EFFECTIVE-INDUCTANCE-CHANGE BASED MAGNETIC PARTICLE SENSING

• US 20090267596A1
• Filed: 03/06/2009
• Published: 10/29/2009
• Est. Priority Date: 03/07/2008
• Status: Active Grant

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Chen, Yan, Wang, Hua, Hajimiri, Seyed Ali
• Granted Patent: US 9,176,206 B2
• Time in Patent Office: Days
• US Class Current: 324/228
• CPC Class Codes: G01R 33/1269 of molecules labeled with magnetic beads magnetic particles for bio assay G01N33/54326

Abstract

The invention relates to an integrated measurement system to detect a quantity of magnetic particles in a sample. The measurement system includes a substrate. An electromagnetic (EM) structure disposed on the surface of the substrate is configured to receive a sample including the magnetic particles in proximity thereof. The integrated measurement system also includes an electrical current generator disposed on the surface of the substrate which is electro-magnetically coupled to the EM structure. The electrical current generator is configured to cause an electrical current to flow in the EM structure. The integrated measurement system also includes an effective inductance sensor disposed on the surface of the substrate which is configured to measure a selected one of an effective inductance and a change in effective inductance. The invention also relates to a method to determine the number of and/or the locations of the magnetic particles in a sample.

Claims

26. A method for determining the number of magnetic particles in a sample, comprising the steps of:

providing an integrated magnetic particle sensor having a sensor sample volume, an electromagnetic (EM) structure, an electrical current generator, and an effective inductance sensor;

providing a sample comprising a plurality of magnetic particles;

delivering said sample to said sensor sample volume;

generating an electrical current in said EM structure to establish a magnetic field in said sensor sample volume;

measuring a parameter of said sensor sample volume; and

determining the number of magnetic particles in said sample based on said parameter.

1. An integrated measurement system to detect a quantity of magnetic particles in a sample comprising:

a substrate having a surface;

an electromagnetic (EM) structure disposed on said surface of said substrate and configured to receive a sample comprising said magnetic particles in proximity thereof;

an electrical current generator disposed on said surface of said substrate and electro-magnetically coupled to said EM structure, said electrical current generator configured to cause an electrical current to flow in said EM structure; and

a sensor comprising a selected one of an effective inductance and a mutual inductance sensor, said sensor disposed on said surface of said substrate and configured to measure a selected one of an effective inductance and a change in effective inductance;

thereby to detect said quantity of magnetic particles.

2. The measurement system of claim 1, wherein said integrated measurement system comprises a CMOS structure.

3. The measurement system of claim 1, wherein said electrical current generator comprises a quasi-static electrical current generator.

4. The measurement system of claim 1, wherein said magnetic particles comprise magnetic beads.

5. The measurement system of claim 4, wherein said magnetic particles comprise magnetic micro/nano beads.

6. The measurement system of claim 1, wherein said measurement system comprises a cell/bio-molecule sensing system.

7. The measurement system of claim 1, wherein said measurement system comprises an impedance based sensing system.

8. The measurement system of claim 1, wherein said measurement system comprises a transmission line based sensing system.

9. The measurement system of claim 1, wherein said measurement system comprises an oscillator based sensing system.

10. The measurement system of claim 9, wherein said oscillator based measurement comprises a low noise oscillator.

11. The measurement system of claim 1, further comprising a temperature regulator.

12. The measurement system of claim 11, wherein said temperature regulator is configured to set a temperature of said integrated measurement system.

13. The measurement system of claim 11, wherein said temperature regulator is configured to set a temperature of said quantity of magnetic particles in said sample.

14. The measurement system of claim 1, further comprising a sample delivery structure.

15. The measurement system of claim 14, wherein said sample delivery structure comprises a microfluidic delivery structure.

16. The measurement system of claim 1, further comprising a second EM structure disposed on said surface of said substrate, wherein said first EM structure is configured to receive a sample comprising a plurality of target particles and said second EM structure is configured to receive a control solution.

17. The measurement system of claim 16, wherein said control solution comprises a sample lacking magnetic particles.

18. The measurement system of claim 16, wherein said control solution comprises a sample having magnetic particles.

19. The measurement system of claim 16, wherein said control solution comprises a sample lacking magnetic properties.

20. The measurement system of claim 16, wherein said control solution comprises a sample having magnetic properties.

21. The measurement system of claim 1, further comprising a sensor configured to make a differential sensing measurement.

22. The measurement system of claim 21, wherein an oscillator based measurement system comprises is a sensing oscillator and a reference oscillator configured to obtain a correlation on a 1/f³ phase noise and wherein said sensing oscillator and said reference oscillator are configured to measure a difference between a first set of frequency counts of said sensing oscillator and a second set of frequency counts of said reference oscillator.

23. The measurement system of claim 1, comprising a differential sensing system configured to suppress a common mode noise.

24. The measurement system of claim 1, further comprising an M×

N array of EM structures disposed on said surface of said substrate, wherein each element of said array of EM structures is configured for a sensitivity to a particular type of target particle and said measurement system is configured to measure a plurality of quantities of said particular types target particles for each of a plurality of sample volumes, each sample volume of said plurality of sample volumes comprising a portion of a common sample.

25. The measurement system of claim 1, further comprising an M×

N array of EM structures disposed on said surface of said substrate, wherein each element of said array of EM structures is configured to measure a quantity of target particles of a respective one of a plurality of different samples.

27. The method of claim 26, wherein said step of measuring a parameter comprises the step of measuring an electrical parameter of said sensor sample volume and said step of determining the number of magnetic particles comprises the step of determining the number of magnetic particles in said sample based on said electrical parameter.

28. The method of claim 26, wherein said step of measuring a parameter comprises the step of measuring a magnetic parameter of said sensor sample volume and said step of determining the number of magnetic particles comprises the step of determining the number of magnetic particles in said sample based on said magnetic parameter.

29. The method of claim 26, wherein said step of providing an integrated magnetic particle sensor comprises providing an impedance measurement based magnetic particle sensor having a sensor sample volume.

30. The method of claim 26, wherein said step of providing an integrated magnetic particle sensor comprises providing a transmission line based magnetic particle sensor having a sensor sample volume.

31. The method of claim 26, wherein said step of providing an integrated magnetic particle sensor comprises providing an oscillator based magnetic particle sensor having a sensor sample volume.

32. The method of claim 26, wherein said step of measuring a parameter comprises measuring a parameter of said sensor sample volume by averaging a set of measurements.

31-1. The method of claim 30, wherein averaging a set measurements comprises averaging a set of frequency counting measurements.

32-2. The method of claim 26, further comprising the following additional steps:

generating an electrical current in said EM structure to establish a magnetic field in a sensor sample volume lacking a sample;

measuring a parameter of said sensor sample volume lacking a sample;

determining an empty sensor sample volume measurement based on said parameter; and

determining the number of magnetic particles in said sample based on said parameter of said empty sensor volume and said sensor volume having a delivered sample.

33. An integrated measurement system to detect a location of magnetic particles in a sample comprising:

a substrate having a surface;

an electromagnetic (EM) structure disposed on said surface of said substrate and configured to receive a sample comprising said magnetic particles in proximity thereof;

an electrical current generator disposed on said surface of said substrate and electro-magnetically coupled to said EM structure, said electrical current generator configured to cause an electrical current to flow in said EM structure; and

a sensor comprising a selected one of an effective inductance and a mutual inductance sensor, said sensor disposed on said surface of said substrate and configured to measure a selected one of an effective inductance and a change in effective inductance;

thereby to detect said location of magnetic particles.