Hybrid electrical device with biological components

• US 20020050611A1
• Filed: 08/22/2001
• Published: 05/02/2002
• Est. Priority Date: 02/22/1999
• 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 6,703,660 B2
• Time in Patent Office: Days
• US Class Current: 257/315
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• 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 29/66825 with a floating gate H01L29/6684 takes precedence
• CPC Class Codes: H01L 29/788 with floating gate H01L29/78391 takes precedence
• CPC Class Codes: H10B 41/00 Electrically erasable-and-programmable ROM [EEPROM] devices comprising floating gates
• CPC Class Codes: H10B 41/40 characterised by the peripheral circuit region
• CPC Class Codes: H10K 10/701 Organic molecular electronic devices

Abstract

The present invention concerns an electrical junction between one transistor and at least one voltage sensitive cell such as a neuron. The invention further concerns transistors to be used in said junction and methods for their preparation. By another aspect the invention concerns “an artificial chemical synapse” i.e. a junction between a cell, which secretes an agent, and a transistor bearing receptors for the agent, wherein binding of the agent to the receptor changes an electrical property off the transistor.

Claims

1. An electrical junction between one transistor and at least one voltage-sensitive cell (VSC) characterized by at least one of the features selected from the group consisting of:

(i) voltage transfer between the transistor and the VSC is bi-directional, the transistor being a floating gate depletion type device, the VSC being associated with the floating gate and being capable of being stimulated by a voltage pulse applied to the source, channel and drain of the transistor;

(ii) there is no DC bias between the transistor and the solution containing the VSC, the transistor being a depletion type device;

(iii) the VSC is anchored to the external surface of the transistor by binding moieties, optionally through spacers;

(iv) the voltage transfer between the membrane of the VSC and the external surface of the transistor, and between the external surface of the transistor and the membrane of the VSC is mediated by hyper-polarizable chromophores;

(v) a combination of two or more of the features of (i) to (iv).

4. A junction according to claim 1, wherein the transistor utilizes a semiconductor-based integrated technology.

5. An electrical junction according to claim 4, wherein the floating gate is shaped such that its one portion is accommodated in an active area defined by an active component of the transistor, and its other portion is accommodated outside said active area defining a site for the VSC accommodation.

6. An electrical junction according to claim 5, wherein the transistor comprises a screening metalization layer accommodated in the vicinity of the active area.

7. An electrical junction according to claim 6, wherein said screening metallization layer is metal of lower chemical activity than the commonly used aluminum.

8. An electrical junction according to claim 7, wherein said metal is gold.

9. An electrical junction according to claim 4, wherein said semiconductor integrated technology is based on Si structures.

10. An electrical junction according to claim 4, wherein said semiconductor integrated technology is based on GaAs structures.

15. A device for detecting voltage changes from at least one VSC and/or for the transfer of voltage changes to at least one VSC comprising:

the junction of claim 1, wherein a floating gate of the transistor is electrically connectable to said at least one VSC within an area outside an active area defined by an active component of the transistor.

18. A device for detecting voltage changes from a plurality of VSCs and/or for the transfer of voltage changes to a plurality of VSCs comprising an array of transistor elements, each transistor element being independently operable and comprising a floating gate depletion type transistor in voltage transfer association with the VSC, thereby forming the junction of claim 1, and two regular type transistors coupled to source and drain electrodes, respectively, of said floating gate depletion type transistor.

24. A junction according to claim 1(iii), wherein the binding moieties are proteins, polypeptides, peptides or lectins immobilized on the external surface of the transistor and capable of binding to membranal components present on the membrane of the VSC.

26. A junction according to claim 1(iv), wherein the hyper-polarizable chromophore is of the general structure A—

Z—

D, wherein;

A is a mono, bi or tricyclic heteroaryl moiety;

Z is a π

-bridging moiety chosen from y=y, wherein y is CH or N;

alkyne, furan, thiophene, pyrrole, styrene, phenyl, biphenyl;

D is B—

NR₁R₂ wherein B is a phenyl, biphenyl or thiophene;

R₁ and R₂, which may be the same or different, are (CH2)_n—

R, R being an amino, hydroxyl or a lower alkyl, or R₁ and R₂ may be part of a polycyclic heteroaryl system.

28. An electrical junction according to claim 1, characterized by a combination of features (i), (ii), (iii) and (iv).

2. An electrical junction between one transistor and at least one voltage-sensitive cell (VSC) characterized by that voltage transfer between the transistor and the VSC is bi-directional, the transistor being a floating gate depletion type device, the VSC being associated with the floating gate and being capable of being stimulated by a voltage pulse applied to the source, channel and drain of the transistor.

3. An electrical junction between one transistor and at least one voltage-sensitive cell (VSC) characterized by that there is no DC bias between the transistor and the solution containing the VSC, the transistor being a depletion type device.

11. A device for selectively detecting voltage changes from a VSC and transferring voltage changes to the VSC, the device comprising:

an electrical junction between a floating gate depletion type transistor and the VSC, which is associated with the floating gate and is capable of being stimulated by a voltage pulse applied to the gate of the floating gate transistor; and

a switching transistor connected by either one of its source and drain electrodes to the gate of said floating gate transistor to apply said voltage pulse by supplying voltage to a gate of the switching transistor.

12. A device according to claim 11, characterized in that the VSC is anchored to the external surface of the transistor by binding moieties, optionally through spacers.

13. A device according to claim 11, characterized in that the voltage transfer between the membrane of the VSC and the external surface of the transistor, and between the external surface of the transistor and the membrane of the VSC is mediated by hyper-polarizable chromophores.

14. A device according to claim 12, characterized in that the voltage transfer between the membrane of the VSC and the external surface of the transistor, and between the external surface of the transistor and the membrane of the VSC is mediated by hyper-polarizable chromophores.

16. A device according to claim 15, wherein the electrical connection is capacitance-based connection.

17. A device according to claim 15, wherein said transistor is a depletion type device, the electrical connection being bi-directional,

20. A transistor according to claim 19, further comprising a screening metalization layer accommodated in the vicinity of the active area.

21. A transistor according to claim 19, further comprising binding moieties located on its external surface within said site.

22. A transistor according to claim 21, wherein the binding moieties are proteins, polypeptides, peptides or lectins immobilized to the external surface of the transistor and capable of binding with membranal components present on the membrane of the VSC.

23. A transistor according to claim 22, wherein the binding moieties are selected from the group consisting of:

antibodies, receptors, ligands, lectins and adhesion molecules.

25. A junction according to claim 24, wherein the binding moieties are selected from the group consisting of:

antibodies, receptors, ligands, lectins and adhesion molecules.

27. A junction according to claim 26, wherein the hyper-polarizable chromophore is selected from the group consisting of azobenzene dyes, stilbene dyes, azomethyne dyes, cyanine, hemicyanine, merocyanine, stylbene, azobenzene, [5-(1-mediyl-thiazolidene-2-ylidene) ethylene]4-oxo-2-thioxo-thiazolidene-3-5-(4-dimethyylacid sodium salt (MMT) 5-(4-Dimethylamino-benzylidene)-rodanine (DBR), thiazolidenes and rodanines.

30. A transistor according to claim 29, wherein the hyper-polarizable chromophores are of varying lengths.

31. A transistor according to claim 29, wherein the hyper-polarizable chromophores are attached to spacers of varying lengths.

32. A transistor according to claim 31, wherein the lengths of the spacers vary between 1 nm to 30 nm.

33. A transistor according to claim 31, wherein the spacers are selected from the group consisting of:

oligosaccharides, straight and branched hydrocarbon, polymers and hetero-atom containing molecules.

34. A method for the production of the transistor of claim 29, comprising the steps of:

coating the transistor outer layer with a monolayer of SiX₃RX moiety, where X is a halogen and R is a (CH₂)_nn=1-18 or (CH₂)_naryl, n=1-6 group thus forming a halogen terminated monolayer,

reacting said halogen terminated monolayer with a hyper-polarizable chromophore or chromophore precursor; and

optionally further attaching to the outerlayer of the hyper-polarizable chromophore a siloxane derivative or a peptide having 5-20 amino acids.

35. A method for the production of the transistor of claim 21, comprising the steps of:

coating the transistor outer layer with a monolayer of SiX₃RX moiety, where X is a halogen and R is a (CH₂)_nn=1-18 or (CH₂)_naryl, n=1-6 group thus forming a halogen terminated monolayer;

optionally converting said terminal halogen to another chemical reactive moiety such as amine, maleimide, succinimide or hydroxyl;

reacting said chemical reactive terminated monolayer with the binding moiety under conditions enabling formation of a covalent binding between the binding moiety and the halogen.

37. An electrochemical junction according to claim 36, wherein the electronic to property is capacitance.

38. An electrochemical junction according to claim 36, wherein the electronic property is change in dipole movement.

39. An electrochemical junction according to claim 36, wherein the cell is a neuron, the secreted agent is a neurotransmitter and the agent secreting region of the cell is tie pre-synaptic region of the neuron.

40. An electrochemical junction according to claim 39, wherein the neurotransistor is acetyl choline and the catalytic moiety is acetyl choline esterase.

19. A floating gate transistor to be used in a hybrid device for communicating with a VSC, the transistor having an active area defined by its active component, and source and drain electrodes making contacts to the active component, wherein the floating gate has its first portion accommodated in the vicinity of the active area thereabove, and a second portion accommodated outside said active area being displaced therefrom in a plane defined by the active component, said second portion defining a site for the VSC accommodation.

29. A transistor having immobilized on its external surface hyper-polarizable chromophores.

36. An electrochemical junction between an agent-secreting cell and a transistor comprising:

the agent-secreting region of the cell positioned at an orientation enabling transfer of the agent to a location on the surface of the transistor, said location having immobilized thereon recognition moieties capable of affinity binding to said agents;

said binding between the recognition moiety and the agent causing the modulation of at least one electronic property of the transistor;

said location further comprising catalytic moieties capable of degradation of said agent.