EP0264704A2 - Pipetting device provided with a conical adapter for a pipette tip, and pipette tip for such a device - Google Patents

Abstract

A pipette has a male cone on which a pointed nozzle can be pushed on with its female cone. This point includes a filter which rests with its lower face on three internal bosses. This filter can be made partly of inorganic material, topped by a layer of Kieselguhr or by a layer of polyester or acetate fibres. This filter is pref. coated with bacterial, fungicidal, or viricidal agents.

Description

The invention relates to a pipetting device with a plug-on cone for a pipette tip and a piston chamber connected to a passage of the plug-on cone for the reciprocation of a piston, with a pipette tip and with a filter.

Pipette aids are known in chemistry and bacteriology to prevent contact with the mouth when a liquid is drawn in. A special attachable stopper with continuous capillaries for cell separation of liquids is already known.

It is also known to use a pipette aid, in particular for blood sedimentation tubes, as in the upper end of a capil lare of the pipette inserted insert that inhibits the suction of the liquid up to a predetermined height and then the further suction and the return of the liquid column. For this purpose, cotton plugs have been used, which are inserted into the upper end of a pipette in a cumbersome manner. Due to the low dimensional stability, it is not possible to fix the length or height of the liquid column precisely. The removal from the stopper bed for glass pipettes is also complex.

To avoid these disadvantages, it is known from DE-PS 21 55 566 to use the capillary tube which fits into the capillary of the pipette. This capillary tube has an expanded head part at its upper end with a filter plug that has a high flow resistance for liquids, but is permeable to air. It consists of a felt, filter, fabric or foam material and is therefore easy to use and can be used with great accuracy.

From DE-GM 1 978 016 it is known to insert preformed filter plugs from a magazine into a mouthpiece formed on the pipette by means of a plunger.

Filters for use with plastic tips of micropipettes are known from US Pat. No. 4,059,020. The filters are made of porous plastic or metal and can be brought into contact with the tip when the liquid sample is taken up so that it is filtered at the same time. This is a pure one Liquid filter that is removed after sampling and before dispensing the filtered liquid. It is included that tips of different sizes and shapes are used. The filter device consists of a holder for a filter which can be plugged onto a pipette tip, the passage at the pluggable end being cylindrical or conical and thus being able to be used on various pipette tip shapes. The porous liquid filter is aligned with the passage in a filter space that is widened relative to the passage.

A pipetting device from US Pat. No. 4,461,328 has one or more pipette tubes to which a hydrophobic filter paper is attached. This restricts the upward movement of an aqueous liquid in each tube to provide a predetermined amount of liquid in each tube. In this way, a filter arrangement in the case of multiple pipettes can be used to control an exact amount of a liquid that is sucked in if only one piston arrangement is connected.

Hydrophobic filters provided in this connection, which allow air or other gases to pass freely, but require increased pressure for the introduction of an aqueous liquid into and through the filter, are also known in the filtering or in the passage of air from a liquid mass.

The hydrophobic filters can be made of paper or plastic and have pore-shaped passages that act as a capillary. Typical plastics consist of polytetrafluoroethylene, polyvinyl chloride and halogenated fluoroalkali. In the known embodiment, the primary aim is to limit the amount of liquid that can be drawn into pipette tubes, while at the same time allowing air or other gases to pass through to absorb or dispense liquid. In particular, the pipetting device consists of a trough with a plurality of pipette tubes, on which a filter sheet is arranged together.

In connection with the use of pipettes to be operated by suction, it is also known to provide an internally subdivided intermediate piece between the pipette and the mouthpiece with a filter membrane for protecting the person handling the pipette, the pores of which are sufficiently small to allow bacteria to pass through to prevent.

As a mouthguard for pipettes it is also known from US Pat. No. 3,995,496 to use a plastic tube with compressed fibers as a liquid barrier. Due to expansion upon contact with liquid, these fibers prevent their passage if pipetted liquid is accidentally sucked over the end of the pipette. The fibers are preferably made of cotton.

A pipette for treating plasma formed from centrifuged blood with a liquid filter is known from US Pat. No. 4,483,825, which only allows plasma and no blood cells to pass through.

Another pipette according to GB-PS 1 592 855, for example for blood, has a parallel drilled channel with a porous stopper as a liquid barrier to limit the sample volume and to keep the sample liquid in the channel by moistening it with liquid. The stopper is a dimensionally stable, open-pored body that tapers at least before being inserted into the channel to facilitate insertion. It is preferably made of sintered polyethylene and is held mechanically in the bore due to its taper. Problems that occur with cotton plugs are to be avoided.

The invention has for its object to improve a pipetting device of the type mentioned, also in connection with a pipette tip as a receptacle, in that the through-air is cleaned of aerosols, bacteria, fungi and fungal spores, with regard to the pipetting device in combination with the Pipette tip an easy-to-use use of the filter is provided in a particularly effective place.

This object is achieved in that the filter as an aerosol filter is detachably arranged in a region which comprises the lower end of the pipetting device with the plug-on cone and the upper end of the pipette tip below the plug-on cone. The invention is based on a composite unit which is known per se, but which has been modified particularly expediently in the special design of its elements to achieve the object. With regard to the elements modified to achieve the object, the invention also relates to a pipetting device and to a pipette tip per se and to an element which may be arranged in the unit.

The filter can be effective in two directions, so that both contamination of the interior of the pipette located above the filter level and back contamination from the upper interior of the pipette to the absorbed liquid is prevented.

Here, a filter can be expediently arranged with a homogeneous filter material. In another preferred embodiment, a filter is also provided from a plurality of layers, which are arranged one above the other in disks and have a progressive filter effect, in that the permeability changes from disk to disk, in particular decreases.

Such a filter has considerable advantages in use because the passages of liquid and air are opposed to various influences, also in accordance with the change in pressure.

From this point of view, according to an advantageous embodiment, disks of different densities are stacked on top of one another. In this case, or in another expedient embodiment, the disks have different heights. In this respect, the filter effect is influenced by the length of the passages in the latter embodiment.

The progressive filter effect is useful because a filter element is created with regard to substances to be filtered that enables a smooth passage with certain substances. For substances with different properties, their gradual filtering out is pre-selected see, depending on the content through the progressive filter effect, a vote on certain content is possible. A filter element with a progressive filter effect over the filter length is advantageous, in which individual filter parts or disks can be exchanged. In this way, a filter element can also be matched to different substances. The range between 0.2 and 0.45 µm is included as the effective pore size.

Using a filter with micropores in the direction of passage, this filter is also designed in a preferred embodiment as a section of inorganic material in connection with a filter disk made of sintered diatomaceous earth. This composition also opens up possibilities for adaptation.

In another advantageous embodiment, a filter is at least partially provided with labyrinth-like passages and baffles, and the other part is designed with a filter disk, in particular made of polyester or acetate fibers. This is particularly advantageous configurations, filter disks made of other materials also being possible. Coatings are particularly included in this context.

This includes an advantageous solution with a filter that has only such labyrinthine passages and baffles, the baffles expediently consisting of a material which reacts adhesively with the substances inherent in the continuous medium.

Basically, the filter arrangement or design has a coating in a particularly preferred embodiment filter material with special bactericidal, fungicidal or virucidal active ingredients as well as with generally disinfectant substances.

A hydrophobic coating, e.g. be provided in the form of a silanized surface of the filter material. This represents an inexpensive version of an aerosol filter because moisture that is carried along is rejected.

In this context, it is also included in a further advantageous embodiment that the filter material, if appropriate also baffle surfaces of the same, can be provided with an adhesive coating made of a reactive material which binds special portions of the continuous medium and then also separates out.

The filter elements described can be used in various ways as an embodiment of the pipetting device.

An advantageous embodiment consists in a conical plug-in filter element which can be placed with its further end on the plug-on cone and on the narrower end of which the pipette tip can be placed, a filter being arranged in this plug-in filter element. This considerably simplifies handling, two advantageous options being included in this advantageous case, namely firstly placing the plug-on filter element on the plug-on cone and thus connecting it to the pipetting device or secondly inserting it into the pipette tip in order to use an additional cone, but which has the filter to equip.

If the working conditions permit multiple use of the filter material, the described embodiment with the plug-in filter element represents a special one an inexpensive solution because the conventional pipette tip can be changed as often as required without using a filter. It is included here that the conical end parts of the plug-in filter element are made from a weakly elastic material, in particular from a plastic, in order to ensure a secure seal of the entire metering system in the receiving area.

The plug-in filter element can have a handle element in the form of a polygon on the outside in the middle, in particular the upper area, but at a distance from the outer end, on the one hand to facilitate handling, but on the other hand also as a support for packaging or storage.

In a further advantageous embodiment, the filter is arranged in the upper end of the push-on tip in the pipetting device, and this is in particular designed with a positioning aid that changes the cross section. This positioning aid is useful for the exact position of the filter material, since a minimum distance from the liquid surface must be maintained in order not to falsify the delivery volumes. Such a positioning aid changes the inner basic shape of the pipette tip.

From this point of view, the positioning aid is designed in an expedient manner in the form of inward projections. These projections serve as a support for a filter plug.

In another embodiment, the positioning aid can be designed as an inwardly directed ring flange. As a result, a filter plug is supported along the lower edge.

In a preferred embodiment, the filter in the form of a prepared stopper is glued into a plug-in filter element or a pipette tip.

The design of the positioning aid in the form of protrusions has the advantage that a seat adjustment is facilitated in that protrusions can penetrate into the filter plug if there is increased pressure either by suction or active pressure, which then also finds a firmer fit on the wall of the plug-on tip. In this case, the positioning aid and the filter are dimensioned in mutual adaptation so that the filter effect is not reduced even if the projections penetrate into the filter plug. This can be achieved in that the penetration brings about a compression of the filter material and thus an increase in the filter effect and, on the other hand, in that such a dimensioning is provided that even a certain deformation does not eliminate the required filter effect.

The projections preferably have a roof-shaped ridge on their upper side. A cutting-like design of the projections is included from the above points of view of a seat adjustment. This design leads to a particularly low deformation of the filter.

In this context, it is also included that the plug-in filter element, possibly in a different version also the pipette tip, has an elastic wall part that can expand when a filter plug element is introduced and thus ensures a firm fit due to the elastic expansion, the un tere, running edge of the expandable wall section also acts as an abutment in the manner of a positioning aid.

Another advantageous embodiment of the filter has a mushroom-like design with a stem that can be inserted into the passage of the plug-on cone. Such a filter is also easy to handle because the mushroom head of the filter can be handled as a handle part. The stem itself represents a special filter element which, according to the above statements, can be configured in particular from several layer-like sections with a progressive filter effect.

In one embodiment of the pipetting device, the plug-on cone can be designed to be openable and it has a cavity for receiving a filter, the parts of the plug-on cone being designed with releasable connecting means and having passages through them. As a result, the pipetting device itself is used as a filter carrier, and conventional pipette tips can be used on it. This solution can be used if long pipetting series without filter replacement are possible. For better control, the plug-on cone with the upper receiving part or filter material can expediently be made of transparent material. This allows special conclusions to be drawn about the condition of the treated materials. The solution in question with a filter inserted into the plug-on cone can also have connecting means, for example in the form of a screw connection in connection with an elastic ring seal, as a result of which quick and easy replacement is possible.

In this sense, the parts of the plug-on cone can also be connected by plug-in connection, optionally with a bayonet lock, and in particular the end part of the plug-on cone is provided with a conical sleeve that can be pushed onto the other part.

Execution of a push-on cone made of transparent material enables a check also in the sense of discoloration, as indicated below.

For all versions it is advantageously included that the filter with an indicator additive for liquid contact, e.g. in the form of cobalt compounds. This feature is particularly advantageous in connection with a filter consisting of several layers and a progressive filter effect, in order to bring about a color change in the event of a one-time liquid contamination or with multiple dosing, in particular with gradual entry of aerosols, i.e. if the dose is applied several times, introduce a slow color change in order to make the level of aerosol contamination recognizable. This results from the discoloration caused by the addition of indicators depending on layers, if a multi-layer version is provided.

Such coated filter materials require absolute dry storage. Dry packaging is therefore also included in connection with the other coatings mentioned, optionally in the form of a blister pack with entries for keeping the contents dry.

• Fig. 1 in schematischer Seitenansciht eine Pipettier­vorrichtung mit einer Aufsteckspitze, zum Teil im Schnitt;
• Fig. 2 eine Seitenansicht einer Aufsteckspitze im Schnitt unter Einbeziehung einer ganz besonde­ren Ausgestaltung einer solchen Pipettenspitze, jedoch mit einem eingebrachten Filterelement;
• Fig. 3 eine Draufsicht auf Fig. 2 im Schnitt längs der Linie III-III;
• Fig. 4 eine der Fig. 2 entsprechende Seitenansicht ei­ner Aufsteckspitze anderer Ausführung;
• Fig. 5 - Fig. 7 Seitenansicht schematischer Art, teilweise im Schnitt für verschiedene Ausgestaltungen ei­nes Filterelementes;
• Fig. 8 das untere Ende einer Pipettiervorrichtung mit einem Aufsteckkonus in besonderer Ausgestal­tung in schematischer Darstellung;
• Fig. 9 das untere Ende einer Pipettiervorrichtung mit einem einteiligen Aufsteckkonus üblicher Aus­führung in Verbindung mit einer Pipettenspitze unter Zwischenschaltung einer Filteranordnung in Seitenansicht und im Schnitt;
• Fig. 10 das schematisch dargestellte untere Ende einer üblichen Ausführung einer Pipettiervorrichtung mit einer besonderen Ausgesaltung einer Fil­terausführung.

The invention is explained below with reference to exemplary embodiments which are shown in the drawing. The drawing shows:

• Fig. 1 in schematic Seitenansciht a pipetting device with a push-on tip, partly in section;
• 2 shows a side view of a push-on tip in section, including a very special design of such a pipette tip, but with an inserted filter element;
• Fig. 3 is a plan view of Figure 2 in section along the line III-III.
• FIG. 4 shows a side view corresponding to FIG. 2 of a push-on tip of another design;
• FIGS. 5-7 are side views of a schematic type, partly in section, for different configurations of a filter element;
• 8 shows the lower end of a pipetting device with a push-on cone in a special embodiment in a schematic representation;
• 9 shows the lower end of a pipetting device with a one-piece plug-on cone of conventional design in connection with a pipette tip with the interposition of a filter arrangement in side view and in section;
• 10 shows the schematically illustrated lower end of a conventional design of a pipetting device with a special configuration of a filter design.

In all figures, the same parts are identified by the same reference numerals.

A pipetting device 1 according to FIG. 1 according to a device body 2, for example of a cylindrical type, with an actuating lever 3 which leads upwards for driving a piston 4 in a cylinder space 5, from which a capillary-like passage 6 to the end face 7 of a plug-on cone 8 extends. It goes without saying that for the arrangement of the actuating lever 3 and the piston 4 additional guide and also latching means and adjusting devices, which can be actuated by a hand lever 9 if necessary, are provided for different stroke sizes.

Such pipetting devices are known. For example, reference is made to DE P 25 49 477.

A pipette tip 10 is placed on the plug-on cone, which is open at its lower end at 11 and can have a wall reinforcement 12 on the outside at its upper further end, so that a secure fit is ensured with the plug-on cone 8 in the same shape.

A filter is arranged in the area 13, which includes the lower end of the pipetting device 1 with the plug-on cone and also the upper end of the pipette tip 10 below the plug-on cone.

Several options are included for the arrangement of the filter.

2 and 3, the filter 14 is arranged in the pipette tip 10 as a conical filter plug according to the conicity of the pipette tip 10.

This arrangement is defined by a position aid.

In Figure 2, a positioning aid is shown in two different versions.

2 and 3, the positioning aid is designed once in the form of inwardly directed projections 15-17, on which the edge of the lower surface 18 of the filter plug rests. A special pressure can be provided here. Preferred is the design of the projections 15-17 with a roof-shaped ridge 19-21 arranged on the top, which makes it easier to insert the filter plug for tight wall contact with the wall of the pipette tip by pressing lower edge sections onto the ridges that penetrate and thus also fix the position in the circumferential direction. Preferred is a design of the projections 15-17 in a narrow form as vertically arranged cutting edges, on which the filter plug easily finds its seat under external influences, be it during use or under operational influences, in that the filter plug is more or less deep over the cutting edges penetrates. This is an embodiment.

2 also shows that the pipette tip 10 has a wall section 54 of lesser wall thickness and is expandable in this area when the pipette tip 10 is made of elastic material. This has the advantage that an inserted filter plug causes an elastic expansion of the walls of the push-on cone and thus finds a firm fit, the lower edge, for example at 55 of the particularly elastic wall section 54, also forming an abutment limit for an inserted filter plug.

Regardless of this, not only in such a last-described embodiment, but also in an apprenticeship a pipette tip with a consistently solid wall part including a snug fit of an inserted filter plug.

4, the positioning aid consists of an inwardly directed annular flange 22 which forms an edge-side contact surface for the plug-shaped filter. In this embodiment, it goes without saying that this filter plug, which is designed as a cone section, is designed with such an oversize that it finds a sealing contact on the inner wall of the pipette tip 10 when the ring flange is reached.

5 to 7 different versions of the filter plug are shown. The conical design shown is advantageous for use in the solutions described, but is not in itself necessary.

5, a filter plug 23 consists of several layers 24-27, which are designed disc-wise. This is a feature because the discs can have different filtering properties, so that a progressive filtering effect then arises. For example, panes of the same height can have different densities, so that different filter effects arise in them because, with increasing density, continuous media come into contact with wall parts of capillary passages several times. This can be used to trigger reactions, but in itself also for an increased filter effect, namely when the suction or pressure force reaches or exceeds a certain level.

As can be seen from Fig. 5, the disks 24-27 ver different heights. When designing panes with the same density, however, the different heights result in substantially proportional passage difficulties, ie filter effects. Such an embodiment is preferred if the filter effect is to be accompanied by selectively acting influences. These influences change in their reaction activity depending on the height of the individual slices, ie the activity increases when the slice is thicker. Design is also possible in this way.

Such an embodiment is preferred if at least individual parts of the filter are provided with a discolouring indicator additive for liquid contact. The further variation that the indicator addition for individual disks 24-27, possibly of the same height, can be of different strengths is also included.

Fig. 6 shows another embodiment of a filter with a section 28 made in particular of inorganic material, e.g. Glass fiber material or rock wool, which has essentially axial microcapillary-like passages 29. Such a section is in particular provided with a filter disk 30, which is made of cellulose or a corresponding plastic, which advantageously does not react with the substance to be treated, but has special filter properties due to its labyrinth-like passages. For this, reference is made to the above explanations for the material and the pore size.

Fig. 7 shows a corresponding solution with a section 31 and a filter disk 30. The section 31 be sits, starting from the lower inlet opening 32, labyrinthine passages, one of which is designated 33. These passageways are delimited by baffles 34-37 which form wall parts for the passageways. These baffles can consist of a reactive material, such as adhesive coatings, which binds special portions of the continuous medium and, apart from the deposit due to the deflection, thereby accepting and thus exiting the medium. In spite of the filter disk 30, this includes the fact that primarily an aerosol filter is created, because then the filter disk 30 can also have special reactions in the event of fluid access.

FIG. 8 shows another solution in which, with reference to FIG. 1, the push-on cone 8 consists of two parts 38 and 39. As a result, this slip-on cone is divisible. The part 38 located on the device body 2 of the pipetting device is penetrated by the capillary passage 6 over a section of its length, but has a free space under a transverse wall 40 located therein.

The other part 39 is fastened to the part 39, for example, by a screw connection 41 with threads. The part 39 is designed as a high shell and is only closed at the bottom by the wall part 42 with the capillary passage 43. In the cavity 44 of the hollow part 39 there is a filter 45 of the type described. This filter is easy to replace because the lower part 39 of the plug-on cone is freely accessible and can be unscrewed. In this arrangement, an elastic sealing ring 56 is appropriate pulled, which enables an adaptable assembly under tension. A plug connection with a bayonet lock is not excluded.

8, the pipetting device retains its shape for the use of customary known pipette tips.

The same applies to FIG. 9. Here, handling is made even easier, because a conical plug-in filter element 46 can be placed on the outside of the plug-on cone 8, which is equipped on the inside with a filter 47.

Due to the conical design, the further end 48 can easily be placed on the push-on cone. This further end can also be made elastic. The pipette tip 10 can be plugged onto the lower, narrower end 49 because the conicity remains the same as a result of the embodiment described.

In this respect, the plug-in filter element 46 is a particularly advantageous embodiment for the arrangement of the filter in the area 13 according to FIG. 1.

The handling of the plug-in filter element can be facilitated by a flange-like handle attachment 53 arranged on the outside and in the upper area, which is expediently designed as a polygon.

With reference to FIG. 8, in which a filter 45 is provided in the plug-on cone, ie on the pipetting device 1, FIG. 10 shows a further and different advantage adhesive embodiment in that a filter 50 is not arranged inside the plug-on cone 8, but outside at its tip. This is achieved by a mushroom-shaped design which has a head piece 51, in particular a hemispherical shape with a base corresponding to the lower surface of the plug-on cone, and a stem 52 which can be inserted into the capillary passage. Such a filter can be easily handled on the head 51. The stem 52 per se and also in relation to the head piece 51 can be made of filter materials of various effects. A commercially available pipette tip is placed on the cone.

The described pipetting device has significant advantages in use, namely with a filter in each case at the specified points.

For the application, an airtight packaging can be provided for the parts which comprise the pipette tip, the filter or filter material for such and for the plug-on cone or for the conical plug-in filter element, by means of which these parts are kept sterile and dry will. These can be blister packs or welded film packs.

Claims (15)

1. Pipetting device with a push-on cone for a pipette tip and a piston chamber connected to a passage of the push-on cone for the reciprocation of a piston, with a pipette tip and with a filter, characterized in that the filter (14, 23, 50) as an aerosol filter in an area (13) is detachably arranged, which comprises the lower end of the pipetting device (1) with the plug-on cone (8) and the upper end of the pipette tip (10) below the plug-on cone. 2. Pipetting device according to claim 1, characterized in that the filter (14, 23) is made of several layers (24-27) which are arranged one above the other in slices and have a progressive filter effect by changing the permeability from slice to slice, in particular decreases. 3. Pipetting device according to claim 2, characterized in that disks (layers 24-27) of different density are layered one above the other and / or have different heights. 4. Pipetting device according to claim 2 having a micropores in the passage direction, characterized in that this filter is designed as a section (28) made of inorganic material in connection with a filter disc (30) made of sintered diatomaceous earth. 5. Pipetting device according to claim 2, characterized in that a filter is at least partially provided with labyrinthine passages (33) and baffle surfaces (34-37) and the other part with a filter disc (30), in particular made of polyester or acetate fibers. 6. Pipetting device according to claim 1 or 5, characterized in that a filter has only labyrinthine passages and baffle surfaces, the baffle surfaces suitably made of a material which reacts adhesively with the substances inherent in the continuous medium. 7. Pipetting device according to one of claims 1 to 6, characterized in that the filter, in particular including a certain filter arrangement, optionally coated or with a graduated filter design, a coating of the filter material with special bactericidal, fungicidal or virucidal Active ingredients as well as with generally disinfectant substances. 8. Pipetting device according to one of claims 6 or 7, characterized in that the filter material, optionally also baffle surfaces thereof, can be provided with an adhesive coating made of a reactive material which binds special portions of the continuous medium and then also excretes. 9. pipetting device according to one of claims 1 to 8, characterized by a conical plug-in filter element (46) which can be placed with its further end (48) on the plug-on cone (8) and on the narrower end (49) of the pipette tip (10 ) can be placed, a filter (47) being arranged in this plug-in filter element (46). 10. Pipetting device according to one of claims 1 to 8, characterized by the arrangement of the filter (14) in the upper end of the pipette tip (10) and in particular its design with a cross-section-changing positioning aid (15-17; 22) in the form of inward projections (15-17), which have a roof-shaped ridge (19-21) on the top. 11. Pipetting device according to claim 9 or 10, characterized in that the filter is glued into a plug-in filter element (46) or a pipette tip (10). 12. Pipetting device according to one of claims 1 to 8, characterized by a mushroom-like design with a stem (52) which can be inserted into the passage (6) of the plug-on cone (8). 13. Pipetting device according to claim 12, characterized in that a head piece of mushroom-shaped, in particular hemispherical shape is provided as a handle. 14. Pipetting device according to one of claims 1 to 13, characterized in that the filter (14, 23, 50) is provided with an indicator additive for liquid contact. 15. Pipetting device according to claim 14, characterized in that an indicator additive is provided in the form of cobalt compounds and advantageously with a filter of several layers and a progressive filtering action in the event of a one-time liquid contamination with a color change or with multiple dosing, especially with gradual entry of aerosols provides for a slow color change.

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