Signal recording of a receptor-effector-system by an extracellular planar potential-sensitive electrode

• US 6,602,399 B1
• Filed: 03/22/2000
• Issued: 08/05/2003
• Est. Priority Date: 03/22/2000
• Status: Expired due to Term

• Current Assignee: Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften e.V. (Max-Planck-Gesellschaft zur Frderung der Wissenschaften e)
• Original Assignee: Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften e.V. (Max-Planck-Gesellschaft zur Frderung der Wissenschaften e)
• Inventors: Meyer, Elisabeth, Straub, Bernhard, Fromherz, Peter
• Primary Examiner(s): Nguyen, Nam
• Assistant Examiner(s): Noguerola, Alex
• Application Number:
  US09/532,871
• Time in Patent Office: 1,231 Days
• Field of Search: 204/403, 204/403.01, 435/4, 436/149, 422/82.01, 422/82.02, 205/777.5
• US Class Current: 205/777.5
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: G01N 33/6872 Intracellular protein regulatory factors and their receptors, e.g. including ion channels

Abstract

The present invention relates to bioelectronic devices comprising living cells which are in operative contact with an extracellular planar potential-sensitive electrode, e.g. a field effect transistor. The cells comprise an ion channel/receptor system which is responsive to stimuli. Thus, the device is suitable as a bioelectronic sensor. The electrode may also have a capacitive stimulating spot, with which the electrical or functional state of the cell or its ion channel/receptor system may be affected.

Claims

1. A bioelectronic device comprising

(a) a cell which expresses an ion channel/receptor system wherein said ion channel/receptor system comprises an ion channel component that mediates an ion current through a cell membrane and a receptor component;

and

(b) an extracellular potential-sensitive electrode wherein the cell is in operative contact with said electrode,

wherein the cell has been manipulated to overexpress said ion channel/receptor system.

2. The device of claim 1, wherein said cell is a eukaryotic cell.

3. The device of claim 1

wherein the cell is transfected with nucleic acid molecules encoding components of the ion channnel/receptor system.

4. The device of claim 1, wherein said ion channel is selected from voltage-gated ion channel, ligand-gated ion channels, mechanically-gated ion channels or combinations thereof.

5. The device of claim 1, wherein the potential-sensitive electrode is located on a chip.

6. The device of claim 5

wherein the chip has at least one integrated field-effect transistor comprising at least one source and a drain or an electrode as stimulating spot for applying voltages.

7. The device of claim 6

wherein the cell is in operative contact with at least one gate region between a source and a drain or stimulating spot.

8. The device of claim 1, wherein the potential-sensitive electrode is a metal-electrode.

9. The device of claim 1, wherein a voltage drop is measured across the ion channel or the membrane.

10. The device of claim 1, wherein the receptor component in response to a change in stimuli causes the ion channel component to change the ion current.

12. A method of using a bioelectric device, the method comprising:

providing the bioelectric device of claim 1; and

using the bioelectric device to detect changes in the ion channel current with an extracellular potential-sensitive electrode.

13. The method of claim 12, wherein a change in an environmental parameter is sensed as a detectable signal on the electrode.

14. The method of claim 12 wherein the environmental parameter is an effector for the receptor component of the ion channel/receptor system.

15. The method of claim 14 further comprising:

determining if a test substance activates or inhibits the receptor component.

11. A bioelectronic device comprising

(a) a cell which expresses an ion channel/receptor system wherein said ion channel/receptor system comprises an ion channel component that mediates an ion current through a cell membrane and a receptor component;

and

(b) an extracellular planar potential-sensitive electrode wherein the cell is in operative contact with said electrode,

wherein the ion channel is the potassium channel hSlo.

16. The device of claim 11 wherein said cell is a eukaryotic cell.

17. The device of claim 11, wherein the potential-sensitive electrode is located on a chip.

18. The device of claim 17, wherein the chip has at least one integrated field effect transistor comprising at least one source and a drain or an electrode as a stimulating spot for applying voltages.

19. The device of claim 18, wherein the cell is in operative contact with at least one gate region between a source and a drain or stimulating spot.

20. The device of claim 11, wherein the potential-sensitive electrode is a metal-electrode.

21. The device of claim 11, wherein the potential-sensitive electrode is a transistor.

22. A bioelectronic device comprising

(a) a cell which expresses an ion channel/receptor system wherein said ion channel/receptor system comprises an ion channel component that mediates an ion current through a cell membrane and a receptor component;

and

(b) an extracellular planar potential-sensitive electrode wherein the cell is in operative contact with said electrode,

wherein the ion channel is the ionotropic glutamate receptor NMDA.

23. The device of claim 22 wherein said cell is a eukaryotic cell.

24. The device of claim 22, wherein the potential-sensitive electrode is located on a chip.

25. The device of claim 24, wherein the chip has at least one integrated field effect transistor comprising at least one source and a drain or an electrode as a stimulating spot for applying voltages.

26. The device of claim 25, wherein the cell is in operative contact with at least one gate region between a source and a drain or stimulating spot.

27. The device of claim 22, wherein the potential-sensitive electrode is a metal-electrode.

28. The device of claim 22, wherein the potential-sensitive electrode is a transistor.