Device for highly sensitive magnetic detection of analytes

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422 62, 422 63, 422186, 42218601, 435283, 4352871, 4352872, 324244, 324252, 324256, 324260, 324262, 505846, 2092231, 210222, G01N 2520, G01N 2100, A01N 102, C12M 100, G01R 3302

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06123902&

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

The invention concerns an apparatus for qualitative and/or quantitative detection of analytes, particularly in biological samples, by means of receptor ligand binding using a magnetizing device for the production of a magnetic field at a location of the sample and having a detection device for measurement of magnetic properties of the sample.
Similar apparatus can be inferred from prior art through the description of a measurement procedure for execution on an appropriate apparatus in accordance with JP 63090765-A2.
Apparatus for the measurement of receptor ligand binding are based on the measurement of signals generated by signal producing labels with which structure-specific substances are marked. The most sensitive current apparatus are based on the detection of radioactive marking substances (Radio Immuno Assay, RIA). The utilization of radioactive labels has obvious disadvantages, for example problems with storage and disposal of the radioactive substances. In addition, this type of apparatus requires a device for separating the bound from the unbound labels. Without this separation, a quantitative prediction is generally not possible.
Alternative apparatus are based on the optical measurement of agglutination, fluorescence, and color reactions. (FIA, ELISA). Herein, one is dealing substantially with photodetectors. Separation is also normally required in these methods for quantitative analysis. On the other hand there are a large number of apparatus for the determination of magnetic properties of samples which, however, have generally not been applied to the direct detection of receptor ligand binding up to this point in time.
A number of apparatus are known in the art which are based on methods using magnetic labels. For example, application of a magnetic field causes motion of magnetically marked particles which can be observed using, for example, a laser. In addition, there are apparatus based on methods with which magnetic labels are utilized for separation of bound and unbound components. In contrast thereto, there are very few apparatus which are based on measurement of the magnetic properties of the sample.
JP 63090765-A2 describes a SQUID immuno assay method based on magnetically marked antibodies or antigens. Unbound portions must, however, be removed from the sample (separation) following the antibody-antigen reaction. An appropriate apparatus therefor must consequently contain a device for separating the bound from the unbound labels. The magnetization of the sample is measured subsequent to separation in the presence of a magnetic field, i.e. measurement of the magnetization takes place in the field.
U.S. Pat. No. 4,913,883 describes an apparatus for immuno-agglutination assay. Same is based on the measurement of the agglutination of antibodies marked with magnetic particles in the .mu.m size range. The apparatus necessarily comprises a device for isolating the agglutinate and a device for transport of this agglutinate through the detection device using a fluid stream.
JP 3-220442 A discloses a measuring process for carrying out agglutination immuno-assays with which the amount of agglutination is antibody determined using a method for measurement of the particle size of agglomerated magnetic particles disclosed in the publication. The method consists of switching a magnetic field which penetrates the stationary fluid sample and measuring the residual magnetic flux density of the agglomerated magnetic particles.
In accordance with JP 3-220442 A determination of the degree of agglutination can also be carried out by means of optical processes for determination of particle sizes. Towards this end the published process solely concerns a method for the determination of the particle size of magnetic particles resulting from agglutination which can only be utilized in the manner described for agglomerates of magnetic particles, wherein the particle size of the agglomerate lies in the micrometer range.
A measuring process described in U.S. Pat. No. 5,486,457 serves f

REFERENCES:
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patent: 5408178 (1995-04-01), Wikswo, Jr. et al.
patent: 5437276 (1995-08-01), Takada
patent: 5486457 (1996-01-01), Butler et al.
patent: 5532592 (1996-07-01), Colclough
patent: 5891031 (1995-09-01), Ohyu
Patent Abstracts of Japan, vol. 15, No. 507 (P-1291), Dec. 20, 1991 & JP 03 220442 A (TDK Corp) Sep. 27, 1991.
Valberg, Peter A.: "Magnetometry of Ingested Particles in Pulmonary Macroges", Science 1984, vol. 424, pp. 513-516.
Philo, J.S.et al.: "High-sensitivity magnetic susceptometer . . . " Rev. Sci. Instrum., vol. 48, No. 12, Dec. 1977, pp. 1529-1536.

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