Nuclear magnetic resonance apparatus, systems, and methods

Patent metadata

Field	Value
Publication number	US-10359378-B2
Application number	US-201314400996-A
Country	US
Kind code	B2
Filing date	May 13, 2013
Priority date	May 14, 2012
Publication date	Jul 23, 2019
Grant date	Jul 23, 2019

Abstract

In one aspect, the disclosure relates to a nuclear magnetic resonance transceiver including: (a) a variable-frequency electromagnetic signal generator with (i) a frequency input and (ii) an EM signal output; (b) an electronic frequency controller including (i) a frequency output coupled to the frequency input of the variable-frequency EM signal generator, (ii) an intermediate frequency set-point input, and (iii) an intermediate frequency measurement input; (c) an NMR transmission probe with an EM signal input coupled to the EM signal output of the variable-frequency EM signal generator; (d) an NMR receiving probe with an EM signal output; and (e) an electronic mixer with (i) a first input coupled to the EM signal output of the NMR receiving probe, (ii) a second input coupled to the EM signal output of the variable-frequency EM signal generator, and (iii) a mixed EM signal output coupled to the frequency measurement input of the frequency controller.

First claim

What is claimed is:

1. A method for measuring nuclear magnetic resonance (NMR) in a sample, the method comprising:
(a) providing an NMR apparatus comprising:
(i) a nuclear magnetic resonance (NMR) transceiver comprising:
(A) a variable-frequency electromagnetic (EM) signal generator comprising a frequency input and an EM signal output;
(B) a frequency controller comprising a frequency output coupled to the frequency input of the variable-frequency EM signal generator, a frequency set-point input, and a frequency measurement input;
(C) an NMR transmission probe comprising an EM signal input coupled to the EM signal output of the variable-frequency EM signal generator;
(D) an NMR receiving probe comprising an EM signal output; and
(E) a mixer comprising a first input coupled to the EM signal output of the NMR receiving probe, a second input coupled to the EM signal output of the variable-frequency EM signal generator, and a mixed EM signal output coupled to the frequency measurement input of the frequency controller;

(ii) a magnet having a magnetic field; and
(iii) a sample container positionable in the magnetic field and proximate to the NMR transmission probe and the NMR receiving probe;

(b) selecting the frequency set-point input to the frequency controller;
(c) placing a sample to be measured for the presence of a magnetic moiety in the sample container;
(d) exciting the sample with an EM signal delivered from the NMR transmission probe, the EM signal having a selected frequency and a selected power;
(e) detecting an NMR signal emitted from the excited sample with the NMR receiving probe; and
(f) determining a new selected frequency for the EM signal delivered from the NMR transmission probe with the frequency controller and an error function determined from (i) the frequency set-point input and (ii) a mixed EM signal from the delivered EM signal and the emitted NMR signal as the frequency measurement input.

2. The method of claim 1 , further comprising:
(g) determining whether the magnetic moiety is present in the sample.

3. The method of claim 1 , wherein:
(i) the NMR transceiver further comprises:
(F) a power amplifier comprising an EM signal input coupled to the signal output of the variable-frequency EM signal generator, an amplifier gain input, and an amplified EM signal output;
(G) a directional coupler comprising an EM signal input coupled to the amplified EM signal output of the power amplifier, an EM signal output coupled to the EM signal input of the NMR transmission probe, and a voltage output; and
(H) a gain controller comprising a gain output coupled to the amplifier gain input of the power amplifier, a voltage set-point input, and a voltage measurement input coupled to the voltage output of the directional coupler; and

(ii) the method further comprises determining a new selected power for the EM signal delivered from the NMR transmission probe with the gain controller and an error function determined from (A) the voltage set-point input and (B) the voltage output from the directional coupler as the voltage measurement input.

4. The method of claim 1 , wherein:
(i) the NMR transmission probe and the NMR receiving probe are in the form of a combined NMR probe coupled to a switch switchable between at least a transmit state and a receive state;
(ii) in the transmit state, the NMR probe is coupled to the EM signal output of the variable-frequency EM signal generator;
(iii) in the receive state, the NMR probe is coupled to the first input of the mixer; and
(iv) the sample container is mountable to the combined NMR probe.

5. The method of claim 1 , wherein the magnetic moiety comprises a magnetic nanoparticle-analyte complex comprising a magnetic nanoparticle bound to a target analyte.

6. The method of claim 5 , wherein the sample is substantially free from magnetic nanoparticles not bound to the target analyte.

7. The method of claim 5 , wherein the sample further comprises magnetic nanoparticles not bound to the target analyte.

8. The method of claim 7 , further comprising:
repeating the method for measuring for nuclear magnetic resonance in a separately analyzed control sample, the control sample comprising magnetic nanoparticles (i) only in the form of magnetic nanoparticles not bound to the target analyte and (ii) in the same amount as total magnetic nanoparticles present in the sample; and
comparing the NMR measurement for the sample with the NMR measurement for the control sample to determine whether the magnetic nanoparticle-analyte complex is present in the sample.

9. The method of claim 5 , wherein the target analyte is selected from the group consisting of bacteria, viruses, oligonucleotides, polynucleotides, proteins, enzymes, and combinations thereof.

10. The method of claim 5 , wherein the magnetic nanoparticle comprises: (i) a magnetic nanoparticle core, (ii) a conductive polymer shell bound to the magnetic nanoparticle core, and (iii) a binding pair member bound to the conductive polymer shell.

11. The method of claim 5 , wherein the magnetic nanoparticle comprises: (i) a magnetic nanoparticle core, and (ii) a binding pair member complementary to the target analyte and immobilized on the magnetic nanoparticle core.

12. The method of claim 1 , comprising selecting the frequency set-point input corresponding to the ambient temperature during measurement.

13. The method of claim 1 , comprising selecting the frequency set-point input to have a value ranging from 0.01 kHz to 10 kHz.

14. The method of claim 1 , wherein the sample comprises a liquid sample medium.

15. The method of claim 1 , comprising performing the method without active or passive temperature control.

16. A nuclear magnetic resonance (NMR) transceiver comprising:
(a) a variable-frequency electromagnetic (EM) signal generator comprising (i) a frequency input and (ii) an EM signal output;
(b) a frequency controller comprising (i) a frequency output coupled to the frequency input of the variable-frequency EM signal generator, (ii) a frequency set-point input, and (iii) a frequency measurement input;
(c) an NMR transmission probe comprising an EM signal input coupled to the EM signal output of the variable-frequency EM signal generator;
(d) an NMR receiving probe comprising an EM signal output; and
(e) a mixer comprising (i) a first input coupled to the EM signal output of the NMR receiving probe, (ii) a second input coupled to the EM signal output of the variable-frequency EM signal generator, and (iii) a mixed EM signal output coupled to the frequency measurement input of the frequency controller.

17. The NMR transceiver of claim 16 , wherein:
(i) the NMR transmission probe and the NMR receiving probe are in the form of a combined NMR probe coupled to a switch switchable between at least a transmit state and a receive state;
(ii) in the transmit state, the NMR probe is coupled to the EM signal output of the variable-frequency EM signal generator; and
(iii) in the receive state, the NMR probe is coupled to the first input of the mixer.

18. The NMR transceiver of claim 17 , wherein the NMR probe comprises a solenoid coil.

19. The NMR transceiver of claim 16 , further comprising:
(f) a power amplifier comprising (i) an EM signal input coupled to the signal output of the variable-frequency EM signal generator and (ii) an amplified EM signal output coupled to the EM signal input of the NMR transmission probe.

20. The NMR transceiver of claim 16 , further comprising:
(f) a power ampl

Assignees

• Univ Michigan State

Inventors

• Alocilja Evangelyn C
• Luo Yilun

Classifications

• G01N24/08 Primary

  by using nuclear magnetic resonance (G01N24/12 takes precedence) · CPC title

• G01R33/28

  Details of apparatus provided for in groups G01R33/44 - G01R33/64 · CPC title

• G01R33/448

  Relaxometry, i.e. quantification of relaxation times or spin density (G01R33/50 takes precedence) · CPC title

• G01R33/302

  Miniaturized sample handling arrangements for sampling small quantities, e.g. flow-through microfluidic NMR chips · CPC title