Pipette operating head for liquid dispensing device

Abstract

A pipetting head for a liquid dispensing apparatus is provided. The pipetting head has a pipette tip clamping mechanism and a plunger clamping mechanism. The pipette tip clamping mechanism and the plunger clamping mechanism each comprise a mounting plate having a plurality of mounts, a clamping plate having a plurality of clamping members, each associated with one of the mounts, and a drive mechanism comprising an actuator operable to cause relative movement axially between the clamping plate and the mounting plate to selectively engage the clamping mechanism. The pipetting head further comprises a drive actuator operable, in use, to move the plunger clamping mechanism axially into or away from the plate of the pipette tip clamping mechanism to aspirate or dispense liquid. The drive actuator is configured to operate independently of the pipette tip clamping drive mechanism and the plunger clamping drive mechanism.

Description

Technical Field

[0001] The present invention relates to a pipette operating head for a liquid dispensing device, particularly to a pipette operating head having a pipette tip tightening mechanism and a plunger tightening mechanism. By the pipette tip tightening mechanism and the plunger tightening mechanism, a pipette having a pipette tip and a plunger can be firmly attached to the pipette operating head.

Background Art

[0002] It is known to use a pipette for sucking or dispensing a liquid sample.

[0003] It is also known to use a pipette having a plunger provided on a pipette tip. A typical pipette, known as a "volumetric" pipette, uses a plunger or piston to suck or dispense a liquid either by direct contact with the sample liquid or through a small air gap. In use, the pipette tip and the plunger are attached to the pipette operating head of a liquid dispensing device. The pipette operating head moves the plunger relative to the tip and sucks or dispenses the liquid from the opening at the distal end of the pipette tip. Such pipettes are used in automated machines and can improve the accuracy and reproducibility of pipette operation movements.

[0004] The inventors have identified several problems with the way pipettes are connected to known pipette operating heads for liquid dispensing devices.

[0005] An improved pipette operating head is needed.

Summary of the Invention

[0006] A first aspect of the present invention is a pipette operating head for a liquid dispensing apparatus for use with a plurality of pipettes, each having a pipette tip and a plunger provided within the pipette tip, wherein the pipette operating head comprises: a pipette tip tightening mechanism for connecting to and tightening the pipette tips of the plurality of pipettes during use; a plunger tightening mechanism for connecting to and tightening the plungers of the plurality of pipettes during use, the pipette tip tightening mechanism comprising: a pipette tip mounting plate having a plurality of pipette tip mounts, each configured to connect to one of the pipette tips during use; a pipette tip tightening plate having a plurality of pipette tip tightening members, each associated with one of the plurality of pipette tip mounts; and a pipette tip tightening drive comprising an actuator operable to selectively engage the pipette tip tightening mechanism by causing relative movement between the pipette tip tightening plate and the pipette tip mounting plate in the axial direction and moving the pipette tip tightening mechanism between a clamped position and a released position. A pipette operating head is provided, comprising a plunger clamping mechanism comprising: a plunger mounting plate having a plurality of plunger mounts, each configured to couple with one of the plungers during use; a plunger clamping plate having a plurality of plunger clamping members, each associated with one of the plurality of plunger mounts; and a plunger clamping drive mechanism having an actuator operable to selectively engage the plunger clamping mechanism by causing relative movement between the plunger clamping plate and the plunger mounting plate in the axial direction and moving the plunger clamping mechanism between a clamped position and a released position, wherein the pipette operating head further comprises a drive actuator operable to move the plunger clamping mechanism axially toward or away from the plate of the pipette tip clamping mechanism during use to aspirate or dispense liquid, the drive actuator being configured to operate independently of the pipette tip clamping drive mechanism and the plunger clamping drive mechanism.

[0007] This provides a very compact configuration in which a large number of pipettes can be precisely and securely mounted to the pipette operating head. This is particularly useful in liquid dispensing devices intended for use with standard 384-well plates, as the compact configuration provides 384 mounting collars and locking members, allowing 384 pipettes to be held in a 16x24 matrix. This allows for aspirating liquid from or dispensing liquid into a conventional 384-well plate in a single operation. As used herein, the terms “clamping” and “clamp” refer to a configuration in which a pipette tip or plunger, or both, is mounted in place and locked to prevent accidental removal. This is in contrast to configurations in which the pipette tip or plunger is mounted without locking, for example, using an interference fit or snap-fit ​​connection in which the pipette tip or plunger can be easily removed by axial pulling. The tightening configuration can also improve the accuracy of aspiration and dispensing operations by preventing small relative movements that may occur between the pipette operating head and the plunger or pipette tip.

[0008] Furthermore, by providing a drive actuator that operates independently for dispensing or aspiration operations, a wider variety of plunger speeds can be obtained, allowing the pipette operating head to be precisely controlled in both contact and non-contact dispensing modes. This contrasts with some known liquid processing devices in which the pipette tip and plunger are coupled to a plate that is positioned along a common series of threaded rods and moves relatively slowly relative to each other along the common rods.

[0009] An independently operated drive actuator allows the plunger clamping mechanism, and consequently any plunger attached thereto, to move relative to the pipette tip clamping mechanism, enabling aspiration and dispensing operations independently of the mechanisms operating the pipette tip clamp and plunger clamp. The distance the plunger travels relative to the dispensing shot is short, for example, in the range of less than 1 mm. Therefore, a high level of acceleration / deceleration is required to reach the target velocity for non-contact dispensing. The independently operated drive actuator can be configured to accelerate and decelerate the plunger clamping mechanism at a sufficiently fast speed for both non-contact and contact dispensing, which are possible using the same mechanism.

[0010] The term "independently operated" refers to a configuration in which the drive actuator has a separate drive mechanism from those of the pipette tip tightening drive mechanism and the plunger tightening drive mechanism. This allows the drive mechanism to be set according to desired acceleration and deceleration characteristics for dispensing and aspiration operations, rather than conforming to desired tightening characteristics or forming a compromise between those characteristics. This is in stark contrast to a configuration in which the pipette tip and plunger are mounted on a plate arranged along a common threaded rod. In this configuration, all drive mechanisms, including the drive mechanism of the actuator controlling the dispensing operation, must operate with the same thread pitch. In this configuration, it may also be necessary for the movement of the plate to be synchronized in order to perform the dispensing operation. This may require more complex control to ensure accurate dispensing and prevent clogging.

[0011] The drive actuator may be an indirect drive actuator comprising, for example, a motor-driven belt or chain that moves a plunger clamping mechanism relative to a pipette tip clamping mechanism. Preferably, the drive actuator is a direct drive actuator. As used herein, the term “direct drive actuator” refers to a drive mechanism comprising a motor that is directly coupled to the plunger clamping mechanism or coupled to the plunger clamping mechanism via a rotationally rigid coupling. Throughout this specification, the term “direct drive actuator” is used to refer to both directly coupled configurations and configurations in which the motor is coupled to the plunger clamping mechanism via a rotationally rigid coupling. The use of a direct drive actuator minimizes rotational movement between the plunger clamping mechanism and the motor. This allows the movement of the plunger clamping mechanism to be started and stopped quickly and precisely. This is in contrast to an indirect drive mechanism in which the motor is coupled to the plunger via one or more belts or chains.

[0012] The drive actuator may be a ball screw actuator comprising a motor fixed in association with the chassis of the pipette operating head, and a ball screw that connects the motor to the plunger tightening mechanism and moves the plunger tightening mechanism axially relative to both the chassis and the pipette tip tightening mechanism.

[0013] Direct drive configurations, for example via ball screws, provide higher levels of acceleration / deceleration for heavy loads than belt drive systems, thus enabling non-contact dispensing of small amounts of liquid samples. Furthermore, direct drive configurations offer higher positional accuracy and reproducibility than comparable belt drive mechanisms. This can significantly impact dispensing performance.

[0014] The plunger clamping drive mechanism preferably comprises a plurality of guide rods, by which the plunger clamping plate is connected to the plunger mounting plate, and the plunger clamping plate and the plunger mounting plate are axially movable relative to each other along the plurality of guide rods by actuators of the plunger clamping mechanism. The plurality of guide rods are preferably axially movable together with the plunger clamping plate and the plunger mounting plate by drive actuators toward and away from the plate of the pipette tip clamping mechanism. This helps to keep the plates parallel. For example, the plurality of guide rods may comprise four guide rods positioned at the four corners of the plunger clamping plate and the plunger mounting plate. In other embodiments, the plunger clamping drive mechanism may comprise a plurality of actuators positioned at different locations around the outer edge of the plunger clamping mechanism and configured to operate together.

[0015] The plunger clamping drive mechanism may include any suitable mechanism for causing axial relative movement between the plunger clamping plate and the plunger mounting plate when the actuator of the plunger clamping drive mechanism is operated. For example, the plunger clamping drive mechanism may include a screw shaft connected to the actuator of the plunger clamping drive mechanism, extending through a screw opening fixed in association with the plunger mounting plate and one of the plunger clamping plates, such that when the screw shaft is rotated by the actuator, it causes axial relative movement between the plunger clamping plate and the plunger mounting plate. The screw output shaft of the plunger clamping drive mechanism may be movable axially independently of the pipette tip clamping mechanism.

[0016] The entire plunger clamping drive mechanism may be axially movable together with the plunger clamping plate and the plunger mounting plate by a drive actuator, both toward and away from the plate of the pipette tip clamping mechanism.

[0017] The pipette tip tightening drive mechanism comprises a pipette tip mounting plate and a screw shaft connected to an actuator of the pipette tip tightening drive mechanism, extending through a screw opening fixed in association with one of the pipette tip tightening plates, wherein the screw output shaft, when rotated by the actuator, causes axial relative movement between the pipette tip tightening plate and the pipette tip mounting plate. The screw output shaft of the pipette tip tightening drive mechanism may be movable axially independently of the plunger tightening mechanism.

[0018] The pipette tip clamping plate is preferably positioned below the pipette tip mounting plate. The pipette tip clamping plate may be the lowest plate on the pipette operating head. As used herein, the terms “low,” “below,” and “lowest” refer to the normal position of the pipette operating head in use.

[0019] Multiple pipette tip clamping members may comprise multiple sleeves that define the clamping area. Multiple pipette tip clamping members may be coaxial with multiple pipette tip mounts. Multiple pipette tip clamping members may surround multiple pipette tip mounts when the pipette tip clamping mechanism is engaged.

[0020] Multiple sleeves may be defined by one or more separate components fixed to the pipette tip clamping plate. In one preferred embodiment, the multiple sleeves are defined by openings in the pipette tip clamping plate itself.

[0021] Each of the multiple pipette tip mounts may have a radially extending mechanism on its outer surface configured to form half of a snap-fit ​​connection. The clamping area of ​​each of the multiple sleeves may be axially adjacent to the radially extending mechanism on the outer surface of its associated pipette tip mount when the pipette tip clamping mechanism is in the clamped position. The clamping area of ​​each of the multiple sleeves may be axially offset from the radially extending mechanism on the outer surface of its associated pipette tip mount when the pipette tip clamping mechanism is in the released position.

[0022] Multiple plunger mounts may include multiple axially extending sleeves. Multiple plunger clamping members may include multiple axially extending clamping rods that extend inside the multiple axially extending sleeves when the plunger clamping mechanism is in the clamped position.

[0023] Each of the multiple axially extending sleeves may have a radially extending mechanism on its inner surface configured to form half of a snap-fit ​​connection. The clamping area of ​​each of the multiple clamping rods may be axially adjacent to the radially extending mechanism on the inner surface of its associated plunger mount when the plunger clamping mechanism is in the clamped position, and may be axially offset from the radially extending mechanism on the inner surface of its associated plunger mount when the plunger clamping mechanism is in the released position.

[0024] The pipette operating head may further include at least one pipette comprising: a pipette tip having a distal end with a dispensing opening and a proximal end with a tip connector portion for connecting the pipette tip to the pipette tip coupling mechanism of the pipette operating head during use; and a plunger having a distal end positioned inside the pipette tip and a proximal end with a hollow plunger connector portion for connecting the plunger to the plunger coupling mechanism of the pipette operating head during use, wherein the tip connector portion has a semicircular connector configured on its inner surface to form a snap-fit ​​connection with a mechanism extending radially from one of the outer surfaces of a plurality of pipette tip mounts. The chip clamping mechanism has a radially extending mechanism and is configured to elastically deflect radially outward from a stationary position having a first outer diameter to an expanded position having a second outer diameter that is larger than the first outer diameter by at least the radial range of the mechanism extending radially to the chip clamping mechanism. Each clamping area of ​​the multiple sleeves of the chip clamping mechanism has an inner diameter that is greater than or equal to the first outer diameter of the chip clamping mechanism and less than the second outer diameter of the chip clamping mechanism. When the chip clamping mechanism is in the clamped position, the clamping area prevents the chip clamping mechanism from deflecting to the expanded position, thereby preventing the snap-fit ​​connection from being released.

[0025] The pipetting operation head has a pipette tip having a distal end with a dispensing opening and a proximal end having a tip connector portion for connecting a pipette tip to the pipette tip connection mechanism of the pipetting operation head during use; and a plunger having a distal end positioned inside the pipette tip and a proximal end having a hollow plunger connector portion for connecting a plunger to the plunger connection mechanism of the pipetting operation head during use. The pipetting operation head may further include at least one pipette. The plunger connector portion has, on its outer surface, a radially extending mechanism that forms a snap-fit connection with a radially extending mechanism on the inner surface of one of a plurality of plunger mounts. The plunger connector portion is configured to elastically deflect in the radially inward direction from a stationary position having a first inner diameter to a pushed-in position having a second inner diameter that is smaller than the first inner diameter by at least the radial extent of the radially extending mechanism of the plunger connector portion. Each clamping region of each of the plurality of axially extending clamping rods has an outer diameter that is less than or equal to the first inner diameter of the plunger connector portion and greater than the second inner diameter of the plunger connector portion. When the plunger clamping mechanism is in the clamped position, the clamping region prevents the plunger connector portion from deflecting to the pushed-in position, thereby releasing the snap-fit connection.

[0026] According to a second aspect of the present invention, there is provided a liquid dispensing device comprising a body having a microplate receiving area; and a pipetting operation head as described in the first aspect, the pipetting operation head being positioned above the microplate receiving area.

[0027] Further features and advantages of the present invention will be further described below by way of example with reference to the accompanying drawings.

Brief Description of the Drawings

[0028] [Figure 1] It is a perspective view of a liquid dispensing device having a pipetting operation head according to the present invention. [[ID=十七]] [Figure 2]Perspective view of the pipetting operation head according to the present invention. [Figure 3] Side view of the pipetting operation head of FIG. 2. [Figure 4] Perspective view of the pipetting operation head of FIG. 2, with various parts omitted for clarity, showing the pipette tip clamping mechanism and the plunger clamping mechanism. [Figure 5] Cross-sectional view of the figure of FIG. 4, showing the plates of the pipette tip clamping mechanism and the plunger clamping mechanism. [Figure 6] Enlarged cross-sectional perspective view of the figure of FIG. 4, showing the plate of the pipette tip clamping mechanism. [Figure 7] Enlarged cross-sectional view of the plate of the pipette tip clamping mechanism of the pipetting operation head of FIG. 2, showing the pipette tip mounting sleeve. [Figure 8] Enlarged cross-sectional perspective view of the pipetting operation head of FIG. 2, with various parts omitted for clarity, showing the plate of the plunger clamping mechanism in more detail. [Figure 9] Enlarged cross-sectional view of the plate of the plunger clamping mechanism of the pipetting operation head of FIG. 2, showing the plunger mount and the clamping member. [Figure 10] Perspective view of the plunger clamping mechanism of the pipetting operation head of FIG. 2, with the plunger mounting plate omitted for clarity, showing the plunger clamping plate in the clamping position. [Figure 11] Perspective view of the plunger clamping mechanism of the pipetting operation head of FIG. 2, with the plunger mounting plate omitted for clarity, showing the plunger clamping plate in the release position. [Figure 12] Front cross-sectional view of the pipetting operation head of FIG. 2. [Figure 13] Side cross-sectional view of the pipetting operation head of FIG. 2. [Figure 14] Cross-sectional view of a pipette for use with the liquid dispensing system of FIG. 1. [Figure 15] Figure 14 is a perspective view of the pipette tip and plunger of the pipette, with the plunger removed from the pipette tip. [Figure 16] Figure 14 is an enlarged cross-sectional view of the pipette, showing the tip connector and plunger connector sections in more detail. [Figure 17] Figure 14 is a perspective view of the pipette showing the tip mount and associated tip clamp of the pipette tip tightening mechanism. [Figure 18] This is an enlarged cross-sectional view of parts of the pipette tip tightening mechanism and plunger tightening mechanism at various stages of pipette coupling. [Figure 19] This is an enlarged cross-sectional view of parts of the pipette tip tightening mechanism and plunger tightening mechanism at various stages of pipette coupling. [Figure 20] This is an enlarged cross-sectional view of parts of the pipette tip tightening mechanism and plunger tightening mechanism at various stages of pipette coupling. [Figure 21] This is an enlarged cross-sectional view of parts of the pipette tip tightening mechanism and plunger tightening mechanism at various stages of pipette coupling. [Figure 22] This is an enlarged cross-sectional view of parts of the pipette tip tightening mechanism and plunger tightening mechanism at various stages of pipette coupling. [Modes for carrying out the invention]

[0029] Figure 1 shows a liquid dispensing device 10 for use with a number of volumetric pipettes 1010. The device 10 comprises a body 12 having a microplate receiving area or deck 14 and a pipette operating head 100 positioned above the microplate receiving area 14. The microplate receiving area 14 has a substantially horizontal top surface 16 positioned to receive laboratory microplates. The receiving area 14 may be located on a height-adjustable support structure 18, which can change the height of the microplate receiving area 14 as needed. The receiving area 14 may be configured to hold laboratory microplates in place. For example, the top surface 16 of the receiving area 14 may have one or more indentations (not shown) positioned to receive the microplate and prevent lateral movement of the microplate relative to the receiving area 14. The device 10 is typically used in the orientation shown in Figure 1, with gravity holding the product in the wells of the microplate. The axis labeled Z in Figure 1 therefore represents the upward direction, and gravity acting in the opposite direction holds the product in the wells of the microplate. References to upward and downward directions or axial directions therefore refer to movement along the axis labeled Z in Figure 1. References to lateral or transverse directions refer to movement in the directions labeled X and Y in Figure 1. References to vertical directions or height also therefore refer to dimensions or movement along the axis labeled Z in Figure 1. The pipette operating head 100 is configured to hold a number of pipettes, as shown below in relation to Figures 2 to 9, and is movable in relation to the deck 14, and may bring pipettes attached to the pipette operating head 100 close to a microplate supported on the deck 14 so that liquid is aspirated from or dispensed into the wells of the microplate.

[0030] Figures 2 to 4 show the pipette operating head 100 in more detail. The pipette operating head comprises a head chassis 101 having an upper head chassis portion 102 and a lower head chassis portion 103, both of which are bolted together to form the body of the pipette operating head 100. The upper and lower head chassis portions are connected to the body of the device by a chassis support plate 104. The chassis support plate 104 can preferably move the entire pipette operating head 100 in the X, Y, and Z directions relative to the receiving area of ​​the device in a conventional manner using one or more head actuators (not shown). The pipette operating head 100 further comprises a pipette tip tightening mechanism 120 for connecting or joining and tightening the pipette tips of multiple volumetric pipette tips during use, and a plunger tightening mechanism 140 for connecting or joining and tightening the plungers of multiple volumetric pipettes during use. When mounted on the upper head chassis 102, the direct drive actuator 160 can be operated during use to move the plunger clamping mechanism 140 axially toward or away from the plate of the pipette tip clamping mechanism, thereby aspirating or dispensing liquid. The direct drive actuator 160 is fixed in association with the head chassis 101 and extends between the head chassis 101 and the plunger clamping mechanism 140.

[0031] The pipette tip tightening mechanism 120 comprises a pipette tip mounting plate 121, a pipette tip tightening plate 125 positioned below the pipette tip mounting plate 121, and a pipette tip tightening drive mechanism 130 that can be operated to cause relative movement between the pipette tip mounting plate 121 and the pipette tip tightening plate 125. In this example, the pipette tip mounting plate 121 is provided as part of the lower head chassis, and the pipette tip tightening drive mechanism 130 is configured to move the pipette tip tightening plate 125 toward and away from the fixed pipette tip mounting plate 121, thereby selectively engaging the pipette tip tightening mechanism 120.

[0032] As is most commonly seen in Figures 5 to 7, the pipette tip mounting plate 121 has a number of openings 122 that extend axially through the thickness of the pipette tip mounting plate 121. When fixed within each opening 122, the pipette tip mount 123 extends downward axially from the plate 121 and is configured to connect with one of the pipette tips during use. Each pipette tip mount 123 is in the form of a tubular tip mount sleeve held in one of the number of openings 122. In this example, each opening 122 has a limiting portion having a diameter less than the outer diameter of the tip mount sleeve 123. The limiting portion prevents the tip mount sleeve 123 from being pushed upward through the tip mounting plate when the tip mount sleeve is first inserted into the pipette tip. The upper end of the tip mount sleeve 123 preferably has an inwardly tapered end face to assist in the insertion of the plunger clamping mechanism components into the hole in the tip mount sleeve 123. The lower end of the tip mount sleeve 123 preferably has a tapered end face on the outside to assist in inserting the lower end of the tip mount sleeve onto the pipette tip. The outer surface of each tip mount sleeve 123 is provided with a radially extending mechanism configured to form half of a snap-fit ​​connection with a mechanism molded to correspond to the inner surface of the pipette tip. In this example, the radially extending mechanism is in the form of an annular groove 124 surrounding the tip mount sleeve 123.

[0033] The pipette tip clamping plate 125 has a number of openings 126 that extend axially through the thickness of the pipette tip clamping plate 125. The number and position of the openings 126 correspond to the number of openings 122 of the pipette tip mounting plate 121. The pipette tip clamping plate 125 further comprises a number of pipette tip clamping members 127, each associated with one of a plurality of pipette tip mounts 123. In this example, the number of pipette tip clamping members 127 are provided in the form of a number of clamp sleeves 127 defined by the region of the pipette tip clamping plate 125, directly surrounding the openings 126 defined within the pipette tip clamping plate 125. Each clamp sleeve 127 has a clamping region 128 having an inner diameter larger than the outer diameter of its respective tip mount sleeve. Thus, as shown in Figure 7, when the pipette tip clamping mechanism is engaged, a small gap is provided between the outer surface of the tip mount sleeve 123 and the inner surface of the clamping region 128.

[0034] Each clamp sleeve may have a substantially constant inner diameter. Alternatively, each clamp sleeve may have regions with different inner diameters, as shown in Figure 7. In the example, each clamp sleeve 127 has a narrow region 129A towards its upper end and a tapered region 129B at its bottom end. The inner diameter of the clamp sleeve 127 decreases in the tapered region 129B from the lowest tip to the clamping region 128. This configuration allows one or more pipette tips to be semi-locked in the pipette tip clamping plate 125 by positioning the tapered region 129B of the clamp sleeve 127 adjacent to a recess 124 on the outer surface of the tip mounting sleeve 123. This can facilitate the picking of a portion of multiple tips from the tip box. Once the picked tip is lifted above the multiple unpicked tips, the picked tip can then be clamped in place by moving the pipette tip clamping plate 125 to the clamping position. A small gap may be provided between the narrow area 129A of the clamp sleeve 127 and the outer surface of the tip mount 123. This can help minimize the force required to move the tip clamping plate 125 axially and facilitate the smooth operation of the pipette tip clamping mechanism.

[0035] As is most commonly seen in Figures 2 to 4, the pipette tip tightening drive mechanism 130 comprises a rotary actuator 131 and a screw shaft 132 operably connected to the output shaft of the rotary actuator 131. The rotary actuator 131 is mounted on a tip motor support plate 135, which is fixed in association with the pipette tip mounting plate 121. In this example, the tip motor support plate 135 is mounted on the outer surface of the lower head chassis portion 103. The tip motor support plate 135 is positioned above an expansion tab 133, which is fixed in association with the pipette tip tightening plate. The expansion tab 133 has a screw opening 133A through which the screw shaft 132 extends. The pipette tip tightening mechanism 130 further comprises a plurality of guide rods 134 connecting the pipette tip mounting plate 121 and the pipette tip tightening plate 125. In the illustrated embodiment, the guide rod 134 is fixed in association with the pipette tip mounting plate 121, each extending axially through the corresponding opening 137 in the pipette tip clamping plate 125. Naturally, it will be understood that the guide rod may be evenly fixed in association with the pipette tip clamping plate and extend through openings in the pipette tip mounting plate or any other part of the pipette operating head fixed in association with the pipette tip mounting plate.

[0036] When the rotary actuator 131 is operated, the screw shaft 132 rotates within the screw opening 133A, moving the expansion tab 133 toward or away from the tip motor support plate 135, thereby moving the pipette tip clamping plate 125 axially toward or away from the pipette tip mounting plate 121. The direction of movement is determined by the direction of rotation of the actuator 131. As the pipette tip clamping plate 125 moves axially toward or away from the pipette tip mounting plate 121, the guide rod 134 helps maintain the parallel relationship between the pipette tip mounting plate 121 and the pipette tip clamping plate 125.

[0037] As best seen in Figures 5 and 8-11, the plunger clamping mechanism 140 comprises a plunger mounting plate 141, a plunger clamping plate 145 positioned on the plunger mounting plate 141, and a plunger clamping drive mechanism 150 operable to cause relative movement between the plunger mounting plate 141 and the plunger clamping plate 145. The plunger clamping mechanism 140 further comprises a plunger clamp motor mount 155 positioned on both the plunger mounting plate 141 and the plunger clamping plate 145. The actuator motor of the plunger clamping drive mechanism 150 is supported on the plunger clamp motor mount 155. The plunger mounting plate 141 and the plunger clamp motor mount 155 are fixed in relation to each other. In this example, the plunger mounting plate 141 and the plunger clamp motor mount 155 are provided as separate parts that are joined together to facilitate manufacturing and assembly. In other examples, the plunger mounting plate 141 and the plunger clamp motor mount 155 may be supplied as a single component. The plunger clamping drive mechanism 150 is configured to move the plunger clamping plate 145 toward and away from the plunger mounting plate 141, and to selectively engage the plunger clamping mechanism 140.

[0038] As best seen in Figures 8 and 9, the plunger mounting plate 141 has a number of openings 142 that extend axially through the thickness of the plunger mounting plate 141. Fixed within each opening 142, plunger mounts 143 extend downward axially from the plate 141 and are configured to connect with one of the plungers during use. Each plunger mount 143 is in the form of a tubular plunger mount sleeve held in one of the number of openings 142. In this example, each plunger mount 143 has an outer diameter larger than the diameter of the opening 142 and has a shoulder that abuts against the lower surface of the plunger mount plate 141. The shoulder helps to set the height of the plunger mount sleeve 143 when it is first inserted into the opening 142 in the plunger mount plate 141. The lower end of the tip mount sleeve 143 preferably has an inwardly tapered end face to assist in inserting the plunger into the hole of the plunger mount sleeve 143. Each plunger mount sleeve 143 is provided with a radially extending mechanism on its inner surface, configured to form half of a snap-fit ​​connection with a correspondingly molded mechanism on the outer surface of the plunger. In this example, the radially extending mechanism is in the form of an annular groove 144 on the inner surface of the plunger mount sleeve 143 toward the lower end.

[0039] The plunger clamping plate 145 has a number of recesses or openings 146 that extend axially. The number and positions of the openings 146 of the plunger clamping plate 145 correspond to the number of openings 142 of the plunger mounting plate 141. The number of openings 146 of the plunger clamping plate 145 may also correspond to the number of openings 122 and 126 of the pipette tip clamping mechanism. The plunger clamping plate 145 further comprises a number of plunger clamping members 147, each associated with one of a plurality of plunger mounts 143. The number of plunger clamping members are provided in the form of a number of clamping rods 147 that extend axially from the plunger clamping plate 145 and into holes defined within the plunger mount sleeves 143. Each clamping rod 147 has an expanding head 148 at its lower end that extends from a narrower neck region 149A. The expanding head 148 has an outer diameter less than the inner diameter of the plunger mount sleeve 143. In this way, when the plunger clamping mechanism is engaged, a small gap is provided between the outer surface of the expanding head 148 and the inner surface of the plunger mount sleeve 143. The neck 149A has an outer diameter less than the outer diameter of the expanding head 148. Preferably, each clamping rod 147 also has a spindle 149B having an outer diameter substantially the same as the inner diameter of the area of ​​the plunger mount sleeve 143 in which it is located. As the plunger clamping plate 145 moves axially up and down relative to the plunger mount plate 141, the spindle 149B moves axially along the hole in the plunger mount 143.

[0040] As best seen in Figure 13, the plunger clamping drive mechanism 150 comprises a rotary actuator 151 and a screw shaft 152 operably connected to the output shaft of the rotary actuator 151. The rotary actuator 151 is mounted on a plunger clamp motor mount 155 and is therefore fixed in association with the plunger mounting plate 141. The rotary actuator 151 is positioned above an opening 153 in the plunger clamping plate 145, which has a screw opening 153A, and the screw shaft 152 extends through the screw opening 153A. The plunger clamping mechanism 150 further comprises a plurality of guide rods 154 that operably connect the plunger mounting plate 141 and the plunger clamping plate 145. In the illustrated embodiment, the guide rods 154 are fixed in association with the plunger clamping plate 145 and each extends axially into a corresponding hole in a cylindrical housing 157 extending from the lower surface of the plunger clamp motor mount 155. Naturally, it will be understood that the guide rod may extend through an opening in the plunger clamping plate 145 or any other part of the pipette operating head that is evenly fixed in relation to the plunger mounting plate 141 and fixed in relation to the plunger clamping plate 145.

[0041] When the rotary actuator 151 is operated, the screw shaft 152 rotates within the screw opening 153A, moving the plunger clamping plate 145 axially toward or away from the plunger mounting plate 141. As the plunger clamping plate 145 moves axially toward or away from the plunger mounting plate 141, the guide rod 154 helps maintain the parallel relationship between the plunger mounting plate 141 and the plunger clamping plate 145. The direction of movement is determined by the direction of rotation of the actuator 151. This can be seen by looking at Figures 10 and 11, in which the plunger mounting plate 141 is omitted for clarity. In Figure 10, the guide rod 154 is extended from the cylindrical housing 157 so that the plunger clamping plate 145 and its support plate 156 are in a low position away from the lower surface of the plunger clamp motor mount 155 and close to the upper surface of the plunger mounting plate (not shown in Figures 10 and 11). This is the clamping position. In Figure 11, the guide rod 154 is retracted into the cylindrical housing 157 so that the plunger clamping plate 145 and its support plate 156 are away from the plunger mounting plate 141 and move axially toward the plunger clamp motor mount plate 155. This is the released position. The relative movement between the plunger clamping plate 145 and the plunger mounting plate 141 allows the plunger clamping mechanism 140 to move to any position between the engaged state, where the plunger is clamped in the appropriate position, and the released or "released" position or state, where the plunger is connected axially to the plunger mount or detached from the plunger mount. The plunger tightening mechanism 140 may be configured to move beyond the tightening position to the plunger mounting plate 141, reaching a removal state.In this position, the enlarged head 148 of the clamping rod 147 is axially aligned with a radially extending mechanism on the inner surface of the plunger mounting sleeve 143, which is instead aligned with the narrower neck portion 149A of the clamping rod. This allows the top of the plunger, i.e., the plunger connector portion, to bend inward. Further downward movement of the clamping plate 145 and the clamping rod 147 pushes the plunger downward, releasing it from the snap-fit ​​connection with the plunger mounting sleeve. When the pipette tip clamping plate 125 is also in the released position, further downward movement of the clamping rod using the plunger clamping drive mechanism presses the plunger against one or more inner surfaces of the pipette tip, for example, the area around the opening at the distal end of the pipette tip, pushing the pipette tip out of the tip clamping mechanism. This removes the entire pipette assembly from the pipette operating head. Alternatively, a direct-drive actuator 160 may be used to move the clamping rod and plunger together downward, pressing them against the pipette, thereby removing the pipette tip from the device. In this removal mode, the plunger may remain in the device after the pipette tip has been removed.

[0042] Figures 12 and 13 show the direct-drive actuator 160 in more detail. The direct-drive actuator 160 comprises an actuator motor 161 mounted on the top surface of the upper head chassis 102. The output shaft of the actuator motor 161 is coupled to a screw rod 162 connected to a ball screw actuator nut 163. The output shaft of the actuator 161 may be integral with the screw rod 162 or fixed to the screw rod 162. In the illustrated embodiment, the output shaft is coupled to the screw rod by a rotationally rigid coupling in the form of a bellows coupling 161A. The bellows coupling 161A allows relative axial movement between the output shaft and the screw shaft 162, but prevents, or substantially prevents, relative rotation between the two parts. The nut 163 is fixed to a ball screw mount 164, and the two move simultaneously. In the illustrated embodiment, the ball screw mount 164 is fixed to a plunger clamp motor mount 155 at the upper end of a plunger clamping mechanism 140. In other embodiments, the ball screw mount 164 may be integrated with the plunger clamp motor mount 155. The direct drive actuator 160 then extends between the head chassis 101 and the plunger clamping mechanism 140.

[0043] When the actuator motor 161 is operated, the entire plunger clamping mechanism 140 moves axially along the guide rod 165 toward or toward the pipette tip clamping mechanism 120, depending on the direction of rotation of the actuator motor 161. The guide rod 165 is not threaded. The plunger mounting plate 141 has a plurality of guide sleeves 166 (see Figure 8), through which the guide rod 165 extends. When the actuator motor 161 is operated, the guide sleeves 166 slide along the outer surface of the guide rod. In this way, the plunger clamped by the plunger clamping mechanism 140 can be abruptly accelerated toward the pipette tip through which the plunger extends, regardless of any limitations imposed by the operating speed of the clamping mechanism. This allows the device to be used in both non-contact dispensing mode (also known as jetting – liquid is dispensed from the pipette slightly away from the target so that the droplet leaves the tip before contact with the target) and contact dispensing mode (a droplet forms on the pipette tip and settles upon contact with the target). For non-contact dispensing, the liquid sample must travel at a sufficiently fast speed to leave the tip. The distance traveled by the plunger relative to the dispensing shot is short, for example, in the range of 1 mm or less. Consequently, a high level of acceleration / deceleration is required to reach the target velocity for non-contact dispensing. For example, a direct-drive configuration via a ball screw provides a higher level of acceleration / deceleration for heavier loads than a belt-driven system, thus enabling non-contact dispensing of small amounts of liquid sample. Furthermore, a direct-drive configuration can provide higher positional accuracy and reproducibility than an equivalent belt-drive mechanism. This can significantly impact dispensing performance.

[0044] Figures 14 to 17 show pipette 1010 for use with the pipette operating heads shown in Figures 2 to 13. Pipette 1010 comprises a pipette tip 1100 and a plunger 1200.

[0045] The pipette tip 1100 may be a receptacle that receives and / or contains a sample fluid or sample liquid. The pipette tip 1100 may be configured to be inserted into or into a container of sample liquid. The pipette tip 1100 has a proximal end 1101 and a distal end 1102, the proximal end 1101 and the distal end 1102 defining a longitudinal axis 1001 extending between them. The pipette tip 1100 has an opening 1108 at its distal end 1102, as shown in Figure 15. The opening 1108 is at the distal end 1102, specifically at the outermost distal point of the pipette tip 1100, and may be defined by the inner wall surface 1111 of the pipette tip 1100. The opening 1108 may be any suitable shape, for example, elliptical, oval, or circular. The pipette tip 1100 has a fluid cavity 1109 that extends at least partially from the opening 1108 to the proximal end 1101. The fluid cavity may be configured to receive and / or hold a fluid, such as an air gap or sample liquid. The fluid cavity 1109 may be substantially elongated. The fluid cavity may be defined by the inner wall surface of the pipette tip 1100. The longitudinal axis 1001 may be a central axis around which the pipette tip 1100 and / or plunger 1200 are arranged. The longitudinal axis 1001 may define a central axis around which the pipette tip 1100 and / or plunger 1200 are arranged uniformly or symmetrically. The pipette tip 1100 and / or plunger 1200 may be configured such that the direction of aspiration and / or dispensing is aligned with the longitudinal axis 1001. The pipette tip 1100 may be substantially elongated and extend between its proximal end 1101 and distal end 1102. The pipette tip 1100 may be substantially or completely hollow. The pipette tip 1100 may contain or consist of a polymer material. The pipette tip 100 may contain or consist of a homogeneous material. The pipette tip 100 may contain or consist of a translucent or transparent material.

[0046] The pipette tip 1100 may comprise a series of parts, each having a different function, distinctive features, and / or different shape or dimensions. The pipette tip 1100 may comprise one or more of the following: a tip connector portion 1103, a central portion 1104, a support portion 1105, a body portion 1106, and a bridging portion 1107, as shown, for example, in Figure 15. From the proximal end 1101 to the distal end 1102, the parts may be arranged in the order of tip connector portion 1103, central portion 1104, support portion 1105, body portion 1106, bridging portion 1107, and end portion 1110. The fluid cavity 1109 may extend through one, more, or all of the parts of the pipette tip 1100. The plunger 1200 may extend through one, more, or all of the parts of the pipette tip 1100.

[0047] The tip connector section 1103 is configured to be connected to a liquid processing system, for example, by a snap-fit ​​connection. The tip connector section 1103 may comprise a divided tubular wall 1120 that can be defined by a plurality of flexible segments 1121. The flexible segments 1121 may be configured to elastically deflect radially outward, and the outer diameter of the proximal end 1101 of the pipette tip 1100 may increase from a first outer diameter where the flexible segments are not deflected and the tip connector section is in a stationary state, to a second outer diameter where the flexible segments are deflected radially outward and the tip connector section is in an expanded state. In the described embodiment, the tip connector section 1103 comprises four axially extending slits or slots 1122 in the tubular wall 1120 that divide into four flexible segments 1121. The tip connector section 1103 is provided with any number of axially extending slits 1122, which may define any number of flexible segments 1121, such as two, three, four, five, or six. The configuration of the flexible segments 1121 and slots 1122 allows the tip connector section to be expanded without requiring a large force to be applied to it. This reduces the insertion force required to engage the tip connector section 1103 with the pipette operating head.

[0048] The tip connector portion 1103 may further include one or more radially extending mechanisms 1123 on its inner surface, thereby enabling a pipette tip to be connected to a pipette operating head. The radially extending mechanisms on the inner surface of the tip connector portion 1103 may include projections extending radially inward and / or recesses or grooves extending radially outward. The radially extending mechanisms may extend circumferentially. In the described embodiment, the radially extending mechanisms on the inner surface of the tip connector portion 1103 include a partial annular rib 1123 protruding from the inner surface of the tip connector portion 1103. Preferably, the second outer diameter to which the tip connector portion expands is greater than the first outer diameter by at least the radial range of the radially extending mechanism 1123. The rib 1123 preferably has an angled upper and lower surface, and along the upper and lower surfaces, the inner diameter of the tip connector portion gradually increases from the rib 1123 to the upper and lower tip connector portions of the rib 1123. The angle of the upper surface may be selected according to the desired insertion force. The angle of the lower surface may be selected according to the desired withdrawal force. The upper or lower surface may each have an angle of 10 to 80 degrees from the axial direction of the pipette tip, for example, 20 to 70 degrees from the axial direction of the pipette tip, 30 to 60 degrees from the axial direction of the pipette tip, or 40 to 50 degrees from the axial direction of the pipette tip.

[0049] The central portion 1104 may be configured to center the plunger 1200 within the pipette tip 1100. The central portion 1104 may have an inner surface that can be tapered or conical in shape. The support portion 1105 may include one or more structural ribs or rings configured to reduce the flexibility of the pipette tip 1100 and / or improve its structural integrity. One or more ribs may extend on the outer surface of the pipette tip, for example, axially along at least a portion of the length between the proximal end 1101 and the distal end 1102, as is most commonly seen in Figure 16. The body portion 1106 may be substantially cylindrical and / or elongated. The body portion 1106 may have a substantially uniform inner and / or outer diameter. The body portion 1106 may extend along at least half the length of the pipette tip 1100. The main body 1106 may have an inner and / or outer diameter larger than any diameter of the end portion 1110. The bridge portion 1107 may be configured to bridge the main body 1106 to the end portion 1110. The bridge portion 1107 may define a gradual transition or step between the main body 1106 and the end portion 1110. The bridge portion 1107 may be substantially tapered, conical, and / or domed.

[0050] The plunger 1200 has a proximal end 1201 and a distal end 1202 and extends along the longitudinal axis 1101. The plunger 1200 is configured to extend at least partially into the end 1110 between the proximal end 1101 and the distal end 1102 of the pipette tip 1100. The plunger 1200 may be configured to extend substantially or completely into the end 1110 between the proximal end 1101 and the distal end 1102 of the pipette tip 1100. The plunger 1200 is movable toward and away from the opening 1108 to aspirate fluid or dispense fluid from the pipette tip 1100. The plunger 1200 may have an outer end wall surface 1212 configured to align with the inner wall surface 1111 of the pipette tip end 1110. The plunger 1200 may contain a polymer material or be made of a polymer material. The plunger 1200 may contain a homogeneous material or be made of a homogeneous material.

[0051] The plunger 1200 may comprise a series of parts, each having a different function, distinctive features, and / or different shape or dimensions. The plunger 1200 may comprise one or more of the plunger connector section 1203, the central section 1204, the body section 1206, and the sealing section 1207. From the proximal end 1201 to the distal end 1202, the parts may be arranged in the order of connector section 1203, central section 1204, body section 1206, sealing section 1207, and end section 1210.

[0052] The plunger connector portion 1203 is configured to be connected to a liquid handling system, for example, by a snap-fit ​​connection. The plunger connector portion 1203 may be configured to be fully received within the tip connector portion 1103 of a pipette tip 100. The plunger connector portion 1203 may comprise a divided tubular wall 1220 that can be defined by a plurality of flexible segments 1221. The flexible segments 1221 may be configured to elastically deflect radially inward, reducing the inner diameter of the proximal end 1201 of the plunger 1200 from a first inner diameter where the flexible segments are not deflected and the plunger connector portion is in a stationary state, to a second inner diameter where the flexible segments are deflected radially inward and the plunger connector portion is in a pressed state. In the described embodiment, the plunger connector portion 1203 comprises three axially extending slits or slots 1222 in the tubular wall 1220 that divide into three flexible segments 1221. The plunger connector portion 1203 may have any appropriate number of axially extending slits 1222 and define any number of flexible segments 1221. The configuration of the flexible segments 1221 and slots 1222 allows the plunger connector portion to be pushed in without large pushing stress. The plunger connector portion 1203 may further have one or more radially extending mechanisms 1223 on its outer surface, thereby allowing the plunger to be coupled to the pipette operating head. The radially extending mechanisms on the outer surface of the plunger connector portion 1203 may have projections extending radially outward and / or recesses or grooves extending radially inward. The radially extending mechanisms may extend circumferentially. In the described embodiment, the radially extending mechanisms on the outer surface of the plunger connector portion 1203 include a spherical head 1223 at the upper end of the plunger, defined on an annular groove on the outer surface of the plunger connector portion 1203. Preferably, the second inner diameter to which the plunger connector portion narrows is smaller than the first inner diameter by at least the radial range of the radially extending mechanism 1223, i.e., by at least half the difference between the outer diameter of the spherical head 1223 and the outer diameter of the narrowest part of the annular groove.

[0053] The plunger connector portion 1203 may further include an internal wall 1224 extending laterally from the inner surface of the plunger connector portion 1203. The internal wall 1224 may be located at the end of the flexible segment 1221. The internal wall 1224 may be located close to the main body portion 1206. The internal wall 1224 forms a limiting portion that crosses the hole in the plunger connector portion. This provides a surface that the head of the clamping rod can contact, allowing the pipette to be removed. The internal wall 1224 may extend across the entire width of the hole inside the plunger 1200, as shown in Figure 17. However, this is not necessarily required. It is sufficient for the internal wall 1224 to limit the size of the hole to less than the outer diameter of the head of the clamping rod.

[0054] The central portion 1204 may have an annular shoulder. The central portion 1204 may be substantially conical or dome-shaped. In the depicted embodiment, the central portion 1204 is a radially extending truncated cone-shaped shoulder. The central portion 1104 of the pipette tip 1100 is preferably configured to receive and engage with the central portion 1204 of the plunger 1200 and to center the plunger in a straight line. In the embodiment shown in Figure 14, its two central portions have corresponding geometric shapes. The body portion 1206 of the plunger 1200 may be configured to be received by the body portion 1106 of the pipette tip 1100. The body portion 1206 may be substantially cylindrical and / or elongated. The body portion 1206 may have a substantially uniform diameter. The body portion 1206 may extend along at least half the length of the plunger, and optionally at least two-thirds of the length of the plunger 1200. The main body portion 1206 may have a diameter larger than the diameter of the end portion 1210. The sealing portion 1207 of the plunger 1200 may be configured to be received by the bridging portion 1107 of the pipette tip 1100. The sealing portion 1207 may be configured to form a seal against the inner wall of the pipette tip 1100. The sealing portion 1207 may form a liquid-tight seal within the pipette tip so that when the plunger 1200 is placed inside the pipette tip 1100, fluid does not flow from the proximal side of the sealing portion 1207 to the distal side of the sealing portion 1207. The sealing portion 1207 may be at least partially flexible. The sealing portion 1207 may be configured to bridge the main body portion 1206 to the end portion 1210. The sealing portion 1207 may define a step between the main body portion 1207 and the end portion 1210. The sealing portion 1207 may be substantially tapered, conical, and / or domed. The end 1210 of the plunger 1200 may be configured to be received by the end 1110 of the pipette tip 1100. The end 1210 may have a smaller diameter than the sealing portion 1207 and / or the body portion 1206.

[0055] Referring to Figures 18 to 22, the method of connecting pipette 1010 to pipette operating head 100 according to the present invention is described below. Although the figures relating to the following description show only a single pipette, it will be understood that one or more of the connection, aspiration, dispensing, and withdrawal operations described can be applied to multiple pipettes simultaneously. For example, if the pipette operating head has 384 mounts, the following description may be applied to the simultaneous connection of 384 pipettes, or any subset thereof.

[0056] In Figure 18, both the pipette tip clamping mechanism 120 and the plunger clamping mechanism 140 are in the released state. When the pipette tip clamping mechanism 120 is in the released state, the pipette tip clamping plate 125 is in its uppermost position relative to the lower surface of the pipette tip mounting plate 121. Importantly, in this position, the clamping area of ​​the tip clamp sleeve is axially offset from the annular groove around the outer surface of the tip mount sleeve. When the plunger clamping mechanism 140 is in the released state, as shown, the plunger clamping plate 145 is in its uppermost position, and the expanding head 148 of the plunger clamping rod 147 is axially offset from the annular groove on each inner surface of the plunger mount sleeve. Subsequently, the entire pipette operating head 100 is moved axially to a number of pipettes 1010 using a pipette head Z motor (not shown) so that the tip mount sleeve is received within the tip connector portion of the pipette tip 1100. While the tip mount sleeve 123 is inserted into the proximal end of each pipette tip 1100, the annular rib 1123 of each pipette tip 1100 rides up onto the outer surface of the tip mount sleeve 123, deflecting the tip connector portion of each tip outward to its expanded position. Once the annular rib 1123 is received into the annular groove 124, as shown in Figure 18, the flexible segment returns to an undefended or partially deflected state. In this position, the tip connector portion is stationary, and each pipette tip 1100 is coupled to its respective pipette tip mount sleeve 123 by a snap-fit ​​connection. This is step 1.

[0057] Step 2 is described with reference to Figure 19. In Step 2, the pipette tip clamping mechanism 120 is engaged by lowering the pipette tip clamping plate 125 and moving it away from the pipette tip mounting plate, as shown in Figure 19. This causes the tip clamping sleeve 127 to extend around the tip connector portion 1103 of each pipette tip 1100, so that the clamping area of ​​each tip clamping sleeve is adjacent to the snap-fit ​​connection between each pipette tip 1100 and its respective tip mounting sleeve 123. The inner diameter of the clamping area 128 is less than the expanded diameter of the tip connector portion 1103 and may be substantially the same as, for example, the unexpanded outer diameter or the "first" outer diameter of the tip connector portion. This configuration prevents the tip connector portion 1103 from fully expanding and thus prevents the radially extending mechanism 1123 on the inner surface of the pipette tip 1100 from being released from the groove 124 on the outer surface of the tip mounting sleeve 123. In this way, the pipette tip 1100 is "locked" or "tightened" in the correct position without requiring any large force to be applied to the tip connector portion of the pipette tip 1100. This reduces the force required to engage the pipette tip tightening mechanism.

[0058] Between steps 1 and 2, the pipette tip clamping mechanism may be optionally moved to a partially engaged “pre-locked” position between the released and engaged states, in which position the tapered region 129B of each clamp sleeve 127 is adjacent to a recess 124 on the outer surface of its respective tip mount sleeve 123. This allows the picked tip to be secured to the tip mount without interference between the pipette tip clamping plate and the unpicked tips, thus facilitating the picking of a portion of the numerous tips from the tip box. Once the picked tip is lifted over the unpicked tips by the pipette operating head, the picked tip can then be fully clamped in place by moving the pipette tip clamping plate 125 to the clamping position.

[0059] Step 3 is described with reference to Figure 20. In Step 3, the entire plunger clamping mechanism 140 is lowered using a direct-drive actuator. This causes the plunger mount sleeve 143 to contact the plunger connector portion 1203 at the upper or proximal end of the plunger 1200. Further downward movement of the plunger clamping mechanism 140 causes the inner surface of the plunger mount sleeve 143 to ride up onto the outer surface of the plunger connector portion, deflecting the plunger connector portion inward to a retracted or pushed-in position, and the spherical head 1223 at the top of the plunger 1200 to be received in the groove 144 on the inner surface of the plunger mount sleeve 143. Once the spherical head 1223 is received in the groove 144 on the inner surface of the plunger mount sleeve 143, as shown in Figure 20, the flexible segment 1221 of the plunger connector portion 1203 returns to an undefended or partially deflected state. In this position, the plunger connector is stationary, and each plunger 1200 is connected to its respective plunger mount sleeve 143 by a snap-fit ​​connection.

[0060] Step 4 is described with reference to Figure 21. In step 4, the plunger clamp plate 145 is moved axially toward the plunger mounting plate 141 by the plunger clamp drive mechanism until the head 148 of the plunger clamp rod is adjacent to the snap-fit ​​connection between the plunger and the plunger mounting sleeve. The outer diameter of the head 148 of each clamp rod is greater than the inner diameter of the plunger when it is retracted, or the “second inner diameter”. For example, the outer diameter of the head 148 of each clamp rod may be substantially the same as the inner diameter of the plunger when it is not deflected, or the “first” inner diameter. This configuration prevents the plunger connector from being fully retracted to the retracted position and thus prevents the spherical head 1223 of the plunger 1200 from being released from the groove 144 on the inner surface of the plunger mounting sleeve 143. In this way, the plunger 1200 is “locked” or “tightened” in the appropriate position without requiring any large pushing force to be applied to the plunger connector. This reduces the force required to engage the plunger tightening mechanism.

[0061] To perform the aspiration operation, the pipette operating head 100 is moved to the desired position relative to the liquid sample using the pipette operating head Z motor. The plunger of each pipette is then lifted within its respective pipette tip using a direct drive actuator, as shown in Figure 22, moving the entire plunger clamping mechanism away from the pipette tip clamping mechanism and drawing the fluid into the pipette tip. Subsequently, by moving the plunger clamping mechanism in the opposite direction using the direct drive actuator, the fluid can be dispensed as desired.

[0062] Once the aspiration and dispensing operation is complete, the pipette or multiple pipettes can be removed as follows: First, each plunger is moved to its lowest end within the pipette tip, and the tip clamping mechanism 120 is released by moving the tip clamping plate 125 to the tip mounting plate 121, and by shifting the clamp sleeve 127 out of alignment with the snap-fit ​​connection between each pipette tip and its respective tip mount 123, and away from the outer surface of the pipette tip. Next, the plunger clamping plate 145 is moved beyond its engaged position towards the plunger mounting plate 141, causing the heads 148 of each clamping rod 147 to move out of alignment with the snap-fit ​​connections between each plunger 1200 and its respective plunger mount 143. Instead, the neck portions 149A of each clamping rod 147 are aligned with the snap-fit ​​connections, and the distal end faces of the clamping rod heads are brought into contact with the inner wall 1224 of the plunger connector portion 1203. Since the neck portions 149A of the clamping rod 147 have an outer diameter less than the second pressed-in inner diameter of the plunger connector portion 1203, the plunger connector portion is not restricted from deflecting inward to a pressed-in state when the clamping rod is in this position. Consequently, the continuous downward movement of the plunger clamping plate 145 releases the spherical head 1223 of the plunger connector portion 1203 from the corresponding radially extending mechanism 144 of the plunger mount 143, thereby removing the plunger 1200 from the pipette operating head. Further downward movement of the plunger clamping plate, and by extension the clamping rod and the plunger itself, presses the distal end of the plunger against the parts of the pipette tip in which they are located. In this way, the plunger and plunger clamping mechanism can be used to release the pipette tip 1100 from the pipette tip mount 123, thereby removing the pipette 1010 from the pipette operating head.

[0063] While the present invention has been described above with reference to one or more preferred embodiments, it will be understood that various changes or modifications can be made without departing from the scope of the invention as defined in the appended claims.

Claims

1. A pipette operating head for a liquid dispensing device, for use with a plurality of pipettes, each having a pipette tip and a plunger provided within the pipette tip, wherein the pipette operating head is A pipette tip tightening mechanism for connecting to and tightening the pipette tips of the numerous pipettes during use, During use, a plunger tightening mechanism is connected to and tightens the plungers of the numerous pipettes. Equipped with, The aforementioned pipette tip tightening mechanism is A pipette tip mounting plate having multiple pipette tip mounts, each configured to connect to one of the pipette tips during use, A pipette tip clamping plate having a plurality of pipette tip clamping members, each associated with one of the plurality of pipette tip mounts, The pipette tip tightening drive mechanism includes an actuator that can be operated to selectively move the pipette tip tightening mechanism between a clamped position and a released position, thereby causing relative movement between the pipette tip tightening plate and the pipette tip mounting plate in the axial direction, and engaging the pipette tip tightening mechanism. The plunger tightening mechanism is, A plunger mounting plate having multiple plunger mounts, each configured to connect with one of the plungers during use, A plunger clamping plate having a plurality of plunger clamping members, each associated with one of the plurality of plunger mounts, A plunger clamping drive mechanism comprising an actuator that can be operated to engage the plunger clamping mechanism by selectively moving the plunger clamping mechanism between a clamped position and a released position, thereby causing relative movement between the plunger clamping plate and the plunger mounting plate in the axial direction, and Equipped with, The pipette operating head further comprises a drive actuator that, during use, can be operated to move the plunger tightening mechanism axially toward or away from the plate of the pipette tip tightening mechanism to aspirate or dispense liquid, wherein the drive actuator is configured to operate independently of the pipette tip tightening drive mechanism and the plunger tightening drive mechanism.

2. The pipette operating head according to claim 1, wherein the drive actuator is a direct drive actuator.

3. The pipette operating head according to claim 2, further comprising a chassis, wherein the drive actuator is a ball screw actuator comprising a motor fixed in association with the chassis and a ball screw, and the motor is coupled to the plunger tightening mechanism by the ball screw.

4. The pipette operating head according to claim 1, wherein the plunger tightening drive mechanism comprises a plurality of guide rods, the plunger tightening plate is operably connected to the plunger mounting plate by the plurality of guide rods, the plunger tightening plate and the plunger mounting plate are axially movable relative to each other along the plurality of guide rods by the actuator of the plunger tightening mechanism, and the plurality of guide rods are axially movable together with the plunger tightening plate and the plunger mounting plate toward and away from the plate of the pipette tip tightening mechanism by the drive actuator.

5. The pipette operating head according to claim 1, wherein the plunger tightening drive mechanism comprises a screw shaft connected to the actuator of the plunger tightening drive mechanism and extending through a screw opening fixed in association with the plunger mounting plate and one of the plunger tightening plates, such that when the screw shaft is rotated by the actuator, the screw shaft causes relative movement between the plunger tightening plate and the plunger mounting plate in the axial direction.

6. The pipette tip tightening drive mechanism comprises a screw shaft connected to the actuator of the pipette tip tightening drive mechanism and extending through a screw opening fixed in association with the pipette tip mounting plate and one of the pipette tip tightening plates, wherein when the screw shaft is rotated by the actuator, the screw shaft causes relative movement between the pipette tip tightening plate and the pipette tip mounting plate in the axial direction.

7. The pipette operating head according to claim 1, wherein the pipette tip clamping plate is positioned below the pipette tip mounting plate.

8. The pipette operating head according to claim 1, wherein the plurality of pipette tip clamping members comprises a plurality of sleeves, the plurality of sleeves define a clamping area, and when the pipette tip clamping mechanism is engaged, are coaxial with the plurality of pipette tip mounts and surround the plurality of pipette tip mounts.

9. The pipette operating head according to claim 8, wherein the plurality of sleeves are defined by openings defined in the pipette tip clamping plate.

10. The pipette operating head according to claim 8, wherein each of the plurality of pipette tip mounts has a radially extending mechanism on its outer surface configured to form half of a snap-fit ​​connection, and the clamping area of ​​each of the plurality of sleeves is axially adjacent to the radially extending mechanism on the outer surface of the associated pipette tip mount when the pipette tip clamping mechanism is in the clamp position, and is axially offset from the radially extending mechanism on the outer surface of the associated pipette tip mount when the pipette tip clamping mechanism is in the release position.

11. The pipette operating head according to claim 1, wherein the plurality of plunger mounts comprises a plurality of axially extending sleeves, the plurality of plunger clamping members comprises a plurality of axially extending clamping rods, and the plurality of axially extending clamping rods extend into the interior of the plurality of axially extending sleeves when the plunger clamping mechanism is in the clamp position.

12. The pipette operating head according to claim 11, wherein each of the plurality of axially extending sleeves is provided with a radially extending mechanism on its inner surface configured to form half of a snap-fit ​​connection, and the clamping area of ​​each of the plurality of clamping rods is axially adjacent to the radially extending mechanism on the inner surface of the associated plunger mount when the plunger clamping mechanism is in the clamp position, and is axially offset from the radially extending mechanism on the inner surface of the associated plunger mount when the plunger clamping mechanism is in the release position.

13. A pipette tip having a distal end having a dispensing opening and a proximal end having a tip connector portion for connecting the pipette tip to the pipette tip tightening mechanism of the pipette operating head during use, A plunger having a distal end positioned inside the pipette tip and a proximal end having a hollow plunger connector portion for connecting the plunger to the plunger tightening mechanism of the pipette operating head during use. Further comprising at least one pipette having, The tip connector portion has a radially extending mechanism on its inner surface configured to form a snap-fit ​​connection with the radially extending mechanism on the outer surface of one of the plurality of pipette tip mounts, and is configured to be elastically deflected radially outward from a stationary position having a first outer diameter to an expanded position having a second outer diameter that is larger than the first outer diameter by at least the radial range of the radially extending mechanism of the tip connector portion. The pipette operating head according to claim 10, wherein each of the clamping regions of the plurality of sleeves of the tip clamping mechanism has an inner diameter greater than or equal to the first outer diameter of the tip connector portion and less than the second outer diameter of the tip connector portion, and when the tip clamping mechanism is in the clamp position, the clamping region prevents the tip connector portion from being deflected to the expanded position, thereby preventing the snap-fit ​​connection from being released.

14. A pipette tip having a distal end having a dispensing opening and a proximal end having a tip connector portion for connecting the pipette tip to the pipette tip tightening mechanism of the pipette operating head during use, A plunger having a distal end positioned inside the pipette tip and a proximal end having a hollow plunger connector portion for connecting the plunger to the plunger tightening mechanism of the pipette operating head during use. Further comprising at least one pipette having, The plunger connector portion has a radially extending mechanism on its outer surface configured to form a snap-fit ​​connection with the radially extending mechanism on the inner surface of one of the plurality of plunger mounts, and is configured to be elastically deflected radially inward from a stationary position having a first inner diameter to a pushed-in position having a second inner diameter smaller than the first inner diameter, by at least the radial range of the radially extending mechanism of the plunger connector portion. The pipette operating head according to claim 12, wherein each of the plurality of axially extending clamping rods has an outer diameter less than or equal to the first inner diameter of the plunger connector portion and greater than the second inner diameter of the plunger connector portion, and when the plunger clamping mechanism is in the clamp position, the clamping region prevents the plunger connector portion from being deflected to the push-in position, thereby preventing the snap-fit ​​connection from being released.

15. A main unit having a microplate receiving area, A pipette operating head according to any one of claims 1 to 14, wherein the pipette operating head is positioned above the microplate receiving area. A liquid dispensing device equipped with the following features.

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