Magnetically induced microspinning for super-detection and super-characterization of biomarkers and live cells

• US 9,816,993 B2
• Filed: 04/11/2012
• Issued: 11/14/2017
• Est. Priority Date: 04/11/2011
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Kopelman, Raoul, Elbez, Remy, Hecht, Ariel, McNaughton, Brandon H.
• Primary Examiner(s): Gabel, Gail R
• Application Number:
  US14/111,142
• Publication Number:
  US 20140248632A1
• Time in Patent Office: 2,043 Days
• CPC Class Codes: G01N 27/84 by applying magnetic powder or magnetic ink
• 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 33/574 for cancer
• CPC Class Codes: G01N 33/587 Nanoparticles

Abstract

Identification, quantification and characterization of biological micro- and nano-systems is enabled by magnetically spinning these natural, non-magnetic systems with the aid of induced magnetization. Biofriendly magnetic micro- and nano-labels enable magnetorotation in extremely weak electromagnetic fields. The spinning of these micromotors can be observed by a simple, CD-like, optical tracking system. The spinning frequency response enables real-time monitoring of single (cancer) cell morphology, with sub-microscopic resolution, yielding previously undeterminable information. Likewise, it enables super-low detection limits for any (cancer) biomarker.

Claims

1. A method of detecting a target, the method comprising:

(a) contacting the target which is immobilized on a non-magnetic substrate particle with a plurality of magnetic particles under conditions in which the magnetic particles are capable of associating or complexing with the target, wherein the diameter of the one or more magnetic particles is smaller relative to the diameter of the non-magnetic substrate particle;

(b) applying a rotating magnetic field to the immobilized target which is associated or complexed with the magnetic particles; and

(c) detecting rotation in the magnetic field arising from association or complex formation of one or more of the magnetic particles associated or complexed with the immobilized target, wherein detection of rotation and/or rate of rotation of the target indicates presence of the target.

2. The method of claim 1 wherein the target is a target cell.

3. The method of claim 2 wherein a change in the rotation of the target cell over time indicates growth of the target cell.

4. The method of claim 2 wherein the target cell is in a population of target cells.

5. The method of claim 4 wherein the population is an aggregate of cells.

6. The method of claim 4 wherein the population of target cells contain target cells of different morphology.

7. The method of claim 6 wherein the population of target cells rotate at different rotation rates based on the different morphologies.

8. The method of claim 6 wherein the different morphology is a cellular deformation.

9. The method of claim 8 wherein the cellular deformation is a cell surface protrusion and/or is due to a genetic or biochemical change within one or more cells of the population.

10. The method of claim 2 wherein the target cell is a cancer cell.

11. The method of claim 2 wherein association is effected by one or more of the magnetic particles being internalized by the cell.

12. The method of claim 11 wherein the magnetic particles are internalized in a non-specific manner.

13. The method of claim 2 wherein magnetic particles associated with the cell induce rotation of the cell.

14. The method of claim 1 wherein one or more of the magnetic particles comprises a targeting moiety and association is effected by binding of the targeting moiety to the target.

15. The method of claim 14 wherein the targeting moiety is a peptide, an antibody, a nucleic acid, an aptamer or a combination thereof.

16. The method of claim 1 wherein the target is an analyte.

17. The method of claim 16 wherein the analyte is a biological analyte.

18. The method of claim 17 wherein the biological analyte is a protein or a nucleic acid.

19. The method of claim 18 wherein the analyte is thrombin.

20. The method of claim 16 wherein the analyte is non-biological.

21. The method of claim 20 wherein the non-biological analyte is a metal.

22. The method of claim 16 wherein the magnetic particles and the substrate particle bind the target to form the complex between the magnetic particle, the target and the substrate particle.

23. The method of claim 22, further comprising determining a rate of rotation of the complex to determine concentration of the analyte.

24. The method of claim 23 wherein a higher concentration of analyte in the sample produces a faster rotation of the complex relative to a lower concentration of analyte in a control sample.

25. The method of claim 1 wherein the diameter of the one or more magnetic particles is from about 0.01 micrometers (μ

m) to about 5 μ

m in diameter, and the diameter of the non-magnetic substrate particle is from about 5 μ

m to about 100 μ

m in diameter.