. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Having thus generally described the subject matter of the present disclosure, reference will now be made to the accompanying drawings, which are not necessarily drawn to scale, and in which:

[0021] Figures 1 to 5 Various perspective views of a multi-channel liquid handling instrument of the present disclosure including a pipetting head including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids are shown;

[0022] Figure 6 , Figure 7 and Figure 8 Various perspective views of a pipetting head of the present disclosure are shown, the pipetting head including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids;

[0023] Fig. 9 , Fig.10 , Fig.11 , Fig.12 , Fig.13 and Fig.14 A front view, a rear view, a side view, another side view, a top view, and a bottom view are respectively shown of a pipetting head of the present disclosure, the pipetting head including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids;

[0024] Fig.15 shows a cross-sectional view of a pipetting head of the present disclosure including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids;

[0025] Fig.16A and Fig. 16B A perspective view showing an example of a positive displacement pipette and a pipette plunger of a pipette head of the present disclosure;

[0026] Fig.17Shows Fig.16A and Fig. 16B A cross-sectional view of an example of a positive displacement pipette and a pipette plunger shown in;

[0027] Fig.18 shows a cross-sectional view of an upper portion of a positive displacement pipette tip of the present disclosure;

[0028] Fig.19A and Fig.19B A side view and a cross-sectional view of a pipette tip of a positive displacement pipette tip are shown, respectively;

[0029] Fig. 20 A close-up side view of a distal tip portion of a pipette plunger relative to a distal tip portion of a pipette tip is shown;

[0030] Fig.21 A perspective view showing an example of a pipette tip cartridge for use with a positive displacement pipette tip;

[0031] Fig. 22 A side view showing an example of a pipette tip clamping mechanism of a pipette head of the present disclosure;

[0032] Fig.23A and Fig. 23B A side view and a cross-sectional view, respectively, of an example of a plunger cartridge for use with a positive displacement pipette tip are shown;

[0033] Fig.24A Shows Fig.23A and Fig. 23B A perspective view of the collet chuck portion of the plunger collet shown in ;

[0034] Fig. 24B Shows relative to Fig.23A and Fig. 23B A cross-sectional view of a pipette plunger having a plunger cartridge shown in FIG.

[0035] Fig.25A and Fig.25B An example of a pipette plunger clamping mechanism and a pipette plunger clamping process of a pipette head of the present disclosure is shown; and

[0036] Fig.26 A flow chart illustrating an example of a method of using a pipetting head of the present disclosure including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids. DETAILED DESCRIPTION

[0037] The disclosed subject matter will now be described more fully hereinafter with reference to the accompanying drawings, in which some but not all embodiments of the disclosed subject matter are shown. Throughout the text, the same reference numerals refer to the same elements. The disclosed subject matter can be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein; on the contrary, these embodiments are provided so that the disclosure will satisfy applicable legal requirements. In fact, the disclosed subject matter benefits from the teachings presented in the foregoing description and the associated drawings, and many modifications and other embodiments of the disclosed subject matter set forth herein will occur to those skilled in the art. Therefore, it should be understood that the disclosed subject matter is not limited to the specific embodiments disclosed, and it is intended that modifications and other embodiments are included within the scope of the appended claims.

[0038] In some embodiments, the disclosed subject matter provides a liquid handling instrument and a pipette head and method for aspirating and / or dispensing liquids. For example, an automated liquid handling instrument is provided for aspirating and / or dispensing liquids from a source medium to a target medium using at least one pipette head and by using a positive displacement pipette tip, wherein the positive displacement pipette tip comprises a pipette tip and a pipette plunger.

[0039] In some embodiments, the automated liquid handling instrument of the present disclosure is a multi-channel liquid handling instrument for aspirating and / or dispensing liquids. In one example, the multi-channel liquid handling instrument is an 8-channel liquid handling instrument for manipulating 8 pipette tips associated with, for example, an 8-well sample plate. In another example, the multi-channel liquid handling instrument is a 96-channel liquid handling instrument for manipulating 96 pipette tips associated with, for example, a 96-well sample plate.

[0040] In some embodiments, the automated liquid handling instrument of the present disclosure is a zero insertion force system that is provided with a mechanism for inserting a positive displacement pipette tip using zero insertion force because it does not require a sealed interface between the instrument and the pipette tip. For example, the automated liquid handling instrument is provided with: (1) one or more zero insertion force pipette tip clamping mechanisms, and (2) one or more zero insertion force pipette plunger clamping mechanisms. Further, each of the clamping mechanisms provides a reliable, zero insertion force, airtight seal that requires substantially no periodic maintenance and / or replacement, thereby ensuring a robust pipetting system.

[0041] In some embodiments, the automated liquid handling instrument of the present disclosure includes certain features for preventing contamination. For example, conventional liquid handling instruments typically have a common air column between all pipette tip interfaces, which may be a common source of contamination that can be carried over to the next workflow. In contrast, the automated liquid handling instrument of the present disclosure does not include a common air column between pipette tips, and therefore does not have this possible source of contamination.

[0042] Reference Figures 1 to 5 1 are various perspective views of a multichannel liquid handling instrument 100 of the present disclosure including a pipetting head 110 including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids. For example, Figure 1 1 shows a perspective view of a multi-channel liquid handling instrument 100 of the present disclosure, Figure 2 shows its front view, Figure 3 The rear view thereof is shown, Figure 4 A side view thereof is shown, and Figure 5 An opposite side view thereof is shown.

[0043] The multi-channel liquid handling instrument 100 of the present disclosure can be an automated liquid handling instrument based on robotics. The multi-channel liquid handling instrument 100 may include, for example, an instrument housing 180 and an instrument platform 182. For example, the instrument platform 182 may be two rails, one rail on each side. The multi-channel liquid handling instrument 100 and the instrument platform 182 are designed to support a removable tray. For example, a removable tray 183 can be placed on top of the instrument platform 182. The removable tray 183 may include a handle 184 for easy carrying.

[0044] The removable tray 183 may include a plurality of microplate or labware positioning portions for accommodating, for example, one or more microplates 185. One or more tip boxes 186 to be processed may be on top of certain microplates 185. Tip boxes 186 are consumable trays or boxes for accommodating / packaging an arrangement of a plurality of pipette tips 150. The multichannel liquid handling instrument 100 may include a pipette head 110 positioned above the instrument platform 182 for aspirating and / or dispensing liquid from a liquid. The pipette head 110 may be equipped with an arrangement of a plurality of pipette tips 150.

[0045] The multichannel liquid handling instrument 100 may also include a robotics instrument 188 and a controller 190. The robotics instrument 188 may be any robotics instrument capable of precisely controlling the movement of the pipetting head 110 relative to the instrument platform 182. The controller 190 may be any standard controller or microprocessor device capable of executing programmed instructions.

[0046] The features of the multi-channel liquid handling instrument 100 of the present disclosure may include, but are not limited to, a removable platform / tray, a fully automated platform / calibration tray, a fully automated probe for calibrating multiple plate positions, multiple microplate positioning parts, a tip box positioning part, a camera, etc., wherein the camera is used to scan the platform / tray coordinate points (ID) and check the availability of the tips on the box, head collision detection, etc.

[0047] In the multi-channel liquid handling instrument 100 of the present disclosure, the removable tray 183 can be set with a unique ID number using, for example, a 2D barcode, which can be scanned / read using a camera (not shown) on the pipetting head 110. In another example, the removable tray 183 can have a unique radio frequency identification (RFID) tag, which can be scanned / read using an RFID reader (not shown) on the pipetting head 110. In operation, each time the multi-channel liquid handling instrument 100 is used, the user places the removable tray 183 with a specific group of microplates 185 on the instrument platform 182 and then runs a specific protocol. After completion, the user then removes his / her removable tray 183. Then, the next user places the next removable tray 183 with the next group of microplates 185 on the instrument tray 182 and then runs a different protocol.

[0048] Thus, a benefit of the multi-channel liquid handling instrument 100 of the present disclosure is that the presence of the removable tray 183 allows the instrument to be easily and quickly shared among multiple users, where each user can have his / her own tray with a specific set of microplates 185 and a specific protocol to be run. Utilizing this shared instrument approach, maximum up / run time for the multi-channel liquid handling instrument 100 can be achieved. This is in contrast to conventional instruments where an entire set of microplates must be swapped out of a non-removable platform from one user to the next, a slow and cumbersome process that results in downtime.

[0049] Multichannel liquid handling instrument 100 and / or pipette head 110 are characterized as positive displacement pipette tips. Each positive displacement pipette tip in the positive displacement pipette tip can include a pipette tip and a pipette plunger, and the pipette tip and the pipette plunger are designed to aspirate and / or distribute precise volumes of liquid. For example, each positive displacement pipette tip in the positive displacement pipette tip includes a minimized gap between the pipette tip and the pipette plunger, thereby optimizing the accuracy of the liquid volume aspirated and / or distributed. In addition, pipette head 110 provides a zero insertion force clamping mechanism for both the pipette tip and the pipette plunger of each positive displacement pipette tip in the positive displacement pipette tip.

[0050] The pipetting head 110 is a multi-channel pipetting head (such as an 8-channel or 96-channel pipetting head, etc.) integrated with a multi-positioning stage for manipulating one or more positive displacement pipette tips 150. For example, the pipetting head 110 can handle only 1 tip, 1-8 tips (in a column), 1-12 tips (in a row), 96 tips, and / or more than one cluster / combination tip configuration. More details of examples of positive displacement pipette tips 150 are provided below with reference to FIG. 16A to FIG. 20is shown and described.

[0051] Reference Figures 6 to 15 , Figure 6 , Figure 7 and Figure 8 1 are various perspective views of an example of a pipetting head 110 including an arrangement of positive displacement pipette tips 150 for aspirating and / or dispensing liquids. Further, Fig. 9 , Fig.10 , Fig.11 , Fig.12 , Fig.13 and Fig.14 The front view, rear view, side view, another side view, top view and bottom view of the pipetting head 110 are shown respectively. Fig.15 Shown along Figure 6 A cross-sectional view of the pipetting head 110 taken along line AA.

[0052] Still refer to Figures 6 to 15 , the pipetting head 110 may include, for example, a plurality of plates 112 stacked relative to four threaded rods (or lead screws) 114, three motors 116 (e.g., 116a, 116b, 116c) driving three respective timing (or drive) belts 118 (e.g., 118a, 118b, 118c), and a top heated mounting plate 113, the pipetting head 110 being combined with various other supports and / or components. For example, the pipetting head 110 may include, but is not limited to, any type of light source (e.g., LED), a camera, a heater, a printed circuit board (PCB), a thermal management device (e.g., a fan, a heat sink), any type of sensor, any type of actuator, etc. In addition, the pipetting head 110 may include a variety of components, such as, but 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, etc.

[0053] The four threaded rods 114 can be arranged in a generally rectangular configuration relative to the four corners of the generally rectangular plate 112. In one example, the pipetting head 110 includes eight plates 112 (112a, 112b, 112c, 112d, 112e, 112f, 112g, 112h). Further, the eight plates 112a, 112b, 112c, 112d, 112e, 112f, 112g, 112h can be arranged in sequence from bottom to top along the four threaded rods 114. For example, the plate 112a (hereinafter referred to as the bottom plate 112a) is held fixed at the bottom end of the four threaded rods 114, and the plate 112h (hereinafter referred to as the top plate 112h) is held fixed at the top end of the four threaded rods 114. The bottom plate 112a may serve as a pipette tip cartridge holder plate into which the positive displacement pipette tips 150 are mounted.

[0054] The remaining plates 112b, 112c, 112d, 112e, 112f, 112g can be arranged in pairs, and then the motors are driven up or down along the four threaded rods 114 to perform certain functions. In one example, the motor 116a (hereinafter referred to as the clamping tip motor 116a) can be used to precisely control the grouped zero insertion force pipette tip clamping mechanism 130 (see Fig. 22 ). The clamping tip motor 116a is supported by plates 112b and 112c. The clamping tip motor 116a drives the timing (or drive) belt 118a (hereinafter referred to as the clamping tip timing belt 118a). For example, a threaded timing belt pulley / nut (not shown) is mounted on each of the four threaded rods 114. Thus, the clamping tip timing belt 118a is arranged on four timing belt pulleys and a motor drive pulley (not shown). When the clamping tip motor 116a is activated, due to the rotational action of the threaded timing belt pulley / nut, the plates 112b and 112c (together with any components mounted thereon) move up or down together along the four threaded rods 114. That is, the plates 112b and 112c move together away from or toward the bottom plate 112a, on which the positive displacement pipette tip 150 is mounted.

[0055] In another example, the motor 116b (hereinafter referred to as the clamping plunger motor 116b) can be used to precisely control the zero insertion force pipette plunger clamping mechanism 140 of the pipetting head 110. The clamping plunger motor 116b is supported by plates 112d and 112e. The clamping plunger motor 116b drives the timing (or drive) belt 118b (hereinafter referred to as the clamping plunger timing belt 118b). For example, a threaded timing belt pulley / nut (not shown) is mounted on each of the four threaded rods 114. Thus, the clamping plunger timing belt 118b is arranged on the four timing belt pulleys and the motor drive pulley (not shown). When the clamping plunger motor 116b is activated, the plates 112d and 112e (together with any components mounted thereon) move up or down together along the four threaded rods 114 due to the rotational action of the threaded timing belt pulley / nut. That is, plates 112d and 112e move together away from or toward base plate 112a on which positive displacement pipette plunger 150 is mounted.

[0056] In yet another example, motor 116c (hereinafter referred to as metering plunger motor 116c) can be used to control the pipette plunger of the pipette head 110 so as to accurately aspirate and / or dispense liquid. The metering plunger motor 116c is supported by plates 112f and 112g. The metering plunger motor 116c drives the timing (or drive) belt 118c (hereinafter referred to as metering plunger timing belt 118c). For example, a threaded timing belt pulley / nut (not shown) is mounted on each of the four threaded rods 114. Thus, the metering plunger timing belt 118c is arranged on four timing belt pulleys and a motor drive pulley (not shown). When the metering plunger motor 116c is activated, due to the rotational action of the threaded timing belt pulley / nut, the plates 112f and 112g (together with any components mounted thereon) move up or down along the four threaded rods 114 together. That is, plates 112f and 112g move together away from or toward base plate 112a on which positive displacement pipette plunger 150 is mounted.

[0057] In all cases, the threaded timing belt pulley / nut (not shown) is a custom component that has a dual function. In the first function, the threaded timing belt pulley / nut acts as a pulley relative to the operation of the timing (or drive) belt 118. In the second function, the threaded timing belt pulley / nut acts as a nut relative to the threaded rod 114. Therefore, when the timing (or drive) belt 118 rotates the threaded timing belt pulley / nut, the threaded timing belt pulley / nut moves up or down along the threaded rod 114 depending on the direction of rotation.

[0058] Further, one or more pipette tip clamping mechanisms 130 (see Fig. 22), the bottom plate 112a is located at the lower part of the pipette head 110. That is, a pipette tip clamping mechanism 130 is provided with respect to each of the positive displacement pipette tips 150. For example, in an 8-channel liquid handling instrument 100, 8 pipette tip clamping mechanisms 130 are provided. In another example, in a 96-channel liquid handling instrument 100, 96 pipette tip clamping mechanisms 130 are provided. Each of the pipette tip clamping mechanisms 130 is used to couple to (or grasp) the interface portion 210 (see Fig. 22 ), so that the pipette head 110 can capture and / or release the positive displacement pipette tip 150. In addition, each of the pipette tip clamping mechanisms 130 is a zero insertion force mechanism. More details of examples of pipette tip clamping mechanisms 130 are provided below with reference to Fig. 22 Show and describe.

[0059] Further, one or more pipette plunger clamping mechanisms 140 (see FIG. 23A to FIG. 25B ) is disposed in the central portion of the pipette head 110. That is, one pipette plunger clamping mechanism 140 is disposed with respect to each of the positive displacement pipette tips 150. For example, in an 8-channel liquid handling instrument 100, 8 pipette plunger clamping mechanisms 140 are disposed. In another example, in a 96-channel liquid handling instrument 100, 96 pipette plunger clamping mechanisms 140 are disposed. Each of the pipette plunger clamping mechanisms 140 is used to couple to (or grip) the plunger 160 of its respective positive displacement pipette tip 150 (see Fig. 16B , Fig.17 and Fig.18 ), so that the pipette head 110 can actuate the plunger 160 for aspirating and / or dispensing liquid. In addition, each of the pipette plunger clamping mechanisms 140 is a zero insertion force mechanism.

[0060] Still refer to Figures 6 to 15 The pipette head 110 of the multi-channel liquid handling instrument 100 of the present disclosure is used to drive the metering operation (e.g., aspiration / dispensing operation) of the pipette tip clamping mechanism 130, the pipette plunger clamping mechanism 140, and the positive displacement pipette tip 150. Further, the multi-channel liquid handling instrument 100 of the present disclosure is characterized by: (1) a zero insertion force pipette tip clamping mechanism 130 and (2) a zero insertion force pipette plunger clamping mechanism 140.

[0061] Reference Fig.16A , Fig. 16B , Fig.17 and Fig.18, are respective views of examples of positive displacement pipette tips 150 and pipette plungers 160 of the present disclosure for aspirating and / or dispensing liquids in liquid handling devices and / or systems. For example, Fig.16A A perspective view of an example of a positive displacement pipette tip 150 is shown. Fig. 16B A perspective view of an example of a pipette plunger 160 is shown. Further, Fig.17 A cross-sectional view of the positive displacement pipette tip 150 is shown with the pipette plunger 160 positioned relative to the positive displacement pipette tip 150 .

[0062] The positive displacement pipette tip 150 includes an interface portion 210 and a pipette tip body 212. The interface portion 210 can be, for example, an open cylindrical structure leading to the pipette tip body 212. Therefore, the interface portion 210 has an inner wall 220. The interface portion 210 of the positive displacement pipette tip 150 can be mounted to, for example, a matching component of the pipette head 110 (see Fig.21 and Fig. 22 ). The fluid channel 214 extends along the length of the pipette tip body 212. There is an opening 216 at the distal end of the fluid channel 214 (see Fig. 20 ), through which fluid can be aspirated and / or dispensed. In addition, the distal end of the pipette tip body 212 leading to the opening 216 has a tapered tip 218 (see Fig. 20 ). Further, the receiving portion (or cavity) 222 is disposed at the lower portion of the interface portion 210 of the positive displacement pipette tip 150. The positive displacement pipette tip 150 may be formed of, for example, a polymer. More details of an example of the positive displacement pipette tip 150 are described below with reference to Fig.19A and Fig.19B Show and describe.

[0063] The pipette plunger 160 is arranged along the inner side of the positive displacement pipette tip 150. The pipette plunger 160 includes a plunger upper portion 232, a plunger centering portion 234, and a plunger tip 236 including a distal tip portion 238. The plunger upper portion 232 can be mounted to a matching component of, for example, the pipette head 110 (see FIG. 23A to FIG. 24B). Further, the plunger centering portion 234 can be installed into the plunger stop receiving portion (or cavity) 222 of the interface portion 210 of the positive displacement pipette tip 150, wherein the plunger stop receiving portion (or cavity) 222 is designed to receive the plunger centering portion 234 of the pipette plunger 160. The plunger centering portion 234 acts as a "stop" feature of the pipette plunger 160. The plunger tip 236 and the distal tip 238 of the pipette plunger 160 can be installed into the fluid channel 214 of the pipette tip body 212 of the positive displacement pipette tip 150. Further, the distal tip 238 of the plunger tip 236 is designed to mate and seal with the opening 216 and the tapered tip 218 at the distal end of the fluid channel 214 of the positive displacement pipette tip 150.

[0064] Further, Fig.18 Shows Fig.17 A cross-sectional view of the upper portion of a positive displacement pipette tip 150 of the present disclosure is shown in FIG. For example, Fig.18 A cross-sectional view of the upper portion of the positive displacement pipette tip 150 and the pipette plunger 160 of the positive displacement pipette tip 150 is shown. In this view, other features of the positive displacement pipette tip 150 and the pipette plunger 160 are depicted. For example, the positive displacement pipette tip 150 further includes a group of vertical inner wall features 224 along the inner wall 220 of the interface portion 210. In one example, the positive displacement pipette tip 150 includes eight vertical inner wall features 224. Each of the vertical wall features 224 is a raised or protruding vertical line feature formed along the inner wall 220 of the interface portion 210.

[0065] The vertical inner wall features 224 are arranged in groups to assist in clamping or mating the interface portion 210 of the positive displacement pipette tip 150 to a mating component of a liquid handling instrument (not shown) (see Fig.21 and Fig. 22 ). For example, the grouped vertical interior wall features 224 may assist by increasing the friction used to hold the positive displacement pipette tip 150 in place, while potentially reducing a given force required to hold the positive displacement pipette tip 150 in place.

[0066] Still refer to Fig.18 , the pipette plunger 160 further includes a set of vertical outer wall features 233 along the outer wall of the plunger upper portion 232. In one example, the pipette plunger 160 includes eight vertical outer wall features 233. Each of the vertical outer wall features 233 is a raised or protruding vertical line feature formed along the outer wall of the plunger upper portion 232.

[0067] The vertical outer wall features 233 are provided in groups to assist in clamping or mating the upper plunger portion 232 of the pipette plunger 160 to a mating component of a liquid handling instrument (not shown) (see FIG. 23A to FIG. 25B ). For example, the grouped vertical outer wall features 233 may assist by increasing the friction used to hold the pipette plunger 160 in place, while potentially reducing a given force required to hold the pipette plunger 160 in place.

[0068] Reference Fig.19A and Fig.19B , are a side view and a cross-sectional view of a positive displacement pipette tip 150 of the present disclosure, respectively. For example, Fig.19B It is along Fig.19A A cross-sectional view taken along line AA.

[0069] Reference Fig. 20 , Fig. 20 2 is a cross-sectional view of the distal head portion 238 of the pipette plunger 160 relative to the distal head portion of the pipette tip body 212 of the positive displacement pipette tip 150. The rounded portion 240 of the distal head portion 238 of the pipette plunger 160 can be designed to match the opening 216 and the tapered tip 218 at the distal end of the fluid channel 214 of the positive displacement pipette tip 150. For example, the distal head portion 238 has a tapered sidewall corresponding to the tapered tip 218 of the fluid channel 214. Further, the outer upper edge 242 of the distal head portion 238 of the plunger tip 236 is sized to abut and slidably seal along the wall of the fluid channel 214 of the pipette tip body 212. The outer upper edge 242 of the distal tip 238 of the plunger tip 236 provides a "sealing" ring feature of the pipette plunger 160 that can remain reliable over many mixing cycles before eventually wearing out and leaking.

[0070] When the distal suction head 238 and the rounded portion 240 of the pipette plunger 160 are sealed against the opening 216 and the tapered tip 218 at the distal end of the fluid channel 214 of the positive displacement pipette tip 150, there may be only a very small gap between the tapered tip 218 of the fluid channel 214 and the tapered sidewall of the distal suction head 238 of the pipette plunger 160. In one example, the aspirated fluid 252 can be captured in this small gap. An advantageous feature of the positive displacement pipette tip 150 is that the design of the distal suction head 238 of the pipette plunger 160 minimizes the size of the gap. Therefore, the volume of liquid aspirated and / or dispensed can be accurately maintained. In addition, the positive displacement pipette tip 150 can be used for substantially any range of liquid categories.

[0071] Fig. 20An example of a positive displacement pipette tip 150 in use is shown. In one example, Fig. 20 The pipette plunger 160 is shown being withdrawn and the aspirated fluid 252 being drawn into the fluid channel 214 of the pipette tip body 212 of the positive displacement pipette tip 150. In another example, Fig. 20 The pipette plunger 160 is shown pushed and the dispensed fluid 252 is pushed out of the fluid channel 214 of the pipette tip body 212 of the positive displacement pipette tip 150 .

[0072] In standard air-displacement pipette tips, factors such as temperature, atmospheric pressure, specific gravity, and viscosity of the solution may affect the performance of the air-displacement pipette. In contrast, positive displacement pipettes can be used to accurately pipette very viscous, volatile, hot or cold, or corrosive samples. The positive displacement pipette tip 150 and pipette plunger 160 of the present disclosure are examples of positive displacement pipettes.

[0073] Reference Fig.21 , is a perspective view of an example of a pipette tip chuck 300 for use with the positive displacement pipette tip 150 of the present disclosure. The pipette tip chuck 300 may include, for example, an upper ring plate 310 and a chuck chuck portion 312 for mounting inside the interface portion 210 of the positive displacement pipette tip 150. Further, the chuck chuck portion 312 of the pipette tip chuck 300 has a serrated feature portion 314 to increase friction against the interface portion 210 of the positive displacement pipette tip 150, for example, as Fig. 22 shown.

[0074] Reference Fig. 22 The pipette tip chuck 300 is a characteristic component of the pipette tip clamping mechanism 130. Further, Fig. 22 The positive displacement pipette tip 150 is shown relative to Fig.211. A perspective view of a pipette tip chuck 300 shown. Typically, a "chuck" is a segmented band or sleeve that can expand and / or contract. The chuck chuck portion 312 of the pipette tip chuck 300 is designed to be clamped on any member around the chuck. For example, the chuck chuck portion 312 of the pipette tip chuck 300 is a segmented band or sleeve for installation in the interface portion 210 of the positive displacement pipette tip 150. The chuck chuck portion 312 of the pipette tip chuck 300 is designed to expand and lock against the inner wall 220 of the interface portion 210 of the positive displacement pipette tip 150. That is, when in the locked position, the chuck chuck portion 312 (or clamping chuck) is clamped to the interface portion 210 of the positive displacement pipette tip 150 around the chuck chuck portion 312. Further, the grouped vertical inner wall features 224 of the interface portion 210 of the positive displacement pipette tip 150 and / or the serrated features 314 of the pipette tip chuck 300 can be used to assist in clamping or matching the interface portion 210 of the positive displacement pipette tip 150 to the chuck chuck portion 312 of the pipette tip chuck 300.

[0075] The pipette tip clamping mechanism 130 is a zero insertion force pipette tip clamping mechanism. The pipette tip clamping mechanism 130 includes a pipette tip chuck 300 and a pipette tip locking mechanism 350. The pipette tip locking mechanism 350 may include, for example, an upper ring plate 352 and a hollow sleeve portion 354 for mounting inside the chuck chuck portion 312 of the pipette tip chuck 300. For example, when the hollow sleeve portion 354 is mounted inside the chuck chuck portion 312 of the pipette tip chuck 300, the chuck chuck portion 312 expands against the inner wall 220 of the interface portion 210 of the positive displacement pipette tip 150. In contrast, when the hollow sleeve portion 354 is withdrawn from the collet chuck portion 312 of the pipette tip cartridge 300 , the collet chuck portion 312 retracts and becomes loose relative to the interface portion 210 of the positive displacement pipette tip 150 .

[0076] With respect to utilizing multiple pipette tip clamping mechanisms 130 in the pipette head 110, the pipette head 110 may include some floating mechanism (not shown) with or without a spring to avoid over-constraint issues with respect to operating multiple pipette tip clamping mechanisms 130. Further, for long life and ease of assembly, the pipette head 110 may include some self-centering mechanism with respect to each of the pipette tip clamping mechanisms 130.

[0077] Reference Fig.23A and Fig. 23B , Fig.23A is a side view of the plunger cartridge 400, and Fig. 23B It is along Fig.23AThe plunger chuck 400 is a cross-sectional view of the plunger chuck 400 taken along the line AA of FIG. The plunger chuck 400 is used for use with the pipette plunger 160 of the positive displacement pipette tip 150 of the present disclosure. The plunger chuck 400 may include, for example, a shaft portion 410 and a chuck chuck portion 412 for mounting around the plunger upper portion 232 of the pipette plunger 160. Further, Fig.24A A perspective view of the collet chuck portion 412 of the pipette plunger 160 is shown, Fig. 24B is a cross-sectional view of the pipette plunger 160 relative to the collet chuck portion 412 of the plunger collet 400 .

[0078] The collet chuck portion 412 of the plunger collet 400 is designed to clamp around any component within the chuck. For example, the collet chuck portion 412 of the plunger collet 400 is a segmented band or sleeve for mounting around the plunger upper portion 232 of the pipette plunger 160. The collet chuck portion 412 of the plunger collet 400 is designed to lock against the outer wall of the plunger upper portion 232 of the pipette plunger 160 (see Fig. 24B ). That is, when in the locked position, the collet chuck portion 412 (or clamping chuck) is clamped onto the plunger upper portion 232 of the pipette plunger 160, and the plunger upper portion 232 is located within the collet chuck portion 412. Further, the set of vertical outer wall features 233 of the plunger upper portion 232 of the pipette plunger 160 can be used to assist in clamping or mating the plunger upper portion 232 to the collet chuck portion 412 of the plunger collet 400.

[0079] Reference Fig.25A and Fig.25B , the plunger collet 400 is a characteristic component of the pipette plunger clamping mechanism 140. The pipette plunger clamping mechanism 140 is a zero insertion force pipette plunger clamping mechanism. The pipette plunger clamping mechanism 140 includes the plunger collet 400 and a pipette plunger locking mechanism 450. The pipette plunger locking mechanism 450 may include, for example, an upper ring plate 452 and a hollow sleeve portion 454 for mounting around the plunger collet 400 including the 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 abuts against (clamps) the plunger upper portion 232 of the pipette plunger 160 and closes. In contrast, when the hollow sleeve portion 454 is withdrawn from the collet chuck portion 412 of the plunger cartridge 400 , the collet chuck portion 412 releases the plunger upper portion 232 of the pipette plunger 160 .

[0080] Fig.25A and Fig.25BA pair of pipette plunger clamping mechanisms 140 are shown, which are mounted relative to two plates (456A and 456B) and have two springs 458 between the two plates (456A and 456B). For example, the upper plate 456A remains fixed, and each spring 458 provides a spring force to the corresponding pipette plunger locking mechanism 450 that passes through the lower plate 456B in a slidable (floating) manner. Further, the upper end of the plunger chuck 400 is fixed to the upper plate 456A. ​​Therefore, the plunger chuck 400 remains fixed relative to the upper plate 456A, while the pipette plunger locking mechanism 450 and the lower plate 456B can move relative to the upper plate 456A. ​​Therefore, the pipette plunger locking mechanism 450 can move relative to the plunger chuck 400.

[0081] For example, Fig.25A The pipette plunger clamping mechanism 140 is shown in an unclamped state. Fig.25A In the embodiment of the present invention, the lower plate 456B is pulled upward toward the upper plate 456A, compressing the two springs 458 at the same time. In this state, the hollow sleeve portion 454 of the pipette plunger locking mechanism 450 is pulled up and away from the collet chuck portion 412 of the plunger cartridge 400, which allows the plunger cartridge 400 to open or expand. In this state, the pipette plunger 160 can be installed into or removed from the plunger cartridge 400.

[0082] In contrast, Fig.25B The pipette plunger clamping mechanism 140 is shown in a clamped state. Fig.25B In this state, the spring force of the two springs 458 pushes the lower plate 456B and the pipette plunger locking mechanism 450 away from the upper plate 456A. ​​In this state, the hollow sleeve portion 454 pushes downward around the collet chuck portion 412 of the plunger collet 400, which causes the plunger collet 400 to close or contract. In this state, the plunger collet 400 is clamped onto the pipette plunger.

[0083] The pipette plunger clamping mechanisms 140 use the springs 458 to independently set the locking preload so that each pipette plunger clamping mechanism 140 can independently handle any different plunger sizes from one pipette plunger 160 to the next.

[0084] In operation of the positive displacement pipette tip 150 of the present disclosure in the pipette head 110 of the multi-channel liquid handling instrument 100 of the present disclosure, the positive displacement pipette tip 150 remains fixed, while the pipette plunger 160 can be actuated relative to the positive displacement pipette tip 150 for extracting and / or dispensing liquid. A benefit of the positive displacement pipette tip 150 of the present disclosure is that the positive displacement pipette tip 150 is designed to be manipulated via a pipette tip clamping mechanism 130. In one example, the pipette tip clamping mechanism 130 for the positive displacement pipette tip 150 is characterized as a pipette tip chuck 300, such as Fig.21 and Fig. 22 As shown. Likewise, the pipette plunger 160 is designed to be manipulated via the pipette plunger clamping mechanism 140. In one example, the pipette plunger clamping mechanism 140 for the positive displacement pipette tip 150 is characterized as a plunger clamp 400, such as FIG. 23A to FIG. 25B shown.

[0085] Reference Fig.26 , is a flow chart of an example of a method 500 of using a pipetting head 110 of the present disclosure, the pipetting head 110 including an arrangement of positive displacement pipette tips 130 for aspirating and / or dispensing liquids. The method 500 may be performed in Figures 1 to 5 The method 500 is performed under the control of the multi-channel liquid handling instrument 100 shown in FIG.

[0086] In step 510, a pipette head including an arrangement of positive displacement pipette tips for aspirating and dispensing liquids is provided. For example, a pipette head 110 including an arrangement of positive displacement pipette tips 150 for aspirating and dispensing liquids is disposed, for example, Figures 1 to 5 In the multi-channel liquid handling instrument 100 shown in FIG. Figures 6 to 15 Shown in.

[0087] In step 515, the pipette plunger is clamped using a pipette plunger clamping mechanism. For example, the pipette plunger clamping mechanism 140 (e.g., Fig.25A and Fig.25B ) clamping the pipette plunger 160.

[0088] In step 520, the pipette tip is clamped to the pipette head using a pipette tip clamping mechanism. For example, the pipette tip clamping mechanism 130 (e.g., Fig. 22 ) to clamp the positive displacement pipette tip 150.

[0089] In step 525, a pipetting head including an arrangement of positive displacement pipette tips is used to perform a liquid aspiration and / or dispensing operation. For example, a pipetting head 110 including an arrangement of positive displacement pipette tips 150 is used to perform a liquid aspiration and / or dispensing operation.

[0090] Following long-standing patent law convention, the terms "a," "an," and "the" when used in this application, including the claims, mean "one or more." Thus, for example, reference to "a subject" includes plural subject matter unless the context clearly dictates otherwise (e.g., multiple subject matter), and so forth.

[0091] Throughout this specification and claims, unless the context requires otherwise, the terms "comprise," "comprises," and "comprising" are used in a non-exclusive sense. Likewise, the term "include" and its grammatical variations are intended to be non-limiting, such that recitation of items in a list is not to the exclusion of other like items that can be substituted or added to the listed items.

[0092] For the purpose of this specification and the appended claims, unless otherwise indicated, all numerical values ​​representing magnitudes, sizes, dimensions, ratios, shapes, formulas, parameters, percentages, quantities, features, and other numerical values ​​used in the specification and claims should be understood to be modified by the term "about" in all cases, even if the term "about" may not be explicitly presented with a value, magnitude, or range. Therefore, unless otherwise indicated, the numerical parameters set forth in the following specification and the appended claims are not and need not be precise, but may be approximate and / or larger or smaller as required, reflecting tolerances, conversion factors, rounding, measurement errors, etc., and other factors known to those skilled in the art, depending on the desired properties sought to be obtained by the subject matter of the present disclosure. For example, when referring to a value, the term "about" can mean to cover the following changes: in some embodiments ±100%, in some embodiments ±50%, in some embodiments ±20%, in some embodiments ±10%, in some embodiments ±5%, in some embodiments ±1%, in some embodiments ±0.5%, and in some embodiments ±0.1%, therefore, such changes are suitable for performing the method of the present disclosure or using the composition of the present disclosure.

[0093] Further, when used in conjunction with one or more numbers or numerical ranges, the term "about" should be understood to refer to all such numbers, including all numbers within the range and to modify the range by extending the boundaries above and below the numerical values ​​set forth. The listing of numerical ranges by endpoints includes all numbers, such as whole integers, including fractions thereof contained within the range, (e.g., a listing of 1 to 5 includes 1, 2, 3, 4, and 5, and fractions thereof, such as 1.5, 2.25, 3.75, 4.1, etc.) and any range within the range.

[0094] Although the foregoing subject matter has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be appreciated by those skilled in the art that certain changes and modifications can be practiced within the scope of the appended claims.

Claims

1. A liquid handling instrument, include: An instrument housing, wherein the instrument housing has an instrument platform; A pipetting head, the pipetting head is located above the instrument platform; as well as A removable tray is supported by the instrument platform.

2. The liquid handling apparatus according to claim 1, in, The removable tray includes a handle.

3. The liquid handling apparatus according to claim 2, in, The removable tray supports one or more microplates.

4. The liquid handling instrument of claim 3, further comprising a tip box on top of one of the one or more microplates.

5. The liquid handling apparatus according to claim 1, in, The removable tray has a unique identification number adapted to be scanned or read.

6. The liquid handling apparatus according to claim 5, in, The unique identification number is a 2D barcode or a radio frequency identification tag.

7. The liquid handling instrument of claim 1, further comprising a robotics instrument and a controller, wherein the robotics instrument is adapted to control movement of the pipetting head relative to the instrument platform, and the controller is adapted to execute program instructions for the liquid handling instrument.

8. The liquid handling instrument according to claim 1 further comprises one or more positive displacement pipette tips, wherein the pipette head is a multi-channel pipette head integrated with a multi-positioning stage for manipulating the one or more positive displacement pipette tips.

9. The liquid handling apparatus according to claim 8, in, The pipetting head comprises: a plurality of plates arranged in a stack relative to the four threaded rods; one or more motors driving one or more respective timing belts, the one or more motors being supported by the plurality of plates; and Top heated mounting plate.

10. The liquid handling apparatus according to claim 9, in, The plurality of plates are generally rectangular, and the four threaded rods are arranged in a generally rectangular configuration relative to four corners of the plurality of plates.

11. The liquid handling apparatus according to claim 9, in, The plurality of plates are eight plates arranged sequentially from bottom to top along the four threaded rods.

12. The liquid handling apparatus according to claim 11, in, The bottom plate of the plurality of plates is held fixed at the bottom ends of the four threaded rods, the top plate is held fixed at the tops of the four threaded rods, and the remaining plates are arranged in pairs between the top plate and the bottom plate and are movable along the four threaded rods.

13. The liquid handling apparatus according to claim 12, in, The base plate is a pipette tip cartridge holder plate to which the one or more positive displacement pipette tips are mounted.

14. The liquid handling instrument of claim 12, further comprising one or more pipette tip clamping mechanisms.

15. The liquid handling apparatus according to claim 14, in, The one or more motors are clamp head motors, wherein the one or more timing belts are clamp head timing belts, and wherein the clamp head motors and the clamp head timing belts are adapted to move one or more of the plurality of plates away from or toward the base plate.

16. The liquid handling apparatus according to claim 9, in, The one or more positive displacement pipette tips include: a pipette tip having an interface portion having an inner wall and a receiving portion and a pipette tip body having a fluid channel along the length of the pipette tip body and the fluid channel having an opening at a distal end of the fluid channel; and A pipette plunger positioned along an interior of the pipette tip, the pipette plunger having a plunger upper portion, a plunger centering portion, and a plunger tip having a distal suction portion, wherein the receptacle is adapted to receive the plunger centering portion, wherein the fluid channel is adapted to receive the distal suction portion of the plunger tip, and wherein the one or more pipette tip clamping mechanisms are zero insertion force pipette clamping mechanisms.

17. The liquid handling apparatus according to claim 16, in, One or more pipette plunger clamping mechanisms are disposed in a central portion of the pipette head, wherein each of the one or more pipette plunger mechanisms is coupled to a plunger of each displacement pipette tip in a respective positive displacement pipette tip.

18. The liquid handling instrument of claim 12, further comprising a set of zero insertion force pipette plunger clamping mechanisms, one of the one or more motors being used to control the set of zero insertion force pipette plunger mechanisms.

19. The liquid handling apparatus according to claim 18, in, The one of the one or more motors is a clamping plunger motor, wherein one of the one or more timing belts is a clamping plunger timing belt, and the clamping plunger motor and the clamping plunger timing belt are adapted to move one or more of the multiple plates away from or toward the base plate.

20. The liquid handling instrument of claim 12, further comprising a pipette plunger, in, One of the one or more motors is used to control the pipette plunger.

21. The liquid handling apparatus according to claim 20, in, One of the one or more motors is a metering plunger motor, wherein one of the one or more timing belts is a metering plunger timing belt, and the metering plunger motor and the metering plunger timing belt are adapted to move one or more of the multiple plates away from or toward the base plate.

22. The liquid handling instrument of claim 12, further comprising one or more pipette plunger clamping mechanisms, the one or more pipette plunger clamping mechanisms being zero insertion force pipette plunger clamping mechanisms.

23. The liquid handling apparatus according to claim 22, in, Each of the one or more zero-insertion force pipette plunger clamping mechanisms includes a plunger collet and a pipette plunger locking mechanism, wherein the plunger collet includes a shaft portion and a collet chuck portion, wherein the collet chuck portion is used to fit around a plunger upper portion of the pipette plunger.

24. The liquid handling apparatus according to claim 23, in, The collet chuck portion is a segmented band or sleeve that fits around the upper portion of the plunger of the pipette plunger.

25. A method for aspirating and / or dispensing a liquid, The following steps are involved: A liquid handling instrument is provided, the liquid handling instrument comprising an instrument housing with an instrument platform, a pipetting head above the instrument platform, and a removable tray, the instrument platform supporting the removable tray, the pipetting head having an arrangement of one or more positive displacement pipette tips for aspirating and dispensing liquids, wherein the pipetting head comprises one or more pipette tip clamping mechanisms and one or more pipette plunger clamping mechanisms, and wherein each of the one or more positive displacement pipette tips comprises a pipette tip and a corresponding pipette plunger; clamping the one or more pipette plungers by the one or more pipette plunger clamping mechanisms; clamping the one or more pipette tips by the one or more pipette tip clamping mechanisms; and The pipetting head is used to perform aspiration and / or dispensing operations.

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