WO2005011868A1

WO2005011868A1 - Pipette tip assembly for nano-liter aspiration and dispensing

Info

Publication number: WO2005011868A1
Application number: PCT/US2004/023769
Authority: WO
Inventors: Gregory Mathus; Marc Hamel
Original assignee: Matrix Technologies Corporation
Priority date: 2003-07-30
Filing date: 2004-07-23
Publication date: 2005-02-10
Also published as: EP1656204A1

Abstract

A pipette tip assembly including a pipette tip having an upper opening and a smaller lower opening and a plug received in the pipette tip. A lower end of the plug is spaced from the lower opening to define a chamber into which liquid is aspirated and from which liquid is dispensed via the lower opening. The interior surface of the pipette tip and the exterior surface of the plug are configured and dimensioned to coact in defining a vent passageway leading from the chamber to the upper opening.

Description

PIPETTE TIP ASSEMBLY FOR NA O-LITER ASPIRATION AND DISPENSING

CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority from provisional p atent application Serial No. 60/491,120 filed July 30, 2003.

BACKGROUND OF THE INVENTION 1. Field of the Invention This invention relates generally to pipettors employing air displacement to aspirate and dispense precisely measured amounts of various liquids and is concerned in particular with the adaptation of the tips of such pipettes for low volume aspiration and dispensing in the nano-liter range.

2. Description of the Prior Art The medical and biotech industry is continuing along a path of requiring ever decreasing small volume liquid dispensing. Whereas 20 years ago 5 ul of liquid was the low end of need in accurately dispensing small volumes of liquid, and 10 years ago 2ul was the low end, currently there is an increasing demand for accurate dispensing of in the nano-liter range with high accuracy and repeatability. Current schemes of nano-liter dispensing use a number of different techniques to accomplish the task with the objective, not always achieved, of high accuracy. Positive displacement employing tips with pistons, ink jet technology, pressure and micro valves, piezo-electric activation are among only a few of the techniques that have been attempted. All of these have tended toward the complex, requiring special instruments for activation, and having relatively high costs. It is important to limit any excess air in the tip and associated piston/cylinder when performing low volume liquid dispensing if one wants to achieve high levels of accuracy and precision. Typically, low volume dispensing equipment locates the piston as close to the tip as possible, sometimes actually entering the tip to minimize the air volume in the tip. This is important because the air acts as a spring and this spring effect varies based on the weight of the liquid being aspirated and dispensed. An additional effect of this air spring is that the liquid can actually bounce up and down until the spring effect stabilizes. This spring effect has a negative impact both on aspirating and dispensing accuracy. An additional need for minimizing the air in the system is that when the temperature of the liquid is different from ambient, the air can either expand or contract as it heats or cools in the tip, thus affecting the amount of liquid aspirated or dispensed. Attempts have also been made at displacing air in pipette tips with filler plugs having vent passageways extending axially therethrough. However, in order for such plugs to be useful in the nano-liter ranges of aspiration and dispensing, the vent passageways have to have extremely small diameters on the order of .2 mm. This precludes molding the vent passageways into the plugs because in order to do so, the core pins of the molds would be too fragile and susceptible to bending. It would be necessary, therefore, to precisely drill the vent passageways, at a substantial and commercially prohibitive cost.

SUMMARY OF THE INVENTION In accordance with the present invention, the vent passageways are relocated to the interface between the exterior surface of the plug and the interior surface of the pipette tip. One or both of these surfaces are configured by molding to precisely define the vent passageways. This can be achieved in accordance with the best practices of molding and mold making, thereby making it possible to produce the plugs at a low cost.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 A is an exploded perspective view of a first embodiment of a pipette tip assembly in accordance with the present invention; Figure IB is a top plan view of the pipette tip assembly of Figure 1 in an assembled state; Figure 1C is a vertical sectional view taken along line 1C-1C of Figure IB; Figure ID is a perspective sectional view showing the components of Figure 1 A in an assembled state; Figure 2A is an exploded perspective view of a second embodiment of a pipette tip assemble in accordance with the present invention; Figure 2B is a top plan view of the pipette tip assembly of Figure 2A in an assembled state; Figure 2C is a vertical sectional view taken along line 2C-2C of Figure 2B; Figure 2D is a perspective sectional view of the pipette tip assembly shown in Figures 2A- 2C; Figure 3 is a vertical sectional view of the pipette tip assembly of Figures 1A and ID, showing the assembly mounted on the end of a pipettor; Figure 4A is an exploded perspective view of a third embodiment of a pipette tip assembly in accordance with the present invention; Figure 4B is a top plan view of the pipette tip assembly of Figure 4A in an assembled state; Figure 4C is a vertical sectional view taken along line 4C-4C of Figure 4B; Figure 4D is an enlarged partial view of the circled portion shown in Figure 4B; Figure 5A is a perspective view of another plug embodiment; Figure 5B is a perspective view of a pipette tip assembly incorporating the plug shown in Figure 5A; Figure 5C is a perspective broken away view of the pipette tip shown in Figure 5B; Figure 5D is a tip plan view of the pipette tip assembly shown in Figure 5B; Figure 5E is a sectional view taken along line 5E-5E of Figure 5D; Figures 6, 7 and 8A are perspective views of other plug embodiments; Figure 8B is a perspective view showing the plug of Figure 8 A assembled in a pipette tip; Figure 8C is a top plan view of the pipette tip assembly shown in Figure 8B; Figure 8D is a sectional view taken along line 8D-8D of Figure 8C; and Figure 8E is a perspective view broken away showing the interior of the pipette tip illustrated in Figure 8B-8D. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS As a preliminary matter, it is to be understood that the above-referenced drawings are not to scale, and have certain features and proportions that have been exaggerated in order to better illustrate concepts of the present invention. With reference initially to Figures 1 A- ID, a solid plug 10a has a tapered or frustum configuration with a microgroove 11a extending vertically along its exterior surface. Microgrove 12a is advantageously molded into the exterior surface of the plug 10a, with a depth typically ranging from about .2 to .8 mm, and with a maximum width ranging from about .2 to .8 mm. The plug 10a is configured and dimensioned for axial insertion into a pipette tip 14a having a smooth interior surface and tapering from an upper opening 12a to a smaller lower opening 13 a. When thus assembled, as shown in Figures IB- ID, the microgroove 11a coacts with the interior surface of the pipette tip to define a vent passageway 16a, with the bottom of the plug being spaced from the lower opening 13a to thereby define a chamber 18a into which liquid may be aspirated and from which liquid may be dispensed via opening 13 a. Vent passageway 16a extends from chamber 18a to the upper opening 12a. The cross sectional area of passageway 16a is not more than about 65 mm², and preferably ranges between about .04 to 025 mm². In figures 2A-2D, the plug 10b and the pipette tip 14b have stepped tapered configurations, with the latter being additionally provided with an enlarged mounting collar 20. The plug 10b is again externally grooved as at 1 lb to coact with the interior pipette surface in defining the vent passageway 16b. In Figure 3, the pipette tip assembly of Figures 1 A- ID is shown mounted on the end of a pipettor 22 having an air passage 24. The external plug groove 11a coacts with the interior tip surface to again provide a vent passage 16a communicating with the pipettor passage 24 via a space 26 between the top of the plug and the end of the pipettor. With reference to Figures 4A-4D, here the plug 10c has a flat external land lie configured and dimensioned to coact with the smooth interior surface the pipette tip 14c in defining the vent passageway 16c. In Figure 5A-5E, the plug lOd has a smooth exterior surface, and the pipette tip 14d is internally grooved as at 1 Id. The groove lid coacts with the smooth outer surface of the plug to define the vent passageway 16d. In Figure 6, the plug lOe has a molded faceted exterior surface, and in Figure 7, the exterior surface of the plug lOf is configured to provide circumferentially spaced vertically extending beads. In Figure 8A-8D, the plug lOg is again smooth surfaced, and the interior surface of the pipette tip 14g has molded radially inwardly projecting circumferentially spaced beads 1 lg. The spaces between the beads 1 lg and the smooth exterior surface of the plug lOg coact in defining multiple vent passageways 16g. It will be seen, therefore, that in each of the above described embodiments, which are to be considered as exemplary and not restrictive, the vent passageways are defined by grooves, ribs or the like molded into one of either the exterior plug surface or the interior surface of the pipette tip. Molding allows for such grooves or ribs to be miniaturized and precisely sized to achieve aspiration and dispensing in nano-liter ranges.

Claims

I claim: ⁶ 1. A pipette tip assembly comprising: a pipette tip having an upper opening and a smaller lower opening; and a plug received in said pipette tip, a lower end of said plug being spaced from said lower opening to define a chamber into which liquid is aspirated and from which liquid is dispensed via said lower opening, the interior surface of said pipette tip and the exterior surface of said plug being configured and dimensioned to coact in defining a vent passageway leading from said chamber to said upper opening.

2. The pipette tip assembly of claim 1 wherein said plug is in the form of a frustum seated in a tapered section of said pipette tip.

3. The pipette tip assembly of claims 1 or 2 wherein said vent passageway is partially defined by a groove in the exterior surface of said plug.

4. The pipette tip assembly of claims 1 or 2 wherein said vent passageway is partially defined by a groove in the interior surface of said pipette tip.

5. The pipette tip assembly of claim 2 wherein said vent passageway is partially defined by flat land in the exterior surface of said plug.

6. The pipette tip assembly of claim 1 wherein the cross sectional area of said vent passageway is not more than about .65 mm².

7. The pipette tip assembly of claim 6 wherein said cross sectional area is between about .04 and .25 mm².

8. The pipette tip assembly of claim 1 wherein a plurality of said vent passageways are provided.

9. The pipette tip assembly of claim 8 wherein said passageways are defined in part by ribs projecting outwardly from the exterior surface of said plug.

10. The pipette tip assembly of claim 8 wherein said passageways are defined in part by ribs projecting inwardly from the interior surface of said pipette tip.

11. A pipette tip assembly comprising: a pipette tip tapering from an upper opening to a smaller lower opening; and a frustum-shaped plug received in said pipette tip, a lower end of said plug being spaced from said lower opening to define a chamber into which liquid is aspirated and from which liquid is dispensed via said lower opening, said pipette tip and said plug having adjacent surfaces configured and dimensioned to coact in defining a vent passageway leading from said chamber to said upper opening.

12. The pipette tip assembly of claim 11 wherein said vent passageway is partially defined by a groove in one of said surfaces.

13. A pipette tip assembly comprising: a pipette tip having an upper opening and a smaller lower opening; and a plug received in said pipette tip, a lower end of said plug being spaced from said lower opening to define a chamber into which liquid is aspirated and from which liquid is dispensed via said lower opening, said pipette tip and said plug respectively having complimentary interior and exterior adjacent surfaces configured and dimensioned to coact in defining a vent passageway leading from said chamber to said upper opening.

14. The pipette tip assembly of claim 13 wherein said vent passageway is partially defined by a groove molded into one of said surfaces.