GB2462606A

GB2462606A - A reading system and method for reading encoded carriers

Info

Publication number: GB2462606A
Application number: GB0814661A
Authority: GB
Inventors: Carl Edward Norman; Katja Franziska Kastl
Original assignee: Toshiba Research Europe Ltd
Current assignee: Toshiba Europe Ltd
Priority date: 2008-08-11
Filing date: 2008-08-11
Publication date: 2010-02-17
Anticipated expiration: 2028-08-11
Also published as: GB0814661D0; GB2462606B

Abstract

An apparatus for measuring an encoded carrier 1 configured for surface plasmon resonance (SPR) comprises first 9 and second 13 sources of radiation for irradiating said encoded carrier, a receiver 29 for measuring radiation from said encoded carrier emitted by said first source, and a receiver 21 for measuring radiation from said encoded carrier emitted by said second source, wherein the radiation from said first and second sources is distinguishable by means of at least one of their wavelength bands, their polarisation states or their temporal or spatial profiles. The detectors may be CCD cameras and a single detector may be used for both sources. Plural carriers 1 may be present in a flow cell system 3. The first radiation is used to image and identify the encoded carriers while the second radiation is used for SPR measurements to determine an analyte binding to the carrier.

Description

A Reading System and Method for Reading Encoded Carriers The present invention relates to the field of apparatus for reading encoded carriers, and for a method for reading a signal from an encoded carrier.

There has always been a need to be able to quickly and efficiently monitor reactions between different chemicals in order to both identify molecules and to study the reactions of both known and unknown molecules. This need is now all the more acute with the substantial and numerous discoveries being made in the biotechnology field.

Currently, there are a number of methods known for performing this analysis. One particular method is taught in GB2404918. In this patent, encoded carriers are formed.

The encoded carriers have a first region, which is a reaction region, and a second region, which is a code region. The reaction region has a variation in its refractive index so that a surface plasmon resonance (SPR) measurement may be made.

In an SPR measurement, if radiation of a certain wavelength, polarisation angle and incident angle irradiates a structure which has a periodic variation in its refractive index, the radiation will couple to the surface plasmon mode causing a decrease in the amplitude of the reflected light. The periodic variation in the refractive index serves to couple radiation with a correct incident angle and properties to the surface plasmon mode.

The incident angle at which SPR occurs will be dependent on any chemical species on the surface. In GB24049 18, probe molecules are attached to the surface of the reaction region. If the probe molecules then react with a further chemical species, the incident angle of the radiation necessary to excite SPR will vary. Therefore, it is possible to determine if a reaction has taken place.

WO 2004/015418 discloses an analysis system for analysing supports that have both capture analytes attached and barcoded regions. The analysis system determines the identity of each support by reading its barcode, and determines whether a target molecule is attached to the capture analytes by illuminating the support and detecting fluorescence.

In GB24049 18, encoded carriers are provided with a code corresponding to the different types of probe molecules used in the reaction region. This code may, for instance, take the form of a barcode. The code provides a means of identifying each type of carrier, and thereby identifying the type of molecules attached to the carrier. Thus, various different molecule types may be tested simultaneously in the same reaction vessel by adding the different types of carriers as desired. The results of the tests may be determined by first determining the location of a carrier, and subsequently determining the type of carrier by reading the code. Finally, a measurement of the SPR angle of the carrier can be made to determine if a reaction has taken place. These steps can be repeated for each carrier in the reaction vessel to determine which molecule types have reacted, arid may also be repeated on the same carriers to track the progress of a reaction.

GB244 1780 discloses methods and apparatus for making SPR measurements on encoded carriers that are orientated at arbitrary angles to the measurement apparatus, and positioned at arbitrary locations within a flow cell. GB2441 780 also discloses an apparatus capable of simultaneously illuminating an encoded carrier with light that has a range of angles to the carriers surface. Using this apparatus, the SPR angle of the illuminated carrier can be determined in a single measurement.

Prior to making SPR measurements on a particular carrier, the location, orientation and code of each carrier must first be determined. Typically, to determine these parameters, one or more images of the carriers will be obtained.

In principle, there is no limit to the number of carriers that may be present in a reaction vessel, however each carrier must be located, identified and measured. If large numbers of carriers are present then a considerable amount of time will be consumed accomplishing these tasks. There is therefore a need to provide an apparatus that can carry out these tasks quickly.

The inventors of the present invention have noted that if the location, identification, and measurement tasks are carried out sequentially, then the length of time required for analysis of the carriers will be particularly long. There is therefore a need for an apparatus that can carry out these tasks in a simultaneous manner.

Accordingly, in a first aspect the present invention provides an apparatus for measuring an encoded carrier, said encoded carrier being configured for surface plasmon resonance, said apparatus comprising; first and second sources of radiation for irradiating said encoded carrier, a receiver for measuring radiation from said encoded carrier emitted by said first source, and a receiver for measuring radiation from said encoded carrier emitted by said second source, wherein the radiation from said first and second sources is distinguishable by means of at least one of their wavelength bands, their polarisation states or their temporal or spatial profiles.

By using two distinguishable sources of radiation the apparatus can operate with two independent channels. Thus, by using one of these channels to obtain positional information and the other to obtain SPR information, the present invention provides a system where both positional information and SPR information may be obtained concurrently.

In a preferred embodiment, the apparatus is configured to illuminate a carrier in a transmissive configuration to produce an image of the outline of the carrier, and in reflective conliguration to perform SPR measurements on the carrier.

In a preferred embodiment, the two sources of radiation emit radiation of differing wavelengths, thus enabling separation of the radiation from the two sources by wavelength-selective means.

In an embodiment, a first receiver measures radiation from said first source, and a second receiver measures radiation from said second source.

In an alternative embodiment, the first and second receivers are the same device, and this is configured to simultaneously or alternately receive light from both the first and second sources.

The apparatus may further comprise filtering means configured to filter radiation from one of said sources depending on the measurement being performed. Thus, if first and second receivers are used, each receiver may have an associated filtering device that is configured to block unwanted radiation from that receiver.

The apparatus of the present invention measures a carrier that exhibits surface plasmon resonance. Such a carrier preferably has a periodic variation in its refractive index in a direction parallel to the surface or interface where the surface plasmon resonance will occur, in order to allow coupling of radiation into the surface plasmon mode.

The carrier preferably comprises a diffraction grating. The grating may be a planar grating achieved by forming elongate holes or trenches in the carrier, or the carrier may be corrugated. The grating may be a one-dimensional or two-dimensional grating.

Preferably, the apparatus comprises means to determine the location and orientation of the carrier on the basis of images obtained of the carriers by the apparatus. This means may, for example, comprise a computer processing system.

Preferably, the apparatus comprises means to adjust the location andlor the orientation of the carrier with respect to the first or second source on the basis of the determined location and/or orientation of the carrier. Such adjustment can facilitate SPR measurements on the carrier.

The apparatus preferably further comprises a reaction vessel to house the carriers and permit reactions to take place with the carriers without their removal from the apparatus.

Preferably, the reaction vessel contains has a high friction layer to maintain the position of each carrier within the reaction vessel while reagents flow into andlor out of the reaction vessel.

In a second aspect, the present invention provides a method of measuring an encoded carrier, said carrier being configured to exhibit surface plasmon resonance, said method comprising; irradiating said encoded carrier with the light from both a first and a second light source receiving at a receiver radiation from said encoded carrier emitted by said first source, and receiving at a receiver radiation from said encoded carrier emitted by said second source, wherein the radiation from said first and second sources is distinguishable by means of at least one of their wavelength bands, their polarisation states or their temporal or spatial profiles.

The present invention will now be described with reference to the following non-limiting embodiments in which: Figure 1 shows a measuring apparatus, which can be used to measure encoded carriers, in accordance with an embodiment of the invention.

Figure 2 shows an example of an encoded carrier configured for SPR that can be measured by the apparatus according to the invention.

Figure 3a shows a schematic view of the active region of an encoded carrier, and a surface plasmon resonance excited within the carrier.

Figure 3b shows the reflectance observed from the carrier as a function of angle of incidence of the illuminating radiation.

Figure 4a shows a schematic view of the carrier of 3a that has reacted with a target chemical.

Figure 4b shows the reflectance plot from the reacted carrier.

Figure 5 shows details of a flow cell, which can be used as part of the apparatus of figure 1.

Figure 6a shows a sample image of carriers produced by the imaging section of the apparatus of figure 1.

Figure 6b shows a sample image of SPR, as produced by the SPR section of the apparatus of figure 1.

Figure 1 shows a reading apparatus in accordance with an embodiment of the invention.

The encoded carriers 1 that are to be measured by the apparatus are housed within a flow cell 3. Both the flow cell 3 and encoded carriers 1 will be described in greater detail below.

Inlet and outlet tubes 5 and 7 are connected to the flow cell 3 to supply and remove reagents respectively. The inlet and outlet tubes 5, 7 are constructed from a flexible material, so that movement of the flow cell 3 is possible without disconnection of the tubes from their supply. Thus, the apparatus is capable of both performing reactions with, and making measurements on the carriers 1 whilst the carriers 1 are within the flow cell 3.

The flow cell 3 is mounted on, or in close proximity to, the light emitting surface of a backlight 9 which, in this example, supplies blue light illuniination from one or more blue LED's. Light emitted by the backlight 9 passes through the bottom surface of the flow cell 3 to illuminate the carriers 1. The backlight 9 may supply illumination other than blue light, such as infrared or light of other wavelengths, and need not necessarily be an LED-based source. The backlight 9 may contain a diffuser to ensure that diffuse illumination is provided to the flow cell and carriers. Alternatively, a diffuser may be formed from one of the lower layers of the flow cell 3. The backlight 9 is configured to provide substantially uniform illumination over all, or a large part of, the lower surface of the flow cell 3.

The flow cell 3 and backlight 9 are mounted together on a translation stage 11 such that motion of the translation stage will move both the backlight 9 and flow cell 3 in unison.

The translation stage shown in the figure has three degrees of translational freedom in the x y and z directions. However, translation stages with fewer degrees of freedom may also be used, so too can translation stages that also have rotational motion capabilities. The translation stage 11 in this example is computer-controlled, however manually controlled stages may also be used. By mounting the flow cell 3 and backlight 9 on a translation stage, the position of the coded carriers 1 may be altered with respect to the rest of the reading apparatus.

By mounting the flow cell 3 on the emitting surface of the backlight 9, a silhouette image of the carriers 1 can be obtained. Light from the backlight 9 passes through the flow cell 3 illuminates the encoded carriers 1 and is collected by a lens 17. The collected light 18 then encounters a beamsplitter 19, which is oriented at 45° to the plane of the flow cell 3. The beamsplitter 19 in this example is an amplitude type beamsplitter and thus a portion of the light 18 from the backlight 9 passes directly through the beamsplitter. The portion of the light reflected by the beamsplitter 19 in this example is not of interest and is directed onto a filter 23, which absorbs blue light.

The light 20 that passes through the beamsplitter 19 then impinges on a second beamsplitter 15 also oriented at 45° to the path of the light.

The second beamsplitter 15 may also be an amplitude beamsplitter, and so will again reflect a portion of the light 20. The reflected portion is again not of interest. The light 22 passing through the second beamsplitter 15 then encounters a filter 25, which is configured to transmit blue light from the LED backlight 9 while substantially blocking light of other wavelengths. After passage through the filter 25 the light 22 encounters a lens 27, which is configured to image the focal plane of the first lens 17 onto a detector 29. Preferably, the detector 29 will be a two-dimensional array of sensors, such as a CCD camera, and thus an image of the encoded carriers 1 inside the flow cell 3 can be produced. By producing an image using the backlight illumination, the images produced of the encoded carriers 1 at the detector 29 will be in the form of a silhouette showing the outline of the carriers 1. The process of identification of the carriers 1, and their orientation from these images will be explained in greater detail below.

In an alternative embodiment, illuminationmay be provided to the carriers in a reflection configuration rather than in transmission as described above. In such a configuration, a light source may be located above the flow cell 3 and configured to provide illumination in reflection such that the light source does not interfere with light propagation through the remainder of the apparatus. If a light source provides light in this way, the flow cell 3 can be located directly on the translation stage 11.

Further illumination is provided to the carriers 1 by means of a second light source 13.

In the example shown here the second light source 13 is a collimated red laser diode, however alternative sources of illumination may be used, such as lasers of other wavelengths. The light 14 from the second source 13 is directed towards the flow cell 3 by reflection from the second beamsplitter 15. A portion of the second illumination will be transmitted through the second beamsplitter 15, however this is not of interest. The reflected portion 16 of the second illumination subsequently encounters the first beamsplitter 19. A portion of the light 16 will be reflected by the beamsplitter 19, and again, the reflected portion is not of interest.

The light 24 transmitted through first beamsplitter 19 will be focussed by focusing lens 17. The focussing lens 17 is positioned such that the focal point of the second illumination is a small distance above or below the plane containing the encoded carriers 1. The size of the focus of the second illumination is arranged to be approximately equal to the lateral size of the encoded carriers 1.

To provide the second illumination to different carriers 1, the translation stage can be moved such that the particular encoded carrier 1 of interest is in the path of the focussed second illumination.

The light 26 that is reflected by an illuminated encoded carrier 1 is collected by focusing lens 17 and is subsequently directed back onto the first beamsplitter 19. A portion of the incident light will be transmitted by the beamsplitter 19, and this is not of interest. However, the portion of the light 28, which is reflected by the first beamsplitter 19, will subsequently pass through a filter 23, which is configured to transmit light from the second light source 13 while substantially blocking light from the backlight 9. Light transmitted by this filter 23 will be incident on a second detector 21. A beam expanding system (not shown) can be employed prior to the detector 21 to form an image of appropriate size at the image plane of the second detector 21. The second detector 21 is configured such that the image produced by the detector can be used to produce an SPR measurement of the illuminated carrier.

Preferably, the second detector 21 is a two-dimensional array image sensor, such as a CCD camera. Alternatively, the second detector 21 may be a one-dimensional array of sensors such as a line-scan camera. The second detector 21 may also be a single point detector that is moved in relation to the rest of the apparatus such that a one or two-dimensional profile of the second illumination image can be obtained.

The process of SPR measurements using this arrangement will be described in greater detail below.

By employing two separate light sources and detectors, the imaging system described above is capable of simultaneously producing both silhouette images of the encoded carriers I and of making SPR measurements of the same encoded carriers 1.

In an alternative configuration, the backlight 9 provides illumination over a small region of the flow cell 3, and is maintained in a stationary position with respect to the flow cell 3 when the flow cell 3 moves. The region of the flow cell illuminated is arranged to correspond to part of, or the entire, region that is imaged by the first detector 29. By implementing such a system of illumination, the need to use a large area diffuse illumination source is removed.

In a further alternative configuration, one or both of the beamsplitters 15, 19 can be dichroictype beamsplitters. In such a configuration, when used with the present example apparatus, the first beamsplitter 19 and second beamsplitter 15 would both be selected such that they transmit a large fraction of the blue backlight 9 illumination.

The first beamsplitter 19 will be selected such that it transmits approximately half of the incident second (red) illumination and reflects the remaining half, while the second beamsplitter 15 will be selected to reflect a large fraction of the second illumination. By using dichroic beamsplitters as described, the illumination 22, 28 transmitted through the system to the first and second detectors 29, 21 can be maximised.

Figure 2 shows the top surface of an example of an encoded carrier 1 that can be measured using the apparatus of the invention. The encoded carrier 1 comprises a code region 37, an SPR region 39, and an orientation indicator 41. The code region 37 contains a code that can be used to identify the encoded carrier 1. In the example shown here, the encoded carrier 1 is formed from a sheet of material, while the code 37 is in the form of a bar code that comprises one or more slots 42 that extend through the sheet of material.

The encoded carrier 1 is made from materials that substantially block the illumination provided by the backlight 3. Thus, when such an encoded carrier 1 is placed in the flow cell 3 of the imaging apparatus as described above, the image formed of the encoded carrier 1 at the first detector 29 will show an outline of the encoded carrier 1 in silhouette. Since the slots 42 that form the code region 37 extend through the encoded carrier 1, the code will appear in the image as a series of light and dark lines. By recording the image, and processing it in, for instance, a computer system, the value of the code can be determined, and thus the type of encoded carrier 1 can be identified from such an image.

Encoded carriers 1 can be randomly orientated and positioned within the flow cell 3, and may even be oriented with their reactive region (SPR region) facing downwards.

The apparatus must therefore be capable of identifying the position and orientation of the encoded carriers 1 before the code can be read and its value extracted. By employing an orientation indicator 41, the rotational orientation of a carrier 1 about an axis perpendicular to the plane of the flow cell 3 can be unambiguously determined, for example by analysis of the position of the orientation indicator 41 with respect to the code region 37. This analysis can also be used to determine whether the carrier 1 is face up or face down in the flow cell. If the carriers 1 are of a type that has only a single surface (the top surface) configured for SPR, then carriers that are determined to be face down in the flow cell 3 can be identified and ignored by the apparatus.

Figure 3a is a schematic cross-section of the SPR region 39 of an encoded carrier 1, the properties of which can be measured by the apparatus of figure 1.

The encoded carrier 1 comprises a first dielectric layer 47 of Si02 and a second metal layer 45 of Au. The order of these two layers may be reversed. Region 43 is the reaction region of the encoded carrier 1, in this region, the first dielectric layer 47 and second metal layer 45 are corrugated to form a diffraction grating.

To interrogate the SPR active region 39, a beam of radiation 50 is incident on said carrier 1 at angle 0. Radiation 50 passes through a dielectric layer 55 and impinges upon the metal layer 45. Typically, the dielectric layer 55 will be a liquid medium, however this layer may alternatively be a gel, gas or a solid. A thin overlayer of solid dielectric material (not shown) may also be present between the dielectric layer 55 and metal layer 45.

When the radiation has the appropriate wavelength, polarisation and angle of incidence, the energy from the incident radiation couples to the electrons of the metal layer 45 to excite surface plasmons at the interface 57 between dielectric layer 55 and metal layer 45. At this "resonance" condition, there is a steep fall in radiation reflected from the reaction region since this radiation is now absorbed by coupling to the surface plasmon mode.

The surface plasmon mode travels along the plane of the interface and extends for a distance of approximately one third to one half of the illuminating wavelength into the dielectric layer 55. Where, for example, the illuminating wavelength is red light, this distance will be approximately 200nm.

The characteristics of the surface plasmon mode can thus be governed by physical properties of layers within which the surface plasmon propagates. Thus, chemical species 51 adhering to the surface of the reaction region may affect the surface plasmon characteristics.

The carrier is primarily intended for determining if molecules of a first type or "probes" 51, react with molecules of a second type or "targets" 53.

In figure 4a, the probes 51 have adhered to the targets 53 and thus both chemical species are attached to metal layer 45. The presence of the targets 53 will further affect the angle at which incident radiation couples to the surface plasmons, known as the resonance angle.

In figure 3a, where just the probes 51 adhere to the surface of the reaction region, the resonance angle is 0 to the surface normal. In figure 4a, where both the probes 51 and targets 53 adhere to the surface of the reaction region, the resonance angle is 0' to the surface normal. This is illustrated in figures 3b and 4b respectively which show a plot of the reflected amplitude of radiation against the incident angle of radiation.

Thus, since the reaction between the probes 51 with the targets 53 causes a variation in resonance angle, measurement of the resonance angle, can be used to determine if the second type of molecules 53 has reacted with the first type of molecules 51.

The measurement of the resonance angle may be accomplished using the apparatus of the invention shown in figure 1 as follows: Collimated radiation 14, 16, 24 from the second source 13 is focussed by lens 17 as described above. The focus produced is arranged to lie in a plane that is shifted by a small amount either above or below the plane in the flow cell 3 containing the encoded carriers 1. By positioning the focus out of the plane of the encoded carriers 1, the illumination will either be converging or diverging when it is incident on an encoded carrier 1. Thus, the light rays that impinge on the surface of an encoded carrier I will arrive from a range of angles, which are symmetrically distributed about the normal to the surface of the carrier 1. By suitable choice of lens 17 and source 13, the range of illumination angles can be arranged to be sufficiently large to include the SPR angle of the carrier type in question when illuminated by the wavelength of illumination used.

The SPR resonance will in general be sensitive to the polarisation of the illuminating light, and an SPR will normally only be observed if the incident light is TM polarised with respect to the grating formed on the encoded carrier 1. Thus, the apparatus may further comprise means for setting the polarisation state of the second illumination.

At the image plane of the second camera 21, the pattern formed will have a spatial component that is related to the angle of incidence of the light rays on the carrier 1. For example, light rays that were incident at a large angle to the normal to the surface of the carrier 1 may be located at a large distance from the optical axis of the system at the image plane of the second camera 21, while light rays that were incident at a low angle may be located near the centre of the image. If an SPR is excited on the carrier 1, then the absorption produced by this SPR will cause a reduction in the reflectance of the carrier 1 at a specific angle of incidence. The reduction in reflectance will appear in the image generated by the second camera 21 as two dark lines. One line will correspond to the SPR observed at an angle of incidence that is in one direction from the normal to the surface of the carrier 1, while the other line corresponds to the SPR observed for radiation incident at an equal but opposite angle of incidence to the normal.

Figure 6 shows an example of such an image obtained by an apparatus according to the invention. This figure will be described in greater detail below.

By measuring the separation of these two dark lines, or by measuring the separation of one line from the centre of the image, a measure of the SPR angle can be determined.

Such measurements can be made using known image analysis techniques.

Figure 5 shows the flow cell 3 in greater detail, figure 5a shows a top view of the flow cell 3, while figure 5b shows a side view. The upper and lower surfaces of the flow cell 3 are formed glass slides 31 and 35. The glass slides 31, 35 substantially transmit both the backlight illumination and the light from the second illumination source 13. The lower surface 35 of the flow cell 3 has a further layer 33 on the surface facing the inside of the flow cell 3, which is comprised of a high friction material, such as Polydimethylsiloxane (PDMS). The further layer 33 provides a high friction layer for the encoded carriers 1 so that the carriers remain substantially stationary in the flow cell even when reagents are flowing through the flow cell 3.

Other substances suitable for providing the high friction layer 33 include silicone compounds, nano-textured surfaces or other materials having a high coefficient of friction that also transmit visible or infrared radiation. The layer 33 may alternatively be formed from a material having adhesive properties rather than a high coefficient of friction.

The ends and sides of the flow cell 3 (not shown) may be sealed with any suitable material such as PDMS to create a sealed cell and inlet and outlet tubes 7 and 5 respectively may be provided at either end to allow the flow of the reagent through the flow cell 3.

If the particular reagents under examination within the flow cell 3 are such that they transmit both the blue LED backlight illumination and the red laser SPR illumination then SPR and imaging measurements may both be made during reaction process. Thus, in these circumstances the system allows real time measurement to observe reactions in progress. However, if the particular reagents under examination do not transmit sufficient illumination from one or both sources, then it may be necessary to flush the flow cell with a clear liquid to permit measurements to take place.

The encoded carriers 1 will not usually be fixed to the flow cell 3, but will rely on friction, as described above, to maintain their position in the flow cell 3. Therefore, it is possible that encoded carriers will move across the flow cell 3 or even turn over during the measurement process, particularly if reagents continue to flow through the flow cell 3. Accordingly, the measuring apparatus may be configured to make repeated measurements of the locations and orientations of the encoded carriers 1 so that the positions of the carriers can be tracked. Carriers 1 that turn over can be ignored from the measurement process since the SPR grating on the carrier may no longer be measurable by the measuring apparatus.

Figure 6 shows examples of images produced the imaging system of figure 1. Figure 6a shows silhouette images from the backlight illumination and figure 6b shows an example of an SPR image from the SPR imaging section.

In figure 6a five encoded carriers 1 are shown, all the encoded carriers 1 shown have the same code which can be seen as an indent in one of the eight sides of the octagonal carriers 1. The carriers 1 have a further indent 61 in the form of a half arrow which indicates both the orientation of the carriers, and also which way up they are with respect to the imaging system. The arrow 61 will point clockwise if a carrier has one surface facing the camera 29 and anticlockwise if the surface is facing away. The arrow 61 can also be used to determine the rotational orientation of the carrier with respect to the system.

Figure 6b shows an image produced by the SPR section of the imaging apparatus. As described above, the image produced by this part of the system is configured such that high angled rays of light from the second source 13 are located towards the edge of the image and low angle rays are located towards the centre of the image, thus this image shows the angular distribution of the reflections from the encoded carriers 1. The two dark lines shown in figure 3b correspond to the two angles at which low reflectance is observed from the encoded carriers 1, these angles will be symmetrically located either side of the normal to the surface of the encoded carrier. These dark lines therefore correspond to the SPR of the encoded carrier 1. By measuring the separation of these lines using an image processing apparatus the SPR angle for the encoded carrier in question can be determined as described above.

In an alternative embodiment, the imaging of each encoded carrier 1 is carried out at a different time to the interrogation of the SPR properties of the encoded carriers 1. For instance, the imaging portion of the system may first determine the location and orientation of an encoded carrier 1 and subsequently the translation stage 11 will position the carrier 1 at the focal point of the SPR source 13. The SPR properties of the carrier 1 can then be determined.

More than one carrier may be imaged at a time, and each of their locations, orientations and codes stored in a memory. The translation stage 11 may then move sequentially from carrier 1 to carrier 1 to determine the SPR angle of each carrier 1.

It will be apparent to those skilled in the art that various modifications and variations can be made without departing from the scope of the invention. Thus, it is intended that the present invention covers the modifications and variations of this invention provided they come within the scope of the appended claims.

Claims

CLAIMS: 1. An apparatus for measuring an encoded carrier, said encoded carrier being configured for surface plasmon resonance, said apparatus comprising; first and second sources of radiation for irradiating said encoded carrier, a receiver for measuring radiation from said encoded carrier emitted by said first source, and a receiver for measuring radiation from said encoded carrier emitted by said second source, wherein the radiation from said first and second sources is distinguishable by means of at least one of their wavelength bands, their polarisation states or their temporal or spatial profiles.
2. An apparatus according to claim 1, wherein a first receiver measures radiation from said first source and a second receiver measures radiation from said second source.
3. An apparatus according to claim 1, wherein said receiver for measuring radiation from said first source and said receiver for measuring radiation from said second source are the same receiver.
4. An apparatus according to either any preceding claim, wherein one of said sources is configured to illuminate said encoded carriers in transmission and the other of said sources is configured to illuminate said encoded carriers in reflection.
5. An apparatus according to any preceding claim, wherein said first and said second sources emit light in substantially non-overlapping wavelength ranges.
6. An apparatus according to any preceding claim, wherein said first source provides diffuse illumination over an extended area for producing silhouette images of said encoded carrier, and said second source provides a focussed beam of radiation for making surface plasmon resonance measurements.
7. An apparatus according to any preceding claim, wherein the radiation from said second source is configured to irradiate said encoded carrier with a substantially frusto-conical beam.
8. An apparatus according to any of claims 1 to 6, wherein said second source is configured to be incident on said encoded carrier at a variable angle.
9. An apparatus according to any preceding claim, further comprising filtering means configured to filter radiation from one of said sources depending on the measurement being performed.
10. An apparatus according to any preceding claim, wherein said receiver or receivers comprises an imaging detector.
11. An apparatus according to any preceding claim, wherein either or both of the location and orientation of a carrier or carriers is determined by examination of said radiation received by said receiver or receivers.
12. An apparatus according to claim 11, wherein either or both of the location and orientation of a carrier or carriers may be adjusted with respect to said second source on the basis of the determined location or orientation.
13. An apparatus according to claim 12, wherein said location of said carrier or carriers is adjusted to be coincident with a region illuminated by said second source.
14. An apparatus according to any preceding claim, further comprising a reaction vessel for housing said encoded carriers.
15. An apparatus according to claim 14, wherein an inner surface of said reaction vessel comprises a high friction layer to prevent motion of said encoded carriers within said reaction vessel.
16. An apparatus according to claim 15, wherein said high friction layer comprises Polydimethylsiloxane.
17. A method of measuring an encoded carrier, said carrier being configured to exhibit surface plasmon resonance, said method comprising; irradiating said encoded carrier with the light from both a first and a second light source receiving at a receiver radiation from said encoded carrier emitted by said first source, and receiving at a receiver radiation from said encoded carrier emitted by said second source, wherein the radiation from said first and second sources is distinguishable by means of at least one of their wavelength bands, their polarisation states or their temporal or spatial profiles.
18. A method of measuring an encoded carrier according to claim 16, implemented using the apparatus according to any of claims 1 to 16.