Amersham International Plc

Oxford Instruments, Inc.

Martin F Finlan

Martin N Wilson

John E Midgley

James Christopher Irlam

Richard P Harvey

Stephen A Charles

Ian A McKay

Michael A Brady

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.

Biological sensors

The present invention is drawn to a surface plasmon resonance (SPR) sensor in which the phenomenon of long-range surface plasmon resonance is used to develop a highly sensitive detector for use in biological, biochemical or general chemical testing. The sensor includes a laminar structure having of a high refractive index glass block, a membrane of dielectric material, a thin metal layer, and a sensitive layer. A sample to be tested is brought into contact with the sensitive layer. The refractive index of the dielectric layer and that of the layer (sensitive layer/sample) on the opposite side of the metallic layer should be equal, or nearly so, and the refractive index of the glass block should be higher than this so that total internal reflection takes place at the interface between the block and the membrane. Light from a laser source is totally internally reflected at this interface, and the strength of the reflected beam is monitored by a light detector. Provided conditions are correct, long-range SPR will take place which will sensitively alter the strength of the light in dependence upon the progress of the reaction between the sensitive layer and sample.

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.

Apparatus for the high resolution imaging of macromolecules and interactions involving macromolecules. The apparatus comprises a surface (10) on which the macromolecule under test is placed and a plurality of fine probes (13). Means (not shown) are provided for scanning each of the probes (13) across a small area of the surface 10 in such a way that the total output from the probes covers the whole surface. Means (not shown) such as a scanning tunnelling and/or atomic force detector are used to monitor the movement of the individual probes in a direction transverse to the surface (10) and display means (not shown) are used to display the transverse movement of the probes, being illustrative of the topography of the surface.

Imaging apparatus and method

A surface plasmon resonance (SPR) sensor is adapted for biochemical and similar testing on large area samples such as the gel of an electrophoresis apparatus. The gel is sandwiched between a pair of plates. One of the plates is of transparent material and, sandwiched between itself and the gel is a metal layer of a mosaic of silver dots. Light from a source is directed via a reflector and undergoes total internal reflection at the interfacce between the transparent plate and metal layer. The reflected light is passed via another reflector to a light detector. The equipment is arranged so that SPR occurs at the metal layer, which resonance is critically dependent upon the refractive index of the gel. The structure including the light source and detector, together with reflectors is caused to scan across the gel surface to enable a two-dimensional representation of the changes in refractive index across the gel to be built up. This enables the progress of sequencing to be monitored.

Surface plasmon resonance sensors

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.

In a proton/neutron source incorporating a cyclotron, in particular a superconducting cyclotron having a cylindrical superconducting magnet incorporating superconducting magnetic coils associated with pole pieces, a stream of ionized particles, such as H.sup.- particles, is continuously injected into the center of the cyclotron beam space and is accelerated outwards in a spiral path under the combined effect of the magnetic field from the superconducting magnet, and RF energization applied to sector-shaped electrodes. When the particles reach the required energy, they are removed from the spiral path by septa electrodes, and are passed across a proton storage ring in a path of rapidly increasing radius under the influence of the falling magnetic field of the superconducting magnets. A certain distance out from the center of the cyclotron, the magnetic field reverses, and the particles turn anticlockwise and enter a bending magnet in which the route of the particles is bent back towards the cyclotron so that they eventually enter the proton storage ring. As they enter the ring, the particles are stripped of their electrons so that they become positively charged protons, which protons will circulate continuously round the storage ring until required. Extraction from the ring may, for example, be effected by septa electrodes.

Proton source

A sensor uses the principle of surface plasmon resonance (SPR) to monitor the progress of the reaction between a sample and a sensitive layer (for example an antibody layer). The layer is applied to the rear surface of a metallic film formed on the surface of an optically transmissive component in the form of a hemicylindrical lens and slide. Collimated light from a source is applied via a lens which focuses the incoming beam to a focus at a point to form a fan-shaped spread of light incident at the point. The light is internally reflected at the point, and emerges from the component to be applied to a dectector array which latter is electronically scanned. The angle of incidence of the light at the point is such as to span that angle which gives rise to surface plasmon resonance, together with a range of angles thereabout so that the progress of the resonant condition, as the reaction between the sample and the sensitive layer proceeds, can be monitored.

A cyclotron having a cylindrical superconducting magnet which generates an axial magnetic field and has a central opening or chamber of substantially circular cross-section. The accelerating beam space is located in this chamber lying normal to the axis of the magnetic field. The azimuth variation of magnetic field as well as the isochronous radial variation of magnetic field required to control the orbiting of the ion beam in the beam space, are provided by ferro-magnetic pole pieces located in the axial chamber, which interact with the magnetic field to cause the required field variations. Interposed between the pole pieces are resonant frequency members which provide the radio frequency energization to accelerate the ion beam around the beam space. Having the whole of the central chamber free for top and bottom access enables the pole pieces to be given an efficient design shape. Also, the radio frequency members are able to be interposed between the pole pieces and are not restricted as to axial length and so can be made a very efficient length, such as quarter wave length resonators. The radio frequency members have axially extending hollow interiors which open into the beam space and this enables vacuum pumping to communicate through these interiors thus allowing very efficient pumping of the beam space. There is no iron yoke for the magnet and the weight and size are consequently much reduced and the cyclotron is highly transportable.

Cyclotron with yokeless superconducting magnet

The apparatus comprises a cell 2 containing the sample 1 under investigation. Electromagnetic waves P1,P2 are applied from opposite directions and interfere with one another in the region of the cell to form a standing wave pattern 6. DUe to electrostriction effects the standing wave pattern causes particles within the sample to concentrate in certain areas in a pattern corresponding to that of the standing wave 6. This pattern of particle concentration forms a grating when seen by an input wave Pin of electromagnetic wave radiation and, provided conditions are correct, results in the generation of a phase conjugate wave Pout. Means (not shown) are provided for measuring the intensity of the phase conjugate wave Pout which gives a sensitive measure of the size of the particles suspended in the sample.

Method and apparatus for particle analysis

A method and apparatus for assaying a species in a biological sample fluid. The apparatus comprises an SAW device (1) comprising a slab (2) of piezoelectric material on the upper surface (5) of which is formed an input transducer (3) and an output transducer (4). A source of RF energy is applied to the input transducer to generate a surface acoustic wave. Applied to the surface (5) is a thin layer (8) of a material capable of binding a species to be assayed. The sample (13) to be tested is applied to the top of the layer (8). A collimated light beam (1) from a source (9) is applied to the thin film from underneath the slab (2) and is collected by a photodetector (12). When the slab (2) is energized, the vibration sets up an effective diffraction grating which is coupled to the thin film and acts to diffract the light beam (10) applied to it. The energy in the diffracted beam, as measured by the photodetector ( 12), is indicative of the progress and result of the reaction between the layer 8 and the sample.

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Aylesbury, United Kingdom

Martin F Finlan