Diagnostic device incorporating a biochemical ligand

• US 4,562,157 A
• Filed: 05/25/1984
• Issued: 12/31/1985
• Est. Priority Date: 05/25/1983
• Status: Expired due to Term

• Current Assignee: British Technology Group Ltd. (Boston Scientific Corporation)
• Original Assignee: National Research Development Corporation
• Inventors: Lowe, Christopher R., Earley, Fergus G. P.
• Primary Examiner(s): Marantz, Sidney
• Application Number:
  US06/614,121
• Time in Patent Office: 585 Days
• Field of Search: 436/806, 436/291, 436/526, 436/527, 435/176, 435/291, 435/14, 324/71.1
• US Class Current: 435/287.2
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C12Q 1/003 Functionalisation
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: Y10S 436/806 Electrical property or magnetic property

Abstract

A device useful in diagnostics in which a biochemical species is attached to the surface of a sensor, especially to the gate of a field effect transistor. In such a "BIOCHEMFET" it has been a problem to attach two or more biochemical species to the surface of the sensor, especially to the gates of a multi-gated FET. It has now been found possible to bond a group having a photoactivatable function covalently to the sensor surface, photo-expose the resultant modified surface selectively, e.g. through a mask, and bond the biochemical species, e.g. a hapten, antigen, antibody, lectin or enzyme, to the photoactivated function. In this way the biochemical species becomes attached in selected areas only. In view of the success of this technique realized under conditions of miniaturization, the invention makes possible "printed circuits for proteins".

In addition to the device are the process of manufacture thereto, use for diagnostic purposes and a diagnostic kit of the device and a partner capable of binding to the biochemical species.

Claims

1. A device for diagnostics comprising:

a sensor having a surface to which a biochemical ligand is attached covalently, in a manner effective to cause a physical characteristic of the sensor to vary according to whether a binding partner becomes bound to the ligand, wherein the biochemical ligand is attached covalently to the surface of the sensor in selected areas only thereof and through a photoactivated covalent linkage.

2. A device according to claim 1, wherein the biochemical ligand is an antigen or hapten and a physical characteristic of the sensor varies according to whether or not an antibody becomes bound to the antigen or hapten.

3. A device according to claim 1, wherein the biochemical ligand is an antibody and a physical characteristic of the sensor varies according to whether or not an antigen or hapten becomes bound to the antibody.

4. A device according to claim 1, wherein the biochemical ligand is an enzyme and a physical characteristic of the sensor varies according to whether or not a substrate becomes bound to the enzyme.

5. A device according to claim 1, wherein the biochemical ligand is a co-enzyme, steroid, sugar, electron mediator or other low molecular weight biochemical.

6. A device according to claim 1, wherein the surface of the sensor is of an inorganic oxide, oxynitride or nitride.

7. A device according to claim 6, wherein the surface is of silica or silicon nitride.

8. A device according to claim 6, wherein the surface is of iron (III) oxide and the sensor measures magnetic field strength.

9. A device according to claim 6, wherein the surface is of silica or silicon nitride and the sensor is a field effect transistor.

10. A device according to claim 1, wherein the photoactivated covalent linkage is provided by the photolysis of an aryl azide group.

11. A device according to claim 10, wherein the surface is of silica and the biochemical ligand is attached to the surface through a group of formula:

##STR7## the left bond is attached to a silicon atom of the surface and the right bond is attached to the biochemical ligand, and n is an integer from 3 to 12.

12. A device according to claim 1, wherein the sensor is a field effect transistor, the surface is of silicon nitride and the photoactivated covalent linkage is an aryl azide group.

13. A process of preparing the device claimed in claim 1, which process comprises modifying the surface of the sensor by attaching to it by covalent bonding a group containing a photoactivatable function, exposing the thus modified surface to photoactivating radiation in selected areas only of the surface to activate the photoactivatable function and reacting the photoactivatable function thus activated to bond covalently the biochemical ligand.

14. A process according to claim 13, wherein the modified surface is exposed to the photoactivating radiation through a mask.

15. A process according to claim 13, wherein different biochemical ligands are attached to different areas of the same surface.

16. A process according to claim 13, wherein the sensor is a field effect transistor, the surface is of silicon nitride and the photoactivatable function is an aryl azide group.

17. A kit for diagnostics comprising the device claimed in claim 1 and at least one binding partner for the biochemical ligand for testing or standardisation of the device.

18. The device of claim 1 wherein said physical characteristic is an electrical, magnetic, optical or thermal characteristic.