Lipid membrane electroanalytical elements and method of analysis therewith

• US 4,490,216 A
• Filed: 01/12/1984
• Issued: 12/25/1984
• Est. Priority Date: 02/03/1983
• Status: Expired due to Term

• Current Assignee: Molecular Devices
• Original Assignee: Molecular Devices
• Inventors: McConnell, Harden M.
• Primary Examiner(s): Kaplan, G. L.
• Application Number:
  US06/570,063
• Time in Patent Office: 348 Days
• Field of Search: 357/25, 324/71.6, 204/403, 204/1 T, 204/1 E, 435/817
• US Class Current: 205/777.5
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
• CPC Class Codes: G01N 33/552 Glass or silica
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode

Abstract

Electroanalytical elements are provided involving a polarity-sensitive layer; a first lipid layer non-diffusively bound to said polarity-sensitive layer; and, a second amphiphilic layer, with hydrophilic heads distal from said first lipid layer and defining a polar layer which interacts with said polarity-sensitive layer. The device is used in polar media to detect variations in the electrostatic interaction between the polar layer and the polarity-sensitive layer.

Claims

1. A device sensitive to changes in polarity, comprising:

a solid electrically conductive layer having a first surface for binding by chemical means and responsive to changes in polarity adjacent to said first surface;

a first hydrophobic layer comprising a plurality of molecules having aliphatic chains of at least six carbon atoms, non-diffusively bound to said binding surface;

a second stable lamellar hydrophobic lipid layer comprising molecules having second chains of at least six carbon atoms and polar heads, with said polar heads defining a polar layer distant from said first hydrophobic layer and separated from said first hydrophobic layer by said second chains of at least six carbon atoms layer, and wherein said individual molecules are laterally diffusible and non-covalently bound to said first lipid layer;

wherein said first and second hydrophobic layers define a bilayer membrane.

2. A device according to claim 1, wherein said electrically conductive layer is a doped silicon layer, said first surface is silicon oxide, and said molecules of said second layer are individual molecules.

3. A device according to claim 1, wherein said electrically conductive layer is a doped silicon layer, said first surface is silicon oxide, and said molecules of said second layer are at least in part cross-linked.

4. A device according to claim 1, wherein said electrically conductive layer is a doped silicon layer defining an FET device having a gate, with said first surface being silicon dioxide over said gate.

5. A device according to claim 1, wherein said electrically conductive layer is a metal.

6. A device according to claim 1, wherein a specific binding member is bound to said second hydrophobic layer.

7. A device according to claim 6, wherein an enzyme is bound to said second hydrophobic layer.

8. A method for detecting a change in the polarity of a polar medium which comprises contacting a device according to claim 1 with said polar medium and a reference electrode;

and

detecting the change in potential between said electrode and said device by effecting a change in the polar state of said medium adjacent to said device.

9. A method according to claim 8, wherein a member of a specific binding pair is bound to said second hydrophobic layer and said change is a result of binding of specific binding pair members.

10. A semiconductive device comprising:

a solid semiconductive layer having at least two areas of different dopants;

means for detecting a change in the electrical properties of said semiconductive layer;

an insulating oxide or nitride layer on a surface of said conductive layer;

bound to said insulating layer, a first hydrophobic layer comprising a plurality of molecules having aliphatic chains of at least six carbon atoms, non-diffusively bound to said insulating layer;

a second stable lamellar hydrophobic lipid layer comprising molecules having aliphatic chains of at least six carbon atoms and polar heads with said polar heads defining an electrostatically charged layer distal from said first hydrophobic layer, and wherein said individual molecules are laterally diffusible;

wherein said first and second hydrophobic layers define a bilayer membrane.

11. A device according to claim 10, wherein said semiconductive layer is silicon and said insulative layer is of from about 10 to 500Å

thick.

12. A device according to claim 11, wherein said insulative layer is of from about 10 to 100Å

thick and said molecules of said second hydrophobic layer have aliphatic chains of from about 14 to 24 carbon atoms and are individual molecules.

13. A device according to claim 11, wherein said insulative layer is of from about 10 to 100Å

thick and said molecules of said second hydrophobic layer have aliphatic chains of from about 14 to 24 carbon atoms and are at least in part cross-linked molecules.

14. A device according to claim 10, wherein a member of a specific binding pair is bound to said second hydrophobic layer.

15. A device according to claim 14, wherein said member of said specific binding pair is a ligand.

16. A device according to claim 14, wherein said member of said specific binding pair is a receptor.

17. A device according to claim 16, wherein said receptor is an enzyme.

18. A device according to claim 10, wherein said first hydrophobic layer is formed by reacting alkylsilyl halides with said insulating layer.

19. A method for detecting a species in an aqueous medium, wherein said species is a member of a specific binding pair, said method comprising:

immersing in said aqueous medium a first electrode comprising a device according to claim 10 and a reference electrode, wherein a first member of said specific binding pair is bound to said second hydrophobic layer and said aqueous medium is suspected of containing a second member which is the reciprocal binding member of said first member; and

detecting the change of potential between said electrodes as related to the amount of said second member which binds to said first member.

20. A field effect transistor transducer for detection of a change in the electrostatic environment in an aqueous medium comprising:

a semiconductor substrate having a gate and source and drain regions spaced apart by said gate;

means for detecting an electrical signal from said source and drain regions;

an insulating layer above said gate;

a first hydrophobic layer comprising a plurality of molecules having aliphatic chains of at least six carbon atoms, non-diffusively bound to said insulating layer;

a second stable lamellar hydrophobic lipid layer comprising individual molecules having chains of at least six carbon atoms and polar heads, wherein said polar heads define a polar layer distal from said first layer, and wherein said individual molecules are laterally diffusible and non-covalently bound to said first layer;

wherein said first and second hydrophobic layers define a bilayer membrane.

21. A transducer according to claim 20, wherein said semiconductor substrate is silicon.

22. A transducer according to claim 21, wherein said molecules of said first and second layers have aliphatic chains of from 6 to 24 carbon atoms.

23. A transducer according to claim 22, wherein a member of a specific binding pair is bound to said second hydrophobic layer.