Monolithically Integrated Hybridisation Sensor Assembly and Associated Production Method

• US 20070236224A1
• Filed: 06/27/2005
• Published: 10/11/2007
• Est. Priority Date: 06/29/2004
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Paulus, Christian, Augustyniak, Marcin
• Granted Patent: US 9,645,106 B2
• Time in Patent Office: Days
• US Class Current: 324/425
• CPC Class Codes: G01N 27/3276 being a hybridisation with immobilised receptors using a FET type sensor G01N27/4145; concerning the hybridisation C12Q1/68

Abstract

A monolithically integrated sensor assembly is for detecting molecules that are potentially contained in an analyte. The assembly includes: a substrate; at least one sensor electrode, which is located on or in the substrate and is coated with a sensor-active layer, on which electrochemically active particles are generated in the present of the molecules to be detected, the particles being detected via an electric sensor signal on the sensor electrode(s); at least one additional electrode that is located on or in the substrate; and an operating circuit that is integrated into the substrate for controlling the sensor electrode and the additional electrode(s).

Claims

1. A monolithically integrated sensor assembly for detecting particles possibly contained in an analyte, comprising:

a substrate;

at least one sensor electrode, arranged at least one of on and in the substrate, coatable with a sensor-active layer at which are generated electrochemically active particles in the presence of particles to be detected, the electrochemically active particles being detectable via detection of an electrical sensor signal at the at least one sensor electrode;

at least one additional electrode, arranged at least one of on and in the substrate;

at least one comparison electrode, at which an electrical comparison signal independent of the sensor signal is detectable; and

an operating circuit, integrated at least one of on and in the substrate, to drive the at least one sensor electrode and the at least one additional electrode, the operating circuit including at least one evaluation unit, by which a sensor event is determinable at the at least one sensor electrode on the basis of the sensor signal and the comparison signal.

2. The monolithically integrated sensor assembly as claimed in claim 1, wherein

the at least one additional electrode includes at least one counterelectrode and at least one reference electrode, the monolithically integrated sensor assembly further comprising:

a potentiostat circuit, integrated at least one of on and in the substrate and serving for providing a predetermined electrical potential.

3. The monolithically integrated sensor assembly as claimed in claim 1, wherein the substrate is a CMOS chip.

4. The monolithically integrated sensor assembly as claimed in claim 1, wherein the monolithically integrated sensor assembly is

set up as at least one of a biosensor assembly and a chemosensor assembly.

5. The monolithically integrated sensor assembly as claimed in claim 1, wherein the monolithically integrated sensor assembly is

set up as at least one of a DNA sensor assembly, a protein sensor assembly and an antibody sensor assembly.

6. The monolithically integrated sensor assembly as claimed in claim 1, wherein the evaluation unit is set up in such a way that it forms a difference between the sensor signal and the comparison signal.

7. The monolithically integrated sensor assembly as claimed in claim 1,

wherein the evaluation unit includes an operational amplifier, integrated in the substrate, to processes the sensor signal and the comparison signal.

8. The monolithically integrated sensor assembly as claimed in claim 7, wherein

the operational amplifier is set up for the integration of electrical charge carriers.

9. The monolithically integrated sensor assembly as claimed in claim 1, wherein the at least one comparison electrode is free of a sensor-active layer.

10. The monolithically integrated sensor assembly as claimed in claim 1, wherein

the at least one comparison electrode includes a signaling coating to generates a predeterminable quantity of electrochemically active particles in the case of a predeterminable change in the electrical potential, independently of the sensor event.

11. The monolithically integrated sensor assembly as claimed in claim 1, wherein

the at least one sensor electrode and the at least one comparison electrode have an essentially identical geometry.

12. The monolithically integrated sensor assembly as claimed in claim 1, further comprising:

a plurality of comparison electrodes, sensor event being determinable at the at least one sensor electrode on the basis of the sensor signal and the comparison signals of the plurality of comparison electrodes.

13. The monolithically integrated sensor assembly as claimed in claim 1, further comprising:

means for keeping constant the electrical potentials at the at least one sensor electrode and at the at least one comparison electrode.

14. The monolithically integrated sensor assembly as claimed in claim 13, wherein

the means for keeping constant the electrical potentials includes at least one capacitance.

15. The monolithically integrated sensor assembly as claimed in claim 1, further comprising:

a subtraction capacitance for forming the difference between the sensor signal and the comparison signal, a first terminal of the subtraction capacitance being coupleable to the at least one sensor electrode, and a second terminal of the subtraction capacitance being coupleable to the at least one comparison electrode.

16. The monolithically integrated sensor assembly as claimed in claim 1, further comprising:

a first comparison electrode, at which a zero signal is generatable;

a second comparison electrode, at which a full signal is generatable.

17. The monolithically integrated sensor assembly as claimed in claim 1, further comprising:

an analog/digital converter for forming a digital output signal on the basis of the sensor signal and the comparison signal.

18. The monolithically integrated sensor assembly as claimed in claim 16, further comprising:

an analog/digital converter for forming a digital output signal on the basis of the sensor signal and the comparison signal, wherein

the zero signal and the full signal form the upper and the lower electrical reference potential of the analog/digital converter.

19. A sensor array, comprising a plurality of monolithically integrated sensor assemblies as claimed in claim 1, formed on and/or in the substrate.

20. The sensor array as claimed in claim 19, wherein

at least one of the comparison electrodes is provided jointly for at least one portion of the sensor assemblies.

21. The sensor array as claimed in claim 19, further comprising:

a drive unit, set up to selectively drive one sensor assembly, a portion of the sensor assemblies or all of the sensor assemblies.

23. The monolithically integrated sensor assembly as claimed in claim 2, wherein the substrate is a CMOS chip.

24. The monolithically integrated sensor assembly as claimed in claim 2, wherein the monolithically integrated sensor assembly is set up as at least one of a biosensor assembly and a chemosensor assembly.

25. A sensor array, comprising a plurality of monolithically integrated sensor assemblies as claimed in claim 2, formed on and/or in the substrate.

26. The sensor array as claimed in claim 20, further comprising:

a drive unit, set up to selectively drive one sensor assembly, a portion of the sensor assemblies or all of the sensor assemblies.

22. A method for producing a monolithically integrated sensor assembly for detecting particles possibly contained in an analyte, the method comprising:

forming, at least one of on and in a substrate, at least one sensor electrode which is coated with a sensor-active layer at which are generated electrochemically active particles in the presence of particles to be detected, the electrochemically active particles being detectable via detection of an electrical sensor signal at the at least one sensor electrode;

forming at least one additional electrode at least one of on and in the substrate;

forming at least one comparison electrode, an electrical comparison signal, indepeNdent of the sensor signal, being detectable at the at least one comparison electrode; and

integrating an operating circuit, for driving the at least one sensor electrode and the at least one additional electrode, at least one of on and in the substrate, the operating circuit including at least one evaluation unit by which a sensor event is determinable at the at least one sensor electrode on the basis of the sensor signal and the comparison signal.