EP1807208B1 - Arrangement for integrated and automated dna or protein analysis in a single-use cartridge, method for producing such a cartridge and operating method for dna or protein analysis using such a cartridge - Google Patents

Description

Arrangement for integrated and automated DNA or protein analysis in a single-use cartridge, production method for such a cartridge and operating method of DNA or protein analysis using such a cartridge

The invention relates to an assembly for integrated and automated DNA or protein analysis in a disposable cartridge. Cartridge is a flat card in credit card format. In addition, the invention relates to the production of such a cartridge. Finally, the invention also relates to an operational method for DNA or protein analysis using such a cartridge.

For nucleic acid analysis, for example for the analysis of white blood cells from whole blood, in order to answer human-genomic questions, the cells must first be broken open in a first station as a sample preparation step and then the DNA released in the process must be isolated. In a second station, a PCR (Polymerase Chain Reaction = polymerase chain reaction) for selective DNA amplification (amplification), in order to increase the concentration of the DNA to be detected so far that it can be detected in a third station.

In the laboratory, the latter sub-processes are carried out separately according to the known state of the art. The three stations explained above each involve several work steps and are performed independently of each other with different devices. The individual steps are largely manual.

The realization of these steps is the presence of laboratory equipment - such as a cell disruption apparatus, a PCR device (so-called Thermocycler), possibly a PCR device, which is for quantitative PCR is suitable, an electrophoresis apparatus, a hybridization station, an optical reader, so-called Eppendorf Tubes, several pipetting devices and a cooling container for reagents - depending and must od trained personnel in compliance with safety regulations regarding risk of infection, waste disposal od . be performed. In particular, multiple volumetric, ie accurate, dosages (pipetting) of reagent solutions must be performed. Such steps are time consuming and costly.

Devices for biochemical analysis are known from the prior art, which correspond to the WO 02/073153 A1 Use of particular silicon-based measurement modules, which can be integrated into a chip card. It will be in accordance with the WO 02/072262 A1 already integrated the reagents used for the analysis in dry stored form in the analysis module.

• Eine vollständige Integration aller Stoffe (evtl. außer Wasser) in einer geschlossenen einmal verwendbaren Cartridge;
• eine Bevorratung der Reagenzien in einer bei Raumtemperatur lagerstabilen Form;
• eine automatische Durchführung aller Prozesse in der Cartridge;
• keine manuellen Arbeitsschritte, außer Injektion der zu analysierenden Probe, z.B. Blut;
• Kein direkter Kontakt mit gesundheitsgefährdenden Stoffen (Blut und Reagenzien-Abfall verbleiben in der Cartridge);
• Cartridge-Geometrie erlaubt eine effiziente und schnelle Thermozyklisierung;
• alle Detektionsvorgänge sollen elektrisch ablaufen und einfach auszulesen sein;
• die verwendete Cartridge ist klein und kostengünstig herzustellen.

On this basis, the object of the invention is the realization of a low-cost, easy-to-handle, complete DNA or protein analysis process in a miniaturized cartridge. In particular, the following improvements should be realized compared to the laboratory method:

• A complete integration of all substances (possibly water) in a closed single-use cartridge;
• storage of the reagents in a storage-stable form at room temperature;
• an automatic execution of all processes in the cartridge;
• no manual operations, except injection of the sample to be analyzed, eg blood;
• No direct contact with harmful substances (blood and reagent waste remain in the cartridge);
• Cartridge geometry allows efficient and fast thermocycling;
• all detection processes should be electrical and easy to read out;
• The cartridge used is small and inexpensive to manufacture.

The object is achieved by an arrangement with a cartridge according to claim 1. The production of such a cartridge is the subject of claim 33. Operating methods with such cartridges are the subject of the independent claims 37 and 41. In this case, claim 37 is directed to the DNA analysis and claim 41 to the protein analysis. Further developments of the arrangement, the manufacturing method and the operation in the analysis are given in the respective subclaims.

The invention is particularly of the WO 02/072262 A1 and the further prior art mentioned there. There, an analysis device is described with dry-stored in fluid channels, stable at room temperature reagents, which are brought into solution by supplying water shortly before their intended use. The invention continues from the unpublished DE 10 2004 021780 A1 and the not pre-published DE 10 2004 021822 A1 out. In addition, it is also known to use specially electrically readable detection modules.

In contrast, the subject of the invention is such a disposable cartridge with a system of microchannels and / or microcavities for a given process flow after sample taking, the cartridge has structures for receiving the dry reagents and these structures means for performing both the cell disruption on the one hand and the PCR on the other , but also associated with electrochemical detection. In particular, the channels have different, problem-adapted structures. Especially the digestion channel advantageously has stepped cross-section for optimal wetting with the dry reagent, while the PCR chamber and Elisa reagent channels have well-shaped wells.

It can thus be achieved that in a procedure the supply and preparation of the sample, the DNA amplification and the actual detection of the DNA is possible.

• Die im Mikrokanal bzw. in der Mikrokavität eingebrachten Reagenzien sind trockenbare Substanzen mit vernachlässigbarem Dampfdruck. Durch die bei Raumtemperatur stabilen Substanzen bleiben deren Eigenschaften für Zellaufschluss und/oder PCR und/oder Detektion erhalten. Dabei können Gemische aus den Substanzen mit Hilfsstoffen Dünnfilme bilden und können die Gemische mit dünnen Paraffinschichten wasserdicht abgedeckt sein.

The system according to the invention of the geometric structures in the microchannels or microcavities for receiving dry reagents results in suitable boundary conditions for DNA analysis on the one hand and protein analysis on the other hand. The following features and measures are essential:

• The reagents incorporated in the microchannel or in the microcavity are dryable substances with negligible vapor pressure. The substances which are stable at room temperature retain their properties for cell disruption and / or PCR and / or detection. In this case, mixtures of the substances with auxiliary substances can form thin films and the mixtures can be covered with thin paraffin layers in a watertight manner.

• einfache und präzise Applikation der Reagenzien bei der Herstellung der Cartridge
• Schutz der Reagenzien beim Befüllen der Reagenzkanäle, d.h. die Reagenzien werden durch einen sog. Wasserflow nicht weggespült, sondern bleiben beim Füllen des gesamten Kanals erhalten. Erst nach dem Befüllen des Kanals lösen sich die Reagenz-Spots über Diffusionsvorgänge auf und es entsteht eine homogene Reagenzlösung.

In the invention, the reagents and auxiliaries are already introduced into depressions of the cartridge channels 4 during the production of the cartridge as dry substances. This results in the following advantages:

• simple and precise application of the reagents during the production of the cartridge
• Protection of the reagents during filling of the reagent channels, ie the reagents are not washed away by a so-called water flow, but are retained when filling the entire channel. Only after filling the channel, the reagent spots dissolve via diffusion processes and there is a homogeneous reagent solution.

In another particular embodiment, the wells are located at predefined intervals along the reagent channel. The distances can be equidistant or be arranged particularly advantageous in variable spacing patterns.

The depressions may advantageously be filled with variable amounts of dry reagent. Through the combination of different dry reagent quantities and well spacing patterns, the desired concentration profiles of the final reagent solutions can be adjusted.

For certain functions, such as Cell disruption in the presence of magnetic beads and lysis reagents is a uniform distribution of the insoluble components, i. of the beads, in dry reagent required. For this purpose, the magnetic beads are dispensed as a suspension in the lysis channel. Upon evaporation of the solvent, it is observed that the beads retreat into the peripheral areas of the lysis channel and thus an even distribution is not present. By stepwise structuring of the lysis channel cross-section, the magnetic beads spread over the steps and a uniform distribution is achieved.

In order that cell disintegration, PCR and a so-called DNA / protein ELISA test can be carried out in the same way with the cartridge according to the invention, it is advantageous that substrates with DNA-binding properties, in particular the DNA-binding properties, are present in the microchannels or microcavities Magnetic beads are present. The lysis reagents and the magnetic beads may be contained together in a single dry matrix. Furthermore, the reagents for an ELISA assay are also present in the card. Specifically, two reagents are required for the ELISA assay, i. the first reagent is a label enzyme and the second reagent is an enzyme substrate.

In particular, a detection module for the electrical detection of the hybridization processes is arranged in the cartridge. The detection module advantageously consists of a precious metal / plastic composite or a semiconductor-processed Silicon chip with precious metal electrodes. In particular, electrochemical, magnetic or piezoelectric measuring methods are suitable for electrical detection.

In particular, an input port for a whole blood sample is available for use of the invention of the cartridge according to the invention. Furthermore, there are means for supplying water, for example inflow ports for connection to an external water supply or an integrated water reservoir. In the microchannels or microcavities dry buffer substances have defined ionic strength after the water supply.

When applying the invention for the analysis of white blood cells from whole blood means are advantageously present for mixing a whole blood sample with water or a buffer solution. In this case, means for flowing through the lysis / bead / reagent coated microchannel or microcavity with blood or blood / water or blood / buffer mixtures are present.

For the PCR to be carried out in the cartridge according to the invention, especially for DNA analysis, there are also means for generating a magnetic field for fixing the DNA / magnetic bead complex in a PCR cavity. For this purpose, the PCR cavity must be suitably sealed and must have means for thermal cycling.

Finally, with the cartridge of the present invention, it is essential that there are means for storing spent sample material and spent reagents that form waste reservoirs. In this case, the means for germ-proof, cell or particle-free ventilation of at least one waste reservoir must be suitable. To read the cartridge in a reading device, which is not the subject of the invention, finally, means for fixing the cartridge must be present.

Figur 1

eine Cartridge mit einer Übersicht über einzelne Mikrokanal-/ Kavitäten-Systeme mit den zugehörigen Funktionsbezeichnungen,

Figur 2

die Draufsicht auf einen Zellaufschlusskanal,

Figur 3

den Querschnitt durch den Zellaufschlusskanal gemäß Figur 5,

Figur 4

zwei Alternativen des Durchflusskanalquerschnittes in vergrößerter Darstellung,

Figur 5

die Draufsicht auf die PCR-Kammer in Figur 1,

Figuren 6

und 7 den Querschnitt durch die PCR-Kammer gemäß Figur 5,

Figur 8

die Draufsicht auf einen ELISA-Reagenzkanal in Figur 1,

Figuren 9, 10

den Querschnitt des ELISA-Reagenzkanals gemäß Figur 8 sowie die

Figuren 11 bis 23

die Draufsicht auf die Cartridge gemäß Figur 1 in verschiedenen Verfahrenszuständen während einer automatisierten Auswertung.

Further details and advantages of the invention will become apparent from the following description of exemplary embodiments with reference to the drawing in conjunction with the claims. They show in a schematic representation

FIG. 1

a cartridge with an overview of individual microchannel / cavity systems with the associated function names,

FIG. 2

the top view of a cell disruption channel,

FIG. 3

the cross section through the Zellaufschlusskanal according to FIG. 5 .

FIG. 4

two alternatives of the flow channel cross-section in an enlarged view,

FIG. 5

the top view of the PCR chamber in FIG. 1 .

FIGS. 6

and Figure 7 shows the cross-section through the PCR chamber according to FIG. 5 .

FIG. 8

the top view of an ELISA reagent channel in Figure 1,

FIGS. 9, 10

the cross-section of the ELISA reagent channel according to FIG. 8 as well as the

FIGS. 11 to 23

the top view of the cartridge of Figure 1 in various process states during an automated evaluation.

In the figures, identical or equivalent elements have the same reference numerals. especially the FIGS. 1 to 10 on the one hand and the FIGS. 11 to 23 On the other hand, they are described together.

In FIG. 1 For example, a cartridge 100 for an ELISA ("Enzyme Linked Immuno Sorbent ASSAY") test is shown with an elevational view of the microchannel or cavity system present therein, wherein for the sake of clarity the associated function designations are additionally designated. The cartridge 100 consists in detail of a plastic base 101 with there introduced fluidic structures that are covered by a Kunstofffie. The structures are based on the FIGS. 2 to 10 described below.

From the top view FIG. 1 is a sample port 102 with adjoining dosing 105, on the defined liquid samples for particular nucleic acid analysis, for example, for the analysis of white blood cells from whole blood, can be introduced to answer human genomic issues, can be seen. This is followed by a channel region 110 for the cell disruption of the sample, and further, specifically for one of the DNA analyzes, a region 120 for a PCR (Polymerase Chain Reaction) for selective DNA amplification to increase the concentration to increase the DNA to be detected so far that it can be detected in a third station. The actual PCR chamber is closed by valves 122, 122 '. The detection of the thus prepared sample, in particular according to the ELISA method, then takes place in the region 130.

Out FIG. 1 Furthermore, water ports 103 to 103 "'can be seen, and water can be introduced as a transport and solvent into the Cartridge 100 during the preparation of a sample, as well as vent ports 104 to 104"'.

In particular, as mentioned, the cartridge 100 has an input port 102 for a whole blood sample. For this purpose, means for supplying water are present. There may be an inflow port for connection to an external water supply or the inflow port may be connected to an integrated water reservoir.

The microchannels or microcavities 101 to 131 are normally filled with dry buffer substances which ensure a defined ionic strength after the supply of water. For the blood analysis are means for mixing whole blood sample and water or the buffer solution and / or means for flowing through a microsphere coated with a lysis bead reagent or the microcavity with blood or with blood-water or blood-buffer mixture available.

In the channel system, wide areas 106, 107, 108, 109 are provided as reservoirs for receiving waste ("waste"). In addition, there is an area with channels 131 and 131 'for receiving different ELISA reagents.

In the FIGS. 2 to 4 In each case, reference numeral 101 again denote the cartridge base body. The body contains, especially for a cell disruption ("lysis"), a specially shaped flow channel 111 with stepped recesses 112 formed by the side edges for receiving dry reagents. The depressions 112 have several steps with step heights of 10 to 500 .mu.m and have an extension of about 1 mm and a depth of about 100 microns.

Especially in the illustration according to the FIG. 4a results in the alternative possibility, in a flow channel without additional recesses to provide for the inclusion of the lysis reagents only in the region 113 of the edges of the flow channel 111. In FIG. 4b On the other hand, reagents of this kind, which in particular also contain magnetic beads for binding the released DNA, are distributed uniformly between the steps 112 via the flow channel 111. Magnetic beads have DNA- and protein-binding properties, provided that they have been pretreated accordingly. They may interfere with DNA-binding properties. optionally also be coated with antibodies. For introducing dry substances as a matrix with lysis reagent and magnetic beads is especially on the older DE 10 2004 021780 A1 and the older one DE 10 2004 021822 referred to the applicant.

In the FIGS. 5 to 7 results in the structure of a PCR chamber 120 in the cartridge body 101 with gas stream passage 111. The valve assembly for completing the PCR chamber when used as intended is not shown here. It is essential that in the PCR chamber 120 round cylindrical recesses 124, 124 'for receiving specific reagents 127, 127 ', which are needed in carrying out the PCR, are present. Specially in FIG. 7 is shown that a dry storable, room temperature stable PCR reagent 127, 127 'is initially covered by a paraffin layer 128, 128'.

The proper implementation of the PCR with valve-controlled thermocyclization within a cartridge is described in detail in the parallel applications DE 10 2004 050576.4 and DE 10 2004 050510.1 Applicant described with the same application priority to which expressly referred to in the present context ("Incorporation by Reference"). In particular, it describes the use of magnetic beads for DNA binding and the concentration of the magnetic beads with the DNA in the PCR chamber 120 by means of controllable magnetic fields, which will not be discussed in detail here.

From the FIGS. 8 to 10 the structure and structure of the ELISA reagent channels 131 and 131 'are evident FIG. 1 , There are each cup-shaped wells 132 to 132 ^{6 '} present, which correspond to the intake of pre-dosed and pre-portioned amounts of reagents for the ELISA process FIG. 9 are suitable. This is in detail in the already mentioned as prior art WO 02/072262 A1 to which reference is expressly made in the present context ("Incorporation by Reference"). In FIG. 10 the circular cylindrical recesses 132-132 ⁶ shown filled ^'with dry reagents 133-133 ^6'. In this case, a first reagent realizes a labeling enzyme and a second reagent an enzyme substrate, as is known to be required in the hybridization of the optionally prepared by a PCR sample with specific capture probes. In the region 130 of the detection, which is indicated only schematically, different sensors for detecting biochemical reactions may be located in a module made of a precious metal / plastic composite. Especially in electrochemical measurements with semiconductor-processed chips, ie in particular silicon-based sensors, the signals electrically detected and processed immediately. In addition to electrochemical and magnetic and / or piezoelectric measuring methods with related sensors are possible.

In the FIGS. 11 to 23 is respectively the cartridge 100 according to FIG. 1 The cartridge 100 is inserted into an analyzer, which is not shown in detail in the figures and is not the subject of the present patent application.

1. a) Es wird ca. 10 µl Blut als Messprobe eingefüllt. Über die Dosierkapillare 105 wird 1 µl automatisch dosiert.
2. b) Das überschüssige Blut wird in den Leerraum 106 (Waste 1) gewaschen.
3. c) Anschließend werden 1 µl Blutprobe mit Wasser verdünnt und in den Zellaufschlusskanal 110 transferiert. Dort finden der Zellaufschluss (Lyse) der Blutzellen sowie das Binden der freigesetzten DNA an die Magnet-Beads statt.
4. d) Anschließend werden die Magnet-Beads in die PCR-Kammer transferiert und dort gesammelt. Es findet ein Waschvorgang statt, wobei die Waschlösung im Leerraum 107 (Waste 2) gesammelt wird.
5. e) Nunmehr ist der Waschvorgang abgeschlossen.
6. f) Anschließend werden die PCR-Kammerventile 122, 122' geschlossen und die PCR durchgeführt.
7. g) Während der PCR wird gleichermaßen der ELISA-Reagenzkanal 131, der das Enzymsubstrat enthält, mit Wasser gefüllt.
8. h) Gleichermaßen wird während der PCR der ELISA-Reagenz kanal 131', der das Label-Enzym enthält, mit Wasser gefüllt.
9. i) Nach der PCR werden die PCR-Kammerventile 122, 122' geöffnet und das PCR-Produkt wird über das Detektionsmodul 130 (in den Waste 3, Kanal 108) geleitet, wo die Hybridisierung mit den spezifischen Fängersonden erfolgt.
10. j) Der Enzym-Substrat-Kanal wird in den Abfallkanal 108 (Waste 3) entlüftet.
11. k) Der Label-Enzym-Kanal wird in den Abfallkanal 108 (Waste 3) entlüftet.
12. l) Die Label-Enzym-Lösung fließt über das Detektionsmodul 130 zum Labeln in den Abfallbereich 109 (Waste 4).
13. m) Die Enzym-Substrat-Lösung fließt über das Detektionsmodul 130 zur enzymatisch-elektrochemischen Detektion der Hybridisierung in den Abfallbereich 109 (Waste 4).

The evaluation is illustrated below with reference to eleven concrete method sub-steps a) to m) after the cartridge has been inserted into an evaluation device with means for receiving the cartridge and the evaluation device is activated with the cartridge fixed therein. With reference to Figur1 The following sub-steps result in detail:

1. a) About 10 μl of blood is added as a test sample. 1 μl is dosed automatically via the dosing capillary 105.
2. b) The excess blood is washed into the void 106 (Waste 1).
3. c) Subsequently, 1 μl of blood sample is diluted with water and transferred into the cell disruption channel 110. There, the cell disruption (lysis) of the blood cells and the binding of the liberated DNA to the magnetic beads take place.
4. d) Subsequently, the magnetic beads are transferred to the PCR chamber and collected there. There is a washing process, wherein the washing solution in the void 107 (Waste 2) is collected.
5. e) Now the washing process is completed.
6. f) Subsequently, the PCR chamber valves 122, 122 'are closed and the PCR is performed.
7. g) Similarly, during the PCR, the ELISA reagent channel 131 containing the enzyme substrate is filled with water.
8. h) Similarly, during the PCR, the ELISA reagent channel 131 'containing the label enzyme is filled with water.
9. i) After the PCR, the PCR chamber valves 122, 122 'are opened and the PCR product is passed over the detection module 130 (into the waste 3, channel 108) where hybridization with the specific capture probes occurs.
10. j) The enzyme-substrate channel is vented into the waste channel 108 (waste 3).
11. k) The label enzyme channel is vented to waste channel 108 (waste 3).
12. l) The label enzyme solution flows into the waste area 109 (waste 4) via the labeling detection module 130.
13. m) The enzyme-substrate solution flows via the detection module 130 for enzymatic-electrochemical detection of the hybridization in the waste area 109 (Waste 4).

This concludes the analysis process. In particular, in an electrochemical detection, the resulting signals can be read out electrically and processor-based evaluated according to a predetermined program.

The basis of the FIG. 1 in detail described with channels and cavities cartridge is made of a polymer material, such as polycarbonate, for example by injection molding. In this case, the card base body 101 is initially produced with structures that are open at the top, and the reagents are spotted into the initially open channels or cavities and then dried. The detection module is suitably introduced into the cartridge, in particular glued. Finally, the channels and the cavities are provided, for example with an elastic film as the top cover and is thus completed for the intended use.

It is also possible that on the open card body 101 before the cover side completion and completion of the Cartridge certain special equipment, for example, as sealing materials and / or ventilation materials can be applied.

The concrete measuring method was based on the FIGS. 11 to 23 for a specific case of DNA analysis of a whole blood sample. It is generally intended to use the described cartridge for DNA analysis on the one hand and / or protein analysis on the other hand, wherein - as already mentioned above - a corresponding read-out device and associated evaluation algorithms are used. This results in defined operating methods which make the cartridges described in the examples only practical for decentralized use in the context of a medical "point of care" application.

• Aufgeben der Probe in Cartridge
• Einschieben der Cartridge in Auslesegerät,
• Starten des vollautomatischen Assays
  • Proben-Dosierung über Dosierstrecke
  • Waschen der Dosierstrecke
  • Verdünnen der Probe und Einbringen in Lyse-Kanal
  • Verweilen im Lyse-Kanal
  • Sammeln des DNA-Bead-Komplexes durch Beadsammler in der PCR-Kammer
  • Waschen des DNA-Bead-Komplexes mit Wasser
  • Verschließen der PCR-Kammer
  • Durchführung der PCR
  • Während der PCR: Füllen der beiden ELISA-Reagenzkanäle mit Wasser
  • Öffnen der PCR-kammer
  • Transport des PCR-Produkts in Detektionskammer
  • Hybridisierung in der Detektionskammer
  • Entlüften der beiden ELISA-Reagenzkanäle
  • Füllen und Spülen der Detektionskammer mit ELISA Reagenz 1
  • Füllen und Spülen der Detektionskammer mit ELISA-Reagenz 2
  • Durchführung der elektrochemischen Messungen.

Finally, especially for the DNA analysis, the integrated operating method of the cartridge described above in detail is summarized again as a combination or in the sequence of the individual substeps:

• Place the sample in cartridge
• Inserting the cartridge into the reader,
• Start the fully automatic assay
  • Sample dosing via dosing line
  • Washing the dosing section
  • Dilute the sample and place in lysis channel
  • Linger in the lysis channel
  • Collect the DNA Bead complex by bead collectors in the PCR chamber
  • Wash the DNA bead complex with water
  • Close the PCR chamber
  • Execution of the PCR
  • During the PCR: Fill the two ELISA reagent channels with water
  • Open the PCR chamber
  • Transport of the PCR product in detection chamber
  • Hybridization in the detection chamber
  • Vent the two ELISA reagent channels
  • Fill and rinse the detection chamber with ELISA reagent 1
  • Fill and rinse the detection chamber with ELISA reagent 2
  • Carrying out the electrochemical measurements.

In electrochemical measurements, the detection chamber is first flushed with an antibody solution carrying an enzyme label (ELISA reagent 1). Then, the rinsing of the detection chamber with enzyme substrate (ELISA reagent 2). The electrochemical measurements are carried out in a manner known per se at predeterminable, different temperatures and changeable flow rates of the enzyme-substrate solution.

For protein analysis, appropriate procedures are used, in which case the PCR does not apply.

Claims (43)

1. Arrangement for the integrated and automated DNA or protein analysis of a measurement sample in a single-use cartridge (card) filled with dried reagents, with the following features for the automatic performance in the cartridge of all measures necessary for the process analysis made up of individual component processes:

   - in the cartridge (100) a system of microchannels and/or of microcavities (101 to 131) for microfluidic process technology is present;

   - the microchannels or the microcavities (101 to 131) have predefined depressions to accommodate reagents, wherein

   - the reagents are stored ready in a storage-stable form at defined sites in the microchannels or the microcavities (101 to 131) of the cartridge (100);

   - means are present for making the dry-stored reagents available for the relevant component process in suitable form, in particular as a liquid reagent.
2. Arrangement according to Claim 1, characterized in that the depressions have at least one step with step heights of 10 to 500 µm.
3. Arrangement according to Claim 1, characterized in that the depressions have a length of ca. 1 mm and a depth of about 100 µm.
4. Arrangement according to Claim 2, characterized in that the depressions are cylindrical, wherein the length represents the diameter.
5. Arrangement according to one of the previous claims, characterized in that the reagents introduced into the micro-channels or into the microcavities (101 to 131) have the following properties:

   - they are dryable substances with negligible vapor pressure, which are stable at room temperature, so that the properties remain unchanged for one cell disintegration or one PCR or for the detection of biochemical quantities.
6. Arrangement according to Claim 5, characterized in that mixtures of the particular substance with additives form thin films which adhere to the walls.
7. Arrangement according to Claim 6, characterized in that the substances or mixtures introduced into parts of the micro-channels or microcavities (101 to 131) are watertightly covered with thin paraffin wax layers.
8. Arrangement according to one of the previous Claims 5-7, characterized in that the substances introduced into parts of the microchannels or microcavities (101 to 131) have DNA- or protein-binding properties.
9. Arrangement according to one of the previous Claims 5-8, characterized in that the substances introduced into parts of the microchannels or microcavities (101 to 131) are magnetic beads with specific binding properties.
10. Arrangement according to Claim 9, characterized in that the magnetic beads are coated with antibodies.
11. Arrangement according to Claim 9, characterized in that the magnetic beads are coated with DNA-binding substances.
12. Arrangement according to one of the previous Claims 9-11, wherein lysis reagents and magnetic beads are simultaneously present, characterized in that the lysis reagents and the magnetic beads are contained in a single dry matrix.
13. Arrangement according to one of the previous claims, characterized in that a so-called DNA ELISA assay or protein ELISA assay (130, 131) can be performed, wherein a label enzyme (reagent 1) and an enzyme substrate (reagent 2) are present as reagents for the ELISA assay (130, 131).
14. Arrangement according to one of the previous claims, characterized in that a detection module (130) for the electrical detection of the hybridization processes is present.
15. Arrangement according to Claim 14, characterized in that the detection module (130) consists of a noble metal/plastic composite.
16. Arrangement according to Claim 14, characterized in that the detection module consists of a semiconductor-processed silicon chip with noble metal electrodes.
17. Arrangement according to Claim 14, characterized in that electrochemical, magnetic and/or piezoelectric measurement methods are used as means for the electrical detection.
18. Arrangement according to one of the previous claims, characterized in that the cartridge (100) has an input port (102) for a whole blood sample.
19. Arrangement according to one of the previous claims, characterized in that means (103 to 103"') for the introduction of water, in particular an inlet port, is present.
20. Arrangement according to claim 19, characterized in that an inlet port for connection to an external water source is present.
21. Arrangement according to Claim 19, characterized in that the inlet port is connected to an integrated water reservoir.
22. Arrangement according to one of the previous claims, characterized in that the microchannels or microcavities (101 to 131) are filled with dry buffer substances of defined ionic strength after addition of water.
23. Arrangement according to one of the previous claims, characterized in that means for the mixing of whole blood samples and water or the buffer solution are present.
24. Arrangement according to one of the previous claims, characterized in that means for passing blood or blood-water or blood-buffer mixture through the microchannel or microcavity coated with lysis bead reagent are present.
25. Arrangement according to one of the previous claims, characterized in that means for generating a magnetic field for the purpose of immobilizing the DNA/magnetic bead or protein/ magnetic bead complex are present.
26. Arrangement according to one of the previous claims, characterized in that means for generating a magnetic field for the purpose of immobilizing the DNA/magnetic bead complex in a PCR cavity are present.
27. Arrangement according to Claim 26, characterized in that means for closure of the PCR cavity are present.
28. Arrangement according to one of the previous claims, characterized in that means for the thermocycling of the sample are present.
29. Arrangement according to one of the previous claims, characterized in that in the cartridge (card) means for the storage of used sample material and/or used reagents are present.
30. Arrangement according to claim 29, characterized in that the means for the storage of used sample material and/or used reagents constitute waste reservoirs.
31. Arrangement according to Claim 30, characterized in that means for the germproof, particle- or cell-free venting of the waste reservoirs are present.
32. Arrangement according to one of the previous claims, characterized in that means for the immobilization of the cartridge in a reading device are present.
33. Method for the production of a cartridge used in the arrangement according to Claim 1 or one of Claims 2 to 32, with the following process steps:

    - a cartridge base with channels and/or cavities is made from polymer,

    - reagents are spotted into the open channels, which comprise geometric structures in the form of depressions, and dried there,

    - the channels and/or cavities are closed with a film.
34. Production method according to Claim 33, characterized in that the card base is produced by injection molding technology.
35. Production method according to Claim 33, characterized in that special materials, such as for example sealing membranes, venting membranes or the like are applied onto the card body.
36. Production method according to Claim 33, characterized in that, before the sealing of the card body, a detection module with measurement devices is introduced, in particular glued in.
37. Operating method for DNA analysis in an arrangement according to Claim 1 or in one of Claims 2 to 32, with the following measures:

    - introduction of the sample into the cartridge,

    - insertion of the cartridge into a reading device,

    - starting of the fully automatic assay.
38. Operating method according to Claim 37, with the following steps during operation of the fully automatic assay:

    - sample dispensing takes place via a dispensing section,

    - the dispensing section is washed,

    - the measurement sample is diluted and introduced into the lysis channel,

    - by residence in the lysis channel, a cell disintegration takes place,

    - the DNA-bead complex formed is carried into the PCR chamber by a liquid flow and held in the PCR chamber by means of a bead collector,

    - a washing of the DNA-bead complex with water takes place,

    - the PCR chamber is closed,

    - the PCR is performed,

    - after completion of the PCR, the PCR product is transported into the detection chamber,

    - hybridization processes with specific capture probes take place in the detection chamber,

    - the flushing of the detection chamber with labeling enzyme takes place,

    - the flushing of the detection chamber with enzyme substrate takes place,

    - the electrochemical measurements are performed,

    - the electrochemical measurements are performed at various temperatures and various flow rates of the enzyme-substrate solution.
39. Operating method according to Claim 38, characterized in that during the PCR the ELISA reagent channels are filled with water.
40. Operating method according to Claim 38, characterized in that after the hybridization both ELISA channels are vented, that next the detection chamber is firstly flushed gas bubble-free with the first ELISA reagent and then flushed gas bubble-free with the second ELISA reagent, and that the electrochemical measurement is then performed.
41. Operating method for protein analysis in an arrangement according to Claim 1 or in one of Claims 2 to 32, with the following measures:

    - introduction of the sample into the cartridge,

    - insertion of the cartridge into a reading device,

    - starting of the fully automatic assay.
42. Operating method according to Claim 41, with the following steps during operation of the fully automatic assay:

    - sample dispensing takes place via a dispensing section,

    - the dispensing section is washed,

    - the measurement sample is diluted and transported into the detection chamber by a liquid flow,

    - binding processes between the proteins of the measurement sample and specific capture antibodies or capture proteins take place in the detection chamber,

    - the flushing of the detection chamber with an antibody solution bearing an enzyme label (ELISA reagent 1) takes place,

    - the flushing of the detection chamber with enzyme substrate (ELISA reagent 2) takes place,

    - the electrochemical measurements are performed.
43. Operating method according to Claim 42, characterized in that after the hybridization both ELISA channels are vented, that next the detection chamber is firstly flushed gas bubble-free with the first ELISA reagent and then flushed gas bubble-free with the second ELISA reagent, and that the electrochemical measurement is then performed.

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