Device for highly sensitive magnetic detection of analytes

• US 6,123,902 A
• Filed: 10/07/1998
• Issued: 09/26/2000
• Est. Priority Date: 04/18/1996
• Status: Expired due to Term

• Current Assignee: Bundesrepublik Deutschland Vertreten Durch DAS Bundesministerium FUER Wirtschaft und Technologie Dieses Vertreten Durch Den Praesidenten Der Physikalisch-Technischen Bundesantalt
• Original Assignee: Institut FUER Diagnostik-Forschung An Der Freien Universitaet Berlin
• Inventors: Drung, Dietmar, Matz, Hartmut, Koch, Hans, Semmler, Wolfhard, Weitschies, Werner, Trahms, Lutz, Kotitz, Roman
• Primary Examiner(s): Chin, Christopher L.
• Assistant Examiner(s): Do, Pensee T.
• Application Number:
  US09/147,093
• Time in Patent Office: 720 Days
• Field of Search: 422/50, 422/62, 422/63, 422/186, 422/186.01, 435/283.1, 435/287.1, 435/287.2, 324/244, 324/252, 324/256, 324/260, 324/262, 505/846, 209/223.1, 210/222
• US Class Current: 422/50
• CPC Class Codes: G01N 33/54333 Modification of conditions of immunological binding reaction, e.g. use of more than one type of particle, use of chemical agents to improve binding, choice of incubation time or application of magnetic field during binding reaction
• CPC Class Codes: G01N 35/0098 involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: Y10S 505/846 using superconductive quantum interference device, i.e. squid

Abstract

An apparatus for the qualitative and/or quantitative measurement of analytes, in particular in biological samples by means of receptor ligand binding and having a magnetizing device for the production of a magnetic field at the location of the sample and with a detection device for measurement of magnetic properties of the sample is characterized in that the magnetizing device is spatially disposed with respect to the detection device in such a fashion that the magnetic field produced by the magnetization device at the location of the magnetization is attenuated by at least a factor of 10, and preferentially by a factor of 1000 or more, at the location occupied by the sample during the measurement, or in that a switching device is provided for which, throughout a predetermined time duration and in particular during the measurement phase of the detection device can switch-off the magnetic field of the magnetizing device at the location of the sample. In this fashion new types of measurements for magnetorelaxometric detection of analytes or for the detection of analytes by means of remanence measurements can be carried out in a routine and economical fashion in vitro or in vivo.

Claims

1. An apparatus for the measurement of analytes in a sample by means of receptor ligand bonding, the apparatus comprising:

a detection device for measurement of magnetic properties of a sample during a measurement time;

a magnetizing device for producing a magnetic field at the sample; and

means for reducing a magnetic field strength of said magnetic field at the sample by a factor of at least 10 during said measurement time.

2. The apparatus of claim 1, wherein said factor is at least 1000.

3. The apparatus of claim 1, wherein said reducing means comprise means for moving the sample during said measurement time.

4. The apparatus of claim 1, wherein said reducing means comprise a circuit for switching-off said magnetic field at the sample for a predetermined time, and a device for moving the sample during said measurement time.

5. The apparatus of claim 1, wherein said reducing means comprises a switching device for switching-off said magnetic field for a predetermined length of time, said switching device having a first member to switch-on and switch-off said magnetic field and having a second member for switching-on and switching-off said detection device.

6. The apparatus of claim 5, wherein said first and said second members can be switched independently of each other.

7. The apparatus of claim 5, wherein said first member can be switched with a predetermined fixed time correlation with respect to said second member.

8. The apparatus of claim 5, wherein said first member can reduce predetermined field amplitudes and field polarities of said magnetic field produced by said magnetizing device.

9. The apparatus of claim 8, wherein said first member for producing predetermined amplitude time dependences and predetermined polarity time dependences of said magnetic field produced by said magnetizing device.

10. The apparatus of claim 1, wherein said detection device comprises means for measurement of a magnetization of the sample.

11. The apparatus of claim 10, wherein said detection device comprises means for magneto-relaxometric detection.

12. The apparatus of claim 1, wherein said detection device comprises means for measurement of a binding remanence of the analyte in the sample.

13. The apparatus of claim 1, wherein said detection device comprises at least one superconducting quantum interference device.

14. The apparatus of claim 1, wherein said detection device comprises at least one induction coil.

15. The apparatus of claim 1, further comprising means for electronic suppression of interfering signals.

16. The apparatus of claim 15, wherein said means for electronic suppression of interfering signals comprises a unit for adaptive filtering.

17. The apparatus of claim 1, further comprising means for vector measurement of interfering fields and means connected thereto for appropriate compensation of at least one of a signal measured by said detection device and said magnetic field produced by said magnetizing device.

18. The apparatus of claim 1, wherein the sample for in-vivo measurements.