Multi-stage pipette tip holder and ejection mechanism for dynamic wide-volume range pipettes

Abstract

Disclosed herein are wide-volume range pipettes with multi-stage pipette tip holders and ejection assemblies, as well as methods for using such pipettes. These pipettes typically include a concentric cylinder arrangement, with each outer cylinder configured to contact and release a pipette tip attached to the tip holder portion of the adjacent inner cylinder. In this manner, pipette tips of different sizes can be used with a single device. Additionally, a locking mechanism is described for locking a large tip holder in a downward position to minimize extension of a small tip holder, thereby enabling attachment of large, filtered pipette tips and reducing / eliminating the risk of contaminating the pipetting device with transferred liquid.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of the filing date of U.S. Provisional Application No. 63 / 402,858, filed August 31, 2022, the entire contents of which are incorporated herein by reference.

[0002] The present invention relates generally to pipetting devices capable of dispensing liquids over a wide range of volumes. In particular, a pipetting device is described herein that has a multi-stage pipette tip holder design and a concentric cylinder ejection mechanism to allow pipette tips of various sizes to be used with a single device. [Background technology]

[0003] Pipettes and other similar liquid dispensing devices are commonly used in laboratories and field research to administer liquids. A typical pipette contains a piston movable within a cylinder that aspirates and dispenses liquid into a disposable pipette tip attached to the dispensing end of the pipette. The amount of liquid is usually adjustable. The piston is moved by manual operation (e.g., applied force to a button) or by an electric motor and associated control system. Electronic pipettes, for example, include a control system and associated user interface for setting the volume and other required pipette functions and for providing commands to perform the operation. Once the desired function is selected and the dose and other settings are entered, the piston is automatically actuated by pressing an operating switch.

[0004] Pipettes are commonly used to dispense liquids in volumes less than approximately 1 mL and in the range of approximately 0.5 μl to approximately 1 mL. However, as experienced technicians understand, current pipette technology does not allow for the use of a single fluid displacement device to dispense liquid volumes across this entire range, at least not without sacrificing accuracy and precision. A typical wet lab task requiring the dispensing of liquids in this range requires the use of three to four different pipette devices, each optimized for accurate and precise aspirating / dispensing a subset of this volume range. For example, researchers typically use 20 μl pipettes to dispense volumes ranging from approximately 2 μl to approximately 20 μl, 200 μl pipettes to dispense volumes ranging from approximately 20 μl to approximately 200 μl, and 1000 μl pipettes to dispense volumes ranging from approximately 100 μl to approximately 1000 μl. Furthermore, each pipette has a tip holder with an outer diameter specifically suited to accommodate disposable pipette tips of a specific size (and volume). Having to use multiple devices clutters the work area and drives up costs. Thus, not only must pipetting devices be designed for the aspiration of a precise volume range of liquids, but such pipettes must also be able to accommodate pipette tip sizes in order to achieve accurate and precise wide volume range capabilities with a single device.

[0005] Therefore, there is a need for a single pipetting device that can use a variety of pipette tip sizes to ensure accuracy and precision in transferring liquids over a wide range of volumes. Summary of the Invention

[0006] Described herein is a wide-volume range pipetting device with a multi-stage pipette tip holder and a concentric cylinder pipette tip ejection design. In particular, the device disclosed herein preferably employs a dispensing unit portion comprising two or more cylindrical housings arranged around a chamber cylinder containing a piston and a vacuum chamber. Each cylinder or cylindrical housing is slightly tapered near its lower end. Each cylinder preferably has an inner diameter at least slightly larger than the outer diameter of the adjacent cylinder with which it is positioned (i.e., a concentric arrangement) and is configured to move along the axis of the adjacent inner cylinder (i.e., move up and down relative to the adjacent inner cylinder). Furthermore, the inner cylinder tends to extend beyond the lower end of the adjacent outer cylinder to provide a pipette tip mounting surface. In this way, the concentric arrangement of cylinders provides a multi-stage pipette tip holder surface for mounting pipette tips of various sizes. Cylinders with smaller outer diameters are configured for mounting small pipette tips, and cylinders with larger outer diameters are configured for mounting large pipette tips. Additionally, the lower end of each outer cylinder can contact and release a pipette tip attached to the tip holder of the adjacent inner cylinder. The pipetting device also includes an ejection element that can be used to apply force to the concentric cylinders and eject the pipette tip. In some embodiments, the pipetting device also includes a locking mechanism to prevent contamination of the dispensing tip when a particular pipette tip is being used.

[0007] In one aspect, the invention features a pipette with a multi-stage pipette tip holder and ejection mechanism. The device includes a pipette body having an upper drive unit portion and a lower dispensing portion. The lower dispensing portion includes a small tip holder portion and a chamber cylinder. The chamber cylinder has a fluid inlet for injecting fluid into and ejecting fluid from the chamber cylinder. The device also includes an ejection assembly including an ejection element, an ejection rod, a first dispenser cylinder having a large tip holder portion and a small tip ejection edge, and a second dispenser cylinder having a large tip ejection edge. The first dispense cylinder is disposed around the chamber cylinder and configured to move up and down relative to the chamber cylinder, and the second dispense cylinder is disposed around the first dispense cylinder and configured to move up and down relative to the first dispense cylinder. In this embodiment, the ejection rod is configured to contact the second dispense cylinder and move the second dispense cylinder to a first position where the large tip ejection edge contacts and ejects a large pipette tip from the large tip holder portion when a first force is applied to the ejection element, or to move the first dispense cylinder to a second position where the small tip ejection edge contacts and ejects a small pipette tip from the small tip holder portion when a second force is applied to the ejection element. In one embodiment, the fluid is air.

[0008] In one embodiment, the pipette further includes a biasing element disposed circumferentially around a portion of the ejection rod and configured to bias the ejection rod toward an upward position. In another embodiment, the large tip holder portion has an outer diameter that is larger than an outer diameter of the small tip holder portion. In a preferred embodiment, the ejection element is disposed in the upper drive unit portion.

[0009] In some embodiments, the pipette includes a first ejection member connected to the first dispense cylinder, and both a second ejection member and an ejection rod connected to the second dispense cylinder, such that the second ejection member contacts the first ejection member and can move to a second position when a second force is applied to the ejection element. In another embodiment, the first and second ejection members are disposed in an upper drive unit portion, and the first and second dispense cylinders form part of a lower dispense portion.

[0010] In some embodiments, the pipette also includes a piston slidably positionable within the chamber cylinder between an open position and a closed position, and a motor disposed within the upper drive unit portion, operably connected to the piston, and configured to actuate the piston between the open and closed positions within the chamber cylinder. Actuation of the piston to the open position thus defines a volume of liquid aspirated by the pipette that is approximately equal to the volume of fluid displaced by movement of the piston. In yet other embodiments, the small tip holder portion is configured to accommodate pipette tips having a maximum liquid capacity ranging from about 2 μl to about 200 μl, preferably from about 20 μl to about 200 μl. In yet other embodiments, the large tip holder portion is configured to accommodate pipette tips having a maximum liquid capacity ranging from about 200 μl to about 5,000 μl, preferably from about 200 μl to about 1,000 μl.

[0011] In another embodiment, the pipette further includes a locking mechanism comprising a trigger, a biasing element, and a locking rod movable between a locked position and an unlocked position. Movement of the second dispense cylinder and the first dispense cylinder to the second position causes the locking rod to move to the locked position and prevent upward movement of the first dispense cylinder. Further, force applied to the trigger against the biasing element causes the locking rod to move to the unlocked position, whereby the locking rod no longer prevents upward movement of the first dispense cylinder. In one embodiment, the locking rod contacts an underside of the trigger when in the locked position.

[0012] In another embodiment, the pipette further includes a printed circuit board for controlling the motor in response to an end-user volumetric input, and a sensor in electronic communication with the printed circuit board. In this embodiment, the sensor is configured to detect when the first dispense cylinder is unlocked and prevents the motor from moving the piston upward to the open position to an extent that defines an amount of liquid aspirated by the pipette that exceeds the maximum liquid capacity of the small pipette tip. The sensor also detects when the first dispense cylinder is locked and allows the motor to move the piston upward to the open position to an extent that defines an amount of liquid aspirated by the pipette that exceeds the maximum liquid capacity of the small pipette tip.

[0013] Another aspect of the invention features a method for changing a pipette tip in the above-described pipette, comprising applying a force to the ejection element until the small tip ejection edge contacts and disengages from the small tip holder portion, or applying a force to the ejection element until the large tip ejection edge contacts and disengages from the large tip holder portion, depending on whether a small or large pipette tip is attached to the corresponding tip holder portion. In one embodiment, the method includes inserting the small tip holder portion into the pipette receiving end of the small pipette tip to form an interference fit. In another embodiment, the method includes inserting the large tip holder portion into the pipette receiving end of the large pipette tip to form an interference fit. In yet another embodiment, the method includes holding down the trigger while applying force to the ejection element.

[0014] Another aspect of the present invention features a pipetting device having a multi-stage pipette tip holder and ejection mechanism, which includes an elongated pipette body with an air inlet at the dispensing end, an ejection element, and a concentric cylinder assembly. The concentric cylinder assembly includes a chamber cylinder in fluid communication with the fluid inlet, a small tip ejection cylinder having a small tip ejection edge and a large tip holder portion, and a cylindrical dispenser housing having a large tip ejection edge. Further, the chamber cylinder is concentrically received within the small tip ejection cylinder. The small tip ejection cylinder is concentrically received within the cylindrical dispenser housing and configured to move up and down relative to the chamber cylinder. The cylindrical dispenser housing is configured to move up and down relative to the small tip ejection cylinder. In this embodiment, the pipetting device also includes an ejection rod in mechanical communication with the ejection element and configured to move the cylindrical dispenser housing to a first position where the large tip ejection edge contacts and ejects the large pipette tip from the large tip holder portion when a first force is applied to the ejection element, or to move the small tip ejection cylinder to a second position where the small tip ejection edge contacts and ejects the small pipette tip from the small tip holder portion when a second force is applied to the ejection element.

[0015] In one embodiment, the pipetting device also includes a first ejection member connected to the small tip ejection cylinder and a second ejection member connected to the ejection rod and the cylindrical dispenser housing. Thus, the ejection rod moves the second ejection member and the cylindrical dispenser housing to a first position when a first force is applied to the ejection element, or the ejection rod moves the second ejection member to a second position, contacting the first ejection member and the small tip ejection cylinder, when a second force is applied to the ejection element. In another embodiment, the pipetting device includes a locking mechanism including a trigger, a biasing element, and a locking rod movable between a locked position and an unlocked position. Movement of the cylindrical dispenser housing and the small tip ejection cylinder to the second position moves the locking rod to a locked position, preventing upward movement of the small tip ejection cylinder.

[0016] In another embodiment, a force applied to the trigger against the biasing element moves the locking rod to an unlocked position whereby the locking rod no longer impedes upward movement of the small chip ejection cylinder. In yet another embodiment, the locking rod contacts the underside of the trigger when in the locked position.

[0017] In some embodiments, the pipetting device includes a piston slidably positionable within the chamber cylinder between an open position and a closed position, and a motor operably coupled to the piston and configured to actuate the piston within the chamber cylinder between the open and closed positions. Actuation of the piston to the open position thus defines a volume of liquid aspirated by the pipette approximately equal to the volume of fluid displaced by the movement of the piston. In one embodiment, the motor is mechanically connected to the threaded piston, which is connected to the piston by one or more magnets. In another embodiment, the pipetting device may include a printed circuit board for controlling the motor in response to an end-user volumetric input, and a sensor in electronic communication with the printed circuit board. The sensor detects when (i) the small tip ejection cylinder is unlocked, preventing the motor from moving the piston upward to the open position to an extent that defines a volume of liquid aspirated by the pipette that exceeds the maximum liquid capacity of the small pipette tip, and / or (ii) the small tip ejection cylinder is locked, allowing the motor to move the piston upward to the open position to an extent that defines a volume of liquid aspirated by the pipette that exceeds the maximum liquid capacity of the small pipette tip.

[0018] Other features and advantages of the present invention will become apparent with reference to the drawings, detailed description, and examples that follow. [Brief explanation of the drawings]

[0019] [Figure 1] FIG. 1 is a side view of one embodiment of a pipetting device described herein. [Figure 2A] FIG. 1 is a side view of an embodiment of a pipetting device with the locking mechanism unlocked for small pipette tip attachment. [Figure 2B] FIG. 1 is a side view of an embodiment of a pipetting device with the locking mechanism engaged for large pipette tip attachment. [Figure 2C]A close-up view of the pipette dispensing end with the locking mechanism unlocked for small pipette tip installation. [Figure 2D] A close-up view showing the small pipette tip mounted in the small tip holder section [Figure 2E] A close-up view of the pipette dispensing end with the locking mechanism engaged for larger pipette tip attachment. [Figure 2F] A close-up view showing a large pipette tip attached to the large tip holder portion of the large tip cylinder [Figure 2G] FIG. 1 is an internal view of an exemplary ejection mechanism and locking mechanism with the locking mechanism disengaged. [Figure 2H] FIG. 1 is an internal view of an exemplary ejection mechanism with the locking mechanism engaged. [Figure 2I] FIG. 1 is a bottom interior perspective view showing an exemplary ejection mechanism and locking mechanism with the locking mechanism engaged. [Figure 3A] 1 is an exploded view of an exemplary pipetting device; [Figure 3B] 1 is an exploded view of an exemplary pipetting device; [Figure 3C] 1 is an exploded view of the drive unit of an exemplary pipetting device; [Figure 3D] 1 is an exploded view of the drive unit of an exemplary pipetting device; [Figure 3E] 1 is an exploded view of the drive unit of an exemplary pipetting device; [Figure 3F] 1 is an exploded view of the drive unit of an exemplary pipetting device; [Figure 4] 1 is a cross-sectional view of an exemplary pipetting device; [Figure 5A] 1 is a cross-sectional view illustrating an alternative embodiment of a locking mechanism. [Figure 5B] FIG. 10 is a perspective view showing an alternative locking mechanism; DETAILED DESCRIPTION OF THE INVENTION

[0020] The pipetting device described herein utilizes a multi-stage pipette tip holder and ejection assembly, allowing different sizes of pipette tips to be used with a single pipette, resulting in accurate and precise transfer of a wide range of liquid volumes. The multi-stage pipette tip holder and ejection assembly includes a dispensing unit with a nested concentric cylinder design. Typically, the innermost cylinder is a chamber cylinder, which typically contains a vacuum chamber and a piston for inducing liquid aspiration. Connected to the lower end (or integral with the chamber cylinder) is the dispensing end of the pipetting device, which also contains a small tip holder portion. Two or more cylinders are then concentrically positioned above the chamber cylinder and small tip holder portion, with inner cylinders extending beyond the lower end of the immediately adjacent outer cylinder to provide a mounting portion or surface for pipette tips. Therefore, each adjacent outer cylinder preferably has an inner diameter slightly larger than the outer diameter of the adjacent inner cylinder. Furthermore, each outer cylinder is configured to move up and down relative to the immediately adjacent inner cylinder, and each outer cylinder preferably has a lower end that functions as an ejection edge for disengaging pipette tips from the tip holder portion of the immediately adjacent inner cylinder.

[0021] The ejection element and rod mechanism can be incorporated to allow an end user to manually or via a motor-controlled actuator mechanism to apply a downward force to one or more ejection cylinders to eject either small or large pipette tips. In this manner, the multi-stage concentric cylinder design allows for the use of both small and large pipette tips with a single pipetting device and can facilitate ejection of multi-stage pipette tips from their mounting locations. Additionally, a locking mechanism can be incorporated into the design to maintain the large tip holder cylinder in a downward position, reducing the extension of the small tip holder beyond the small tip ejection edge of the large tip holder cylinder, thereby allowing the attachment of large pipette tips while minimizing or eliminating the possibility of contamination from the aspirated liquid. The pipetting device and ejection assembly are described in more detail below.

[0022] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Standard techniques are used unless otherwise specified. Although methods and materials similar or equivalent to those described herein can be used to practice or test the present disclosure, suitable methods and materials are described below. The materials, methods, and examples are illustrative only and are not intended to be limiting. All publications, patents, and other documents mentioned herein are incorporated by reference in their entirety.

[0023] As used herein, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise.

[0024] The term "about" refers to the variation in the numerical value of a measurement, e.g., diameter, area, length, volume, etc., due to the typical error rate of the device used to obtain the measurement. In one embodiment, the term "about" means within 5% of the reported numerical value.

[0025] As used herein, the term "approximately equivalent" is used to refer to the volume of fluid displaced by the device compared to the volume of liquid aspirated by the device, and means that due to the difference between the density of the fluid and the density of the liquid, the volume of fluid (e.g., air) displaced by the movement of the plunger element in the vacuum chamber is not exactly equal to the volume of liquid aspirated into the tip attached to the end of the device. The design of the device is adjusted to take this factor into account and is within the knowledge of a skilled engineer.

[0026] The terms "interference fit" and "friction fit" are used interchangeably herein and refer to a fixation between two parts that is achieved by friction after the parts are pressed together.

[0027] As used herein, the terms "up" and "down," "upward" and "downward," and "horizontal" and "vertical" refer to the orientation of a pipetting device (see, e.g., FIG. 1). In a pipetting device, the pipette housing and dispenser portion are oriented so that the actuating element or handle is at the top and the dispensing end is at the bottom. In this orientation, a pipette tip fixed or attached to the dispensing end of the pipetting device can be pointed toward a vessel located below it to aspirate or dispense liquid.

[0028] As used herein, the term "outer diameter" or "outer circumferential diameter" refers to the diameter across a cylindrical part measured from one point on the outer surface of the cylinder wall to another point on the outer surface of the cylinder wall. As used herein, the term "inner diameter" refers to the diameter across a cylindrical part measured from one point on the inner surface of the cylinder wall to another point on the inner surface of the cylinder wall.

[0029] Air-displacement pipettes are commonly used in the art. While the exemplary embodiments described herein disclose a single-piston, motor-driven air-displacement pipette device, other pipette designs, such as dual-motor nested plunger designs and manually operated plunger designs, can also be adapted for use with the pipette tip ejection assembly and locking mechanism. As understood in the art, single-piston air-displacement designs utilize the movement of a piston within a cylindrical vacuum chamber to aspirate and dispense a volume of liquid. Typically, an appropriately sized disposable pipette tip is attached to the dispensing end of the pipette device. The end of the pipette tip can be placed into and transferred into a liquid. Upward movement of the piston within the vacuum chamber expands the size of the chamber, thereby creating a vacuum and causing the inflow of fluid (e.g., air). This fluid displacement facilitates the aspirating of a roughly equivalent volume of liquid into the attached pipette tip. Downward movement of the piston within the vacuum chamber forces the fluid (e.g., air) out of the chamber, dispensing the liquid from the pipette tip. By precisely controlling the movement of the piston within the vacuum chamber, the end user can accurately and precisely control the amount of liquid transferred. However, to better ensure accuracy and precision of the liquid transferred, disposable pipette tips with appropriate volumetric capacity must be selected and used. Larger pipette tips capable of accurately transferring larger volumes of liquid tend to have larger attachment circumferences than pipette tips optimized for transferring smaller volumes of liquid, thus emphasizing the need for a pipetting device dimensioned to accommodate a wide range of pipette sizes.

[0030] Exemplary pipetting device designs are shown in Figures 1-4. The piston-driven air-displacement pipette designs shown in the figures are capable of accommodating a wide volume range (e.g., from about 1 μl to about 1000 μl), but such a wide volume range requires the use of both small disposable pipette tips (e.g., having a maximum liquid transfer volume of up to about 5 μl, about 20 μl, about 100 μl, or about 200 μl) and large disposable pipette tips (e.g., having a maximum liquid transfer volume of up to about 1000 μl). As one skilled in the art will recognize, small pipette tips require a smaller tip holder circumference for an interference / friction fit than the tip holder circumference required to accommodate larger pipette tips. Thus, provided herein is a concentric cylinder design in which the increasing outer diameters of successive cylinders form a multi-tiered tip-retaining system, with each successive cylinder having a larger outer diameter for mounting larger pipette tips. These mounting portions or seats are preferably designed with an appropriately sized outer diameter to allow for a sufficient interference fit for either small or large pipette tips. In a preferred embodiment, the small and large tip holders each taper slightly from top to bottom, allowing for easy attachment by inserting the tip holder into the open end of a disposable pipette tip. Because standard sizes of disposable pipette tips are well known in the art, it is well within the purview of a skilled technician to design the shape and size of the small and large tip holders to optimally accommodate the appropriate pipette tip.

[0031] For example, a small tip holder portion suitable for mounting small pipette tips may have an outer diameter that tapers from about 5 mm to about 6 mm (preferably from about 5.2 mm to about 5.6 mm) at the top and from about 4 mm to about 5.2 mm (preferably from about 4.7 mm to about 5.1 mm) at the bottom. In an exemplary embodiment, a large tip holder portion suitable for mounting large pipette tips may have an outer diameter that tapers from about 7.5 mm to about 8.5 mm (preferably from about 7.5 mm to about 7.8 mm) at the top and from about 6.5 mm to about 8 mm (preferably from about 7 mm to about 7.5 mm) at the bottom. For example, the exemplary embodiment described in the Examples has a small tip holder portion with an outer diameter of about 5.6 mm at the top and tapering to about 4.9 mm at the bottom, while the large tip holder portion has an outer diameter of about 8.06 mm at the top and tapering to about 7.3 mm at the bottom. A suitable fluid opening at the dispensing end of the device may have a diameter ranging from about 1.3 mm to about 2 mm (preferably from about 1.5 mm to about 1.8 mm). The multi-tiered arrangement of concentric cylinders provides a pipette tip mounting area or seat suitable for accommodating pipette tips of different sizes.

[0032] The small tip holder portion is suitable for mounting small disposable pipette tips having a maximum liquid transfer volume of about 2 μl to about 200 μl, e.g., 2 μl, 5 μl, 10 μl, 20 μl, 100 μl, or 200 μl. Alternatively, the small tip may have a maximum liquid transfer volume of about 20 μl to about 200 μl. The large tip holder portion is suitable for mounting large disposable pipette tips having a maximum liquid transfer volume of about 200 μl to about 5000 μl, preferably between about 200 μl and about 1000 μl, e.g., 200 μl, 500 μl, or 1000 μl.

[0033] In other embodiments, the outer diameter of the large tip holder and / or the outer diameter of the small tip holder may be designed to accommodate disposable pipette tips with a maximum liquid transfer volume of greater than 1000 μl or less than 2 μl, respectively. For example, the outer diameter of the large tip holder can be increased to a diameter suitable for accommodating disposable pipette tips with a maximum liquid transfer volume of about 1000 μl to about 5000 μl, e.g., 1000 μl, 1500 μl, 2000 μl, 2500 μl, 3000 μl, 3500 μl, 4000 μl, 4500 μl, or 5000 μl (e.g., P5000 disposable pipette tips). Similarly, the outer diameter of the small tip holder can be decreased to a diameter suitable for accommodating disposable pipette tips with a maximum liquid transfer volume of about 2 μl or less, or about 1 μl or less (e.g., P2 disposable pipette tips). Alternatively, rather than changing the outer diameter of the large and / or small tip holders, tip holders with larger or smaller outer diameters can be added to the multi-stage tip holder design to further expand the range of pipette tip sizes that can be accommodated.

[0034] In a preferred design, the large tip cylinder (also referred to as the small tip ejection cylinder or first dispenser cylinder) may have an inner diameter at least slightly larger than the outer diameter of the chamber cylinder and may be disposed around the chamber cylinder. The large tip cylinder serves as a mounting surface for large pipette tips, and the ejection edge serves as a mounting surface for small pipette tips. The chamber cylinder includes or is attached to a small tip holder portion suitable for mounting small pipette tips to the dispensing end of the pipetting device. This arrangement results in the small tip holder portion extending or protruding beyond the ejection edge of the large tip cylinder. At its furthest, the small tip holder portion extends beyond the discharge edge of the large tip cylinder by about 5 mm to about 10 mm, e.g., 5 mm, 5.1 mm, 5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6 mm, 5.7 mm, 5.8 mm, 5.9 mm, 6 mm, 6.1 mm, 6.2 mm, 6.3 mm, 6.4 mm, 6.5 mm, 6.6 mm, 6.7 mm, 6.8 mm, 6.9 mm, 7 mm, 7.1 mm, 7.2 mm, 7.3 mm, 7.4 mm, 7.5 mm, 7.6 mm, 7.7 mm, 7.8 mm, 7.9 ...6 mm, 6.1 mm, 6.2 mm, 6.3 mm, 6.4 mm, The small tip holder portion may extend or protrude by 0.2 mm, 7.3 mm, 7.4 mm, 7.5 mm, 7.6 mm, 7.7 mm, 7.8 mm, 7.9 mm, 8 mm, 8.1 mm, 8.2 mm, 8.3 mm, 8.4 mm, 8.5 mm, 8.6 mm, 8.7 mm, 8.8 mm, 8.9 mm, 9 mm, 9.1 mm, 9.2 mm, 9.3 mm, 9.4 mm, 9.5 mm, 9.6 mm, 9.7 mm, 9.8 mm, 9.9 mm, or 10 mm. Preferably, it extends or protrudes by about 6 mm to about 9 mm beyond the ejection edge of the large tip cylinder. In one exemplary embodiment, the small tip holder portion may extend or protrude by about 9 mm beyond the ejection edge of the large tip cylinder.The large tip cylinder is disposed around the chamber cylinder and is configured to move parallel to the chamber cylinder (i.e., up and down) along the vertical axis of the chamber cylinder, so that when force is applied to the ejection element and rod mechanism, the large tip cylinder moves downward and, if a small pipette tip is attached to the small tip holder portion, the small tip ejection edge contacts the small pipette tip to remove it.

[0035] The next cylinder in the arrangement is a cylindrical dispenser housing (or second dispenser cylinder) having an inner diameter at least slightly larger than the outer diameter of the large tip cylinder, disposed around the large tip cylinder, and configured to move parallel to (i.e., up and down) the large tip cylinder along the vertical axis of the large tip cylinder. The cylindrical dispenser housing has a large tip ejection edge. The cylindrical dispenser housing is disposed around the large tip cylinder and configured to move up and down relative to the large tip cylinder so that when a force is applied to the ejection element and rod mechanism, the cylindrical dispenser housing moves downward, and if a large pipette tip is attached to the large tip holder portion, the large tip ejection edge contacts the large pipette tip and removes it.

[0036] The pipetting devices described herein may include a locking mechanism to prevent upward movement of the large tip cylinder (i.e., lock the large tip cylinder in a downward position) when using large pipette tips, which reduces the length that the chamber cylinder and small tip holder portion extend or protrude beyond the small tip ejection edge of the large tip cylinder. In the locked position, the small tip holder portion may extend or protrude beyond the ejection edge of the large tip cylinder by about 0 mm to about 3 mm, e.g., about 0 mm, 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.1 mm, 1.2 mm, 1.3 mm, 1.4 mm, 1.5 mm, 1.6 mm, 1.7 mm, 1.8 mm, 1.9 mm, 2 mm, 2.1 mm, 2.2 mm, 2.3 mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, or 3 mm. Preferably, it extends or protrudes beyond the ejection edge of the large tip cylinder by about 0 mm to about 1.5 mm. In one exemplary embodiment, when in the locked position, the small tip holder portion may extend or protrude approximately 1.3 mm beyond the discharge edge of the large tip cylinder. In this manner, when a large pipette tip or a large, filtered pipette tip is attached to the large tip holder portion, the risk of contaminating the dispenser opening of the pipetting device when liquid is drawn up into the large pipette tip is reduced. Furthermore, this locking design allows for the attachment of large, filtered pipette tips because the extension of the small tip holder portion does not contact the filter element and does not interfere with the secure interference fit of the large, filtered pipette tip into the large tip holder portion.

[0037] 1-4 illustrate an exemplary embodiment of a multi-stage, concentric pipette tip holder and ejection design on a pipetting device. While a single-piston, air-displacement pipetting device is shown, the ejection mechanism described herein can be adapted for use with many other types of pipetting devices available in the art, such as concentric, dual-piston designs. Additionally, manually operated piston designs are also suitable. As shown in FIG. 1, pipetting device 10 generally has an elongated or rod-like shape and includes an upper drive unit section at its upper portion, including a drive unit, and all associated components housed within pipette housing 15. Pipetting device 10 also generally includes a lower fluid displacement and dispensing section at its lower portion, which generally includes two or more inner cylinders and a cylindrical dispenser housing 20 disposed over most of the dispensing components. In particular, the dispensing section of pipetting device 10 includes concentric cylinders or housings that cooperate to form a multi-stage pipette tip mounting and tip ejection mechanism, as described in detail below. The dispenser section has an opening 45 at the dispensing end and includes a large tip holder 25 and a small tip holder 30. As shown in FIG. 3A, the large tip holder 25 is a portion of the lower portion of the large tip cylinder lower portion 65 nearest the opening 45, and the small tip holder 30 is attached to the end of the chamber cylinder 70. The dispenser housing 20, large tip cylinder 65, and small tip holder 30 / chamber cylinder 70 form a concentric cylinder configuration, with the large tip holder 25 extending from the dispenser housing 20 beyond the large tip discharge edge 35 and the small tip holder 30 extending from the large tip cylinder 65 beyond the small tip discharge end 40, as shown in FIG. 1, for example. This creates a multi-tiered tip holder design, where the circumference of the device at the large tip holder 25 is larger than the circumference at the small tip holder 30.The multi-stage design allows for various sized tips to be fitted or secured via an interference or friction fit, using the circular force of the pipette tip against the tip holder portion of the pipetting device to secure larger pipette tips (e.g., 1000 μl pipette tips) to the larger tip holder 25 or smaller tips (e.g., 10 μl, 20 μl, 100 μl, 200 μl pipette tips) to the smaller tip holder 30. In this manner, the pipetting device 10 can provide a volume of fluid ranging from about 0.1 μl to about 1500 μl, e.g., about 0.1 μl, 0.2 μl, 0.3 μl, 0.4 μl, 0.5 μl, 1.0 μl, 1.5 μl, 2.0 μl, 2.5 μl, 3.0 μl, 4.5 μl, 5.0 μl, 10 μl, 15 μl, 20 μl, 25 μl, 30 μl, 40 μl, 50 μl, 60 μl, 70 μl, 80 μl, 90 μl, 100 μl, 110 μl, 120 μl, 130 μl, 140 μl, 150 μl, 160 μl, 170 μl, 180 μl, 190 μl, 200 μl, 210 μl, 220 μl, 230 μl, 240 μl, 250 μl, 260 μl, 270 μl, 280 μl, 290 μl, 300 μl, 310 μl, 320 μl, 330 μl, 340 μl, 350 μl, 360 μl, 370 μl, 380 μl, 390 μl, 400 μl, 410 μl, 420 μl, 430 μl, 440 μl, 450 μl, 460 μl, 470 μl, 480 μl, 490 μl, 500 μl, 510 μl, 520 μl, 530 μl, 540 μl, 550 1, 190 μl, 200 μl, 210 μl, 220 μl, 230 μl, 240 μl, 250 μl, 260 μl, 270 μl, 280 μl, 290 μl, 300 μl, 350 μl, 400 μl, 450 μl, 500 μl, 550 μl, 600 μl, 650 μl, 700 μl, 750 μl, 800 μl, 850 μl, 900 μl, 950 μl, 1000 μl, 1100 μl, 1200 μl, 1300 μl, 1400 μl, or 1500 μl. In certain embodiments, the pipetting device 10 is capable of aspirating and dispensing liquids in a volume range of between about 0.5 μl and about 1000 μl.

[0038] As one skilled in the art will appreciate, typical pipettes use disposable pipette tips that must be quickly removed and replaced between handling different liquid samples to prevent contamination or unwanted mixing of the liquids. Thus, the ejection mechanism of the present disclosure utilizes a concentric cylinder design to quickly and easily remove both large and small pipette tips without the user having to touch the tip itself.

[0039] Both the dispenser housing 20 and the large tip cylinder 65 have ejection edges, large tip ejection edge 35 and small tip ejection edge 40, respectively, at the ends nearest the opening 45. The pipetting device 10 includes an ejection element 50 at the top of the device that can be depressed to activate the pipette tip ejection mechanism. When a user presses down on the ejection element 50, the dispenser housing 20 moves downward relative to the large tip cylinder 65, large tip holder 25, and small tip holder 30. The large tip ejection edge 35 contacts a large pipette tip attached to the large tip holder 25, disengaging the large pipette tip. As the user continues to press down on the ejection element 50, both the dispenser housing 20 and the lower portion of the large tip cylinder move downward relative to the small tip holder 30. The small tip ejection edge 40 contacts a small pipette tip attached to the small tip holder 30, disengaging the small pipette tip. While the ejection mechanism in this embodiment is manually operated, motor-driven designs are also contemplated and function in a similar manner.

[0040] As shown in FIG. 2A, the small tip holder 30 extends beyond the small tip ejection edge 40 of the large tip cylinder 65 (i.e., by approximately 9 mm), thereby providing a mounting surface for a small pipette tip to be securely attached to the small tip holder 30. FIGS. 2C and 2D are close-up views of the small tip holder 30. A small tip ST is attached to the small tip holder 30 by an interference fit (see FIG. 2D). When an end user aspirates liquid and wishes to change a tip, they manually (or, in an alternative embodiment, electronically via a motor) move the ejection element 50 downward, thereby moving the dispenser housing 20 downward. As the dispenser housing continues to move downward, the small tip ejection edge 40 contacts the small pipette tip ST, disengaging the small pipette top ST from the small tip holder 30, causing the large tip cylinder 65 to also move downward. 2B and 2E, the small tip holder 30 extends slightly beyond the small tip ejection edge 40 (i.e., by about 1.3 mm or less) compared to when the large tip cylinder 65 is in the upper position. In some embodiments, when in the locked position, the small tip holder 30 extends beyond the small tip ejection edge 40 by between about 0 mm and about 3 mm, preferably less than about 2 mm, and more preferably less than about 1.3 mm.

[0041] The ejection mechanism of the present invention may include a locking mechanism configured to maintain the large tip cylinder 65 in a lowered position. In this way, the small tip holder 30 does not extend significantly beyond the small tip ejection edge 40 (see FIG. 2E). The extension of the small tip holder 30 may come into contact with the liquid being aspirated when a large tip is attached to the large tip holder 25 (e.g., when a large volume of liquid is aspirated) or may interfere with the attachment of a large pipette tip containing a filter element. To address this issue, the locking mechanism is configured to maintain the large tip cylinder 65 in a lowered position. As shown in FIG. 2F, a large, filtered pipette tip ST can now be attached to the large tip holder 25 without the small tip holder 30 getting in the way. When the end user wishes to return to using the small pipette tip, pressing the locking trigger 60 returns the large tip cylinder 65 to its upper, open position (see FIGS. 2A and 2C). This allows the end user to easily switch from large to small pipette tips and from small to large pipette tips by utilizing the locking trigger 60.

[0042] Figures 3A-3F show various exploded views of an exemplary pipetting device, including both the ejection mechanism and the locking mechanism. A portion of the pipette housing 15 has been removed, exposing parts of the drive section. Figures 3A-3F also reveal various dispensing section components. The motor 80 is powered by a rechargeable battery 90 controlled by a printed circuit board 95 and is located on a motor holder 85. The motor 80 drives a threaded piston rod 155 and a piston 115. The threaded piston rod 155 is connected to the piston 115 by a pair of magnets 130, which compensate for misalignment in the system; however, magnets may not be required in other embodiments. In this particular embodiment, the motor 80 is a stepper motor. However, other suitable motors may include servo motors, DC motors, or other linear actuator-type motors. As shown in the drawings, the pair of magnets 130 are connected to the threaded piston rod 155 by an upper magnet holder 125 and are coupled to the piston 115 by a lower magnet holder 135. The exemplary magnet may be formed from any suitable material, such as, but not limited to, any type of neodymium, and the magnet holder may be formed from magnetic or non-magnetic materials, including, but not limited to, steel, stainless steel, aluminum, plastic, etc. The motor 80 moves the piston 115 up and down along with the chamber cylinder 70. As the piston 115 moves upward within the chamber cylinder 70, a vacuum is created, forcing air into the device's dispensing unit, which in turn forces liquid into the pipette tip attached to the pipetting device. As the piston 115 moves downward within the chamber cylinder 70, air is forced out of the dispensing unit, which in turn forces liquid out of the pipette tip. The chamber cylinder 70 is attached to the bottom of the motor holder 85 by mating threads 87 and 72. Additionally, an O-ring 120 may be included to form an airtight seal between the piston 115 and the chamber cylinder 70 and prevent air from leaking as the piston 115 moves up and down.The small chip holder 30 is attached to the bottom of the chamber cylinder 70 by screws 74. Another O-ring 75 may be included to form an airtight seal between the small chip holder 30 and the bottom of the large chip cylinder 65.

[0043] FIG. 3A shows the concentric arrangement of the chamber cylinder 70, large tip cylinder 65, and dispenser housing 20. The large tip cylinder 65 is positioned around the chamber cylinder 70 and attached to the small tip ejection member 165 by screws 67, 175 (see also FIG. 3F for the best view of the small tip ejection member 165). The dispense housing 20 is then positioned around the large tip cylinder 65 and attached to the large tip ejection member 55 by screws 22. The ejection element 50 is connected to the ejection rod 140. A biasing element 145 (e.g., a spring) is positioned circumferentially around the ejection rod 140 and biases the ejection rod to an upward position. The ejection rod 140 is connected to the large tip ejection member 55 by passing through hole 86 in the flange of the motor holder 85 and inserting into hole 57. A C-washer 160 and a washer 150 may be included to hold the biasing element 145 in place. When the ejection element 50 is depressed, the ejection rod 140 moves relative to the biasing element 145. The ejection rod 140 moves the large tip ejection member 55 and the dispenser housing 20 downward relative to the large tip holder 25. When a large pipette tip is attached to the large tip holder 25, the large tip ejection edge 35 of the dispenser housing 20 contacts the large pipette tip, disengaging it from the large tip holder 25. The large tip cylinder 65 and the small tip ejection member 165 are separate components in the exemplary embodiment for ease of disassembly and cleaning, although they may be integral or part of the same component. Similarly, the dispenser housing 20 and the large tip ejection member 55 are separate components in the exemplary embodiment for ease of disassembly and cleaning, although they may be integral or part of the same component.

[0044] When a small tip is attached to the small tip holder 30 and needs to be ejected, the end user continues to press the ejection element 50. As the large tip ejection member 55 continues to move downward, the spacer 110 beneath the spacer arm 112 of the large tip ejection member 55 contacts the seat 114 of the small tip ejection member 165. As the large tip ejection member 55 and the small tip ejection member 165 move together, the small tip ejection member 165 moves the large tip cylinder 65 downward. The small tip ejection edge 40 of the large tip cylinder 65 contacts the small pipette tip, disengaging it from the small tip holder 30. When the ejection element 50 is released, the biasing element 145 moves the ejection rod 140 upward, resetting the cylinder position. Thus, the concentric cylinder design of the ejection mechanism allows for the ejection of both small and large tips.

[0045] A locking mechanism is also shown in Figures 2G-2I and 3A-3F. As described above, the locking mechanism can maintain the large tip cylinder 65 in the lower position, preventing contamination when using large pipette tips and allowing for the use of large pipette filter tips. The embodiment of the locking mechanism shown in the figures includes a lock trigger 60 having a trigger protrusion 62 and a lock rod hole 108 extending through a lower portion 109 of the trigger protrusion 62, a biasing element 100 (e.g., a leaf spring), and a lock rod 105 having an upper surface 107. In this embodiment, the ejection mechanism and locking mechanism are shown on opposite sides of the device, but they could also be positioned close to each other or on the sides of the device. The lock rod 105 is inserted through a hole in a spacer element 110 and into a hole 170 in a seat 114 of a small tip ejection member 165. When in the upper, unlocked position, as shown in Figure 2G, the upper surface 107 of the lock rod 105 passes through the lock rod hole 108 in the trigger protrusion 62. The biasing element 100 biases the lock trigger 60 to a lateral and outward position relative to the pipette housing 15 in both the locked and unlocked positions of the trigger 60. In the unlocked position, the lock trigger protrusion 62 presses inward against the contact area 102 on the face of the biasing element 100, simultaneously resisting this force. At the same time, the lock rod 105 prevents the lock trigger 60 from moving outward due to the resisting force of the biasing element 100 against the lock trigger protrusion 62. As the ejection element 50 and ejection rod 140 are biased downward against the biasing element 145, the large tip ejection member 55 continues to move downward until the spacer 110 contacts the seat 114 of the small tip ejection member 165, causing the small ejection member 165 to move downward.

[0046] The downward position of the small ejection member 165 moves the lock rod 105 downward, causing the upper end 107 of the lock rod to move out of the lock hole 108 and unblock the lock trigger 60. This causes the upper part 107 of the lock rod to contact the lower part 109 of the lock trigger protrusion 62, thereby snapping the lock trigger 60 into a horizontal / outward locked position (see FIGS. 2H and 2I). The contact between the upper part 107 of the lock rod and the lower part 109 of the lock trigger protrusion 62 prevents upward movement of the small ejection member 165, and therefore the large tip cylinder 65. Therefore, the small tip holder 30 does not extend significantly beyond the small tip ejection edge 40 (see FIG. 2E).

[0047] To release the locking mechanism, an end user presses the lock trigger 60, moving the lock trigger protrusion 62 laterally toward the biasing element 100. The trigger protrusion 62 slides across the top surface 107 of the lock rod 105 until the top surface 107 meets the lock rod bore 108 of the trigger protrusion 62 and is no longer in direct contact with the bottom surface 109 of the trigger protrusion 62. The top surface 107 of the lock rod 105 then slides up into the lock rod bore 108 due to the upward force applied by the biasing element 145 to the small tip ejection member 165 and the large tip cylinder 65. When the lock rod 105 returns to its upward position, the device is returned to the small tip configuration, which means that the small tip ejection member 165 and the large tip cylinder 65 move upward (see also FIG. 2C ).

[0048] FIG. 4 illustrates an exemplary pipetting device 10 having a concentric cylinder ejection mechanism and a locking mechanism. The dispensing unit of the pipetting device 10 includes an opening 45 that fluidly communicates with a fluid path 180 that leads to a vacuum chamber 185 within the chamber cylinder 70. When using small pipette tips, small pipette tips (e.g., 200 μl volume tips) are attached to a small tip holder 30. In some embodiments, the pipetting device 10 includes an LCD screen and interface that allows the end user to input the desired dispense volume. In other embodiments, the pipetting device 10 may include a volume adjustment button or knob, as known in the art. In motor-controlled embodiments, the user presses the actuator element 17, which sends a signal to the motor 80 via the instrument control PCB 95. The motor moves the threaded piston rod 155 and piston 115 upward. As the piston 115 moves upward within the vacuum chamber 185, the volume of the vacuum chamber 185 increases, creating the vacuum necessary to cause a corresponding displacement of air into the fluid path 180, which in turn draws a corresponding volume of liquid into a small pipette tip (e.g., about 1 μl to about 200 μl) (pipette tip not shown). The end user then presses the actuator element 17 again to move the piston 115 downward, dispensing the liquid from the small pipette tip.

[0049] To eject a small pipette tip, the end user presses the ejection element 50, moving the ejection rod 140 relative to the biasing element 145. The large tip ejection member 55 and dispenser housing 20 move downward until the spacer 110 contacts the seat 114 of the small tip ejection member 165. The small tip ejection member 165 and large tip cylinder 65 then move downward, and the small tip ejection edge 40 disengages the small pipette tip from the small tip holder 30. The end user can then install another small pipette tip and repeat the process, or switch to a larger pipette tip. To use another small pipette tip, the end user presses the lock trigger 60 against the biasing element 105, moving the lock rod 105 through the lock rod hole 108 of the lock trigger protrusion 62, thereby moving the small tip ejection member 165 and large tip cylinder 65 upward.

[0050] If an end user wishes to use a larger pipette tip (e.g., a 1000 μl capacity pipette tip), the end user first fully depresses the ejection element 50 to lock the locking rod 105 in a downward position without pressing / holding the lock trigger 60. This causes the lock trigger 60 to move outward, and the lock trigger protrusion 62 engages the upper surface 107 of the locking rod 105, preventing upward movement of the locking rod 105, the small tip ejection member 165, and the large tip cylinder 65. In the locked configuration, the small tip holder 30 does not extend significantly beyond the small tip ejection edge 40, allowing the attachment of a larger pipette tip, preventing potential contamination of the fluid pathway 180 with liquid, and allowing the attachment of a larger pipette tip with a filter component.

[0051] The end user then adjusts the volume setting as desired and presses the actuator element 17 to move the piston 115 upward within the vacuum chamber 185, forcing liquid up into the large pipette tip (e.g., about 100 μl to about 1000 μl) as described above. Pressing the actuator element 17 again dispenses the liquid. The end user then presses the ejection element 50 to move the ejection rod 140 against the biasing element 145, thereby moving the large tip ejection member 55 and the dispenser housing 20 downward until the large tip ejection edge 35 of the dispenser housing 20 disengages the large pipette tip. To return to using the small pipette tip, the end user presses the locking trigger 60 against the biasing element 100, forcing the locking rod 105 back into its upward position.

[0052] While the above illustrates a leaf spring as the biasing element 100, other preferred embodiments employ a compression spring as the biasing element 100 that can be positioned between the lock trigger 60 and the lock rod 105 or between the lock trigger 60 and the pipette housing 15. FIGS. 5A and 5B illustrate an embodiment of a locking mechanism including a compression spring as the biasing element 100 positioned between the lock trigger 60 and the lock rod 105. In this embodiment, the biasing element 100 (e.g., a compression spring) is positioned within a bore 63 of the lock trigger 60. An end 101 of the biasing element 100 contacts the lock rod 105, biasing the lock trigger 60 to a sideways and outward position. Other suitable designs for maintaining pressure on the lock trigger 60 include a tensioned spring, an elastic material, or other suitable biasing element.

[0053] To further prevent contamination of the fluid pathway by liquid, some embodiments of the device include, but are not limited to, an electronic sensor, such as an optical sensor, and a microcontroller programmed to recognize when the large tip cylinder is in a downward, locked position relative to the small tip holder or when the locking trigger is engaged. In this manner, the electronic sensor can detect when the small tip holder is exposed and therefore prevent the end user from selecting an aspiration volume that exceeds the capacity of the small pipette tip, e.g., more than 200 μl. Furthermore, when the locking mechanism is activated, the electronic sensor allows the selection of volumes up to the large tip pipette capacity, such as up to 1000 μl. In this way, the electronic sensor provides an additional mechanism for preventing contamination caused by aspirating an amount of liquid that exceeds the capacity of the small tip and can prevent the fluid pathway from being flooded with overflowing liquid. In some embodiments, a sensor can be attached to the bottom of the PCB (or elsewhere) and can detect the position of the locking trigger. The locking trigger may include a small flange ("flag") that extends in and out of the detection path of the optical sensor. In this way, when the optical sensor is blocked by the flag, the optical sensor sends a signal to the microcontroller to provide only the appropriate volume range for selection on the device's display screen (e.g., LCD) and further prevent motor commands that would move the motor beyond the appropriate volume. [Explanation of symbols]

[0054] 10 Pipetting Device 15 Pipette Housing 17 Actuator Elements 18 Hand Rest 20 Dispenser housing 22 screws 25 Large Chip Holder 30 Small Chip Holder 35 Large chip ejection edge 40 Small chip ejection edge 45 Opening 50 Emission elements 55 Large chip ejector 57 holes 60 Lock Trigger 62 Trigger protrusion 63 Bore (Lock Trigger) 65 Large Tip Cylinder 67 Screw 70 chamber cylinder 72 screws 74 screws 75 O-rings 80 motor 85 motor holder 87 holes 87 Screw 90 Secondary battery 95 Printed Circuit Board 100 bias elements 101 End of bias element (for contact with lock rod) 102 Contact area 105 Lock Rod 107 Upper part of lock rod 108 Lock rod hole 109 Bottom of trigger protrusion 110 Spacer 112 Spacer arm 114 Spacer sheet 115 Piston 120 O-rings 125 Upper Magnet Holder 130 Magnet 135 Lower Magnet Holder 140 Discharge Rod 145 bias element 150 washer 155 Piston rod 160 C washer 165 Small chip ejection member 170 Lock rod hole 175 screws 180 Fluid Path 185 Vacuum Chamber

Claims

1. A pipette having a multi-stage pipette tip holder and an ejection mechanism, a pipette body comprising an upper drive unit portion and a lower dispensing portion, the lower dispensing portion comprising a small tip holder portion and a chamber cylinder, the lower dispensing portion having a fluid inlet for drawing fluid into the chamber cylinder or discharging fluid therefrom; an ejection assembly comprising an ejection element, an ejection rod, a first dispense cylinder having a large tip holder portion and a small tip ejection edge, and a second dispense cylinder having a large tip ejection edge, wherein the first dispense cylinder is disposed in the chamber cylinder and configured to move up and down relative to the chamber cylinder, and the second dispense cylinder is disposed in the first dispense cylinder and configured to move up and down relative to the first dispense cylinder; Equipped with The ejection rod is configured as follows: (i) contacting the second dispense cylinder to move the second dispense cylinder to a first position, and when a first force is applied to the ejection element, the large tip ejection edge contacts a large pipette tip to eject the large pipette tip from the large tip holder portion; or (ii) moving the first dispense cylinder to a second position, such that when a second force is applied to the ejection element, the small tip ejection edge contacts the small pipette tip to eject the small pipette tip from the small tip holder portion; pipette.

2. The fluid is air.

2. The pipette of claim 1.

3. and a biasing element circumferentially disposed about a portion of the ejection rod and biasing the ejection rod toward an upward position.

3. A pipette according to claim 1 or 2.

4. the large chip holder portion has an outer diameter greater than an outer diameter of the small chip holder portion; A pipette according to any one of claims 1 to 3.

5. the ejection element is disposed in the upper drive unit part; A pipette according to any one of claims 1 to 4.

6. moreover, a first discharge member connected to the first dispense cylinder; a second discharge member connected to the second dispense cylinder; Equipped with the discharge rod is connected to the second dispense cylinder; the second ejection member contacts the first ejection member to move the first ejection member to the second position when the second force is applied to the ejection element; A pipette according to any one of claims 1 to 5.

7. the first discharge member and the second discharge member are located within the upper drive unit portion, the first and second dispense cylinders form part of the lower dispense section; 7. The pipette of claim 6.

8. moreover, a piston slidably positionable within the chamber cylinder between an open position and a closed position; a motor disposed within the upper drive unit portion and operatively connected to the piston, the motor configured to actuate the piston within the chamber cylinder between the open position and the closed position; Equipped with Actuation of the piston to the open position defines a volume of liquid aspirated by the piston that is approximately equal to the volume of fluid displaced by movement of the piston. A pipette according to any one of claims 1 to 7.

9. the small tip holder portion is configured to mount pipette tips having a maximum liquid volume ranging from about 2 μl to about 200 μl; A pipette according to any one of claims 1 to 8.

10. the small tip holder portion is configured to mount pipette tips having a maximum liquid volume ranging from about 20 μl to about 200 μl; 10. The pipette of claim 9.

11. the large tip holder portion is configured to mount pipette tips having a maximum liquid volume ranging from about 200 μl to about 5000 μl; A pipette according to any one of claims 1 to 10.

12. the large tip holder portion is configured to mount pipette tips having a maximum liquid volume ranging from about 200 μl to about 1000 μl; 12. The pipette of claim 11.

13. moreover, a locking mechanism comprising a trigger, a biasing element, and a locking rod movable between a locked position and an unlocked position; Equipped with Movement of the second dispense cylinder and the first dispense cylinder to the second position causes the locking rod to move to the locked position to prevent upward movement of the first dispense cylinder. A pipette according to any one of claims 1 to 12.

14. a force applied to the trigger against the biasing element causes the locking rod to move to the unlocked position, whereby the locking rod no longer impedes upward movement of the first dispense cylinder; 14. A pipette according to claim 13.

15. The locking rod contacts an underside of the trigger when in the locked position.

15. A pipette according to claim 13 or 14.

16. moreover, a printed circuit board for controlling the motor in response to an end user's capacitive input; a sensor in electronic communication with the printed circuit board; Equipped with The sensor (i) the first dispense cylinder is unlocked, preventing the motor from moving the piston upward to the open position to an extent that defines a volume of liquid aspirated by the pipette that exceeds the maximum liquid capacity of a small pipette tip; (ii) the first dispense cylinder is locked, allowing the motor to move the piston upward to the open position to an extent that defines a volume of liquid aspirated by the pipette that exceeds the maximum liquid capacity of a small pipette tip; or (iii) both (i) and (iii); Detecting A pipette according to any one of claims 13 to 15.

17. 1. A method for changing pipette tips in a pipette, comprising: (a) providing a pipette according to any one of claims 1 to 16, wherein a small pipette tip is attached to the small tip holder part, and applying a force to the ejection element until the small tip ejection edge contacts the small pipette tip to remove the small pipette tip from the small tip holder part, or (b) providing a pipette according to any one of claims 1 to 16, wherein a large pipette tip is attached to the large tip holder portion; and applying a force to the ejection element until the large tip ejection edge contacts the large pipette tip to remove the large pipette tip from the large tip holder portion. method.

18. moreover, inserting the small tip holder portion into the pipette receiving end of a small pipette tip to form an interference fit; Including, 18. The method of claim 17.

19. moreover, inserting the large tip holder portion into the pipette receiving end of a large pipette tip to form an interference fit; Including, 18. The method of claim 17.

20. moreover, continuing to depress the trigger while applying force to the ejection element; Equipped with 18. The method of claim 17.

21. A pipetting device having a multi-stage pipette tip holder and an ejection mechanism, an elongated pipette body having a fluid inlet at a dispensing end; Emission elements; A concentric cylinder assembly comprising: (i) a chamber cylinder in fluid communication with the fluid inlet; (ii) a small tip ejection cylinder having a small tip ejection edge and a large tip holder portion; and (iii) a cylindrical dispenser housing having a large tip ejection edge, (i) the chamber cylinder is concentrically received within the small chip discharge cylinder; (ii) the small tip discharge cylinder is concentrically received within the cylindrical dispenser housing and configured to move up and down relative to the chamber cylinder; (iii) the cylindrical dispenser housing is configured to move up and down relative to the small tip discharge cylinder; a concentric cylinder assembly; an ejection rod in mechanical communication with the ejection element, (i) configured to move the cylindrical dispenser housing to a first position, such that when a first force is applied to the ejection element, the large tip ejection edge contacts a large pipette tip to eject the large pipette tip from the large tip holder portion; or (ii) configured to move the small tip ejection cylinder to a second position, such that when a second force is applied to the ejection element, the small tip ejection edge contacts a small pipette tip to eject the small pipette tip from the small tip holder portion; A discharge rod; Equipped with Pipetting device.

22. moreover, a first discharge member connected to the small chip discharge cylinder; a second discharge member connected to the discharge rod and the cylindrical dispenser housing; Equipped with (i) the ejection rod moves the second ejection member and the cylindrical dispenser housing to the first position when a first force is applied to the ejection element; or (ii) the ejection rod moves the first ejection member and the small chip ejection cylinder into contact with each other and to the second position when a second force is applied to the ejection element; 22. A pipetting device according to claim 21.

23. moreover, a locking mechanism comprising a trigger, a biasing element, and a locking rod movable between a locked position and an unlocked position; Equipped with Movement of the cylindrical dispenser housing and the small tip discharge cylinder to the second position causes the locking rod to move to a locked position to prevent upward movement of the small tip discharge cylinder.

23. A pipetting device according to claim 21 or 22.

24. a force applied to the trigger against the biasing element causes the locking rod to move to the unlocked position, whereby the locking rod no longer impedes upward movement of the small chip ejection cylinder; 24. A pipetting device according to any one of claims 21 to 23.

25. The locking rod contacts an underside of the trigger when in the locked position.

25. A pipetting device according to any one of claims 21 to 24.

26. moreover, a piston slidably positionable within the chamber cylinder between an open position and a closed position; a motor operably connected to the piston and configured to actuate the piston within the chamber cylinder between the open position and the closed position; Equipped with Actuation of the piston to the open position defines a volume of liquid aspirated into the pipette that is approximately equal to the volume of fluid displaced by movement of the piston.

26. A pipetting device according to any one of claims 21 to 25.

27. the motor is mechanically connected to a threaded piston; the threaded piston is connected to the piston by one or more magnets; 27. A pipetting device according to any one of claims 21 to 26.

28. moreover, a printed circuit board for controlling said motor in response to an end user's capacitive input; a sensor in electronic communication with the printed circuit board; Equipped with The sensor (i) the small tip ejection cylinder is unlocked, preventing the motor from moving the piston upward to the open position to an extent that defines a volume of liquid aspirated by the pipette that exceeds the maximum liquid capacity of a small pipette tip; (ii) the small tip ejection cylinder is locked, allowing the motor to move the piston upward to the open position to an extent that defines a volume of liquid aspirated by the pipette that exceeds the maximum liquid capacity of a small pipette tip; or (iii) both (i) and (iii); Detecting 28. A pipetting device according to any one of claims 21 to 27.

Images