Asynchronous magnetic bead rotation sensing systems and methods

• US 8,846,331 B2
• Filed: 08/29/2011
• Issued: 09/30/2014
• Est. Priority Date: 08/27/2010
• 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: McNaughton, Brandon H., Kinnunen, Paivo, Kopelman, Raoul, Hunt, Alan, Clarke, Roy, Sinn, Irene, Elbez, Remy, Albertson, Theodore
• Primary Examiner(s): Ford, Allison
• Assistant Examiner(s): FERNANDEZ, SUSAN EMILY
• Application Number:
  US13/220,381
• Publication Number:
  US 20120164680A1
• Time in Patent Office: 1,128 Days
• Field of Search: None
• US Class Current: 435/29
• CPC Class Codes: C12M 41/36 of biomass, e.g. colony counters or by turbidity measurements electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404
• CPC Class Codes: G01N 33/54326 Magnetic particles
• CPC Class Codes: G01N 33/569 for microorganisms, e.g. protozoa, bacteria, viruses

Abstract

Described herein are various methods, devices and systems for performing asynchronous magnetic bead rotation (AMBR) to detect and monitor cellular growth and/or behavior. Cluster rotation of magnetic particles for AMBR is descried. In particular, described herein are systems for the parallel analysis of multiple wells of a sample plate. Also described herein are methods for controlling the illumination and imaging of rotating magnetic particles.

Claims

1. A method of monitoring cell growth and/or binding by asynchronous magnetic bead rotation (AMBR) in a cluster of magnetic particles, the method comprising:

allowing cells to bind to magnetic particles;

forming a cluster of the magnetic particles and bound cells such that the cluster of magnetic particles and bound cells are restrained against individual rotation, but are free to rotate together, wherein forming the cluster comprises forming the cluster by magnetic-field-induced magnetic interaction between the magnetic particles to establish a low interparticle distance between the magnetic particles;

applying a rotating magnetic field, wherein the orientation of the rotating magnetic field changes over time and the field intensity is maintained constant, at a driving rate so that the cluster of magnetic particles rotate asynchronously to the applied magnetic field at an asynchronous rotation rate, wherein the rotating magnetic field rotates around an axis and wherein the cluster of magnetic particles and bound cells rotate asynchronously about the axis when the rotating magnetic field is above a critical rotation rate for inducing asynchronous rotation of the cluster of magnetic particles and wherein the critical rotation rate varies depending on the cluster of magnetic particles; and

detecting a change in the asynchronous rotation rate indicative of cellular binding and/or growth in the cells.

2. The method of claim 1, further comprising magnetically separating the magnetic particles from a sample containing the cells.

3. The method of claim 1, wherein forming comprises forming a cluster of magnetic particles in a planar surface.

4. The method of claim 1, wherein allowing the cells to bind to the magnetic particles comprises combining the magnetic particles and cells before the magnetic particles are clustered.

5. The method of claim 1, wherein allowing cells to bind to the magnetic particles comprises adding a sample including the cells to the magnetic particles.

6. The method of claim 1, wherein forming the cluster of magnetic particles comprises forming a cluster of greater than about 5 particles.

7. The method of claim 1, wherein forming the cluster of magnetic particles comprises forming a cluster of between about 10 and about 10,000 particles.

8. The method of claim 1, wherein applying a rotating magnetic field comprises applying a rotating magnetic field of constant amplitude.

9. The method of claim 1, wherein the cells comprise bacterial cells.

10. The method of claim 1, wherein forming the cluster of magnetic particles comprises applying a magnetic field to establish the low interparticle distance between the magnetic particles and applying the magnetic field before applying the rotating magnetic field.

11. The method of claim 1, further comprising positioning the clustered magnetic particles within a curved interface.

12. The method of claim 1, wherein forming the cluster comprises forming a cluster of magnetic particles in a globular geometry.

13. The method of claim 1, wherein forming the cluster comprises forming a cluster of magnetic particles in a linear geometry.

14. The method of claim 1, wherein forming the cluster comprises:

initially applying the rotating magnetic field at an increased intensity or an increased rate of rotation to establish the low interparticle distance between the magnetic particles; and

subsequently applying the rotating magnetic field at the driving rate so that the cluster of magnetic particles rotate asynchronously to the applied magnetic field at the asynchronous rotation rate.

15. The method of claim 1, further comprising binding at least one of the magnetic particles to a protein that further binds the cluster.

16. The method of claim 1, further comprising binding at least one of the magnetic particles to a surfactant that further allows rotation of the cluster at an interface.