Magnetic resonance-based viscometers and methods

• US 9,097,644 B2
• Filed: 08/15/2008
• Issued: 08/04/2015
• Est. Priority Date: 08/17/2007
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology, The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: Massachusetts Institute of Technology, The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Josephson, Lee, Cima, Michael J., Weissleder, Ralph, Hong, Rui
• Primary Examiner(s): Williams, Hezron E
• Assistant Examiner(s): Eyassu, Marrit
• Application Number:
  US12/673,866
• Publication Number:
  US 20110124744A1
• Time in Patent Office: 2,545 Days
• Field of Search: 73/544.1, 73/614.1, 73/614.3, 324/309, 324/307
• US Class Current: 1/1
• CPC Class Codes: G01N 24/08 by using nuclear magnetic resonance G01N24/12 takes precedence
• CPC Class Codes: G01N 27/745 for detecting magnetic beads used in biochemical assays concerning the assays G01N33/54326; sensors therefor G01R33/1269; automatic analysers therefor G01N35/0098
• CPC Class Codes: G01R 33/465 applied to biological material, e.g. in vitro testing
• CPC Class Codes: G01R 33/50 based on the determination of relaxation times , e.g. T1 measurement by IR sequences; T2 measurement by multiple-echo sequences
• CPC Class Codes: G01R 33/5601 involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent

Abstract

This invention relates generally to magnetic resonance (MR)-based methods and kits for measuring the viscosity of liquid samples.

Claims

1. A method for determining viscosity of a liquid, wherein the liquid comprises a solvent, the method comprising:

(i) exposing a sample comprising the liquid and two or more non-settling particles, each of the particles having a positive magnetic susceptibility and a magnetic moment of at least about 6 ×

10<sup>−

16</sup> emu per particle, to an applied magnetic field, wherein the applied magnetic field is of a strength sufficient to induce the particles to aggregate; and

(ii) measuring a change in a nuclear relaxation property of the solvent caused by aggregation of the particles in the applied magnetic field;

wherein a change in the nuclear relaxation property relates to the viscosity of the liquid.

2. The method of claim 1, wherein the nuclear relaxation property of the solvent is a relaxation time of the solvent.

3. The method of claim 2, wherein step (ii) comprises performing two or more measurements to determine the relaxation time of the solvent, wherein at least two of the measurements are performed over a time interval when the sample is exposed to the applied magnetic field.

4. The method of claim 3, wherein the method further comprises determining a rate of relaxation time change by:

(a) calculating a difference between a relaxation time measured at a start of the time interval and a relaxation time measured at an end of the time interval; and

(b) dividing the difference calculated in step (a) by a duration of the time interval.

5. The method of claim 4, wherein the method further comprises determining the viscosity of the liquid by locating the rate of relaxation time change for the sample on a plot of rates of relaxation time change versus 1/viscosity for two or more liquid standards, wherein viscosity for each standard is known.

6. The method of claim 2, wherein the relaxation time is T2.

7. The method of claim 1, wherein the solvent is water.

8. The method of claim 1, wherein the solvent is an organic solvent.

9. The method of claim 1, wherein the particle is a microparticle having a size greater than 100 nanometers to about 5 microns.

10. The method of claim 9, wherein the microparticle is a superparamagnetic microparticle.

11. The method of claim 10, wherein the microparticle comprises a superparamagnetic metal oxide.

12. The method of claim 9, wherein the microparticles have an R2 relaxivity of at least about 1×

10⁸ s<sup>−

1</sup> per mM particle.

13. The method of claim 9, wherein the microparticles have a magnetic moment of at least about 6×

10<sup>−

12</sup> emu per particle.

14. The method of claim 9, wherein the microparticles have a size of from 1 to 5 microns.

15. The method of claim 14, wherein the microparticles have a magnetic moment of at least about 6×

10<sup>−

12</sup> emu per particle.

16. The method of claim 1, wherein the particle has a buoyant density that is about the same as that of the solvent.

17. The method of claim 16, wherein the nanoparticles have an R2 relaxivity of at least about 1×

10⁸ s<sup>−

1</sup> per mM particle.

18. The method of claim 1, wherein a hydrophilic or hydrophobic moiety is covalently linked to the particle.

19. The method of claim 1, wherein a carboxylic acid group is covalently linked directly or indirectly to the particle.

20. The method of claim 1, wherein the particles have an R2 relaxivity of at least about 1×

10⁸ s<sup>−

1</sup> per mM particle.