GB2247749A

GB2247749A - Sensor utilising surface plasmon resonance

Info

Publication number: GB2247749A
Application number: GB9019326A
Authority: GB
Inventors: Simon Charles Webster; Leslie Charles Laycock
Original assignee: GEC Marconi Ltd; Marconi Co Ltd
Current assignee: BAE Systems Electronics Ltd
Priority date: 1990-09-05
Filing date: 1990-09-05
Publication date: 1992-03-11
Also published as: GB9019326D0

Abstract

A biosensor comprises a surface plasmon resonance interface (15), a source (10) for producing a beam of light (9) of suitable wavelength, a scanner (11) which scans the light beam through a predetermined angle, a lens system (14) for directing the scanned beam at a point (16) on the interface, and a detector (19) which detects the optical density of the beam after reflection from that point. The output of the detector (19) is measured as a function of time which is related to the angular position of the scanned beam. Particular absorption peaks occur at particular times and equivalent angles. <IMAGE>

Description

Sensing Apparatus This invention relates to sensing apparatus, and particularly to biosensors.

In the known surface plasmon resonance (SPR) type of biosensor, an interface is provided between an optically transparent medium and a biological reagent which is selected to react with certain biological species which are to be detected. If the interface is addressed by light at the correct wavelength, an absorption peak occurs at a certain angle of incidence of the light.

In order to detect the species, the absorption peak must be located, and its shift due to the presence of the reagent, together with its rate of shift, must be measured.

The conventional method of detecting an absorption peak is illustrated in Figures 1 and 2 of the accompanying drawings. A cone of light 1 of suitable wavelength is directed at the SPR interface 2 such that the apex of the cone impinges on the interface at a point 5.

The cone comprises an infinite number of beams of light, each of which makes an angle with the normal 4 to the interface at the point 5.

The axis 3 of the cone is shown, by way of example, as making an angle A with the normal, but each light beam will, in effect, be at a respective, different, angle A to the normal. If a beam angle corresponds to the resonance angle of the biological material, an absorption peak occurs. The existence of an absorption peak is detected by determining the optical power density of the reflected light cone 6 at a transverse plane 7.

Figure 2 illustrates the occurrence of an absorption peak (i.e. a power density minimum) 8 as the angle A is varied. The actual value of the angle A at resonance may be determined by use of a linear CCD array at the plane 7, but the resolution is poor. For example, if a 2000 element array is used, the resolution will only be 1 in 2000.

It is an object of the present invention to provide an improved optical arrangement for use in determining a resonance angle occurring in a surface plasmon resonance biosensor.

According to one aspect of the invention there is provided a biosensor comprising a surface plasmon resonance interface; means to produce a beam of light of suitable wavelength; means to scan the light beam through a predetermined angle; means to direct the scanned light beam at a point on the interface; and means to detect the optical density of the scanned beam after reflection from said point.

According to another aspect of the invention there is provided a biosensor comprising a surface plasmon resonance interface; means to direct a convergent bundle of light beams at a point on the interface; and scanning means to direct the light beams, after reflection from said point, sequentially on to means for detecting the optical density of the light beams.

According to a further aspect of the invention there is provided a biosensor comprising a surface plasmon resonance interface; means to produce a multiplicity of beams of light substantially in a single plane; means to scan said plane through a predetermined angle; means to direct the scanned light at a line on the interface; and a linear array of photodetectors to detect the optical density of the scanned light after reflection from said line.

Embodiments of the invention will now be described, by way of example, with reference to the accompanying drawings, in which Figures 1 and 2 are schematic diagrams illustrating the detection of an absorption peak at the interface between a reagent and a transparent medium, as described above, Figure 3 illustrates, schematically, a first embodiment of the invention, and Figures 4 to 11 ilustrate, schematically, further embodiments of the inventon.

The present invention provides a number of arrangements for achieving rapid detection of an absorption peak and any shift therein caused by the presence of a biological species to be detected.

Referring to Figure 3, in a first such arrangement a collimated beam of light 9 from a light source 10 is caused by a scanning device 11 to sweep between a position 12 and a position 13.

A projection lens 14, positioned in the path of the light beam, causes the beam at all scanning positions to impinge on an SPR interface 15 at a point 16.

After reflection at the point 16, the beam scans between positions 17 and 18 and is directed towards a detector 19 by a receiver lens 20. The detector is shown schematically as a photodiode, but other fast-acting photodetectors may alternatively be used.

The output signal from the detector 19 is measured as a function of time (Figure 4), the passage of time being related to the angular position of the scanned input light beam 9. The scanning device 11 may be, for example, a holographic scanner, a polygonal reflecting scanner or a rotating cube scanner, incorporating a rotating element, in which case the passage of time may be related to the output of a position encoder on a shaft associated with the rotation of the element.

Alternatively, for any type of scanning device, passage of time during each scan period may be determined by producing a pulse at the end of each successive scan period and determining the time elapsed since the end-of-scan pulse of the immediately preceding scan.

Figure 5 illustrates schematically an arrangement for producing the end-of-scan pulses. The beam reflected from the point 16 of the interface 15 scans in an anticlockwise direction, as indicated by an arrow 21. At the end of the scan the beam inpinges on a photodetector 22 disposed just beyond the edge of the lens 20.

The output of the photodetector is fed to detector circuitry 23, which may include a counter for counting clock pulses between successive end-of-scan pulses for determining the elapsed time.

Figure 6 shows, schematically, an alternative arrangement for producing end-of-scan pulses. In this case the photodetector 22 is moved to a position further from the lens 20, and at the end of the scan the beam impinges on a prism or mirror 24, which directs the beam on to the photodetector.

A further alternative arrangement is shown in Figure 7, in which the beam, at the end of each scan period, is directed on to the photodetector 22 by means of an optical fibre 25, so that the photodetector can be located at any suitable position.

By any of these arrangements the angular response of the SPR interface 15 is converted to a temporal signal as illustrated in Figure 4. This signal is then processed, preferably electronically, to extract information concerning the location of the absorption peak, its angular shift with time, taken over a number of scan periods, and its rate of shift. The processing may involve differentiating the temporal signal to produce a second signal which is proportional to the gradient of the output of the photodetector.

Figures 8 and 9 show alternative arrangements for monitoring the optical power density of light reflected from the SPR interface.

In Figure 8 the receiver lens 20 is omitted, and the scanning beam is directed on to a large-area photodetector 26 which spatially integrates the light over all possible scan angles by virtue of its large area. In Figure 9 a diffuser 27 is placed in the path of the scanning beam and in front of the detector 19, to integrate the light over all possible scan angles by virtue of its scattering properties.

This reduces the tolerance required in the assembly of the optical components.

An alternative scanning arrangement for use in the invention is illustrated schematically in Figure 10 of the drawings. In this case a fixed divergent cone of light 28 is produced by a light source 29. A projection lens 30 in the path of the light changes it into a convergent beam 31 having its apex at a point 32 on an SPR interface 33. The beam of light 34 reflected from the point 32 is made convergent by a receiver lens 35, so that the resultant beam 36 is focused at a scanning device 37. The device 37 scans in one plane across the beam 36, and produces an output beam 38 in a fixed direction. The beam 38 impinges on a photodetector 39. This arrangement gives a temporal signal similar to that described above, and similar signal processing techniques may be used.

In any of the described embodiments any of the above-mentioned scanning devices might be used. Alternatively, an acousto-optic scanner or any other suitable scanner could be used.

The light source may produce either coherent or non-coherent light.

Figure 11 illustrates, schematically, an arrangement for addressing a larger area of the interface 15. In this case a scanner 40 produces a wide planar area of light 41 which is scanned between limits 42 and 43. The scanning light impinges on a cylindrical lens 44 which causes it to converge at a line 45 on the interface 15. The scanning reflected light is caused by a cylindrical lens 46 to focus on a linear array 47 of discrete photodetectors 48. This arrangement allows a plurality of discrete areas on the interface 15 to be analysed by the separate detector elements 48. Either multiple biochemical test samples or multiple SPR layer types could be employed in this "multichannel" system. A single "end-of-scan" detector could be provided, as described above.

The high-speed scanning techniques of the invention allow the time evolution of the shift of the absorption peak to be determined accurately. The use of discrete high-speed photodetectors allows a high degree of resolution in the output signal to be achieved. For example, for a scan period of lems, a detector bandwidth of 100MHz and a detector electronics sampling rate of 200MHz, an output signal resolution of 1 in 100,000 is possible* as compared with the 1 in 2,000 resolution mentioned above for the conventional SPR biosensor.

Furthermore, replacing the conventional linear detector array with a single space-integrating detector simplifies the detector electronics.

Claims

1. A biosensor comprising a surface plasmon resonance interface; means to produce a beam of light of suitable wavelength; means to scan the light beam through a predetermined angle; means to direct the scanned light beam at a point on the interface; and means to detect the optical density of the scanned beam after reflection from said point.

2. A biosensor as claimed in Claim 1, wherein the means to direct the scanned light beam comprises a convergent lens.

3. A biosensor as claimed in Claim 1, wherein the means to detect the optical density comprises a photodetector.

4. A biosensor as claimed in Claim 3, including means to focus the scanned light beam at the photodetector.

5. A biosensor as claimed in Claim 3, including means disposed between said point on the interface and the photodetector, to diffuse the scanned light beam.

6. A biosensor comprising a surface plasmon resonance interface; means to direct a convergent bundle of light beams at a point on the interface; and scanning means to direct the light beams, after reflection from said point, sequentially on to means for detecting the optical density of the light beams.

7. A biosensor as claimed in any preceding claim, wherein the scanning means comprises a rotary scanner.

8. A biosensor as claimed in Claim 7, wherein the rotary scanner comprises a rotating holographic element.

9. A biosensor as claimed in Claim 7, wherein the rotary scanner comprises a polygonal reflecting scanner.

10. A biosensor as claimed in Claim 7, wherein the rotary scanner comprises a rotating cube scanner.

11. A biosensor as claimed in any one of Claims 7 to 10, including means associated with the rotary scanner to provide an end-of-scan pulse.

12. A biosensor as claimed in Claim 11, wherein the means to provide an end-of-scan pulse comprises a shaft position encoder.

13. A biosensor as claimed in any one of Claims 1-10, including means to receive light at the end of the scanning through said predetermined angle, and thereby to generate an end-of-scan pulse.

14. A biosensor as claimed in Claim 13, wherein the means to receive light comprises a photodetector.

15. A biosensor as claimed in Claim 13, wherein the means to receive light comprises a prism or a mirror, and a photodetector on to which said light is directed by the prism or mirror.

16. A biosensor as claimed in Claim 13, wherein the means to receive light comprises an optical fibre, and a photodetector on to which said light is directed by the optical fibre.

17. A biosensor as claimed in any one of Claim 1 to 6, wherein the scanning means comprises an acousto-optic scanner.

18. A biosensor comprising a surface plasmon resonance interface; means to produce a multiplicity of beams of light substantially in a single plane; means to scan said plane through a predetermined angle; means to direct the scanned light at a line on the interface; and a linear array of photodetectors to detect the optical density of the scanned light after reflection from said line.

19. A biosensor substantially as hereinbefore described with reference to the accompanying drawings.