DE202007007706U1 - Measuring device for the quantitative photometric detection of biomolecules in the low density range (low-density biochips) - Google Patents

Abstract

Measuring device for the automated quantitative photometric detection of biomolecules in the low density range, comprising
a detection reaction management unit (1) with one or more auxiliary solution tanks (2) and a container (3) for receiving waste solutions and feed (4) and discharge lines (5) to the tanks (2, 3),
a measuring unit (6) having a means (7) for the photometric, pixel-oriented detection of a color reaction of at least one reaction solution with at least one biomolecule to be detected,
a computer-assisted evaluation unit (13) for evaluating the measurement results,
a measuring cassette (9) containing a low-density biochip (14) with a glass or plastic carrier provided with functionalized reaction areas, the measuring cassette (9) having at least one insertion opening (15) for the sample (16) or samples to be analyzed,
wherein the detection reaction guide unit (1) has at least one receiving area (8) for snugly receiving a measuring cassette and this has connections for the inlets and outlets of the containers (2, 3) for auxiliary solutions and waste solutions, wherein at the ...

Description

The The invention relates to a measuring device with a disposable measuring cassette for the automated quantitative photometric detection of biomolecules in low Density area.

From the patent DE 101 48 102 B4 a biochip for photometric, pixel-oriented quantitative detection of biomolecules is known, the 2-8 mm ² large reaction areas (spots) on the glass surface of a commercial glass slide has. The spots are functionalized such that the biochip can be used as an assay using an enzyme-labeled biomolecule (probe). The conversion of the color substrate used is evaluated by detecting the color spots on the spots in both optical density and relative number per spot. The color intensity of the colors red, green and blue (RGB) of all pixels is measured and evaluated by means of a transmitted light scanner.

From the utility model DE 20 2005 006 854 U1 is known a low density biochip, which is made of transparent plastic and has the size of a slide.

adversely At the known biochips is that these manually with the sample loaded, rinsed and with the color-reactive marker solution need to be offset. The handling is thus subject to the individual procedure of the laboratory technician, making only measurement results from the hand of a lab assistant as comparable can be viewed even with routine work done with almost identical Hand gripped and time management inaccuracies due to pipetting errors and room conditions occur.

Further are the reaction surfaces the well-known biochips unprotected towards external mechanical and chemical influences like touches through fingers or laboratory equipment and by airborne compounds or particles which also a distortion and inaccuracy of the measurement results.

The obtained measurement results are therefore only with a correspondingly high error rate comparable.

One Another disadvantage of the known biochips is that only one biomolecule per chip can be detected.

task The present invention is therefore, by means of detection of biomolecules Low Density Biochips based on photometric, pixel-oriented to automate the quantitative acquisition of measurement results and to increase the reproducibility and accuracy of the evidence.

The Task is performed by a measuring device for automated quantitative photometric detection of biomolecules in the low density range solved, the one detection reaction control unit with one or more containers for auxiliary solutions and a container for receiving waste solutions as well as supply and discharge lines to the containers, a measuring unit with a means for photometric, pixel-oriented detection of a Color reaction of a reaction solution with a biomolecule to be detected, a computer-assisted evaluation unit for evaluating the measurement results and containing a measuring cassette a low-density biochip with a functionalized reaction area having provided glass or plastic carrier. In the reaction control unit is at least one receiving area for accurately recording a Measuring cassette set up over connections for the Inlets and outlets of the containers for auxiliary solutions. At the Measuring cassette itself are corresponding to the terminals in the receiving area connections set up, wherein the mutually corresponding connections after Insert a detachable tight connection when inserting the measuring cassette. At least the loading and rinsing the measuring cassette with reaction and Auxiliary solutions, the reaction procedure as well as the evaluation of the color reaction is processor-controlled and preferably fully automatic.

The auxiliary solutions can depending on the assay from a buffer, for example, an electrolyte solution with be a certain pH, which in a particular embodiment Eggs, detergents (e.g., Tween) are added.

The detection reaction control unit is used for controlling and regulating and performing the detection reaction on the low density biochip. For this purpose, a measuring cassette containing a low-density biochip is introduced into a receiving area provided for this purpose, which is preferably designed as a slot-in compartment. In this case, the corresponding connections to the measuring cassette and to the detection reaction guidance unit are connected to one another. These are preferably connections of the type "male" and "female", which can be inserted into one another in the correct manner. In a particular embodiment, the measuring cassette has a septum in the connections. The connections to the detection reaction management unit, however, are equipped with a cannula or pick-up needle, so that when inserting the measuring cassette and the simultaneous Ver bind the connections, the septa are pierced by the cannulas or picking needles. The provision of septa-mounted connections to the measuring cassette has the advantage of being able to store the measuring cassette in a dustproof and moisture-proof manner before use. Next they guarantee the re-closure or a seal upon removal of the cassette from the detection reaction guide unit.

The Measuring cassette is with a pump, preferably an oscillating Membrane or balloon pump equipped by a drive, in the detection reaction control unit is set up, is driven. This pump is used both for homogenization and even distribution the sample, the auxiliary solutions as well as the color reagent in the measuring chamber of the measuring cassette. Of the Drive, for example, an electric motor, the diaphragm pump is such in the detection reaction control unit set up that when inserting the measuring cassette with the drive the pumping device is coupled in the cassette, preferably with a pestle or a connecting rod in an established in the measuring cassette guide channel to the leadership the plunger or engages the connecting rod, wherein the plunger or the connecting rod to the diaphragm of the pump ends. When driving the membrane through the pestle or the connecting rod oscillates up and down and causes so a mixing in the subsequent to the pump measuring chamber. The detection reaction control unit itself is with pumps for promotion of auxiliary solutions from the storage containers into the measuring cassette and to aspirate sample, auxiliary solutions or Color reagent from the measuring cassette fitted in a corresponding collecting container.

In the detection reaction control unit preferably provided a plurality of receiving areas for receiving measuring cassettes. Each detection reaction can be done separately and independently of parallel Detection reactions in further measuring cassettes by the evaluation unit to be controlled. An advantage of this is that several detection reactions performed simultaneously can be.

In a particular embodiment is the detection reaction control unit tempered and air-conditioned, so that the detection reaction under optimal Reaction conditions can expire. The reaction conditions are stored in the detection program or separately manually adjustable. Preferably, each receiving area for a measuring cassette is separate tempered and air-conditioned.

The measuring unit is used for the photometric, pixel-oriented detection of a color reaction of a reaction solution with a biomolecule to be detected. The Low Density Biochip of the measuring cassette is a biochip with preferably 2-8 mm ² large reaction areas (spots), which are applied to the glass surface of a commercially available glass or plastic Objektträgers. The spots are functionalized such that the biochip can be used as an assay using a labeled biomolecule (probe). The conversion of the color substrate used is evaluated by detecting the color spots on the spots in both optical density and relative number per spot. To detect the color intensity of the colors red, green and blue (RGB) of all pixels, the measuring unit is preferably equipped with a CCD camera, a camera with CMOS technology or a scanner with scattered light for generating data in file formats for raster graphics. The list is not exhaustive. Basically, any camera technology can be used, with which color intensities can be recorded evaluable. After the end of the detection reaction, the measuring cassette of the detection reaction guide unit is removed and introduced into the measuring unit, which has a corresponding holder for receiving the measuring cassette. In a particular embodiment, the measuring unit can also be integrated in the detection reaction control unit, so that the measurement of the spots can be made directly after completion of the detection reaction, without the measuring cassette of the measuring unit must be supplied separately. The color intensities of the individual spots are detected by illuminating the measuring chamber from below and taking an image with the scanner or the CCD camera from above. The image format is a raster graphics file format, preferably a tif format or bmp format.

The CCD camera is preferably a 12-bit CCD camera. This can generate 1024 color values per color. With commercially available 8-bit CCD cameras, however, only 256 color values per color can be displayed. Due to the high number of color values with a 12-bit CCD camera, a significantly higher sensitivity compared to scanners or 8-bit CCD cameras is achieved. When evaluating the color intensities of the spots, which depends on the number of bound biomolecules per spot, the use of a 12-bit CCD camera leads to a higher accuracy of the measurement results while at the same time lowering the detection limit. At a color intensity of a spot of 0%, no biomolecules are bound to the binding sites, whereas at a color intensity of 100%, all binding sites are occupied. The 12-bit CCD camera now allows a 4-fold higher number of steps (one step is the smallest unit to which a concentration of the biomolecules contained in the sample can be assigned) compared to an 8-bit CCD camera. The levels here are around 0.5% on the color intensity scale. The 8-bit CCD camera can display a maximum of 3% of the color intensity values. This clearly demonstrates the advantage and higher accuracy of a 12-bit CCD camera. As a result, samples of very small volumes can be evaluated. Accordingly, the detection limit drops down so that even low concentrations of the biomolecule in the sample after can be shown. Also, the size of the spots can be reduced and so a significantly higher number of spots placed on the biochip, as the prior art indicates.

simultaneously software-controlled zero values are recorded with the camera. For this purpose, preferably up to four color values are determined for each spot, which correspond to a mean color intensity of 0%, one so-called "shading correction." These areas lie outside of the spot to be measured. These four zero values will be for each Spot determined individually and when calculating the color intensity of the associated spot based on. This allows Errors or deviations in the illumination of the measuring cassette excluded become. About that can out Spots that are only partially occupied, be it through patchy Occupation of the spot with binding sites or inadequate Wetting with the color reagent, included in the evaluation because color ranges are calculated out with 0% color intensity and not included in the mean calculation of the color value calculation of the spot become.

The Acquisition of color intensity values is based on Bayer filter values, with which unadulterated color values can be determined.

The The digital image taken by the CCD camera is then turned on the evaluation unit transmits, where this can be displayed on a screen. The evaluation of the color intensities and the assignment to certain concentrations of the biomolecule takes place software support. In the evaluation unit, color reference values are preferably used as calibration or calibration values stored. Also, calibration and calibration values by means of a second measuring cassette, the corresponding conditioning of the spots, read in and the values based on the following Detection reactions are used. In a preferred embodiment can manually spots from the calculation, for example, due to faulty Occupancy, scratches or defects removed in the measuring cassette become. For this purpose, these spots are marked by the evaluation software. additionally is provided, certain spots of a biochip as reference color values define.

The Measuring device thus consists of four individual components, in a housing can be integrated or as separate components, so-called stand-alone components, connected via data transmission lines can be made.

The computerized Evaluation unit has control and regulation units for controlling and regulating both the detection reaction guidance unit as well as the measuring unit, which is in particular a PC or MAC. In the computer-aided evaluation unit is a Storage unit established in the color reference values and / or Zero values for evaluation of the measurement results stored and retrievable are. About that In addition, in the memory unit of the computer-aided evaluation unit Programs for controlling the detection reaction management unit for defined detection reactions variously conditioned low density biochips for detection different biomolecules stored and retrievable. additionally can be a control panel for entering and / or starting programs for the control of defined detection reactions and an output and / or display unit for measurement results be furnished.

The Proof reaction unit can be used in the recording area for a precise recording of a measuring cassette with a reading and / or decrypting unit be equipped by coded information stored on the measuring cassette.

As well can the measuring cassette with a storage unit and readout unit containing coded information, preferably one or more information selected from the group "Art and conditioning the biochip, detection reaction, lot number, Program for controlling the detection reaction, used measuring cassette, new measuring cassette, security code ".

The read and / or decryption unit of the detection reaction management unit and the storage unit and readout unit of the measurement cassette are respectively arranged on or in the components such that these data can be exchanged when inserting the measurement cassette into the detection reaction guidance unit. Preferably, data are stored on the storage unit and read-out unit of the measuring cassette, which is the nature and conditioning of the biochip, for example, for the detection of mycotoxins or eicosanoids, and which detection reaction to load and start, stored and retrievable. In addition, the batch number, the program necessary for the detection reaction for controlling the detection reaction can be stored. Also, information about the condition of the measuring cassette may be stored, in particular whether it is an already used measuring cassette or a new measuring cassette. Preferably, after the first use of a measuring cassette in the detection reaction guidance unit, information is transferred from the reading and / or decrypting unit to the memory unit and readout unit which, in the case of a second use of the measuring cassette, triggers a signal which indicates or prevents the measuring cassette from becoming white teres time is used. Also, a security code may be stored which is verified by the detection reaction management unit. Only after the validity of the security code, the measuring cassette for the analysis of biomolecules in the detection reaction management unit is released and the detection program started. In addition, the storage of further information in both the memory unit and readout unit and in the reading and / or decrypting unit are possible.

to solution The problem underlying the invention proposes the invention also a measuring cassette in front.

The Measuring cassette is for single use in the inventive Prepared measuring device. It consists of a translucent cassette housing, in a measuring chamber in which a low density biochip with a functionalized reaction areas provided glass or plastic carrier used is, an overflow chamber, a sample supply, if necessary with sample filter, and a sample line to the measuring chamber, a chamber into which a reservoir with a reaction solution a color-reactive marker insertable is as well as an activation stamp or activation device to the opening of the storage container is set up. additionally is a supply line for the reaction solution the color-reactive marker from the reservoir to the measuring chamber, at least a supply connection and a supply line for a first auxiliary solution, at least a discharge and a discharge connection for waste solutions available. The measuring cassette is with a mixing device for homogenizing the sample and the solutions mentioned in the measuring chamber and a gas-permeable seal and / or a Valve and / or a membrane equipped for pressure equalization in the cassette housing.

Preferably is the measuring cassette housing made of a plastic.

The Mixing device can be a balloon pump or an oscillating one Be a diaphragm pump. In this case, at the bottom of the measuring cassette is a guide channel to the leadership the plunger or the connecting rod is set up to drive the pump, the guide channel is configured such that the plunger or the connecting rod to the diaphragm of the pump ends.

Of the into the chamber of the measuring cassette insertable reservoir containing the reaction solution of a color-reactive marker, preferably a tetramethylbenzidine solution (TMB solution). Preferably, the Chamber cylindrical designed, at the Meßkammerseitigen end a hollow thorn-like Pointed cone is centrally arranged. In this chamber we closed reservoir introduced and by means of a cylindrical Stamp, which subsequently introduced into the chamber and closing with the inner wall of the chamber slidingly close, against pressed the hollow thorn-like cone. As a result, the reservoir is opened and the reaction solution released. By further pressing the punch in the direction of the thorn-like Spitzke gels, the reaction solution in pressed the measuring chamber. This can be done manually or automatically.

The Measuring cassette may be a disposable cassette, after conditioning and inserting the low-density biochip into the measuring chamber of the measuring cassette, the measuring cassette was sealed. In a preferred embodiment the measuring chamber is closed with the Low Density Biochip. For this becomes the Low Density Biochip with the functionalized reaction areas placed on the measuring chamber like a lid and the biochip then fixed and air and moisture impermeable connected to the measuring cassette housing. The advantage of this is that the measuring cassette only from a molded part and a biochip, and not two moldings containing the Cover the biochip. This reduces costs in the production of moldings and simplifies the assembly of the measuring cassette.

Of the Low Density Biochip can for the detection or determination of biomolecules selected from the group "mycotoxins, Eicosanoids, lung markers, anti-IgE IgE " However, measuring cassette is all evidence of biomolecules in one Assay transferable and should not be limited to the above proofs.

Of the Low Density Biochip can for prepared for the simultaneous detection of different biomolecules be, with the reaction areas of a low density biochip different functionalized. Thus, it is possible to have several biomolecules of a sample detect with a biochip, for example, various mycotoxins containing in a cereal sample.

By different concentrations of the detection molecules on the Spots may additionally be achieved that the biochip an extremely wide measuring range can cover. This is especially useful for unknown Samples with very low or very high concentration of the analyte Perform analysis to be able to without having to record a new calibration curve.

Preferably, the measuring cassette with a storage unit and / or read-out unit containing encoded information, preferably one or more information selected from the group "type and conditioning of the biochip, detection reaction, Batch number, program for controlling the detection reaction, used measuring cassette, new measuring cassette, security code. "The storage and / or readout unit can be a barcode or a memory chip in addition, all other systems can be used to query and check stored coded information ,

Advantageous on the inventive measuring cassette is that the low used Density biochip protected before environmental influences or mechanical or chemical influences in the measuring cassette is. This facilitates the handling of sensitive biochips considerably in use. By the enclosed atmosphere in the Measuring cassette can also over this longer Be stored without the Biochip loses functionality. Thus, you can Cassettes are made in stock. Likewise, the Reaction solution and Measuring cassette according to specification their necessary storage conditions are kept separate from each other and must be assembled just before use. The measuring cassette is easy to manufacture with low production costs.

One Drying out the low density biochip before acquiring the measurement data, as it can occur in the known open biochips, inevitably leads to a falsification the measurement results. This can not be done with the inventive measuring cassette occur because the biochip in the measuring cassette while and after the detection reaction in its own completed and optimized atmosphere and does not dry out due to the sealing of the measuring cassette can.

below the invention is explained in more detail with reference to an embodiment:

1 : schematic representation of the measuring device

2 : Measuring cassette

3 : software-based evaluation of the biochip

The 1 shows an embodiment of the inventive measuring device for automated quantitative photometric detection of biomolecules in the low density range. It consists of an evaluation unit 13 a detection reaction control unit 1 with a container 2 for an auxiliary solution and a container 3 for the reception of waste solutions as well as 4 and derivatives 5 to the containers and a measuring unit 6 with a means 7 for the photometric, pixel-oriented detection of a color reaction of a reaction solution with a biomolecule to be detected. The measuring unit 6 is with a slot 8th for inserting and receiving the measuring cassette 9 and a bottom-mounted lighting 10 for transmitted-light illumination of the measuring cassette after insertion into the measuring unit 6 fitted. Both the detection reaction control unit 1 as well as the measuring unit 6 are via data transmission cables 11 . 12 with a computer-aided evaluation unit 13 connected to the evaluation of the measurement results. The 1 , shows an alternative embodiment with stand-alone devices. However, all components can also be set up in a housing.

The measuring cassette 9 contains a low density biochip 14 with a glass or plastic carrier provided with functionalized reaction areas, wherein the measuring cassette has an insertion opening 15 for the sample to be analyzed 16 features.

The detection reaction control unit 1 has several recording areas 17a . 17b . 17c for accurately fitting a measuring cassette 9 ( 1 shows only one measuring cassette). The functionalized measuring cassettes are inserted into these. Subsequently, through the sample opening 15 the sample 16 into the measuring cassette 9 injected. This process can also be done before inserting the measuring cassette 9 in the detection reaction control unit 1 be made. The measuring cassette 9 has connections 18 for the inlets and outlets of the auxiliary solution containers, which seal tightly after insertion of the measuring cassette with the corresponding connections in the receiving area. After inserting the measuring cassette 9 in the detection reaction control unit 1 is from the evaluation unit 13 a detection reaction program is started, which programmatically controls the detection reaction in the detection reaction control unit 1 performs, wherein the loading and rinsing of the measuring cassette with reaction and auxiliary solutions is processor-controlled and fully automatic.

After completion of the detection reaction, the measuring cassette 9 in the measuring unit 6 inserted. The measuring cassette is illuminated during the photographic recording from below in the transmitted light method. For this purpose, a lamp is arranged on the bottom side in the measuring unit. By means of the CCD camera 7 becomes the color intensity of the individual reaction areas of the biochip 14 photographed in the top view. At the same time, zero values of each individual reaction area are taken as the basis for calculating each color value of each individual reaction area. The control and triggering of the CCD camera takes place via the evaluation unit 13 ,

The digital image created by the CCD camera as well as the determined zero point values of the individual reaction areas are transmitted via the data link grounding cable 12 to the evaluation unit 13 , here a PC, transmitted, in which software-based the evaluation of the detection reaction takes place. In a particular embodiment, reaction areas can be assigned to specific color intensity values by means of the evaluation software or manually. The calculated results are displayed on the screen of the evaluation unit 13 displayed.

The 2 shows an inventive measuring cassette for single use in the inventive measuring device. This has a translucent cartridge housing 19 and a measuring chamber 20 in which a low density biochip 14 is used with a provided with functionalized reaction areas glass or plastic support on.

Behind the measuring chamber 20 is an overflow chamber 21 equipped to hold excess sample, reaction or auxiliary solutions. In the measuring chamber 20 is the sample 16 via a sample supply 22 with sample filter 23 and a sample line 24 to the measuring chamber 20 insertable. The sample input can be done manually or process controlled, for example via a sample sampler. In the chamber 25 is a storage container 26 used with a reaction solution of a color-reactive marker. The storage tank 26 with a reaction solution of a color-reactive marker is with an activation stamp 27 pressed into the chamber and by pressing on, for example, a hollow pointed spike, which is at the opening of the chamber 25 opposite end of the chamber 25 is set up, open. By further depressing the activation punch 27 becomes the reaction solution of the color-reactive marker from the reservoir 26 into the measuring chamber 20 pressed. This can be done manually or automatically. The measuring cassette 9 has a feeder connection 28 and a supply line for a first auxiliary solution and a discharge and a discharge connection 29 for waste solutions. In front of the measuring chamber 20 is a mixing device 30 for homogenizing the sample and said solutions in the measuring chamber. To balance the pressure in the measuring cassette, it has a gas-permeable seal 31 ,

The 3 shows the digital picture 32 of the Low Density Biochip, which passes through the CCD camera 7 has been recorded. The image is displayed on the screen of the evaluation unit 13 displayed. These include the color values calculated using the evaluation software with appropriate assignment 33 a concentration of a detected biomolecule displayed. Mean values of the determined zero point values are included in the output values.

1

Proof reaction unit

2

Container for auxiliary solution

3

Container for Inclusion of waste solutions

4

supply

5

derivation

6

measuring unit

7

CCD camera

8th

Tray / reception area for measuring cassette

9

measuring tape

10

lighting

11

Data transmission cable

12

Data transmission cable

13

evaluation

14

low Density biochip

15

Introduction opening for the sample

16

sample

17

ABC Recording areas for measuring tapes

18

connections

19

translucent measuring cassette housing

20

measuring chamber

21

Overflow chamber

22

sample supply

23

sample filter

24

sample line

25

chamber for storage tank

26

reservoir

27

activation stamp

28

supply connection

29

exhaust port

30

mixing device

31

gas permeable seal

32

digital Image of the Low Density Biochip

33

Measurement results

Claims (21)

Measuring device for the automated quantitative photometric detection of biomolecules in the low density range, comprising a detection reaction guidance unit ( 1 ) with one or more containers ( 2 ) for auxiliary solutions and a container ( 3 ) for the reception of waste solutions and supply ( 4 ) and derivatives ( 5 ) to the containers ( 2 . 3 ), a measuring unit ( 6 ) with a means ( 7 ) for the photometric, pixel-oriented detection of a color reaction of at least one reaction solution with at least one biomolecule to be detected, a computer-assisted evaluation unit ( 13 ) for the evaluation of the measurement results, a measuring cassette ( 9 containing a low density biochip ( 14 ) with a glass or plastic carrier provided with functionalized reaction areas, wherein the measuring cassette ( 9 ) via at least one insertion opening ( 15 ) for the sample to be analyzed ( 16 ) or samples, wherein the detection reaction management unit ( 1 ) at least one receiving area ( 8th ) to the exact fit en has a measuring cassette and this via connections for the inlets and outlets of the container ( 2 . 3 ) for auxiliary solutions and waste solutions, wherein on the measuring cassette ( 9 ) to the terminals in the receiving area corresponding terminals ( 18 ) are arranged, wherein the mutually corresponding connections after inserting the measuring cassette ( 9 ) enter a releasable tight connection, wherein the loading and rinsing of the measuring cassette ( 9 ) with reaction and auxiliary solutions, the reaction and the evaluation of the color reaction is processor-controlled. Measuring device according to claim 1, characterized in that the computer-aided evaluation unit ( 13 ) via control and regulation units for controlling and regulating both the detection reaction management unit ( 1 ) as well as the measuring unit ( 6 ). Measuring device according to claim 1 or 2, characterized in that the detection reaction guidance unit ( 1 ), the measuring unit ( 6 ) and the computer-aided evaluation unit ( 13 ) Are stand-alone devices, wherein the detection reaction management unit ( 1 ) and the measuring unit ( 6 ) with the evaluation unit ( 13 ) via data transmission cable ( 11 . 12 ) are connected. Measuring device according to one of claims 1 to 3, characterized in that the computer-controlled evaluation unit ( 13 ) is a PC or MAC. Measuring device according to one of claims 1 to 4, characterized in that the means ( 7 ) For photometric, pixel-oriented detection of a color reaction, a CCD camera or a scanner with scattered light for generating data in Da teiformaten for raster graphics. Measuring device according to claim 5, characterized in that that the CCD camera is a 12-bit CCD camera. Measuring device according to one of claims 1 to 6, characterized in that in the computer-aided evaluation unit ( 13 ) the evaluation of the measurement results software-based on the basis of the 7 ) for the photometric, pixel-oriented detection of a color reaction recorded data in file formats for raster graphics. Measuring device according to one of claims 1 to 7, characterized in that the computer-aided evaluation unit ( 13 ) has a memory unit in which color reference values and / or zero values for the evaluation of the measurement results can be stored or stored and retrieved. Measuring device according to one of claims 1 to 8, characterized in that in the memory unit of the computer-aided evaluation unit ( 13 ) Programs for Controlling the Detection Reaction Management Unit ( 1 ) for defined detection reactions of variously conditioned low-density biochips ( 14 ) are stored and retrievable for the detection of different biomolecules. Measuring device according to one of claims 1 to 9, characterized in that a control panel for input and / or Starting programs to control defined detection reactions and set up an output and / or display unit for measurement results is. Measuring device according to one of claims 1 to 10, characterized in that the receiving area ( 8th ) is equipped for accurately recording a measuring cassette with a reading and / or decrypting unit of information stored on the measuring cassette. Measuring device according to one of claims 1 to 11, characterized in that the measuring cassette ( 9 ) with a memory unit and readout unit containing encoded information, preferably one or more information selected from the group "type and conditioning of the biochip, detection reaction, batch number, program for controlling the detection reaction, used measuring cassette, new measuring cassette, security code" equipped. Measuring cassette for single use in the measuring device according to one of claims 1 to 12, consisting of a translucent Kassettengehäu se ( 19 ), a measuring chamber ( 20 ), in which a Low Density Biochip ( 14 ) can be used with a provided with functionalized reaction areas glass or plastic carrier, an overflow chamber ( 21 ), a sample feed ( 22 ) with sample filter ( 23 ) and a sample line ( 24 ) to the measuring chamber ( 20 ), a chamber ( 25 ) into which a storage container ( 26 ) is insertable with a reaction solution of a color-reactive marker, and an activation stamp ( 27 ) for opening the storage container, a supply line for the reaction solution of the color-reactive marker from the storage container to the measuring chamber, at least one supply connection ( 28 ) and a supply line for a first auxiliary solution, at least one derivative and a discharge connection ( 29 ) for waste solutions, a mixing device ( 30 ) for homogenizing the sample ( 16 ) and said solutions in the measuring chamber ( 20 ) and a gas-permeable seal ( 31 ) and / or a valve and / or a diaphragm for pressure equalization in the cassette case ( 19 ). Measuring cassette according to claim 13, characterized in that the measuring cassette housing ( 19 ) consists of translucent plastic. Measuring cassette according to claim 13 or 14, characterized in that the mixing device ( 30 ) is a balloon pump or an oscillating diaphragm pump. Measuring cassette according to one of claims 13 to 15, characterized in that the reaction solution of a color-reactive marker a tetramethylbenzidine solution (TMB solution) is. Measuring cassette according to one of claims 13 to 16, characterized in that the measuring cassette ( 9 ) is a disposable cassette, wherein preferably the measuring cassette consists of a single molded part, and a low-density biochip ( 14 ) between the Low Density Biochip and the measuring cassette housing ( 19 ) the measuring chamber ( 20 ), wherein the low density biochip ( 14 ) that the measuring cassette ( 9 ) is occlusive component. Measuring cassette according to one of claims 13 to 17, characterized in that the low density biochip ( 14 ) for the detection or determination of biomolecules selected from the group "mycotoxins, eicosanoids, lung marker, anti-IgE-IgE" prepared. Measuring cassette according to one of claims 13 to 18, characterized in that the low density biochip ( 14 ) is prepared for the simultaneous detection of different biomolecules, wherein the reaction areas of a low density biochip ( 14 ) are functionalized differently. Measuring cassette according to one of claims 13 to 19, characterized in that the measuring cassette ( 9 ) is equipped with a memory unit and / or readout unit containing coded information, preferably one or more information selected from the group "Type and conditioning of the biochip, detection reaction, batch number, program for controlling the detection reaction, used measuring cassette, new measuring cassette, security code" equipped. Measuring cassette according to one of claims 13 to 20, characterized in that the storage and / or read-out unit a barcode or memory chip is.