Pipette tips for liquid dispensing devices

Abstract

A pipetting head for a liquid dispensing apparatus is provided. The pipetting head has a pipette tip coupling mechanism and a plunger clamping mechanism. The plunger clamping mechanism has a plurality of mounts for holding plungers of multiple pipettes during use, a plurality of clamping rods each extending into one of the mounts, and a clamping drive mechanism operable to cause relative movement between the mounts and the clamping rods to selectively engage the clamping mechanisms. The mounts each have a radially extending mechanism configured to form one half of a snap-fit ​​connection. A clamping region of each of the clamping rods is axially adjacent to the radially extending mechanism of its associated mount when in the clamped position and is axially offset from the radially extending mechanism of its associated mount when in the released position. The clamping rod prevents the snap-fit ​​connection with the plunger from being released when in the clamped position.

Description

[Technical field]

[0001] The present invention relates to a pipetting head for a liquid dispensing device, in particular to a pipetting head having a pipette tip coupling mechanism and a plunger coupling mechanism by which a pipette having a pipette tip and a plunger can be securely attached to the pipetting head. [Background technology]

[0002] It is known to use pipettes to aspirate or dispense liquid samples.

[0003] It is also known to use pipettes with a plunger mounted on the pipette tip. A typical pipette, known as a "positive displacement" pipette, uses a plunger or piston to aspirate or dispense liquid either by direct contact with the sample liquid or through a small air gap. In use, the pipette tip and plunger are attached to a pipetting head of a liquid dispensing device. The pipetting head moves the plunger relative to the tip to aspirate or dispense liquid from an opening at the distal end of the pipette tip. Such pipettes can be used in automated machines to improve the accuracy and repeatability of pipetting movements.

[0004] The present inventors have identified several problems with the way pipettes are coupled to pipetting heads for known liquid dispensing devices.

[0005] There is a need for an improved pipetting head. Summary of the Invention

[0006] A first aspect of the invention provides a pipetting head for a liquid dispensing apparatus for use with a plurality of pipettes, each pipette having a pipette tip and a plunger disposed within the pipette tip, the pipetting head comprising: a pipette tip coupling mechanism having a plurality of tip mounts for holding, in use, pipette tips of the plurality of pipettes; and a plunger coupling mechanism having a plurality of plunger mounts for holding, in use, plungers of the plurality of pipettes, each of the plurality of tip mounts comprising radially extending features on an outer surface thereof configured to form one half of a snap-fit ​​coupling, the pipette tip coupling mechanism comprising a plurality of tip clamping members, each associated with one of the plurality of tip mounts, each having a clamping region. and a tip clamping drive mechanism comprising an actuator operable to selectively engage the pipette tip clamping mechanism by causing relative movement axially between the tip mount and the tip clamping member to move the pipette tip clamping mechanism between a clamped position and a released position, wherein the clamping region of each tip clamping member is axially adjacent to the radially extending feature of the outer surface of its associated tip mount when the pipette tip clamping mechanism is in the clamped position, and the clamping region of each tip clamping member is axially offset from the radially extending feature of the outer surface of its associated tip mount when the pipette tip clamping mechanism is in the released position.Alternatively or in addition, each of the plurality of plunger mounts has a radially extending feature on an inner surface thereof configured to form one half of a snap-fit ​​connection, the plunger connection mechanism further comprising: a plurality of plunger clamping members, each associated with one of the plurality of plunger mounts, each having a clamping area; and a plunger clamping drive mechanism comprising an actuator operable to axially cause relative movement between the plunger mounts and the plunger clamping members to selectively engage the plunger clamping mechanism by moving the plunger clamping mechanism between the clamped position and the released position, the clamping area of ​​each plunger clamping member being axially adjacent the radially extending feature on the inner surface of its associated plunger mount when the plunger clamping mechanism is in the clamped position and the clamping area of ​​each plunger clamping member being axially offset from the radially extending feature on the inner surface of its associated plunger mount when the plunger clamping mechanism is in the released position.

[0007] This provides a very compact arrangement in which a large number of pipettes can be precisely and securely attached to the pipetting head. This is particularly useful in liquid dispensing devices intended for use with standard 384-well plates, as the compact arrangement provides 384 mounting collars and locking members to hold 384 pipettes in a 16×24 matrix. This allows liquid to be aspirated from or dispensed into a conventional 384-well plate in a single motion. As used herein, the terms "clamping" and "clamp" refer to an arrangement in which pipette tips or plungers are attached and locked together in place to prevent inadvertent removal. This is in contrast to an arrangement in which the pipette tips or plungers are attached without locking, for example, using an interference or snap-fit ​​connection that can be easily removed by pulling the pipette tips or plungers axially. The clamping arrangement can also improve the accuracy of aspirating and dispensing operations by preventing small relative movements that may occur between the pipetting head and the plunger or pipette tip.

[0008] Furthermore, by configuring the tip coupling mechanism as a tip clamping mechanism and / or the plunger coupling mechanism as a plunger clamping mechanism, the clamping members can be moved into and out of register with the snap-fit ​​features of the mount, and the pipette tip and / or plunger can be clamped into place on the mount by simply limiting deflection of the connector portion of the tip or plunger to prevent it from disengaging from the snap-fit ​​connection with the mount. This allows the pipette tip and / or plunger to be attached and securely clamped in place without the need to exert significant force on the tip connector portion of the pipette tip and / or the plunger connector portion of the plunger. This reduces the force required to engage the pipette tip and / or plunger clamping mechanism. This contrasts with some known tip coupling mechanisms in which clamping is achieved by expanding a collet in the pipette tip and forcing it outward against the top of the pipette tip, thereby creating a hoop stress within the pipette tip. It also contrasts with some known plunger coupling mechanisms in which clamping is accomplished by forcing a collet against the exterior surface of the upper end of the plunger, creating a compressive stress on the plunger.

[0009] Each of the plurality of tip clamping members may comprise any suitable component capable of limiting radial movement of a pipette tip on its associated tip mount when the pipette tip clamping mechanism is in the clamped position. The plurality of tip clamping members may comprise a plurality of sleeves each defining a clamping region. The sleeve may be axially aligned with the plurality of tip mounts. The sleeve may be coaxial with the plurality of tip mounts. The sleeve may be discontinuous or continuous. The sleeve may circumscribe the plurality of tip mounts when the pipette tip clamping mechanism is in the clamped position. The sleeve may have a substantially constant inner diameter. The sleeve may have regions with differing inner diameters.

[0010] The pipette tip clamping mechanism may include a pipette tip clamping plate on which a plurality of tip clamping members are provided, the pipette tip clamping plate being axially movable relative to the plurality of pipette tip mounts to selectively engage the pipette tip clamping mechanism.

[0011] The multiple sleeves may be defined by one or more separate pieces secured to the pipette tip clamping plate. The multiple sleeves may be defined by openings defined in the pipette tip clamping plate.

[0012] The radially extending feature on the outer surface of each of the plurality of chip mounts may have any suitable shape. The radially extending feature on the outer surface of one or more of the plurality of chip mounts may be a recess or groove. This configuration is particularly suitable for use with a pipette tip having a correspondingly shaped protrusion configured for receipt in the groove. The radially extending feature on the outer surface of each of the plurality of chip mounts may be a circumferential groove. The circumferential groove may include a circumferential break. For example, the circumferential groove may be partially annular.

[0013] In other embodiments, the radially extending features on the outer surfaces of one or more of the plurality of tip mounts may be protrusions, which is particularly suited for use with pipette tips having correspondingly shaped recesses or grooves in the tip mount configured to receive the protrusions.

[0014] The plurality of plunger mounts may comprise a plurality of axially extending sleeves. The plurality of plunger clamping members may comprise a plurality of axially extending clamping rods each defining a clamping region. The clamping rods may extend within the plurality of axially extending sleeves when the plunger clamping mechanism is engaged. The sleeves may have a substantially constant inner diameter. Alternatively, the sleeves may have regions with differing inner diameters. The plurality of axially extending sleeves may each comprise a plurality of axial slots at their distal ends. This may help to allow compliance between a channel defined by the pipetting head and multiple pipettes attached to the pipetting head.

[0015] The multiple clamping rods may each have an enlarged distal end connected to a narrower shaft, the enlarged distal end defining a clamping region. In this configuration, the multiple clamping rods may be moved in either axial direction to move the clamping mechanism from a clamped position to a released position. This may facilitate the release of both the plunger and pipette tip of the pipette by moving the clamping rod downward, releasing the clamping mechanism and pushing the plunger and pipette tip out of their respective mounts.

[0016] According to a second aspect of the invention there is provided a pipette for use with a pipetting head according to the first aspect of the invention, comprising a pipette tip having a distal end with a dispensing opening and a proximal end having a tip connector portion for coupling the pipette tip, in use, to a pipette tip coupling mechanism of the pipetting head; and a plunger having a distal end positioned within the pipette tip and a proximal end having a hollow plunger connector portion for coupling the plunger, in use, to a plunger coupling mechanism of the pipetting head. The tip connector portion has a radially extending feature on an inner surface thereof configured to form a snap-fit ​​connection with a radially extending feature on an outer surface of one of a plurality of pipette tip mounts, the tip connector portion being configured to resiliently deflect radially outwardly from a rest position in which the tip connector portion has a first outer diameter to an extended position in which the tip connector portion has a second outer diameter greater than the first outer diameter by at least the radial extent of the radially extending feature of the tip connector portion. Alternatively or in addition, the plunger connector portion has a radially extending feature on its outer surface configured to form a snap-fit ​​connection with a radially extending feature on an inner surface of one of the plurality of plunger mounts, and the plunger connector portion is configured to be resiliently deflected radially inwardly from a rest position in which the plunger connector portion has a first inner diameter to a pushed-in position in which the plunger connector portion has a second inner diameter smaller than the first inner diameter by at least the radial extent of the radially extending feature of the plunger connector portion.

[0017] The tip connector portion may comprise a segmented tubular wall defined by a plurality of flexible segments configured to elastically deflect in a radially outward direction to deflect the tip connector portion from a rest position to an extended position. The flexible segments may be defined by a series of axially extending cuts or slots in the tubular wall. The axially extending cuts may be spaced equidistant from a longitudinal axis of the pipette. The axially extending cuts may have the same or different axial lengths. The axially extending cuts may be aligned with the pipette axis or may be at an angle to the pipette axis.

[0018] The radially extending features on the inner surface of the tip connector portion may comprise projections or ribs that project radially inward from the inner surface of the tip connector portion. This configuration is particularly suitable for use with a chip mount having correspondingly shaped recesses or grooves configured to receive the projections or ribs of the tip connector portion. The projections or ribs may be circumferential ribs. The circumferential ribs may comprise circumferential breaks. For example, the circumferential ribs may be partially annular. Alternatively, or in addition, the radially extending features on the inner surface of the tip connector portion may comprise recesses or grooves that extend radially outward into the inner surface of the tip connector portion. This configuration is particularly suitable for use with a chip mount having correspondingly shaped projections or ribs configured to be received in the recesses or grooves of the tip connector portion.

[0019] The plunger connector portion may comprise a segmented tubular wall defined by a plurality of flexible segments configured to resiliently deflect in a radially inward direction to deflect the plunger connector portion from a rest position to a depressed position. The flexible segments may be defined by a series of axially extending cuts or slots in the tubular wall. The axially extending cuts may be equidistantly spaced from a longitudinal axis of the pipette. The axially extending cuts may have the same or different axial lengths. The axially extending cuts may be aligned with the pipette axis or may be at an angle to the pipette axis.

[0020] The radially extending feature on the outer surface of the plunger connector portion may comprise a molded head portion adjacent a recess or groove extending radially inwardly into the outer surface of the plunger connector portion. The recess or groove defines a lower portion of the molded head. The molded head may have substantially the same outer diameter as a region of the plunger connector portion directly below the recess or groove. This configuration is particularly suitable for use with a plunger mount having a correspondingly shaped recess configured to receive the molded head of the plunger connector portion. The recess or groove of the plunger connector portion may be a circumferential groove. The circumferential groove may comprise a circumferential break. For example, the circumferential groove may be partially annular. The second inner diameter to which the plunger connector portion reduces is smaller than the first inner diameter by at least the radial extent of the radially extending feature, i.e., by at least half the difference between the outer diameter of the molded head and the outer diameter of the narrowest portion of the annular recess directly below it.

[0021] The clamping region of each of the multiple sleeves of the tip clamping mechanism may have an inner diameter that is greater than or equal to a first outer diameter of the tip connector portion and less than a second outer diameter of the tip connector portion, such that when the tip clamping mechanism is in the clamped position, the clamping region prevents the tip connector portion from deflecting to an expanded position, thereby releasing the snap-fit ​​connection.

[0022] The clamping region of each of the plurality of axially extending clamping rods may have 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, such that when the plunger clamping mechanism is in the clamped position, the clamping region prevents the plunger connector portion from deflecting into a depressed position, thereby releasing the snap-fit ​​connection.

[0023] According to a third aspect of the present invention, there is provided a liquid dispensing device comprising: a body having a microplate receiving area; and a pipetting head according to the first aspect of the present invention, the pipetting head being positioned above the microplate receiving area.

[0024] Further features and advantages of the present invention will be further described hereinafter, by way of example only, with reference to the accompanying drawings, in which: [Brief description of the drawings]

[0025] [Figure 1] 1 is a perspective view of a liquid dispensing device having a pipetting head according to the present invention; [Diagram 2] FIG. 1 is a perspective view of a pipetting head according to the present invention; [Diagram 3] FIG. 3 is a side view of the pipetting head of FIG. 2. [Figure 4] FIG. 3 is a perspective view of the pipetting head of FIG. 2 with various parts removed for clarity, showing the pipette tip clamping mechanism and the plunger clamping mechanism. [Diagram 5] FIG. 5 is a cross-sectional view of the view of FIG. 4, showing the plates of the pipette tip clamping mechanism and the plunger clamping mechanism. [Figure 6] FIG. 5 is an enlarged cross-sectional perspective view of the view of FIG. 4, showing the plate of the pipette tip clamping mechanism. [Figure 7] FIG. 3 is an enlarged cross-sectional view of a plate of the pipette tip clamping mechanism of the pipetting head of FIG. 2, showing the pipette tip mounting sleeve; [Figure 8] FIG. 3 is an enlarged perspective cross-sectional view of the pipetting head of FIG. 2 with various parts omitted for clarity, showing the plate of the plunger clamping mechanism in greater detail; [Figure 9] FIG. 3 is an enlarged cross-sectional view of a plate of the plunger clamping mechanism of the pipetting head of FIG. 2, showing the plunger mount and clamping member; [Figure 10] FIG. 3 is a perspective view of the plunger clamping mechanism of the pipetting head of FIG. 2 with the plunger mounting plate omitted for clarity and the plunger clamping plate shown in the clamping position; [Figure 11]FIG. 3 is a perspective view of the plunger clamping mechanism of the pipetting head of FIG. 2 with the plunger mounting plate omitted for clarity and the plunger clamping plate shown in the released position; [Figure 12] FIG. 3 is a cross-sectional front view of the pipetting head of FIG. 2. [Figure 13] FIG. 3 is a cross-sectional side view of the pipetting head of FIG. 2. [Figure 14] 2 is a cross-sectional view of a pipette for use with the liquid dispensing system of FIG. 1. [Figure 15] FIG. 15 is a perspective view of the pipette tip and plunger of the pipette of FIG. 14, with the plunger removed from the pipette tip. [Figure 16] FIG. 15 is an enlarged cross-sectional view of the pipette of FIG. 14 showing the tip connector portion and the plunger connector portion in further detail. [Figure 17] FIG. 15 is a perspective view of the pipette of FIG. 14, showing the tip mount and associated tip clamp of the pipette tip clamping mechanism. [Figure 18] 1A-1C are enlarged cross-sectional views of a portion of the pipette tip clamping mechanism and the plunger clamping mechanism at various stages of pipette connection. [Figure 19] 1A-1C are enlarged cross-sectional views of a portion of the pipette tip clamping mechanism and the plunger clamping mechanism at various stages of pipette connection. [Figure 20] 1A-1C are enlarged cross-sectional views of a portion of the pipette tip clamping mechanism and the plunger clamping mechanism at various stages of pipette connection. [Figure 21] 1A-1C are enlarged cross-sectional views of a portion of the pipette tip clamping mechanism and the plunger clamping mechanism at various stages of pipette connection. [Figure 22] 1A-1C are enlarged cross-sectional views of a portion of the pipette tip clamping mechanism and the plunger clamping mechanism at various stages of pipette connection. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] FIG. 1 shows a liquid dispensing device 10 for use with multiple positive displacement pipettes 1010. The device 10 comprises a body 12 having a microplate receiving area or deck 14 and a pipetting head 100 positioned above the microplate receiving area 14. The microplate receiving area 14 has a substantially horizontal upper surface 16 arranged to receive a laboratory microplate. The receiving area 14 may be located on a height adjustable support structure 18 that allows the height of the microplate receiving area 14 to be changed as required. The receiving area 14 may be configured to hold a laboratory microplate in a fixed position. For example, the upper surface 16 of the receiving area 14 may include one or more recesses (not shown) arranged 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 FIG. 1, where gravity holds the product in the wells of the microplate. The axis marked Z in FIG. 1 therefore represents an upward direction, while 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 labelled Z in Figure 1, while references to sideways or transverse directions refer to movement in the directions labelled X and Y in Figure 1. References to vertical directions or height therefore also refer to dimensions or movement along the axis labelled Z in Figure 1. The pipetting head 100, as shown below in connection with Figures 2-9, is configured to hold a number of pipettes and is movable relative to the deck 14 so that pipettes mounted on the pipetting head 100 may be brought into proximity with a microplate supported by the deck 14 so that liquid may be aspirated from or dispensed into the wells of the microplate.

[0027] 2-4 show the pipetting head 100 in further detail. The pipetting head comprises a head chassis 101 having an upper head chassis part 102 and a lower head chassis part 103 which are bolted together to form the body of the pipetting head 100. The upper and lower head chassis parts are connected to the body of the apparatus by a chassis support plate 104. The chassis support plate 104 is preferably capable of moving the entire pipetting head 100 in the X, Y and Z directions relative to a receiving area of ​​the apparatus in a conventional manner using one or more head actuators (not shown). The pipetting head 100 further comprises a pipette tip coupling mechanism for coupling to pipette tips of multiple positive displacement pipettes during use, and a plunger coupling mechanism for coupling to plungers of multiple positive displacement pipettes.

[0028] In this embodiment, the pipette tip coupling mechanism is a pipette tip clamping mechanism 120 for coupling or mating with and clamping the pipette tips of multiple positive displacement pipette tips during use, and the plunger coupling mechanism is a plunger clamping mechanism 140 for coupling or mating with and clamping the plungers of multiple positive displacement pipette tips during use. Thus, both are configured to couple to and clamp the pipette tips and plungers, respectively. In other embodiments, the clamping feature of either the pipette tip coupling mechanism or the plunger coupling mechanism may be omitted, with the mechanism only coupling to the pipette tips or plungers, respectively.

[0029] When mounted to the upper head chassis portion 102, the direct drive actuator 160 is operable, during use, to axially move the plunger clamping mechanism 140 towards or away from the plate of the pipette tip clamping mechanism to aspirate or dispense liquid. The drive actuator may otherwise be an indirect drive actuator, for example comprising a motor-driven belt or chain configured to move the plunger clamping mechanism relative to the pipette tip clamping mechanism and operate independently of the pipette tip clamping drive mechanism and the plunger clamping drive mechanism. Preferably, the drive actuator is a direct drive actuator. Whether the drive actuator is a direct drive actuator or an indirect drive actuator with an independently operated drive actuator, the plunger clamping mechanism, and thus any plunger mounted thereto, moves relative to the pipette tip clamping mechanism and can perform aspirating and dispensing operations independently of the mechanisms that operate the pipette tip clamp and the plunger clamp. For example, if the drive actuator uses a drive mechanism that includes one or more threaded rods, the pitch of the threads can be specifically tailored to the desired speed of movement of the plunger tightening mechanism, rather than being determined by the operation of the plunger tightening mechanism itself. The direct drive actuator 160 is fixed relative to the head chassis 101 and extends between the head chassis 101 and the plunger tightening mechanism 140.

[0030] The pipette tip clamping mechanism 120 comprises a pipette tip mounting plate 121, a pipette tip clamping plate 125 positioned below the pipette tip mounting plate 121, and a pipette tip clamping drive mechanism 130 operable to cause relative movement between the pipette tip mounting plate 121 and the pipette tip clamping plate 125. In this example, the pipette tip mounting plate 121 is provided as part of a lower head chassis portion, and the pipette tip clamping drive mechanism 130 is configured to move the pipette tip clamping plate 125 towards and away from the fixed pipette tip mounting plate 121 to selectively engage the pipette tip clamping mechanism 120.

[0031] As best seen in Figures 5-7, the pipette tip mounting plate 121 has a number of openings 122 extending axially through the thickness of the pipette tip mounting plate 121. When secured within each opening 122, a pipette tip mount 123 extends axially downward from the plate 121 and is configured to mate 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, the openings 122 each have a restriction having a diameter less than the outer diameter of the tip mount sleeve 123. The restriction prevents the tip mount sleeve 123 from being forced in an upward direction through the tip mounting plate when the tip mount sleeve is initially inserted onto the pipette tip. The upper end of the tip mount sleeve 123 preferably includes an inwardly tapered end face to aid in the insertion of components of a plunger clamping mechanism into the bore of the tip mount sleeve 123. The lower end of the tip mount sleeve 123 preferably includes an externally tapered end surface to aid in the insertion of the lower end of the tip mount sleeve into the pipette tip. The outer surface of each tip mount sleeve 123 includes a radially extending feature thereon that is configured to form one half of a snap-fit ​​connection with a correspondingly shaped feature on the inner surface of the pipette tip. In this example, the radially extending feature is in the form of an annular groove 124 that circumscribes the periphery of the tip mount sleeve 123.

[0032] The pipette tip clamping plate 125 has a number of openings 126 extending axially through the thickness of the pipette tip clamping plate 125. The number of openings 126 correspond in number and location 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 the plurality of pipette tip mounts 123. In this example, the number of pipette tip clamping members 127 come in the form of a number of clamping sleeves 127 defined by areas of the pipette tip clamping plate 125 that immediately surround the openings 126 defined in the pipette tip clamping plate 125. Each clamping sleeve 127 has a clamping region 128 having an inner diameter larger than the outer diameter of its respective tip mount sleeve. In this way, a small gap is provided between the outer surface of the tip mount sleeve 123 and the inner surface of the clamping region 128 when the pipette tip clamping mechanism is engaged, as shown in FIG. 7.

[0033] Each clamp sleeve may have a substantially constant inner diameter. Alternatively, each clamp sleeve may have regions with different inner diameters, as shown in FIG. 7. In the illustrated example, each clamp sleeve 127 has a narrow region 129A toward its top 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 bottommost tip to the clamping region 128. With this configuration, one or more pipette tips may be semi-fixed by being positioned in the pipette tip clamping plate 125 in an intermediate "pre-lock" position where the tapered region 129B of the clamping sleeve 127 is adjacent to the recess 124 on the outer surface of the tip mount sleeve 123. This may facilitate picking of a portion of a stack of tips from a tip box. Once the picked tip has been raised above the stack of unpicked tips, the picked tip may then be clamped in place by moving the pipette tip clamping plate 125 to a clamping position. A small clearance may be provided between narrow area 129A of clamp sleeve 127 and the outer surface of tip mount 123. This may help minimize the force required to move tip clamping plate 125 axially and promote smooth operation of the pipette tip clamping mechanism.

[0034] As best seen in FIGS. 2-4, the pipette tip clamping drive mechanism 130 includes a rotary actuator 131 and a threaded shaft 132 operably coupled to an output shaft of the rotary actuator 131. The rotary actuator 131 is attached to a tip motor support plate 135 that is fixed in relation to the pipette tip mounting plate 121. In this example, the tip motor support plate 135 is attached to an outer surface of the lower head chassis portion 103. The tip motor support plate 135 is positioned over an extension tab 133 that is fixed in relation to the pipette tip clamping plate. The extension tab 133 includes a threaded opening 133A through which the threaded shaft 132 extends. The pipette tip clamping mechanism 130 further includes a plurality of guide rods 134 that connect the pipette tip mounting plate 121 and the pipette tip clamping plate 125. In the illustrated embodiment, the guide rods 134 are fixed in relation to the pipette tip mounting plate 121 and each extend axially through a corresponding opening 137 in the pipette tip clamping plate 125. Of course, it will be understood that the guide rods may be equally fixed in relation to the pipette tip clamping plate and extend through openings in the pipette tip mounting plate, or any other part of the pipetting head that is fixed in relation to the pipette tip mounting plate.

[0035] When the rotary actuator 131 is operated, the threaded shaft 132 rotates within the threaded opening 133A, moving the extension tab 133 toward or away from the tip motor support plate 135, which causes the pipette tip clamping plate 125 to move axially toward or away from the pipette tip mounting plate 121. The direction of movement is dictated 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 to maintain a parallel relationship between the pipette tip mounting plate 121 and the pipette tip clamping plate 125.

[0036] As best seen in Figures 5 and 8-11, the plunger clamping mechanism 140 includes 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 includes a plunger clamp motor mount 155 positioned on both the plunger mounting plate 141 and the plunger clamping plate 145. An 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 relative to one another. In this example, the plunger mounting plate 141 and the plunger clamp motor mount 155 are provided as separate parts that are combined for ease of manufacturing and assembly. In other examples, the plunger mounting plate 141 and the plunger clamp motor mount 155 may be provided as a single piece. The plunger clamping drive mechanism 150 is configured to move the plunger clamping plate 145 towards and away from the plunger mounting plate 141 to selectively engage the plunger clamping mechanism 140.

[0037] As best seen in Figures 8 and 9, the plunger mounting plate 141 has a number of apertures 142 extending axially through the thickness of the plunger mounting plate 141. Fixed within each aperture 142, a plunger mount 143 extends axially downward from the plate 141 and is configured to mate 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 apertures 142. In this example, the plunger mounts 143 each have an outer diameter larger than the diameter of the aperture 142 and have a shoulder that abuts the underside of the plunger mount plate 141. The shoulder serves to set the height of the plunger mount sleeve 143 when initially inserted into the aperture 142 in the plunger mount plate 141. The lower end of the tip mount sleeve 143 preferably has an inwardly tapered end face to aid in the insertion of the plunger into the bore of the plunger mount sleeve 143. Each plunger mount sleeve 143 includes a radially extending feature on its inner surface that is configured to form one half of a snap-fit ​​connection with a correspondingly molded feature on the outer surface of the plunger. In this example, the radially extending feature is in the form of an annular recess 144 in the inner surface of the plunger mount sleeve 143 toward the bottom end.

[0038] The plunger clamping plate 145 has a number of axially extending recesses or openings 146. The number of openings 146 of the plunger clamping plate 145 correspond in number and location to the number of openings 142 of the plunger mounting plate 141. The number of openings 146 of the plunger clamping plate 145 may correspond in number 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 the plurality of plunger mounts 143. The number of plunger clamping members are provided in the form of a number of clamping rods 147 extending axially from the plunger clamping plate 145 and into holes defined in the plunger mount sleeve 143. Each clamping rod 147 has an enlarged head 148 at its lower end extending from a narrower neck region 149A. The enlarged head 148 has an outer diameter that is less than the inner diameter of the plunger mount sleeve 143. In this way, a small clearance is provided between the outer surface of the enlarged head 148 and the inner surface of the plunger mount sleeve 143 when the plunger clamping mechanism is engaged. The neck 149A has an outer diameter that is less than the outer diameter of the enlarged head 148. Preferably, each clamping rod 147 also has a main shaft 149B that has an outer diameter substantially the same as the inner diameter of the region 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 main shaft 149B moves axially along the bore of the plunger mount 143.

[0039] As best seen in FIG. 13, the plunger clamping drive mechanism 150 includes a rotary actuator 151 and a threaded shaft 152 operably coupled to an output shaft of the rotary actuator 151. The rotary actuator 151 is mounted to a plunger clamp motor mount 155 and is thus fixed in relation to the plunger mounting plate 141. The rotary actuator 151 is positioned over an opening 153 in the plunger clamping plate 145 having a threaded opening 153A, and the threaded shaft 152 extends through the threaded opening 153A. The plunger clamping mechanism 150 further includes a plurality of guide rods 154 operably coupling the plunger mounting plate 141 and the plunger clamping plate 145. In the illustrated embodiment, the guide rods 154 are fixed in relation to the plunger clamping plate 145 and each extends axially into a hole in a corresponding cylindrical housing 157 extending from the underside of the plunger clamp motor mount 155. It will of course be understood that the guide rods may be equally fixed in relation to the plunger mounting plate 141 and extend through openings in the plunger clamping plate 145, or any other part of the pipetting head that is fixed in relation to the plunger clamping plate 145.

[0040] When the rotary actuator 151 is operated, the threaded shaft 152 rotates within the threaded opening 153A, axially moving the plunger clamping plate 145 into or away from the plunger mounting plate 141. The guide rods 154 help maintain a parallel relationship between the plunger mounting plate 141 and the plunger clamping plate 145 as the plunger clamping plate 145 moves axially into or away from the plunger mounting plate 141. The direction of movement is dictated by the direction of rotation of the actuator 151. This can be seen in Figures 10 and 11, where the plunger mounting plate 141 has been omitted for clarity. In FIG. 10, the guide rods 154 are seen extended from the cylindrical housing 157 such that the plunger clamping plate 145 and its support plate 156 are in a lower position away from the underside of the plunger clamp motor mount 155 and closer to the top surface of the plunger mounting plate (not shown in FIGS. 10 and 11). This is the clamped position. In FIG. 11, the guide rods 154 are retracted within the cylindrical housing 157 such that the plunger clamping plate 145 and its support plate 156 are moved axially away from the plunger mounting plate 141 and towards the plunger clamp motor mount plate 155. This is the released position. Relative movement between the plunger clamping plate 145 and the plunger mounting plate 141 allows the plunger clamping mechanism 140 to be moved anywhere between an engaged state, where the plunger is clamped in place, and a released or "released" position or state, where the plunger is axially connected to or removed from the plunger mount. The plunger clamping mechanism 140 may be configured to move to an ejection state in which the plunger clamping plate 145 is moved beyond the clamping position towards the plunger mounting plate 141 .In this position, the enlarged head 148 of the clamping rod 147 is axially below the radially extending feature on the inner surface of the plunger mount sleeve 143, which is instead aligned with the narrower neck 149A of the clamping rod. This allows the top of the plunger, i.e. the plunger connector, to bend inward. Further downward movement of the clamping plate 145 and the clamping rod 147 pushes the plunger downward and releases 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, and ejects the pipette tip from the tip clamping mechanism. This removes the entire pipette assembly from the pipetting head. Alternatively, the direct drive actuator 160 may be used to move the clamping rod and plunger together down against the pipette, thereby ejecting the pipette tip from the device. In this ejection mode, the plunger may remain in the device after the pipette tip has been ejected.

[0041] 12 and 13 show the direct drive actuator 160 in further 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 threaded rod 162 which is connected to a ball screw actuator nut 163. The output shaft of the actuator 161 may be integral with the threaded rod 162 or may be fixed to the threaded rod 162. In the illustrated embodiment, the output shaft is coupled to the threaded 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 threaded shaft 162 but prevents or substantially prevents relative rotation between the two parts. The nut 163 is fixed to a ball screw mount 164 so that the two move simultaneously. In the illustrated embodiment, the ball screw mount 164 is fixed to the plunger clamp motor mount 155 at the top end of the 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 thus extends between the head chassis 101 and the plunger clamping mechanism 140.

[0042] When the actuator motor 161 is operated, the entire plunger clamping mechanism 140 moves axially along the guide rod 165 toward or away from 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 includes a number of guide sleeves 166 (see FIG. 8 ) through which the guide rods 165 extend. When the actuator motor 161 is operated, the guide sleeves 166 slide along the outer surfaces of the guide rods. In this way, the plunger clamped by the plunger clamping mechanism 140 can be rapidly accelerated relative to the pipette tip into which it extends, independent of any limitations imposed by the speed of operation of the clamping mechanism. This allows the device to be used in non-contact dispensing mode (also known as jetting - liquid is dispensed from the pipette at a distance from the target such that a droplet leaves the tip before contacting the target) and in contact dispensing mode (droplets form at the pipette tip and precipitate on contact with the target). When performing non-contact dispensing, the liquid sample must travel at a sufficiently fast speed to leave the tip. The distance traveled by the plunger for the dispensing shot is short, e.g., in the range of 1 mm or less. As a result, high levels of acceleration / deceleration are required to reach the target speed for non-contact dispensing. A direct drive configuration, e.g., via a ball screw, allows higher levels of acceleration / deceleration for heavy loads than a belt-driven system, thus enabling non-contact dispensing of small liquid samples. Furthermore, a direct drive configuration can provide higher positional accuracy and repeatability than a comparable belt-driven mechanism. This can have a significant impact on dispensing performance.

[0043] Figures 14 to 17 show a pipette 1010 for use with the pipetting head of Figures 2 to 13. The pipette 1010 comprises a pipette tip 1100 and a plunger 1200.

[0044] The pipette tip 1100 may be a receptacle for receiving and / or containing a sample fluid or liquid. The pipette tip 1100 may be configured to be inserted into a container of sample liquid or into the 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 therebetween. The pipette tip 1100 has an opening 1108 at its distal end 1102, as shown in FIG. 15. The opening 1108 may be defined by an inner wall surface 1111 of the pipette tip 1100 at the distal end 1102, specifically at an outermost distal point 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 extending from the opening 1108 at least partially to the proximal end 1101. The fluid cavity may be configured to receive and / or hold a fluid, such as an air gap or a sample liquid. The fluid cavity 1109 may be substantially elongated. The fluid cavity may be defined by an inner wall surface of the pipette tip 1100. The longitudinal axis 1001 may be a central axis about which the pipette tip 1100 and / or the plunger 1200 are disposed. The longitudinal axis 1001 may define a central axis about which the pipette tip 1100 and / or the plunger 1200 are disposed uniformly or symmetrically. The pipette tip 1100 and / or the plunger 1200 may be configured such that the direction of aspiration and / or dispensing is along 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 comprise or consist of a polymeric material. The pipette tip 100 may comprise or consist of a homogenous material. The pipette tip 100 may comprise or consist of a translucent or transparent material.

[0045] The pipette tip 1100 may include a series of sections, each having a different function, distinguishing feature, and / or different shape or size. The pipette tip 1100 may include one or more of a tip connector section 1103, a center section 1104, a support section 1105, a body section 1106, and a bridge section 1107, for example as shown in FIG. 15. From the proximal end 1101 to the distal end 1102, the sections may be arranged in the following order: tip connector section 1103, center section 1104, support section 1105, body section 1106, bridge section 1107, and end section 1110. The fluid cavity 1109 may extend through one, more than one, or all of the sections of the pipette tip 1100. The plunger 1200 may extend through one, more than one, or all of the sections of the pipette tip 1100.

[0046] The tip connector portion 1103 is configured to be coupled to a liquid handling system, for example, by a snap-fit ​​connection. The tip connector portion 1103 may comprise a divided tubular wall 1120 that may be defined by a number of flexible segments 1121. The flexible segments 1121 may be configured to elastically deflect in a radially outward direction to increase the outer diameter of the proximal end 1101 of the pipette tip 1100 from a first outer diameter where the flexible segments are not deflected and the tip connector portion is in a resting state to a second outer diameter where the flexible segments are deflected radially outward and the tip connector portion is in an expanded state. In the depicted embodiment, the tip connector portion 1103 comprises four axially extending breaks or slots 1122 in the tubular wall 1120 that separate the four flexible segments 1121. The tip connector portion 1103 may include any suitable number of axially extending breaks 1122 to define any number of flexible segments 1121, such as two, three, four, five, or six. The configuration of flexible segments 1121 and slots 1122 allows the tip connector portion to expand without the need to exert significant force on the tip connector portion, thereby reducing the insertion force required to engage the tip connector portion 1103 with the pipetting head.

[0047] The tip connector portion 1103 may further comprise one or more radially extending features 1123 on its inner surface by which a pipette tip may be coupled to the pipetting head. The radially extending features on the inner surface of the tip connector portion 1103 may comprise radially inwardly extending protrusions and / or radially outwardly extending depressions or grooves. The radially extending features may extend in a circumferential direction. In the depicted embodiment, the radially extending features on the inner surface of the tip connector portion 1103 comprise a partially annular rib 1123 that protrudes 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 extent of the radially extending features 1123. The rib 1123 preferably comprises angled upper and lower surfaces along which the inner diameter of the tip connector portion gradually increases from the rib 1123 to the areas of the tip connector portion above and below the rib 1123. The angle of the upper surface may be selected according to a desired insertion force. The angle of the lower surface may be selected according to a desired removal force. The upper or lower surface may each be angled 10-80 degrees from the axial direction of the pipette tip, e.g., 20-70 degrees from the axial direction of the pipette tip, 30-60 degrees from the axial direction of the pipette tip, or 40-50 degrees from the axial direction of the pipette tip.

[0048] The core 1104 may be configured to center the plunger 1200 within the pipette tip 1100. The core 1104 may have an inner surface that may have a tapered or conical shape. The support 1105 may include one or more structural ribs or rings configured to reduce flexibility and / or improve structural integrity of the pipette tip 1100. The one or more ribs may extend on the outer surface of the pipette tip, e.g., axially, along at least a portion of the length between the proximal end 1101 and the distal end 1102, as best seen in FIG. 16. The body 1106 may be substantially cylindrical and / or elongated. The body 1106 may have a substantially uniform inner and / or outer diameter. The body 1106 may extend along at least half of the length of the pipette tip 1100. The body portion 1106 may have an inner and / or outer diameter that is larger than any diameter of the end portion 1110. The bridge portion 1107 may be configured to bridge the body portion 1106 to the end portion 1110. The bridge portion 1107 may define a gradual transition or step between the body portion 1106 and the end portion 1110. The bridge portion 1107 may be substantially tapered, conical, and / or dome-shaped.

[0049] The plunger 1200 has a proximal end 1201 and a distal end 1202 and extends along a 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 into and away from the opening 1108 to aspirate 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 include or be made of a polymeric material. The plunger 1200 may include or be made of a homogenous material.

[0050] The plunger 1200 may comprise a series of sections, each having a different function, distinguishing feature, and / or different shape or size. The plunger 1200 may comprise one or more of a plunger connector section 1203, a center section 1204, a body section 1206, and a sealing section 1207. From the proximal end 1201 to the distal end 1202, the sections may be arranged in the following order: connector section 1203, center section 1204, body section 1206, sealing section 1207, and end section 1210.

[0051] The plunger connector portion 1203 is configured to be coupled 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 the pipette tip 100. The plunger connector portion 1203 may comprise a divided tubular wall 1220 that may be defined by a plurality of flexible segments 1221. The flexible segments 1221 may be configured to resiliently deflect in a radially inward direction to reduce an 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 resting state to a second inner diameter where the flexible segments are deflected radially inward and the plunger connector portion is in a depressed state. In the depicted embodiment, the plunger connector portion 1203 comprises three axially extending breaks or slots 1222 in the tubular wall 1220 that separate the three flexible segments 1221. The plunger connector portion 1203 may include any suitable number of axially extending cuts 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 compressed without significant compression stress. The plunger connector portion 1203 may further include one or more radially extending features 1223 on its outer surface by which the plunger may be coupled to the pipetting head. The radially extending features on the outer surface of the plunger connector portion 1203 may include radially outwardly extending protrusions and / or radially inwardly extending recesses or grooves. The radially extending features may extend in a circumferential direction. In the depicted embodiment, the radially extending features on the outer surface of the plunger connector portion 1203 include a molded head 1223 at the upper end of the plunger, the lower portion of which is defined by an annular groove on the outer surface of the plunger connector portion 1203. Preferably, the second inner diameter to which the plunger connector portion reduces is smaller than the first inner diameter by at least the radial extent of the radially extending feature 1223, i.e., by at least half the difference between the outer diameter of the molding head 1223 and the outer diameter of the narrowest portion of the annular recess.

[0052] The plunger connector portion 1203 may further comprise an interior wall 1224 extending laterally from an inner surface of the plunger connector portion 1203. The interior wall 1224 may be located at the end of the flexible segment 1221. The interior wall 1224 may be located proximate to the body portion 1206. The interior wall 1224 forms a restriction across the bore of the plunger connector portion, providing a surface against which the head of the fastening rod can abut to eject the pipette. The interior wall 1224 may extend the entire width of the bore within the plunger 1200, as shown in FIG. 17. However, this is not necessary. It is sufficient that the interior wall 1224 limits the size of the bore to less than the outer diameter of the head of the fastening rod.

[0053] The central portion 1204 may include 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 frustoconical shoulder. The central portion 1104 of the pipette tip 1100 is preferably configured to receive and engage the central portion 1204 of the plunger 1200 to center the plunger in a straight line. In the embodiment shown in FIG. 14, the two central portions have corresponding geometric shapes. The body portion 1206 of the plunger 1200 may be configured to be received in 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, optionally at least two-thirds of the length of the plunger 1200. The 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 in the bridge portion 1107 of the pipette tip 1100. The sealing portion 1207 may be configured to form a seal against an inner wall of the pipette tip 1100. The sealing portion 1207 may form a fluid-tight seal within the pipette tip such that when the plunger 1200 is placed within the pipette tip 1100, fluid does not flow from a proximal side of the sealing portion 1207 to a 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 body portion 1206 to the end portion 1210. The sealing portion 1207 may define a step between the body portion 1207 and the end portion 1210. The sealing portion 1207 may be substantially tapered, conical, and / or dome-shaped. The end 1210 of the plunger 1200 may be configured to be received in 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.

[0054] 18-22, a method of coupling a pipette 1010 to a pipetting head 100 of the present invention will now be described. Although the figures associated with the following description only show a single pipette, it will be understood that one or more of the coupling, aspirating, dispensing, and removing operations described may be applied to multiple pipettes simultaneously. For example, if a pipetting head includes 384 mounts, the following description may apply to the simultaneous coupling of 384 pipettes, or any subset thereof.

[0055] In Fig. 18, both the pipette tip clamping mechanism 120 and the plunger clamping mechanism 140 are in a released state. When the pipette tip clamping mechanism 120 is in a 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 a released state, as shown, the plunger clamping plate 145 is in its uppermost position and the enlarged head 148 of the plunger clamping rod 147 is axially offset from the annular recess in the inner surface of each of the plunger mount sleeves. The entire pipetting head 100 is then moved axially using the pipette head Z motor (not shown) to multiple pipettes 1010 so that the tip mount sleeves are received within the tip connector portions of the pipette tips 1100. During insertion of the tip mount sleeves 123 onto the proximal ends of the pipette tips 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 outwardly to an extended position. Once the annular rib 1123 is received in the annular groove 124, as shown in FIG. 18, the flexible segments return to an undeflected or only partially deflected state. In this position, the tip connector portion is at rest and each pipette tip 1100 is coupled to its respective pipette tip mount sleeve 123 with a snap-fit ​​connection. This is step 1.

[0056] Step 2 is described with reference to FIG. 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 FIG. 19. This causes the tip clamping sleeve 127 to extend around the tip connector portion 1103 of each pipette tip 1100 such that the clamping region of each tip clamping sleeve is adjacent to the snap-fit ​​connection between each pipette tip 1100 and its respective tip mount sleeve 123. The inner diameter of the clamping region 128 is less than the expanded diameter of the tip connector portion 1103 and may, for example, be substantially the same as the unexpanded outer diameter or "first" outer diameter of the tip connector portion. This configuration prevents the tip connector portion 1103 from fully expanding, thus preventing the radially extending feature 1123 on the inner surface of the pipette tip 1100 from releasing from the groove 124 on the outer surface of the tip mount sleeve 123. In this manner, the pipette tip 1100 is "locked" or "clamped" in place without the need to apply any significant force to the tip connector portion of the pipette tip 1100. This reduces the force required to engage the pipette tip clamping mechanism.

[0057] Between steps 1 and 2, the pipette tip clamping mechanism may be optionally moved to a partially engaged "pre-lock" position between the released and engaged states, in which the tapered region 129B of each clamp sleeve 127 is adjacent to the recess 124 in the outer surface of its respective tip mount sleeve 123. This may facilitate picking of a portion of the stack of tips from the tip box, since the picked tip may be secured to the tip mount without interference between the pipette tip clamping plate and the stack of unpicked tips. Once the picked tip has been raised above the stack of unpicked tips by the pipetting head, the picked tip may then be fully clamped in place by moving the pipette tip clamping plate 125 to the clamping position.

[0058] Step 3 is described with reference to FIG. 20. In step 3, the entire plunger clamping mechanism 140 is lowered using a direct drive actuator, causing the plunger mount sleeve 143 to contact the plunger connector portion 1203 at the top 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 against the outer surface of the plunger connector portion, deflecting the plunger connector portion inwardly to a contracted or depressed position, where the shaped head 1223 on the top of the plunger 1200 is received in the indentation 144 on the inner surface of the plunger mount sleeve 143. Once the shaped head 1223 is received in the indentation 144 on the inner surface of the plunger mount sleeve 143, as shown in FIG. 20, the flexible segment 1221 of the plunger connector portion 1203 returns to an undeflected or partially deflected state. In this position, the plunger connector portion is stationary and each plunger 1200 is coupled to its respective plunger mount sleeve 143 with a snap fit connection.

[0059] Step 4 is described with reference to FIG. 21. In step 4, the plunger clamping plate 145 is moved axially by the plunger clamp drive mechanism towards the plunger mounting plate 141 until the heads 148 of the plunger clamp rods are adjacent to the snap-fit ​​connection between the plunger and the plunger mount sleeve. The outer diameter of the heads 148 of each clamping rod is greater than the inner diameter, or "second inner diameter", of the plunger in the contracted state. For example, the outer diameter of the heads 148 of each clamping rod may be substantially the same as the inner diameter, or "first" inner diameter, of the undeflected plunger. This configuration prevents the plunger connector portion from fully contracting to the contracted position, thus preventing the molded head 1223 of the plunger 1200 from releasing from the recess 144 on the inner surface of the plunger mount sleeve 143. In this manner, the plunger 1200 is "locked" or "clamped" in place without the need to apply any significant pushing force to the plunger connector portion. This reduces the force required to engage the plunger clamping mechanism.

[0060] To perform an aspiration operation, the pipetting head 100 is moved to a desired position relative to the set of liquid samples using the pipetting head Z motor. The plunger of each pipette is then raised within its respective pipette tip using a direct drive actuator, as shown in Figure 22, to move the entire plunger clamping mechanism away from the pipette tip clamping mechanism and aspirate the fluid into the pipette tip. Fluid can then be dispensed as desired by moving the plunger clamping mechanism in the opposite direction using the direct drive actuator.

[0061] Once the aspirating and dispensing operations are completed, the pipette or pipettes may be removed as follows: First, the plungers are each moved to the bottom end where they travel inside each pipette tip, and the tip clamping mechanism 120 is released by moving the tip clamping plate 125 towards the tip mounting plate 121, moving 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. The plunger clamping plate 145 is then moved toward the plunger mounting plate 141 beyond the engaged position, causing the head 148 of each clamping rod 147 to be moved out of alignment with the snap-fit ​​connection between each plunger 1200 and its respective plunger mount 143, and instead causing the neck portion 149A of each clamping rod 147 to be aligned with the snap-fit ​​connection and abut a distal end face of the clamping rod's head against the interior wall 1224 of the plunger connector portion 1203. Because the neck portion 149A of the clamping rod 147 has an outer diameter that is less than the second depressed inner diameter of the plunger connector portion 1203, the plunger connector portion is not restricted from deflecting inwardly to the depressed state when the clamping rods are in this position. Continued downward movement of the plunger clamping plate 145 thus releases the molded head 1223 of the plunger connector portion 1203 from the corresponding radially extending feature 144 of the plunger mount 143, removing the plunger 1200 from the pipetting head. Further downward movement of the plunger clamping plate, and thus the clamping rod and plunger itself, causes the distal ends of the plungers to press against the portions of the pipette tip within which they are located. In this manner, the plunger and plunger clamping feature can be used to release the pipette tip 1100 from the pipette tip mount 123, thereby removing the pipette 1010 from the pipetting head.

[0062] Although the invention has been described above with reference to one or more preferred embodiments, it will be appreciated that various changes or modifications can be made without departing from the scope of the invention as defined in the appended claims.

[0063] The present invention may be described or defined according to the following clauses.

[0064] 1. A pipetting head for a liquid dispensing apparatus for use with a number of pipettes, each pipette having a pipette tip and a plunger disposed within the pipette tip, the pipetting head comprising: a pipette tip coupling mechanism having a plurality of tip mounts for holding pipette tips of multiple pipettes during use; a plunger coupling mechanism having a plurality of plunger mounts for holding multiple pipette plungers during use; Equipped with (i) each of the plurality of tip mounts includes a radially extending feature on an outer surface thereof configured to form one half of a snap-fit ​​connection, the pipette tip connection feature comprising: a plurality of chip clamping members, each associated with one of the plurality of chip mounts, each having a clamping region; a tip clamping drive mechanism including an actuator operable to selectively engage the pipette tip clamping mechanism by causing relative movement axially between the tip mount and the tip clamping member to move the pipette tip clamping mechanism between a clamped position and a released position; a pipette tip clamping mechanism further comprising: the clamping region of each tip clamping member is axially adjacent to the radially extending feature on the outer surface of its associated tip mount when the pipette tip clamping mechanism is in the clamped position, and the clamping region of each tip clamping member is axially offset from the radially extending feature on the outer surface of its associated tip mount when the pipette tip clamping mechanism is in the released position; and / or (ii) each of the plurality of plunger mounts has a radially extending feature on an inner surface thereof configured to form one half of a snap-fit ​​connection, the plunger connection feature comprising: a plurality of plunger clamping members, each associated with one of the plurality of plunger mounts, each having a clamping region; a plunger clamping drive mechanism including an actuator operable to selectively engage the plunger clamping mechanism by causing relative movement axially between the plunger mount and the plunger clamping member to move the plunger clamping mechanism between a clamped position and a released position; The plunger tightening mechanism further comprises: A pipetting head, wherein the clamping area of ​​each plunger clamping member is axially adjacent to the radially extending feature on the inner surface of its associated plunger mount when the plunger clamping mechanism is in the clamped position, and the clamping area of ​​each plunger clamping member is axially offset from the radially extending feature on the inner surface of its associated plunger mount when the plunger clamping mechanism is in the released position.

[0065] 2. A pipetting head as described in paragraph 1, wherein the plurality of tip clamping members comprises a plurality of sleeves, the plurality of sleeves defining a clamping area when the pipette tip clamping mechanism is in a clamped position, being coaxial with the plurality of tip mounts and surrounding the plurality of tip mounts.

[0066] 3. The pipetting head of claim 2, wherein the pipette tip clamping mechanism comprises a pipette tip clamping plate on which a plurality of tip clamping members are provided, the pipette tip clamping plate being axially movable relative to a plurality of pipette tip mounts to selectively engage the pipette tip clamping mechanism.

[0067] 4. The pipetting head of claim 3, wherein the plurality of sleeves are defined by openings defined in the pipette tip clamping plate.

[0068] 5. The pipetting head of any one of claims 1 to 4, wherein the radially extending feature on the outer surface of each of the plurality of tip mounts is a circumferential groove.

[0069] 6. A pipetting head as described in any one of claims 1 to 5, wherein the plurality of plunger mounts include a plurality of axially extending sleeves, and the plurality of plunger clamping members include a clamping rod that extends in a plurality of axial directions and defines a clamping region when the plunger clamping mechanism is engaged, the clamping rod extending in a plurality of axial directions within the plurality of axially extending sleeves.

[0070] 7. A pipetting head as described in paragraph 6, wherein the plurality of clamping rods each have an enlarged distal end connected to a narrower shaft portion, the enlarged distal ends defining a clamping region.

[0071] 8. A pipette for use with the pipetting head according to any one of claims 1 to 7, 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 a pipette tip connection mechanism of a pipetting head in use; a plunger having a distal end positioned within the interior of the pipette tip and a proximal end having a hollow plunger connector portion for connecting the plunger to a plunger coupling mechanism of the pipetting head during use; Equipped with (i) the tip connector portion has a radially extending feature on an inner surface thereof configured to form a snap-fit ​​connection with a radially extending feature on an outer surface of one of the plurality of pipette tip mounts, the tip connector portion being configured to resiliently deflect in a radially outward direction from a rest position in which the tip connector portion has a first outer diameter to an expanded position in which the tip connector portion has a second outer diameter that is greater than the first outer diameter by at least the radial extent of the radially extending feature on the tip connector portion; and / or (ii) the plunger connector portion has a radially extending feature on an outer surface thereof configured to form a snap-fit ​​connection with a radially extending feature on an inner surface of one of the plurality of plunger mounts, the plunger connector portion being configured to be resiliently deflected in a radially inward direction from a rest position in which the plunger connector portion has a first inner diameter to a pushed-in position in which the plunger connector portion has a second inner diameter smaller than the first inner diameter by at least the radial extent of the radially extending feature of the plunger connector portion.

[0072] 9. The pipette of claim 8, wherein the tip connector portion comprises a segmented tubular wall defined by a plurality of flexible segments configured to elastically deflect in a radially outward direction to deflect the tip connector portion from a rest position to an extended position.

[0073] 10. A pipette according to claim 8 or 9, wherein the radially extending feature on the inner surface of the tip connector portion comprises a circumferential rib that projects radially inward from the inner surface of the tip connector portion.

[0074] 11. A pipette as described in any one of claims 8 to 10, wherein the plunger connector portion comprises a segmented tubular wall defined by a plurality of flexible segments configured to resiliently deflect in a radially inward direction to deflect the plunger connector portion from a rest position to a pushed-in position.

[0075] 12. A pipette as described in any one of claims 8 to 11, wherein the radially extending feature on the outer surface of the plunger connector portion comprises a molded head portion immediately adjacent a circumferential groove that extends radially outwardly onto the inner surface of the plunger connector portion.

[0076] 13. A pipetting head as described in any one of claims 2 to 4, further comprising at least one pipette as described in any one of claims 8 to 12, wherein the clamping region of each of the plurality of sleeves of the tip clamping mechanism has an inner diameter that is 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 clamped position, the clamping region prevents the tip connector portion from deflecting to an extended position, thereby releasing the snap-fit ​​connection.

[0077] 14. A pipetting head as described in claim 6 or 7, further comprising at least one pipette as described in any one of claims 8 to 12, wherein the clamping region of 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 clamped position, the clamping region prevents the plunger connector portion from deflecting into the pushed-in position, thereby releasing the snap-fit ​​connection.

[0078] 15. A body having a microplate receiving area; A pipetting head according to any one of claims 1 to 7, 13, or 14, the pipetting head being positioned above a microplate receiving area; A liquid dispensing device comprising:

Claims

1. A pipette operating head for use with a number of pipettes, each having a pipette tip and a plunger provided within the pipette tip, the pipette operating head comprising: a pipette tip coupling mechanism having a plurality of tip mounts for holding the pipette tips of the number of pipettes during use; a plunger coupling mechanism having a plurality of plunger mounts for holding the plungers of the number of pipettes during use and each of the plurality of plunger mounts has a radially extending mechanism on its inner surface configured to form half of a snap fit connection, the plunger coupling mechanism comprising: a plurality of plunger clamping members, each associated with one of the plurality of plunger mounts and each having a clamping region; a plunger clamping drive mechanism comprising an actuator operable to selectively engage the plunger clamping mechanism by causing relative movement between the plunger mount and the plunger clamping member in an axial direction and moving the plunger clamping mechanism between a clamped position and a released position; a plunger clamping mechanism further comprising wherein the plurality of plunger mounts comprise a plurality of axially extending sleeves, the plurality of plunger clamping members comprise a plurality of axially extending clamping rods, the clamping rods define the clamping regions when the plunger clamping mechanism is engaged, extend inside the plurality of axially extending sleeves, the clamping region of each plunger clamping rod is 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 the clamping region of each plunger clamping rod is 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, a pipette operating head.

2. The pipette operating head according to claim 1, wherein each of the plurality of clamping rods has an expanded distal end connected to a narrower shaft portion, the expanded distal end defining the clamping region.

3. Each of the plurality of chip mounts is provided on its outer surface with a radially extending mechanism configured to form half of a snap-fit connection, and the pipette tip connection mechanism includes a plurality of chip clamping members each associated with one of the plurality of chip mounts and each having a clamping region, a chip clamping drive mechanism including an actuator operable to selectively engage the pipette tip clamping mechanism by causing relative movement between the chip mount and the chip clamping member in an axial direction and moving the pipette tip clamping mechanism between a clamping position and a release position and further includes a pipette tip clamping mechanism, wherein the clamping region of each chip clamping member is axially adjacent to the radially extending mechanism on the outer surface of its associated chip mount when the pipette tip clamping mechanism is in the clamping position, and the clamping region of each chip clamping member is axially offset from the radially extending mechanism on the outer surface of its associated chip mount when the pipette tip clamping mechanism is in the release position. The pipette operating head according to claim 1. **Claim 4** The plurality of chip clamping members include a plurality of sleeves, the plurality of sleeves defining the clamping region when the pipette tip clamping mechanism is in the clamping position, being coaxial with the plurality of chip mounts, and surrounding the plurality of chip mounts. The pipette operating head according to claim 3. **Claim 5** The pipette tip clamping mechanism includes a pipette tip clamping plate on which the plurality of chip clamping members are provided, the pipette tip clamping plate being axially movable relative to the plurality of pipette tip mounts and selectively engaging the pipette tip clamping mechanism. The pipette operating head according to claim 4. **Claim 6** The plurality of sleeves are defined by openings defined in the pipette tip clamping plate. The pipette operating head according to claim 5. **Claim 7** The radially extending mechanism on the outer surface of each of the plurality of chip mounts is a circumferential groove. The pipette operating head according to claim 3. **Claim 8** A pipette operating head for use with a number of pipettes, each having a pipette tip and a plunger provided within the pipette tip, wherein the pipette operating head comprises a plunger coupling mechanism having a plurality of plunger mounts for holding the plungers of the number of pipettes during use a pipette tip coupling mechanism having a plurality of tip mounts for holding the pipette tips of the number of pipettes during use, each of the plurality of tip mounts being provided on its outer surface with a radially extending mechanism configured to form half of a snap-fit connection, the pipette tip coupling mechanism comprising a plurality of tip clamping members, each associated with one of the plurality of tip mounts and each having a clamping region a tip clamping drive mechanism comprising an actuator operable to selectively engage the pipette tip clamping mechanism by causing relative movement between the tip mount and the tip clamping member in an axial direction and moving the pipette tip clamping mechanism between a clamped position and a released position a pipette tip clamping mechanism further comprising the pipette tip coupling mechanism comprising the plurality of tip clamping members comprising a plurality of sleeves, the plurality of sleeves defining the clamping regions and being coaxial with the plurality of tip mounts, each of the plurality of sleeves surrounding the plurality of tip mounts by the clamping region of each sleeve axially adjacent to the radially extending mechanism on the outer surface of its associated tip mount when the pipette tip clamping mechanism is in the clamped position, the clamping region of each sleeve being axially offset from the radially extending mechanism on the outer surface of its associated tip mount when the pipette tip clamping mechanism is in the released position, a pipette operating head. **Claim 9** The pipette operating head according to claim 8, wherein the plurality of tip clamping members comprise a plurality of sleeves, the plurality of sleeves defining the clamping regions and being coaxial with the plurality of tip mounts and surrounding the plurality of tip mounts when the pipette tip clamping mechanism is in the clamped position. **Claim 10** The pipette tip clamping mechanism includes a pipette tip clamping plate, on which a plurality of tip clamping members are provided. The pipette tip clamping plate is axially movable relative to the plurality of pipette tip mounts and selectively engages the pipette tip clamping mechanism. The pipette operating head according to claim 9.

11. The plurality of sleeves are defined by openings defined in the pipette tip clamping plate. The pipette operating head according to claim 10.

12. The radially extending mechanism on the outer surface of each of the plurality of tip mounts is a circumferential groove. The pipette operating head according to claim 8.

13. A pipette for use with the pipette operating head according to claim 1, A pipette tip having a distal end with a dispensing opening and a proximal end having a tip connector portion for connecting the pipette tip to the pipette tip connection 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 connection mechanism of the pipette operating head during use Comprising, The plunger connector portion has a radially extending mechanism configured to form half of a snap-fit connection on its outer surface. The plunger connector portion is configured to elastically deflect radially inward from a rest position where the plunger connector portion has a first inner diameter to a pushed-in position where the plunger connector portion has a second inner diameter smaller than the first inner diameter by at least the radial extent of the radially extending mechanism of the plunger connector portion. A pipette.

14. The tip connector portion comprises a split tubular wall defined by a plurality of flexible segments configured to elastically deflect radially outward to deflect the tip connector portion from the rest position to the expanded position. The pipette according to claim 13.

15. The radially extending mechanism on the inner surface of the tip connector portion extends circumferentially. The pipette according to claim 13.

16. The mechanism extending in the radial direction on the inner surface of the tip connector part includes a circumferential rib protruding radially inward from the inner surface of the tip connector part. The pipette according to claim 15.

17. The plunger connector part includes a split tubular wall defined by a plurality of flexible segments configured to elastically deflect in the radially inner direction to deflect the plunger connector part from the stationary position to the pushing-in position. The pipette according to claim 13.

18. The mechanism extending in the radial direction on the outer surface of the plunger connector part extends in the circumferential direction. The pipette according to claim 13.

19. The mechanism extending in the radial direction on the outer surface of the plunger connector part includes a molded head part directly adjacent to a circumferential groove extending radially outward to the inner surface of the plunger connector part. The pipette according to claim 18.

20. The pipette operation head according to claim 1, further comprising at least one pipette according to claim 13, wherein each of the tightening regions of the plurality of axially extending tightening rods has an outer diameter that is less than or equal to the first inner diameter of the plunger connector part and greater than the second inner diameter of the plunger connector part. When the plunger tightening mechanism is in the clamping position, the tightening region prevents the plunger connector part from deflecting to the pushing-in position, thereby releasing the snap-fit connection.

21. A body having a microplate receiving area, A liquid dispensing device comprising the pipette operation head according to claim 1, which is positioned above the microplate receiving area.

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