Biochip

• US 8,753,874 B2
• Filed: 12/15/2003
• Issued: 06/17/2014
• Est. Priority Date: 12/19/2002
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Siemens AG
• Inventors: Gumbrecht, Walter, Stanzel, Manfred
• Primary Examiner(s): Bhat, Narayan
• Application Number:
  US10/540,208
• Publication Number:
  US 20060137984A1
• Time in Patent Office: 3,837 Days
• Field of Search: 435/283.1, 435/287.2, 204/600, 204/643, 422/68.1, 422/82.01, 536/23.1
• US Class Current: 435/287.2
• CPC Class Codes: C12M 1/34 Measuring or testing with condition measuring or sensing means, e.g. colony counters
• CPC Class Codes: G01N 27/026 Dielectric impedance spectroscopy electrochemical impedance spectroscopy for measuring corrosion G01N17/02
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

A biochip includes a flat carrier and an array of spots containing catcher molecules which are arranged on the carrier. Each spot is associated with a microelectrode arrangement for impedance spectroscopic detection of binding events occurring between the catcher molecules and the target molecules applied via an analyte solution. In order to increase the sensitivity or the binding-specific measuring effects of the bio-chip, the electrode arrangement is at least partially embedded in a hydrophilic reaction layer containing catcher molecules and which is permeable to target molecules.

Claims

1. A DNA chip, comprising:

a flat carrier;

an array of spots containing catcher molecules, each spot being assigned a microelectrode arrangement for detecting binding events between the catcher molecules and target molecules applied via an analyte solution, wherein the microelectrode arrangement is at least a two-pole system,

the microelectrode arrangement being at least partially embedded in a hydrophilic reaction layer which is permeable to target molecules and in which immobilized catcher molecules are distributed three-dimensionally, wherein the catcher molecules are configured to cause the binding events,

the hydrophilic reaction layer having a thickness approximately in the range of 1L to 5 L, L being the sum of electrode width and electrode spacing, the electrode width and the electrode spacing being approximately 1 μ

m,

wherein the chip is configured for application of an alternating voltage in a megahertz frequency, and

wherein the chip is configured to detect a capacitance change caused by the binding events within the hydrophilic reaction layer with a megahertz frequency applied to the electrodes.

2. The DNA chip as claimed in claim 1, wherein the microelectrode arrangement is a two-pole system, and wherein the hydrophilic reaction layer has a thickness of approximately 3 μ

m.

3. The DNA chip as claimed in claim 1, wherein the microelectrode arrangement is a four-pole system, and wherein the hydrophilic reaction layer has a thickness of approximately 7 μ

m.

4. The DNA chip as claimed in claim 3, wherein the hydrophilic reaction layer is an acrylamide-based radical-crosslinkable hydrogel including at least one of maleic anhydride and glycidyl (meth)acrylate as coupling groups.

5. The DNA chip as claimed in claim 1, wherein the hydrophilic reaction layer is thermally stable up to approximately 95°

C.

6. The DNA chip as claimed in claim 1, wherein the hydrophilic reaction layer contains coupling groups for the covalent binding of catcher molecules.

7. The DNA chip as claimed in claim 1, wherein the microelectrode arrangement is an interdigital electrode arrangement.

8. The DNA chip as claimed in claim 7, wherein the interdigital electrode arrangement is a two-pole microelectrode system.

9. The DNA chip as claimed in claim 7, wherein the interdigital electrode arrangement is a four-pole microelectrode system.

10. The DNA chip as claimed in claim 1, wherein the flat carrier includes a semiconductor layer and an insulating layer connected thereto, the insulating layer carrying the microelectrode arrangement and the hydrophilic reaction layer on its side remote from the semiconductor layer.

11. The DNA chip as claimed in claim 10, wherein the semiconductor layer is a silicon layer.

12. The DNA chip as claimed in claim 1, wherein the hydrophilic reaction layer comprises a hydrogel containing a cross-linking agent.

13. The DNA chip as claimed in claim 12, wherein the cross-linking agent is a dimethylacrylate or methylene bisacrylamide.

14. The DNA chip as claimed in claim 13, wherein the dimethylacrylate is tetraethylene glycol dimethylacrylate.

15. The DNA chip as claimed in claim 12, wherein the hydrophilic reaction layer is thermally cross-linked by the cross-linking agent.

16. The DNA chip as claimed in claim 12, wherein the hydrophilic reaction layer is photo-cross-linked by the cross-linking agent.