Electronic device for communication with living cells

• US 20070099173A1
• Filed: 06/10/2004
• Published: 05/03/2007
• Est. Priority Date: 06/10/2003
• Status: Active Grant

• Current Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Original Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Inventors: Shappir, Joseph, Yitzchaik, Shlomo, Spira, Micha
• Granted Patent: US 7,795,039 B2
• Time in Patent Office: Days
• US Class Current: 435/4
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07K 17/14 Peptides being immobilised on, or in, an inorganic carrier
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: G01N 2333/918 Carboxylic ester hydrolases (3.1.1)
• CPC Class Codes: G01N 27/4146 involving nanosized elements, e.g. nanotubes, nanowires
• CPC Class Codes: G01N 33/48728 Investigating individual cells, e.g. by patch clamp, voltage clamp investigating individual particles in general G01N15/10
• CPC Class Codes: H01L 29/788 with floating gate H01L29/78391 takes precedence

Abstract

The present invention provides a surface-substrate for adherence of cells thereto. The surface-substrate comprises at least one micronail structure protruding from the surface, at least a region of the micronail having cellular-internalization promoting properties. The invention also provides an electronic device comprising a transistor structure, in which a gate electrode is formed with the at least one micronail protruding from the surface thereof.

Claims

1. A surface-substrate for adherence of cells thereto comprising:

at least one micronail structure protruding from the surface, at least a region of said micronail having cellular-internalization promoting properties.

2. The surface-substrate of claim 1, wherein the cellular-internalization promoting properties are obtained by coating at least the region of the micronail with cellular internalization-promoting moieties.

3. A surface-substrate according to claim 1, wherein the micronail has a base portion and a head portion, and wherein the head portion has the cellular internalization promoting properties.

4. A surface-substrate according to claim 3, wherein the head portion is coated with cellular internalization-promoting moieties.

5. The surface-substrate of claim 2, wherein the cellular internalization-promoting moieties are selected from:

(a) hydrolytic enzymes that facilitate degradation of extracellular matrix;

(b) molecules that recognize plasma membrane components located on the external surface of the plasma membrane of cells;

or

(c) a combination of (a) and (b).

6. The surface-substrate of claim 3, wherein the head portion is composed of or coated with a metal containing material.

7. The surface-substrate of claim 6, wherein the metal is selected from:

gold, copper, aluminum, platinum, silver, or alloys of such metals or combinations of such metals.

8. The surface-substrate of claim 5, wherein the hydrolytic enzyme is selected from polysaccharide-degrading enzymes, proteinases and lipid-degrading-enzymes.

9. The surface-substrate of claim 8, wherein said hydrolytic enzyme is connected to the micronail through a biodegradable spacer molecule.

10. The surface-substrate of claim 5, wherein the molecules that recognize plasma membrane components are selected from:

ligands of plasma membrane receptors or receptor binding-parts of said ligands;

receptors that recognize plasma membrane components;

lectins that bind to plasma-membrane glycoproteins;

antibodies that recognize plasma-membrane components or binding fragments thereof;

integrins that recognize short linear amino acid sequences in ECM proteins;

or a combination of two or more of the above.

11. The surface-substrate of claim 5, wherein the molecules that recognize plasma components are molecules which bind to polysaccharides that are part of proteoglycans in the ECM plasma membrane.

12. The surface-substrate of claim 1, further comprising molecules that promote adhesion of cells.

13. The surface-substrate of claim 12 wherein the molecules that promote adhesion of cells are present on at least one of the following:

the base portion of the micronail, and the region surrounding the base portion.

14. The surface-substrate of claim 12, wherein said adhesion molecules are in the form of a charged monolayer.

15. The surface-substrate of claim 14, wherein said charged monolayer is a positively charged monolayer of polylysine, or polyaniline and a like.

16. The surface-substrate of claim 15, wherein said positively charged monolayer of polylysine, or polyaniline is assembled on a polystyrenesulfonate layer, said polystyrenesulfonate layer comprising anion units connected through a linker to the micronail.

17. A surface-substrate according to claim 1, adapted to form a cell-communicating part of an electrode.

18. A surface-substrate according to claim 17, wherein the electrode is a gate electrode.

19. A surface-substrate according to claim 17, wherein a base portion of the micronail is electrically isolated from its surrounding.

20. A surface-substrate according to claim 17, wherein the micronail is electrically isolated from its surrounding.

21. A surface-substrate according to claim 18, wherein the micronail is a conductive rod such as poly-silicon rod, which is an integral part of the polysilicon gate electrode, and is insulated from the surrounding by a thin insulating layer.

22. A surface-substrate according to claim 18, in the form of an integrated structure manufactured by lithography and etching techniques.

23. A surface-substrate according to claim 19, wherein the base portion of the micronail is made of tungsten, and is isolated from the surrounding by a layer of silicon nitrade.

24. An electrode, comprising the surface-substrate of claim 17.

25. An electrode according to claim 24 being a gate electrode.

26. An electrode according to claim 25 having a single micronail.

27. An electrode according to claim 25 having a cluster of micronails.

28. An electrode according to claim 27, wherein the size of the cluster is smaller than the size of the cell to be in communication with the electrode.

29. An electrode according to claim 24, coated with a layer of immobilized recognition molecules that, in the presence of cell-secreted components, catalyze a reaction that causes release of ions in a media surrounding said recognition molecule.

30. An electrode according to claim 29, being a gate electrode.

31. A electrode according to claim 29, wherein the distance between the recognition molecules and the surface of the coated gate is smaller than 15 Å

.

32. An electrode according to claim 29, wherein the receptor molecules are enzymes or peptides.

33. An electrode according to claim 32, wherein the recognition molecules catalyze said reaction in the presence of a cell-secreted component selected from acetylcholine, glutamate, GABA, serotonin, neurotransmitters and/or neuroendocrines, growth factors, or cytokines.

34. An electrode according to claim 33, wherein said recognition molecule is acetylcholine esterase.

35. An electrode according to claim 30, wherein said gate-electrode is an ion sensitive gate.

36. An electrode according to claim 35, wherein the ion-sensitive material is Aluminum Oxide (Al₂O₃), Silicon Nitride (Si₃N₄), Indium Tin Oxide (In₃O₃Sn₂O₃), Silicon Oxide (SiO₂) or Tantalum Oxide (Ta₂O₅).

37. An electrode according to claim 29, wherein the recognition molecules are immobilized via linker molecules that are covalently bound to at least one of the surface-substrate and the recognition molecules.

38. An electrode according to claim 37, wherein said linker molecules are selected from conjugated or unconjugated aliphatic, aromatic or heteroaromatic molecules, having at least one functional group capable of covalently binding to said surface and at least one functional group capable of covalently binding to said recognition molecules.

39. A device for the detection of cell secreting components comprising an electrode arrangement having at least one electrode of claim 29.

40. A device for the detection of cell secreting components comprising at least one pair of source-drain electrodes and at least one gate-electrode of claim 31 forming together at least one Field Effect Transistor (FET).

41. A device for electric communication with a cell comprising an electrode arrangement having at least one electrode of claim 24.

42. A device for electrical communication with a cell comprising at least a pair of source-drain electrodes and at least one gate electrode as defined in claim 25, thereby defining together at least one Field Effect Transistor (FET).

43. A device according to claim 41, wherein the electrical communication with the cell is achieved by a property selected from:

(a) detecting the presence of currents, or current changes in cells;

(b) detecting field potential or field potential change in cells;

(c) providing a current to cells;

(d) providing field potential to cells;

or

(e) a combination of two or more of (a) to (d).