DE10228124A1 - Biosensor array comprising a substrate on which biosensors are mounted which have two connectors, one of which is connected to control lead while other is connected to detector lead - Google Patents

Abstract

Biosensor array (700) comprising a substrate (601), on which biosensors (602) are mounted which have two connectors, is new. One of these (603) is connected to a control lead (605) while the other (604) is connected to a detector lead (606). A control unit supplies a signal to the desired biosensor and the detector lead feeds the signal produced by it to a processor. Independent claims are also included for: (a) a similar array in which control and detector leads are both replaced by signal leads (b) a method for operating the array with control and detector leads; and (c) a method for operating the array with signal leads.

Description

The invention relates to a biosensor array and a method for operating a biosensor array.

Biosensors are state of the art known according to the principle of redox recycling work (cf. [1] to [4]).

In l is a redox recycling biosensor 100 shown according to the prior art.

For such a redox recycling sensor 100 a four-electrode system is required, which is on a substrate 101 is trained. The redox recycling biosensor 100 has a first interdigital electrode 102 and a second interdigital electrode toothed with this clearly finger-shaped 103 on. Typical values for the width and the distance of the interdigital electrodes 102 . 103 are in the range between approximately 0.5 μm and approximately 2 μm.

On the interdigital electrodes 102 . 103 capture molecules (not shown) are immobilized, which can hybridize with particles to be detected in a solution to be examined. According to the redox recycling principle, when operating the redox recycling biosensor 100 in the event of a sensor event on the interdigital electrodes 102 . 103 Oxidation and reduction processes caused by electrochemically activated particles. By means of a label molecule which is chemically bound to particles of an analyte to be detected by hybridized with capture molecules, electrochemically activated particles are generated when a special component is added to the solution.

In the 1 shown further electrodes, namely a reference electrode 104 and a counter electrode 105 , form together with a differential amplifier 106 a potentiostat. A non-inverting input 106a of the differential amplifier 106 is with the electrical ground potential 107 coupled, whereas an inverting input 106b of the differential amplifier 106 with the reference electrode 104 is coupled. An exit 106c of the differential amplifier 106 is with the counter electrode 105 coupled. Using the reference electrode 104 becomes the electrochemical potential of one in the redox recycling biosensor 100 introduced electrolyte measured. By means of the counter electrode 105 becomes the differential amplifier 106 regulated as a control amplifier to a predetermined electrical potential. It should be noted that the given potential clearly shows the electrical potential at the non-inverting input 106a of the differential amplifier 106 is, according to the example shown, the electrical ground potential 107 ,

For operating the redox recycling biosensor 100 are connected to the interdigital electrodes 102 . 103 , which are operated as generator or collector electrodes, by means of a first DC voltage source 108 and by means of a second DC voltage source 109 electrical voltages of different signs related to the reference potential (ground potential 107 ) created. The amount of these voltages should be chosen so high that the processes of oxidation and reduction of the redox recycling material work safely and efficiently, but on the other hand they should not be chosen too high to avoid unintended electrochemical processes (e.g. electrolysis) electrodes 102 . 103 to avoid.

It should be noted that none very much sharp thresholds for the onset of oxidation and reduction of certain substances exist. In practice, values are chosen the amount of each is sufficiently secure (typically a few tens mV) lies above these threshold ranges. In practice they are applied voltages in the range of less than 100 mV (for example +300 mV and –100 mV) for the substances used in [5].

As further in 1 shown is one with the first DC voltage source 108 coupled first ammeter 110 and one with the second DC voltage source 109 coupled second ammeter 111 intended. Using the first ammeter 110 an electrical current resulting from the applied voltages and the reduction / oxidation processes at the second interdigital electrode 103 be recorded. Using the second ammeter 111 an electrical current resulting from the applied voltages and the reduction / oxidation processes at the first interdigital electrode 102 be recorded. The values of these currents are a characteristic measure of those at the electrodes 102 . 103 sensor events and thus for the concentration of particles to be detected in a solution to be examined.

Electrochemical sensors known from the prior art, such as the redox recycling biosensor 100 have so far only been presented as individual sensors in small "passive" arrays, vividly as a sequence of a few individual sensors, or in "active" arrays which, apart from the actual biosensors, contain other active components on which either switching mattresses, cf. [4], or complex circuit technology, cf. [5] is included.

For many applications, it is desirable not only to perform one test with a biosensor, but to perform many tests in a given sample, the analyte, in parallel. Miniaturized bio- / chemosensor arrays that can be realized on corresponding chips serve for the simultaneous detection of different particles to be detected in one analyte to be examined. The corresponding sensors can be implemented in large numbers on a substrate, for example on a glass, plastic, silicon or other substrate. Due to the high degree of parallelization, such sensor arrangements, including the corresponding evaluation system, have a variety of applications in medical diagnostic technology, in which Pharmaceutical industry (e.g. for pharmaceutical screening, "high throughput screening", HTS), in the chemical industry, in food analysis, in environmental and food technology and analysis.

When realizing passive Arrays with sensors according to the principle of redox recycling (redox cycling) the challenge is that the signals of all sensors are to be fed to a reading device. Unless, for example a passive substrate with 8 × 12 = 96, 32 × 48 = 1536 or generally with a matrix arrangement with m rows and there are n columns of m × n positions, are 2 × 96 = 192, 2 × 1536 = 3072 or generally 2m × n separate Electrode terminals of the sensors as well as two further connections for the reference and counter electrodes the potentiostat arrangement required. Every biosensor field should be readable separately, the number of connections ("pads") of the chip used for reasons of Effort (for chip and reader) and above all for reasons security when making contact (signal integrity) is not should be too high.

A simple approach, for example all electrode connections with the reader coupling yields 2m × n + 2, in the example 194 or 3074 Connections, and is therefore not or not satisfactorily realizable. something similar applies to the approach of operating one electrode of all sensor fields together and all remaining electrode connections as well as the common electrode with the reader to couple. In this case, the number of connections is true less, namely n × m + 1 + 2 (in the example 99 or 1539), but still way too big.

The disadvantage of those described in [4], [5] Approaches, in which active arrays with a complex CMOS technology for the individual Sensor fields used are made up of high manufacturing costs across from purely passive arrays, in which CMOS circuits for the sensor fields are saved.

The invention is based on the problem To provide a biosensor array, where it can be done with reasonable effort allows is, sensor signals from an arrangement of miniaturizable biosensor fields read out with sufficient accuracy.

The problem is solved by a biosensor array and by a method for operating a Biosensor arrays with the features according to the independent claims.

The biosensor array according to the invention has a Substrate and a plurality of biosensor fields arranged on the substrate, of which each has a first port and a second port. Furthermore contains the biosensor array at least one first signal line and at least one second signal line, wherein the at least one first signal line from the at least one second signal line is electrically isolated. Always the first Connection of each biosensor field is exactly one of the at least coupled a first signal line, and the second connection of a each biosensor field is with exactly one of the at least one second Signal line coupled. At least one of the at least one first signal line and at least one of the at least one second signal line coupled to at least two of the biosensor fields. Furthermore, one first control unit for providing a first electrical Control signal and a second control unit for providing a second electrical control signal provided. Furthermore contains the biosensor array is coupled to the first control unit first detection unit and / or one with the second control unit coupled second detection unit, which is set up in this way or are that they are one of the first and the second electrical Control signal resulting first and / or second electrical Detection signal of a selected one Biosensor field detected or capture. A selection unit is set up such that the first control unit with the first signal line of a biosensor field to be selected and the second control unit with the second signal line of the one to be selected Biosensor field couples, with which the biosensor field is selected.

Furthermore, a method for Operating a biosensor array with the features described above created. According to the procedure the first control unit with the first signal line to be selected Biosensor field and the second control unit with the second signal line the one to be selected Biosensor zone coupled, whereby the at least one biosensor field is selected. Furthermore, the first signal line of the selected biosensor field becomes a first one electrical control signal and the second signal line of the selected biosensor field a second electrical control signal is provided. Furthermore becomes one of the first or the second electrical control signal resulting first detection signal on the first signal line of the chosen Biosensor field and / or one of the first and the second electrical Control signal resulting second detection signal at the second Signal line of the selected Biosensor field detected.

A basic idea of the invention is to provide first signal lines or second signal lines, which are provided jointly for a plurality of biosensor fields of a biosensor array, whereby the number of signal lines required to operate the biosensor array is considerably reduced. This makes it possible to operate a biosensor array (in particular on a passive chip) with a relatively small number of signal lines or a small number of pads coupled to the signal lines. There This saves space on the biosensor array, which enables a higher integration density and reduces the manufacturing costs. However, the array architecture according to the invention can also be used with active chips, since it allows the circuitry complexity per biosensor field to be kept low, which in turn enables the production of high-density arrays. In the case of active biosensor arrays, additional circuit devices (for example preamplifiers, AD converters, etc.) are provided on the substrate.

For one, for example, matrix-shaped Arrangement of the biosensor fields along lines provided second signal lines and along provided as column lines first signal lines can e.g. m Splitting optionally with a stimulating first voltage source the first control unit or with electrical ground potential be coupled. The n lines can be optional with a second exciting voltage source of the second control unit or be coupled with electrical ground potential. Choosing the Coupling the connections the biosensor fields with the voltage sources or with the ground potential takes place by means of the selection unit.

For example, at exactly one Column line a positive electrical voltage as the first electrical Control signal can be applied and can be connected to exactly one row an electrical voltage of negative sign as the second electrical Control signal can be applied. Only one in the intersection area the selected one Line with the selected one Column biosensor array has between its two terminals (i.e. its two electrodes) a sufficiently large potential difference that Redox recycling processes can be done on the biosensor field. All other biosensor fields have between their connections a potential difference that the first electrical voltage or corresponds to the second electrical voltage, since the other Connection is at ground potential. As a result, there are redox recycling processes in these biosensor fields not or not to a sufficient extent to make a detectable generate a signal that rises over time.

Occurs on a selected biosensor field Sensor event, for example a hybridization event, between capture molecules and particles to be detected immobilized on the biosensor field of an analyte, can using a label on the particles to be recorded, one chemical component introduced in the analyte and one sufficient huge electrical potential difference between the sensor electrodes redox recycling processes occur. As a result, flows on the with the selected one Biosensor field coupled first signal line and on the with the selected one Biosensor field coupled second signal line each an electrical Current as a detection signal. By capturing a value or preferably both values of currents can conclude the occurrence of hybridization events become.

For the case of a matrix Arrangement of the biosensor fields with m columns and n rows are only n according to the invention + m + 2 connections required, namely m first signal lines, n second signal lines and (optional) two more connections for reference and counter electrode of a potentiostat. For a chip with, for example 8 × 12 = 96 positions are therefore only 22 signal lines required for a chip with 32 × 48 = 1536 positions are 82 signal lines required. This contrasts the prior art represents a significant reduction in effort. The optimal attainable ratio from number of connections normalized to the number of sensor positions on the chip for the case n = m, that is for a Sensor array with a square architecture (number of lines = number of columns).

It is clearly possible according to the invention the manufacturing outlay for a biosensor array significantly reduce that at least one of the at least one first signal line and at least one of the at least one second Signal line coupled to at least two of the biosensor fields is. In other words, are for a respective plurality of signal lines common to biosensor fields provided for control and detection.

Preferred developments of the invention result themselves from the dependent Claims.

The biosensor array can be an evaluation unit have, which is set up such that it for the at least a selected one Biosensor field based on the first and / or the second detection signal determines whether sensor events occur on the at least one selected biosensor field and / or in what quantity at the at least one selected biosensor field Sensor events have occurred.

At least one of the biosensor fields can be set up as an electrochemical biosensor field. In particular At least one of the biosensor fields can be a redox recycling biosensor field. At a redox recycling biosensor field Particles to be detected are preferably provided with a label which after a hybridization event has taken place on the sensor field immobilized capture molecules is used, one to be introduced into the arrangement, in the used To split potentials of electrochemically inactive substance into two sub-molecules, at least one of which is electrochemically active. This leads to a change the electrical properties of the respective sensor position of the Biosensor array.

The biosensor field can have a first and a second electrode, the first electrode de with the first connection and wherein the second electrode is coupled to the second connection of the biosensor field. The first and the second electrode are preferably an interdigital electrode. In other words, the first and / or the second electrode can be like that in FIG 1 shown first or second interdigital electrode 102 . 103 be designed and operated.

The biosensor fields can too a plurality of biosensor groups be grouped in such a way that each biosensor group is optionally separate from the other biosensor groups or together with at least one Part of the other biosensor groups is operable. A compartmentalization of the biosensor array is clear possible. is for example for a certain application a sub-area of the biosensor fields is sufficient and the other biosensor fields are not required for this application, so can the biosensor fields of the sub-area grouped into a group and this group is operated separately from the other biosensor fields become.

The substrate can be a ceramic substrate, a semiconductor substrate (in particular a silicon substrate, i.e. a silicon wafer or a silicon chip), a glass substrate or a plastic substrate his.

The first and the second electrical Control signals are preferably electrical direct voltage signals with different signs related to a reference potential, which reference potential is present at at least one connection of an unselected biosensor field can, and the first and / or the second electrical detection signal is preferably an electric current.

It is alternatively provided that the first and second electrical control signals are in phase opposition to one another Are voltage signals. Condition for the occurrence of redox recycling processes on a selected one Sensor field is only that the potential difference between the first and the second electrical control signal a certain Threshold exceeded.

Usually it is connected to a connector or to both connections one not selected Biosensor field an electrical reference potential (e.g. the ground potential) created. However, it is also possible that at least one not selected Biosensor field "floats", i.e. that the connectors this Biosensor field does not reach a defined electrical potential to be brought.

The amplitudes and signs of the first and second electrical drive signals are preferred chosen so that as a result of a sensor event in a biosensor field in the Only then a significant first and / or second Detection signal is generated when the first connection of the biosensor field with the first control unit and simultaneously the second connection of the biosensor field is coupled to the second control unit. In other words, the values of the first and second are electrical Control signals are preferably selected such that a non-selectable one Biosensor field, at the first connection of which the first control signal is applied and at the second connection of the second control signal is not designed, not capable is to carry out redox recycling processes. Furthermore, the values of the first and second electrical control signals preferably chosen so that an unselectable Biosensor field, at the first connection of which the first control signal is not applied and at the second connection the second control signal is not capable is to carry out redox recycling processes. Only those biosensor fields are selected at its first connection the first control signal and at its second Connection of the second control signal is present.

An embodiment is advantageous of the biosensor array according to the invention as an active sensor chip, in which integrated circuits with any Functions may be included. An analog-to-digital converter circuit can be located in the substrate of the biosensor array be integrated, which is set up such that it is an analog converts electrical signal into a digital signal and the evaluation unit provides. Furthermore, an electrical supply unit in be integrated into the substrate, which is set up in such a way that the first and / or the second control unit and / or the Selection unit electrical voltage signals and / or electrical Can provide current signals. In addition, in the substrate a digital-to-analog converter circuit be integrated, which is set up in such a way that it is a digital one Convert the signal of the supply unit into an analog signal and the control unit and / or the selection unit can provide. An input / output interface for connecting a external device can be provided on the biosensor array. This can be set up, for example, as a digital I / O interface. Furthermore, an amplifier unit can be integrated in the substrate, set up for reinforcement of the first and / or the second electrical detection signal. Due to an amplification "on-chip" it is avoided that a prone to failure, analog signal runs along a long signal line and hence interference is exposed. This improves the signal-to-noise ratio.

The at least one first signal line, on the one hand, and the at least one second signal line, on the other hand, are preferably formed at least partially in two different conductor levels (for example metallization levels) in and / or on and / or below the substrate. The use of two different line levels enables an electrically insulated line crossing between the first and second signal lines. The two line levels (in particular metal levels) can be implemented in the same way as in processes in microelectronics is known. There, the metal levels above the bulk material (the substrate) are often embedded in intermetallic dielectrics. Alternatively, however, it is also possible for one of the line levels to be implemented in the same level (and preferably made of the same material) as the transducer elements themselves (for example gold material from interdigital electrodes). In other words, the biosensor fields can be formed in exactly one of the line levels.

Furthermore, in a first line section, in which the at least one first signal line and the at least a second signal line free of mutual intersection are, the at least one first signal line and the at least one second signal line running in the same plane. Can also in a second line section, in which the at least one first Signal line and the at least one second signal line itself cross each other, the at least a first signal line and the at least one second signal line running on different levels be trained.

In other words, a second Manager level not necessarily buried with respect to a first manager level be provided. It is also possible, both levels partly in the same level as the transducers realize, and to manufacture from the same material as the transducers. Then there is only in intersection areas between first and second signal lines a bridging of the Junction area required to provide electrical insulation between To ensure control lines and detection lines. Between those in the bridging area is in different levels of line sections preferably an electrically insulating material between the lines to use.

The first line section is preferably the at least one first signal line and / or the at least one second signal line with the second line section of the at least a first signal line and / or the at least one second Signal line by means of at least one essentially vertical to the substrate arranged electrical contacting element coupled. In particular, vias are possible to line sections a first signal line (and / or a second signal line), that run in different levels, each with each other couple.

The at least one first signal line and / or the at least one second signal line can be on an underside of the substrate or extending beneath the substrate his.

In other words, a management level for example on the underside of a substrate (e.g. printed circuit board) be realized. Therefor plated-through holes are required. Furthermore, below the A dielectric layer are formed in the substrate electrically conductive Structures are embedded to form signal lines.

The biosensor fields of the biosensor arrays according to the invention can in a substantially rectangular, preferably square, hexagonal or triangular matrix. With a matrix-shaped rectangular Arrangement of the biosensor fields with the same number of rows and columns (square matrix) is a particularly favorable ratio of Number of required signal lines (or pads) to the number of biosensor fields.

The control unit can be used for all biosensor fields common first supply unit and / or the second control unit can one for all biosensor fields have a common second supply unit, wherein the first supply unit is set up in such a way that with it to the at least one selected biosensor field the first electrical control signal can be applied, and / or wherein the second Supply unit is set up so that with it to the at least one selected Biosensor field, the second electrical control signal can be applied.

In other words, for example only common voltage source as the first supply unit or a single common voltage source as a second supply unit be provided using the functionality of the selection unit each with a biosensor field or part of the biosensor fields (e.g. a column or row of biosensor fields) to this biosensor field or these biosensor fields provide appropriate electrical control signal. The usage a single common first supply unit or one single common second supply unit reduces manufacturing costs of the biosensor array.

The first and the second control unit can be set up in such a way that an electrical reference signal can be applied to at least some of the non-selected biosensor fields, the value of which is essentially the mean value of the first and the second control signal. Redox recycling processes can only take place on a selected biosensor field if the first control signal is applied to its first connection and the second control signal is preferably applied to the second connection with the opposite sign, since the occurrence of redox recycling processes is sufficient large potential difference between the connections required. By using the arithmetic mean of the first and second electrical control signals (or a voltage close to the arithmetic mean) as a reference potential for the biosensor fields that are not to be selected, it is ensured that undesired redox recycling processes are avoided in unselected biosensor fields are. In other words, to one port or an electrical reference potential (for example the ground potential) is frequently applied to both connections of an unselected biosensor field. However, it is also possible that at least one non-selected biosensor field "floats", that is to say that the connections of this biosensor field are not brought to a defined electrical potential.

The first control unit can be used for one first group of biosensor fields one belonging to the respective group Have supply unit, which first supply unit such is set up that with it to the biosensor fields of the associated first Group the first electrical control signal can be applied, and / or the second control unit can for a second group of biosensor fields, a second one belonging to the respective group Have supply unit, which second supply unit such is set up that with it to the biosensor fields of the associated second Group the second electrical control signal can be applied.

For example, in a matrix arrangement the biosensor fields for each column of sensor fields as a common voltage source the supply unit associated with the biosensor fields arranged along a column be provided. Furthermore, for each row of sensor fields another common voltage source than that along the line arranged second biosensor fields associated second supply unit be provided.

The control units or the selection unit can in particular be set up such that one of the supply units in each case the associated Group of biosensor fields provides an electrical drive signal, whereas the others Supply units the associated Biosensor fields a reference potential, for example the electrical Ground potential, provide.

The first detection unit can one for all biosensor fields have a common first measuring unit (for example an ammeter), which first measuring unit is set up in such a way that with it exactly one selected Biosensor field, the electrical first detection signal can be detected is. Alternatively or in addition the second detection unit can be a common one for all biosensor fields have second measuring unit (for example an ammeter), which second measuring unit is set up in such a way that it is accurate a selected biosensor field the electrical second detection signal can be detected.

The first detection unit can for one each third group of biosensor fields one of the respective third Group associated have first measuring unit, each of the first measuring units being such is set up with it at exactly one selected biosensor field the associated third group, the electrical first detection signal can be detected is.

Furthermore, the second detection unit for each a fourth group of biosensor fields one of the fourth Group associated have second measuring unit, each of the second measuring units is set up in such a way that it is at exactly one selected biosensor field the associated fourth group, the electrical second detection signal can be detected is.

Furthermore, the biosensor array according to the invention have a potentiostat device that is set up in this way is that with it at least part of the biosensor fields constant electrical potential can be predetermined.

In particular, the potentiostat device have a reference electrode, a counter electrode and an operational amplifier, a first input of the operational amplifier with the reference electrode, a second input of the operational amplifier with a reference potential (for example the electrical ground potential) and an output of the operational amplifier is coupled to the counter electrode.

Furthermore, for each row of biosensor fields each has its own first DC voltage source and can be used for each column biosensor fields each have their own second DC voltage source be provided. About that can also for each row of biosensor fields has its own first current detection unit and can for each column of biosensor fields has its own second current detection unit be provided. Then can simultaneously for all biosensor fields collect the sensor events, by recording total flows in all rows and columns. Under use A suitable correlation calculation can be made from correlated row and column streams the individual sensor signals of the individual biosensor fields are calculated back become. This works especially well when in a particular Operating state very few or even a single biosensor field has a sensor signal. In the latter case it is essentially only in a row line and in a column line an electrical one Current detectable, so that a sensor event in the biosensor field in the intersection of the row line with the column line can be closed.

Furthermore, the method according to the invention for operating the biosensor array according to the invention described. Refinements of the biosensor array also apply to the method for operating the biosensor array according to the invention.

For the at least one selected biosensor field, it is preferably determined based on the first and / or the second detection signal whether sensor events have taken place on the at least one selected biosensor field and / or in what quantity sensor events take place on the at least one selected biosensor field are.

Examples are the biosensor fields as redox recycling biosensor fields configured, and is a first DC voltage as a first control signal and as a second control signal a second DC voltage with respect to the If the first DC voltage is selected with an inverse sign, it can be applied to a selected redox recycling biosensor field hybridization event that has occurred can be demonstrated by the fact that Redox recycling processes at the selected redox recycling biosensor field due to the applied between the electrodes of this biosensor field sufficiently strong voltage is generated. This is done using Detecting an electrical current on one of the signal lines or recorded on both signal lines, the value and the time dependency of the stream information about it returns whether on the selected Biosensor field a sensor event has occurred or in what quantity sensor events have occurred there. This can be used to determine whether particles contained in an analyte to be examined contain are, and possibly in what concentration the particles to be detected in which analytes are contained.

Embodiments of the invention are shown in the figures and are explained in more detail below.

Show it:

1 an interdigital electrode arrangement according to the prior art,

2 a sensor array according to a first embodiment of the invention,

3A to 3C Cross-sectional views of a redox recycling biosensor field in the 2 shown biosensor arrays in different operating states,

4 a biosensor array according to a second embodiment of the invention,

5 a biosensor array according to a third embodiment of the invention,

6 a biosensor array according to a fourth embodiment of the invention,

7 a biosensor array according to a fifth embodiment of the invention,

8th a biosensor array according to a sixth embodiment of the invention,

9 a biosensor array according to a seventh embodiment of the invention,

10 a biosensor array according to an eighth embodiment of the invention.

11 is a schematic plan view of an intersection of three signal lines according to the in 10 shown biosensor array.

Are in different embodiments Identical components with the same reference numbers.

The following will refer to 2 a redox recycling biosensor array 200 described according to a first embodiment of the invention.

The redox recycling biosensor array 200 has a silicon substrate 201 and four in matrix form on the silicon substrate 201 arranged redox recycling biosensor fields 202 on, each of which has a first connection 203 and a second connector 204 having. There are also two first signal lines 205 and two second signal lines 206 provided, the first signal lines 205 from the second signal lines 206 are electrically isolated. The first connection in each case 203 of every redox recycling biosensor field 202 is with exactly one of the at least one first signal line 205 coupled and the second connector 204 of every redox recycling biosensor field 202 is with exactly one of the at least one second signal line 206 coupled. As in 2 is shown, each of the first signal lines 205 with two of the redox recycling biosensor fields 202 coupled, and it's every other signal line 206 also with two of the redox recycling biosensor fields 202 coupled. There is also a first control unit 207 for providing a first electrical control signal and a second control unit 208 provided for providing a second electrical control signal. In addition, one with the first control unit 207 coupled first detection unit 209 and one with the second control unit 208 coupled second detection unit 210 are provided, which are set up in such a way that they detect a first and second electrical detection signal of a selected biosensor field resulting from the first and the second control signal. There is also a selection unit 211 provided, which is set up in such a way that it is the first control unit 207 with the first signal line 205 of a redox recycling biosensor field to be selected 202a and the second control unit 208 with the second signal line 206 of the redox recycling biosensor field to be selected 202a couples with which the redox recycling biosensor field 202a is selected. By means of the selection unit 211 , in the 2 schematically by a first switching device 211 and a second switching device 211b is symbolized, according to the exemplary embodiment described, exactly one of the redox recycling biosensor fields 202 selected. To do this, use the selection unit 211 the biosensor field to be selected, according to the in 2 scenario shown the redox recycling biosensor field 202a , with the first control unit 207 and with the second control unit 208 coupled in such a way that to the selected redox recycling biosensor field 202a by means of the first control unit 207 a first electrical control signal is applied, and that to the selected redox recycling biosensor field 202a a second control signal is applied by means of the second control unit. The first switching device 211 points for every first signal line 205 an associated switch on, the schal between two positions can be tet, the corresponding first signal line with the first control unit according to a first switch position 209 is coupled, and wherein according to a second switch position the respective first signal line 205 at electrical ground potential 212 lies. Analogously, the second switching device 211b for every second row line 206 a switch that can be in one of two possible switch positions. The associated second signal line is in accordance with a first switch position 206 with the second control unit 208 coupled, according to a second switch position, the respective second signal line is located 206 at electrical ground potential 212 , According to the in 2 shown scenario is only according to 2 bottom left redox recycling biosensor field 202 selected because according to the switch positions of 2 only this sensor field on the first connection 203 with the first control unit 207 and on the second connector 204 with the second control unit 208 is coupled. By means of the first control unit 207 will be connected to the first 203 of the selected redox recycling biosensor field 202a a positive electrical voltage is applied, and by means of the second control unit 208 is connected to the second connector 204 of the selected redox recycling biosensor field 202a a negative electrical voltage is applied. Therefore, the potential difference between the two connections 203 . 204 in the selected redox recycling biosensor field 202a larger than for the three non-selected redox recycling biosensor fields 202 , In the latter case, one of the connections is in each case 203 . 204 at electrical ground potential 212 , and the other connector 204 . 203 is either on that of the first control unit 207 provided positive electrical potential or on that of the second control unit 208 provided negative electrical potential. Therefore, only the selected redox recycling biosensor field is sufficient 202a the potential difference between the two connections 203 . 204 in the event of a hybridization event at the selected redox recycling biosensor field 202a Generate electrochemical redox recycling processes to a sufficient extent.

The following will refer to 3A to 3C the design of one of the redox recycling biosensor fields 202 . 202a using the example of the selected redox recycling biosensor field 202a described.

In 3A is the selected redox recycling biosensor field 202a with a first electrode 300 and a second electrode 301 shown that in the silicon substrate 201 are integrated. On the first electrode 300 is a stopping area 302 applied from gold material. The holding area 302 is used to immobilize DNA probe molecules 303 as capture molecules on the first electrode 300 , On the second electrode 301 such a holding area is not provided.

Should be using the redox recycling biosensor field 202a DNA strands 304 with a base sequence that is complementary to the sequence of the immobilized DNA probe molecules 303 , are recorded, so the redox recycling biosensor field 202a with a solution to be examined, namely an electrolyte 305 , brought into contact in such a way that in the solution to be examined 305 DNA strands possibly contained 304 with one to the sequence of the DNA probe molecules 303 complementary sequence with the DNA probe molecules 303 can hybridize.

In 3B is shown a scenario in which in the solution to be examined 305 DNA strands to be detected 304 are included, one with a DNA probe molecule 303 is hybridized. The DNA strands 304 are in the solution to be examined with an enzyme label 306 marked, with which it is possible to split molecules described below into electrochemically activated partial molecules. Usually a significantly larger number of DNA probe molecules 303 provided as DNA strands to be detected 304 in the solution to be examined 305 are included.

After that in the solution to be examined 305 contained DNA strands 304 including the enzyme label 306 with the immobilized DNA probe molecules 303 are hybridized, a special flushing of the redox recycling biosensor field is preferably carried out 202a , During the rinsing, DNA molecules that are not hybridized with capture molecules can be removed. An electrochemically inactive substance is added to the rinsing solution used for rinsing, which contains molecules by means of the enzyme 306 can be split into two sub-molecules 308 , of which at least one is electrochemically active and usually has an electrical charge.

The partial molecules negatively charged according to the described embodiment 308 be like in 3C shown to the positively charged electrode 300 drawn what by means of an arrow 309 is indicated. The negatively charged sub-molecules 308 are on the first electrode 300 to the one above the first port 203 by means of the first control unit 207 a positive electrical potential is applied, oxidized, and are called oxidized sub-molecules 310 to the negatively charged second electrode 301 pulled to the above the second connector 204 by means of the second control unit 208 a negative electrical potential is applied. There they are reduced again. The reduced sub-molecules 311 in turn migrate to the positively charged first electrode 300 , In this way, an electrical circuit current is generated which is proportional to the number of each by means of the enzymes 306 generated charge carriers.

For the functionality of the selected redox recycling biosensor field 202a is essential that one of the electrodes 300 sufficiently strong positive towards one of the other electrodes 301 is loaded so that the reduction and oxidation processes can take place. For this reason, the redox recycling biosensor fields are not selected 202 out 2 not able according to the operating state shown, by the detection units 211 . 209 generate detectable, sufficiently strong currents, even if a sensor event has occurred on them.

An example of a chemical system suitable for redox recycling is the use of a salt solution as a buffer solution, an alkaline phosphatase as a label molecule 306 and of para-aminophenol phosphate as an electrochemically inactive substance 307 , The subspecies to be oxidized generated by means of the label can be para-aminophenol, the subspecies generated by means of the label to be reduced can be quinonimine.

The following will refer to 4 a biosensor array 400 described according to a second embodiment of the invention.

With the biosensor array 400 is a variety of redox recycling biosensor fields 202 matrix-shaped on a silicon substrate 201 arranged. The biosensor array 400 has n rows and m columns of redox recycling biosensor fields arranged in a matrix 202 on. Furthermore, as in 4 shown, m first signal lines 205 and n second signal lines 206 provided, that is, n + m signal lines. A first signal line in the intersection area 205 each with a second signal line 206 is a redox recycling biosensor field designed as an interdigital electrode arrangement 202 arranged. This contains two interdigital electrodes that interlock with one another in a finger shape 401 . 402 that are similar to those in 1 shown interdigital electrodes 102 . 103 ,

The first control unit 207 has a first DC voltage source Vg 403 and a further connection to which an electrical ground potential 212 is provided. The first switching device 211 has m first switch 404 on, each with one of the first signal lines 205 is coupled. A column of redox recycling biosensor fields is selected by the redox recycling biosensor fields of the column with the first DC voltage source Vg 403 be coupled. All other columns from the redox recycling biosensor fields 202 are the first switches due to the appropriately selected switch positions 404 with the electrical ground potential 212 coupled as in 4 shown. According to the in 4 The scenario shown is only the redox recycling biosensor fields 202 in the second column from the left with the first DC voltage source Vg 403 coupled.

A row of redox recycling biosensor fields 202 is selected by the line to be selected, according to the in 4 shown scenario, the second line from above, with a second DC voltage source Vc 405 of the second control unit 208 is coupled. This is done by means of a suitable choice of the switch positions of second switches 406 the second switching device 211b , Furthermore, the second control unit contains a connection that has the electrical ground potential 212 provides.

The first detection unit is a first current detection unit Ig 407 for detecting an electrical current of a selected column line 205 realized, and the second detection unit is implemented as a second current detection unit Ic 408, by means of which an electric current flowing on a selected line can be detected.

Furthermore, the biosensor array 400 a potentiostat device. This is made up of a reference electrode 409 on the substrate 201 , a counter electrode 410 on the substrate 201 and an operational amplifier 411 , which is arranged outside the chip ("off-chip"). A non-inverting input 411a of the operational amplifier 411 is at an electrical ground potential 212 , An inverting input 411b of the operational amplifier 411 is with the counter electrode 410 coupled. Together, these components form a potentiostat circuit. This can be used to advantage to an analyte that is in the biosensor array 400 is introduced to assign a stable electrochemical potential with low resistance. This configuration with a potentiostat device is particularly advantageous if the biosensor fields are set up as redox recycling biosensor fields.

With the biosensor array 400 are the first control lines 205 and the second drive lines 206 formed in different levels so that electrically insulated cable crossings are possible. All m columns can optionally with the first DC voltage source Vg 403 or with electrical ground potential 212 be coupled. Every n rows can optionally with the second DC voltage source Vc 405 or with the electrical ground potential 212 be coupled. Using the current detection instruments Ig 407 and IC 408 can the electrical currents through the associated DC voltage sources 403 . 405 flow, be measured. In the configuration given, generator and collector current can therefore be characterized. Since these currents are approximately of the same magnitude, only one of the currents can optionally be measured. The detection of a current is sufficient and represents a realization with minimal effort. The detection of both currents enables a redundant detection of a sensor event and therefore an increased detection sensitivity and error robustness.

For readout operation, the positive voltage Vg is applied to exactly one column and the negative voltage Vc to exactly one row. The electrical is on all other rows and columns ground potential 212 , As in 4 Sketched with "+" and "-" signs is only due to the redox recycling biosensor field 202a in the crossing area of the selected line 206 and the selected column 205 there is a sufficiently large potential gradient to allow both the processes of oxidation and reduction. On all other redox recycling biosensor fields 202 is the voltage on at least one of the connections 203 . 204 in terms of amount, it is smaller than the threshold value which must be exceeded in order to initiate both desired electrochemical processes. If necessary, you can use one of the electrodes 401 or 402 when the voltages are applied, there is a one-time short current surge, which, however, subsides quickly and not as in the selected redox recycling biosensor field 202a is a continuously increasing current. On most of the redox recycling biosensor fields 202 the matrix is on both connections 203 . 204 the electrical ground potential 212 ,

The following will refer to 5 a biosensor array 500 described according to a third embodiment of the invention.

Generator and collector current, ie Ig and Ic, are often very similar in terms of amount in redox recycling biosensor fields, but have different signs. In principle, it is therefore sufficient to measure and evaluate only one of the two currents. An embodiment of the biosensor array according to the invention based on this fact is shown in 5 shown.

With the biosensor array 500 is going to all column lines 205 by means of the first DC voltage source Vg 403 the voltage Vg is applied. Furthermore, everyone except one of the row lines 206 the voltage Vg of the first DC voltage source Vg 403 placed. Only at the according 5 second line from the top is the second switch due to the switch positions 406 a coupling between the associated second signal line 206 and the second DC voltage source Vc 405 manufactured. This is due to all redox recycling biosensor fields 202 except for the redox recycling biosensor fields 202 in the selected second line 501 the potential difference zero. For all redox recycling biosensor fields 202 the selected line 501 the requirement for the applied voltages for the occurrence of oxidation and reduction processes is fulfilled. That means that all ORP recycling biosensor fields of the selected row 501 can supply electrical current if sensor events take place on them. However, since only the electric current complies with the 2 second column of redox recycling biosensor fields 202 due to the switch positions of the first switches 404 is measured according to the in 5 shown scenario, only the electrical current of the selected redox recycling biosensor field 202a detected. In this way, selective switch positions can be selected 404 . 406 each of the redox recycling biosensor fields 202 can be selected separately within the matrix.

Alternatively, the functions of lines and Columns are interchanged, as are the roles of Vg and Vc, the is called then the value Ic is recorded instead of the value Ig.

The following will refer to 6 a biosensor array 600 described according to a fourth embodiment of the invention.

With the biosensor array 600 is for every first signal line 205 , that is to say for each column of redox recycling biosensor fields 202 , a separate first DC voltage source 601 Vy, i with i = 1, 2, ..., m and a first current detection device 603 Iy, i provided with i = 1, 2, ..., m. Furthermore, for every second signal line 206 , that is to say for each row of redox recycling biosensor fields 202 , each a separate second DC voltage source 602 Vx, j with j = 1, 2, ..., n and a separate second current detection device 604 Ix, j with j = 1, 2, ..., n provided. Each column and each row is clearly provided with a separate voltage source and with a separate current measuring instrument. Depending on the assignment of voltages to the voltage sources shown, this configuration can be used to operate the sensor arrangement 4 or off 5 can be achieved. An advantage with the biosensor array 600 is that parallel or row-by-column reading is possible. The in 6 Embodiment shown, the selection unit in the control of the DC voltage sources 601 respectively. 602 integrated because each of the voltage sources can be switched on or off.

The following will refer to 7 a biosensor array 700 described according to a fifth embodiment of the invention.

With the biosensor array 700 is every column of redox recycling biosensor fields 202 , that means every first signal line 205 , with a separate first DC voltage source 601 and with a separate first current detection device 603 coupled. In contrast, for the different lines of redox recycling biosensor fields 202 a common third DC voltage source Vg 701 and fourth DC voltage source Vc 702 provided, by means of the second switch 406 exactly one row of redox recycling biosensor fields with the fourth DC voltage source Vc 702 is coupled, whereas all other lines with the third DC voltage source Vg 701 are coupled. According to the in 7 The embodiment shown is only the selected line 501 with the fourth DC voltage source Vc 702 coupled. According to the scenario shown, all first DC voltage sources deliver 601 the electrical potential Vg, so that only at the redox recycling biosensor fields 202 the selected line 501 there is a sufficiently large potential difference that Redox recycling processes can occur to a sufficient extent. These sensor signals are read out line by line by each of the first current detection devices 603 the electrical current from exactly one assigned redox recycling biosensor field of the selected line 501 detected.

According to a similar principle, each can can be read column by column.

The following will refer to 8th a biosensor array 800 described according to a sixth embodiment of the invention.

The biosensor array 800 has a first circuit block 801 and a second circuit block 802 on, as well as an input / output interface 803 that with the two circuit blocks 801 . 802 is coupled. At the input / output interface 803 For example, a sensor signal can be provided, for example an electrical control signal or an electrical detection signal.

The biosensor array 800 represents a so-called "active" chip. This is understood to mean a semiconductor substrate in which monolithic circuits are integrated which can have different functions. In particular, the components are voltage sources 403 respectively. 601 , Current detection units 407 respectively. 603 , Operational amplifier 411 and parts of the selection unit 211 in the first circuit block 801 integrated, and there are other components like the second voltage sources 405 respectively. 602 , Current detection devices 408 respectively. 604 , other parts of the selection unit 211 , etc. in the second circuit block 802 integrated. Furthermore, there are further components for signal preprocessing and signal processing in the circuit blocks 801 . 802 Realized on-chip. In addition, the chip of the biosensor array points 800 a defined (e.g. digital) interface configured according to the needs of the respective application 803 (I / O) on.

The use of the architecture according to the invention on active chips can be advantageous, for example, if a size Number of relatively small areas Interdigital structures are used, the area of which no longer allows an active control circuit below each sensor of the respective sensor. There are also special ones Advantages when the performance requirements the circuits implemented on-chip is very large. The latter applies in particular when the area of a sensor element is decisive Impact on performance (e.g. the noise).

The following will refer to 9 a biosensor array 900 described according to a seventh embodiment of the invention.

The biosensor array 900 is an arrangement of redox recycling biosensor fields 202 , which are provided as a triangular matrix with three wiring directions. Furthermore, there is a common first DC voltage source 403 Vg as the first control unit and a common first current detection device 407 Ig provided as the first detection unit. It also has a second DC voltage source 405 Vc and a second current detection unit coupled to it 408 Ic provided as a second detection unit. The selection unit 211 is by means of a variety of switches 901 symbolized with controllable switch positions. The switch positions are by means of the selection unit 211 controllable. Furthermore, in 9 first lines 902 , second lines 903 and third lines 904 arranged in such a way that in (electrically isolated from each other) crossing areas of the lines 902 to 904 they intersect at 60 ° angles. In particular, in 9 a selected redox recycling biosensor field 202a shown that as a result of the in 9 shown switch positions of the switches 901 is selected. A first switch 901 is in such a switch position that the first connection 203 of the selected redox recycling biosensor field 202a with the first DC voltage source 403 Vg and with the first current detection device 407 Ig is coupled. There is also a second switch 901b in such a switch position that the second connection 204 of the selected redox recycling biosensor field 202a with the second DC voltage source Vc 405 and with the second current detection unit 408 Ic is coupled. The switch positions of all other switches 901 are in such a position that the on this switch 901 adjacent first, second and third signal lines 902 to 904 at electrical ground potential 212 are. In other words, according to the in 9 shown scenario the selected redox recycling biosensor field 202a the only one of the redox recycling biosensor fields 202 that both with the DC voltage source 403 Vg, as well as with the DC voltage source 405 Vc is coupled. According to the in 9 The scenario shown acts on the selected redox recycling biosensor field 202a connected first line 902 as a second signal line 206 , whereas the selected redox recycling biosensor field 202a connected second line 903 as the first signal line 205 acts. Each of the switches 901 has three switch positions, so that the associated lines 902 to 904 optionally with the electrical ground potential 212 , the DC voltage source Vg 403 or the DC voltage source Vc 405 can be coupled. This makes an independent measurement at every position of the sensor array 900 possible. The configuration of 9 corresponds to the configuration of 4 , but in an architecture with a triangular matrix.

The following will refer to 10 a biosensor array 1000 described according to an eighth embodiment of the invention.

The biosensor array 1000 corresponds to the configuration of 5 , however, is in an architecture with a triangular matrix arrangement of the redox recycling biosensor fields 202 executed. According to the in 10 The scenario shown is the first switch 901 in such a switch position that the associated second line 903 with the current detection unit 407 Ig is coupled. Furthermore, the second switch 901b in such a position that the associated first line 902 as the only one with the second DC voltage source Vc 405 is coupled. All other switches of the switches 901 are in such a position that the associated lines 902 to 904 with the first voltage source 403 Vg are coupled. This will get between the connectors 203 . 204 of the selected redox recycling biosensor field 202a the potential difference Vg - Vc is applied, and it becomes that on the first signal line 205 flowing current by means of the first current detection unit 407 detected.

The following will refer to 11 described how an intersection area 1001 between one of the first lines 902 , one of the second lines 903 and one of the third lines 904 can be realized using only two wiring levels.

In 11 is a first level of metallization 1100 and is a second level of metallization 1101 shown in top view. The first level of metallization 1100 is in a direction perpendicular to the paper plane of 11 opposite the second level of metallization 1101 shifted, that is, the paper plane of 11 is parallel to the surface of the biosensor array 900 , In the intersection area 1101 meet one of the first lines 902 that are completely in the first level of metallization 1100 is provided, one of the second signal lines 903 that are completely in the second metallization level 1101 is provided, and one of the third lines 904 who, as in 11 shown, partly in the first metallization level 1100 and to another part in the second metallization level 1101 is provided. To in the intersection area 1001 electrical insulation of the signal lines 902 to 904 The third line is to enable each other 904 in 11 in a first section 904 , in a second section 904b and into a third section 904c divided up. The first paragraph 904 and the third section 904c run in the second metallization level 1101 , whereas the second section 904b in the first level of metallization 1100 runs. Using vertical contacting elements 1102 that are perpendicular to the paper plane of 11 are arranged in a trending manner is the first section 904 with the second section 904b or the second section 904b with the third section 904c the third line 904 coupled. This allows three lines using only two metallization levels 902 to 904 cross each other without breaking the electrical insulation.

In this context, it should be noted that a matrix-like arrangement with three (or more) wiring directions does not necessarily have to be implemented with three (or more) independent wiring levels. In any case, two wiring levels are sufficient, as in 11 shown schematically.

The following are in this document Publications quotes:

• [1] R. Hintsche et al, "Microelectrode arrays and application to biosensing devices ", Biosensors & Bioelectronics, p. 697-705, 1994
• [2] R. Hintsche et al., "Microbiosensors using electrodes made in Si-technology "in" Frontiers in Biosensorics I ", F. Scheller et al. ed., Birkhäuser, Basel, Switzerland, 1997
• [3] M. Paeschke et al, "Highly sensitive electrochemical microsensors using submicrometer electrode arrays ", sensors and Actuators B, p. 394-397, 1995
• [4] WO 00/62048
• [5] R. Thewes et al., "Sensor Arrays for Fully Electronic DNA Detection on CMOS ", Proc. Int. Solid-State Circuits Conf. (ISSCC), p. 350, 2002

100

Redox recycling biosensor

101

substratum

102

first Interdigital electrode

103

second Interdigital electrode

104

reference electrode

105

counter electrode

106

differential amplifier

106a

non-inverting entrance

106b

inverting entrance

106c

output

107

ground potential

108

first DC voltage source

109

second DC voltage source

110

first ammeter

111

second ammeter

200

Redox recycling biosensor array

201

Silicon substrate

202

Redox recycling biosensor zones

202a

selected redox recycling biosensor fields

203

first connection

204

second connection

205

first signal line

206

second signal line

207

first control unit

208

second control unit

209

first detection unit

210

second detection unit

211

selector

211

first switching device

211b

second switching device

212

ground potential

300

first electrode

301

second electrode

302

holding area

303

DNA probe molecules

304

DNA strands

305

electrolyte

306

Enzyme Label

307

molecules

308

part molecules

309

arrow

310

oxidized part molecules

311

reduced part molecules

400

Biosensor array

401

first Interdigital electrode

402

second Interdigital electrode

403

first DC voltage source

404

first switch

405

second DC voltage source

406

second switch

407

first Current detecting unit

408

second Current detecting unit

409

reference electrode

410

counter electrode

411

operational amplifiers

411a

non-inverting entrance

411b

inverting entrance

411c

output

500

Biosensor array

501

selected row

600

Biosensor array

601

first DC voltage sources

602

second DC voltage sources

603

first Current detecting devices

604

second Current detecting devices

700

Biosensor array

701

third DC voltage source

702

fourth DC voltage source

800

Sensor array

801

first circuit block

802

second circuit block

803

Input / output interface

900

Biosensor array

901

switch

901

first switch

901b

second switch

902

first cables

903

second cables

904

third cables

904

first section

904b

second section

904c

third section

1000

Biosensor array

1001

crossing area

1100

first metallization

1101

second metallization

1102

contacting

Claims (25)

Biosensor array - With a substrate; - With a plurality of biosensor fields arranged on the substrate, each of which has a first connector and a second connector having; - With at least one first signal line and at least one second Signal line, whereby - the at least one first signal line from the at least one second Signal line is electrically isolated; - the first connection in each case of each biosensor field coupled with exactly one of the at least one first signal line and the second connection of each biosensor field with exactly one of the at least one second signal line is coupled; - at least one of the at least one first signal line and at least one the at least one second signal line with at least two of the Biosensor fields is coupled; - With a first control unit for providing a first electrical control signal and with a second control unit for providing a second electrical control signal, - with one with the first Control unit coupled first detection unit and / or with a second detection unit coupled to the second control unit, which is or are set up in such a way that they are one from the first and the second electrical control signal resulting first and / or second electrical detection signal of a selected biosensor field captured or captured; - With a selection unit which is set up in such a way that it first control unit with the first signal line to be selected Biosensor field and the second control unit with the second signal line the one to be selected Biosensor field couples, with which the biosensor field is selected. Biosensor array according to claim 1, with an evaluation unit, which is set up in such a way that it is based on the at least one selected biosensor field determined on the first and / or the second detection signal, whether sensor events on the at least one selected biosensor field and / or in what quantity at the at least one selected biosensor field Sensor events have occurred. Biosensor array according to claim 1 or 2, wherein at least one the biosensor field is an electrochemical biosensor field. Biosensor array according to claim 3, wherein at least one of the Biosensor fields a redox recycling biosensor field is. Biosensor array according to one of claims 1 to 4, wherein the biosensor field has a first and a second electrode, the first electrode with the first connection and the second electrode with the second connection of the biosensor field is coupled. The biosensor array of claim 5, wherein the first and second Electrode are interdigital electrodes. Biosensor array according to one of claims 1 to 6, wherein the biosensor fields to a plurality of biosensor groups are grouped in such a way that each biosensor group is optionally separate from the other biosensor groups or together with at least one Part of the other biosensor groups is operable. Biosensor array according to one of claims 1 to 7, wherein the substrate - a ceramic substrate; - a semiconductor substrate; - a glass substrate; or - on Plastic substrate is. Biosensor array according to one of claims 1 to 8, wherein the first and the second electrical control signal with electrical DC signals are of different sign and in which the first and / or second electrical detection signal is an electrical current. Biosensor array according to one of claims 1 to 9, wherein the values of the first and the second electrical control signal are set in this way are that as a result of a sensor event occurring on a biosensor field essentially only then a significant first and / or second Detection signal is generated when the first connection of the biosensor field with the first control unit and the second connection of the biosensor field is coupled to the second control unit. Biosensor array according to one of claims 2 to 10, in which in the substratum - on Analog-digital converter circuit is integrated, which is set up in this way is that it converts an analog electrical signal into a digital signal convert and provide the evaluation unit; and or - an electric one Integrated supply unit, which is set up in such a way that the first and / or the second control unit and / or the selection unit electrical voltage signals and / or electrical Can provide current signals; and or - A digital-to-analog converter circuit is integrated, which is set up in such a way that it is a digital one Convert the signal of the supply unit into an analog signal and can provide the control unit and / or the selection unit; and or - one Input / output interface is integrated; and or - an amplifier unit, set up to reinforce the first and / or the second electrical detection signal, integrated is. Biosensor array according to one of claims 1 to 11, wherein the at least a first signal line and the at least one second signal line at least partly in two different management levels in and / or on and / or are formed under the substrate. The biosensor array of claim 12, wherein the biosensor fields are trained in exactly one of the management levels. Biosensor array according to claim 12 or 13, wherein in a first Line section in which the at least one first signal line and the at least one second signal line from one another Crossing are free, the at least a first signal line and the at least one second signal line running in the same plane are formed, and in which in a second line section, in which the at least one first signal line and the at least a second signal line cross each other, at least a first signal line and the at least one second signal line are trained in different levels. The biosensor array of claim 14, wherein the first line section the at least one first signal line and / or the at least one a second signal line with the second line section of the at least a first signal line and / or the at least one second Signal line by means of at least one essentially vertical to the substrate arranged electrical contacting element are coupled. Biosensor array according to one of claims 12 to 15, wherein the at least one first signal line and / or the at least one second signal line on an underside of the substrate or below of the substrate is designed to run. Biosensor array according to one of claims 1 to 16, wherein the first Control unit one for all biosensor fields common first supply unit and / or the second control unit one for all Biosensor fields has a common second supply unit, wherein the first supply unit is set up in such a way that with it to the at least one selected biosensor field the first electrical Control signal can be applied, and / or wherein the second supply unit is set up in such a way that it connects to the at least one selected biosensor field the second electrical control signal can be applied. The biosensor array according to claim 17, in which the first and second control units are set up in such a way that an electric Re is connected to at least some of the non-selected biosensor fields Reference signal can be applied, the value of which is essentially the average of the first and second control signal. A biosensor array according to any one of claims 1 to 18, in which the first Control unit for a first group of biosensor fields each one of the respective Group associated has first supply unit, which first supply unit is set up in such a way that it connects to the biosensor fields associated the first electrical control signal can be applied to the first group, and / or in which the second control unit for each second group of biosensor fields, a second one belonging to the respective group Has supply unit, which second supply unit such is set up that with it to the biosensor fields of the associated second Group the second electrical control signal can be applied. A biosensor array according to any one of claims 1 to 19, in which the first Detection unit one for all Biosensor zones common first measuring unit, which first measuring unit is set up in such a way that it is at exactly one selected biosensor field the electrical first detection signal is detectable and / or at which the second detection unit has in common for all biosensor fields has second measuring unit, which second measuring unit is set up in this way is that with it the electrical at exactly one selected biosensor field second detection signal is detectable. Biosensor array according to one of claims 1 to 20, wherein the first Detection unit for a third group of biosensor fields each one of the respective belonging to the third group has first measuring unit, each of the first measuring units being such is set up with it at exactly one selected biosensor field the associated third group, the electrical first detection signal can be detected and / or in which the second detection unit for each a fourth group of biosensor fields one of the fourth Group associated has second measuring unit, each of the second measuring units is set up in such a way that it is used in exactly one selected biosensor field associated fourth group, the electrical second detection signal can be detected is. Biosensor array according to one of Claims 1 to 21, with a potentiostat device, which is set up in such a way that it can be used in at least part of the biosensor fields introduced electrolytes a constant electrical Potential can be specified. The biosensor array of claim 22, wherein the potentiostat device has a reference electrode, a counter electrode and an operational amplifier, a first input of the operational amplifier with the reference electrode, a second input of the operational amplifier with a reference potential and an output of the operational amplifier with the counter electrode is coupled. Method for operating a biosensor array - with a biosensor array - with a substrate; With a plurality of biosensor fields arranged on the substrate, each of which has a first connection and a second connection; With at least one first signal line and with at least one second signal line, the at least one first signal line being electrically insulated from the at least one second signal line; - The first connection of each biosensor field is coupled to exactly one of the at least one first signal line and the second connection of each biosensor field is coupled to exactly one of the at least one second signal line; - At least one of the at least one first signal line and at least one of the at least one second signal line is coupled to at least two of the biosensor fields; With a first control unit for providing a first electrical control signal and with a second control unit for providing a second electrical control signal, with a first detection unit coupled to the first control unit and / or with a second detection unit coupled with the second control unit, which is set up in this way or are that they detect or detect a first and / or second electrical detection signal of a selected biosensor field resulting from the first and the second electrical control signal; With a selection unit that is set up in such a way that it couples the first control unit to the first signal line of a biosensor field to be selected and the second control unit to the second signal line of the biosensor field to be selected, whereby the biosensor field is selected; - According to the method - the first control unit is coupled to the first signal line of a biosensor field to be selected and the second control unit is coupled to the second signal line of the biosensor field to be selected, whereby the biosensor field is selected; The first signal line of the selected biosensor field is provided with a first electrical control signal and the second signal line of the selected biosensor field with a second electrical control signal; A first detection signal resulting from the first and the second electrical control signal on the first signal line of the selected Bi o-sensor field and / or a second detection signal resulting from the first and the second electrical control signal is or are detected on the second signal line of the selected biosensor field. 25. The method of claim 24, wherein for the at least one selected biosensor field determined based on the first and / or the second detection signal whether there are sensor events on the at least one selected biosensor field and / or in what quantity at the at least one selected biosensor field Sensor events have occurred.