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

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.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS The subject matter of this disclosure is related to U.S. Provisional Patent Application No. 62 / 797,687, filed January 28, 2019, and entitled "Liquid Handling Apparatus and Pipette Head for Aspirating and / or Dispensing Liquids and Methods Thereof," the entire disclosure of which is incorporated herein by reference.

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

[0003] Automated liquid handling equipment includes robots used to transfer specific amounts of liquid, such as reagents or samples, between designated containers. Liquid handling equipment is useful in a variety of applications, including cell biology, genomics, forensics, and drug research. The equipment assists humans in the repetitive task of transferring a wide range of volumes of liquid to improve the speed and efficiency of operations and the precision and accuracy of delivered volumes. Benefits of automating liquid handling processes include increasing the throughput and efficiency of operations and eliminating human error.

[0004] In conventional liquid handling instruments, there is typically a sealed interface between the instrument and each pipette tip. This sealed interface is typically a compressible rubber O-ring, which requires periodic maintenance and / or replacement over the life of the instrument. Compressible rubber O-rings also have the disadvantage of high friction during pipette tip insertion, ultimately requiring (1) a powerful actuator to achieve the necessary downforce and (2) a strong / heavy mechanical structure to handle the high friction from the multiple O-rings and implement a reliable sealing interface for multiple pipette tips (e.g., 96 pipette tips used in a 96-well sample plate). For example, in conventional liquid handling instruments, a single pipette tip requires an insertion force of approximately 100 grams, and therefore the actuator for that tip must provide a downforce of approximately 100 grams. Therefore, in a multichannel liquid handling instrument that processes, for example, 96 pipette tips, the actuator must be capable of a downforce of approximately 9.5 kilograms. Therefore, powerful actuators are required, along with strong / heavy mechanical support structures that can handle the high forces. Summary of the Invention

[0005] The present subject matter describes instruments and methods for aspirating and / or dispensing liquids using pipette tips. In one embodiment, a liquid handling instrument includes an instrument housing with an instrument deck, a pipette head on the instrument deck, and a removable tray, where the instrument deck holds the removable tray.

[0006] The removable tray includes a handle. The removable tray holds one or more microplates and a chip caddy over the one or more microplates. The removable tray has a unique identification number configured to be scanned or read. The unique identification number is a two-dimensional barcode or a radio frequency identification tag.

[0007] Additionally included in the instrument is a robotic instrument and a controller, for example, the robotic instrument can control the movement of the pipetting head relative to the instrument deck, and the controller can execute program instructions.

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

[0009] The pipette head further includes a plurality of plates arranged in a stacked manner for four screw paths, one or more motors driving one or more respective timing belts, the one or more motors being supported by the plurality of plates, and an upper heated mounting plate.

[0010] The plurality of plates is substantially rectangular, and the four threaded rods are arranged in a substantially rectangular configuration relative to the four corners of the plurality of plates. In one embodiment, the plurality of plates is eight plates arranged in order from bottom to top along the four threaded rods.

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

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

[0013] In another embodiment, the one or more positive displacement pipette tips include a pipette tip having a boundary and a pipette tip body, the boundary having an interior wall and a receptacle, the pipette tip body having a fluid channel along a length of the pipette tip body, the fluid channel having an opening at a distal end of the fluid channel, and a pipette plunger disposed along the interior of the pipette tip, the pipette plunger having a plunger tip having a plunger top, a plunger center, and a distal tip, 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 the 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 a central portion of the pipette head, each of the one or more pipette plunger mechanisms being coupled to a respective plunger of a respective positive displacement pipette tip.

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

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

[0017] The instrument further includes one or more pipette plunger gripping mechanisms that 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 locking mechanism, the plunger collet including a shaft portion and a collet chuck portion for fitting around the plunger top of the pipette plunger. Further, the collet chuck portion is a segmented band or sleeve for fitting around the plunger top of the pipette plunger.

[0018] The present subject matter further describes a method for aspirating and / or dispensing liquid. In one embodiment, the method includes providing a liquid handling device, the liquid handling device including an instrument housing with an instrument deck, a pipette head on the instrument deck, and a removable tray, the instrument deck holding the removable tray, the pipette head having an arrangement of one or more positive displacement pipette tips for aspirating and dispensing liquid, the pipette head including one or more pipette tip gripping mechanisms and one or more pipette plunger gripping mechanisms, each of the one or more positive displacement pipette tips including a pipette tip and a corresponding pipette plunger; gripping one or more pipette plungers with the one or more pipette plunger gripping mechanisms; gripping one or more pipette tips with the one or more pipette tip gripping mechanisms; and performing an aspirating and / or dispensing operation using the pipette head.

[0019] Having described the subject matter of the present disclosure in general terms, reference is now made to the accompanying drawings, which are not necessarily drawn to scale. [Brief explanation of the drawings]

[0020] [Figure 1] 1A-1D depict various schematic perspective views of a multi-channel liquid handling device of the present disclosure, including a pipette head that includes an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids. [Figure 2] 1A-1D depict various schematic perspective views of a multi-channel liquid handling device of the present disclosure, including a pipette head that includes an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids. [Figure 3] 1A-1D depict various schematic perspective views of a multi-channel liquid handling device of the present disclosure, including a pipette head that includes an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids. [Figure 4] 1A-1D depict various schematic perspective views of a multi-channel liquid handling device of the present disclosure, including a pipette head that includes an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids. [Figure 5] 1A-1D depict various schematic perspective views of a multi-channel liquid handling device of the present disclosure, including a pipette head that includes an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids. [Figure 6] 1A-1D depict various schematic perspective views of a pipette head of the present disclosure including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids; [Figure 7] 1A-1D depict various schematic perspective views of a pipette head of the present disclosure including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids; [Figure 8] 1A-1D depict various schematic perspective views of a pipette head of the present disclosure including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids; [Figure 9] 1 depicts a front view of a pipette head of the present disclosure including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids. [Figure 10]1 depicts a rear view of a pipette head of the present disclosure including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids. [Figure 11] 1 depicts a side view of a pipette head of the present disclosure including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids. [Figure 12] 1 depicts another side view of a pipette head of the present disclosure including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids. [Figure 13] 1 depicts a top view of a pipette head of the present disclosure including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids. [Figure 14] 1 depicts a bottom view of a pipette head of the present disclosure including an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquids. [Figure 15] 1 depicts a cross-sectional view of a pipette tip of the present disclosure including a positive displacement pipette tip arrangement for aspirating and / or dispensing liquid. [Figures 16A-16B] 1 depicts a schematic perspective view of an example of a positive displacement pipette and pipette plunger of a pipette head of the present disclosure. [Figure 17] 16A and 16B depict cross-sectional views of the example positive displacement pipette and pipette plunger shown in FIG. [Figure 18] 1 depicts a cross-sectional view of the top of a positive displacement pipette tip of the present disclosure. [Figures 19A-19B] 1A and 1B depict a side view and a cross-sectional view, respectively, of a positive displacement pipette tip. [Figure 20] 1 depicts a detailed side view of the distal tip of a pipette plunger relative to the distal tip of a pipette tip. [Figure 21] 1 depicts a schematic perspective view of an example pipette tip collet for use with a positive displacement pipette tip. [Figure 22] 1 illustrates a side view of an example of a pipette tip gripping mechanism of a pipette head of the present disclosure. [Figures 23A-23B] 1A-1C depict side and cross-sectional views, respectively, of an example plunger collet for use in a positive displacement pipette tip. [Figure 24A]23B is a schematic perspective view of the collet chuck portion of the plunger collet shown in FIG. 23A and FIG. 23B. [Figure 24B] 23A and 23B depict cross-sectional views of a pipette plunger relative to the plunger collet shown in FIGS. 23A and 23B. [Figures 25A-25B] 1 illustrates an example of a pipette plunger gripping mechanism and process for gripping a pipette plunger in a pipette head of the present disclosure. [Figure 26] 1 depicts a flow diagram of an example method of using a pipette head of the present disclosure, including the placement of a positive displacement pipette tip to aspirate and / or dispense liquid. DETAILED DESCRIPTION OF THE INVENTION

[0021] The presently disclosed subject matter will now be described more fully and in more detail hereinafter with reference to the accompanying drawings, in which some, but not all, embodiments of the presently disclosed subject matter are shown. Like numerals refer to like elements throughout. The presently disclosed subject matter may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. Indeed, many modifications and other embodiments of the presently disclosed subject matter described herein will come to mind to one skilled in the art to which the presently disclosed subject matter pertains having the benefit of the teachings set forth in the foregoing descriptions and the associated drawings. Therefore, it should be understood that the presently disclosed subject matter is not to be limited to the particular embodiments disclosed, and that modifications and other embodiments are intended to be included within the scope of the appended claims.

[0022] In some embodiments, the presently disclosed subject matter provides liquid handling instruments and pipette heads and methods 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 destination medium using at least one pipette head and using a positive displacement pipette tip, the positive displacement pipette tip including a pipette tip and a pipette plunger.

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

[0024] In some embodiments, the automated liquid handling instruments of the present disclosure are zero-insertion-force systems that provide a mechanism for inserting positive displacement pipette tips using zero insertion force, as they do not require a sealing interface between the instrument and the pipette tip. For example, the automated liquid handling instrument 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 of the gripping mechanisms provides a reliable, zero-insertion-force, airtight seal that requires substantially no periodic maintenance and / or replacement, thereby ensuring a robust pipette system.

[0025] In some embodiments, the automated liquid handling instruments of the present disclosure include specific features that protect against contamination. For example, conventional liquid handling instruments typically have a shared air column between all of the pipette tip boundaries, which is a common source of contamination that may carry over to the next workflow. In contrast, the automated liquid handling instruments of the present disclosure do not include a shared air column between pipette tips and are therefore free of this potential source of contamination.

[0026] Reference is now made to Figures 1 through 5 for various schematic perspective views of a multi-channel liquid handling device 100 of the present disclosure, including a pipette head 110 that includes an arrangement of positive displacement pipette tips for aspirating and / or dispensing liquid. For example, 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 of a multi-channel liquid handling device 100 of the present disclosure.

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

[0028] The removable tray 183 includes multiple microplate or labware positions for holding, for example, one or more microplates 185. One or more tip caddies 186 to be processed reside above the particular microplate 185. The tip caddy 186 is a consumable tray or box for holding / packing an arrangement of multiple pipette tips 150. The multichannel liquid handling instrument 100 includes a pipette head 110 disposed on the instrument deck 182 for aspirating liquid from and / or dispensing liquid. The pipette head 110 comprises an arrangement of multiple pipette tips 150.

[0029] The multichannel liquid handling instrument 100 also includes a robotic instrument 188 and a controller 190. The robotic instrument 188 is any robotic instrument capable of precisely controlling the movement of the pipetting head 110 relative to the instrument deck 182. The controller 190 is any standard controller or microprocessor device capable of executing program instructions.

[0030] Features of the multi-channel liquid handling instrument 100 of the present disclosure include, but are not limited to, removable trays / decks, fully automatic deck / tray calibration, fully automatic probes for calibrating multiple plate placements, multiple microplate positions, tip caddy positions, deck / tray ID scanning and Tips caddy Pipette tip on of presence or absenceIncludes cameras to check the vehicle's position, head collision detection, etc.

[0031] In the multichannel liquid handling instrument 100 of the present disclosure, the removable tray 183 is provided with a unique ID number using, for example, a two-dimensional barcode that is scanned / read using a camera (not shown) on the pipetting 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 pipetting head 110. In operation, each time the multichannel liquid handling instrument 100 is used, a user places a removable tray 183 with a particular set of microplates 185 on the instrument deck 182 and then runs a particular protocol. Upon completion, the user then removes their / her removable tray 183. The next user then places a next removable tray 183 with a next set of microplates 185 on the instrument deck 182 and then runs a different protocol.

[0032] Thus, a benefit of the multichannel liquid handling instrument 100 of the present disclosure is that, due to the presence of removable trays 183, the instrument can be easily and quickly shared among multiple users, each user having their own tray with a specific set of microplates 185 and a specific protocol to run. With this shared instrument approach, maximum uptime of the multichannel liquid handling instrument 100 is achieved, compared to conventional instruments in which an entire set of microplates must be switched from one user to the next from a non-removable deck, a slow and cumbersome process that causes downtime.

[0033] The multichannel liquid handling device 100 and / or pipette head 110 feature positive displacement pipette tips. Each positive displacement pipette tip includes a pipette tip and a pipette plunger designed to aspirate and / or dispense a precise volume of liquid. For example, each positive displacement pipette tip includes a minimal amount of space between the pipette tip and the pipette plunger, thereby optimizing the accuracy of the volume of liquid aspirated and / or dispensed. Additionally, the pipette head 110 provides a zero-insertion-force gripping mechanism for both the pipette tip and the pipette plunger of each positive displacement 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 that manipulates one or more positive displacement pipette tips 150. For example, the pipette head 110 may handle only one tip, 1-8 tips (in a row), 1-12 tips (in a row), 96 tips, and / or two or more cluster / group tip configurations. Further details of example positive displacement pipette tips 150 are shown and described below with reference to Figures 16A through 20.

[0035] 6-15, Figures 6, 7, and 8 show various schematic perspective views of an example pipette head 110 including an arrangement of positive displacement pipette tips 150 for aspirating and / or dispensing liquid. Additionally, Figures 9, 10, 11, 12, 13, and 14 show front, back, side, another side, top, and bottom views, respectively, of the pipette head 110. Additionally, Figure 15 shows a cross-sectional view of the pipette head 110 taken along line AA in Figure 6.

[0036] 6-15, the pipette head 110 includes, for example, multiple plates 112 arranged in a stacked manner about 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), an upper heated mounting plate 113, in combination with various other support members and / or components. For example, the pipette 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., fan, heat sink), any type of sensor, any type of actuator, etc. Additionally, the pipette head 110 may include a wide 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, and the like.

[0037] The four threaded rods 114 are arranged in a substantially rectangular configuration relative to the four corners of the substantially rectangular plates 112. In one example, the pipette head 110 includes eight plates 112 (112a, 112b, 112c, 112d, 112e, 112f, 112g, and 112h). Furthermore, the eight plates 112a, 112b, 112c, 112d, 112e, 112f, 112g, and 112h are arranged in order from bottom to top along the four threaded rods 114. For example, plate 112a (hereinafter referred to as lower plate 112a) is fixed to the lower ends of the four threaded rods 114, while plate 112h (hereinafter referred to as upper plate 112h) is fixed to the upper ends of the four threaded rods 114. The bottom plate 112a serves as a pipette tip collet holder plate onto which positive displacement pipette tips 150 are attached.

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

[0039] In another example, motor 116b (hereinafter referred to as gripper plunger motor 116b) is used to precisely control the zero-insertion-force pipette plunger gripping mechanism 140 of pipette head 110. Gripper plunger motor 116b is supported by plates 112d and 112e. Gripper plunger motor 116b drives timing (or drive) belt 118b (hereinafter referred to as gripper plunger timing belt 118b). For example, a screw timing belt pulley / nut (not shown) is attached to each of the four threaded rods 114. Thus, gripper plunger timing belt 118b is disposed on the four timing belt pulleys and motor drive pulley (not shown). When gripper plunger motor 116b is operated, plates 112d and 112e (along with any components attached thereto) ride up and down the four threaded rods 114 together due to the rotational action of the screw timing belt pulley / nut. That is, plates 112d and 112e move together, either away from or towards the bottom plate 112a to which the positive displacement pipette plunger 150 is attached.

[0040] In yet another example, motor 116c (hereinafter referred to as metering plunger motor 116c) is used to control the pipette plungers of pipette head 110 to accurately aspirate and / or dispense liquid. Metering plunger motor 116c is supported by plates 112f and 112g. Metering plunger motor 116c drives timing (or drive) belt 118c (hereinafter referred to as metering plunger timing belt 118c). For example, a screw timing belt pulley / nut (not shown) is attached to each of four threaded rods 114. Thus, metering plunger timing belt 118c is disposed on the four timing belt pulleys and motor drive pulley (not shown). When metering plunger motor 116c is operated, plates 112f and 112g (along with any components attached thereto) ride up and down the four threaded rods 114 together due to the rotational action of the screw timing belt pulley / nut. That is, plates 112f and 112g move together, either away from or towards the bottom plate 112a to which the positive displacement pipette plunger 150 is attached.

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

[0042] Additionally, one or more pipette tip gripping mechanisms 130 (see FIG. 22 ) are provided in association with the lower plate 112a below the pipette head 110. That is, one pipette tip gripping mechanism 130 is provided in association with each positive displacement pipette tip 150. For example, in an eight-channel liquid handling instrument 100, eight pipette tip gripping mechanisms 130 are provided. In another example, in a ninety-six-channel liquid handling instrument 100, ninety-six pipette tip gripping mechanisms 130 are provided. Each of the pipette tip gripping mechanisms 130 is used to couple with (or grasp) the interface 210 (see FIG. 22 ) of its respective positive displacement pipette tip 150 so that the pipette head 110 can capture and / or release the positive displacement pipette tip 150. Furthermore, each of the pipette tip gripping mechanisms 130 is a zero-insertion force mechanism. Further details of example pipette tip gripping mechanisms 130 are shown and described below with reference to FIG. 22 .

[0043] Additionally, one or more pipette plunger gripping mechanisms 140 (see FIGS. 23A-25B) are provided in a central portion of the pipette head 110. That is, one pipette plunger gripping mechanism 140 is provided in association with each positive displacement pipette tip 150. For example, in an eight-channel liquid handling instrument 100, eight pipette plunger gripping mechanisms 140 are provided. In another example, in a ninety-six-channel liquid handling instrument 100, ninety-six pipette plunger gripping mechanisms 140 are provided. Each of the pipette plunger gripping mechanisms 140 is used to engage (grasp) the plunger 160 (see FIGS. 16B, 17, and 18) of its respective positive displacement pipette tip 150 so that the pipette head 110 can actuate the plunger 160 to aspirate and / or dispense liquid. Additionally, each of the pipette plunger gripping mechanisms 140 is a zero-insertion force mechanism.

[0044] 6-15, the pipette head 110 of the multi-channel liquid handling device 100 of the present disclosure is used to drive the metering operations (e.g., aspirating / dispensing operations) of the pipette tip gripping mechanism 130, the pipette plunger gripping mechanism 140, and the positive displacement pipette tips 150. Additionally, the multi-channel liquid handling device 100 of the present disclosure features (1) a zero insertion force pipette tip gripping mechanism 130, and (2) a zero insertion force pipette plunger gripping mechanism 140.

[0045] Reference is now made to Figures 16A, 16B, 17, and 18 for various views of an example positive displacement pipette tip 150 and a pipette plunger 160 of the present disclosure for aspirating and / or dispensing liquids into a liquid handling device and / or system. For example, Figure 16A shows a schematic perspective view of an example positive displacement pipette tip 150. Figure 16B shows a schematic perspective view of an example pipette plunger 160. Additionally, Figure 17 shows a cross-sectional view of the positive displacement pipette tip 150 and the pipette plunger 160 positioned relative to the positive displacement pipette tip 150.

[0046] The positive displacement pipette tip 150 includes a boundary portion 210 and a pipette tip body 212. The boundary portion 210 is, for example, an open barrel-type structure that connects to the pipette tip body 212. Accordingly, the boundary portion 210 has an inner wall 220. The boundary portion 210 of the positive displacement pipette tip 150 is adapted to, for example, a connecting component of the pipette head 110 (FIGS. 21 and 22). A fluid channel 214 extends along the length of the pipette tip body 212. At the distal end of the fluid channel 214 is an opening 216 (see FIG. 20) through which fluid is aspirated and / or dispensed. Furthermore, the distal end of the pipette tip body 212 that connects to the opening 216 has a tapered tip 218 (see FIG. 20). Furthermore, a receptacle (or cavity) 222 is provided below the boundary portion 210 of the positive displacement pipette tip 150. The positive displacement pipette tip 150 is formed, for example, from a polymer. Further details of an example positive displacement pipette tip 150 are shown and described below with reference to Figures 19A and 19B.

[0047] The pipette plunger 160 is disposed along the interior of the positive displacement pipette tip 150. The pipette plunger 160 includes a plunger tip 236 that includes a plunger top 232, a plunger center 234, and a distal tip 238. The plunger top 232 is adapted to fit, for example, a connecting piece of the pipette head 110 (see FIGS. 23A to 24B). Furthermore, the plunger center 234 is adapted to fit into a plunger stop receptacle (or cavity) 222 in the interface 210 of the positive displacement pipette tip 150, where the plunger stop receptacle (or cavity) 222 is designed to receive the plunger center 234 of the pipette plunger 160. The plunger center 234 serves as a "stop" mechanism for the pipette plunger 160. The plunger tip 236 and distal tip 238 of the pipette plunger 160 are fitted into the fluid channel 214 of the pipette tip body 212 of the positive displacement pipette tip 150. Furthermore, the distal tip 238 of the plunger tip 236 is designed to connect to and seal with the opening 216 and tapered tip 218 at the distal end of the fluid channel 214 of the positive displacement pipette tip 150.

[0048] Additionally, Figure 18 shows a cross-sectional view of the top of the positive displacement 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 positive displacement pipette tip 150 and the pipette plunger 160 of the positive displacement pipette tip 150. 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 set of vertical interior wall features 224 along the interior wall 220 of the boundary portion 210. In one example, the positive displacement pipette tip 150 includes eight vertical interior wall features 224. Each of the vertical interior wall features 224 is a raised or protruding vertical line feature formed along the interior wall 220 of the boundary portion 210.

[0049] The set of vertical inner wall features 224 are provided to assist in gripping or connecting the interface 210 of the positive displacement pipette tip 150 to a connecting component (FIGS. 21 and 22) of a liquid handling device (not shown). For example, the set of vertical inner wall features 224 may reduce the amount of force required to hold the positive displacement pipette tip 150 in place while assisting by increasing the frictional force to hold the positive displacement pipette tip 150 in place.

[0050] 18 , the pipette plunger 160 further includes a set of vertical outer wall features 233 along the outer wall of the plunger top 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 top 232.

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

[0052] Reference is now made to Figures 19A and 19B, which are side and cross-sectional views, respectively, of a positive displacement pipette tip 150 of the present disclosure. For example, Figure 19B is a cross-sectional view taken along line AA of Figure 19A.

[0053] 20 for 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 positive displacement pipette tip 150. 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 positive displacement pipette tip 150. For example, the distal tip 238 has tapered sidewalls that correspond to the tapered tip 218 of the fluid channel 214. Additionally, the outer upper end 242 of the distal tip 238 of the plunger tip 236 is sized to slidably seal against and along the walls of the fluid channel 214 of the pipette tip body 212. The outer top edge 242 of the distal tip 238 of the plunger tip 236 provides a "sealing" ring mechanism for the pipette plunger 160 that remains reliable through 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 positive displacement 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, aspirating fluid 252 is trapped within this small space. A beneficial feature of the positive displacement 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 accurately retained. Furthermore, the positive displacement pipette tip 150 can be used with virtually any liquid class range.

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

[0056] In standard air-displacement pipette tips, factors such as temperature, air pressure, specific gravity, and solution viscosity affect the performance of the air-displacement pipette tip. In contrast, positive displacement pipettes are used for accurately pipetting samples that are highly viscous, volatile, hot or cold, or corrosive. The positive displacement pipette tip 150 and pipette plunger 160 of the present disclosure are examples of positive displacement pipettes.

[0057] 21, which is a schematic perspective view of an example of a pipette tip collet 300 for use with a positive displacement pipette tip 150 of the present disclosure. The pipette tip collet 300 includes, for example, an upper ring plate 310 and a collet chuck portion 312 that fits inside the interface 210 of the positive displacement pipette tip 150. Additionally, the collet chuck portion 312 of the pipette tip collet 300 includes a sawtooth feature 314 to increase friction against the interface 210 of the positive displacement pipette tip 150, as shown, for example, in FIG.

[0058] Referring now to FIG. 22, the pipette tip collet 300 is a feature of the pipette tip gripping mechanism 130. Additionally, FIG. 22 shows a perspective view of the positive displacement pipette tip 150 relative to the pipette tip collet 300 shown in FIG. 21. Generally, a "collet" is a segmented band or sleeve that can expand and / or contract. The collet chuck portion 312 of the pipette tip collet 300 is designed to grip onto any member that surrounds the chuck. For example, the collet chuck portion 312 of the pipette tip collet 300 is a segmented band or sleeve that fits inside the boundary portion 210 of the positive displacement pipette tip 150. The collet chuck portion 312 of the pipette tip collet 300 is designed to expand and secure against the inner wall 220 of the boundary portion 210 of the positive displacement pipette tip 150. That is, when in the locked position, the collet chuck portion 312 (or gripping chuck) grips onto the boundary portion 210 of the positive displacement pipette tip 150 that surrounds the collet chuck portion 312. Additionally, the vertical inner wall features 224 of the boundary portion 210 of the positive displacement pipette tip 150 and / or the set of sawtooth features 314 of the pipette tip collet 300 are used to help grip or connect 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 securing mechanism 350. The pipette tip securing 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 against the inner wall 220 of the interface 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 collet 300, the collet chuck portion 312 retracts and becomes loose relative to the interface 210 of the positive displacement pipette tip 150.

[0060] With regard to utilizing multiple pipette tip gripping mechanisms 130 in the pipette head 110, the pipette head 110 includes a specific floating mechanism (not shown) with or without springs to avoid over-constraint issues with operating multiple pipette tip gripping mechanisms 130. Additionally, the pipette head 110 includes a specific self-centering mechanism for each of the pipette tip gripping mechanisms 130 that is long-lasting and easy to assemble.

[0061] 23A and 23B, FIG. 23A is a side view of plunger collet 400, while FIG. 23B is a cross-sectional view of plunger collet 400 taken along line AA in FIG. 23A. Plunger collet 400 is for use with pipette plunger 160 of positive displacement pipette tip 150 of the present disclosure. Plunger collet 400 includes, for example, a shaft portion 410 and a collet chuck portion 412 for fitting around plunger top 232 of pipette plunger 160. Additionally, FIG. 24A shows a schematic perspective view of collet chuck portion 412 of pipette plunger 160, and FIG. 24B is a cross-sectional view of pipette plunger 160 relative to collet chuck portion 412 of 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 segmented 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 secure to the outer wall of the plunger top 232 of the pipette plunger 160 (see FIG. 24B). That is, when in the locked position, the collet chuck portion 412 (or gripping chuck) grips onto the plunger top 232 of the pipette plunger 160 inside the collet chuck portion 412. Additionally, a set of vertical outer wall features 233 on the plunger top 232 of the pipette plunger 160 are used to help grip or connect the plunger top 232 to the collet chuck portion 412 of the plunger collet 400.

[0063] 25A and 25B, the plunger collet 400 is a feature 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 a pipette plunger locking mechanism 450. The pipette plunger locking mechanism 450 includes a hollow sleeve portion 454 that fits around the plunger collet 400, which includes, for example, an upper ring plate 452 and a collet chuck portion 412. For example, when the hollow sleeve portion 454 slides down around the collet chuck portion 412 of the plunger collet 400, the collet chuck portion 412 closes against (grapples) 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 plunger upper portion 232 of the pipette plunger 160 .

[0064] 25A and 25B show a pair of pipette plunger gripping mechanisms 140 mounted on two plates (456A and 456B) and including two springs 458 between the two plates (456A and 456B). For example, the upper plate 456A is fixed, while each spring 458 provides a spring force to a corresponding pipette plunger locking mechanism 450 that slides through the lower plate 456B in a slidable (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 relative to the upper plate 456A, while the pipette plunger locking mechanism 450 and the lower plate 456B are movable relative to the upper plate 456A. ​​Thus, the pipette plunger locking mechanism 450 is movable relative to the plunger collet 400.

[0065] For example, Figure 25A shows the pipette plunger gripping mechanism 140 in an ungripped 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 locking mechanism 450 is pulled up and away 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 can be installed in and removed from the plunger collet 400.

[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 locking mechanism 450 away from the upper plate 456A. ​​In this state, the hollow sleeve portion 454 presses 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 onto the pipette plunger.

[0067] The pipette plunger gripping mechanisms 140 use springs 458 to independently set fixed preloads, and each pipette plunger gripping mechanism 140 can handle arbitrarily varying plunger sizes independently from one pipette plunger 160 to the next.

[0068] During operation of the disclosed positive displacement pipette tip 150 in the pipette head 110 of the disclosed multi-channel liquid handling instrument 100, the positive displacement pipette tip 150 is fixed while the pipette plunger 160 is operated relative to the positive displacement pipette tip 150 to aspirate and / or dispense liquid. An advantage of the disclosed positive displacement pipette tip 150 is that the positive displacement pipette tip 150 is designed to be manipulated through a pipette tip gripping mechanism 130. In one example, the pipette tip gripping mechanism 130 of the positive displacement pipette tip 150 features a pipette tip collet 300, as shown, for example, in FIGS. 21 and 22 . Similarly, the pipette plunger 160 is designed to be manipulated by a pipette plunger gripping mechanism 140. In one example, the pipette plunger gripping mechanism 140 for the positive displacement pipette tip 150 features a plunger collet 400, as shown, for example, in FIGS. 23A-25B .

[0069] Reference is now made to Figure 26 for a flow diagram of an example method 500 of using a pipette head 110 of the present disclosure, including the placement of positive displacement pipette tips 130, to aspirate and / or dispense liquid. Method 500 is performed under control of the multi-channel liquid handling device 100 shown in Figures 1-5. Method 500 includes, but is not limited to, the following steps:

[0070] 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 provided in a multi-channel liquid handling device 100, such as that 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 a pipette plunger gripping mechanism, for example, the pipette plunger 160 is grasped using the pipette plunger gripping mechanism 140 of the pipette head 110, for example, as shown in Figures 25A and 25B.

[0072] In step 520, a pipette tip is gripped in the pipette head using a pipette tip gripping mechanism. For example, a positive displacement pipette tip 150 is gripped using the pipette tip gripping mechanism 130 of the pipette head 110, as shown, for example, in FIG.

[0073] In step 525, a liquid aspirating / dispensing operation is performed using a pipette tip head including a positive displacement pipette tip arrangement. For example, a liquid aspirating and / or dispensing operation is performed using a pipette head 110 including a positive displacement pipette tip arrangement 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. Thus, for example, a reference to "one subject matter" includes a plurality of subjects unless the context clearly dictates otherwise (e.g., a plurality of subjects), and so forth.

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

[0076] For purposes of this specification and the appended claims, unless otherwise noted, all numbers expressing quantities, sizes, dimensions, ratios, shapes, formulations, parameters, percentages, amounts, properties, and other numerical values ​​used in this specification and claims are to be understood as being modified in all instances by the term "about," even if the term "about" does not explicitly appear in any value, amount, or range. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and appended claims are not, and need not be, precise, but may be approximate and / or desired larger or smaller, reflecting tolerances, conversion factors, rounding, measurement errors, and the like, and other factors known to those of ordinary skill in the art depending upon the desired properties sought to be obtained by the subject matter of the present disclosure. For example, the term "about," when referring to a value, is meant to include variations of ±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% in some embodiments, and ±0.1% in some embodiments from the particular amount, where such variations are appropriate for practicing the disclosed methods or using the disclosed compositions.

[0077] Furthermore, the term "about," when used in connection with one or more numbers or numerical ranges, should be understood to refer to all such numbers, inclusive of every number in the range, and to modify that range by extending to the boundaries above and below the numerical values ​​recited. The recitation of numerical ranges by endpoints includes all numbers and any range within that range, such as whole integers, including fractions thereof, within that range (e.g., recitation of 1 to 5 includes 1, 2, 3, 4, 5, and fractions thereof, e.g., 1.5, 2.25, 3.75, 4.1, etc.).

[0078] 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 understood by those skilled in the art that certain changes and modifications may be practiced within the scope of the appended claims.

Claims

1. A multi-channel liquid handling device (100) comprising: an equipment deck (182) having a plurality of rails; a removable tray (183) removably supported on said instrument deck (182) and holding three or more microplates (185); a tip caddy (186) on one of the three or more microplates (185) for holding an array of a plurality of positive displacement pipette tips (150); a pipette head (110) above the instrument deck (182); the removable tray (183) has a two-dimensional barcode containing a unique ID number and the pipetting 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 manipulating the one or more positive displacement pipette tips (150) disposed on the pipette head (110); The multi-channel liquid handling device (100) further comprises: a robotic instrument configured to control movement of the pipetting head (110) relative to the instrument 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 on the removable tray (183).

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

3. 10. The multi-channel liquid handling device of claim 1, wherein the chip caddy (186) is used with a microplate (185) that is not covered by the chip caddy (186).

4. The pipette head (110) comprises a plurality of plates (112) stacked along four threaded rods (114), the four threaded rods (114) passing through the stacked plates (112); One or more timing belts (118) attached to the four threaded rods (114); one or more motors (116) for driving each of the one or more timing belts (118); 2. The liquid handling device of claim 1, wherein each of the one or more motors (116) is attached to one or more of the plurality of plates (112) and drives the one or more timing belts (118) to initiate movement of the plurality of plates (112) within the pipette head (110).

5. The plurality of plates (112) are rectangular; 5. The liquid handling apparatus of claim 4, wherein the four threaded rods (114) are disposed at four corners of the plurality of plates (112), respectively.

6. The plurality of plates (112) comprises a lower plate (112a), an upper plate (112h) disposed on the lower plate (112a), and 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); 6. The liquid treatment device according to claim 5, wherein the remaining plates (112b to 112g) are arranged in pairs between the lower plate (112a) and the upper plate (112h) and are movable along the four threaded rods (114).

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

8. 7. The liquid handling device of claim 6, wherein the pipette head comprises one or more pipette tip gripping mechanisms that couple to a boundary of the positive displacement pipette tip to capture or release the one or more positive displacement pipette tips.

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

10. the one or more positive displacement pipette tips (150) comprise a pipette tip and a pipette plunger (160); The pipette tip comprises: a boundary portion (210) and a pipette tip body (212); The boundary (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) comprises an opening (216) at a distal end of the fluid channel (214); The pipette plunger (160) disposed along the inside of the pipette tip; a plunger tip (236) having a plunger top (232), a plunger center (234), and a distal tip (238); The receptacle (222) is configured to receive the plunger center (234); the fluid channel (214) is configured to receive the distal tip (238); 6. The liquid handling device of claim 5, wherein the one or more pipette tip gripping mechanisms (130) are zero insertion force pipette gripping mechanisms.

11. one or more pipette plunger gripping mechanisms (140) are provided in the central portion of the pipette head (110); 11. The liquid handling device of claim 10, wherein each of the one or more pipette plunger gripping mechanisms (140) is coupled to the pipette plunger (160) of each of the one or more positive displacement pipette tips (150).

12. further comprising a set of zero insertion force pipette plunger gripping mechanisms; 11. The liquid handling device of claim 10, wherein one of the one or more motors (116) is used to control a set of the zero insertion force pipette plunger gripping mechanisms.

13. one of the one or more motors (116) is a gripper plunger motor; one of the one or more timing belts (118) is a gripper plunger timing belt; 13. The liquid handling apparatus of claim 12, wherein the gripper plunger motor and the gripper plunger timing belt are configured to move one or more of the plurality of plates (112) in a direction away from or towards the lower plate (112a).

14. Further comprising a pipette plunger (160); 7. The liquid handling device of claim 6, wherein the one or more motors (116) are used to control the pipette plunger (160).

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; 15. The liquid handling apparatus of claim 14, wherein 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 or towards the lower plate (112a).

16. 12. The liquid handling device of claim 11, wherein said one or more pipette plunger gripping mechanisms (140) are one or more zero insertion force pipette plunger gripping mechanisms.

17. each of the one or more zero insertion force pipette plunger gripping mechanisms includes a plunger collet (400) and a pipette plunger locking mechanism (450); 17. The liquid handling device of claim 16, wherein the plunger collet (400) includes a shaft portion and a collet chuck portion for fitting around the plunger top (232) of the pipette plunger (160).

18. 18. The liquid handling device of claim 17, wherein the collet chuck portion is a segmented band or sleeve for fitting around the plunger top (232) of the pipette plunger (160).

19. 1. A method of aspirating and dispensing a liquid, comprising: (a) providing a liquid handling instrument comprising an instrument housing having an instrument deck (182), a pipette head (110) disposed above said instrument deck (182), and a tray (183) removable from said instrument deck (182) configured to hold three or more microplates (185); The removable tray (183) has a unique ID; the equipment 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 liquids; 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, a pipette plunger corresponding to the pipette tip, The method of aspirating and dispensing liquid further comprises: (b) scanning the unique ID with the camera and confirming the presence or absence of the one or more positive displacement pipette tips (150); (c) gripping one or more pipette plungers with said one or more pipette plunger gripping mechanisms (140); (d) gripping one or more available positive displacement pipette tips with the one or more pipette tip gripping mechanisms (130) based on the scan; (e) performing an aspirating and / or dispensing operation using the pipette head; (f) combining the three or more microplates on the removable tray (183) with a protocol corresponding to the removable tray (183).

Images