Chemistry: analytical and immunological testing – Involving an insoluble carrier for immobilizing immunochemicals – Carrier is inorganic
Patent
1998-02-23
2000-02-22
MacMillan, Keith D.
Chemistry: analytical and immunological testing
Involving an insoluble carrier for immobilizing immunochemicals
Carrier is inorganic
436501, 436149, 436173, 436806, 435 71, G01N 2518, G01N 33566, G01N 33553
Patent
active
06027946&
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The invention relates to processes for magnetorelaxometric qualitative and/or quantitative detection of analytes in liquid and solid phases, compounds for magnetorelaxometric detection, and their use in analysis and immunomagnetography.
It is known that immunoscintigraphy makes it possible to detect pathological structures in vivo with the aid of radiolabeled structure-specific substances, which are also referred to below as markers. To this end, antibodies that are labeled with .gamma.-rays or antibody fragments are usually used. In addition, other structure-specific substances, such as, e.g., peptides or oligonucleic or polynucleic acids are also used or are being researched. The portion of specifically bound radioactivity is, however, generally small in all these processes. Consequently, in the case of these studies, the level of markers that are not specifically bound and thus circulate in the blood or accumulate in organs such as the liver, kidney, efferent urinary passages, or bladder is very high. In many cases, this high background radiation impedes adequate detection of pathological structures. Panchapakesan [Immunol. Cell Biol., 70 (1992) 295] and Ziegler [New England Journal of Medicine, 324 (1991) 430] therefore refer to ways of improving immunoscintigraphy. Such ways are also described in EP 0 251 494. The goal of most of the processes is to accelerate the elimination of radioactivity that is not specifically bound.
In addition, the use of antibodies that are conjugated with paramagnetic or superparamagnetic substances or antibody fragments for locating pathological structures in vivo has been proposed on various occasions. To date, nuclear spin tomography or magnetometry that is based on changes in susceptibility (WO 93/05818 and WO 91/15243) have been considered as detection processes for such labeled antibodies. In the case of these detection processes, the problem of the variable portion of the signal owing to unbound portions of the marker as well as owing to natural variations in the susceptibility and relaxivity of the tissue also remains present. In addition, the methods often are not sensitive enough to be able to detect just small amounts of specifically bound markers.
A process that makes it possible to detect only the portion of bound markers and thus is not influenced by the extent of the unbound markers is not known, however.
It is also known that quantitative immunoassays as well as other binding assays (e.g., receptor binding assays) make it possible to determine a very large number of substances that can also be of biological relevance in samples of varying composition. Generally, however, only one parameter per sample in an assay is determined in this way. An existing survey of the various processes is: T. Chard [An Introduction to Radioimmunoassay and Related Techniques: Laboratory Techniques in Biochemistry and Molecular Biology, 4th ed., Elsevier Science Publishers, Amsterdam (1990)]. The basis of all binding assays is the high detection sensitivity of compounds that are labeled with isotopes or by some other means with the high specificity of ligand-receptor reactions.
The known assay processes have the following drawbacks, however: same sample are based on the binding of various radio-, fluorescence- or enzymologically-labeled probes to the analytes. In this case, the unbound or bound activity of the probes for quantitative determination of the analyte is generally measured after subsequent separation and washing. In this case, the amount of usable different probe labels is greatly limited. Thus, for example, in the case of different radioisotopes as probe labels, so-called overlapping phenomena occur which lead to a rapid loss of the quantitative accuracy of individual signals. The combination of various enzymes as probe labels causes comparable problems, whereby the feasibility here is further hampered by the necessary search for reaction conditions that allow the simultaneous determination of enzyme reactions in a system. interactions betw
REFERENCES:
patent: 5164297 (1992-11-01), Josephson et al.
Bunte Thomas
Kotitz Roman
Trahms Lutz
Weitschies Werner
MacMillan Keith D.
Ponnaluri P.
Schering AG
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