Radiant energy – Invisible radiant energy responsive electric signalling – Semiconductor system
Patent
1996-03-22
1998-10-27
Hannaher, Constantine
Radiant energy
Invisible radiant energy responsive electric signalling
Semiconductor system
G01T 1208
Patent
active
058280677
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INVENTION
This invention concerns methods and apparatus for detecting radioisotope labelled materials which emit radiation such as beta particles.
The invention is of application in the field of radioisotopic diagnostics and analysis and for performing measurements and analysis on labelled immunoassays, tissue sections, microbiological specimens, cellular specimens, cellular monolayers, reporter genes. DNA and/or protein gels and blots.
It is of particular application to diagnostic analysis of samples in which the concentration of radioisotope varies considerably from one region to another in the field of view and/or in which two or more different radioisotopes are used to label different materials in a sample and in which some or all of the different radioisotopes may be present in the field of view. In this type of differential labelling, the different radioisotopes are selected so as to possess significantly different radio active energies to allow them to be identified, so that in consequence a wide dynamic range of energy levels is present in a sample.
The term phosphor as will be employed herein is not intended to be restricted to conventionally understood phosphors such as zinc cadmium sulphide: silver which when bombarded by alpha or beta particles or by gamma radiation in response to this incident energy will emit photons of electromagnetic energy in the visible range of the em spectrum, but is intended also to include any material which, when stimulated by incident energy, will emit energy which is capable of directly or indirectly altering the charge pattern on a CCD camera and which may be of the same type (or a different type) from the incident stimulating energy and includes polymer media doped with rare earth chelates or other scintillating material, with or without activators or wavelength shifting devices.
BACKGROUND OF THE INVENTION
As two examples (a) the extent by which drugs are taken in by tissue and/or cells and (b) the detection of antigen sites and receptor binding sites for example in medical diagnosis, research and pharmacology assays, can be determined by labelling the drug or antigen with a radioisotope such as Tritium or Carbon 14, or Sulphur 35 or Phosphorus 32, exposing the organism or sample therefrom or other assay to the labelled drug (or to the labelled antigen or antibody or other biological marker) and after a take-up period, examining the sample for beta particles, gamma rays or other radiation emitted from any isotope present in the sample. Historically this has been achieved by exposing a photographic plate to the sample in contact therewith, which when the former is developed will contain visually distinctive regions corresponding to any emitted radiation, surrounded by visually different regions corresponding to areas from which no radiation has been emitted. An alternative approach, usually for small samples, is to introduce a Phosphor film between the sample and the plate as a means of increasing sensitivity and/or facilitating direct electronic detection. Typically after exposure and development, black regions in a monochrome photographic plate correspond to radiation (such as beta particle emissions) and light regions the converse. However depending on the photographic emulsion employed and the development process, the contrast may be reversed.
Unfortunately the small amount of radio isotope present in a typical sample and the rate of radiation (such as beta particle emission) from such isotopes as are appropriate for labelling in such techniques, is such that photographic exposure times of days or weeks have been found necessary and this coupled with the poor dynamic range of photographic emulsions has led to alternative techniques being investigated.
PRIOR ART
WO92/03836 (Charon et al) describes inter alia a system in which radio isotope labelled material is exposed to a primary phosphor which emits photons in response to the impingement thereon of beta particles. The primary phosphor is imaged onto an image intensifier photocathode the light
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patent: 5475225 (1995-12-01), Stettner
Ljunggren, "Beta Camera For Static And Dynamic Imaging of Charged-Particle Emitting Radionuclides in Biologic Samples", Journal of Nuclear Medicine, vol. 31, No. 12, Dec, 1990, pp. 2058-2063.
Eikenberry, "A Two-Dimensional X-Ray Detector With A Slow-Scan Charge-Coupled Device Readout", IEEE Transactions On Nuclear Medicine, vol. 33, No. 1, Feb./1986, pp. 542-545.
Dominik, "A Gaseous Detector For High-Accuracy Autoradiography of Radioactive Compounds With Optical Readout of Avalanche Positions", Nuclear Instrumen. & Methods In Physics Research, vol. A278, No. 3, Jun./15/1989, pp. 779-787.
Ansorge Richard Eric
Hooper Claire Elizabeth
Neale William Wray
Rushbrooke John Gordon
Cambridge Imaging Limited
Hannaher Constantine
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