Electrochemical detection of magnetic particle mobility

• US 8,974,658 B2
• Filed: 07/13/2007
• Issued: 03/10/2015
• Est. Priority Date: 07/17/2006
• Status: Active Grant

• Current Assignee: Universal Biosensors Pty Ltd. (Universal Biosensors, Inc.)
• Original Assignee: Universal Biosensors Pty Ltd. (Universal Biosensors, Inc.)
• Inventors: Newman, Peter Michael, Chatelier, Ronald Christopher
• Primary Examiner(s): Van, Luan
• Assistant Examiner(s): Kessel, Maris R
• Application Number:
  US12/374,276
• Publication Number:
  US 20090301901A1
• Time in Patent Office: 2,797 Days
• Field of Search: 205/792, 205/775, 204/411, 204/412, 204/545, 204/554, 204/557, 20440301-40315, 422/73, 73/540.1, 73/540.2, 435/13
• US Class Current: 205/792
• CPC Class Codes: G01N 2011/0086 magnetic properties
• CPC Class Codes: G01N 2011/147 Magnetic coupling
• CPC Class Codes: G01N 2015/1027 Determining speed or velocity of a particle
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/54

Abstract

An exemplary embodiment of the invention may include a method for electrochemically monitoring the mobility of particles in a fluid in response to an external field, the method may include monitoring an electrical characteristic of the fluid in an electrochemical cell, the fluid comprising particles that can be moved under the influence of an externally applied field; observing changes in the electrical characteristic caused by particle movement induced by the external field; and inferring a change in the physical state of the fluid from a change in the magnitude of the electrical characteristic observed.

Claims

1. A method for electrochemically monitoring the mobility of particles in a fluid in response to an external field, the method comprising:

monitoring an electrical characteristic of the fluid in an electrochemical cell, the fluid comprising particles that can be moved under the influence of the external field, wherein the particles are magnetic, wherein the external field comprises a changing external magnetic field;

observing the electrical characteristic caused by the movement of the magnetic particles induced by the external field, wherein the magnitude of the electrical characteristic can change due to a change in the mobility of the magnetic particles; and

detecting a change in the mobility of the magnetic particles from a change in the magnitude of the electrical characteristic observed.

2. The method of claim 1, wherein the fluid further comprises at least one soluble electroactive species that is capable of being oxidized or reduced at an electrode in the electrochemical cell.

3. The method of claim 2, wherein the electrical characteristic being measured is the electrochemical current by amperometry.

4. The method of claim 2, wherein the electroactive species are salts of ferricyanide and ferrocyanide.

5. The method of claim 2, wherein the fluid is whole blood or plasma and the change in the physical state of the blood or plasma is due to coagulation.

6. The method of claim 5, wherein the electrical characteristic is the electrochemical current, wherein an algorithm is adapted to identify peaks in the electrochemical current that are caused by magnetic particle movement and determine the clotting time of blood or plasma.

7. The method of claim 6, wherein the algorithm defines the clot time based on when the n^th percentile of the data around each point falls below a predetermined threshold, where the n^th percentile is in the range of 50-100^th percentile.

8. The method of claim 7, wherein the n^th percentile is around the 80^th percentile.

9. The method of claim 6, wherein the algorithm calculates the height of peaks in current and defines the clot time based on when the peak height falls below a predetermined threshold.

10. The method of claim 6, wherein the algorithm makes peaks in current easier to identify by calculating i_t−

i<sub>t−

2</sub>+i_t−

i<sub>t−

1</sub>+i_t−

i_t+2+i_t−

i_t+1 or i_t−

i<sub>t−

1</sub>+i_t−

i_t+1, where i_t is the current measured at a given point in time and i<sub>t−

1</sub> the current measured one time point earlier;

i<sub>t−

2</sub>, two time points earlier;

i_t+1, one time point later and i_t+2, two time points later.

11. The method of claim 6, wherein the algorithm determines if a peak in current occurred within a predetermined time of changing the magnetic field and defines the clot time based on whether such a peak is under a predetermined threshold.

12. The method of claim 2, wherein the electrochemical cell comprises a strip comprising two electrodes.

13. The method of claim 12, wherein said two electrodes are parallel to each other and are separated by 0.05 to 0.5 mm.

14. The method of claim 12, wherein said two electrodes are parallel to each other and are separated by 0.075-0.15 mm.

15. The method of claim 12, wherein said two electrodes are parallel to each other and are separated by 0.09-0.13 mm.

16. The method of claim 12, wherein said two electrodes are coplanar.

17. The method of claim 12, wherein said two electrodes are separated by an electrically insulating layer, where the layer has a cavity cut in it to receive fluid, as well as an entry port to allow the fluid to enter the cavity and an exit port for the displaced air.

18. The method of claim 12, wherein the fluid is whole blood or plasma and a change in the physical state of the blood or plasma is due to coagulation, wherein the fluid is deficient in clotting factors, wherein said strip contains one or more clotting factors which can replace the deficient clotting factors in the fluid.