Biological sensors

• US 5,047,213 A
• Filed: 01/18/1989
• Issued: 09/10/1991
• Est. Priority Date: 01/27/1988
• Status: Expired due to Fees

• Current Assignee: Biacore AB
• Original Assignee: Amersham International Plc (General Electric Company)
• Inventors: Harvey, Richard P., Finlan, Martin F.
• Primary Examiner(s): Warden, Robert J.
• Assistant Examiner(s): Trembley, Theresa A.
• Application Number:
  US07/299,564
• Time in Patent Office: 965 Days
• Field of Search: 422/82.05, 422/82.11, 356/318, 356/445
• US Class Current: 422/82.11
• CPC Class Codes: G01N 21/553 and using surface plasmons fluorescence excitation G01N21/648; enhanced Raman G01N21/658
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

A biological sensor which utilizes the phenomenon of surface plasmon resonance to detect the refractive index change which occurs when two components--for example antibody and corresponding antigen--react with one another. Surface plasmon resonance takes place at the sloping exit surface of an optical waveguide such as a fiber optic 23. The input end of fiber optic 12 is connected to a light source 12. A layer 25 of metal is applied to the sloping exit surface so as to cause total internal reflection of the light proceeding down the fiber optic. Reflected light is detected by a detector 13. A sensitive, for example antibody, layer 26 is applied to the metal layer. Sample (not shown) reacts with layer 26 in such a way that the refractive index changes. Provided conditions are correct, this variation in refractive index can be monitored in detector 13 by virtue of the surface plasmon resonance which occurs in the area of total internal reflection.

Claims

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

an optical waveguide having an input end and an output end and along which radiation may propagate by means of internal reflections off its internal surfaces,

a source of electromagnetic radiation whose output is applied to the input end of said optical waveguide, and

wherein said output end of the optical waveguide is cut off at an angle to its axis to provide a sloping end face,

wherein said radiation is input to the waveguide as a focussed beam so that the beam is incident at said end face as a spread of angles, and

wherein the angle of the sloping end face is such as to (1) cause the incident beam to be totally internally reflected at said face, and (2) cause the thus-reflected beam to be incident on the wall of the waveguide at an angle sufficiently great for it to exit from the waveguide without being subject to further internal reflection,

means for monitoring the radiation from said source which is internally reflected at said face,

a layer of metallic material applied to said sloping face,

a layer of sensitive material applied to the metallic layer, and

means for introducing onto the sensitive layer so as to react therewith a sample to be analyzed,

the arrangement being such that the aforesaid spread of radiation incident at said face of the optical waveguide is such as to include that angle at which surface plasmon resonance occurs, and allows the changing characteristics of the resonance to be monitored, which characteristics, as detected by said monitoring means, are dependent upon the reaction between the sample and the sensitive layer.

2. The sensor as claimed in claim 1 wherein said optical waveguide is formed of solid material transparent to the radiation in use, and along which the radiation propagates by means of internal reflections off its internal surfaces.

3. The sensor as claimed in claim 2 wherein the optical waveguide is a fiber optic.

4. The sensor as claimed in claim 2 wherein the optical waveguide is a rectangular slab of transparent material, such as a microscope slide.

5. The sensor as claimed in any one of claim 2 to 4 wherein the material of the waveguide is clad with a material having a refractive index which is lower than that of the waveguide material.

6. The sensor as claimed in any one of claim 2 to 5 wherein the material of the waveguide, and its cladding (if any) is embedded in a block of transparent material.

7. The sensor as claimed in claim 6 wherein the material of said block has a refractive index which is lower than that of the waveguide material.

8. The sensor as claimed in either one of claims 6 or 7 wherein said block is arranged to receive light internally reflected off said sloping end face and passing out of said waveguide medium, and wherein said block has an output face through which such internally reflected light passes, to be incident on said monitoring means.

9. The sensor as claimed in claim 8 wherein said output face is curved, having a center of curvature coincident with the point at which the radiation is incident on said end face.

10. The sensor as claimed in any one of claims 2 to 9 or a further including focussing means for focussing the radiation from the source onto the sloping end face.

11. The sensor as claimed in any one of claims 2 to 9 or 1 further including focussing means for focussing the radiation from said source onto the input of the optical waveguide.

12. The sensor as claimed in claim 11 wherein the optical waveguide is of circular cross-section, further including means for forming the radiation from the source into a series of separate radially spaced, coaxial beams of annular section.

13. The sensor as claimed in claim 11 wherein the optical waveguide is of rectangular cross section, further including means for forming the radiation from the source into a series of separate spaced planar beams.

14. The sensor as claimed in either one of claim 12 or 13 wherein the axial length of the optical waveguide is such that all of the separate input beams come to a common focus at the end face.

15. The sensor as claimed in any one of claims 2 to 14 or 1 including one or more further optical waveguides illuminated by a common source of radiation or by respective separate sources of radiation to enable testing of multiple analytes in a single sample, or multiple samples, to be carried out simultaneously.