Method and apparatus for detection and measurement of accumulations of magnetic particles

• US 20020135358A1
• Filed: 02/16/2001
• Published: 09/26/2002
• Est. Priority Date: 02/16/2001
• Status: Active Grant

• Current Assignee: Quantum Design International, Inc.
• Original Assignee: Quantum Design, Inc.
• Inventors: Sager, Ronald E., Jensen, Kurt G., Diederichs, Jost H., Simmonds, Michael B., Black, Randall C.
• Granted Patent: US 6,518,747 B2
• Time in Patent Office: Days
• US Class Current: 324/204
• CPC Class Codes: G01N 27/745 for detecting magnetic beads used in biochemical assays concerning the assays G01N33/54326; sensors therefor G01R33/1269; automatic analysers therefor G01N35/0098
• CPC Class Codes: G01R 33/1215 Measuring magnetisation; Particular magnetometers therefor G01R33/14 takes precedence; electrodynamic magnetometers G01R33/028

Abstract

Apparatus for detection and measurement of agglutinations of magnetic particles employing Hall sensors. A low frequency AC signal is employed to excite or bias the Hall sensors which reside in a DC magnetic field. The particles are moved into operative relationship with the Hall sensors in order to generate a signal representing the number of particles on the substrate. The method for such detection and measurement is also part of the invention.

Claims

1. Apparatus for making quantitative measurements of agglutinations of target magnetic particles, said apparatus comprising:

a substrate configured to receive samples including said target particles in defined patterns thereon, the samples being comprised of magnetic particles of known size and magnetic characteristics bound to the target particles to form magnetic bound complex samples;

a magnet for generating a DC magnetic field;

at least one magnetic field sensing element having an output signal conductor;

means for causing movement between said substrate and the magnetic field so that the samples are placed in operative relationship with said at least one sensing element which has a resultant output signal; and

,

a signal processor for converting said output signals from said at least one sensing element to provide a signal indicative of the quantity of the samples in a pattern.

2. The apparatus of claim 1, wherein said at least one sensing element comprises a Hall sensor with a bias excitation current flowing through said Hall sensor.

3. The apparatus of claim 1, wherein said at least one sensing element comprises a magneto-resistive sensor.

4. The apparatus of claim 1, wherein said at least one sensing element comprises two Hall sensors with a bias excitation current flowing through said sensors.

5. The apparatus of claim 1, wherein said at least one sensing element comprises two Hall sensors, each adapted to connect to a source of bias excitation current to be applied to said sensors.

6. The apparatus of claim 4, wherein the excitation current flows through said Hall sensors in series.

7. The apparatus of claim 4, wherein the excitation current flows through said Hall sensors in parallel.

8. The apparatus of claim 2, wherein the excitation current is an AC excitation current connected to said at least one Hall sensor.

9. The apparatus of claim 4, wherein the excitation current is an AC excitation current connected to said Hall sensors.

10. The apparatus of claim 1, and further comprising:

a code element on said substrate; and

a code reader mounted in position to read said code element when the samples are moved into operative relationship with said at least one sensing element.

11. The apparatus of claim 1, wherein said at least one sensing element senses the difference in the DC magnetic field caused by the presence of the samples.

12. The apparatus of claim 1, wherein said at least one sensing element is positioned in the DC magnetic field.

13. The apparatus of claim 4, wherein said at least one sensing element senses the difference in the DC magnetic field caused by the presence of the samples.

14. The apparatus of claim 5, wherein said at least one sensing element senses the difference in the DC magnetic field caused by the presence of the samples.

15. The apparatus of claim 4, wherein said at least one sensing element is positioned in the DC magnetic field.

16. The apparatus of claim 5, wherein said at least one sensing element is positioned in the DC magnetic field.

17. The apparatus of claim 1, wherein said signal processor comprises:

an amplifier connected to the output of said at least one sensing element;

a balancing stage connected to said amplifier; and

a lock-in stage, the output of which is the signal indicative of the quantity of said samples in a pattern.

18. The apparatus of claim 4, wherein said signal processor comprises:

an amplifier connected to the output of said at least one sensing element;

a balancing stage connected to said amplifier;

a lock-in stage, the output of which is the signal indicative of the quantity of said samples in a pattern; and

means for synchronously coupling excitation current to said lock-in stage.

19. The apparatus of claim 5, wherein said signal processor comprises:

an amplifier connected to the output of said at least one sensing element;

a balancing stage connected to said amplifier;

a lock-in stage, the output of which is the signal indicative of the quantity of said samples in a pattern; and

means for synchronously the said lock-in stage to the sources of excitation current.

20. Apparatus for making quantitative measurements of agglutinations of target magnetic particles, said apparatus comprising:

a substrate configured to receive samples including said target particles in defined patterns thereon, the samples being comprised of magnetic particles of known size and magnetic characteristics bound to the target particles to form magnetic bound complex samples;

means for generating a DC magnetic field;

magnetic field sensing means having output signal means and positioned in the DC magnetic field;

means for causing movement between said substrate and the magnetic field so that the samples are placed in operative relationship with said sensing means which has a resultant output signal; and

,

signal processor means for converting said output signals from said sensing means to provide a signal indicative of the quantity of the samples in a pattern.

21. The apparatus of claim 20, and further comprising:

means for connecting said sensing means to a source of excitation current;

said sensing means comprises a Hall sensor connected to said means for connecting to the bias excitation current source;

22. The apparatus of claim 20, wherein said sensing means comprises a magneto-resistive sensor.

23. The apparatus of claim 20, wherein said sensing means comprises two Hall sensors, each adapted to connect to a source of bias excitation current to be applied to said sensors.

24. The apparatus of claim 23, wherein the excitation current flows through said Hall sensors in series.

25. The apparatus of claim 23, wherein the excitation current flows through said Hall sensors in parallel.

26. The apparatus of claim 21, wherein the excitation current is an AC excitation current.

27. The apparatus of claim 23, wherein the excitation current is an AC excitation current.

28. The apparatus of claim 20, and further comprising:

a code element on said substrate; and

a code reader mounted in position to read said code element when the samples are moved into operative relationship with said sensing means.

29. The apparatus of claim 20, wherein said signal processor comprises:

an amplifier connected to the output of said at least one sensing element;

a balancing stage connected to said amplifier; and

a lock-in stage, the output of which is the signal indicative of the quantity of said samples

30. The apparatus of claim 23, wherein said signal processor comprises:

an amplifier connected to the output of said at least one sensing element;

a balancing stage connected to said amplifier;

a lock-in stage, the output of which is the signal indicative of the quantity of said samples in a pattern; and

means for synchronously coupling excitation current to said lock-in stage.

31. A method for quantitatively measuring target particles, said method comprising:

applying at least one sample pattern in a predetermined configuration on a substrate, the sample pattern being comprised of magnetic particles of known size and magnetic characteristics coupled to the target particles to form magnetic bound complex samples;

creating a DC magnetic field;

causing relative motion between the substrate and the magnetic field to place the sample pattern within the magnetic field to excite the magnetic particles in the pattern and cause the magnetic particles to perturb the magnetic field;

sensing the magnetic field changes caused by the magnetic particles; and

creating a signal representative of the quantity of magnetic particles in the field.

32. The method of claim 31, wherein said sensing is accomplished by means of at least one Hall sensor.

33. The method of claim 32, and further comprising applying an AC bias excitation current to the at least one Hall sensor.

34. The method of claim 31, and further comprising sensing the position of the substrate as the sample pattern is moved into the magnetic field.

35. The method of claim 31, wherein the magnetic field is created by means of a magnet.

36. The method of claim 31, wherein the signal representing the quantity of magnetic particles in the field is created by a signal processor.

37. The method of claim 36, and further comprising applying an AC bias excitation current to the at least one Hall sensor and to the signal processor.

38. The method of claim 31, wherein said sensing is accomplished by means of two Hall sensors connected in gradiometer configuration.

39. The method of claim 38, and further comprising applying an AC bias excitation current in series through the Hall sensors.

40. The method of claim 38, and further comprising applying an AC bias excitation current in parallel through the Hall sensors.

41. The method of claim 32, and further comprising determining the position of the substrate with respect to the at least one Hall sensor by means of a code element on the substrate and a code reader mounted in fixed relationship to the sensor.

42. The method of claim 31, wherein said sensing is accomplished by means of at least one magneto-resistive sensor.

43. The method of claim 42, and further comprising determining the position of the substrate with respect to the at least one magneto-resistive sensor by means of a code element on the substrate and a code reader mounted in fixed relationship to the sensor.

44. A method for quantitatively measuring target particles, said method comprising:

applying at least one sample pattern in a predetermined configuration on a substrate, the sample pattern being comprised of magnetic particles of known size and magnetic characteristics coupled to the target particles to form magnetic bound complex samples;

creating a DC magnetic field;

causing relative motion between the substrate and the magnetic field to place the sample pattern within the magnetic field to excite the magnetic particles in the pattern and cause the magnetic particles to generate a magnetic field;

sensing the fields generated by the magnetic particles; and

creating a signal representative of the quantity of magnetic particles in the field.

45. The method of claim 44, wherein said sensing is accomplished by means of at least one Hall sensor.

46. The method of claim 45, and further comprising applying an AC bias excitation current to the at least one Hall sensor.

47. The method of claim 44, and further comprising sensing the position of the substrate as the sample pattern is moved into the magnetic field.

48. The method of claim 44, wherein the magnetic field is created by means of a magnet.

49. The method of claim 44, wherein the signal representing the quantity of magnetic particles in the field is created by a signal processor.

50. The method of claim 49, and further comprising applying an AC bias excitation current to the at least one Hall sensor and to the signal processor.

51. The method of claim 44, wherein said sensing is accomplished by means of two Hall sensors connected in gradiometer configuration.

52. The method of claim 51, and further comprising applying an AC bias excitation current in series through the Hall sensors.

53. The method of claim 51, and further comprising applying an AC bias excitation current in parallel through the Hall sensors.

54. The method of claim 45, and further comprising determining the position of the substrate with respect to the at least one Hall sensor by means of a code element on the substrate and a code reader mounted in fixed relationship to the sensor.

55. The method of claim 44, wherein said sensing is accomplished by means of at least one magneto-resistive sensor.

56. The method of claim 55, and further comprising determining the position of the substrate with respect to the at least one magneto-resistive sensor by means of a code element on the substrate and a code reader mounted in fixed relationship to the sensor.