WO2000051737A1

WO2000051737A1 - Self-washable nozzle tip

Info

Publication number: WO2000051737A1
Application number: PCT/US2000/005806
Authority: WO
Inventors: Teva C. Rothwell; Masato Mitsuhashi
Original assignee: Hitachi Chemical Co., Ltd.; Hitachi Chemical Research Center, Inc.
Priority date: 1999-03-05
Filing date: 2000-03-03
Publication date: 2000-09-08

Abstract

A self-washable nozzle tip has a dual nozzle structure. An inner nozzle (1) is adapted to be connected to an aspiration instrument such as a vacuum pump, and an outer nozzle (2) is adapted to be connected to a dispensing instrument such as a repetitive pipette (5). The inner nozzle (1) protrudes from the edge of the outer nozzle (2) so that the inner nozzle (1) can access a solution in a well to remove it while the outer nozzle (2) is kept away from the solution. A washing solution is then provided between the inner nozzle (1) and the outer nozzle (2) so that the outer surface of the inner nozzle (1) can be washed with the washing solution when the well is washed with washing solution.

Description

SELF-WASHABLE NOZZLE TIP

Background of the Invention Field of the Invention

The present invention relates to an aspirator nozzle or tip for a repetitive pipetter or dispenser usable in bioscience and clinical diagnostics. Description of the Related Art

Multi-well microplates are widely used in bioscience and clinical diagnostics. Many accessories are also available, such as multi-well washer/dispensers, multi channel pipet, robotics, etc., to make entire assays simple and easy. However, because an individual assay solution is packed in a small space, well-to-well cross-over of solutions can be problematic. Avoiding such cross-over is very important especially when highly sensitive assays, such as chemiluminescence, gene amplification, etc., are conducted. In order to completely avoid cross-over of solutions between wells, researchers must change pipet tips frequently. For example, in the case of washing a 96-weli plate twice, 480 tips may be required; that is, 96 tips for a first aspiration, 96 tips for dispensing a first washing solution, 96 tips for a second aspiration, 96 tips for dispensing a second washing solution, and 96 tips for a third aspiration. Changing pipet tips so many times is not practical, and thus researchers usually use the same pipet tips to access different wells.

Summary of the Invention The present invention provides a self-washable nozzle tip which has a dual nozzle structure. An inner nozzle is adapted to be connected to an aspiration instrument such as a vacuum pump, and an outer nozzle is adapted to be connected to a dispensing instrument such as a pipet, repeating pipetter, repetitive pipetter, and dispenser. These dispensing instruments may hereinafter be referred to as "repetitive pipetter" which sucks a given amount of solution and discharges a portion of the solution at a time. The inner nozzle protrudes from the edge of the outer nozzle so that the inner nozzle can access a solution in a well to remove it while the outer nozzle is kept away from the solution. A washing solution is then provided between the inner nozzle and the outer nozzle so that the outer surface of the inner nozzle can be washed with the washing solution, when the well is washed with the washing solution. This self- washable nozzle tip can be used as follows: (i) placing the point of the inner nozzle in a solution contained in a well to remove the solution through the inner nozzle by aspiration force; (n) after removal of the solution, supplying a washing solution between the inner nozzle and the outer nozzle to provide the washing solution into the well to wash the well while washing the inner nozzle with the washing solution passing between the inner nozzle and the outer nozzle; (in) placing the point of the inner nozzle in the washing solution contained in the well to remove the washing solution through the inner nozzle by aspiration force; and (iv) repeating (n) and (m) as required. In the above, the outer surface of the inner nozzle is washed by a washing solution in each washing step, and thus residual materials remaining on the outer surface of the inner nozzle can easily be removed. Therefore, unlike conventional pipet tips, there is no need to change the inner nozzle during multiple washing procedures, and the washing procedures can continuously and efficiently be conducted. Further, the outer nozzle can be connected universally to various types of dispensing devices. No special equipment is required.

In another aspect, the inner nozzle is not a hollow tube but is a pin, probe, or needle (hereinafter referred to as "pin"). The other structure can be the same as above. This type of self-washable nozzle tip can be used as a self- washable picker. For example, the pin is useful as a bacterial colony picker. The pin can be washed after each use by passing a washing solution between the pin and the outer nozzle.

Accordingly, the self-washable nozzle tip of the present invention can increase the efficiency of laboratory performance and minimize plastic waste.

Brief Description of the Drawings Figure 1 is a perspective and partial cross sectional view showing an embodiment of the self-washable nozzle tip of the present invention.

Figures 2a, 2b, and 2c show an embodiment of the self-washable nozzle tip of the present invention. In Figure 2a, the inner nozzle is detached from the outer nozzle. In Figure 2b, the inner nozzle is attached in place, and the outer nozzle is to be connected to a repetitive pipetter. Figure 2c shows an enlarged view of the point of the self- washable nozzle tip.

Figures 3a, 3b, and 3c show another embodiment of the self-washable nozzle tip of the present invention. In Figure 3a, the inner nozzle is detached from the outer nozzle. In Figure 3b, the inner nozzle is attached in place, and the outer nozzle is to be connected to a repetitive pipetter. Figure 3c shows an enlarged view of the point of the self- washable nozzle tip. Detailed Description of the Preferred Embodiment

In the present invention, a self-washable nozzle tip comprising: (a) an inner nozzle having a proximal end for connecting an aspiration instrument and a distal end for sucking a subject solution; (b) an outer nozzle having a proximal end for connecting a dispensing instrument and a distal end for discharging a solution from the dispensing instrument; and (c) a support structure for supporting the inner nozzle inside the outer nozzle at a position where the distal end of the inner nozzle protrudes from the distal end of the outer nozzle to a length effective to access the subject solution, wherein an outer surface of the inner nozzle is washable by the solution passing from the dispensing instrument passing between the inner nozzle and the outer nozzle.

The self-washable nozzle tip has a dual nozzle structure having an inner nozzle and an outer nozzle. The inner nozzle protrudes from the edge of the outer nozzle to the extent that the inner nozzle can access a material present in a container such as a well whereas, preferably, the outer nozzle can be kept away from the material (as long as the inner nozzle can access the material, the outer nozzle may touch the material). However, the inner nozzle does not protrude from the edge of the outer nozzle to the extent that the point of the inner nozzle cannot be washed by passing a washing solution between the outer nozzle and the inner nozzle. The degree of the protrusion of the inner nozzle may vary mainly depending on the designed aoplication of the nozzle. If the nozzle tip is used for washing wells of a 96 well plate, for example, the inner nozzle and the outer nozzle have dimensions such that the point of the inner nozzle accesses a material in each well and removes it by suction, and the edge of the outer nozzle does not touch the material but supplies a washing solution therethrough. In the above, the size of the nozzle tip depends on the size of each well.

In an embodiment, the inner nozzle has an outer diameter of 0.5 to 1.0 mm at the point of the inner nozzle, and the outer nozzle has an outer diameter of 2 to 3 mm at the edge of the outer nozzle. In another embodiment, the inner nozzle has an outer diameter of 1 to 2 mm at the point of the inner nozzle, and the outer nozzle has an outer diameter of 3 to 4 mm at the edge of the outer nozzle. The protrusion of the point of the inner nozzle is in the range of 4 to 5 mm in an embodiment, 3 to 4 in another embodiment, as measured from the edge of the outer nozzle. In the above, the inner and outer nozzles may have a cross-section which is circular, oval, triangular, or rectangular, etc. The inner nozzle can be either hollow or solid. If the nozzle tip is used for washing wells or other containers, the inner nozzle is hollow and is connected to a vacuum pump or other vacuum supply device, so that the inner nozzle can function to remove a material therethrough by aspiration action. If the nozzle tip is used for picking bacterial colonies, the inner nozzle need not have an opening and can be solid. The inner nozzle and outer nozzle may be made of a plastic, such as polypropylene, a metal such as stainless steel, or glass. A wall constituting the inner nozzle may be in the range of 0.1 to 0.3 mm (if it is hollow), and a wall constituting the outer nozzle may be in the range of 0.3 to 0.5 mm. An inner wall and/or outer wall of the inner nozzle or the outer nozzle can be treated to render it water-repellent or hydrophilic, or can be coated with any desired material.

In order to effectively wash the outer surface of the inner nozzle by passing a washing solution between the inner nozzle and the outer nozzle, in an embodiment, the inner nozzle is disposed substantially in a coaxial position, i.e., the inner nozzle is positioned on the axis of the outer nozzle, so that a washing solution can evenly pass between the inner nozzle and the outer nozzle, with respect to the circumference of the inner nozzle. In an embodiment, the average clearance between the outer surface of the inner nozzle and the inner surface of the outer nozzle is in the range of 0.5 to 1.0 mm, so that a washing solution can effectively pass through with washing force over the outer surface of the inner nozzle. To position the inner nozzle inside the outer nozzle, internal support ribs or guides can be formed inside the outer nozzle in such a way that the ribs or guides do not block a stream of liquid passing therethrough.

The inner nozzle can be either detachably or permanently attached to the outer nozzle, depending on the designed application. If the inner nozzle is detachable, it can be disposed of separately from the outer nozzle and replaced with another inner nozzle of the same type or a different type, or it can be washed after detaching it from the outer nozzle.

In an embodiment, the inner nozzle is connectable to a vacuum means, and the inner nozzle has an attachment or adapter to be connected to such a vacuum means.

In an embodiment, the outer nozzle can be detachably connected to a repetitive pipetter or other dispensing means. In another embodiment, however, the outer nozzle can be permanently connected to a repetitive pipetter or other dispensing means, or can be integrated therewith. If the self-washable nozzle tip is detachable, replaceable, or disposable, the outer nozzle may be a length of 20 to 40 mm.

In an embodiment, the outer nozzle has a Y shape; that is, the outer nozzle has three ports. The first port is for accessing a material to be removed, the second port is for connecting a repetitive pipetter or other dispensing means, and the third port is for inserting the inner nozzle. In the above, the inner nozzle is supported in place with a stopper which is provided around the inner nozzle and which is fitted to the third port. In an embodiment, the first port and the second port are formed to have a common axis, and the third port is formed on the side between the first port and the second port at an angle with respect to the common axis. In another embodiment, the first port and the third port are formed to have a common axis, and the second port is formed on the side between the first port and the third port at an angle with respect to the common axis.

In an embodiment, the outer nozzle has more than three ports for using multiple washing solutions. In an embodiment, the inner nozzle may be Y-shaped, each connected to a vacuum means. The solution passing between the inner nozzle and the outer nozzle is not limited to a washing solution, but includes various types of solution such as water, alcohol, buffer, organic solvent, acid solution, base solution, etc. Further, a plurality of self washable nozzle tips can be connected so that washing can be conducted for multiple wells simultaneously.

The invention will be explained in more detail with reference to the drawings which show embodiments of the present invention, although the invention should not be limited to the embodiments.

Figure 1 is a perspective and partial cross sectional view showing an embodiment of the self-washable nozzle tip of the present invention. An inner nozzle 1 is inserted inside an outer nozzle 2. The inner nozzle 1 is adapted to be connected to a vacuum means, and a point 3 of the inner nozzle 1 protrudes from the edge of the outer nozzle 2 so that only the point 3 of the inner nozzle 1 touches a material to be removed while the edge of the outer nozzle 2 is kept away from the material. The inner nozzle 1 is supported by internal support ribs 3. The internal support ribs 3 structurally support the inner nozzle 1 while providing a washing solution between the inner nozzle 1 and the outer nozzle 2. The washing solution can pass through the internal support ribs 3. An upper end 5 of the outer nozzle 2 is adapted to be connected to a dispensing means. To ease attaching and detaching the outer nozzle 2, finger grips 6 are formed on an outer surface of the outer nozzle 2. The inner nozzle 1 can be detachable or can be fixed to the outer nozzle 2.

Figures 2a, 2b, and 2c show an embodiment of the self-washable nozzle tip of the present invention. In Figure 2a, an inner nozzle 21 is detached from an outer nozzle 22. The outer nozzle 22 comprises a side branch 23 having a vacuum port 28 for receiving the inner nozzle 21. Through the vacuum port 28, the inner nozzle 21 is inserted and protrudes from a working port 27 of the outer nozzle 22. In this embodiment, the working port 27 and the pipetter port 26 are positioned to have a common axis, the In Figure 2b, the inner nozzle 21 is attached in place, and a pipetter port 26 of the outer nozzle 22 is to be connected to a repetitive pipetter 25. The inner nozzle 21 comprises a stopper 24 which is fitted to the vacuum port 28 of the side branch 23 to close the vacuum port 28 and support the inner nozzle 21. The other end of the inner nozzle 21 is adapted to be connected to a vacuum means. Additionally, internal support ribs or guides are formed inside the outer nozzle 22 (not shown) to fix the inner nozzle 21 in place. Figure 2c shows an enlarged view of the working port 27 of the self washable nozzle tip. The surface of the inner nozzle 21 is washed with the washing solution provided from the repetitive pipetter 25. Figures 3a, 3b, and 3c show another embodiment of the self-washable nozzle tip of the present invention. In

Figure 3a, An inner nozzle 31 is detached from an outer nozzle 32. In this embodiment, a vacuum port 38 and a working port 37 are positioned to have a common axis, and a side branch 33 of the outer nozzle 32 has a pipetter port 36. In Figure 3b, the inner nozzle 31 is attached in place, and the side branch 33 is to be connected to a repetitive pipetter 35. As in Figure 2a or 2b, the inner nozzle 31 has a stopper 34 for closing the vacuum port 38 and supporting the inner nozzle 31 in place. Figure 3c shows an enlarged view of the working port 37 of the self-washable nozzle tip. In order to position the inner nozzle 31 in the center of the interior of the outer nozzle 32 (i.e., the inner nozzle 31 and the outer nozzle 32 are coaxial), internal support ribs 36 are provided at the working port 37. A washing solution passes between the inner nozzle 31 and the outer nozzle 32, thereby washing the surface of the inner nozzle 31.

In the above, if the inner nozzle is not hollow or is not connected to a vacuum means, the nozzle tip can be used as a picker for bacterial colonies for plasmid preparations.

As explained earlier, in association with an appropriate dispensing instrument and an appropriate aspiration instrument, the self-washable nozzle tip can be used as follows, for example: (i) placing the point of the inner nozzle in a solution contained in a well to remove the solution through the inner nozzle by aspiration force; (n) after removal of the solution, supplying a washing solution between the inner nozzle and the outer nozzle to provide the washing solution into the well to wash the well while washing the inner nozzie with the washing solution passing between the inner nozzle and the outer nozzle; (in) placing the point of the inner nozzle in the washing solution contained in the well to remove the washing solution through the inner nozzle by aspiration force; and (iv) repeating (n) and (in) as required. The self-washable nozzle tip can allow researchers to efficiently perform various types of bio assays, diagnostics, and other laboratory tests. In the above, when the self-washable nozzle tip comprises an inner pin instead of the inner nozzle, in association with an appropriate dispensing instrument, the tip can be used as a sampling nozzle, probe, or picker as follows, for example: (i) placing the point of the inner pin in a material such as bacterial colonies to collect a sample of the material; (n) after collection of the sample, supplying a washing solution between the inner pin and the outer nozzle to wash off the sample from the pin with the washing solution to a container; and (in) further washing the inner pin with the washing solution passing between the inner pin and the outer nozzie until washing is complete. The self- washable nozzle tip can allow researchers to efficiently prepare various types of chemical or biological materials including plasmid preparations for DNA researches, for example.

It will be understood by those of skill in the art that numerous and various modifications can be made without departing from the spirit of the present invention Therefore, it should be clearly understood that the forms of the present invention are illustrative only and are not intended to limit the scope of the present invention.

Claims

WHAT IS CLAIMED IS.

1. A self-washable nozzle tip comprising: an inner nozzle having a proximal end for connecting an aspiration instrument and a distal end for sucking a subject solution; an outer nozzle having a proximal end for connecting a dispensing instrument and a distal end for discharging a solution from the dispensing instrument; and a support structure for supporting the inner nozzle inside the outer nozzle at a position where the distal end of the inner nozzle protrudes from the distal end of the outer nozzle to a length effective to access the subject solution, wherein an outer surface of the inner nozzle is washable by a solution passing from the dispensing instrument and passing between the inner nozzle and the outer nozzle.

2. The self-washable nozzle tip according to Claim 1 , wherein the distal end of the inner nozzle protrudes to a length effective to keep the distal end of the outer nozzle away from the subject solution when the distal end of the inner nozzle accesses the subject solution.

3. The self-washable nozzie tip according to Claim 1 , wherein the inner nozzle is detachably supported by the supporting structure.

4. The self-washable nozzle tip according to Claim 1 , wherein the outer nozzle has three ports, wherein port #1 receives the inner nozzle inserted therethrough, port #2 is adapted to be connected to the dispensing instrument, and port #3 is a port from which the distal end of the inner nozzle protrudes.

5. The self-washable nozzle tip according to Claim 4, wherein port #1 and port #3 are positioned to have a common axis, and port #2 is positioned between port #1 and port #3.

6. The self-washable nozzle tip according to Claim 4, wherein port #2 and port #3 are positioned to have a common axis, and port #1 is positioned between port #2 and port #3.

7. The self-washable nozzle tip according to Claim 1 , wherein the inner nozzle and the outer nozzle are made of a plastic or metal.

8. The self-washable nozzle tip according to Claim 1, which is connected to a dispensing instrument selected from the group consisting of a pipet, repeating pipetter, repetitive pipetter, and dispenser.

9. A self-washable nozzle tip comprising: an inner pin having a distal end for contacting a subject medium; an outer nozzle having a proximal end for connecting a dispensing instrument and a distal end for discharging a solution from the dispensing instrument; and a support structure for supporting the inner pin inside the outer nozzle at a position where the distal end of the inner pin protrudes from the distal end of the outer nozzle to a length effective to access the subject medium, wherein an outer surface of the inner pin is washable by a solution passing from the dispensing instrument and passing between the inner pin and the outer nozzle.

10. The self-washable nozzle tip according to Claim 9, wherein the distal end of the inner pin protrudes to a length effective to keep the distal end of the outer nozzle away from the subject medium when the distal end of the inner pin accesses the subject medium.

11. The self washable nozzie tip according to Claim 9, wherein the inner pin is detachably supported by the supporting structure.

12. The self-washable nozzle tip according to Claim 9, which is connected to a dispensing instrument selected from the group consisting of a pipet, repeating pipetter, repetitive pipetter, an dispenser.

13. A repetitive pipetter comprising the self -washable nozzle tip of Claim 1.

14. A repetitive pipetter comprising the self-washable nozzle tip of Claim 9.

15. A method of washing a well accommodating a biological material, by using the self-washable nozzle tip of Claim 1 , comprising the steps of:

(i) placing the distal end of the inner nozzle in the biological material contained in the well to remove the material through the inner nozzle by aspiration force;

(n) after removal of the material, supplying a washing solution between the inner nozzle and the outer nozzle to provide the washing solution into the well to wash the well while washing the inner nozzle with the washing solution passing between the inner nozzie and the outer nozzle;

(in) placing the distal end of the inner nozzle in the washing solution contained in the well to remove the washing solution through the inner nozzle by aspiration force; and (iv) repeating (n) and (in) as required.

16. A method of preparing a chemical or biological material by using the self-washable nozzle tip of

Claim 9, comprising the steps of:

(i) placing the point of the inner pin in a material such as bacterial colonies to collect a sample of the material;

(n) after collection of the sample, supplying a washing solution between the inner pin and the outer nozzle to wash off the sample from the pin with the washing solution to a container; and

(in) further washing the inner pin with the washing solution passing between the inner pin and the outer nozzle until washing is complete.