WO2003039751A1

WO2003039751A1 - Pipette or syringe

Info

Publication number: WO2003039751A1
Application number: PCT/FI2002/000872
Authority: WO
Inventors: Antti Manninen
Original assignee: Antti Manninen
Priority date: 2001-11-09
Filing date: 2002-11-07
Publication date: 2003-05-15
Also published as: FI20012167A; FI20012167A0

Abstract

A pipette or syringe for transferring small amounts of liquid, comprising a cylinder (1) and a piston (2). The cylinder (1) and possibly also the piston (2) are formed from silica capillary tubes of different sizes, which can be surfaced if desired. The piston (2) is formed from either a capillary tube, or from solid silica rod or fibre. Multi-channel pipettes can be easily formed from units according to the invention.

Description

Pipette or syringe

The present invention relates to a pipette or syringe and particularly to such a pipette that is especially suitable for so-called multiple tip dosing.

In biotechnology, and particularly in gene technology, the simultaneous dosing of extremely small amounts is important. This is to be able to create efficient processing for large number of samples and, on the other hand, because reagents are expensive. Significant savings in analysis costs can be obtained by reducing the number of samples.

At present, traditional glass syringes are used, with the aid of which a accuracy can be obtained even at the microlitre scale. The syringes are placed next to one another to form series of 8 - 12 syringes, or matrices of up to 96 syringes, making it possible to handle the 96-place well racks (in an 8 * 12 matrix form) used in biotechnology. The same pipette arrangement can also be used to dose samples in 384-place well racks (in a 16 * 24 matrix form). Of course, this means that dosing must be carried out four times, instead of once. Glass syringes not only take up space, they are also quite expensive. Various syringe solutions are described in the literature and patent applications have also been made for many solutions.

Multi-channel pipettes often have replaceable tips, which eliminates the need to wash the pipettes. Disposal tips can, however, become a significant cost factor. In addition, repeatability begins to suffer when using pipettes that dose very small amounts in microlitres and less.

A later development is the so-called pin technology in the case of the repeated dosing of small sample amounts, which demands a great many pipette tips, tightly packed together. In these solutions, a small pit is made axially in the bottom of a thin steel bar, into which the substance being dosed enters due to the force of surface tension, when contact is made with the surface of the liquid. In other models, instead of a pit the bar is split at the bottom for a small distance and the liquid to be transferred rises into the gap through the effect of capillary forces. In the case of both models, the liquid is transferred to the target location be lightly touching the surface. In so-called floating pin models, the pins more or less hang in mounting strips, thus gently controlling the surface contact with the target rack. The pins are cleaned by pushing them several times into various cleaning solutions.

It is essential for the good operation of the pins that their surface has been suitably treated for the solutions being transferred and that the surface tension fills the gap or pit correctly. The tip of the pin must also usually be dried before a new dosing.

The present invention is intended to provide a simple, adjustable, accurate, and economical solution for the construction of dense multiple-tip pipettes comprising up to hundreds of units.

This is achieved in the manner stated to be characteristic in the accompanying Claims.

In the following, the invention is described in greater detail with reference to the accompanying drawings, which show schematic diagrams of various embodiments of the pipette according to the invention.

Thus:

Figure 1 shows the unit construction of the pipette according to the invention;

Figure 2 shows an example of the attachment of one pipette unit to the holder structure;

Figure 3 shows in turn the use of the invention in a so-called multi-channel doser, seen from the side; Figure 4 shows the construction of Figure 3 seen from beneath the holder plate; and

Figures 5 - 8 show how the tip of a pipette according to the invention is placed in the bottom of a well rack.

The general construction of one pipette unit or syringe unit is, as such, conventionally known, as shown in Figure 1. In the pipette according to the invention, there are, in the conventional manner, two basic components, a cylindrical body component 1 , which in the following is often referred to as the cylinder component, and a cylindrical piston component 2 with a smaller diameter. Preferably both the inner surface of the body component and the outer surface of the piston component are treated with a protective substance, which supports the structure and prevents scratching. The reference number 3 refers to a plug or similar component, which closes at least the lower end of the cylindrical component 2.

According to the invention, silica capillary tubes are used as the components 1 and 2, this being, as such, a known material and is used in various chemical applications, for example, for the transportation of sample liquids and gases.

According to the present invention, particularly polyimide is used as the surfacing. The layer prevents the body and piston components from rubbing against each other, so that the piston component of the pipette moves smoothly and lightly. The piston component is closed using, for example, a suitable glue. However, it is often sufficient for the end of the capillary tube to be pushed into a suitable material, such as paraffin wax, to close it. If desired, it is also possible to use surfaced fibre drawn from a bar as the piston component. In that case, there is naturally no need to use any kind of plug or similar, as the piston component is solid.

A widely used silica capillary tube with an internal diameter of 0,32 mm is highly suitably as the raw material for the capillary tube, while a second widely used capillary tube, with an external diameter of 0,31 mm is suitable as the piston component. An air gap of 5 micrometres remains between them, and is, in itself, sufficiently small to make the piston tight, but in practice the solution fills the gap, thus further improving the tightness. By using such a pipette with a 155- mm long cylinder component, it is possible to dose 0 - 3-microlitre amounts of liquid. By using capillary pipettes of various diameters and lengths, it is possible to dose larger or smaller amounts.

Figure 2 shows the attachment of one unit pipette to the holder. The cylinder component 1 of the pipette is set through support plates 6. Between the support plates 6, there is a friction plate 7, which can be of silicon, rubber, or some other suitable material, or can also be a mechanically arranged clamp, which holds the body of the pipette in place during dosing, but which permits the pipette to slide in the hole when greater force is applied. The piston component 5 is pushed tightly into an attachment plate 5, which can be of silicon or some other suitable material. The attachment plate is further attached to a backing plate 4. The piston 2 moves, when the backing plate 4 is moved in relation to the plates 6.

Figure 3 shows the use of the pipettes in a multi-channel doser, seen from the side, while Figure 4 shows the solution of Figure 3 seen from beneath. This example has 8 * 12 pipettes, which is a very standard arrangement, but naturally the manner shown permits the number and arrangement of the pipettes to be freely varied to suit other configurations.

Figures 5 - 8 show the positioning of the tip of a pipette according to the invention on the bottom of a well in a well rack. This takes place as follows. The pipette 1 , 2 is moved to the location of the well 8. According to Figure 6, the piston is pressed downwards by moving the plate 4 enough to move the cylinder 1 of the pipette downwards sufficiently, but not, however, to the bottom of the well. Figure 7 shows how the piston 2 is next pulled up to give the cylinder 1 of the pipette sufficient space to travel upwards. Finally, the entire pipette arrangement is pushed down, so that the cylinder component of the pipette moves to the desired level.

In the case of multi-channel pipettes, the positioning takes place simultaneously according to Figures 5 - 8.

With the aid of pipettes/syringes according to the invention, it is possible to achieve numerous excellent properties, which have been difficult to achieve with the aid of the state of the art. Thus, the pipettes according to the invention are flexible, sturdy, inert, and both easy and cheap to manufacture.

The pipette according to the invention is flexible and its tip component always straightens itself, if it unintentionally strikes some external object. This is particularly important in the case of densely packed multi-channel pipettes, when the tip of the pipette should be aligned with the bottom of the sample well with an accuracy of fractions of a millimetre. Flexibility and re-straightening are also important because often when dosing the tip of the pipette is not pushed to the bottom of the vessel or liquid, but instead the drop is transferred to the desired location by carefully pressing the tip of the pipette against the wall of the vessel.

When dosing small amounts, it is important to control the vertical position of the tip. The tip of the capillary pipette according to the invention is easily positioned vertically, even in the case of multi-channel dosing units.

These superior properties are based on silica capillary tubes, which are in general use as gas-chromatography and electrophoresis columns. The highly developed capillary drawing and surfacing technology produces capillary tubes of very uniform quality. In chemical applications, the silica capillary tubes are often surfaced with an inert polyimide polymer that resists high temperatures, which reinforces the capillary tubes, for instance, by preventing scratching. It is, however, obvious that many other surfacing substances, that are as such known, can be used for surfacing silica and glass capillary tubes. The internal surface of the silica in the cylinder component of the capillary pipette can be treated chemically, thus making it reject or attract various solutions, which can be significant in terms of repeated pipetting and cleaning.

The advantages of the pipette according to the invention also include the ease of cleaning the capillary tube, which is due to the fact that the piston travels through the entire capillary tube. Thus solid residues remaining on the walls of the cylinder are detached from the pipette.

Several pipette units are placed in holders, which can be attached to dosing devices. Due to the simple attachment, it is possible to use multi-channel pipettes of different sizes in the same device. If the pipettes are damaged, the pipettes can be replaced at one time in the holder. After this, individual pipettes can be changed manually outside the device.

The various embodiments of the invention are not restricted to only the forms shown, instead variations are possible while remaining within the scope of the protection of the Claims.

Claims

1. A pipette or syringe for transferring small amounts of liquids, comprising a cylinder (1 ) and a piston (2), characterized in that the cylinder (1 ) and the piston (2) are formed from silica capillary tubes of different sizes.

2. A pipette or syringe according to Claim 1 , characterized in that the cylinder (1 ) and correspondingly the piston (2) are surfaced on their internal and corresponding external surfaces.

3. A pipette or syringe according to Claim 2, characterized in that the surfacing substance of the components (1 and/or 2) is polyimide polymer.

4. A pipette or syringe according to Claim 1 , characterized in that the piston (2) is formed from either a capillary tube or from solid silica rod or fibre.

5. A pipette or syringe according to Claim 1 , characterized in that at least one end of the capillary tube forming the piston (2) is closed.

6. A pipette or syringe according to Claim 1 , characterized in that the capillary tube forming the piston is connected at one end to a valve, pump, or other system.

7. A pipette or syringe according to Claim 1 , characterized in that a group of units formed of cylinders (1 ) and pistons (2) is attached to suitable holders (4 -

7) in a desired configuration, in order to form a series pipette or syringe.

8. A pipette or syringe according to Claim 7, characterized in that the cylinders (1) of the units are attached to a friction-inducing plate (7), which, if desired, is supported by a backing plate or plates (6) and that the piston components (2) are also attached to their own backing plate (4).

9. A pipette or syringe according to Claim 8, characterized in that the piston components (2) of the unit are attached to the backing plate (4) by using an attachment plate (5) in connection with it.

10. A pipette or syringe according to Claim 8 or 9, characterized in that the cylinder (1) can be moved longitudinally within the retaining hole in the plate (7).

11. A pipette or syringe according to any of the above Claims 7 - 10, characterized in that the positions of the plates (4 - 7) in relation to each other can be adjusted to position the pipette/pipettes in relation to each other and to use them in the application.