EP2417461B1

EP2417461B1 - Automated pipette tip loading devices and methods

Info

Publication number: EP2417461B1
Application number: EP10762529.5A
Authority: EP
Inventors: Arta Motadel
Original assignee: Biotix Inc
Current assignee: Biotix Inc
Priority date: 2009-04-11
Filing date: 2010-04-09
Publication date: 2024-01-10
Anticipated expiration: 2030-04-09
Also published as: EP2417461A4; EP2417461A2

Description

Field of the Technology

The present invention related to pipette tip dispensing devices and methods for dispensing an array of multiple pipette tips. Moreover, described herein are methods and devices for storing, loading or handling of pipette tips. Some devices allow for convenient loading of multiple batches of pipette tips into loading blocks or plates with a minimal amount of waste and minimal effort by the user.
DE 44 19 291 A1 discloses a process and a device which are directed to pipette points on a support according to a predetermined grid arrangement. Objects are stacked in layers in a container in such a way that the narrow side of the outer contour of objects directly engages the wide part of the openings of the objects in the underlying layer.
US 5 915 284 A discloses a multiple channel pipetting device for aspirating and dispensing volumes of liquid using disposable or non-disposable tips. The device is comprised of a main body made of a hard synthetic material with multiple channels and an associated ram plate activated by a four-quadrant synchronous drive. The drive assembly is mounted on four standoffs, and the ram plate moves up and down by the means of four lead screws moved with a synchronous fibrous belt moved with a motor. A moveable plate mounted to the bottom of the device to remove disposable tips is activated by a set of automated ejector plate arms. The entire device can be mounted in a self-contained housing or attached to another device allowing it to be moved.

Background

Pipette tips are used in large quantities for a wide variety of applications related to liquid material handling, such as measuring, dispensing and aspirating of the liquids. Pipette tips are often used in conjunction with hand held pipettors, such as mechanical or electrical pipettors, that have distal nozzles that are configured to be releasably engaged with a proximal port or opening of a pipette tip in a sealed relationship. The pipettor may then be used to apply a vacuum or otherwise decrease the pressure in the interior volume of the pipette tip in order to aspirate liquid into the pipette tip for transfer to another location. For some applications a single pipettor may be used, however, for some applications, particularly automated or robotic applications, pipettors or manifolds having multiple distal nozzles may be used to engage multiple pipettor tips disposed in a loading plate or block simultaneously.
For such configurations, after the pipette tips are seated onto the nozzles and removed from the loading block, a new set of pipette tips must be provided for the next cycle of liquid handling. Typically, a new set of pipette tips are taken from a package in a storage plate and loading block in a regularly spaced array and positioned for seating with the distal nozzles of the manifold. Because of the difficulty of manually handling large numbers of pipette tips due to the time consuming nature of such handling as well as the risk of contamination, pipette tips are generally pre-packaged in regularly spaced arrays spaced in pre-determined spacing to match the spacing of the array of distal nozzles. The pipette tips may be transferred from the packaging in a loading plate that is part of the packaging but may also include an entire loading plate and loading block in order to maintain the array configuration during handling and transfer to a location for seating to the manifold or pipettor.
For such multiple pipette tip arrays, because each pipette tip may require a significant amount of axial force between the respective nozzle and proximal opening of the pipette tip in order to be properly seated, the cumulative force required to seat an array of pipette tips may be quite high. For example, a 96 tip manifold may exert about 75 pounds to about 250 pounds of force on a loading block having a 96 tip array. Because of the amount of force generated, the loading block that supports the loading plate must be structurally strong and able to withstand the cumulative axial force without significant deformation. To be this strong, the block requires a significant amount of mass of material which is typically a polymer. Once the distal nozzles of the manifold have engaged and seated the pipette tips and withdrawn them from the loading plate and block, the loading block and plate are disposed of and replaced with a new loading block and plate that is full of new pipette tips. As a result, a user performing a high volume of such liquid handling cycles will be disposing of a large volume of loading blocks and plates which generates a large volume of polymer waste which may be environmentally unsound in many instances.
For examples of pipette tip arrays that transferred in a loading plate without the loading block of the package, the loading tray is lifted or moved from the packaging and positioned in a loading block. After each seating of an array of pipette tips, the loading plate must be removed or the z-axis position of the top of the plate will change with the addition of each new loading plate from a new package of pipette tips.

Summary

The subject-matter of the present invention is defined by the features of independent device claim 1 and independent method claim 12. Further preferred embodiments of the present invention are defined in the dependent claims.
Moreover, a plurality of examples are disclosed which are useful for the understanding of the present invention. In particular, in some examples of a pipette tip dispensing device include (a) a sleeve; (b) an activator plate within the sleeve, (c) a distal barrier plate within the sleeve disposed opposite to and spaced away from the activator plate, (d) two or more connectors in connection with the activator plate and distal barrier plate, (e) a plurality of nested pipette tip units between the activator and barrier plates, where: (i) each unit is aligned with a channel in the distal barrier plate, and (ii) the distal barrier plate comprises (1) a plurality of channels, where each channel comprises a diameter larger than the widest portion of a pipette tip, (2) a top surface, and (3) a bottom surface. In some examples, the bottom surface optionally comprises a plurality of tails around some or all of the channels, wherein (i) the tails extend in a nearly perpendicular orientation from the bottom surface, and (ii) the tails around each channel contact a pipette tip when a pipette tip is dispensed and passes by the tails, thereby imparting (e.g., applying) a frictional force on the pipette tip when it is dispensed. In some examples, the optional tails deflect outwards against the pipette tip before, and/or at the same time the pipette tip is being dispensed (e.g., the pipette tip is translating), and sometimes the tails contact the proximal portion of a pipette tip. In some examples, a subset of channels in the distal barrier plate are optionally surrounded by tails that eject pipette tips of an array at one time, and another subset of channels in the plate are optionally surrounded by tails that eject pipette tips of the same array at another time. A distal barrier plate may include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 of such subsets of channels. In some examples, the top surface and/or the bottom surface are substantially flat. In certain examples, the sleeve can comprise a degradable or biodegradable material (e.g., banana peel, bamboo, and the like).
In some examples, the channel can have 2, 3, 4, 5, 6, 7, 8, 9, 10 or more optional tails. Each channel of the barrier plate can have tails of the same length. In some examples, each channel of the barrier plate can have tails of different lengths. Channels located in the center of the barrier plate can have the longest tails. Channels located in the center of the barrier plate can have the shortest tails. In certain examples, subsequent channels concentrically disposed about a central longitudinal axis can have sequentially shorter tails in length in a stepwise manner. In some examples, subsequent channels concentrically disposed about a central longitudinal axis can have sequentially longer tails in length in a stepwise manner. Channels located in the center of the barrier plate along the X axis can have tails of the same length and channels along the Y axis comprise tails of varying length. In some examples, channels located in the center of the barrier plate along the Y axis can have tails of the same length and channels along the X axis comprise tails of varying length. Channels located in the center of the barrier plate along the X and Y axes can have tails of varying length in certain examples. Each channel can have an even number of tails in some examples. Tails directly opposite one another around a channel can have the same length in certain examples. Tails directly opposite one another around a channel can have a different length in some examples. Tails adjacent to one another can have a different length in certain examples. In some examples, the activator plate, distal barrier plate, connectors, and plurality of pipette tips are located in the sleeve. The sleeve in certain examples further comprises a top portion, four sides and a bottom lid. In some examples, the sleeve is comprised of one or more of a polymer material, chipboard, glass, Styrofoam, wood, metal, plastic, paper, or combination thereof. In some examples, the distal barrier plate further comprises one or more fasteners along one or more of its vertical lateral sides configured to connect with the sleeve. The term "fastener" as used herein refers to a member that connects a distal barrier plate to a sleeve member, including but not limited to Velcro, button, hook, adhesive, prong and the like. The distal barrier plate also can also have one or more connections along one or more of its vertical lateral sides configured to connect with sleeve in certain examples.
In certain examples, optional tails can be at an internal angle of about 89° to about 80° from the bottom surface of the distal barrier plate. Tails can be at an internal angle between 88-85°, 87-84°, 86-83° or 86-85° from the bottom surface of the distal barrier plate in certain examples. The tails can be at an internal angle of about 87° from the bottom surface of the distal barrier plate. The tails can be between 0.01pm-2.0mm in length in some examples, and sometimes the tails can be between 0.05µm- 2.0mm in length. The tails around a channel are not in the channel in some examples.
The housing unit further can have a top portion and four sides in some examples. The movable bottom platform positions a loading block directly distal to the barrier plate to receive an ejected array of pipette tips from the dispensing device in certain embodmients. The housing can be made of any suitable material, and sometimes is a polymer material, and the polymer material of the housing can be made of a molded polypropylene in some examples. The polymer material of the housing can be a thickness of about 0.005 inches to about 0.05 inches in certain examples. The activator plate can have a member on the top portion of the plate that maintains contact with and restricts lateral displacement of the proximal portion of the pipette tips. The member can be selected from the group consisting of foam, a raised grid, and a plurality of proximal alignment members in some examples. The activator plate can be made from a polymer material, and the polymer material of the activator plate can be made of a molded polypropylene in some examples. The polymer material of the activator plate can be a thickness of about 0.30 inches to about 0.65 inches. The activator plate can have a top portion and a roof portion in some examples. The polymer material is molded with raised ridges on the top portion and the roof portion in certain examples. The ridges can provide strength and rigidity to the activator plate in some examples. In some examples, the housing unit also includes a motor, electrical engine or other type of drive mechanism that can translate a plate in an automated dispensing unit.
A pipette tip array can have 96, 384, or more numbers of pipette tips, and a pipette tip unit can be arranged in an array of pipette tip units. Each nested pipette tip unit can have 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or more pipette tips. The connectors are rods in some examples. The rods in connection with the activator plate and the distal barrier plate can have threads. The activator plate and the distal barrier plate are translated towards one another by rotation of the rods in certain examples. The activator plate can have threaded members, and each threaded member engages a threaded portion of each rod, whereby the activator plate translates towards the distal barrier plate by rotation of the rods in some examples. The rods sometimes are rotated by a motor. The motor is activated by a user controlled mechanism in some examples. The user controlled mechanism is a lever switch, button, or sensor in certain examples. The motor stops rotating the rods by a pressure sensor gauge in some examples. The pipette tips that have passed through the distal barrier plate are sterilized in certain examples, and sterilization sometimes is by UV irradiation, ionization, alcohol or gamma radiation. In some examples, the sterilization can be initiated by a controller or switch activated by a user.
Certain examples of a method of simultaneously dispensing an array of multiple pipette tips into a loading block, include (a) providing a dispensing device that includes a nested array of regularly spaced pipette tips between a top activator plate and a bottom distal barrier plate, wherein: (i) the activator plate and the distal barrier plate are in connection with two or more connectors, (ii) the distal barrier plate includes (1) a plurality of channels, where each channel has a diameter larger than the widest portion of a pipette tip, (2) a top surface, and (3) a bottom surface, (b) engaging the dispensing device with a loading block such that distal ends of the pipette tips are disposed above and/or within receptacles of the loading block, and (c) actuating a motor of the dispensing device in effective connection with the connectors that moves the connectors, whereby (i) the activator plate and the distal barrier plate are translated towards one another thereby applying an axial force on the array of pipette tips, and (ii) the array of pipette tips is ejected into respective receptacles in the loading block. In some examples, the connectors are rods. In certain examples, the bottom surface comprises a plurality of tails around some or all of the channels, wherein the tails extend in a nearly perpendicular orientation from the flat bottom surface. In some examples the axial force dispenses the array of pipette tips through the channels and past the optional tails and the tails contact and deflect outwards against the pipette tips and impart a frictional force on the pipette tips. In some examples, the optional tails deflect outwards against the pipette tip before, and/or at the same time the pipette tip is being dispensed (e.g., the pipette tip is translating), and sometimes the tails contact the proximal portion of a pipette tip. In some examples, a subset of channels in the distal barrier plate are surrounded by tails that eject pipette tips of an array at one time, and another subset of channels in the plate are surrounded by tails that eject pipette tips of the same array at another time. A distal barrier plate may include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 of such subsets of channels. In some examples, the top surface and/or the bottom surface are substantially flat.
In some examples pertaining to the method examples of the preceding paragraph, the barrier plate can have 2, 3, 4, 5, 6, 7, 8, 9, 10 or more optional tails. Each channel of the barrier plate can have tails of the same length. In some examples, each channel of the barrier plate can have tails of different lengths. Channels located in the center of the barrier plate can have the longest tails. In certain examples, channels located in the center of the barrier plate can have the shortest tails. Subsequent channels concentrically disposed about a central longitudinal axis can have sequentially shorter tails in length in a stepwise manner. In some examples, subsequent channels concentrically disposed about a central longitudinal axis can have sequentially longer tails in length in a stepwise manner. Channels located in the center of the barrier plate along the X axis can have tails of the same length and channels along the Y axis comprise tails of varying length. In certain examples, channels located in the center of the barrier plate along the Y axis can have tails of the same length and channels along the X axis comprise tails of varying length. In certain examples, channels located in the center of the barrier plate along the X and Y axes can have tails of varying length. Each channel can have an even number of tails in some examples. Tails directly opposite one another around a channel can have the same length in certain examples. Tails directly opposite one another around a channel can have a different length in some examples. Tails adjacent to one another can have a different length in certain examples. Optional tails can be at an internal angle of about 89° to about 80° from the bottom surface of the distal barrier plate. In some examples, tails can be at an internal angle between 88-85°, 87-84°, 86-83° or 86-85° from the bottom surface of the distal barrier plate. Tails can be at an internal angle of about 87° from the bottom surface of the distal barrier plate in some examples. Optional tails can be between 0.01pm-2.0mm in length, and sometimes tails can be between 0.05µm-2.0mm in length. Tails around a channel are not in the channel in certain examples. The actuating step can be repeated by automatic or manual activation until all the nested pipette tips are ejected from the dispensing device in some examples. The automatic activation can be performed by a pressure gauge sensor in certain examples. The manual activation can be performed by a lever switch, button, or sensor in some examples.
Certain examples are described further in the following description, claims and drawings. As mentioned above, it should be noted that the subject-matter of the present invention is defined by the features of independent device claim 1 and independent method claim 12. Further preferred embodiments of the present invention are defined in the dependent claims.

Brief Description of the Drawings

The drawings illustrate examples of the technology and are not limiting. For clarity and ease of illustration, the drawings are not made to scale and, in some instances, various aspects may be shown exaggerated or enlarged to facilitate an understanding of particular examples.
Certain features common to some or all the figures (e.g., FIG., or FIGS.) presented herein are identified by a prime symbol (`) after the reference character. For example a feature labeled 14 in one drawing and substantially similar or substantially identical to a feature in one or more additional drawings, would be labeled 14' in the second and subsequent drawings. In instances where a figure is not explicitly described, but contains reference characters containing the prime symbol (`), it will be understood the description given for the reference character in one figure, will be substantially identical for the reference character with the prime symbol.

FIG. 1A shows a perspective view of a distal barrier plate with optional tails pointing in an upward orientation. FIG. 1B shows an enlarged cut away view of FIG. 1A (see arrows in FIG. 1A) detailing the optional tails. FIG. 1C shows a lateral partial profile view of the tails, where all the tails are the same length. FIG. 1D shows an enlarged cut away, lateral partial profile view of one channel, where the tails are angled.
FIG. 2A shows a bottom view of a distal barrier plate with optional tails arranged in a nearly perpendicular orientation with respect to the bottom surface of the plate. FIG. 2A shows X and Y axes referenced herein. FIG. 2B shows an enlarged cut away view of
FIG. 2A (see arrows in FIG. 2A) detailing certain aspects of tails and their orientation to channels. FIG. 2C shows a lateral profile view of the optional tails, where the tails are varied in length.
FIG. 3 shows an optional base plate. FIG. 3A shows the top surface and FIG. 3B shows the bottom surface.
FIG. 4 shows a rod of the automated pipette tip dispensing device.
FIG. 5 shows an activator plate or actuator plate. FIG. 5A shows the top portion of the plate. FIG. 5B shows an enlarged corner section of the plate from FIG. 5A. FIG. 5C shows a lateral view of the activator plate in FIG. 5A.
FIG. 6A shows another view of an activator plate. FIG. 6A shows the roof surface of the plate. FIG. 6B shows the plate from FIG. 6A at a slanted angle.
FIG. 7 shows an elevation view of an embodiment of a pipette tip.
FIGS. 8A and 8B show the assembly of components of the automated pipette tip dispensing device.
FIG. 9 shows an auto eject cartridge and its components.
FIG. 10A shows a perspective view of a distal barrier plate. FIG. 10B shows a width side view of a distal barrier plate. FIG. 10C shows a top view of a distal barrier plate. FIG. 10D shows a length side view of a distal barrier pate. FIG. 10E shows a bottom view of a distal barrier plate.
FIG. 11A shows a perspective view of an activator plate, also referred to herein as an actuator plate. FIG. 11B shows a width side view of an activator plate. FIG. 11C shows a top view of an activator plate. FIG. 11D shows a length side view of an activator plate. FIG. 11E shows a bottom view of an activator plate.
FIGS 12A-12H illustrate various views of an auto eject cartridge with a transparent sleeve, with and without pipette tips. FIG. 12A shows a perspective view of an auto eject cartridge with a transparent sleeve without pipette tips. FIG. 12B shows a front view of an auto eject cartridge with a transparent sleeve without pipette tips. FIG. 12C shows a rear view of an auto eject cartridge with a transparent sleeve without pipette tips. FIGS. 12D and 12E show side views of an auto eject cartridge with a transparent sleeve without pipette tips. FIG. 12F shows a top view of a cartridge with a transparent sleeve without pipette tips. FIG. 12G shows a bottom view of cartridge with a transparent sleeve without pipette tips. FIG. 12H shows a front view of an auto eject cartridge with a transparent sleeve loaded a nested array of regularly spaced pipette tips between a top activator plate and a bottom distal barrier plate. A cartridge may be provided with or without a nested array of spaced pipette tips.
FIG. 13A shows a perspective view of the auto eject housing unit. FIG. 13B shows a front view of the auto eject housing unit. FIG. 13C shows a rear view of the auto eject housing unit. FIG. 13D shows a right side view of the auto eject housing unit. FIG. 13E shows a left side view of the auto eject housing unit. FIG. 13F shows a top view of the auto eject housing unit. FIG. 13G shows a bottom view of the auto eject housing unit.
FIGS. 14A-14G show various views of an auto eject cartridge with an opaque sleeve, without pipette tips. FIG. 14A shows a perspective view of an auto eject cartridge with an opaque sleeve without pipette tips. FIG. 14B shows a front view of an auto eject cartridge with an opaque sleeve without pipette tips. FIG. 14C shows a rear view of an auto eject cartridge with an opaque sleeve without pipette tips. FIGS. 14D and 14E show side views of an auto eject cartridge with an opaque sleeve without pipette tips. FIG. 14F shows a top view of an auto eject cartridge with an opaque sleeve without pipette tips. FIG. 14G shows a bottom view of an auto eject cartridge with an opaque sleeve without pipette tips. A cartridge may be provided with or without a nested array of regularly spaced pipette tips.
FIG. 15 shows a perspective view of a motor or drive embodiment (e.g., robot drive) utilized to directly or indirectly rotate connector rods that operationally connect the activator and distal barrier plates, and enable the activator and distal barrier plates to vertically translate towards each other to dispense pipette tips into a pipette tip rack or loading block. FIG. 16 shows a top view of a drive motor embodiment, with the top covering plate removed to show a non-limiting embodiment of an indirect drive mechanism.

Detailed Description

Discussed herein are method and device examples for handling, storage and dispensing of pipette tips used for a variety of material handling applications. Pipette tips may generally be engaged with a distal nozzle of a pipettor or similar device in order to draw and drop liquid slugs in precise amounts. Such tips may be used for the transfer and handling of liquids for applications such as titration and dispensing of liquids, DNA sequencing, cycle sequencing, PCR and other DNA analysis as well as other liquid handling applications. For many of these applications, large numbers of samples must be processed in a precise manner and, as such, a large number of pipette tips are used for such methods. In order to avoid cross contamination of samples, pipette tips are typically used only once for each sample being processed. Because of the large number of samples being processed and the single use nature of the pipette tips, a large number of pipette tips need to engaged with pipettor type devices and then removed from those devices and disposed of.
Due to such large volume handling and disposal, it is desirable for some applications to have devices and methods for pipette tip transfer and loading in arrays of multiple tips from a single packaging source to avoid the need for disposing of a package for each array loaded onto a pipettor device. What is also desirable for some applications are devices and methods for loading an array of multiple pipette tips without the need to transfer a separate loading plate from the packaging of the tips which may cause additional waste for disposal in addition to affecting the cumulative z-axis height of the pipette tips being loaded. Some pipette tip dispensing device and method examples discussed herein are directed to the handling, storage and simultaneous dispensing of a plurality of pipette tips disposed in a regularly spaced array into a loading plate or block. The present invention, as defined in the claims is directed to pipette tip dispensing devices and methods for dispensing an array of multiple pipette tips. Some of the examples have the capacity to serially dispense multiple arrays or pipette tips without transferring loading plates or the need for handling of individual pipette tips. Some examples of pipette tip dispensing devices discussed herein are also capable of dispensing arrays of multiple pipette tips accurately and conveniently without the need to transfer a loading tray from the packaging of the pipette tips.
Device and method examples described herein provide several advantages. Device and method examples herein allow for storing, loading or handling of pipette tips, and allow for convenient loading of pipette tips without the need to transfer a storage plate that may affect the z-axis location of the top surface of the loading block into which the pipette tips are transferred. Device and method examples herein also allow for multiple pipette tips to be loaded simultaneously without the transfer of a storage plate. Such examples also allow for pipette tips to be stored in a nested configuration, in one or more nested column arrays for some examples, and allow the bottom pipette tip of each nested column to be conveniently dispensed into a loading plate or loading block.

Pipette Tips

A pipette tip can be of any geometry useful for dispensing fluids in combination with a dispensing device. Pipette tips sometimes are available in sizes that hold from 0 to 10 microliters, 0 to 20 microliters, 1 to 100 microliters, 1 to 200 microliters and from 1 to 1000 microliters, for example. The external appearance of pipette tips may differ, and certain pipette tips can have a continuous tapered wall forming a central channel or tube that is roughly circular in horizontal cross section, in some examples. A pipette tip can have any cross-sectional geometry that results in a tip that (i) provides suitable flow characteristics, and (ii) can be fitted to a dispenser (e.g., pipette), for example. Pipette tips sometimes taper from the widest point at the top-most portion of the pipette tip (pipette proximal end or end that engages a dispenser), to a narrow opening at the bottom most portion of the pipette tip (pipette distal end or end used to acquire or dispel fluid). In certain examples, a pipette tip wall includes two or more taper angles. The inner surface of the pipette tip sometimes forms a tapered continuous wall, in some examples, and in certain examples, the external wall may assume an appearance ranging from a continuous taper to a stepped taper or a combination of smooth taper with external protrusions. An advantage of an externally stepped taper is compatibility with pipette tip racks from different manufacturers. The bore of the top-most portion of the central channel or tube generally is wide enough to accept a particular dispenser apparatus (e.g., nozzle, barrel).
In some examples, a pipette tip has (i) an overall length of about 1.10 inches to about 3.50 inches (e.g., about 1.25, 1.50, 1.75, 2.00, 2.25, 2.50, 2.75, 3.00, 3.25 inches); (ii) a fluid-emitting distal section terminus having an inner diameter of about 0.01 inches to about 0.03 inches (e.g., about 0.015, 0.020, 0.025 inches) and an outer diameter of about 0.02 to about 0.7 inches (e.g., about 0.025, 0.03, 0.04, 0.05, 0.06 inches); and (iii) a dispenser-engaging proximal section terminus having an inner diameter of about 0.10 inches to about 0.40 inches (e.g., about 0.15, 0.20, 0.25, 0.30, 0.35 inches) and an outer diameter of about 0.15 to about 0.45 inches (e.g., about 0.20, 0.25, 0.30, 0.35, 0.45 inches). In the latter examples, the inner diameter is less than the outer diameter.
The wall of the distal section of a pipette tip sometimes is continuously tapered from the wider portion, which is in effective connection with the proximal section, to a narrower terminus. The wall of the distal section, in some examples, forms a stepped tapered surface. The angle of each taper in a distal section is between about zero degrees to about thirty degrees from the central longitudinal vertical axis of the pipette tip (e.g., about 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 degrees), in certain examples. In some examples, the wall of the distal section forms stepped vertical sections. The wall thickness of a distal section may be constant along the length of the section, or may vary with the length of the section (e.g., the wall of the distal section closer to the proximal section of the pipette tip may be thicker or thinner than the wall closer to the distal section terminus; the thickness may continuously thicken of thin over the length of the wall). The distal section of a pipette tip generally terminates in an aperture through which fluid passes into or out of the distal portion. A distal section of a pipette tip may contain a filter, insert or other material.
The wall of the proximal section of a pipette tip sometimes is continuously tapered from the top portion, a narrower terminus. The top portion generally is open and often is shaped to receive a pipette tip engagement portion of a dispensing device. The wall of a proximal section, in some examples, forms a stepped tapered surface. The angle of each taper in the proximal section is between about zero degrees to about thirty degrees from the central longitudinal vertical axis of the pipette tip (e.g., about 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 degrees), in certain examples. The wall thickness of a proximal section may be constant over the length of the section, or may vary with the length of the proximal section (e.g., the wall of the proximal section closer to the distal section of the pipette tip may be thicker or thinner than the wall closer to the top of the proximal section; the thickness may continuously thicken or thin over the length of the wall). A proximal section of a pipette tip may contain a filter, insert or other material.
In certain examples, pipette tips in a pipette tray comprise one or more of a filter component and/or an insert component. A filter may be located in any suitable portion of a pipette tip, and sometimes is located in a proximal portion of a pipette tip near a pipette tip aperture that can engage a dispensing device. A filter can be of any shape (e.g., plug, disk; U.S. Patent Nos. 5156811 and 7335337 ) and can be manufactured from any material that impedes or blocks migration of aerosol through the pipette tip to the proximal section terminus, including without limitation, polyester, cork, plastic, silica, gels, and the like, and combinations thereof. In some examples a filter may be porous, non-porous, hydrophobic, hydrophilic or a combination thereof. A filter in some examples may include vertically oriented pores, and the pore size may be regular or irregular. Pores of a filter may include a material (e.g., granular material) that can expand and plug pores when contacted with aerosol (e.g., U.S. Patent No. 5,156,811 ). In certain examples, a filter may include nominal, average or mean pore sizes of about 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5, or 0.05 micrometers, for example. A section of a pipette tip also may include an insert or material that can interact with a molecule of interest, such as a biomolecule. The insert or material may be located in any suitable location for interaction with a molecule of interest, and sometimes is located in the distal section of a pipette tip (e.g., a material or a terminus of an insert may be located at or near the terminal aperture of the distal section). An insert may comprises one or more components that include, without limitation, multicapillaries (e.g., US 2007/0017870 ), fibers (e.g., randomly oriented or stacked, parallel orientation), and beads (e.g., silica gel, glass (e.g. controlled-pore glass (CPG)), nylon, Sephadex^®, Sepharose^®, cellulose, a metal surface (e.g. steel, gold, silver, aluminum, silicon and copper), a magnetic material, a plastic material (e.g., polyethylene, polypropylene, polyamide, polyester, polyvinylidenedifluoride (PVDF)), Wang resin, Merrifield resin or Dynabeads^®). Beads may be sintered (e.g., sintered glass beads) or may be free (e.g., between one or two barriers (e.g., filter, frit)). Each insert may be coated or derivitized (e.g., covalently or non-covalently modified) with a molecule that can interact with (e.g., bind to) a molecule of interest (e.g., C18, nickel, affinity substrate).
A specific embodiment of pipette tip 50 is shown in FIG. 7, however, pipette tips may have a wide variety of configurations, dimensions and materials, each of which may be accommodated for use with any of the dispensing device examples discussed herein. For example, pipette tips may be configured as filter tips that include one, two, three or more filter elements disposed within a barrel of the tip in order to block aerosols from the pipettor device as well as other purposes.
The pipette tip 50 shown has a generally barrel shaped configuration which is concentrically disposed about a longitudinal axis 52 of the pipette tip 50. An inner lumen, not shown, extends coaxially along the length of the pipette tip 50 and tapers generally from the proximal opening of the pipette tip to a smaller distal opening. The proximal opening at a proximal end 56 of the tip 50 may have an inside surface with a tapered contour that is configured to engage an outer surface of a distal nozzle of a pipettor device, such as a pipettor device, in a sealed and releasable arrangement.
An outer surface of the proximal end of the pipette tip may have a rim, shoulder or other structure 58 that forms a major outer transverse dimension of the tip 50 which is disposed at the axial position of the pipette tip 50 having the largest transverse dimension. The barrel shaped configuration may have a generally round transverse cross section with the major outer transverse dimension at the proximal end 56 of the pipette tip of about 0.2 inches to about 0.4 inches, more specifically, about 0.25 inches to about 0.35 inches, for some examples. The outer transverse dimension of the pipette tip may taper to a minor outer transverse dimension at a distal end of the pipette tip 50 of about 0.02 inches to about 0.05 inches, more specifically, about 0.03 inches to about 0.04 inches, for some examples. The inner lumen may have a contour and taper that substantially corresponds to the taper and contour profile of the outer surface. The distal port or opening at the distal end of the inner lumen of the pipette tip may have a transverse dimension or diameter of about 0.01 inches to about 0.03 inches, more specifically, about 0.015 inches to about 0.025 inches, for some examples.
The shoulder portions 54 of the outer surface of some pipette tip examples 50 may have a minor transverse dimension that will fit within the proximal opening of another similar pipette tip and a major transverse dimension that is larger than the proximal opening of a similar pipette tip. With such an arrangement, the shoulder portion 54 of a first pipette tip thereby includes a distal surface or feature that may engage a proximal end or surface of another corresponding second pipette tip that is in nested engagement with the first pipette tip. The engagement of the shoulder portion of the first pipette tip with a proximal surface of the second pipette tip allows the transfer axial force between the first and second nested pipette tips without engaging the respective inner and outer tapered surfaces of the tips which might cause them to bind together making release of the tips from each other difficult.
The wall thickness of some examples of pipette tips may be about 0.003 inches to about 0.01 inches and the overall length of some pipette tip examples may be about 1.5 inches to about 3.5 inches, more specifically, about 2 inches to about 3 inches. Some examples of pipette tips may be made of suitable polymers such as polypropylene, polyethylene, polystyrene, polyurethane and the like as well as any other suitable polymers.
A pipette tip unit is arranged in an array of pipette tip units in some examples. Each unit has a plurality of nested pipette tips, and units are arranged in an array in certain examples. The relative configuration of nested pipette tips often is determined where a first portion of an inner surface of a first pipette tip interferes with a second portion of the outer surface of a second pipette tip nesting in and above the first pipette tip (e.g., the inner diameter of the first portion is about equal to the outer diameter of the second portion). Pipette tips can be dispensed as an array of pipette tips one pipette tip (i.e., one level) high. For example, a pipette tip array can fill all the holes in a loading block. When a device of the present technology is filled with an array of pipette tip units and actuated, a one-layer pipette tip array would be ejected into an empty loading block 7, thus filling it, in some examples. Each pipette tip unit comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or more nested pipette tips in some examples. The pipette tips often are nested continuously, and there often are no intermediate plates or intermediate components between the nested pipette tips.

Distal Barrier Plate

In some examples, the distal barrier plate 25, FIGS. 1A-1C, 2A-2C and 10A-10E may have a thickness and material rigidity sufficient to prevent significant deformation upon the application of actuation force to the pipette tips 50 disposed in the plate 25. As such, the distal barrier plate 25 may have a thickness of about 0.05 inches to about 0.3 inches, more specifically, about 0.1 inches to about 0.25 inches. For some examples, the barrier plate 25 may be made from suitable metal, such as aluminum, or polymers such as polypropylene, polycarbonate, polyethylene, polystyrene, polyurethane and the like as well as any other suitable polymers that may be molded, thermoformed or the like. For some examples, the barrier plate 25 may have a length of about 2 inches to about 6 inches and a width of about 1 inch to about 4 inches.
In some examples, certain geometric aspects of the distal barrier plate, through which pipette tips are dispensed, are substantially similar to, or the same as, geometric aspects of a pipette tip rack or holder configured for use in conjunction with automated dispensing devices and/or biological workstations. Such geometric aspects can include, for example, center-to-center distances between channels, channel diameter, rectangular dimensions around the perimeter of the channels. In some examples, a distal barrier plate of a pipette tip dispenser device is configured to load pipette tips into racks that conform to American National Standards Institute (ANSI) standard dimensions, accepted by the Society for Biomolecular Sciences (SBS), for devices used in high throughput applications related to the use of microtiter plates (e.g., multi-channel dispensers (manual or automated), pipette tip racks, pipette tips, and the like), in certain examples. In certain examples, barrier plate 25 may have a footprint length of between about 5 inches and about 5.1 inches (e.g., length of about 5.00 inches, about 5.01 inches, about 5.02 inches, about 5.03 inches, about 5.04 inches, about 5.05 inches, about 5.06 inches, about 5.07 inches, about 5.08 inches, about 5.09 inches and about 5.10 inches), and in some examples barrier plate 25 has a footprint width of between about 3.3 and about 3.4 inches (e.g., length of about 3.30 inches, about 3.31 inches, about 3.32 inches, about 3.33 inches, about 3.34 inches, about 3.35 inches, about 3.36 inches, about 3.37 inches, about 3.38 inches, about 3.39 inches, and about 3.40 inches), as measured from edge to edge across the appropriate dimension (e.g., length dimension or width dimension). In examples configured to dispense 96 pipette tips, the pipette tip center to center distance, which conforms with the center to center distance of many commercially available pipette tip racks, is in the range of between about 0.35 to about 0.36 inches. In examples configured to dispense 384 pipette tips, the pipette tip center to center distance, which also conforms with the center to center distance of many commercially available pipette tip racks, is in the range of about 0.17 inches to about 0.18 inches. Pipette tips often are dispensed in an array compatible with a wide variety of commercially available pipette tip holders by devices described herein.
In some examples, a distal barrier plate can be configured as a one-piece plate, and in certain examples a distal barrier plate can be configured as a two-piece plate. A one-piece distal barrier plate embodiment is illustrated in FIGS. 10A-10E. Distal barrier plates configured as a two-piece plate sometimes comprise a base plate or carrier plate (see FIG. 3A-3B) operably connected to a barrier plate or a plate with the functionality of a barrier plate (e.g., a plate with optional tails that provides the functionality of the distal barrier plate (see FIG. 1A and FIG. 2A)). The optional tails are pointed upward in FIGS. 1A-1D and 2A-2C, and pointed downward in FIGS. 10A-10E. The tails of the distal barrier plate normally point downward in an assembled, functional cartridge for an automated pipette tip loading device.
In some one-piece examples, the distal barrier plates comprise bores through which the connector rods are disposed. In certain examples, the barrier plate bores can be threaded. Threaded barrier plate bores allow rotation of the connector rods, thus enabling translation of the barrier plate and activator plate toward one another. The mode of action of barrier and activator plate movement is described below. In certain two-piece distal barrier plate examples, the bores or threaded bores, through which the connector rods are disposed, can be part of the base plate described in further detail below. In some examples, bores of a distal barrier plate are substantially smooth.
In some examples, the vertical spacing between the top of the barrier plate 25 and the top of the loading block 7 below it, may be configured such that the most distal end or distal portion of a pipette tip 50, which is more distal to the optional tails 21 of the barrier plate 25, is disposed within a hole of a loading block 7 so long as that loading block is engaged with the moving plate 3 of the housing (see FIG. 8A). In this arrangement, the pipette tips 50 are preloaded into the holes of the loading block 7. After being ejected from the barrier plate 25 passing through the channels 18 and past the optional tails 21, the pipette tips 50 will continue down into the holes of the loading block 7. Such distal tip engagement of the pipette tips into the holes of the loading block 7 reduces or prevents potential jams or mis-feeds of the pipette tips after ejection from the channels 18 of the barrier plate 25.
FIGS. 1, 2 and 10 illustrate an embodiment of a pipette tip dispensing device distal barrier plate 25 having a plurality of channels 18, where each channel has a diameter larger than the widest portion of a pipette tip, which can be the major outer transverse dimension 58 of a pipette tip or the largest outer diameter of the proximal portion of a pipette tip. The barrier plate 25 in FIGS. 1, 2 and 10 has a substantially flat top surface 23, and a substantially flat bottom surface 29 that optionally has a plurality of tails 21 around some or all of channels 18. The bossed arrangement of substantially flat surface 29 having a thickness 33 in conjunction with substantially flat surface 19 is optional, and surface 29 may be continuous to the perimeter of the plate in some examples with no bossed region. FIG. 1B illustrates optional tails 21 extending in a nearly perpendicular orientation from the flat bottom surface 19. The tails 21 around each channel 18 contact the pipette tip, and optionally deflect outwards against the proximal portion of a pipette tip, when a pipette tip is dispensed and passes by the tails 21, thereby imparting a frictional force on the pipette tip when it is dispensed. Distal barrier plate 25 sometimes also includes optional tails 21 with inner surface 31 and optional pins 17.
Each channel optionally can have 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 or more tails. FIGS. 1, 2 and 10 illustrate an embodiment of the barrier plate having four tails 21 per channel. FIG. 1 illustrates an embodiment of the barrier plate where each channel of the barrier plate comprises tails of the same length. FIG. 1B shows an enlarged view of each channel with tails of the same length. FIG. 1C shows a profile view of the tails 21 where they are all of the same length in the barrier plate. FIGS. 2C and 10D show an example of channels of the barrier plate having tails of different lengths, where tail 20 is longer than tail 22. Channels located in the center of the barrier plate can also be the longest tails, as seen in FIGS. 2C and 10D. Subsequent channels concentrically disposed about a central longitudinal axis can have sequentially shorter tails in length in a stepwise manner, also seen in FIG. 2C. FIGS. 10A-10E also show a barrier plate embodiment having tails of different lengths surrounding a channel. In some examples channels located in the center of the barrier plate can have the shortest tails, which are not shown in the drawings. And in certain examples, subsequent channels concentrically disposed about a central longitudinal axis can have sequentially longer tails in length in a stepwise manner.
Downward movement of the pipette tips within the housing unit often is achieved by pressure or force, not gravity in most examples, and downward movement often is actuated by a user. In some examples, downward force or pressure often begins with user-induced activation on the actuator plate, with the pressure or axial force greatest at the sides of the plate. In certain examples, downward force or pressure sometimes begins with the arrival or detection of a pipette tip rack or holder in the appropriate position to receive pipette tips. The pressure or axial force then spreads peripherally to the center of the activator and distal barrier plates.
A user may actuate the device several times, unloading or ejecting an array of pipette tips from the bottom of the distal barrier plate each time. Pipette tips may be dispensed until, for example, the device is empty of pipette tips and/or insufficient axial force is placed on the device, for example.
It has been determined that providing a distal barrier plate that releases pipette tips in an array at different times can be advantageous. A distal barrier plate in which all channels have the same frictional profile ejects all tips of an array at the same time, which requires a particular actuating force by the user or operator, referred to hereafter as total force or "F_T." A distal barrier plate in which some channels have a different frictional profile compared to other channels, however, ejects tips in an array at different times. Without being limited by theory, a portion of force F_T first ejects one subset of pipette tips in the array through channels having a first frictional profile, and another portion of F_T then ejects a second subset of pipette tips in the array through channels having a second frictional profile. Thus, releasing tips in an array at different times effectively spreads out F_T over time, and effectively reduces the actuating force required to eject tips of an array at any one point of time.
The term "same frictional profile" as used herein refers to channels in a distal barrier plate that apply the same frictional force to pipette tips in an array for the same amount of time. The term "different frictional profile" refers to a channel in a distal barrier plate that applies a different frictional force and/or applies the same or different frictional force to a pipette tip for a different amount of time, as compared to another channel in the plate.
In some examples, a distal barrier plate includes a subset of channels that ejects pipette tips at a rate different than another subset of channels. In certain examples, a distal barrier plate includes 2 to 100 different subsets of channels, each of which eject a pipette tip of one array at a different time (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 different subsets). Thus, a distal barrier plate can include 2 to 100 different subsets of channels, each of which have a different frictional profile. The time lapse between the time one set of tips is released from one subset of channels to the time another set of tips is released from another subset of channels can be between about 0.00001 seconds to about 5 seconds (e.g., 0.0001, 0.001, 0.01, 0.1, 1 second), and the total time required to eject pipette tips in an array can vary from about 0.001 seconds to about 5 seconds (e.g., 0.01, 0.1, 1 second). In some examples, a distal barrier plate is provided in which all channels have the same frictional profile and all dispense pipette tips at the same time.
In some examples, pipette tips at or near the center of a distal barrier plate eject first, and pipette tips near the edge of a distal barrier plate eject last. In certain examples, subsets of channels disposed in a linear and/or radial orientation away from the center to the periphery of the plate sequentially eject tips at progressively increasing times.
In certain examples, pipette tips at or near the center of a distal barrier plate are ejected last, and pipette tips at or near the edge of a distal barrier plate are ejected first. In such examples, subsets of channels disposed in a linear and/or radial orientation from the periphery of the plate to the center of the plate sequentially eject tips at progressively increasing times.
Where it is noted herein that a channel applies a particular frictional force to a pipette tip for particular period of time, the channel periphery or channel walls may apply a frictional force to the pipette tip. Often, however, a feature outside a channel applies a frictional force to the pipette tip (e.g., projections or tails around a channel in connection with a top and/or bottom surface of the plate).
Certain features of a distal barrier plate can apply a particular frictional force to a pipette tip. For example, channel features, including but not limited to channel diameter; channel texture; the presence or absence of one or more projections in the channel (e.g., connected to a channel interior wall); the shape, size, length, thickness, width, rigidity, texture, and/or angle of one or more projections in a channel; or combination of the foregoing, can affect the frictional force applied to a pipette tip as it is ejected. Also, the presence or absence of one of more optional projections outside a channel (e.g., connected to top and/or bottom surface of a distal barrier plate); the shape, size, length, thickness, width, texture and/or angle of one of more projections outside a channel, or a combination of the foregoing, can affect the frictional force applied to a pipette tip as it is ejected.
Any suitable number of optional projections can be present around or near a channel, including without limitation about 1 to about 50 projections. Projections can contact one or more surfaces of a pipette tip, in some examples. Projections can contact the widest portion (e.g., largest diameter portion) of a pipette tip (e.g., proximal region portion), and sometimes do or do not contact lower diameter portions of a pipette tip (e.g., distal region portion). Projections sometimes flex against a portion of a pipette tip (e.g., proximal region portion) when the pipette tip is dispensed past the projections. Projections in some examples are elastic, and can return to about the same position after a pipette tip is ejected. Projections in connection with the top surface or bottom surface of a distal barrier plate sometimes are referred to herein as "tails," as described herein.
The length of an optional projection (e.g., tail) can affect the time at which pipette tips are ejected. Without being limited by theory, tails having a relatively longer length apply a frictional force for a longer period of time and result in a tip ejection time that is longer than for relatively shorter tails. FIGS. 2A and 2C show channels located in the center of the barrier plate along the X axis can have tails of the same length and channels along the Y axis can have tails of varying length. In some examples, channels located in the center of the barrier plate along the Y axis can have tails of the same length and channels along the X axis can have tails of varying length or channels located in the center of the barrier plate along the X and Y axes comprise tails of varying length, which is not shown. Channels can have an even or odd number of tails. For channels having even number of tails, the tails directly opposite one another around a channel can have the same length. And in certain examples tails directly opposite one another around a channel can have a different length. Tails adjacent to one another can also have a different length. The tails can be between 0.01µm - 2.0mm in length. The tails can be between 0.05µm- 2.0mm in length. The tails can be about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.12, 0.14, 0.16, 0.18, 0.2, 0.22, 0.24, 0.26, 0.28, 0.30, 0.32, 0.34, 0.36, 0.38, 0.4, 0.42, 0.44, 0.46, 0.48, 0.5, 0.52, 0.54, 0.56, 0.58, 0.6, 0.62, 0.64, 0.66, 0.68, 0.7, 0.72, 0.74, 0.76, 0.78, 0.8, 0.82, 0.84, 0.86, 0.88, 0.9, 0.92, 0.94, 0.96, 0.98, 1.0, 1.2, 1.4, 1.6, 1.8, or 2.0 mm in length, in certain examples. A distal barrier plate in some examples may include tails having different lengths at different channels (e.g., tails around a first channel have a first length, and tails around a second channel have a second length). For example, in certain examples the length of tails for each channel progressively increases or decreases (i) from the center of the X-axis to each end of the X-axis and/or (ii) from the center of the Y-axis to each end of the Y-axis. As used herein, the term "progressive" refers to linear, stepwise, sigmoidal, and exponential, in particular examples.
The internal angle of optional projections or tails also can affect the time at which pipette tips are ejected. For example, a relatively smaller internal angle for tails or projections can result in a relatively longer time required to eject a pipette tip. The term "internal angle" as used herein with respect to a tail around a channel is an angle measured from the midpoint of a channel at the bottom surface of the plate towards the tail surface facing the channel (e.g., surface 31 in FIG. 1D), as illustrated in FIG. 1D as angle theta. For example, an internal angle of 90° from the bottom surface 19 of the distal barrier plate would be exactly parallel to the Z axis as shown in FIG. 1C. Tails of the barrier plate often are nearly perpendicular with respect to, and often are at an internal angle of almost 90° from, the bottom surface 19 of the distal barrier plate. In some examples, tails 21 are at an internal angle of about 89° to about 80° from the bottom surface 19 of the distal barrier plate. Tails can be at an internal angle between 88-85°, 87-84°, 86-83° or 86-85° from the bottom surface of the distal barrier plate. Tails are at an internal angle of about 87° from the bottom surface of the distal barrier plate in some examples. A distal barrier plate in some examples may include tails having different angles at different channels (e.g., tails around a first channel have a first internal angle, and tails around a second channel have a second internal angle). For example, in certain examples the internal angle of tails for each channel progressively increases or decreases (i) from the center of the X-axis to each end of the X-axis and/or (ii) from the center of the Y-axis to each end of the Y-axis.
Texture of the optional tails or projections can affect the time required to eject a pipette tip from a distal barrier plate. In some examples, texture can modulates the length, thickness or angle of a tail. Tails can comprise smooth surfaces in some examples, and in certain examples, tails can comprise texture on one or more surfaces. A tail can be entirely smooth, may be entirely textured, or may include textured and smooth surfaces, in some examples. A plate can comprise tails that are smooth and some tails that comprise texture. Tail texture can include, without limitation, ridges, barbs, grooves, grains, embossed, etches, pores, pits, lines, scratches, scores, scrapes, cuts, carvings, incisions and the like. Tail texture can increase frictional force on pipette tips moving past the tails when dispensed. Texture also can aid in channeling pipette tips through the tails and into a loading block (e.g., linear or twisted grooves (e.g., rifled grooves) extending from a tail top to tail bottom). A distal barrier plate in some examples may include tails having different textures at different channels (e.g., tails around a first channel have a first texture that applies a first frictional force to pipette tips, and tails around a second channel have a second texture that applies a second frictional force to pipette tips). For example, in certain examples the texture of tails for each channel progressively increases or decreases the frictional force (i) from the center of the X-axis to each end of the X-axis and/or (ii) from the center of the Y-axis to each end of the Y-axis.
Optional tails around a channel often are not in the channel, and the portion of a tail joined to the distal barrier plate bottom surface sometimes is co-extensive with the edge of a channel. In some examples, the base portion of a tail joined to the distal barrier plate bottom surface is displaced a distance from the channel perimeter that it surrounds, which distance can be a mean, nominal, average or maximum distance of about 0.001 millimeters to about 2 millimeters (e.g., the portion of the tail closest to the channel perimeter that the tail surrounds is offset 0.005, 0.01, 0.05, 0.1, 0.5 or 1 millimeters from the perimeter). The term "displaced" as used herein with respect to tail orientation refers to displaced away from channel perimeter such that the tail base is partially over the channel perimeter, or displaced away from the channel perimeter so that there is a gap between the channel perimeter and the tail base on the plate bottom surface equal to the displaced distance. Thus, the term "surrounds" as used herein with respect to a tail refers to a tail associated with a channel, where the tail base is co-extensive with, or displaced towards or away from, the channel perimeter. For example, tail 21 surrounds channel 18, and tail 21' surrounds channel 18', but tail 21 does not surround channel 18', as shown in FIG. 2B.
Optional tails described herein generally are not prone to breakage as pipette tips are dispensed through a distal barrier plate comprising the tails. Without being limited by theory, the nearly perpendicular orientation of tails with respect to the bottom surface of a distal barrier plate contributes to tail stability, as this orientation requires little flexion of tails to apply a force to the pipette tips. In certain examples, the maximum, mean, median or nominal tail flexion is about 0.01 degrees to about 10 degrees (e.g., about 0.05, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9 degrees). The term "flex outward" as used herein refers to a tail flexing a certain number of degrees added to the internal angle. For example, a tail that flexes outwards by 2 degree adds 2 degrees to the internal angle in the flexed state; if the tail in the unflexed state has an internal angle of 87 degrees, the tail in the flexed state has an internal angle of 89 degrees. In certain examples, no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 tails, or portions thereof, are separated from the distal barrier plate for a set of 480 pipette tips dispensed through the plate.
A tail may have any convenient shape. A surface of a tail can be of a shape that includes without limitation, square, rectangle, rhombus, parallelogram, circle, oval, arced, curved, planar, non-planar, and the like. The thickness of a tail can be continuous or tapered (e.g., tapered towards the top (i.e., in association with the plate) or bottom (i.e., at the tail terminus) of the tail).

Base Plate

In some examples, an automated pipette tip loading device can have a distal barrier plate configured in two pieces, a base plate and a barrier plate. FIGS. 3A and 3B show an optional embodiment for base plate 27 which the distal barrier plate 25 can snap into by pins 17 at the four corners of the barrier plate. The pins 17 match the four holes in the base plate so that the distal barrier plate 25 can be centered in the middle of the base plate 27. One of ordinary skill in the art will recognize other ways the base plate 27 and distal barrier plate 25 can be held together. For example, magnets, guides, fasteners, and buttons can also hold the plates together. The base plate 27 is shown having two holes 24 for placement of rods 28 to connect the distal barrier plate 25 and actuator plate 41. In certain examples, the distal barrier plate and the base plate are formed into one plate serving both functions. A one piece distal barrier plate/base plate embodiment is illustrated in FIGS. 10A-10E.
FIG. 3A shows the proximal surface of the base plate and FIG. 3B shows the distal surface of the base plate. The base plate 27 also has prongs 26 which are used in packaging the auto eject cartridge 6. The prongs 26 aid in placement of the disposable, recyclable, rectangular sleeve that covers the auto eject cartridge 6, as seen in FIGS. 8A and 8B, 12A-12H and 14A-14G. The prongs also secure a removable, disposable, recyclable bottom lid, not shown, that protects the pipette tips from damage or contamination during shipment. The lip of the bottom lid slightly telescopes above the prongs to be secured. The bottom lid is removed when the auto eject cartridge is place into the housing unit.

Proximal Actuator Plate

In some examples, the proximal actuator plate, also referred to as an "activator plate" (e.g., 41 in FIGS. 5A-5C, also see FIGS. 11A-11E), has a member on the top portion 42 of the actuator that maintains contact with and restricts lateral displacement of the proximal portion 56 of the pipette tips 50. The member can be any material known to one of skill in the art, for example the member can be foam, a raised grid, or a plurality of proximal alignment members 40. As noted above for the distal barrier plate, the raised grid or plurality of proximal alignment members 40, are spaced and configured to conform to the footprint of a pipette tip rack or holder that conforms to American National Standards Institute (ANSI) standard dimensions, accepted by the Society for Biomolecular Sciences (SBS), for devices used in high throughput applications related to the use of microtiter plates (e.g., multi-channel dispensers (manual or automated), pipette tip racks, pipette tips, and the like), in some examples.
FIGS. 5A-5C (see also FIGS. 11B and 11E) show examples with a plurality of proximal alignment members 40 disposed substantially in a plane in a regularly spaced array and each proximal alignment member 40 is configured to releasably engage and restrict lateral displacement of a proximal end 56 of a pipette tip 50 that is engaged with the alignment member 40. The proximal alignment members can be of any convenient shape suitable for engaging and aligning pipette tips held in a nested array in the automated pipette tip loading device. Non-limiting examples of cross-sectional shapes useable for alignment members in actuator plate examples described herein include circular, square, star shaped, triangular, cone shape, hexagonal, octagonal, a polygon shape and the like.
In some examples, the proximal alignment members 40 may be cone shaped abutments extending from a distal surface of the actuator plate 41 that may be configured to engage or fit within the proximal port of corresponding pipette tips to be used with the proximal actuator plate 41. The proximal actuator plate 41 may be made from suitable metals, such as aluminum, or polymers such as polypropylene, polycarbonate, polyethylene, polystyrene, polyurethane and the like as well as any other suitable polymers that may be molded, thermoformed or the like. The proximal actuator plate 41 and proximal alignment members 40 may be molded from a monolithic structure of the same material for some examples. The proximal actuator plate 41 may have a thickness of about 0.05 inches and about 0.25 inches. The proximal actuator plate 41 may be secured to a plurality of rods and may be configured with sufficient rigidity to maintain a generally planar configuration when applying axial force to an array of pipette tips 50 engaged with the proximal members 40 thereof as the pipette tips are being pushed through the tips 21 of the distal barrier plate 25. Some pipette tip array examples of the actuator plate 41 and barrier member may include 96 pipette tip arrays of 8 x 12 pipette tips spaced about 9 mm apart center to center, some other examples may include 384 pipette tip arrays of 16 x 24 pipette tips spaced about 4.5 mm apart center to center. Other pipette tip array examples may include more or less pipettes depending on the application.
The proximal actuator plate 41 in FIGS. 5A and 5B (see also FIGS. 11A, 11C and 11E) show two holes or bores 24 for placement of rods 28 to connect the distal barrier plate 25 and actuator plate 41. The holes or bores, 24, through which the connector rods exert a downward force on the actuator plate, sometimes are threaded, and in some examples are smooth. In certain examples, plate 41 includes a recess configured to receive a threaded nut that engages with a connector rod. A threaded feature in the bore and/or nut in plate 41, in some examples, can interact with a threaded connector rod and facilitate displacement of the actuator plate and barrier plate towards each other (e.g., by rotation of the threaded connector rod). The barrier plate often has corresponding bores or threaded bores through which a distal portion of the connector rods translate, enabling the rods to exert an upward force on the barrier plate. The corresponding bores in the barrier plate aid in the displacement of the actuator plate and barrier plate towards each other.
Optionally, the top portion of the actuator plate 41 has ridges or grooves 38 which provide strength and ridgidity to the actuator plate 41. As seen in FIGS. 6A and 6B, the roof portion 46 of the actuator plate also can have ridges or grooves 48 which can also provide strength and ridgidity to the plate. In some examples, the roof portion of the actuator plate can have a smooth surface as illustrated in FIGS. 11A, 12A, 14A and 14F.
A force may be effectively applied to an actuator plate in a number of manners. In some examples, an actuator plate is pulled downward, and in certain examples, an actuator plate is pushed downwards, to dispense pipette tips. In examples where a motor effectively applies a force to an actuator plate, the motor may be located in any orientation with respect to the actuator plate, including, for example, above, below or to the side of the actuator plate. The applied force sometimes it the result of rotation of the connector rods through threaded bores and/or threaded nuts in the actuator and distal barrier plates, which in turn mechanically displaces the actuator and distal barrier plates towards each other, as described in further detail below. In examples where a threaded nut is utilized, bores in the actuator plate sometimes are smooth.

Connectors

Referring to FIG. 4, a rod 28 is shown in detail as one embodiment of a connector that connects the actuator plate 41 and distal barrier plate 25. Any suitable connectors that can perform the same or a similar function of connecting actuator plate 41 and distal barrier plate 25 and facilitating displacement of the plates towards each other, can be used. Non-limiting examples of connectors include a bar (rectangular, L-shaped cross section), tube (e.g., telescoping, non-telescoping), piston (e.g., piston in sleeve configuration), spring, chain, vise, crank, screw, lever, dolly, clamp, hook, or grapple can be connectors in some examples. A rod has any suitable shape, and can comprise a circle, oval, square, rectangle, rhombus, L-shaped, S-shaped, or parallelogram cross section in some examples, and in certain examples, can comprise a substantially planar, non-planar or curved surface. Connectors also are illustrated in FIGS. 12A-12E and 12H.
In FIG. 4, the rod has a shaft 30, grommet 32, bolt 34 and a distal portion 36. The shaft 30 of the rod can be threaded. A connector may be movably engaged (e.g., slidably engaged) with a distal barrier plate, and in some examples a connector may translate through the distal barrier plate when pipette tips are dispensed. A connector may be fixed while pipette tips are dispensed in some examples, and an actuator plate may translate with respect to the connector, in certain examples. A connector may rotate, translate vertically (e.g., with respect to a distal barrier plate), ratchet, telescope and the like, or combination of the foregoing, while pipette tips are dispensed, in some examples. A connector may be effectively fixed with respect to a distal barrier plate and/or an actuator plate in certain examples. A connector may translate with respect to a distal barrier plate and or actuator plate in some examples.

Connector Drive System

As noted above, connectors can facilitate translation of the proximal activator plate and distal barrier plate towards each other, thereby dispensing pipette tips into a waiting pipette tip rack or holder. The connectors, illustrated as rods in some examples described herein, can be rotated, sometimes by a force imparted by a motor, to cause the required movement of the activator and barrier plates with respect to each other. Bolt 34 and distal portion 36 of connector rods 30 sometimes can be configured to functionally engage a drive mechanism of connector drive system, or robot drive, 70, illustrated in FIGS. 15 and 16.
Connector drive system or mechanism 70 can include: motor or drive 72, motor base and drive housing 74, connector drive 76, optional mounting system 78 and pipette tip rack staging area cutout 80, as illustrated in FIG. 15. Connector drive system 70 also can include drive belts/ chains 82 and 84 and intermediate drive mechanism 86. Motor or drive 72 often provides sufficient energy or force to rotate the connectors through the functional engagement of bolt 34, 34' and connector distal portion 36, 36' with connector drive 76. Any method of transmitting the force of motor or drive 72 to connector drive 76 can be utilized. In some examples, force is transmitted directly (e.g., direct connection of motor output to connector drive 76), and in certain examples, force is transmitted indirectly (e.g., the output of the motor operates an intermediate drive mechanism 86 that is functionally coupled to connector drive 76). Non-limiting examples of methods for transmitting the force of motor or drive 72 to connector drive 76, directly or indirectly, include gear drives, shaft drives, belt drives, chain drives, the like and combinations thereof. Optional mounting system 78 can be used to secure connector drive system 70 to a frame or housing unit, thereby stabilizing and/or immobilizing connector drive system 70 in an appropriate location to allow functionality of connector drive system 70.
Shown in an embodiment described in FIG. 16 is an indirect force transmission approach, where the force of motor or drive 72 is transmitted using belt system 84 to cause rotation of intermediate drive 86 (e.g., pulley, cam, or gear). The rotation of intermediate drive 86 is translated to rotation of connector drive 76 by the action of a second belt system 82, as illustrated in FIG. 16. Use of indirect force transmission methods as described herein and others available to a user allow the force imparted by a single motor or drive 72 to be split and transmitted to two or more remote locations, with the added benefit of being able to deliver the force to a desired location without the need for a direct path from motor 70 to connector drive 76.
Rotation of connector drives 76 rotates connector shafts 30, 30' via the functional engagement of nut 34, 34' and distal portion 36, 36'. Distal portion 36, 36' sometimes is configured as a nut or bolt to engage socket shaped drive 76, as illustrated in some examples provided herein (see FIG. 15). Any suitable pairing of geometries can be selected provided that the chosen shapes are capable of transmitting the required force to translate the plates towards each other, and overcome the frictional force imparted by the plurality of optional tails surrounding each channel in distal barrier plate 25. Non-limiting examples of geometric pairings suitable for use as connector drive 76 and base or distal portion of rod 30, 30' include 3 sided, 4 sided, 6 sided, 8 sided, or 12 sided "nuts" or "bolts" with the corresponding "socket", slots and tabs, pegs and holes, the like or combinations thereof.
Rotation of shafts 30 via connector drives 76, movably translate proximal activator plate 41, 41' and distal barrier plate 25, 25' towards each other, thereby forcing a layer of pipette tips through the channels in barrier plate 25, 25' into a pipette tip rack or holder staged on a platform occupying the space left by drive system cutout 80. Pipette tip racks can be placed manually on a platform or tray placed in drive system cutout 80, in some examples. In certain examples, an automated platform can insert or remove a pipette tip rack in the appropriate location in drive system cutout 80 to receive dispensed pipette tips as described herein. In some examples, the pipette tip dispensing cycle is initiated by the insertion of a pipette tip rack in the receiving position by a manual or automated platform. In certain examples, the platform or movable stage moves horizontally, and in some examples, the platform or stage moves vertically, into the space left by drive system cutout 80. In certain examples, arrival of a platform or movable stage into drive cutout 80 triggers pipette tip dispensing and sterilization cycles.
As noted above, the movement of the platform or stage that holds an empty pipette tip rack or holder can be manually or automatically activated by a user. In certain examples, the platform movement is controlled manually by a user-activated switch or level. In some examples, the platform movement is automated, and can be activated by a user by a switch or controller, or by placing a pipette tip rack on the moveable platform, which then initiates the pipette tip dispensing and sterilization cycles by automated sensor (e.g., sensor detects the arrival of pipette tip rack, and initiates dispensing and sterilization cycles). In examples utilizing an automated platform, the platform movement sometimes is controlled by a motor that can insert the platform into drive system cutout 80. In certain examples, motor or drive 72 can be activated by a user controlled mechanism. In some examples, a user controlled mechanism is a switch (e.g., lever switch), button, or sensor. In some examples, the motor stops rotating the rods by a pressure sensor gauge. In some examples, a user is a person or machine (e.g., robot, computer).

Auto Eject Cartridge

An auto eject cartridge (e.g., element 6 of FIGS. 8A, 8B and 9 (see also FIGS. 12A-12H)), often includes several components. In some examples, cartridge 6 includes arrays of pipette tips 50, activator plate 41, distal barrier plate 25, base plate 27, rods 28, nuts 62, and rectangular sleeve 61 and bottom lid 64. Aside from the outer sleeve 61 and lid 64, other mechanical components work together in dispensing an array of pipette tips from the bottom of the auto eject cartridge 6 and into the loading block 7 below. Sleeve 61 in some instances may refer to both the sleeve 61 as seen in FIG. 9A and the bottom lid 64 as one storage unit that houses all the components seen in FIG. 9A. In some instances, sleeve 61 only refers to the top and side portions of the sleeve without the bottom lid 64 as seen in FIG. 8A and 8B. In some examples, the distal barrier plate 25 and base plate 27 are one in the same and not two separate components. Together they can be referred to as the distal barrier plate 25, as described below within this section. In some examples, connectors of the activator 41 and distal barrier plate 25 are rods 28. The rods 28 can have threads etched into their outer surface such that another threaded component can be securely engaged to it. The activator plate 41 can include threaded members, and each threaded member engages a threaded portion of each rod. 28. Rotation of the rods 28 by a motor can translate the activator plate 41 towards the distal barrier plate 25 by rotation of the rods 28. The motor 13 is activated by a user controlled mechanism. The user controlled mechanism can be a variety of known devices. For example, a controlled mechanism can be a lever switch, button, or sensor. The motor can stop rotating the rods by a pressure sensor gauge after ejection of an array of pipette tips 50 from the distal barrier plate 25.
The term "sleeve" as used herein refers to a structure around plates and pipette tips of a cartridge. The sleeve is of any convenient shape for use with a pipette tip dispenser, and sometimes has a circle, oval, square, rectangle, rhombus, parallelogram and the like cross section, and sometimes a sleeve includes one or more surfaces that are planar, non-planar, curved, arced and the like. A sleeve sometimes includes four vertical sides, and sometimes includes a top. A sleeve comprises any suitable materials, and comprises in some examples, a polymer, biodegradable polymer, other degradable or biodegradable materials (e.g., bamboo, recycled banana peel, and the like), fiber product, paper, metal and the like, or a combination thereof. The material from which the sleeve is made can be of any suitable color or transparency. In some examples, the sleeve may be transparent. In certain examples, the sleeve can be semi-transparent. In some examples, the sleeve can be opaque. In certain examples, a sleeve can be semi-opaque. Opaque sleeves can be of any desired color, in certain examples. In some examples, the sleeve can be opaque in some regions and transparent in some regions. In certain examples, a sleeve can be translucent. In some examples, the sleeve comprises writing, and in certain examples the sleeve does not comprise writing. A cartridge with a transparent sleeve is illustrated in FIGS. 12-12H. A cartridge with an opaque sleeve is illustrated in FIGS. 14A-14G. The sleeve also may be optional.
FIG. 9A (see also FIGS. 12A-12C) shows components in an auto eject cartridge with FIG.9B showing an enlarged detail figure of the distal barrier plate 25, base plate 27, rod with grommet 32. FIG. 9C shows an enlarged detail figure of a plurality of proximal alignment members 40 and placement of one pipette tip 50 underneath.
FIG. 12H illustrates a cartridge with a transparent outer sleeve loaded with a nested array of regularly spaced pipette tips between a top activator plate and a bottom distal barrier plate. Pipette tips can be seen protruding below the distal barrier plate in FIG. 12H.

Housing Unit

Referring to FIGS. 8A - 8B (see also FIGS. 13A-E), an automated pipette tip dispensing device is shown in detail. The structural housing components top 4, back 8, side 9, door 10 may be made from any type of material known to one of skill in the art, such as for example a clear, thin rigid material formed into a substantially rectangular configuration with a closed bottom portion such as a base plate and driver 1. The housing unit 60 substantially has planar back 8, sides 9, and door 10 components that may be arranged substantially perpendicular to each other and to the top surface 4 disposed on the upper end of the housing. For some examples, the housing may be made from a thin clear polymer material that is transparent or translucent and may have a thickness of about 0.005 inches to about 0.05 inches. For some examples, the housing may be made from suitable metals, such as aluminum or steel, or polymers such as polypropylene, polycarbonate, polyethylene, polystyrene, polyurethane and the like as well as any other suitable polymers that may be molded, thermoformed or the like. The housing may have a thickness that allows for some flexibility but provides sufficient structural strength to maintain its general shape upon manual manipulation, e.g., loading and unloading the auto eject cartridge, and automatic dispensing. The housing is also sufficiently rigid to be self-supporting and maintains integrity sufficient to support the full procedure of the automated pipette tip dispensing device. The procedure involves steps such as having a full auto eject cartridge 6 being placed within the housing, automated dispensing of the pipette tips 50 into the loading device 7. After a cartridge 6 is emptied, it can be removed from the housing unit 60, and replaced with a full cartridge 6.
In some examples, other housing components can include t-slot posts 2 which provide support as an inner frame for the housing unit. The posts 2 may also be optional, where the planar back 8, sides 9 and door 10 of the housing unit 60 may provide the structure for the housing without the posts 2. Vertical rails or tracks can facilitate placement and/or movement of components within the device, for example such as guide posts 16, see FIG.8A. The guides 16 can provide alignment so that the moving plate 3 is raised and lowered to the correct positions within the device. The guides 16 may function manually or with a motor. Other components may also provide the same function as the guide posts 16, such as a lever or pulley that raises and lowers the moving plate 3 into position below the distal barrier plate 25. Posts, rails and tracks can be of any suitable geometry for vertically translating plates in an automated dispensing unit. The moving plate 3 is shown having two holes where the guides 16 pass through. One or more guides 16 can be included in the device for this function. The moving plate 3 may function by use of a motor 13 or electrical engine (see FIGS. 15 and 16) and functions to move the loading block 7 up and down in some examples, and sometimes a user can operate a lever that manually moves the loading block up and/or down. A user can place an empty loading block 7 onto the lowered moving plate 3. Upon activation the moving plate 3 transports the loading block 7 up and directly beneath the center plate 5 which holds the auto eject cartridge 6 in place in some examples. The proximity of the moving plate 3 to the center plate 5 aids in aligning the pipette tips into the loading block 7 before ejection into the block 7. And when the moving plate 3 and loading block 7 are most distal to the center plate 5 or resting above the base plate 1, the space between the loading block 7 and the center plate 5 allows for the user to remove the loading block and/or replace it with another block. Alternatively, the moving plate 3 can be optional, for example, the loading block 7 can be placed on the base plate 1 which can be directly distal to the center plate 5. The base plate 1 can provide a platform for the moving plate 3 and loading block 7 as well as an area for the controller 15 and motor 13 to be housed. However, the controller 15 and/or motor 13 may be housed in another area or areas of the housing unit. There also may be one or more motors 13, for example, one for powering the rods 28 in the cartridge 6 and another motor for powering the moving plate 3 and/or guide posts 16. Alternatively, there may be one motor 13 powering all electric functions including for example, an ionizer, UV light source, or other structure that can sterilize pipette tips. A device can include one or more sterilization components (e.g., UV light emitter, ionizer unit, gamma irradiation unit, sterilizing gas emitter, the like and combinations thereof). In some examples, sterilization components can be actuated by a user controlled mechanism, or by an automated mechanism that acts in conjunction with or whose action is initiated by movement of a device component or the action of a controller (e.g., controller 15). Sterilization can occur during the tip dispensing cycle or after the tips are dispensed into the waiting pipette tip rack, while the rack is still positioned on the platform occupying drive system cutout 80.
The controller 15 can centrally coordinate different functions occurring within the device, such as UV light emitter 11, ionizer 12, limit switch 14, etc. and have a user friendly display for adjusting settings and/or keeping track of how many pipette tip arrays are remaining in the auto eject cartridge 6 and/or when a new cartridge needs to be exchanged for an empty one and/or the type of pipette tips being housed in the device as well as specifications for the pipette tips themselves. The controller 15 may also provide a digital time/date and or history log of types of pipette tips used within the device as well as how many cartridges 6 have been used within a give time or history. Such inventory may be useful for budgeting purposes. The controller 15 may aid in a variety of other such user friendly support as well as coordinate other functioning mechanisms within the housing unit. The limit switch 14 can allow for one array of pipette tips to be ejected from the auto eject cartridge 6 per loading block 7. The limit switch 14 can also allow for more than one array of pipette tips to be ejected. The limit switch 14 can be performed by any variety of mechanisms necessary for this function. For example, the limit switch 14 can be a pressure sensor that stops the motor 13 powering the rods 28 from rotating and thereby stopping the activator plate 41 and the distal barrier plate 25 from translating towards one another. The limit switch 14 may function when a specific pressure is sensed on the loading block 7, rods 28, base plate 27, distal barrier plate 25, actuator plate 41, pipette tips 50, moving plate 3, center plate 5, guide posts 16 or any other component. The limit switch 41 may also be a motion sensor that can allow one array of pipette tips to be ejected from the auto eject cartridge 6 per loading block 7 by sensing the ejection of tips as movement and thereby stop power to the motor 13.
The housing unit 60 may also support other devices for example such as voice activated power controls, lighting, automated locks and releases, audio sounds such as a chime or an audio narrative for the various functions occurring within the device and/or when the pipette tips have been loaded and are ready for use.

Pipette Tip Sterilization

Pipette tip sterilization ensures that living microorganisms (e.g., pathogenic or saprophytic bacteria, vegetative forms and spores or any unwanted organisms) are eliminated (e.g., partially eliminated or substantially eliminated) from pipette tips. Sterilization can be performed in any variety of methods. For example, sterilization can be performed by sterilizing gas treatment, UV irradiation, ionization, alcohol or gamma radiation. FIGS. 8A shows a UV light 12 beneath the auto eject cartridge. UV light can bathe the array of pipette tips hanging down from the auto eject cartridge before, during and after ejection into the loading block 7. Any controller mechanism can activate a UV light source, such a motion sensor that detects movement of a loading block into the housing, a switch that is tripped by the pipette tip loading block, or a manual switch used by the operator, for example. The UV light source may work in conjunction with the motor 13 of the device and be activated when the loading block is lifted by the moving plate 3 into position underneath the center plate 5 in some examples.

Electrically Conductive Member(s)

Static charge can develop on pipette tips during use or shipping. This static charge can remain on the tips as they reside in dispensers or trays because there often is no flow or discharge of the electric charge from the tips to a ground source. Static charge in/on the tips and other components of a tray or dispenser may cause some of the tips to repel away from each other and other tray or dispenser components. This repulsion can result in the tips arranged in a different orientation than intended, and can negatively impact interaction with pipette devices (e.g., automated dispensers).
Pipette tips often are jostled within their pipette tip trays during shipment. The rubbing of the tips within the apertures of the perforated card that contains them can cause an electrostatic charge to develop on the exterior of the tips. This phenomenon often is applicable to tips of a smaller size (e.g., pipette tips that fit in 384 tip trays). The static charge can remain on the tips as they sit within their trays because there is no flow of the electric charge from the tips to the tip rack. The static charges on the tips and other components of the tray may cause some of the tips to repel away from each other and other tray components. This repulsion can result in the tips arranged in a different orientation than intended, and can negatively impact interaction with pipette devices (e.g., automated dispensers).
In certain examples, the pipette tips are in contact with an electrically conductive member, or portions thereof, which is in communication with the exterior of the sleeve and/or housing unit. This contact may allow static charge from the pipette tips to be discharged. Often the contact of an electrically conductive member or portions thereof, with the pipette tips involves the top proximal edges of the tips, which may involve direct, indirect, and/or in effective communication with the inner portion of the lid. The contact may also sometimes involve contact of the sides of the tips which may be in direct, indirect, and/or in effective communication with the card of the tray. In some examples, an electrically conductive member, or portions thereof, is in direct, indirect, and/or in effective communication with the pipette tips which ultimately aids in discharging the static charge within the pipette tips. The electrically conductive member, or portions thereof, may be in effective communication with any components of the device and be in effective communication with the exterior of the sleeve and/or housing. In certain examples, an electrically conductive member, or portions thereof, is located in any of the components of the device such as for example, the sleeve, housing, activator plate, distal barrier plate, channels, tails, and the like, which is in effective communication with the pipette tips, and is exposed through the sleeve and/or housing.
An electrically conductive member may comprise any type of electrically conductive material known, such as a conductive metal, for example. Examples of conductive metals include, without limitation, platinum (Pt), palladium (Pd), copper (Cu), nickel (Ni), silver (Ag) and gold (Au). The metals may be in any form in or on the conductive member, for example, such as metal flakes, metal powder, metal strands or coating of metal. An electrically conductive member, or portions thereof, may comprise a metal, polymeric material, foam, film, sheet, foil, salt or combinations thereof. In some examples, a conductive metal foil may be utilized for one or more components of a pipette tip device (e.g., copper-aluminum foil; label adhered to an electrically conductive tab on exterior of the housing or sleeve component). The electrically conductive materials, or portions thereof, may be any material that can contain movable electric charges, for example such as carbon. In some examples, the electrically conductive member comprises about 5% to about 40% or more carbon by weight (e.g., 7-10%, 9-12%, 11-14%, 13-16%, 15-18%, 17-20%, 19-22%, 21-24%, 23-26%, 25-28%, 27-30%, 29-32%, 32-34%, 33-36%, or 35-38% carbon by weight). In certain examples, an electrically conductive film is utilized that includes carbon (e.g., commercially available from Gemini Plastic Enterprises, Inc., California). An electrically conductive film in some examples contains ethylene vinyl acetate (EVA), which can impart a supple quality to the film (e.g., about 5% to about 25% EVA by weight; about 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24% EVA). In some examples a conductive tab may be in effective communication with any one or combination or all of the components of the device and aid in discharging an electrical charge from the device. A tab often is in effective communication with a conductive material contacting the pipette tips and the exterior of the device (e.g., exterior surface of the housing or sleeve). The tab may be affixed to one or more portions of a device (e.g., by an electrically conductive label).
The term "effective communication" as used herein refers to direct (e.g., part of the conductive member) or indirect (e.g., via component not part of the conductive member) in communication with exterior of the housing and/or sleeve. The term "exposure of conductive member" as used herein may refer to exposure by a reveal in a plate or member which may extend to the sleeve and/or housing exterior or can be free hanging or may be affixed to an external surface of the sleeve, housing and/or loading block. The external surfaces of the housing are for example the roof or sides of the housing. The term "affixed" as used herein refer to attachment for example such as embossed or adhesive.
A component that dissipates electrostatic charge from the pipette tips, such as an ionizer or humidifier, may be included in the device. An ionizer 12, as depicted in FIGS 8A and 8B, blows, directs and/or circulates an amount of ionized air towards the pipette tips 50 and loading block 7 that reduces or substantially eliminates any existing or potential build up of electrostatic charge on the tips. One of ordinary skill in the art will recognize various ways to activate such a device. Any controller mechanism can activate the ionizer, such as for example a motion sensor that detects movement of a loading block into the housing or a manual switch used by the operator. Or the ionizer may work in conjunction with the motor 13 of the device and be activated when the loading block is lifted by the moving plate 3 into position underneath the center plate 5.
Components described herein reduce the potential for static build-up and/or provide an alternate grounding path for harmlessly dissipating built-up electrostatic charge, or for discharging an electrostatic charge well before a substantial amount of charge may build up.

Method of Use

A pipette tip dispensing device described here can be used in conjunction with a method of simultaneously dispensing an array of multiple pipette tips into a loading block. In some examples, methods include: providing a dispensing device that includes a nested array of regularly spaced pipette tips between a top activator plate and a bottom distal barrier plate, wherein the activator plate and the distal barrier plate are in connection with two or more rods, wherein the distal barrier plate comprises: a plurality of channels, wherein each channel has a diameter larger than the widest portion of a pipette tip; a substantially flat top surface, and a substantially flat bottom surface that comprises a plurality of tails around some or all of the channels, wherein the tails extend in a nearly perpendicular orientation from the flat bottom surface; and actuating a motor of the dispensing device in effective connection with the rods that moves the rods, whereby the activator plate and the distal barrier plate are translated towards one another thereby applying an axial force on the array of pipette tips, wherein: (i) the axial force dispenses the array of pipette tips through the channels and past the tails, and (ii) the tails contact and deflect outwards against the pipette tips and impart a frictional force on the pipette tips, whereby the array of pipette tips is ejected into respective receptacles in the loading block. In certain examples, a pipette tip rack is loaded into the pipette tip dispenser housing unit, seated on the pipette tip rack holding platform in an appropriate location to receive pipette tips from the dispense, prior to activation of the pipette tip dispensing mechanism. In some examples, the pipette tip rack can be seated on the holding platform using manual loading methods, and in certain examples, the pipette rack can be seated on the holding platform using automated loading methods, prior to dispensing pipette tips into the pipette tip rack.
Citation of the above patents, patent applications, publications and documents is not an admission that any of the foregoing is pertinent prior art, nor does it constitute any admission as to the contents or date of these publications or documents.
The subject-matter of the present invention is defined by the features of independent device claim 1 and independent method claim 12. Further preferred embodiments of the present invention are defined in the dependent claims.

Claims

A pipette tip (50) dispensing device, comprising:
a) a sleeve (61);

b) an activator plate (41) within the sleeve;

c) a distal barrier plate (25) within the sleeve (61) disposed opposite to and spaced away from the activator plate (41);

d) two or more threaded rods (30) in connection with the activator plate (41) and distal barrier plate (25);

e) a plurality of nested pipette tip units between the activator (41) and barrier plates (25), wherein:
(i) each unit is aligned with a channel (18) in the distal barrier plate (25), and

(ii) the distal barrier plate (25) comprises:
a plurality of channels (18), wherein each channel (18) has a diameter larger than the widest portion of a pipette tip (50);

a substantially flat top surface (23),

a substantially flat bottom surface (29) that comprises a plurality of tails (21) around some or all of the channels (18), wherein the tails (21) extend in a perpendicular orientation from the flat bottom surface (29);

wherein the tails (21) around each channel (18) are able to contact and deflect outwards against the proximal portion of a pipette tip (50) when a pipette tip is dispensed and passes by the tails (21), thereby imparting a frictional force on the pipette tip (50) when it is dispensed;

the plurality of channels (18) comprises two or more different subsets of channels and each subset of channels has a different frictional profile from another subset and is configured to eject pipette tips at different times; and

f) an actuating motor (72) in effective connection with the threaded rods (30), able to rotate the threaded rods (30) whereby the activator plate (41) and the distal barrier plate (25) are translated towards one another thereby applying an axial force on the array of pipette tips (50) to eject the array of pipette tips into respective receptacles in a loading block.
The pipette tip dispensing device of claim 1, wherein each channel (18) comprises 3 or more tails (21).
The pipette tip dispensing device of claim 1 or 2, wherein channels (18) of the barrier plate (25) comprise tails (21) of different lengths.
The pipette tip dispensing device of any one of claims 1 to 3, wherein the tails (21) are at an internal angle of 89° to 80° from the bottom surface of the distal barrier plate (25).
The pipette tip dispensing device of any one of claims 1 to 4, wherein the tails (21) are between 0.01µm-2.0mm in length.
The pipette tip dispensing device of claim 1, wherein the tails (21) around a channel are not in the channel.
The pipette tip dispensing device of claim 1, wherein the activator plate (41), distal barrier plate (25), threaded rods (30), and plurality of pipette tips (50) are located in the sleeve.
The pipette tip dispensing device of any one of claims 1 to 3, which is in association with a housing unit (60).
The pipette tip dispensing device of claim 1, wherein the distal barrier plate (25) comprise one or more fasteners along one or more of its vertical lateral sides configured to connect the plate (25) with the sleeve (61).
The pipette tip dispensing device of claim 1, wherein the motor (72) stops rotating the rods (30) by a pressure sensor gauge.
The pipette tip dispensing device of claim 1, wherein the activator plate (41) comprises threaded members, and each threaded member engages a threaded portion of each rod, whereby the activator plate (41) is able to translate towards the distal barrier plate (25) by rotation of the rods (30).
A method of dispensing an array of multiple pipette tips (50) into a loading block using the pipette tip dispensing device of claim 1 that includes a top activator plate (41), a bottom distal barrier plate (25), and an actuating a motor (72), comprising:
- providing a dispensing device that includes a nested array of regularly spaced pipette tips between the top activator plate and the bottom distal barrier plate; and

- actuating a motor of the dispensing device in effective connection with the threaded rods that move the threaded rods,
wherein:
(i) the axial force dispenses the array of pipette tips (50) through the channels (18) and past the tails (21), and

(ii) the tails (21) contact and deflect outwards against the pipette tips (50) and impart a frictional force on the pipette tips (50), whereby the array of pipette tips (50) is ejected into respective receptacles in the loading block.
The method of claim 12, wherein each channel of the barrier plate (25) comprise tails (21) of different lengths.
The method of claim 12 or 13, wherein the tails (21) are at an internal angle of 89° to 80° from the bottom surface of the distal barrier plate.
The method of any one of claims 12 to 14, wherein the tails (21) are between 0.01µm-2.0mm in length.
The method of claim 12, wherein the tails (21) around a channel (18) are not in the channel.