DE19852947A1 - Micro-liter automatic dispensing apparatus comprises needle moving vertically to penetrate cover over micro-titration plate, to dispense liquid into cells - Google Patents

Abstract

The dispenser needle (8) is moved vertically to penetrate a cover (13) over a micro-titration plate (10), dispensing liquid into its cells (9). The needle is retracted and moved between them under automatic control. The cover prevents evaporation, contamination and aerosol release. A resilient damping system absorbs and stores impulses when motion is interrupted. The dispenser needle (8) is moved vertically to penetrate a cover (13) over a micro-titration plate (10), dispensing liquid into its cells (9). It is retracted and moved between them under automatic control. The cover prevents evaporation, contamination and aerosol release. Residual droplets on the needle end are wiped off, preventing error, and contaminants are kept away, by the cover. A resilient damping system absorbs and stores impulses when motion is interrupted. Preferred Features: Droplets adhering to the needle following delivery are deposited in contact with the cell liquid contents, or its wall, preventing error. The needle rises appropriately, for movement between cells. The needle is given a shake, to detach any residual droplet. This is transmitted to and by e.g. the flexible supply tube (4). Cell temperature is adjusted for careful treatment and to reduce evaporation errors. The cover is slit during penetration, to assist liquid handling techniques, avoiding cover removal.

Description

The invention relates to a method and an apparatus for collecting Fractions, preferably on a microliter scale, and is for analytical and preparative applications in biochemistry, molecular biology, Chemistry, pharmacy, pharmacology, but especially in the Biotechnology. The possible uses for drug screening in the pharmaceutical industry, for the clinical-chemical Analytics, for protein analysis after fragmentation and for called combinatorial chemistry.

The methods of separation, especially with chromatographic Processes have evolved considerably over the past decade been miniaturized. This miniaturization was particularly important required because for the routine characterization of many biological active substances often only very small quantities in µg- or mg- Area are available. In addition, in recent years Requirements for the sample throughput of the analysis, in the search for active substances, Biotechnology and molecular biology have risen sharply. Due to the state of the Pump column and detection technology becomes a separation in the area less microliters possible. In addition to tracking Chromato online graphic result has been in need especially recently result in the individual collected in a high-resolution grid Analyze fractions offline (e.g. peptide separations with subsequent Mass spectrometry: Courchesne P.L., Patterson S.D .: Manual micro  column chromatography for sample cleanup before mass spectrometry, Biotechnics 22, 1998, No. 2, 244-250). From the required densities Fractionation results in many incremental samples, for their high resolution Characterization of an effective parallel processing is necessary.

Known chromatographic separation methods used however, a sequential flow and must therefore be effective parallel processing of the available grids for multipipetting Dispensing and multi-channel measuring technology can be adapted. Currently is a widespread standard for the sample vessels through the so-called Multiwell analysis plate (e.g. Gerasimova N. S., Steklova I. V., Tuuminen T .: Fluorometric method for phenylalanine microplate assay adapted for phenylketonuria screening, Clin-Chem. 1989, Oct. 35 (10), 2112-2115 or Matthews P. D., Wurtzel E. T .: high throughput microplate format for producing and screening riboprobes from bacterial cells, Biotechniques. 1995 Jun, 18 (6), 1000-1002, 1004 or Wu P., Daniel-Issakani S., LaMarco K., Strulovici B .: an automated high throughput filtration assay: application to polymerase inhibitor identification ,; Anal biochem. 1997, Feb 15; 245 (2), 226-230 or Rashed M. S., Bucknall M. P., Little D., Awad A., Jacob M., Alamoudi M., Alwattar M., Ozand P. T .: screening blood spots for inborn errors of metabolism by electrospray tandern mass spectrometry with a microplate batch process and a computer algorithm for automated flagging of abnormal profiles, Clin-Chem. 1997, Jul; 43 (7), 1129-1141) and those of her derived grid determined. The dimensions are defined in the SBS standard. There are a total of 96 sample tubes from this starting size derived grid with 384, 864 and 1536 sample vessels (catalogs of Greiner and Corning Costar). Almost all devices for a high Sample throughput of "liquid handling" and parallel processing are this Grid adjusted and thus compatible with each other in the area.  

The separation process with liquid volume-moving separation techniques, such as HPLC or FPLC with a sequential process, collect the separate ones Samples with fraction collectors in a specific order or with a certain grid, either continuously by volume and the time, a time program or according to a predetermined Threshold value of the respective detector. Different types are known automatic fraction collector, which often also automated liquid separating processes are coupled (US 4,422,151, US 4,049,031 or DE 35 20 055). These consist of holders for the sample vessels, one Delivery of the solution to be collected and an internal or external one Control unit. There are the following for the arrangement of the sample vessels Variants: firstly carousel-shaped (US 3 838 719), secondly spiral (US 3,570,555), third in rows and columns (US 4,422,151) fourth in rows and columns in movable containers (US 4,077,444).

The positioning of the sample vessels under the outlet opening for the Sample solution is done either by moving the holder of the Sample vessels or by moving the outlet opening.

The collection volume in the lower area reaches 5 µl (company brochure Pharmacia Biotech: Fraction collector on the Smart ™ system). For low Volumes and high numbers of samples are often formats that fit the grid Multiwell analysis plate correspond to used (INTERNET publication of Gilson company to fraction collector FC203, to fraction collector on Combinatorial chromatography system and to the µ-fractionator on the Base of a Gilson 221XL). These faction collectors have one Space for at least one sample container. A mobile Element feeds the samples horizontally over the grid standing individual sample vessels and fills them as specified. There are designs that include the feeding element, a capillary or a  Capillary tube in addition to the horizontal positioning movement over the move the respective vessel vertically into the vessel to deposit the sample (Gilson's INTERNET publication on the fraction collector on Combinatorial chromatography system and to the µ-fractionator on the Basis of a Gilson 221XL and the company Pharmacia Biotech zum Frak tion collector on the Smart ™ system). Another vertical movement to The last drop at the outlet is patented (DE 43 03 275).

A disadvantage of the previous fraction collectors are the small ones Amounts of liquid in the samples, especially evaporation losses (high Surface / volume ratio), carry-over contamination of the Frak interactions, airborne contamination such as dust particles and Microorganisms, as well as the possibility of aerosol formation of the collection good.

A reduction in evaporation and an improvement in durability can can be achieved by tempering below room temperature (Gilson's INTERNET publication on temperature-controlled samples Fraction collector FC206).

Another way to reduce evaporation losses and Avoiding contamination is to cover the panels with covers to be provided or taped or welded and thus each Hermetically seal the sample vessel of the plate (US Pat. No. 5,056,427, US 5,604,130). The Gilson company uses for contamination protection of the collection vessels at their fraction collector FC206 Protection. For covering with foils there is both the possibility manually glue foils, as well as commercially available devices automated process for film gluing and welding (INTERNET- Publication of the company Zymark for their Presto Automated Microplate Sealer). The disadvantage of all of these covers for use as evaporation and  Protection against contamination for fraction collector samples consists in that the Openings of the collection vessels are primarily closed and thus the lid or foils removed before collecting and again after collecting must be applied. First, that means a corresponding one Processing effort for sample handling, d. H. for handling the Collection containers for preparing and reworking the collection process. Secondly, it is particularly problematic that with the at times not closure present during fractionation is not sufficient Protection is given. The risk of sample loss, contamination and Misfractionation, especially due to carryover, during fractionation continues. Automation of the Collecting is therefore not possible in an effective way. From these For reasons, the closure of the collection vessels is practically as good no use.

The invention has for its object fractions on a microliter scale without risk of contamination, loss of fluid, of Fraction mixtures and aerosol formation as well as possible low handling effort for pre and post treatment Collect sample vessels.

According to the collecting vessels with a perforable Cover, for example an adhesive film, closed, or the Collecting vessels can already have such a hermetic seal to be provided. With a thin, hollow perforating tip each penetrated the cover when positioning and when reaching the Collect the fractionated liquid through the cover dispensed into the selected receptacle. The cover prevents that Aerosol release into the environment and closes the collection containers  safe from evaporation and contamination. It also prevents largely that misfractionate substance components, for example, on drip the multiwell analysis plate, get into its collection vessels and mix with the collected fraction. After sample delivery the hollow needle to be sampled moves back into hers Starting position above the collecting vessel. To safely avoid Incorrect fractionation becomes the perforator during the positioning movement tip the supply of the liquid to be fractionated to the perforating tip as substance-releasing element interrupted. This interruption will advantageously realized by an electromechanical valve. That before Volume continues to flow continuously through a valve elastic deformation body, preferably by an elastic thin Feed hose, picked up and buffered. At the The remaining droplets hanging from the perforating tip are removed by wiping them off Vessel bottom or on the surface of the liquid to be collected or submitted liquid and / or by a pulse to expel the Dispense residual solution from the needle tip into the collecting vessel. The preferably use of one or the other option depends on the sample to be collected, the collection vessels used and according to the Collection volume.

The collecting vessels remain in the fractionation except for the tiny one Perforation puncture closed, so that even while collecting said protection against loss of evaporation, pollution, aerosol education in the area etc. is given. Applying additional Covers for protected storage, transportation and There is no further processing of the fractions in the collecting vessels, since the Collecting vessels, apart from the perforation, after the Fractionation are still largely covered. The handling up  wall for applying the perforable thin cover film, for. B. one Adhesive film on a multiwell analysis plate is small and possibly can already capped multiwell analysis plates be used.

Advantageous refinements are in subclaims 2 to 7 and 9-27 the process or device features listed.

The invention will now be described with reference to one in the drawing Embodiment will be explained in more detail.

Show it:

Fig. 1: Schematic structure of the fraction collector,

Fig. 2: perforating in collecting position after piercing the cover from the receptacle,

Fig. 3: Time schedule of the control for the collecting time of a fraction having a pulse for residual substance discharge,

Fig. 4: Timing of the control for the collecting time of a fraction without pulse for residual substance discharge,

Fig. 5. Embodiments of the hollow perforating,

Fig. 6: perforating with additional cutting in different embodiments

FIG. 7 shows the clamping device for perforating,

Fig. 8: Comparison of the evaporation losses of an open and covered multiwell analysis plate.

In Fig. 1 the basic structure of the fraction collector is shown on a microliter scale. The substance to be fractionated is fed via a connection adapter 1 to a multi-way valve 2 . The multi-way valve 2 , controlled by a control unit 3 , directs the volume flow either to a waste container 6 or via an elastic hose 4 , a fractionating valve 5 and via an ejection device 7 in the direction of a hollow perforating tip 8 , with which the fractions to be collected are each in selected collection vessels 9 are delivered to a multiwell analysis plate 10 . For relative xy positioning of the hollow perforating tip 8 to the collecting vessels 9 , the multiwell analysis plate 10 is connected to a positioning unit 11 , for example an xy coordinate table known per se, which is also motion-controlled by the control unit 3 . For each fraction, the corresponding collecting vessel 7 of the multiwell analysis plate 10 is selected via the control unit 3 and the positioning unit 11 by positioning the multiwell analysis plate 10 relative to the perforating tip 6 . In addition, the control unit 3 controls a lifting unit 12 for z-movement of the perforating tip 8 in order to move it into the collecting vessel 9 after selection of a collecting vessel 9 for the respective fraction for substance delivery. During its vertical movement to reach the collecting position for the substance delivery, the perforating tip 8 pierces a cover film 13 applied to the multiwell analysis plate 10 and releases the fraction through the cover film 13 thus perforated into the selected collecting vessel 9 (cf. FIG. 2).

The cover film 13 , for example an adhesive film, prevents aerosol formation in the environment, evaporation and contamination by dust and dirt particles of the very small fraction volumes in the collecting vessels 9 before, during and after the fractionation. In the event that from the perforating tip 8 , which is moved over the collecting vessels 9 , for example in the event of inadequate closing of the valves or leaky connections, drops emerging therefrom, which no longer belong to the respective fraction, reach the multiwell analysis plate 10 , these drops will pass through the cover film 13 also kept away from the collecting vessels 9 and can therefore not cause any incorrect fractionation. The multiwell analysis plate 10 can also be provided for this preventive contamination protection and sterility of the collecting vessels 9 provided with this cover sheet 13 , stored and made available for fractionation. It is also possible to present a solution or solid substance in the multiwell analysis plate 10 , for example stabilizers for proteins, to close the multiwell analysis plate 10 with the cover film 13 and to collect the fractions in the collecting vessels 9 with the material presented.

For additional evaporation protection, the multiwell analysis plate 10 is connected to a temperature control unit 14 , by means of which the collecting vessels 9 of the multiwell analysis plate 10 arranged in a defined grid, for example n × 8 × 12, are kept at a temperature below room temperature.

After the substance has been dispensed, the perforating tip 8 is moved back from its collecting position in the collecting vessel 9 into an upper starting position by z-positioning. Another collecting vessel 9 can then be selected for the next fraction to be collected.

During the positioning movement of the perforating tip 8 from or to its collecting position in the respectively selected collecting vessel 9 , including the relative positioning movement of the multiwell analysis plate 10 , the volume flow flowing continuously through the multi-way valve 2 is interrupted by means of the fractionation valve 5 .

The hose 4 is elastic and has a small inner diameter (less than or equal to 0.5 mm). This ensures that, firstly, the pressure pulse occurring as a result of the closing of the fractionation valve 5 in the substance to be collected is damped, and secondly, the substance to be fractionated without substantial substance mixing, for example as a result of turbulence, is taken up and temporarily stored until the next substance release. A liquid drop still located on the perforating tip 8 is repelled by a pulse from the ejection device 7 . In Fig. 1, the ejection device 7 consists of an electromagnetically moved stamp 15 from the control unit 3 , which, after substance delivery of the perforating tip 8 into the selected collecting vessel 9 , gives a brief mechanical impulse against an abutment 16 on the elastic tube 17 . The short impulse could also be given in another way, for example other mechanical elements, such as cams and levers, a piezoelectric element, ultrasound, compressed gas or vacuum, acting on the substance in the perforating tip 8 or its feed. It is also possible that residual drops on the surface of the collected and / or already submitted substance or on the inner wall of the collecting vessel 9 are wiped off by touch, for which purpose the lifting device 12 for the very precise and sensitive movement control of the perforating tip 8 suitably has a high-resolution stepping drive or associated with one. (The named alternative solutions for the pulse generation of the ejection device 7 are not shown in the drawing for reasons of clarity.)

In Fig. 3 is a timing diagram, based on the collection time for a fraction, with such a pulse for the remaining ejection of liquid drops (ejection device 7 ), for the control of the positioning unit 11 , the lifting unit 12 and the fractionating valve 5 and with an illustration of the pressure curve in the elastic Hose 4 shown. For comparison, Fig. 4 shows a relevant timing diagram without the impulse for the remaining output.

Fig. 5 shows in two views possible embodiments to which the cover film 13 by abutting perforating 8, wherein the invention is not limited to the illustrated forms. The perforating tip 8 can have, for example, single tips 18 , multiple tips 19 , chamfering 20 , chamfering 21 , arbitrarily shaped phases 22, etc., alone or in combination. The selection of the suitable perforating tip shape depends on the intended use, in particular with regard to the type of cover film 13 to be pierced.

In FIG. 6 Cut (6a 6c FIG. To FIG. Four cutting edges, and Fig. 6d to Fig. 6f double-edged, respectively shown in two views) are attached to the perforating tip 8 an additional 23 different shape arranged. During the lifting movement of the perforating tip 8 into the collecting vessel 9, the cutting edges 23 slit the cover film 13 in addition to the perforation for the substance delivery with a single or multiple slit. Due to the slots, the collecting vessels 9 remain essentially covered by the cover film 13 with the advantages of the invention, but further processing of the collected fractions by devices of the "liquid handling" technique known per se is simple. especially multipipettes, possible without removing the cover film 13 beforehand. The device elements can also penetrate into the collecting vessels 9 through the slots for sample treatment, the slot openings automatically closing again after the treatment due to the flexible cover film 13 .

It is expedient to provide the cover film 13 with adhesive points only in the area of the contact surfaces to the multiwell analysis plate 10 , so that the perforating tip 8 is not contaminated with the adhesive and the adhesion of material to be fractionated via the adhesive to the perforating tip 8 is avoided.

The perforating 8 to secure a fast and yet capable accurately interchangeability with little handling and adjustment to the lifting device 12, the perforating tip 8 in Fig. 7 is provided with a receiving flange 24 for receiving in a clamping device 25 of the lifting device 12. The receiving flange 24 with the perforating tip 8 is inserted up to the annular stop in the clamping device 25 and locked by turning a clamping screw 26 . In this way, the perforating tip 8 can be changed quickly and easily, depending on the application conditions, but at the same time the positional precision required for exact vertical movement control (also with regard to wiping off residual liquid after the substance has been dispensed) can be ensured. For universal applicability, the perforating tip 8 , as well as the supply system for the liquid, should be connected by plug connectors, quick couplings, etc., in order to implement a structure which can be used quickly and, above all, can be converted. For example, perforating tips 8 and feed elements with different flow size and quantity and, depending on the fractionation requirement, in particular tubes 4 , 17 with variable size and elasticity can be set up in a very short time.

Since the thin, hollow perforating tip 8 represents a very sensitive component for substance delivery with its inner diameter less than or equal to 0.5 mm and its outer diameter less than or equal to 0.9 mm, in particular for bending stress, a sensor (not shown in the drawing) on the perforating tip 8 , which detects its bending load, for example in the event of an unforeseen obstacle during positioning. In the event of an accident, this switches off the motion control. Furthermore, moisture sensors (also not shown in the drawing) are helpful for detecting leaks under the hose system and under the multiwell analysis plate 10 in order to be able to quickly switch off the device in order to avoid damage due to liquid losses.

In FIG. 8, the evaporation loss of a known commercially available multiwell analysis plate 10 arranged on both open and to closed by the cover film 13 and the grid 8 × 12 receptacles 9 of the multiwell analysis plate were 10 measured at different temperatures compared. The perforation of the cover film 13 was simulated by means of vertical punctures above each collecting vessel 9 with a puncture hole of approximately 0.5 mm in diameter. The collecting vessels 9 were each filled with 150 μl deionized water and were placed either at room temperature or on a copper plate cooled to 4 ° C. in a laboratory room at room temperatures of 18-23 ° C. over a period of 18.4 hours. The evaporation was measured by weight measurement before and after the experiment.

List of the reference symbols used

1

Connection adapter

2nd

Multi-way valve

3rd

Control unit

4th

elastic hose

5

Fractionation valve

6

Waste bin

7

Ejection device

8th

Perforating tip

9

Collecting vessel

10th

Multiwell analysis plate

11

Positioning unit

12th

Lifting unit

13

Cover film

14

Temperature control unit

15

stamp

16

Abutment

17th

tube

18th

Single tip

19th

Multiple tip

20th

Phasing

21

Chamfering

22

phase

23

Cutting edge

24th

Mounting flange

25th

Clamping device

26

Clamping screw

Claims (27)

1. A method for collecting fractions after material separation, in which a substance-releasing element is positioned relative to them via collecting vessels arranged in a defined grid which is suitable for the known "liquid handling" technique, each brought into the collecting position with a vertical relative movement and there releases a quantity of substance to be fractionated into the selected collecting vessel, characterized in that the substance-releasing element on its vertical relative movement for the substance delivery each has a residual drop on the collecting vessels and preventing the formation of aerosols in the environment, which prevents evaporation and contamination perforated cover which repels substance-releasing element and also other incorrectly fractioning substance portions, releases the substance in the collecting position through this cover into the selected collecting vessel and then emerges from the sealed cornered collecting vessel is moved back to the starting position and that the liquid flow to the substance-dispensing element is interrupted during the positioning movement of the substance-dispensing element, and to dampen the pressure changes acting on the substance-dispensing element with this interruption, it is absorbed and stored between. 2. The method according to claim 1, characterized in that the substance-releasing element to further avoid a wrong fraction or a carryover of substances so far into the selected one Collector is moved in that residual drops on the substance-releasing Element after interrupting the liquid flow by touching  the collected and / or presented substance or by contact with be stripped from the inner wall of the collecting vessel. 3. Process according to claims 1 and 2, characterized in that the Positioning movement of the substance-releasing element in high-resolution Steps is controlled. 4. The method according to claim 1, characterized in that for further Avoiding incorrect fractionation or carryover of substances after the substance has been dispensed into a selected collection container, still in Drop form on the substance-releasing element residual liquid by a pulse acting mechanically on this or its feed line is repelled. 5. The method according to claim 4, characterized in that the pulse on an elastic element of the substance supply, for example one Feed hose is given. 6. The method according to claim 1, characterized in that the collection vessels to further reduce the risk of evaporation and more gentle Handling of the fractions can be tempered. 7. The method according to claim 1, characterized in that on the Cover containers located except the one with the substance donor element for collecting the fractions made Perforation is additionally slotted to the collected fractions Devices of the known "liquid handling" technology without removal to continue treating the cover.   8. Apparatus for collecting fractions after material separation with means, in particular a connection adapter and supply hose, for providing and supplying the substance to be fractionated, with a fractionation unit for the substance, for example a control valve, with a substance-releasing element for dispensing the substance to be fractionated in Collection vessels, which are arranged in a defined grid that is compatible with the known "liquid handling" technique, and with means for positioning the substance-dispensing element relative to the collection vessels, including a lifting unit for lowering it to the respectively selected collection vessel, characterized in that that a hollow perforating tip ( 8 ) is provided as the substance-releasing element, both for piercing a located on the collecting vessels ( 9 ) and preventing aerosol formation in the environment, evaporation and contamination-proof s owie also other incorrectly fractionating substance portions keeping cover ( 13 ) and for a through this cover ( 13 ) through the substance delivery into the selected collection vessel ( 9 ) that means ( 5 ) for interrupting the substance supply to the perforating tip ( 8 ) during it Positioning movement are provided and that at least one elastic deformation body ( 4 ) for elastic absorption and intermediate storage of the pent-up substance by interrupting the substance supply is present. 9. The device according to claim 8, characterized in that the means for interrupting the substance supply to the perforating tip ( 8 ) are also provided for after the substance has been dispensed still on the perforating tip ( 8 ) residual drops by a mechanical on the liquid before or in to repel the perforating tip ( 8 ). 10. The device according to claim 8, characterized in that an electromagnetically controlled valve ( 5 ) are provided as means for interrupting the substance supply to the perforating tip ( 8 ) during its positioning movement. 11. The device according to claim 8, characterized in that a flexible feed hose ( 4 ) with a small inner diameter, preferably less than 0.5 mm, is provided as the elastic deformation body. 12. The apparatus according to claim 8, characterized in that a well-known multiwell analysis plate ( 10 ) is provided as collecting vessels, the collecting vessels ( 9 ) arranged for example in an n × 8 × 12 grid are closed by a film ( 13 ). 13. The apparatus according to claim 8, characterized in that the collecting vessels ( 9 ) are closed by a film ( 13 ) which has adhesive for fixing them exclusively on the support surfaces. 14. The apparatus according to claim 8, characterized in that the collecting vessels ( 9 ) for tempering the fractions contained therein with a temperature control unit ( 14 ), for example a temperature-adjustable metal plate with Peltier elements or a water-cooled base plate, are connected. 15. The apparatus according to claim 8, characterized in that the lifting unit ( 12 ) for fine positioning of the perforating tip ( 8 ) is connected to a high-resolution stepper drive. 16. The apparatus according to claim 8, characterized in that the perforating tip ( 8 ) for the purpose of an exchangeable, quick and location-precise attachment to the lifting unit ( 12 ) for a clamping device ( 25 , 26 ) provided position-defined receptacle, for example a cylindrical flange ( 24 ) with an annular stop. 17. The apparatus according to claim 8, characterized in that at least one sensor, for example for detecting the bending load of the perforating tip ( 8 ), is arranged on the perforating tip ( 8 ) to protect it against mechanical stress in the event of an unforeseen obstacle to movement, which means is connected to the positioning movement of the perforating tip ( 8 ) and to the substance guidance and interrupts the positioning movement and substance feeding in the event of an accident. 18. The apparatus according to claim 8, characterized in that below the collecting vessels ( 9 ) and / or the liquid-carrying elements, in particular under the hoses ( 4 , 17 ), sensors for detecting leaks are arranged and that the sensors with a shutdown unit of the system are coupled. 19. The apparatus according to claim 8, characterized in that the perforating tip ( 8 ) consists of a material of high mechanical strength and high chemical resistance, for example of an inert stainless steel, and in that the inside diameter is less than or equal to 0.5 mm and the outside diameter is less than or are equal to 0.9 mm. 20. The apparatus according to claim 8, characterized in that the perforating tip ( 8 ) has a single tip ( 18 ). 21. The apparatus according to claim 8, characterized in that the perforating tip ( 8 ) has a multiple tip ( 19 ). 22. The apparatus according to claim 8, characterized in that the perforating tip ( 8 ) has chamfering or chamfering ( 20 , 21 ). 23. The device according to claim 8, characterized in that the perforating tip ( 8 ) has an arbitrarily curved phase ( 22 ). 24. The device according to claim 8, characterized in that the perforating tip ( 8 ) has one or more tips ( 18 , 19 ) and / or and at least one phase ( 20 , 21 , 22 ). 25. The device according to claim 8, characterized in that at least the deformation body ( 4 ) and the perforating tip ( 8 ) for interchangeable use have means for quick connection, for example a connector or a quick coupling. 26. The apparatus according to claim 8, characterized in that in addition to the perforating tip ( 8 ) at least one cutting edge ( 23 ) is provided which slits the cover ( 13 ) around the fractions collected in the collecting vessels ( 9 ) with devices of the per se known "liquid handling" technology to process without having to remove the cover ( 13 ). 27. The apparatus according to claim 26, characterized in that the at least one cutting edge ( 23 ) is also arranged on the perforating tip ( 8 ) or on the lifting device ( 12 ) and is moved with their positioning for the slitting in of the cover ( 13 ).