Biological sensors

• US 5,064,619 A
• Filed: 05/10/1989
• Issued: 11/12/1991
• Est. Priority Date: 05/10/1988
• Status: Expired due to Term

• Current Assignee: GE Healthcare Bio-Sciences AB (General Electric Company)
• Original Assignee: Amersham International Plc (General Electric Company)
• Inventors: Finlan, Martin F.
• Primary Examiner(s): NOT, DEFINED
• Assistant Examiner(s): Trembley, Theresa A.
• Application Number:
  US07/350,034
• Time in Patent Office: 916 Days
• Field of Search: 422/82.05, 422/82.11, 422/82.09, 422/68.1, 356/318, 356/445, 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: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

A surface plasmon resonance (SPR) detector includes a laser source for generating radiation which is reflected off a concave reflector to a point or line of incidence on the interface between a glass slide and a metal layer. A single pencil beam from the laser is scanned by a moving mirror across a small arc, covering those angles of incidence within which surface plasmon resonance occurs. A sensitive, for example antibody, layer overlies the metal layer to form a combined layer, and a sample to be tested is passed across the antibody layer. Any binding which occurs with the antibody layer results in the refractive index of the layer changing, and this change may be detected by monitoring the strength of the beam internally reflected at the point or line. A light detector enables the beam to be measured.

Claims

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

a block of material transparent to electromagnetic radiation;

a layer of metallic material disposed over at least part of a first surface of said block;

a layer of sensitive material disposed over the metallic material;

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

electromagnetic radiation producing means for producing a beam of electromagnetic radiation;

reflective optic means for directing the beam into said transparent block in such a way as to be internally reflected off said at least part of the first surface of said block at an angle of incidence which will cause surface plasmon resonance to occur, said reflective optic means including a reflective element having a generally concave reflecting surface that from a given position will reflect beams of radiation impinging the reflecting surface at different locations thereon toward the same point on said at least one surface but at different respective angles of incidence; and

detector means positioned in the sensor for receiving the internally reflected beam and for detecting the characteristics of the surface plasmon resonance that are dependent upon the reaction between the sample and the sensitive layer.

2. A sensor as claimed in claim 1, wherein the reflecting element is shaped to compensate for refractive effects as the beam enters the transparent block.

3. A sensor as claimed in either one of claims 1 or 2, wherein said electromagnetic radiation producing means produces a solid beam of radiation, the reflecting element reflecting the solid beam toward said first surface in such a way that the incoming beam is fan-shaped and spans a range of angles of incidence at said first surface which covers those which cause surface plasmon resonance to occur.

4. A sensor as claimed in either one of claims 1 or 2, further including scanning means, situated between said radiation producing means and said reflecting element, for continuously altering the angle of incidence of the beam that impinges the reflecting surface of said reflecting element, the reflecting element reflecting the beam at said first surface in such a way that the beam incident at said first surface has an angle of incidence which varies, with said scanning, about those angles which cause surface plasmon resonance to occur.

5. A sensor as claimed in claim 4, wherein said scanning means deflects the output beam from the radiation producing means backwards and forwards about a small arc.

6. A sensor as claimed in claim 4, wherein said scanning means comprises sweeping means for continuously sweeping the output beam from the radiation producing means over 360°

, and means for masking off all but a small arc of the swept output beam for application to said transparent block.

7. A sensor as claimed in claim 4, wherein said sweeping means comprises a mirror onto which said radiation beam is incident, and means for rotating said mirror to in turn sweep the beam over 360°

.

8. A sensor as claimed in claim 7, further including synchronizing means for synchronizing the mirror rotating means with information output from said detector means.

9. A sensor as claimed in claim 4, wherein said radiation source is a phased array source and said scanning means alters the phases of the individual sources making up said array in such a way that the output beam of radiation is caused to scan.

10. A sensor as claimed in claim 7, further including a second reflecting element positioned to receive radiation internally reflected at said first surface and directing such radiation into said detector means.

11. A sensor as claimed in claim 10, wherein said second reflecting element has a reflective surface so shaped as to reflect light toward the same point on said detector when the light impinges the reflecting element at any one of a plurality of locations thereon.

12. A sensor as claimed in either of claims 10 or 11, wherein said second reflecting element has a generally concave reflective surface.

13. A sensor as claimed in claim 7, wherein said detector means comprises a large area detector of a size sufficient to allow the internally reflected beam to be incident thereon whatever the emergent angle of said beam might be.