Artificial synapse chip interface for electronic prosthetic retina

• US 20030032946A1
• Filed: 06/27/2002
• Published: 02/13/2003
• Est. Priority Date: 06/29/2001
• Status: Active Grant

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Inventors: Ziebarth, Jonathan M., Bloom, David M., Peterman, Mark C., Blumenkranz, Mark, Bent, Stacey F., Fishman, Harvey A., Leng, Theodore, Lee, Christina
• Granted Patent: US 7,001,608 B2
• Time in Patent Office: Days
• US Class Current: 604/890.1
• CPC Class Codes: A61N 1/0543 Retinal electrodes
• CPC Class Codes: A61N 1/326 for promoting growth of cells, e.g. bone cells
• CPC Class Codes: A61N 1/36046 of the eye
• CPC Class Codes: C12M 35/00 Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion machines for extracting juice from animal or plant tissue by electroplasmolysis A23N1/006, processes employing electric or wave energy B01J19/08; treatment of microorganisms or enzymes with electrical or wave energy C12N13/00; methods for cell fusion C12N15/02; introduction of foreign genetic material C12N15/87
• CPC Class Codes: C12M 35/02 Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
• CPC Class Codes: C12M 35/08 Chemical, biochemical or biological means, e.g. plasma jet, co-culture
• CPC Class Codes: C12N 2503/00 Use of cells in diagnostics
• CPC Class Codes: C12N 2535/10 Patterned coating
• CPC Class Codes: C12N 5/0619 Neurons

Abstract

The invention provides microfabricated devices and methods for directing the growth of a cell process to form an artificial synapse. The devices are called artificial synapse chips. The artificial synapse comprises a nanofabricated aperture (about 50-100 nm in size) that connects the cell process to a chemical or electrical means of neuronal excitation. Such an aperture width mimics the length scales of a natural synapse and thus emphasizes the localized spatial relationship between a neuron and a stimulation source. The invention further provides devices and methods for regenerating a nerve fiber into an electrode. The invention thus provides a regeneration electrode that uses a novel neural interface for stimulation and that uses novel surface methods for directing neuronal growth making possible in vivo connection of the devices to neural circuitry in a retina and other anatomical locations.

Claims

1. A device for directing the growth of a cell process, comprising a substrate with a surface configured to receive a cell process and a micropattern effective to direct the growth of a cell process in a desired direction on said surface.

2. The device of claim 1, wherein said surface further comprises a desired location, and wherein the micropattern is effective to direct the growth of a cell process to said desired location on said surface.

3. The device of claim 2, wherein said desired location is selected from the group consisting of a nanoaperture, an electrical contact, and a micropattern feature.

4. The device of claim 1, wherein the micropattern comprises features selected from the group consisting of chemoattractant factors, adhesion molecules, repulsive molecules, surface contours, and at least one region enriched in particular atoms.

5. The device of claim 1, wherein the micropattern is produced by contacting a substrate surface with a microcontact printing stamp.

15. The regeneration electrode assembly of claim 14, wherein the neurite-directing device comprises a device of claim 1.

6. A device for delivering neuromodulatory agents to at least a portion of a cell, comprising a surface and a reservoir, said reservoir being effective to contain said neuromodulatory agents, said surface having an exterior face, an interior face and a nanoaperture, said nanaperture providing a connecting path between said interior and said exterior faces, said exterior face being configured to contact a cell, said interior face being in contact with said reservoir, said nanoaperture effective to provide a conduit for the delivery of said neuromodulatory agents from said reservoir to at least a portion of said cell.

7. The device of claim 6, wherein said exterior surface comprises a micropattern effective to direct the growth of a cell process.

8. The device of claim 6, wherein the micropattern comprises features selected from the group consisting of chemoattractant factors, adhesion molecules, repulsive molecules, a surface contours, and at least one region enriched in particular atoms.

9. The device of claim 6, wherein the neuromodulatory agents are selected from the group consisting of neurotransmitters, hormones, ions, messenger molecules, nucleic acids, nucleic acid vectors, drugs, cells, cell fragments, cell organelles, liposomes, and other biologically active materials.

10. A device for contacting and stimulating at least a portion of a cell, the device comprising a surface, said surface having an exterior face and a circuit, said exterior face being configured to contact a cell, said circuit having at least one contact, said circuit being effective stimulate at least a portion of a cell adjacent said contact.

11. The device of claim 10, wherein said stimulation of at least a portion of a cell comprises cell stimulation selected from the group consisting of stimulation of a neurite, stimulation of a cell through a neurite, and direct stimulation of a cell.

12. The device of claim 10, wherein the surface comprises a micropattern.

13. The device of claim 12, wherein the micropattern comprises features selected from the group consisting of chemoattractant factors, adhesion molecules, repulsive molecules, surface contours, and at least one region enriched in particular atoms.

17. The regeneration electrode assembly of claim 14, wherein the circuit comprises a device of claim 10.

34. A method for producing an intra-ocular device, comprising providing a device of claim 10 configured for implantation into an eye.

35. The method of claim 34, wherein the device is configured for implantation into a region of the eye.

36. The method of claim 35, wherein the region is selected from the group consisting of the retina, the region adjacent the inner limiting membrane and the subretinal space.

14. A regeneration electrode assembly comprising a neurite-directing device and a circuit effective to contact and stimulate at least a portion of a cell.

16. The regeneration electrode assembly of claim 14, wherein the neurite-directing device comprises a device of claim 6.

37. A method for producing an intra-ocular device, comprising providing a regeneration electrode assembly of claim 14 configured for implantation into an eye.

38. The method of claim 37, wherein the regeneration electrode assembly is configured for implantation into a region of the eye.

39. The method of claim 38, wherein the region is selected from the group consisting of the retina, the region adjacent the inner limiting membrane and the subretinal space.

18. A method of directing the growth of a cell process in a desired manner from a cell capable of growing a cell process, the method comprising:

providing a surface comprising a micropattern, and

contacting a cell capable of growing a cell process, effective to direct the growth of a cell process from said cell in a desired manner.

19. The method of claim 18, wherein said micropattern comprises features selected from the group consisting of chemoattractant factors, adhesion molecules, repulsive molecules, surface contours, and at least one region enriched in particular atoms.

20. The method of claim 18, further comprising contacting a surface with a microcontact printing stamp.

21. A method of directing the growth of a cell process from a cell capable of growing a cell process to a location adjacent a contact of a circuit, the method comprising:

providing a surface comprising a circuit and a micropattern, and

contacting a cell capable of growing a cell process with said surface, effective to direct the growth of a cell process from said cell to a location adjacent said contact.

22. The method of claim 21, wherein said micropattern comprises features selected from the group consisting of chemoattractant factors, adhesion molecules, repulsive molecules, surface contours, and at least one region enriched in particular atoms.

23. The method of claim 21, further comprising contacting a surface with a microcontact printing stamp.

25. The method of claim 23, wherein said desired location comprises a nanoaperture.

26. The method of claim 23, wherein said desired location comprises a contact of a circuit, said circuit being effective stimulate at least a portion of a cell adjacent said contact.

27. The method of claim 23, wherein providing a stimulus further comprises delivering a neuromodulatory agent.

28. The method of claim 26, wherein said neuromodulatory agent is selected from the group consisting of neurotransmitters, hormones, ions, messenger molecules, nucleic acids, nucleic acid vectors, drugs, cells, cell fragments, cell organelles, liposomes, and other biologically active materials.

29. The method of claim 23, wherein stimulating a cell comprises stimulating selected from the group consisting of stimulating a cell process, stimulating a cell through a cell process, and stimulating a cell directly.

31. The microfabricated artificial synapse of claim 29, wherein said micropattern comprises features selected from the group consisting of a chemoattractant factors, adhesion molecules, repulsive molecules, surface contours, and at least one region enriched in particular atoms.

32. The microfabricated artificial synapse of claim 29, further comprising a reservoir connected to said nanoaperture, said reservoir configured to contain neuromodulatory agents.

33. The microfabricated artificial synapse of claim 31, wherein the neuromodulatory agents are selected from the group consisting of neurotransmitters, hormones, ions, messenger molecules, nucleic acids, nucleic acid vectors, drugs, cells, cell fragments, cell organelles, liposomes, and other biologically active materials.

24. A method of stimulating at least a portion of a cell capable of growing a cell process, comprising:

contacting a cell with a surface comprising a micropattern and a desired location;

directing the growth of a cell process from the cell to a position adjacent said desired location; and

providing a stimulus from said desired location to said cell process effective to stimulate at least a portion of the cell.

30. A microfabricated artificial synapse comprising a microfabricated device having a surface with a micropattern and a nanoaperture, said micropattern effective to direct the growth of a cell process, and a cell having a cell process, said cell process being directed by said micropattern to contact said nanoaperture.

40. A system for implantation into an animal comprising an artificial synapse chip (ASC), a photosensitive device, a communication link between the ASC and the photosensitive device, and a power source.

41. The system of claim 40, wherein the photosensitive device is in operative contact with the ASC.

42. The system of claim 40, wherein the photosensitive device is part of the ASC.

47. The system of claim 40, wherein the ASC comprises a microfluidic system comprising a fluid delivery channel.

48. The system of claim 47, further comprising a means for causing fluid flow in said fluid delivery channel.

49. The system of claim 48, wherein said means for causing fluid flow in said fluid delivery channel comprises a piston configured to move within a cylinder.

43. A device for contacting a portion of a cell with a fluid, comprising a substrate with a surface configured to receive a cell process and a micropattern effective to direct a cell process to a desired location on said surface, and a microfluidic system comprising a fluid delivery channel configured to direct a fluid to said desired location.

44. The device of claim 43, wherein said desired location comprises an aperture.

45. The device of claim 44, further comprising a means for causing fluid flow in said fluid delivery channel.

46. The device of claim 45, wherein said means for causing fluid flow in said fluid delivery channel comprises a piston configured to move within a cylinder.

50. A method for treating an eye disorder, comprising implanting a photosensitive assembly into an eye, said photosensitive assembly comprising a photosensitive device effective to respond to light with photoactivated signals, an artificial synapse chip, a power source effective to power said photosensitive device, and an operative connection between said photosensitive device and said artificial synapse.

51. The method of treating an eye disorder of claim 50, further comprising directing the growth of cell processes of retinal neurons effective to contact said photosensitive assembly effective to stimulate retinal neurons by photoactivated signals derived from said photosensitive assembly.

52. The method of claim 51, wherein said directing the growth of cell processes of retinal neurons comprises contacting cell processes of retinal neurons with a micropatterned surface.

53. The method of claim 52, wherein said micropatterned surface comprises a surface of an artificial synapse chip.

54. The method of claim 53, wherein said micropatterned surface comprises a micropattern configured to direct cell processes towards a desired location on a surface of an artificial synapse chip.

55. The method of claim 54, wherein said desired location comprises an aperture.