Biological sensors

• US 5,023,053 A
• Filed: 05/22/1989
• Issued: 06/11/1991
• Est. Priority Date: 05/20/1988
• Status: Expired due to Fees

• Current Assignee: Biacore 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:
  US07/355,187
• Time in Patent Office: 750 Days
• Field of Search: 422/82.05, 422/58, 422/66, 422/98, 356/318, 356/445
• 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 21/75 Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated systems in which material is burnt in a flame or plasma G01N21/72, G01N21/73
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

A surface plasmon resonance (SPR) sensor in which a membrane is used to enable the sensitive material to be readily changed to enable tests to be carried out on a sequential basis simply by moving or changing the membrane. In one embodiment, the membrane takes the form of a continuous film (24) which lies against and is moveable across by means not shown, a transparent plate (17) which forms part of the SPR sensor. The film (24) comprises a layer (31) of flexible transparent material to which is applied a thin layer (32) of metal such as silver. Applied to layer (32) is a layer (33) of sensitive material. The final layer (34) is a preformed layer of hydrophyllic plastics material which incorporates troughs (37) and passageways (35,38) for the transfer of sample across the sensitive layer. Light from a laser (not shown) is subject to total internal reflection at the interface between the transparent layer (31) and metal layer (32), and the reflected light is collected by a light detector (not shown). Provided conditions are correct, surface plasmon resonance occurs at the area of total internal reflection, the characteristics of which resonance are sensitively dependent upon the reaction between the sample and the sensitive layer.

Claims

1. A sensor for use in biological, biochemical or chemical testing, said sensor comprising a source of electromagnetic radiation for producing a beam of electromagnetic radiation, membrane in the form of a laminate comprising a first film of transparent material, a second film of metal applied to at least part of one surface of said first film and a third film of sensitive material applied to the second film, said membrane further including a sample feeding means whereby the sample to be analyzed is transferred in a controlled manner to said sensitive layer, said sample feeding means comprising a further layer in the laminate comprising said membrane, which further layer is applied to said third film of sensitive material, said further layer being made of a porous material through which a sample may be passed from the side opposite the sensitive layer, in order to react with said sensitive layer, means for directing said beam of electromagnetic radiation into said first film of transparent material in such a way as to be internally reflected off said part of said one surface, and detector means positioned to receive the internally reflected beam, wherein the angle of incidence of said beam at said one surface is such as to cause surface plasmon resonance to occur, the characteristics of which resonance, as detected by the monitoring means, is dependent upon the reaction between the sample and the sensitive layer.

2. The sensor as claimed in claim 1 wherein said membrane is flexible.

3. The sensor as claimed in claim 1 or 2 wherein said membrane is in the form of a semi-continuous film which may be moved between tests to bring a fresh area into use.

4. The sensor as claimed in claim 3 wherein the membrane is package in the form of a cassette.

5. The sensor as claimed in claim 1 further including a block of rigid material transparent to the electromagnetic radiation, and positioned such that said membrane lies against a first surface of said block.

6. The sensor as claimed in claim 5 wherein there is provided an optical coupling fluid between said membrane and said block, such that, in use, the beam enters the block, then passing from the block through said first surface and into said transparent film.

7. The sensor, as claimed in claims 5 or 6 wherein said block is made of a material having the same refractive index as that of said transparent film.

8. The sensor as claimed in claim 1 wherein said further layer takes the form of a structural layer comprising passage means extending from its face remote from the sensitive layer to the opposite face.

9. The sensor as claimed in claim 8 wherein said further layer incorporates an absorbent material which is operable to draw the sample across the sensitive film.

10. The sensor as claimed in claims 8 or 9 wherein a plurality of passage means are provided to enable simultaneous testing of a number of samples, such passage means being spaced apart across the surface of the membrane, and wherein scanning means are provided for scanning the point of incidence of said beam on said one surface across the passage means.

11. The sensor as claimed in claim 10 wherein said sensitive film is not continuous, but takes the form of a plurality of discrete areas of sensitive material applied to said metal film, each of said discrete areas being associated with one of said passage means.

12. A sensor for use in biological, biochemical or chemical testing, said sensor comprising a source of electromagnetic radiation for producing a beam of electromagnetic radiation, a membrane in the form of a laminate comprising a first film of transparent material, a second film of metal applied to at least part of one surface of said first film and a third film of sensitive material applied to the second film, means for introducing onto the sensitive layer so as to react therewith a sample to be analyzed, means for directing said beam of electromagnetic radiation into said first film of transparent material in such a way as to be internally reflected off said part of said one surface, and detector means positioned to receive the internally reflected beam, and wherein the angle of incidence of said beam at said one surface is such as to cause surface plasmon resonance to occur, the characteristics of which resonance, as detected by the monitoring means, is dependent upon the reaction between the sample and the sensitive layer and

wherein said sensitive film is not continuous, but takes the form of a plurality of discrete areas of sensitive material applied to said metal film, and wherein scanning means are provided for scanning the point of incidence of said beam on said one surface across said discrete areas.

13. A sensor for use in biological, biochemical or chemical testing, said sensor comprising a source of electromagnetic radiation for producing a beam of electromagnetic radiation, an elongate film in the form of a laminate comprising a first layer of transparent material, a second layer of metal applied to at least part of one surface of said first layer and a third layer of sensitive material applied to the second layer, means for introducing onto the sensitive layer so as to react therewith a sample to be analyzed, means for directing said beam of electromagnetic radiation into said first layer of transparent material in such a way as to be internally reflected off said part of said one surface, detector means positioned to receive the internally reflected beam, and wherein the angle of incidence of said beam at said one surface is such as to cause surface plasmon resonance to occur, the characteristics of which resonance, as detected by the monitoring means, is dependent upon the reaction between the sample and the sensitive layer, and means for moving said film between tests in order to bring a fresh area into use.