Biological sensors

• US 5,055,265 A
• Filed: 05/30/1989
• Issued: 10/08/1991
• Est. Priority Date: 06/06/1988
• Status: Expired due to Term

• Current Assignee: GE Healthcare Bio-Sciences AB (GE Healthcare Technologies, Inc.)
• Original Assignee: Amersham International Plc (General Electric Company)
• Inventors: Finlan, Martin F.
• Primary Examiner(s): NOT, DEFINED
• Assistant Examiner(s): NOT, DEFINED
• Application Number:
  US07/358,612
• Time in Patent Office: 861 Days
• Field of Search: 422/82.05, 422/58, 422/66, 422/98, 422/82.09, 356/318, 356/445, 436/44, 436/805, 435/808
• US Class Current: 422/82.05
• CPC Class Codes: G01N 21/553 and using surface plasmons fluorescence excitation G01N21/648; enhanced Raman G01N21/658
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10T 436/110833 Utilizing a moving indicator strip or tape

Abstract

The present invention is drawn to a surface plasmon resonance (SPR) sensor in which the phenomenon of long-range surface plasmon resonance is used to develop a highly sensitive detector for use in biological, biochemical or general chemical testing. The sensor includes a laminar structure having of a high refractive index glass block, a membrane of dielectric material, a thin metal layer, and a sensitive layer. A sample to be tested is brought into contact with the sensitive layer. The refractive index of the dielectric layer and that of the layer (sensitive layer/sample) on the opposite side of the metallic layer should be equal, or nearly so, and the refractive index of the glass block should be higher than this so that total internal reflection takes place at the interface between the block and the membrane. Light from a laser source is totally internally reflected at this interface, and the strength of the reflected beam is monitored by a light detector. Provided conditions are correct, long-range SPR will take place which will sensitively alter the strength of the light in dependence upon the progress of the reaction between the sensitive layer and sample.

Claims

1. A sensor for use in biological, biochemical or chemical testing, said sensor comprising:

a structure comprising a block of material, a membrane of dielectric material disposed over a surface of said block, a layer of metallic material disposed over that surface of said membrane opposite said block, and a layer of sensitive material disposed over said metallic layer;

means for introducing onto the sensitive layer so as to react therewith a sample to be analyzed in which the index of refraction of the sample and/or said sensitive layer is equal or nearly equal to that of said membrane, and the index of refraction of the material of said block is higher than that of said membrane and the sample;

means for generating electromagnetic radiation that is transmittable through said block of material and for directing the radiation through said block at a location within said structure in a manner which causes long range surface plasmon resonance to occur and which causes the radiation to be internally reflected by said structure from said location; and

detecting means for monitoring radiation from said source which has been internally reflected within the structure and for detecting the characteristics of the resonance that are dependent upon the reaction between the sample and the sensitive layer.

2. A sensor as claimed in claim 1, wherein the transparent block is made from high refractive index glass or polymer.

3. A sensor as claimed in claim 2, wherein the thickness of the membrane is such as to prevent the occurrence of multiple resonances.

4. A sensor as claimed in claim 2, wherein said structure further comprises an intermediate optical coupling layer of fluid or grease extending between and optically coupling said membrane and said transparent block.

5. A sensor as claimed in claim 2, wherein the sensitive layer comprises an antibody layer.

6. A sensor as claimed in claim 2, wherein the thickness of said membrane and the thickness of said metal layer satisfy the following equations ##EQU3## i=dielectric constant of medium i, d_i =thickness of medium i,

θ

_i,j =angle of wave vector of p-polarized light in medium i, j,

ω

=angular frequency of incident wave of p-polarized light, and

the subscripts 1 to 4, for the characters i, j, respectively represent the block, the membrane, the metal layer, and the layer with sample introduced thereon.

7. A sensor as claimed in claim 2, wherein the refractive index of the material of the transparent block is about 2.

8. A sensor as claimed in claim 3, wherein the thickness of the membrane is such as to prevent the occurrence of multiple resonances.

9. A sensor as claimed in claim 3, wherein said structure further comprises an intermediate optical coupling layer of fluid or grease extending between and optically coupling said membrane and said transparent block.

10. A sensor as claimed in claim 3, wherein the sensitive layer comprises an antibody layer.

11. A sensor as claimed in claim 3, wherein the thickness of said membrane and the thickness of said metal layer satisfy the following equations ##EQU4## i=dielectric constant of medium i, d_i =thickness of medium i,

θ

_i,j =angle of wave vector of p-polarized light in medium i, j,

ω

=angular frequency of incident wave of p-polarized light, and

the subscripts 1 to 4, for the characters i, j, respectively represent the block, the membrane, the metal layer, and the layer with sample introduced thereon.

12. A sensor as claimed in any one of claim 1, wherein the thickness of the membrane is such as to prevent the occurence of multiple resonances.

13. A sensor as claimed in claim 4, wherein said structure further comprises an intermediate optical coupling layer of fluid or grease extending between and optically coupling said membrane and said transparent block.

14. A sensor as claimed in claim 4, wherein the sensitive layer comprises an antibody layer.

15. A sensor as claimed in claim 4, wherein the thickness of said membrane and the thickness of said metal layer satisfy the following equations ##EQU5## i=dielectric constant of medium i, d_i =thickness of medium i,

θ

_i,j =angle of wave vector of p-polarized light in medium i, j,

ω

=angular frequency of incident wave of p-polarized light, and

the subscripts 1 to 4, for the characters i, j, respectively represent the block, the membrane, the metal layer, and the layer with sample introduced thereon.

16. A sensor as claimed in claim 1, wherein said structure further comprises an intermediate optical coupling layer of fluid or grease extending between and optically coupling said membrane and said transparent block.

17. A sensor as claimed in claim 6, wherein the sensitive layer comprises an antibody layer.

18. A sensor as claimed in claim 6, wherein the refractive index of the intermediate layer is equal to that of the membrane.

19. A sensor as claimed in claim 7, wherein the sensitive layer comprises an antibody layer.

20. A sensor as claimed in claim 1, wherein the sensitive layer comprises an antibody layer.

21. A sensor as claimed in claim 20, wherein the thickness of said membrane and the thickness of said metal layer satisfy the following equations ##EQU6## i=dielectric constant of medium i, d_i =thickness of medium i,

θ

_i,j =angle of wave vector of p-polarized light in medium i,j,

ω

=angular frequency of incident wave of p-polarized light, and

the subscripts 1 to 4, for the characters i, j, respectively represent the block, the membrane, the metal layer, and the layer with sample introduced thereon.

22. A sensor as claimed in claim 21, wherein said structure further comprises an intermediate optical coupling layer of fluid or grease extending between and optically coupling said membrane and said transparent block.

23. A sensor as claimed in claim 5, wherein the sensitive layer comprises an antibody layer.