Magnetic immunoassay system

Abstract

A magnetic immunoassay system with a mechanism for compensating the direct current residual magnetic field in the vicinity of the specimen measurement position, in a direction perpendicular to the magnetic marker direction of magnetization for the measurement target. This invention reduces the effects of the magnetic field emitted from the unbound magnetic marker due to the residual magnetic field in the specimen solution and detects with high sensitivity the signal of the bound target magnetic marker. The magnetic field at the measurement position is regulated so as to intersect the direction of magnetization of the magnetic marker for the measurement target, in order to make the magnetization direction of the magnetic marker that is unbound due to residual magnetism or remanence in the sample solution, intersect the magnetization direction of the magnetic marker for the measurement target. The signal of the bound target magnetic marker can be therefore measured with high sensitivity since it is isolated from the unbound magnetic marker signal.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A through FIG. 1E are drawings showing a typical procedure for the immunoassay method of the related art;

FIG. 2A and FIG. 2B are drawings showing the state of the magnetic markers when the magnetic field is completely blocked, and the magnetic marker state when there is a residual magnetic field;

FIG. 3A, FIG, 3B and FIG. 3C are drawings showing the relation between the magnetization direction of the sample when using a magnetometer, to the detected magnetic signal waveform;

FIG. 4A, FIG, 4B and FIG. 4C are drawings showing the relation between the magnetization direction of the sample when using a first-order planar gradiometer, to the detected magnetic signal waveform;

FIG. 5 is a drawing showing a typical structure of the immunoassay system including a compensation coil for the first embodiment of this invention;

FIG. 6 is a drawing showing a sample container used in the first embodiment;

FIG. 7 is a drawing showing the high-temperature superconducting SQUID used in the embodiment of this invention;

FIG. 8 is a flow chart showing the test protocol used in the embodiment;

FIG. 9A is a magnetic signal waveform obtained from a sample containing 100 pg of IgE measured with no electrical current flowing in the compensation coil;

FIG. 9B is a magnetic signal waveform obtained from a reference sample not containing IgE and measured with no electrical current flowing in the compensation coil;

FIG. 10 is magnetic signal waveforms from the reference sample showing the compensation coil current dependence;

FIG. 11A is a magnetic signal waveform obtained from a sample containing 100 pg of IgE measured with an electrical current of 200 μA flowing in the compensation coil;

FIG. 11B is a magnetic signal waveform obtained from a reference sample not containing IgE measured with an electrical current of 200 μA flowing in the compensation coil;

FIG. 12A is a waveform obtained from a sample where bilaterally symmetrical components were eliminated from the magnetic signal waveform measured with an electrical current of 200 μA flowing in the compensation coil;

FIG. 12B is a waveform of the reference sample not containing IGE and measured with an electrical current of 200 μA flowing in the compensation coil;

FIG. 13 is a drawing showing the structure of the immunoassay system of the second embodiment;

FIG. 14A is a magnetic signal waveform obtained in the second embodiment from a sample containing 100 pg of IgE;

FIG. 14B is a magnetic signal waveform obtained in the second embodiment from a reference sample not containing IgE.

FIG. 15 is a drawing showing the structure of the immunoassay system of the third embodiment;

FIG. 16A is a magnetic signal waveform obtained in the third embodiment from a sample (solid line) containing 100 pg of IgE; and

FIG. 16B is a magnetic signal waveform obtained in the third embodiment from a reference sample (dotted line) not containing IgE.

Claims

1. A magnetic immunoassay system comprising: a nonmagnetic reaction chamber where an antibody for binding to an antigen for detection is affixed to one surface of the chamber;a mechanism for moving the reaction chamber;a magnetic sensor for measuring the magnetic signal from the sample in a liquid state containing antibodies labeled with a magnetic nanoparticles for binding to the antigen to be detected, is injected;a magnetic shield for blocking the magnetic noise in the periphery of the magnetic sensor;a mechanism for making a first summed magnetization direction of magnetic nanoparticles labeling the antibodies bound to sample antigen bound to antibodies affixed to the nomnagnetic reaction chamber; intersect a second summed magnetization direction of only unbound magnetic nanoparticles for labeling antibodies and magnetic nanoparticles labeling antibodies bound to sample antigen that are not bound to antibodies affixed to the nonmagnetic reaction chamber; anda means for processing signals from the magnetic sensor.

2. The magnetic immunoassay system according to claim 1, wherein the magnetic sensor is a superconducting quantum interference device.

3. The magnetic immunoassay system according to claim 1, wherein the mechanism for making a first summed magnetization direction intersect the second summed magnetization direction, applies a magnetic field acting in a direction perpendicular to the pickup coil surface of the magnetic sensor for detecting magnetism.

4. The magnetic immunoassay system according to claim 2, wherein the mechanism for making a first summed magnetization direction intersect the second summed magnetization direction, applies a magnetic field acting in a direction perpendicular to the pickup coil surface of the magnetic sensor for detecting magnetism.

5. The magnetic immunoassay system according to claim 1, wherein the mechanism for making a first summed magnetization direction intersect the second summed magnetization direction, applies a magnetic field acting in a direction parallel to the pickup coil surface of the magnetic sensor for detecting magnetism.

6. The magnetic immunoassay system according to claim 2, wherein the mechanism for making a first summed magnetization direction intersect the second summed magnetization direction, applies a magnetic field acting in a direction parallel to the pickup coil surface of the magnetic sensor for detecting magnetism.

7. The magnetic immunoassay system according to claim 1, wherein the mechanism for making a first summed magnetization direction intersect the second summed magnetization direction, is an magnetic shield for blocking the magnetic field perpendicular to the pickup coil surface of the magnetic sensor for detecting magnetism.

8. The magnetic immunoassay system according to claim 2, wherein the mechanism for making a first summed magnetization direction intersect the second summed magnetization direction, is an RF shield for blocking the magnetic field perpendicular to the pickup coil surface of the magnetic sensor for detecting magnetism.

9. The magnetic immunoassay system according to claim 7, wherein the magnetic shield is comprised of cylindrical-shaped high permeability material formed with an opening on both side surfaces.

10. The magnetic immunoassay system according to claim 8, wherein the magnetic shield is comprised of cylindrical-shaped high permeability material formed with an opening on both side surfaces.

11-20. (canceled)