This application claims benefit, under 35 U.S.C. §119(e), of
This invention relates generally to multichannel air displacement pipettors employing disposable pipette tips, and is concerned in the particular with the provision of an adapter for providing an interface between the pipette tips and the pipettor.
Air displacement pipettors are typically used to transfer liquids between vessels as part of an assay. Common vessels are microtiter plates, test tubes and reservoirs.
Air displacement pipettors frequently make use of a piston and cylinder arrangement, which is used to create positive and negative pressure in an attached pipette tip. When the open end of the tip is placed into a liquid, the change in pressure causes the liquid to be aspirated into, or dispensed from, the interior of the pipette tip.
Cross contamination can occur when a first liquid sample aspirated into and then dispensed from a pipette tip leaves a residual amount of sample in the tip. A subsequently aspirated sample mixes with the residual first sample and is thus contaminated. This type of cross contamination can also occur through residual sample on the exterior of the pipette tip.
In order to avoid cross contamination errors, most air displacement pipettors are designed to make use of pipette tips that are relatively low cost and therefore, in critical applications, disposable after each aspirate-dispense cycle. The design of the pipette tip and its associated mounting shaft is well established. The pipette tips are commonly injection molded in a chemically resistant material such as polypropylene. They are conical in shape. The pipettor's mounting shaft is typically cylindrical with a slight taper that closely matches the conical angle and diameter of the tip. The tip is installed by applying an axial force to the mounting shaft that forces the tapered portion of the shaft into the tip. Flexibility of the tip material allows it to stretch radially and provide both an air-tight seal and mechanical stability of the tip to the pipetting device. The typical axial force required to securely mount a single tip onto a tip mounting shaft is between 1.5 and 4 lbs. To remove the pipette tip from the pipettor, a stripper mechanism is typically used to push the tip from the mounting shaft. Tip ejection forces are in the same range as the mounting forces.
In order to increase productivity, air displacement pipettors with 96, 384 and higher numbers of channels have been developed. These multichannel pipettors must generate relatively high force in the direction of the axis of the tips in order to simultaneously install the array of tips. For example, a 96 channel pipettor using tips with average insertion forces will require over 200lbs of axial force to successfully install all of the tips. These forces are typically generated through the use of mechanical force multipliers (levers) or powered electromechanical systems. The structure of the pipettor has to be robust in order to support the high tip loading force without distortion. This leads to heavier designs that require more power to operate effectively. In addition to these design issues, the safety of the user is also a significant concern when such high forces are present.
Pipette tips are frequently packaged in a rack that positions them with their top surfaces in a common plane with centerline spacing that matches that of the instrument. For example, a 96 channel pipette tip rack holds an 8 x 12 array of tips with 9mm between centers. The high forces required to attach all of the tips in the rack often causes the tip rack to bow in the center of the array, resulting in poor sealing and attachment of centrally located tips. To counter this, tip manufacturers reinforce the tip racks intended for use with multichannel pipettors. This, in turn, increases the cost of the racks and therefore the cost to operate the instrument.
Other multichannel pipettor manufacturers have developed proprietary pipette tips that are designed to lower the insertion and ejection forces. These tips are often more complex and expensive to produce and usually lock the customer into purchasing the manufacturer's specially designed tip for the life of the instrument.
The present invention is directed to an assembly comprising an adapter and an array of pipette tips, as defined by independent claim 1. Broadly stated, embodiments of the present invention address the drawbacks of the prior art by providing a pipette tip adapter whose purpose is to adapt commonly available low cost pipette tips to a multichannel air displacement pipettor in a way that reduces the mounting and ejection forces described above. Any universal pipette tip available in the marketplace can be assembled to the pipette tip adapter. End users of the related multichannel air displacement pipettor designed to accept the pipette tip adapter would install the assembly onto the pipettor. The pipette tip adapter reduces the forces required to mount and seal the tips to less than 10 lbs. Ejection forces are equally reduced.
In exemplary embodiments, the pipette tip adapter as part of the assembly of the present invention comprises a planar base with an array of openings extending between its top and bottom surfaces. Sealing tubes project upwardly from top surface of the base, and tip mounting tubes project downwardly from the bottom surface of the base. Pairs of sealing tubes and tip mounting tubes re arranged coaxially and in communication with respective ones of the openings in the base. The tip mounting tubes are externally dimensioned and configured for insertion into the conical upper ends of pipette tips, and the sealing tubes are externally configured and dimensioned for insertion into ports of a multichannel air displacement pipettor. The pipette tips comprise through bores with conical upper ends, and each of the tip mounting tubes of the adapter is engaged with one of the pipette tips.
The base may preferably be strengthened by networks of reinforcing ribs on its top and/or bottom surfaces.
These and other objects, features and advantages of the present invention will become more apparent from a reading of the following detailed description in conjunction with the accompanying drawings.
With reference initially to
Sealing tubes indicated typically at 20 project upwardly from the top surface 16, and tip mounting tubes indicated typically at 22 project downwardly from the bottom surface 18. Pairs of sealing tubes 20 and mounting tubes 22 are arranges coaxially and in communication with respective ones of the openings 14 in the base 12.
The sealing tubes 20 and tip mounting tubes 22 may be arranged in an array of rows and columns. The spacing of the rows and columns matches the commonly available tip spacing of both multichannel pipettors and associated racks found in the marketplace. These in turn match the well positions of commonly available microtiter plates. Nine and four and a half millimeters are two common spacing distances. By way of example, a 96 channel pipettor has twelve rows and eight columns of tips on nine millimeter spacing, while a 384 channel pipettor has a twenty four by sixteen matrix on a four and a half millimeter spacing. This invention can also be used in a one-dimensional array format. For example, a single row of twelve on a nine mm spacing.
As can be best seen in
Base 12 may be advantageously strengthened by a network of upper reinforcing ribs 28 on its top surface 16, and/or a similar network of lower reinforcing ribs 30 on its bottom surface 18. The sealing tubes 20 may be located where the upper reinforcing ribs 28 converge, whereas the tip mounting tubes 22 may be located in areas of the bottom surface bracketed by the lower reinforcing ribs 30.
The sealing tubes 20 have cylindrical walls with chamfered upper ends 20a. The tip mounting tubes 22 project downwardly below the lower reinforcing ribs 30, and the sealing tubes 20 project upwardly above the upper reinforcing ribs 28.
With reference to
As shown in
The chamfered upper ends 20a of the sealing tubes serve to lower the insertion forces of the sealing tubes into the ports of the pipettor cylinders 38 while also reducing wear and tear of the O-rings 40 or other like compliant sealing surfaces.
Pistons indicated typically at 42 are arranged for reciprocal movement in the cylinders 38. In
The tip adapter 10 is preferably injection molded using standard tooling methods and common processing techniques. Materials can include any rigid injection moldable polymer, with polypropylene being preferred. Additionally, a polymer with an internal lubricant that blooms to the surface of the part is preferable because the presence of the lubricant on the surface will reduce insertion forces and wear and tear on the seals.
The exemplary embodiment herein described is preferably disposable. A non-disposable version is also possible, its design being essentially identical but produced from a material that is more robust and autoclavable. In such a design, the tips are installed to the adapter by the user with a dedicated fixture.
To reduce the capital cost required to build injection molds, multiple tip size geometries can be accommodated in a single adapter by arranging the tip mounting tubes in a tiered geometry, where the larger tips fit on one tier and the smaller tips on a second tier.
Often, disposable pipette tips incorporate filters. The purpose of the filter is to avoid aerosol contamination of the pipette mechanism by the liquid being pipetted. The pipette tip adapter of the present invention may be configured to accept such filters, thereby eliminating the need to use expensive tips with filters pre-installed in them.
In light of the above, it will now be appreciated by those skilled in the art that the adapter of the present invention offers significant and heretofore unavailable advantages. The chamfered upper ends 20a of the sealing tubes 20 interact with the O-rings or equivalent compliant sealing materials to beneficially reduce the forces required to connect the pipette tips to the pipettor. For example, in the case of a 96 channel pipettor, the adapter's sealing tubes 20 can be successfully inserted into the cylinder ports of the pipettor with a minimal coupling force on the order of 10lbs. This can be accomplished safely without exposing an operator to potential injury.
The adapter base 12, preferably when strengthened by the upper and/or lower reinforcing ribs 28, 30, provides a rigid platform supporting the tip mounting tubes 22 and sealing tubes 20. Thus, the adapter can be pressed onto an array of pipette tubes without undergoing deflection that might otherwise compromise uniform and reliable sealed insertion of the tip mounting tubes 22. This same rigidity, when coupled with the minimal coupling forces referenced above, results in a more uniform and reliable insertion of the sealing tubes into the pipettor cylinder ports.
Higher forces may be required to install the pipette tips on the adapter, but this can be accomplished in a factory setting prior to supplying the loaded adapter to a user, or by the user with a specially designed press incorporating appropriate safety features.
This list of references cited by the applicant is for the reader's convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.