Photodetector and the use of the same

Details Photodetector and the use of the same Photodetector and the use of the same

2000-09-26

2003-12-16

Ceperley, Mary E. (Department: 1641)

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving antigen-antibody binding, specific binding protein...

C257S043000, C257S635000, C257S642000, C257S644000, C435S007910, C435S006120, C435S040500, C435S040520, C435S176000, C435S177000, C435S180000, C435S808000, C436S172000, C436S525000, C436S544000, C436S545000, C436S546000, C436S805000

Reexamination Certificate

active

06664071

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to an opto-electronic detector for the qualitative and quantitative determination of electromagnetic radiation, in particular visible radiation. It furthermore relates to a structured matrix of opto-electronic detectors, to arrangements for optical data storage and reading, and to sensor elements and arrangements for immunodiagnostics and DNA analysis.
2. Description of the Prior Art
Specifically, the invention relates to a photodetector, or a matrix of photo-detectors, whose particular use is in the area of detection of labeled or non-labeled chemical substances for quantitative or qualitative diagnostics, for quality assurance or for chemical analysis.
Such detectors are preferably used where the occurrence, the intensity and the wavelength of electromagnetic radiation, in particular visible and near infra-red radiation, is to be determined, the radiation preferably having a wavelength in the range from 400 to 1000 nm, particularly preferably from 400 to 700 nm, very particularly preferably from 450 to 700 nm.
Typical detectors for visible radiation are Si or Ge photodiodes, CdS or CdSe photoconductivity detectors, and vacuum photodiodes and photo-multipliers. Such detectors and their use are described in “Building Scientific Instruments” (J. Moore, C. Davis and M. Coplan, London: Addison-Wesley, 1983).
A special application is the specific detection of biologically relevant molecules by so-called “molecular recognition reactions”, such as immuno-diagnostics or gene probe techniques. These methods are known to the person skilled in the art (Lit C. Kessler (Ed.)
Nonradioactive Labeling and Detection of Biomolecules
, Springer-Verlag Berlin, Heidelberg 1192): these include, in particular: immunoassays (determination of metabolites, hormones, DNA, proteins, viruses, environmental toxins, etc.), DNA fingerprinting, DNA sequencing, nucleic acid hybridization assay; Northern blotting, reporter gene assay, Southern blotting, Western blotting, peptide or allergen arrays, combinatorial arrays (arrays are fields or matrices) and the investigation of tissue samples, microsections, and living cells stained directly (dye) or indirectly (for example dye conjugates with antibodies) or immobilized on the surface, cell organelle or in the cell interior (“cell lawns”) or cell constituents.
In a simple, specific example, a molecule (for example an antibody, an antigen, an anti-antibody, or a fragment of the above) which is complementary (i.e. adheres specifically) to the molecule to be recognized is, to this end, chemically labeled by means of chemiluminescent substrates or chemiluminescent catalysts (for example enzymes). These labels can be utilized to amplify the signal, since, for example, enzyme reactions can, through high conversion, supply a multiple of photons per bound enzyme or bound molecule.
Other methods utilize substrates which manifest themselves in a color reaction, i.e. can be measured through the specific absorption of a light beam through shadowing at the detector.
FIG. 1
describes an illustrative diagram of a selective immunotest in sandwich arrangement. The soluble antigen (
13
) binds selectively to the immobilized antibody I (
14
), and a soluble antibody II (
12
) is specific for the same antigen and is bound to an enzyme (
11
). The products (
17
) of the enzyme-catalyzed reaction (
18
) can be detected directly (chemiluminescence) or indirectly (fluorescence, scintillation proximity, colorimetric shadowing) by the detector described here (
16
). In the case of a position-resolving detector, further tests can be carried out simultaneously with the same sample, such as, for example, antibody III (
19
), which, in the example, has not bound any antigen which selectively binds to it. Other (especially ELISA) tests with and without immobilization techniques are conceivable (cf. also A. M. Campbell “Monoclonal antibody and immuno-sensor technology”, Elsevier, Amsterdam, 1991).
Fluorescence chromophores, which, due to excitation, emit light having a different wavelength, and radioactive labels, which, in the scintillation proximity assay, apply a radioactive label in the molecular vicinity of a scintillation dye in the event of binding, are amongst the most sensitive methods, since the energy which generates the signal at the detector is not identical with the excitation energy. All these methods emit light having a very precisely defined wavelength.
If a molecule is recognized in a localized manner, qualitative and/or quantitative detection takes place by measurement of the light absorption or emission. The detection limits for such systems are in the molecular range; large dynamics, i.e. a quantitative statement over many orders of magnitude of the analyte concentrations, is often necessary. For analysis of tissue samples or blotting techniques, and for analysis of electrophoresis gels, and for every miniaturization and parallelization of an analytical instrument, position resolution in an arrangement which can be structured as desired is desirable. These requirements are satisfied to a very particular extent by the detector described here (Bullock, Petrusz, Techniques in Immunochemistry, Acad. Press 1982).
The commercially available instruments are large, expensive or not suitable as “field instrumentation”. They use complex photomultipliers or cooled vacuum or CCD cameras. A particularly advantageous embodiment for diagnostic application is a portable diagnosis system or one which can be connected to conventional personal computer stations. With respect to the risk of cross-contamination in the case of analysis robots, the disposable detector analysis kit is recommended. With regard to very sensitive diagnosis samples which basically require fast, direct analysis at the site of sampling owing to stability problems, the risk of contamination and a restriction to the amount of sample, miniaturization is necessary.
However, miniaturization of the known optical methods comes up against feasibility limits (cf. A. M. Campbell “Monoclonal antibody and immuno-sensor technology”, Elsevier, Amsterdam, 1991).
Only a limited number of semi-quantitative, convenient test systems are known which allow “field analysis” of this type without further technical complexity, for example after color reactions directly on a color location scale.
U.S. Pat. No. 5,384,764 describes a device for optical data storage which comprises a storage medium into which holes can be burnt by writing by means of a light source and later read out as information, wherein a matrix of microlenses is positioned in the spatial vicinity of the storage medium for imaging purposes. However, the invention contains no details of a detector matrix or any teaching regarding inexpensive production of an integrated component.
The journal c't, issue March/1998, p. 18, describes a component for optical data storage which consists of a light-generating layer of a polymer, a switchable storage layer of a protein and a detector layer of a second polymer, and also a network of crossed electrodes. The color of the protein layer can be switched through the electroluminescence of a pixel defined by the crossing of two electrodes, so that on reading the same pixel, the intensity of the light penetrating into the corresponding photodetector pixel is changed.
For applications in sensor technology, diagnostics and DNA analysis and in optical data storage, it is advantageous for a matrix to be produced from small photodetectors. Vacuum photodiodes and photomultipliers can have high sensitivity, but are unsuitable for the production of matrices comprising a large number of small detectors. Conventional solid-state photodetectors can be converted into matrices, and photodiode arrays and CCD cameras are known. However, these products are too expensive for many of the above-described applications, in particular for disposable elements. Polymeric detectors, as described in c't, can be produced inexpensively, but their sensitivity is limited; furthermore, t

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