DE102004025269A1 - Biochip cell, useful for performing rapid DNA assays, e.g. for assessing response to treatment, comprises a chip substrate, with analytical islands on its surface, and a sealed cover - Google Patents

Abstract

A biochip cell (A) comprises a biochip substrate (1) and a cover (2), for reception and analysis of biological samples. A biochip cell (A) comprises: (a) a biochip substrate (1) having, on its upper surface, many spatially separated and uniformly distributed analytical islands (6) and at least one analytical region (7) for receiving the sample material; (b) at least one plastic frame (9), made of rubber-like material, that is arranged on the upper surface and defines a region (7) containing a limited number of (6); and (c) a cover (2), adhesive on one side and having an area that matches that of (1) or (7), to provide hermetic sealing of (7). An independent claim is also included for a method for preparing (A).

Description

The The invention relates to a biochip cell with biochip substrate and cover for one Recording and optical analysis of biological samples and a procedure for preparation and implementation the analysis.

in the Average takes the development and testing phase of a new drug 12 to 15 years. Every shortening This test phase can on the one hand the chances of recovery for patients improve and on the other hand the introduction of new pharmaceutical Accelerate products into the market. A significant contribution can do this so-called biochip system solutions deliver. The heart of this Biochip systems is a biochip cell that has a whole laboratory can accommodate in miniature form. For an optical analysis can a square centimeter at the same time the reaction from present to to 400 known genes are checked for a particular drug. The "laboratory in miniature "Analysis Islands that coated with different genetic substances and then can the reactions of these 400 different gene samples in their response be checked for an active substance.

With Such biochip cells can Investigations of inflammations, of various types of cancer, neurological diseases, multiples Sclerosis, etc. are examined. In addition, such biochip cells in food research, paternity analysis, phoroscopy, the pre-disposition diagnostics or for higher resistance studies be used.

So far are used as biochip cells cavity injection molded housing, the various chambers and channels to the leadership the reaction liquids exhibit. This solution for biochip cells has disadvantageous big ones Dimensions, is complex in its manufacture and causes high Production costs.

task The invention is a biochip cell with biochip substrate and Cover for To create recording and optical analysis of biological samples, the economical can be produced and allows a minute-fast analysis. It is another object of the invention a method for preparation and execution the analysis with a correspondingly high time gain.

These The object is achieved with the subject matter of the independent claims. advantageous Further developments of the invention will become apparent from the dependent claims.

According to the invention is a Biochip cell with biochip substrate and cover for recording and optical Analysis of biological samples created. This biochip cell points a substrate having on its top a plurality of spatially isolated from each other and evenly distributed on top Owns analysis islands. These analysis islands are used for docking of biological sample material The biochip cell has at least a plastic frame made of rubber-elastic material, on the top of the semiconductor substrate is arranged and an analysis area encloses with a limited number of analysis islands. To the hermetic Covering the analysis area, the biochip cell has a one-sided adhesive cover, which in its planar extension of the biochip substrate or at least one analysis area is adjusted.

A Such a biochip cell has the advantage of being easy for the user is manageable and for a variety of applications can be used. So a doctor can be in his office in minutes for one Patients determine an individual medication. He can do that with him a blood sample that he distributes to the analysis islands, the specific one Check for a drug and have side effects and reaction times make statements. This is a significant progress in the treatment of diseases, such as depression or high blood pressure, where the duration until onset of action of a drug of greatest importance is.

With The biochip cell of the present invention can save time be achieved in the development of new drugs from one to two years, where a "blockbuster" drug is an accordingly prior approval can cause significant savings in development costs means.

In a preferred embodiment According to the invention, the analysis island has an annular structure, whereby spatial the individual analysis island is delimited from neighboring analysis islands is. With this ring-shaped Structure made of a coating material is ensured that the individual microdroplets of each DNA sample do not interfere run and mingle. For this, the biochip substrate can be a coating have, in which are arranged as analysis islands recesses.

In a further embodiment of the invention, the biochip substrate has a coating of two layers, a lower layer which is arranged on the biochip substrate and an upper layer, having as analysis islands annular openings to the lower layer out. In this case, the substrate may comprise a glass plate or a semiconductor wafer, which are covered with a closed metal layer as the lower layer. On the metal layer may be arranged as a second layer, a structured insulating layer having openings to the metal layer, so that the samples to be analyzed in the openings on the metal layer to an electrical potential for improving the analysis statements can be connected in an advantageous manner. The potential can be applied outside of the biochip cell to the lower layer of metal.

at a further embodiment The invention relates to the analysis island with an integrated circuit a semiconductor substrate electrically connected, wherein electrodes of the integrated circuit on top of the biosubstrate for wetting a biological sample material, in particular with DNA samples, lie free. Such analysis islands have the advantage that in addition to the inclusion of biological sample material, this sample material can be lifted to a predetermined potential to the analysis statements to improve.

Farther it is intended to make frames on the biosubstrate so that they have a height, which is bigger as an outer diameter of a Injection needle. In this embodiment of the Invention, there is the advantage that after the manufacture of Analysis areas, each of the rubber-elastic plastic frame are surrounded and covered by an op table transparent plate are, the possibility consists of a reaction solution in the cavity between the cover and biochip substrate with a To inject injection needle, then the reaction of the biological Optically observe sample material on the analysis islands.

In a further embodiment The invention provides for the plastic frames on the biochip substrate with an opening to provide. This opening is bigger than the outer diameter of a Injection needle and serves with other aids a reaction solution in to introduce the cavity between cover and biochip substrate. There are also two openings provided, as an inlet opening and the other as an outlet, so the reaction solutions through an analysis area can be.

There is also the possibility, a system of connection channels and analysis areas, with which a networked analysis becomes possible. After all is it over the inlet and outlet also possible, successively different reaction solutions over the same analysis ranges stream allow. For an optical examination, the cover has an optically transparent carrier on, the one-sided with an optically transparent adhesive layer is covered. This adhesive layer combines with the rubber-elastic Plastic frame and ensures a hermetic seal of individual biochip cells.

When transparent carrier can for the cover will be provided a glass plate, similar to one Cover plate on a microscope slide. On the other hand it is too possible, as a transparent carrier for the Cover to provide an acrylic plate. Instead of an adhesive layer can also have a dop pelseitig adhesive optically transparent film glued on a glass plate or other transparent carrier which significantly reduces manufacturing costs.

One Procedure for preparation a bio cell with biochip substrate and cover for a biochemical Analysis has the following method steps. First, will a biochip substrate having a plurality of spatially isolated ones, on top of the substrate of uniformly distributed analysis islands for docking biochemical sample material. there can the Anlayseinseln be divided into analysis areas. Subsequently, will applied at least one plastic frame made of rubber-elastic material. This is arranged on top of the biochip substrate in such a way that each have a limited number of analysis islands for each an analysis area is enclosed.

To producing the biochip substrate with the corresponding plastic frame becomes a biological sample material on the analysis islands of the biochip substrate applied using micropipettes. Subsequently, the analysis areas with a one-sided adhesive cover covered and hermetically sealed. Subsequently The analysis can begin by a series of reaction solutions in the Change with rinsing solutions in the Analysis areas is injected. Each after application and rinsing a reaction solution can be an optical analysis of the reaction products on the analysis islands respectively.

This Method has the advantage that with relatively simple means with a substrate and a transparent cover, and the application of rubber-elastic plastic frame, a variety of analysis islands, not only can be equipped with sample material, but also can be examined and thus a quick statement about the reaction between the reactive solution and the biochemical samples, such as DNA samples in the short term and can be determined inexpensively.

The plastic frame made of rubber elastic The material can be applied by injection molding, or by means of a dispensing process. In addition, it is also possible to apply a variety of plastic frame made of rubber-elastic material by means of printing technology. These can be done with and without a stencil or mask by using a jet printing technique, as is common in ink jet printers.

To the Applying biological sample material to the analysis islands can Harp micropipettes before covering the analysis areas with a transparent cover done. Such micropipette harps have a plurality of micropipettes arranged in a row, which in turn different DNA samples of the so-called Take sample trays and transfer them to the analysis islands can. Once an analysis area hermetically sealed by a cover is, with the help of an injection cannula, a reaction solution through the rubber-elastic plastic frame in the space between Cover and biochip substrate are injected so that short-term optical analysis can connect. Also, it is possible to create a sequence of reaction solutions alternating with rinsing solutions in the Anlaysenbereiche means of introducing liquids a reaction solution in appropriately designed composite channels of an analysis area to the next perform.

In a preferred implementation of the procedure become the molecules the reaction solution with provided fluorescent markers, so that when reacted with the analyzing material on the analysis islands an optically recognizable Fluorescence occurs.

• 1. Das Aufbringen der Analyse-DNA kann auf Waferebene nach dem Erzeugen der Kunststoffrahmen erfolgen, wenn als Substrat ein Halbleiterwafer zur Verfügung gestellt wird. Danach kann als Deckel die einseitig klebende Abdeckung aufgebracht werden, sodass die mit der Analyse-DNA geimpften aktiven Chipflächen im Bereich der Analyseinseln beim nachfolgenden Sägeprozess des Halbleiterwafers in einzelne Biochipzellen geschützt sind. Somit können kostengünstig, sowohl die Hohlraumerzeugung für die Untersuchung, als auch die "Microspotting" im so genannten "Batch-Prozess" auf Waferebene stattfinden.
• 2. Die Technologie und das entsprechende Design ermöglichen kleinste Gehäuse im "Chip Scale Package"-Bereich, einem Gehäuse, das nur unwesentlich größer ist als das Halbleitersubstrat für den entsprechenden Analysebereich.
• 3. Wird die Hohlraumbewandung, die aus dem Kunststoffrahmen gebildet ist, aus einem gummielastischen Material ausgeführt, so kann die Injektion der zu analysierenden Substanz in einfachster Weise erfolgen, indem die gummi elastische Kunststoffwand des Kunststoffrahmens mit einer kanülenartigen Spitze durchstoßen wird.

In summary, it should be noted that the biochip cell according to the invention and the method presented here have the following advantages:

• 1. The application of the analysis DNA can be done at the wafer level after the production of the plastic frame when a semiconductor wafer is provided as a substrate. Thereafter, the one-sided adhesive cover can be applied as a lid so that the active chip surfaces seeded with the analysis DNA are protected in the region of the analysis islands during the subsequent sawing process of the semiconductor wafer into individual biochip cells. Thus, both cavity generation for the assay and "microspotting" in the so-called "batch process" at the wafer level can be cost-effective.
• 2. The technology and design allow the smallest packages in the "Chip Scale Package" range, a housing that is only slightly larger than the semiconductor substrate for the corresponding analysis area.
• 3. If the cavity wall, which is formed from the plastic frame, made of a rubber-elastic material, the injection of the substance to be analyzed can be done in the simplest way by the rubber elastic plastic wall of the plastic frame is pierced with a cannula-like tip.

The The invention will now be described with reference to the accompanying figures.

1 shows a schematic cross section of a biochip cell of a first embodiment of the invention;

2 - 5 show schematic diagrams for the preparation of the biochip cell according to 1 ;

2 shows a schematic cross section through a biochip substrate with several analysis areas;

3 shows a schematic cross section through the biochip substrate and a micropipette when filling an analysis island with biological sample material;

4 shows a schematic cross section through the biochip substrate after covering the analysis areas with a cover;

5 shows a schematic cross section through the biochip substrate while dividing the biochip substrate into a plurality of biochip cells;

6 shows a schematic perspective sketch of a biochip cell according to another embodiment of the invention;

7 shows a perspective schematic diagram of a biochip cell according to a third embodiment of the invention;

8th shows a schematic perspective view of a biochip cell according to a fourth embodiment of the invention;

9 shows a schematic diagram for docking a DNA indicator to a DNA sample;

10 shows a schematic diagram of providing a DNA sample to be analyzed on an analysis island;

11 shows a schematic diagram of a docking of a DNA indicator on an analysis island;

12 shows a schematic diagram of DNA-In dicators docked on DNA samples on an analysis island;

13 shows a schematic diagram of providing DNA samples to be analyzed;

14 shows a schematic diagram of a rejection of DNA indicators on an analysis island;

15 shows a schematic diagram of a non-labeled DNA sample on an analysis island;

16 shows a schematic plan view of an analysis area under UV light.

1 shows a schematic cross section of a biochip cell 10 a first embodiment of the invention. The biochip cell 10 has a biochip substrate 1 on, which in this case is a semiconductor substrate 4 from a semiconductor wafer. On the top 5 is a plastic frame 9 arranged, which has an analysis area 7 surrounds. Inside the plastic frame 9 an analysis area 7 are a variety of analysis islands 6 arranged. The number of analysis islands 6 can be several hundred pieces. In the schematic cross-sectional view of 1 are only three analysis islands 6 shown by way of example.

The biochip cell 10 comes from an optically transparent cover 2 hermetically sealed by the cover 2 on the plastic frame 9 is glued on. Before hermetically sealing the biochip cell 10 with a cover 2 is on the analysis island 6 a biological sample material 8th a biological sample 3 been applied. The analysis island 6 is here as a mesa structure on the top 5 of the semiconductor substrate 4 shown. This mesa structure consists in this embodiment of the invention of a plastic ring on the top 5 of the semiconductor substrate 4 is applied. The analysis islands 6 however, can also be achieved by introducing depressions into a coating on the semiconductor substrate 4 will be realized.

The bottom of the analysis islands 6 can be a metallic electrode 11 to which from outside the biochip cell 10 a potential for improving the analysis results can be created. The plastic frame 9 consists of a rubber-elastic plastic and has a height h which is greater than an outer diameter of an injection needle. Thus, it is possible to use a reaction liquid 15 into the biochip cell 10 through the rubber-elastic plastic frame 9 through. Furthermore, it is possible over the optically transparent cover 2 optical reactions of the biological sample 3 with the injected reaction liquid 15 to observe.

The 2 to 5 show schematic diagrams for the preparation of the biochip cell 10 according to 1 , Components with the same functions as in 1 be in the 2 - 5 denoted by the same reference numerals and not discussed separately.

2 shows a schematic cross section through a biochip substrate 1 with several analysis areas 7 , This biochip substrate 1 is a large-area semiconductor wafer in this manufacturing step 17 on which a variety of analysis islands 6 are arranged. These analysis islands 6 consist of "borders" and are even on the top 5 of the semiconductor wafer 17 distributed.

Furthermore, the semiconductor wafer 17 on its top 5 Plastic frame 9 on that a limited number of analysis islands 6 surrounded and thus the multitude of analysis islands 6 in analysis areas 7 split. This plastic frame 9 made of a rubber-elastic plastic are applied, for example, by applying a SU8 lacquer in a spin coating process, followed by a photolithographic step of the spin coated SU8 lacquer in the in 2 shown plastic frame 9 is structured. Such a prepared top 5 a semiconductor wafer 17 can then be provided with a sample material, as it is 3 shows.

3 shows a schematic cross section through the biochip substrate 1 and a micropipette 16 when filling an analysis island 6 with biological sample B. The first analysis island 18 already has a biological sample 3 on, from which the micropipette 16 in the direction of arrow A to a second analysis island 19 procedure and also here is the loading of the second analysis island 19 already ended, so that in the direction of arrow B, the micropipette 16 to the next analysis island 6 can be moved.

With such a serial method can successively all analysis islands 6 a semiconductor wafer 17 be provided with sample material. A higher throughput when loading the analysis islands 6 with biological samples 3 is achieved by a micropipette harp, at the same time a whole line of analysis islands 6 with biological samples 3 is equipped. After filling up all analysis islands 6 with biological samples 3 becomes, as the next figure shows, the semiconductor wafer 17 covered by a glass plate.

4 shows a schematic cross section through the biochip substrate 1 after covering the analysis areas 7 with a cover plate 2 , This cover plate 2 is transparent, since the biochip cells produced in this way should be prepared for optical analysis and has a glass plate 21 on. For hermetically sealing the analysis areas 7 has the glass plate 21 on its back an adhesive layer on, with the glass plate 21 on the plastic frame 9 is pressed. This construction is so dense that now the semiconductor wafer 17 together with the glass plate 21 and the samples to be examined in a next step in individual biochip cells 10 as they are in 1 can be shown, can be separated.

5 shows a schematic cross section through the biochip substrate 1 dividing the biochip substrate 1 in several biochip cells 10 , While in 5 both glass plate 21 as well as semiconductor wafers 17 from a saw blade 22 It is also possible to cut a large number of glass plates at the same time 21 for the variety of analysis areas 7 provide these separately to the analysis areas 7 apply, leaving the saw blade 22 only the semiconductor wafer 17 has to cut through. This is the areal extent of the respective glass plate 21 per analysis area 7 bigger than the plastic frame 9 but smaller than the semiconductor substrate 4 every biochip cell 10 , Such an example of an embodiment is shown in the next figure.

6 shows a schematic perspective sketch of a biochip cell 20 according to a further embodiment of the invention. The biochip cell 20 according to 6 is different from the biochip cell 10 according to 1 in that the areal extent of the transparent cover 2 is smaller than the areal extent of the semiconductor substrate 4 , The plastic frame 9 For example, here only encloses six analysis islands 6 In order to simplify the illustration, in reality, a plastic frame 9 several hundred analysis islands 6 enclose.

Furthermore, in this 6 with the reference number 15 a reaction solution, which is the cavity 23 between the transparent cover 2 and the top 5 inside the plastic frame 9 and with the biological samples 3 on the analysis islands 6 in response. This reaction solution 15 was made by the rubber elastic plastic frame 9 in the cavity 23 injected with the help of an injection cannula. Due to the rubber-elastic properties of the plastic frame 9 becomes the injection port, which is created when piercing through the cannula, after penetration of the reaction solution 15 in the cavity 23 when pulling out the cannula is closed.

7 shows a perspective schematic diagram of a biochip cell 30 according to a third embodiment of the invention. The third embodiment of the invention according to 7 differs from the second embodiment of the biochip cell 20 according to 6 in that the plastic frame 9 openings 12 has, on two opposite sides of the plastic frame 9 are arranged so that an inlet opening 13 and an outlet opening 14 result. The cross section of these inlet and outlet openings 13 and 14 is larger than the cross section of a cannula. About these inlet and outlet openings 13 respectively. 14 is it possible, even reaction solutions 15 through the cavity 23 for example, to flow in the direction of arrow D.

It is also possible to use reaction solutions 15 exchange, so that after an active reaction phase can follow a neutralization phase. Also, this biochip cell allows 30 successively different reaction solutions, over the analysis islands, with sample material 8th are filled up, let flow. The sample material 8th can also do DNA samples 26 include to make genetic analyzes. Furthermore, it is possible to have several such biochip cells 30 over the entrance or exit openings 13 and 14 couple together and build a system with connection channels.

8th shows a schematic perspective view of a biochip cell 40 according to a fourth embodiment of the invention. In this embodiment of the invention, the biochip substrate 1 as analysis island 6 wells 24 on that in a coating 25 on the top 5 of the semiconductor substrate 4 are introduced. These depressions 24 are circular and are pipetted over 16 in the direction of arrow C with biological sample material 8th refilled. The production of such with windows, wells 24 or apertured coatings 25 on a semiconductor wafer is advantageously feasible by using standard semiconductor technologies. The padding with a single micropipette 16 the wells 24 in the coating 25 However, it is a serial process, resulting in a long production time for a biochip cell 40 caused. To shorten this time, fill in the wells 24 in the coating 25 with sample material 8th Also used pipette harp, synchronously and simultaneously several wells 24 in a row with sample material 8th can fill.

The 9 to 15 show schematic diagrams of a docking or a rejection of DNA indicators 27 on analysis islands 6 using DNA samples 26 are equipped.

9 shows a schematic diagram for docking a DNA indicator 27 to a DNA sample 26 , The DNA sample 26 has receptors in a given series and type 28 on, to the only DNA indicators 27 can dock if their receptors 29 in arrangement and type of receptors 28 the DNA sample 26 correspond. In addition, the DNA Indicator 27 a marker 31 which in this embodiment of the invention consists of a fluorescent material. Upon irradiation of the sample 3 on the analysis island 6 the docked DNA indicator illuminates with ultraviolet light 27 due to the attached fluorescent marker 31 opposite analysis islands 6 in which no DNA indicators 27 could moor up. A starting situation for such an analysis is shown in the next figure.

10 shows a schematic diagram of providing a DNA sample to be analyzed 26 on an analysis island 6 , This DNA sample 26 is on the analysis island 6 limited to which it was applied with a micropipette. This THEN sample 26 is now using a reaction solution 15 that over the analysis island 6 is placed in contact.

11 shows a schematic diagram of a docking of a DNA indicator 27 to the DNA samples 26 on the analysis island 6 , There type and arrangement of the receptors 28 the DNA sample 26 and the receptors 29 of the DNA indicator 27 agree, the DNA indicators prove 27 in the reaction solution 15 contained on the analysis island 6 arranged DNA samples 26 so that the next one 12 results.

12 shows a schematic diagram of docked DNA indicators 27 on DNA samples 26 on an analysis island 6 , Due to the marker 31 of the DNA indicators 27 can this DNA sample 26 on the analysis island 6 be clearly identified, especially in UV irradiation of the marker 31 lights.

13 shows a schematic diagram of providing a DNA sample to be analyzed 26 , This is the same starting situation as they already are 10 shows. This time, however, are like 14 indicates none for docking to the DNA samples 26 matching DNA indicators 27 in the reaction solution 15 so that they are rejected and in the reaction liquid 15 remain. The result shows 15 ,

15 shows a schematic diagram of unlabeled DNA samples 26 on the analysis island 6 , Because no suitable DNA indicator from the reaction solution 15 to the DNA samples 26 docked, this analysis island remains 6 dark when irradiated with a UV source. The overall result of these processes within one analysis area is shown in the next figure.

16 shows a schematic plan view of an analysis area 7 under UV light. On all brightly marked analysis islands 6 have docked DNA indicators from the reaction solution and their markers spread a bright UV-excited fluorescence glow. The other analysis islands 6 with DNA samples remained dark because no DNA indicators could dock.

1

biochip substrate

2

cover

3

biological sample

4

Semiconductor substrate

5

top of the semiconductor substrate

6

analysis island

7

analysis area

8th

biological sample material

9

Plastic frame

10

biochip cell

11

electrodes

12

Opening in Plastic frame

13

Inlet opening in Plastic frame

14

Outlet opening in Plastic frame

15

Reaction solution or Reaktonsflüssigkeit

16

micropipette

17

Semiconductor wafer

18

first analysis island

19

second analysis island

20

biochip cell

21

glass plate

22

sawblade

23

cavity

24

deepening

25

coating

26

DNA sample

27

DNA Indicator

28

receptor a DNA sample

29

receptor a DNA indicator

30

biochip cell

31

marker

40

biochip cell

A

arrow

B

arrow

C

arrow

D

arrow

H

Height of the plastic frame

Claims (20)

Biochip cell with biochip substrate ( 1 ) and cover ( 2 ) for recording and optical analysis of biological samples ( 3 ) with - a biochip substrate ( 1 ) on its top ( 5 ) a plurality of spatially isolated on the top side ( 5 ) evenly distributed analysis islands ( 6 ), at least one analysis area ( 7 ) for docking biological sample material ( 8th ) having; - at least one plastic frame ( 9 ) made of rubber-elastic material, which on the top ( 5 ) and an analysis area ( 7 ) with a limited number of analysis islands ( 6 ) encloses; - a one-sided adhesive cover ( 2 ), which in ih surface extension of the biochip substrate ( 1 ) or the at least one analysis area ( 7 ) for a hermetic completion of the analysis area ( 7 ) is adjusted. Biochip cell according to claim 1, characterized in that the analysis island ( 6 ) with an integrated circuit of a semiconductor substrate ( 4 ) is electrically connected, whereby electrodes ( 11 ) of the integrated circuit on the top side ( 5 ) of the biochip substrate ( 1 ) for wetting with biological sample material ( 8th ) especially DNA samples ( 26 ) are free. Biochip cell according to claim 1 or claim 2, characterized in that the analysis island ( 6 ) by an annular structure spatially from neighboring analysis islands ( 6 ) is delimited. Biochip cell according to one of the preceding claims, characterized in that the plastic frames ( 9 ) on the biochip substrate ( 1 ) have a height (h) which is greater than an outer diameter of an injection needle. Biochip cell according to one of the preceding claims, characterized in that the plastic frames ( 9 ) on the biochip substrate ( 1 ) an opening ( 12 ), which is larger than the outer diameter of an injection needle. Biochip cell according to one of the preceding claims, characterized in that the plastic frames ( 9 ) on the biochip substrate ( 1 ) an inlet opening ( 13 ) and an outlet opening ( 14 ) exhibit. Biochip cell according to one of the preceding claims, characterized in that the biochip substrate ( 1 ) a system of plastic frames ( 9 ) and compound channels that contain multiple analysis areas ( 7 ) connect. Biochip cell according to one of the preceding claims, characterized in that the cover ( 2 ) has an optically transparent support, which is covered on one side by an optically transparent adhesive layer. Biochip cell according to one of the preceding claims, characterized in that the cover ( 2 ) as a support a glass plate ( 21 ) having. Biochip cell according to one of claims 1 to 8, characterized in that the cover ( 2 ) has as carrier a acrylic plate. Biochip cell with cover according to one of the preceding claims, characterized in that the cover ( 2 ) As adhesive layer has a double-sided adhesive optically transparent film. Method for preparing a biochip cell ( 10 ) with biochip substrate ( 1 ) and cover ( 2 ) for a biochemical analysis, the method comprising the following steps: - producing a biochip substrate ( 1 ) with a plurality of spatially isolated on the top side ( 5 ) of the biochip substrate ( 1 ) evenly distributed analysis islands ( 6 ) for docking biological sample material ( 8th ), whereby the analysis islands ( 6 ) in analysis areas ( 7 ) are structured; - applying at least one plastic frame ( 9 ) made of rubber-elastic material, which on the top ( 5 ) and in each case a limited number of analysis islands ( 6 ) of an analysis area ( 7 ) encloses; - application of biological sample material ( 8th ) on the analysis islands ( 6 ) of the biochip substrate ( 1 ); - covering the analysis areas ( 7 ) with a one-sided adhesive cover ( 2 ); Introduction of a series of reaction solutions ( 15 ) alternating with rinsing solutions in the analysis areas ( 7 ); - optical analysis of the reaction products on the analysis islands ( 6 ). A method according to claim 12, characterized in that the application of at least one plastic frame ( 9 ) made of rubber-elastic material by means of an injection molding process. A method according to claim 12, characterized in that the application of at least one plastic frame ( 9 ) made of rubber-elastic material by means of a dispensing process. A method according to claim 12, characterized in that the application of at least one plastic frame ( 9 ) made of rubber-elastic material by means of a printing process. Method according to one of claims 12 to 15, characterized in that applying biological sample material ( 8th ) on the analysis islands ( 6 ) by means of micropipettes ( 16 ) before covering the analysis areas ( 7 ) he follows. Method according to one of claims 12 to 15, characterized in that the application of biological sample material ( 8th ) on the analysis islands ( 6 ) using a harp made of micropipettes ( 16 ) he follows. Method according to one of claims 12 to 17, characterized in that the introduction of a series of reaction solutions ( 15 ) alternating with rinsing solutions in the analysis areas ( 7 ) by means of a Injektionskanüle erflogt that the rubber-elastic plastic frame ( 9 ) pierces. Method according to one of claims 12 to 17, characterized in that the introduction of a series of reaction solutions in alternation with rinsing solutions in the analysis areas ( 7 ) by introducing the liquids into correspondingly designed composite channels to the analysis areas ( 7 ) he follows. Method according to one of claims 12 to 17, characterized in that the optical analysis of the reaction products on the analysis islands ( 6 ) by detecting fluorescence phenomena of the reaction products.