Abstract:
The invention relates to an apparatus for isolating nucleic acids from biological fluids and suspensions containing nucleic acids, a reaction compartment  17  for receiving an adsorption medium  100  being connected to a removal compartment  50,  and the nucleic acids being able to be moved and enriched from the reaction compartment  17  into the removal compartment  50  by an electrophoresis apparatus  20   a,    20   b.

Description:
This application is a divisional of U.S. patent application Ser. No. 09/142,958, filed Jan. 25, 1999, now allowed, which is a 371 of PCT/DE97/00517, filed Mar. 14, 1997, now abandoned. 
    
    
     BACKGROUND OF THE INVENTION 
     The invention relates to a process and an apparatus for isolating nucleic acids. 
     Before the analysis by polymerase chain reaction (PCR) of nucleic acids obtained from cells, it is necessary to purify and concentrate the nucleic acids. In addition, it can be necessary to remove from the sample to be analyzed certain substances interfering with the polymerase chain reaction, such as the hemoglobin prosthetic group. 
     In addition, in other techniques of nucleic acid analysis, for example hybridization, purification and concentration of the nucleic acids to be analyzed also plays an important role. 
     “Methods of Enzymology”, Vol. 68, pp. 170-182, discloses using “spin-columns” for the isolation of nucleic acids. In a variant of this technique disclosed by DE 41 39 664 A1, the following working steps are used: 
     aa) cell disintegration, 
     bb) adsorption of the nucleic acids to a glass fiber fleece in the presence of a high ionic strength buffer, and 
     cc) elution of the nucleic acids by a low ionic strength buffer. 
     In the step aa), the liquid sample is passed through a glass fiber fleece to which the nucleic acids adsorb. The glass fiber fleece is then washed with various solutions. Finally, the nucleic acids are eluted from the solid phase in the presence of low ionic strength buffers. 
     The known process is disadvantageous in a number of respects: contamination of the sample can occur during washing of the solid phase. In addition, because of the capillary forces prevailing in the glass fiber fleece, the nucleic acids can only be partially recovered therefrom. 
     Furthermore, “Methods in Enzymology 65” (1980), pp. 371-380 discloses gel electrophoretic methods in which nucleic acids are bound to gels and are then brought back into solution by electroelution. Contamination of the solution can also occur in this case. The nucleic acids are present in the solution at high dilution. Concentration does not occur. 
     The object of the present invention is to specify a process and an apparatus by which the disadvantages of the prior art are avoided. In particular, a process and an apparatus for isolating nucleic acids which enable simple and inexpensive purification and concentration of nucleic acids are to be specified. Furthermore, a substantially automated isolation and concentration of nucleic acids is to be able to be carried out. Finally, the purpose of the invention is to avoid contaminations. 
     SUMMARY OF THE INVENTION 
     According to the invention, a process is provided for isolating nucleic acids from biological fluids and suspensions containing nucleic acids, 
     a) the nucleic acids being bound to an adsorption medium, 
     b) the nucleic acids being eluted from the adsorption medium, and 
     c) being moved by electrophoresis from a reaction compartment into a removal compartment connected thereto and enriched there. 
     The process makes possible in a simple manner purification and concentration of nucleic acids from liquids. In particular in an automatic process procedure, the risk of contamination can be largely excluded. The elution can be performed by buffer change or electrically by electroelution or electrophoresis. 
     Further according to the invention, an apparatus for isolating nucleic acids from biological fluids and suspensions containing nucleic acids is provided, a reaction compartment for receiving an adsorption medium laden with nucleic acids being connected to a removal compartment, and the nucleic acids being able to be moved by an electrophoresis device from the reaction compartment into the removal compartment and enriched there. This apparatus makes a simple and inexpensive concentration and isolation of nucleic acids possible. By the provision of a separate removal compartment, contamination can be largely excluded. 
     Exemplary embodiments of the invention are described in more detail below with reference to the drawing. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 shows a diagrammatic cross-section of a first exemplary embodiment of the apparatus, 
     FIG. 2 shows the exemplary embodiment according to FIG. 1 with a “spin column”, 
     FIG. 3 shows a diagrammatic cross-section of a second exemplary embodiment of the apparatus, 
     FIG. 4 shows a diagrammatic cross-section through a first exemplary embodiment of a purification and enrichment apparatus having an apparatus according to FIG. 3, 
     FIG. 5 shows a plan view of a flat bed agarose gel, 
     FIG. 6 a  shows a diagrammatic cross-section of a third exemplary embodiment of the apparatus, 
     FIG. 6 b  shows a modification of the exemplary embodiment shown in FIG. 6 a,    
     FIG. 6 c  shows a diagrammatic cross-section of a fourth exemplary embodiment of the apparatus, 
     FIG. 7 a  shows a bottom view of a fifth exemplary embodiment of the apparatus, 
     FIG. 7 b  shows a plan view of the exemplary embodiment according to FIG. 7 a,    
     FIG. 7 c  shows a diagrammatic side view of the exemplary embodiment according to FIG. 7 a,    
     FIG. 7 d  shows a perspective view of a cover for a first exemplary embodiment of an elution apparatus, 
     FIG. 7 e  shows a perspective view of the first exemplary embodiment of the elution apparatus without a cover, 
     FIG. 7 f  shows a perspective view of the exemplary embodiment according to FIGS. 7 a  to  7   c,    
     FIG. 8 shows a diagrammatic cross-section through a sixth exemplary embodiment of the apparatus, 
     FIG. 9 shows a diagrammatic cross-section through a coated electrode, 
     FIG. 10 shows a diagrammatic cross-section through a seventh exemplary embodiment of the apparatus, 
     FIG. 11 shows a diagrammatic cross-section through an eight exemplary embodiment of the apparatus, 
     FIG. 12 shows a plan view of a second exemplary embodiment of an elution apparatus, and 
     FIG. 13 shows a diagrammatic cross-section through a second exemplary embodiment of a purification and enrichment apparatus. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     FIG. 1 shows a diagrammatic cross-section of a first exemplary embodiment of the apparatus. A container  15  is held in an electrophoresis buffer tank  10  having a bottom-side breakthrough  43 . The container  15  encloses a reaction compartment  17  which is connected via a channel  49  to a removal compartment  50 . The volume of the reaction compartment  17  is preferably from 1 to 20 ml. The removal compartment  50  is in ion-conducting connection, by means of a first permeable membrane  30  sealing a first orifice  42 , with an electrophoresis buffer held in the electrophoresis buffer tank  10 . The volume of the removal compartment  50  is preferably from 0.005 to 0.1 ml. The first permeable membrane  30  is formed, for example, from a dialysis membrane which is impassable to nucleic acids, but is passable to salts, in particular chaotropic salts. The first permeable membrane  30  is fixed by a flexible ring, for example an O-ring, on a first nozzle  41 . An adsorption medium  100 , for example a glass fiber fleece, silica, glass beads, glass-encoated magnetic particles, anion exchanger or the like, is held in the reaction compartment  17 . A cathode  20   a  projects through a second orifice  80  into the reaction compartment  17 . An anode  20   b  dips into the electrophoresis buffer situated in the electrophoresis buffer tank  10 , the level of which buffer is indicated by  70 . Beneath the adsorption medium  100 , a second nozzle  85  which passes through the breakthrough  43  extends from the container  15 . The second nozzle  85  is sealed from the electrophoresis buffer tank  10  by an O-ring  40 . The removal compartment  50  has a removal orifice  60 . It is designed in such a manner that air inclusions are avoided. The removal compartment  50  can be designed, in particular, as capillary. 
     FIG. 2 essentially shows the first exemplary embodiment shown in FIG.  1 . In this case a spin column  90  is held in the reaction compartment  17 . The second nozzle  85  passing through the electrophoresis buffer tank  10  is not provided here. 
     FIG. 3 shows a diagrammatic cross-sectional view through a second exemplary embodiment of the apparatus. In this case the cathode  20   a  is situated outside the reaction compartment  17 . It dips directly into the electrophoresis buffer tank  10 . On the part of the container  15  surrounding the reaction compartment  17 , a third nozzle  45  is provided, the third orifice  46  of which is sealed by a second permeable membrane  31 . 
     FIG. 4 shows a diagrammatic cross-sectional view through a first exemplary embodiment of a purification and enrichment apparatus having the apparatus according to FIG.  3 . The apparatus according to FIG. 3 is situated in the area of action of an x,y,z pipettor, whose x,y,z pipetting arm is designated  190 . The x,y,z pipetting arm  190  holds a pipetting tip  180 , preferably a disposable tip. A suitable x,y,z pipettor is available from, for example, TECAN AG, Switzerland. In addition, a heatable shaker frame  170  is arranged in the area of action of the x,y,z pipettor. Reaction tubes  150  for the lysis are held in the shaker frame  170 . Beside this there are situated a first vessel  160  for the lysis, a second vessel  162  for holding a wash solution and sample vessels  165 .  185  designates a store of pipette tips and  210  indicates PCR vessels. 
     The electrophoresis buffer tank  10  is provided with a filling port  125 , which is connected to an electrophoresis buffer reservoir  110 , with intermediate connection of a pump  120 . The second nozzle  85  and an outlet line  140  provided at the bottom of the electrophoresis buffer tank  10  are connected to a second pump  130 . The second pump  130  is preferably constructed as a peristaltic pump. A suitable peristaltic pump is available, for example, from Cavro, Calif., USA. The cathode  20   a  and the anode  20   b  are connected via electrical leads  225   a  and  225   b  to a power supply  220 . The first pump  120  and the second pump  130 , the shaking frame  170 , the x,y,z pipettor and the power supply  220  are constructed in such a way that they can be controlled by a process computer. Thus fully automatic operation of the purification and enrichment apparatus is possible. 
     FIG. 5 shows a plan view of a particularly simple variant of a container  15 . This is made from a flat bed agarose gel  11 , on the opposite transverse sides of which lie the cathode  20   a  and the anode  20   b.  In the flat bed agarose gel  11  are provided a first recess  81  forming the reaction compartment  17  for holding adsorption medium and a second recess  61 . The second recess  61  is formed as a slot. It serves for removing the nucleic acids enriched therein. 
     FIG. 6 a  shows a diagrammatic cross-section through a third exemplary embodiment of the apparatus. In this case the container  15  is constructed in the form of a cross-connection piece. The adsorption medium  100  is situated on a support fleece  302 . The cathode  20   a  and the anode  20   b  are constructed as electrically conductive plastic pipette tips, which are connected to the electrophoresis buffer tank (not shown here). They are connected to the container  15  via tubing pieces  318 . Nucleic acids accumulated in the removal compartment  50  can be taken off through the removal orifice  60 . 
     As shown in FIG. 6 b,  further support fleeces  303  can be arranged between the removal compartment  50  and an intermediate compartment  321 . In the fourth exemplary embodiment shown in FIG. 6 c,  the orifices of the electrodes  20   a  and  20   b  formed as plastic pipette tips are sealed. 
     In FIGS. 7 a  to  7   c,  a fifth exemplary embodiment of the apparatus is shown in several views. In this case, the container  15  comprises a rectangular component. The reaction compartment  17  is formed by a borehole. On both sides, next to the reaction compartment  17 , recesses  320 ,  321  for holding the cathode  20   a  and the anode  20   b,  respectively, are provided. The wall between the recesses  320 ,  321  and the reaction compartment  17  is fabricated to be ion-conducting. The recesses  321  serve to hold electrophoresis buffer. They are sealed with stoppers  340 . The electrophoresis buffer tank, in this embodiment, consists of two part-containers which enclose the reaction compartment  17 . A multiplicity of such apparatuses, one of which FIG. 7 f  again shows in a perspective view, can be constituents of the first exemplary embodiment shown in FIGS. 7 d  and  7   e  of an elution apparatus. The elution apparatus essentially consists of a multiple compartment container  410  for holding a plurality of apparatuses according to FIG. 7 f.  The multiple compartment container  410  has a vacuum connection  401  and connections  402  for a liquid circuit for heating the elution apparatus. A cover  400  shown in FIG. 7 d  is provided with leads  226   a,    226   b  for the electrodes. 
     FIG. 8 shows a sixth exemplary embodiment of the apparatus. In this case the cathode  20   a  is integrated into the wall of the reaction compartment  17  and the anode  20   b  is integrated into the opposite wall of the removal compartment  50 . In the removal compartment  50 , a permeable, in particular a semipermeable, membrane  310  is provided which is impermeable to nucleic acids. The membrane  310  prevents the nucleic acids from passing directly to the anode  20   b  and being destroyed there by redox processes. The adsorption medium  100  is supported by the support fleece  302  at the entry of the second nozzle  85 . 
     FIG. 9 shows a diagrammatic cross-section through a coated electrode. A cathode or anode  20   a  or  20   b  fabricated from a noble metal, such as gold, silver or platinum, or electrically conductive plastic, is provided with a coating consisting of a plurality of layers. A first layer  323  applied to the noble metal or the plastic consists of biotinylated bovine serum albumin, a second layer  325  superposed thereupon consists of a streptavidin of polystreptavidin and an outer third layer  324  is formed of an oligonucleotide. 
     In the case of the seventh exemplary embodiment of the apparatus shown in FIG. 10, a movable permanent magnet  312  is arranged on the outside of the container  15  in such a manner that its north pole is in the vicinity of the cathode  20   a.  The reaction compartment  17  is sealed by a transparent snap-on cover  316 . The removal compartment  50  is sealed by a snap-on cover  326  which is provided with a septum  328 . The septum  328  can be pierced by a needle  327  for removal or addition of liquid. Thus contamination of the liquid present in the apparatus can be avoided.  314  designates a photomultiplier which is arranged above the transparent snap-on cover  316 . 
     FIG. 11 shows a diagrammatic cross-section of an eighth exemplary embodiment. In contrast to the seventh exemplary embodiment, here, the movable permanent magnet  312  is arranged with its south pole in the vicinity of the outside of the anode  20   b.  The bottom of the removal compartment  50  is transparent. Opposite the removal orifice  60 , the photomultiplier  314  is situated beneath the bottom of the removal compartment  50 . 
     FIG. 12 shows a plan view of a second exemplary embodiment of an elution apparatus. In this case, a multiplicity of the apparatuses shown in FIG. 11 are arranged one beside the other. Thermostat plates  329 , by which the temperature can be set, are provided on each of the longitudinal sides of the apparatuses. 
     FIG. 13 shows in diagrammatic cross-section a second exemplary embodiment of a purification and enrichment apparatus. In this case, the electrodes  20   a  and  20   b  of an apparatus according to FIG. 11 are connected to the power supply  220 . The apparatus according to FIG. 11 is situated in the area of action of the x,y,z pipetting arm  190  of the robot x,y,z pipettor. The power supply  220 , the second pump  130  for disposing of solutions to be discarded, an apparatus (not shown here) for moving a permanent magnet  312  and the robot x,y,z pipettor can be controlled fully automatically by a process computer, for example a personal computer. 
     The functioning of the described apparatuses is as follows: 
     Biological fluids which contain nucleic acids and are to be analyzed are brought into contact with the adsorption medium  100 . In the course of this contact, the nucleic acids present in the solution are adsorbed to the adsorption medium  100 . The nucleic-acid laden adsorption medium  100 , for example the spin column  90 , is inserted into the reaction compartment  17  through the second orifice  80 . A direct current voltage in the range from 1 to 5000 V, preferably from 25 to 500 V, is then applied to the electrodes  20   a,    20   b.  The negatively charged nucleic acids are detached as a result from the adsorption medium  100  and transported in the direction of the anode  20   b  arranged in the vicinity of the removal compartment  50 . In order to avoid a direct contact of the nucleic acids with the anode  20   b,  the first permeable membrane  30  which is impassable to nucleic acids is provided. On account of the motion of the nucleic acids directed toward the anode  20   b,  these accumulate in the removal compartment  50 . After an electrophoresis period of from 1 to 180 min, the current passed through the electrophoresis buffer is switched off. An elution volume comprising enriched nucleic acids can then be taken off through the removal orifice  60  of the removal compartment  50 . 
     In order to avoid contamination, the removal orifice  60  can be sealed with the snap-on cover  326  which is provided with the septum  328 . To remove elution volume, the septum  328  can be pierced by the needle  327 . 
     Depending on the type of nucleic acids to be isolated, differently formed electrodes  20   a,    20   b  can be used. The use of electrodes made from noble metal or conductive plastics, which electrodes can be coated, is suitable. 
     The apparatus according to the invention can be combined with a device for detecting chemiluminescence. For this purpose, the photomultiplier  314  is arranged in the vicinity of the container  15 . The nucleic acids are first transported electrophoretically from the adsorption medium  100  toward the anode  20   b.  In the region of the anode  20   b,  an amplification of the nucleic acids, for example according to the polymerase chain reaction, can then be carried out. The amplified nucleic acids are then bound by addition of magnetic particles. By guiding the permanent magnet  312  to the anode  20   b,  the magnetic particles laden with nucleic acids are drawn to the anode  20   b.  After adding a chemiluminescence buffer and applying a voltage to the electrodes  20   a,    20   b,  a chemiluminescence is initiated. The light emitted in this process is detected by the photomultiplier  314 . 
     The abovementioned functions can be automated by a robot x,y,z pipettor. It is possible by this means to operate a multiplicity of the apparatuses according to the invention in succession automatically. 
     Nucleic acids can be isolated automatically using the purification and enrichment apparatuses shown in FIGS. 4 and 13. In this case, the following control program has proved to be expedient: 
     
       
         
               
               
               
             
               
               
               
             
           
               
                   
               
               
                 Step 
                 Equipment 
                   
               
               
                 No. 
                 module 
                 Working step 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 1 
                 x,y,z 
                 fetch pipette tip from store 185 
               
               
                   
                 pipettor 
               
               
                 2 
                 x,y,z 
                 go to sample vessel 165 
               
               
                   
                 pipettor 
               
               
                 3 
                 x,y,z 
                 take 210 μl of sample 
               
               
                   
                 pipettor 
               
               
                 4 
                 x,y,z 
                 go to reaction tube 150 
               
               
                   
                 pipettor 
               
               
                 5 
                 x,y,z 
                 dispense 200 μl 
               
               
                   
                 pipettor 
               
               
                 6 
                 x,y,z 
                 discard pipette tip 
               
               
                   
                 pipettor 
               
               
                 7 
                 x,y,z 
                 fetch pipette tip from store 185 
               
               
                   
                 pipettor 
               
               
                 8 
                 x,y,z 
                 go to first vessel 160 
               
               
                   
                 pipettor 
               
               
                 9 
                 x,y,z 
                 take 710 μl of lysis reagent 
               
               
                   
                 pipettor 
               
               
                 10 
                 x,y,z 
                 go to reaction tube 150 
               
               
                   
                 pipettor 
               
               
                 11 
                 x,y,z 
                 dispense 700 μl of lysis reagent 
               
               
                   
                 pipettor 
               
               
                 12 
                 x,y,z 
                 discard pipette tip 
               
               
                   
                 pipettor 
               
               
                 13 
                 thermomixer 
                 shake for 1 min 
               
               
                 14 
                 thermomixer 
                 heat to 75° C. 
               
               
                 15 
                 controller 
                 wait 10 min 
               
               
                 16 
                 thermomixer 
                 cool to 25° C. 
               
               
                 17 
                 x,y,z 
                 fetch pipette tip from store 185 
               
               
                   
                 pipettor 
               
               
                 18 
                 x,y,z 
                 go to reaction tube 150 
               
               
                   
                 pipettor 
               
               
                 19 
                 x,y,z 
                 take 810 μl of lysis mixture 
               
               
                   
                 pipettor 
               
               
                 20 
                 x,y,z 
                 go to second opening 80 
               
               
                   
                 pipettor 
               
               
                 21 
                 x,y,z 
                 dispense 800 μl of lysis mixture 
               
               
                   
                 pipettor 
               
               
                 22 
                 x,y,z 
                 discard pipette tip 
               
               
                   
                 pipettor 
               
               
                 23 
                 pump (130) 
                 pump lysis mixture through adsorption 
               
               
                   
                   
                 medium and discard 
               
               
                 24 
                 x,y,z 
                 fetch pipette tip from store 185 
               
               
                   
                 pipettor 
               
               
                 25 
                 x,y,z 
                 go to second vessel 162 
               
               
                   
                 pipettor 
               
               
                 26 
                 x,y,z 
                 take 710 μl of wash reagent 
               
               
                   
                 pipettor 
               
               
                 27 
                 x,y,z 
                 go to second opening 80 
               
               
                   
                 pipettor 
               
               
                 28 
                 x,y,z 
                 dispense 700 μl of wash solution 
               
               
                   
                 pipettor 
               
               
                 29 
                 x,y,z 
                 discard pipette tip 
               
               
                   
                 pipettor 
               
               
                 30 
                 second pump 
                 pump wash solution through adsorption 
               
               
                   
                 130 
                 medium and discard 
               
               
                 31 
                 first pump 
                 pump electrophoresis buffer into the 
               
               
                   
                 120 
                 tank 
               
               
                 32 
                 x,y,z 
                 fetch pipette tip from store 185 
               
               
                   
                 pipettor 
               
               
                 33 
                 x,y,z 
                 go to electrophoresis buffer 
               
               
                   
                 pipettor 
                 reservoir 110 
               
               
                 34 
                 x,y,z 
                 take 250 μl of electrophoresis buffer 
               
               
                   
                 pipettor 
               
               
                 35 
                 x,y,z 
                 go to second opening 80 
               
               
                   
                 pipettor 
               
               
                 36 
                 x,y,z 
                 discard pipette tip 
               
               
                   
                 pipettor 
               
               
                 37 
                 power supply 
                 apply voltage to electrodes 20a, 20b 
               
               
                   
                 220 
               
               
                 38 
                 controller 
                 wait 20 min 
               
               
                 39 
                 x,y,z 
                 fetch pipette tip from store 185 
               
               
                   
                 pipettor 
               
               
                 40 
                 x,y,z 
                 take 60 μl of isolated nucleic acid 
               
               
                   
                 pipettor 
                 from removal orifice 60 
               
               
                 41 
                 x,y,z 
                 go to PCR vessels 210 
               
               
                   
                 pipettor 
               
               
                 42 
                 x,y,z 
                 dispense 50 μl into PCR vessels 210 
               
               
                   
                 pipettor 
               
               
                 43 
                 x,y,z 
                 discard pipette tip 
               
               
                   
                 pipettor 
               
               
                 44 
                 second pump 
                 pump electrophoresis buffer from the 
               
               
                   
                 130 
                 tank and discard 
               
               
                   
               
             
          
         
       
     
     EXAMPLE 1 
     Work-up of a Whole Blood Sample with Spin Column and Electrophoresis 
     All reagents are taken from the QIAamp™Blood Kit (Cat. No. 29104) from Qiagen, Hilden. After lysis and adsorption of the nucleic acid, in accordance with the manufacturer&#39;s procedure, the glass fiber fleece was taken out of the QIAamp spin column and placed in a specially prepared flat bed agarose gel in accordance with FIG.  5 . The first recess  81  serves for holding the glass fleece and the second recess  61  is filled with electrophoresis buffer. In this manner, the nucleic acid can be eluted from the glass fleece electrophoretically and transferred into the subsequent agarose gel and the second recess  61 . The isolated concentrated nucleic acid was removed from the second recess  61 . 
     EXAMPLE 2 
     Work-up of a Plasma Sample 
     All reagents are taken from the QIAamp™Blood Kit (Cat. No. 29104) from Qiagen, Hilden. For the work-up, the glass fiber fleece was removed from the QIAamp spin column and inserted into the apparatus according to FIG. 1 in such a manner that it was positioned at the bottom outlet. The volume of the entire reaction vessel was 2 ml. 200 μl of plasma were processed in accordance with the manufacturer&#39;s operating instructions. Instead of centrifugation, suction using an Eppendorf diaphragm pump was used. For the electrophoretic elution, an electrophoresis buffer described by Andrews A. T. (Andrew A. T.: Electrophoresis, Clarendon Press, Oxford, 1985, p. 160) was used. The permeable membrane used was dialysis tubing from Neolab, Heidelberg (catalogue No.: 2-9022). As electrodes  20   a,    20   b,  use was made of wires 0.3 mm in diameter of a platinum/ruthenium alloy and as a power source, the electrophoresis power source from Hölzel, Dorfen, was used. 30 μl of elution volume containing the nucleic acid were removed from the removal orifice  60 . 
     EXAMPLE 3 
     Isolation of DNA from Chicken Blood 
     Whole blood was collected from the carotid artery from a freshly slaughtered white fattening chicken and immediately admixed with ethylenediaminetetraacetic acid (Sigma, Munich, catalogue No. E-5513) at a concentration of 0.06 g of EDTA/ml of whole blood. The EDTA/whole blood was frozen in portions and stored at −15° C. All the reagents are taken from the “High Pure PCR Template Preparation Kit” from Boehringer Mannheim (catalogue No. 1 796 828). 100 μl of EDTA/whole blood (see above) were mixed with 200 μl of lysis buffer and 60 μl of proteinase K, in each case from the abovementioned reagent set, and incubated for 15 min at 70° C. After cooling to room temperature, 100 μl of isopropanol (Roth, Karlsruhe, catalogue No. 9866) are added and the mixture is shaken vigorously. The viscous reaction mixture is then sucked through the glass fleece using a vacuum pump (Eppendorf, Hamburg, No. 4151). The fleece was then washed five times with 500 μl of wash buffer (from kit, see above) containing 80% ethanol (Roth, Karlsruhe, catalogue No. 5054). The fleece was then removed from the filter tube and transferred into an apparatus according to FIG. 5, into the first recess  81 . Approximately 0.5 ml of electrophoresis buffer (10 mM tris-HCl [Sigma, Munich catalogue No. T-8529] 5 mM sodium acetate [Sigma, Munich catalogue No. S-3272] 0.5 mM EDTA [see above] pH 8.2) were then pipetted onto the fleece into the first recess  81  which buffer had previously been heated to 70° C. Thereafter, the electroelution was performed by applying a direct current voltage of a maximum of 10 mA at approximately 60° C. The power supply used was an electrophoresis transformer from Hölzel, Dorfen (No. 0628/1985). The eluate was collected in fractions 1-7, after a defined time (10-15 min) fractions of approximately 50 μl being taken and collected from the orifice ( 61 ) using an Eppendorf pipette. The fractions were analyzed on an agarose gel (0.05 mg of agarose in 60 ml of electrophoresis buffer containing 40 μl of ethidium bromide solution (100 mg of ethidium bromide [Sigma, Munich No. E-8751] in distilled water)). 40 μl of lysis mixture were used as control. The control and fractions after electroelution for 15 min showed a fluorescent band after electrophoresis of 5 min at approximately 40 V and a maximum of 50 mA with illumination under a UV lamp from Roger Electronic Products (No. MD-1782GS). The power supply used was an electrophoresis transformer from Hölzel, Dorfen (No. 0628/1985). 
     EXAMPLE 5 
     Production of a Coated Electrically Conductive Plastic Electrode (FIG. 9) 
     Biotinylated bovine immunoglobulin G (B-IgG) was first prepared. For this purpose, 0.5 ml of a B-IgG solution (2 mg-of B-IgG [Boehringer Mannheim Cat. No. 1293621103] in 1 ml of PBS (NaH 2 PO 4 .1H 2 O 2.76 g/l; NA 2 HPO 4 .2H 2 O 3.56 g/l; NaCl 8 g/l; pH 7.25)) was mixed with 6 μl of D-biotinoyl-ε-aminocaproic acid N-hydroxysuccinimide ester solution in PBS and DMSO (batch in accordance with Biotin Labeling Kit from Boehringer Mannheim catalogue No. 1418165) and stirred for 2.5 h at room temperature on a magnetic stirrer and then allowed to stand overnight. The molar ratio of biotin:B-IgG is 20:1 in this batch. 
     To coat electrically conductive plastic with biotinylated B-IgG, disks of 4 mm in diameter were cut from a blank piece produced in the injection molding process from PRE-ELEC TP 4474 (Premix Oy, Finland), placed in a well of an uncoated microtiter plate and washed three times in a solution of 0.2 ml of coating buffer (NaHCO 3  4.2 g/l; pH 9.6), then in a solution of 40 ml of coating buffer (NAHCO 3  4.2 g/l; pH 9.6) and 6 μl of B-IgG biotin solution. Coating was performed overnight. 
     The disks are then washed three times each time with 100 ml of milli-Q water, the solid and liquid phases being separated by sedimentation or centrifugation. The disks are then taken up in 40 ml of PBS again. 
     EXAMPLE 6 
     Performing a Sample Preparation with Electroelution, Amplification and Electrochemiluminescence Measurement for Detection of Material Amplified by PCR 
     The apparatus shown in FIG. 14, to carry out the isolation, amplification and chemiluminescence measurement, was automatically controlled by a computer program having the following program steps: 
     
       
         
               
               
             
           
               
                   
               
               
                 Process modules 
                   
               
               
                 Sample preparation 
                 Individual steps 
               
               
                   
               
             
             
               
                 Lysis 
                 pipette sample, lysis mixture, 
               
               
                   
                 proteinase K into reaction compartment 17 
               
               
                   
                 close reaction compartment 17 
               
               
                   
                 heat reaction compartment 17 to 70° C. 
               
               
                   
                 cool reaction compartment 17 to room 
               
               
                   
                 temperature 
               
               
                   
                 open reaction compartment 17 
               
               
                   
                 add isopropanol 
               
               
                   
                 draw off reaction mixture from reaction 
               
               
                   
                 compartment 17 by suction through second 
               
               
                   
                 nozzle 85 
               
               
                 Electroelution 
                 add elution buffer 
               
               
                   
                 apply voltage to electrodes 20a, 20b 
               
               
                   
                 nucleic acid migrates into the removal 
               
               
                   
                 compartment 50 
               
               
                 Amplification 
                 addition of PCR mix to the removal 
               
               
                   
                 compartment 50 
               
               
                   
                 closure of the second nozzle 85, second 
               
               
                   
                 orifice 80 and removal orifice 60 
               
               
                   
                 cyclic heating and cooling of the 
               
               
                   
                 removal compartment 50 
               
               
                 Denaturation 
                 opening the removal orifice 60 
               
               
                 Probe annealing 
                 addition of RU probe 
               
               
                   
                 closure of removal orifice 60 
               
               
                   
                 heating and cooling of the removal 
               
               
                   
                 compartment 50 
               
               
                 Detection 
                 opening removal orifice 60 
               
               
                   
                 addition of SA magnetic particles 
               
               
                   
                 through removal orifice 60 
               
               
                   
                 closure of removal orifice 60 
               
               
                 Magnetic 
                 applying permanent magnet 312 with 
               
               
                 separation 
                 magnetic field for the removal 
               
               
                   
                 compartment 50 
               
               
                   
                 drawing off reaction mixture from the 
               
               
                   
                 removal compartment 50 by suction 
               
               
                 Wash magnetic 
                 addition of wash solution through 
               
               
                 particles (option) 
                 removal orifice 60 
               
               
                   
                 removal of the magnetic field for the 
               
               
                   
                 removal compartment 50 
               
               
                   
                 drawing off the wash solution by suction 
               
               
                   
                 through the second nozzle 85 
               
               
                   
                 addition of assay buffer through removal 
               
               
                   
                 orifice 60 
               
               
                 Electro- 
                 applying voltage to the electrodes 20a,b 
               
               
                 chemiluminescence 
               
               
                 measurement 
               
               
                   
                 luminescence measurement by 
               
               
                   
                 photomultiplier 314 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
             
           
               
                   
               
               
                 List of designations 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 10 
                 electrophoresis buffer tank 
               
               
                 11 
                 flat bed agarose gel 
               
               
                 15 
                 container 
               
               
                 17 
                 reaction compartment 
               
               
                 20a 
                 cathode 
               
               
                 20b 
                 anode 
               
               
                 30 
                 first permeable membrane 
               
               
                 31 
                 second permeable membrane 
               
               
                 40 
                 O-ring 
               
               
                 41 
                 first nozzle 
               
               
                 42 
                 first orifice 
               
               
                 43 
                 breakthrough 
               
               
                 44 
                 second nozzle 
               
               
                 45 
                 third nozzle 
               
               
                 46 
                 third orifice 
               
               
                 49 
                 channel 
               
               
                 50 
                 removal compartment 
               
               
                 60 
                 removal orifice 
               
               
                 61 
                 second recess 
               
               
                 70 
                 filling level 
               
               
                 80 
                 second orifice 
               
               
                 81 
                 first recess 
               
               
                 85 
                 second nozzle 
               
               
                 90 
                 spin column 
               
               
                 100 
                 adsorption medium 
               
               
                 110 
                 electrophoresis buffer reservoir 
               
               
                 120 
                 first pump 
               
               
                 125 
                 filling port 
               
               
                 130 
                 second pump 
               
               
                 140 
                 outlet line 
               
               
                 150 
                 reaction tube 
               
               
                 160 
                 first vessel 
               
               
                 162 
                 second vessel 
               
               
                 165 
                 sample vessel 
               
               
                 170 
                 shaker frame 
               
               
                 180 
                 pipette tip 
               
               
                 185 
                 store of pipette tips 
               
               
                 190 
                 x,y,z pipetting arm 
               
               
                 210 
                 PCR vessels 
               
               
                 220 
                 power supply 
               
               
                 225a,b 
                 electrical leads 
               
               
                 302 
                 support fleece 
               
               
                 303 
                 further support fleece 
               
               
                 310 
                 semipermeable membrane 
               
               
                 312 
                 permanent magnet 
               
               
                 313 
                 magnetic particles 
               
               
                 314 
                 photomultiplier 
               
               
                 316 
                 transparent snap-on cover 
               
               
                 318 
                 tubing piece 
               
               
                 320,321 
                 recesses 
               
               
                 323 
                 first layer 
               
               
                 324 
                 third layer 
               
               
                 325 
                 second layer 
               
               
                 326 
                 snap-on cover 
               
               
                 327 
                 needle 
               
               
                 328 
                 septum 
               
               
                 329 
                 heating plates 
               
               
                 340 
                 stopper 
               
               
                 400 
                 cover 
               
               
                 401 
                 vacuum connection 
               
               
                 402 
                 connections 
               
               
                 410 
                 multiple compartment container