Effective-inductance-change based magnetic particle sensing

• US 9,176,206 B2
• Filed: 03/06/2009
• Issued: 11/03/2015
• Est. Priority Date: 03/07/2008
• Status: Active Grant

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Wang, Hua, Hajimiri, Seyed Ali, Chen, Yan
• Primary Examiner(s): Soderquist, Arlen
• Application Number:
  US12/399,603
• Publication Number:
  US 20090267596A1
• Time in Patent Office: 2,433 Days
• Field of Search: 738/611.1, 324/207.22, 436/86, 436/94, 436/149, 436/151, 436525-526, 436/806
• US Class Current: 1/1
• 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

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

a substrate having a surface;

first and second sample delivery structures;

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

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

a sensing oscillator electrically coupled to said first EM structure, said sensing oscillator comprising a selected one of a self inductance sensor and a mutual inductance sensor, said sensing oscillator disposed on said surface of said substrate and configured to measure a selected one of an effective inductance and a change in effective inductance; and

a second EM structure disposed on said surface of said substrate, wherein said second EM structure is configured to receive a control solution via said second sample delivery structure;

said integrated measurement system being configured to detect said quantity of said magnetic particles based on a differential sensing measurement that is based on a first signal associated with said first EM structure and a second signal associated with said second EM structure.

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 measurement system comprises a cell/bio-molecule sensing system.

5. The measurement system of claim 1, wherein said sensing oscillator comprises a low noise oscillator.

6. The measurement system of claim 1, wherein said first sample delivery structure comprises a microfluidic delivery structure.

7. An integrated measurement system configured to detect a quantity of magnetic particles in a first sample, the system comprising:

a substrate having a surface;

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

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

a sensing oscillator disposed on said surface of said substrate and configured to provide an indication of a selected one of an effective inductance and a change in effective inductance associated with said first EM structure;

a second EM structure disposed on said surface of said substrate and configured to receive a second sample in proximity thereof;

a reference oscillator disposed on said surface of said substrate and configured to provide an indication of a selected one of an effective inductance and a change in effective inductance associated with said second EM structure;

wherein said integrated measurement system is configured to make a differential sensing measurement to detect said quantity of said magnetic particles based on a difference between a first signal associated with said sensing oscillator and a second signal associated with said reference oscillator.

8. The measurement system of claim 7, 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.

9. The measurement system of claim 7, wherein said sensing oscillator and said reference oscillator are arranged to suppress a common mode noise.

10. The measurement system of claim 7, 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.

11. The measurement system of claim 7, 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.

12. The measurement system of claim 7, further comprising a first sample delivery structure configured to provide said first sample in proximity of said first EM structure, and a second sample delivery structure configured to provide said second sample in proximity of said second EM structure.

13. The measurement system of claim 12, wherein said first sample delivery structure comprises a micro-fluidic channel.

14. The measurement system of claim 7, wherein the system is configured to disable said reference oscillator while said sensing oscillator is enabled, and to enable said reference oscillator while said sensing oscillator is disabled.

15. The measurement system of claim 7, wherein said first EM structure and said second EM structure are situated physically close together such that said first EM structure and said second EM structure experience substantially the same operation environment.

16. The measurement system of claim 7, wherein said first EM structure and said second EM structure are electrically coupled to the same supply voltage.

19. The measurement system of claim 7, wherein said measurement system comprises a cell/bio-molecule sensing system.

17. The measurement system of 7, wherein said integrated measurement system comprises a CMOS structure.

18. The measurement system of 7, wherein said electrical current generator comprises a quasi-static electrical current generator.

20. The measurement system of 7, wherein said sensing oscillator comprises a low noise oscillator.