Optical nuclear magnetic resonance microscope and measurement methods

Patent metadata

Field	Value
Publication number	US-11313817-B2
Application number	US-201917271445-A
Country	US
Kind code	B2
Filing date	Aug 27, 2019
Priority date	Aug 27, 2018
Publication date	Apr 26, 2022
Grant date	Apr 26, 2022

Abstract

A variety of application can use nuclear magnetic resonance as an investigative tool. Nuclear magnetic resonance measurements can be conducted using a nuclear magnetic resonance microscope. An example nuclear magnetic resonance microscope can comprise a film embedded in a coverslip, where the film is doped with reactive centers that undergo stable fluorescence when illuminated by electromagnetic radiation having a wavelength within a range of wavelengths and a magnetic field generator to provide a magnetic field for nuclear magnetic resonance measurement of analytes when disposed proximal to the film. Microwave striplines on the coverslip can be arranged to generate microwave fields to irradiate the analytes for the nuclear magnetic resonance measurement. Control of the microwave signals on the microwave striplines can be used for dynamic nuclear polarization in the nuclear magnetic resonance measurement of analytes.

First claim

What is claimed is:

1. A nuclear magnetic resonance microscope comprising:
a coverslip;
a film embedded in the coverslip, the film doped with reactive centers that undergo stable fluorescence;
a magnetic field generator to provide a magnetic field for nuclear magnetic resonance measurement of analytes disposed proximal to the film;
two microwave striplines on the coverslip, the two microwave striplines arranged to generate microwave fields to irradiate the analytes for the nuclear magnetic resonance measurement; and
a photodetector to detect fluorescence of the reactive centers, illuminated by the electromagnetic radiation, in response to resonance of the analytes.

2. The nuclear magnetic resonance microscope of claim 1 , wherein the nuclear magnetic resonance microscope includes a laser to illuminate the reactive centers.

3. The nuclear magnetic resonance microscope of claim 1 , wherein the film is a magneto-fluorescent diamond film.

4. The nuclear magnetic resonance microscope of claim 3 , wherein the magneto-fluorescent diamond film includes diamond doped with a layer of fluorescent sensors at a surface of the magneto-fluorescent diamond film.

5. The nuclear magnetic resonance microscope of claim 1 ; wherein the film is structured with a nanograting having sidewalk with the sidewalls doped with the reactive centers.

6. The nuclear magnetic resonance microscope of claim 5 , wherein the nanograting is structured having a diamond nanograting with the reactive centers being nitrogen vacancy color centers.

7. The nuclear magnetic resonance microscope of claim 1 , wherein the reactive centers undergo stable fluorescence in a range of about 650 nm to about 800 nm.

8. The nuclear magnetic resonance microscope of claim 1 , wherein the magnetic field generator includes two magnets arranged to place the coverslip between the two magnets.

9. A nuclear magnetic resonance microscope comprising:
a coverslip;
a magneto-fluorescent diamond film embedded in the coverslip, the magneto-fluorescent diamond film including diamond doped with a layer of fluorescent sensors at a surface of the diamond film, with each sensor being a nitrogen vacancy color center that exhibits photostable fluorescence;
a magnetic field generator to provide a bias magnetic field for nuclear magnetic resonance measurement of analytes disposed proximal to the magneto-fluorescent film;
two microwave striplines on the coverslip, the two microwave striplines arranged to generate microwave fields to irradiate the analytes for the nuclear magnetic resonance measurement; and
a photodetector to detect fluorescence of the nitrogen vacancy color centers in response to resonance of the analytes in the nuclear magnetic resonance measurement.

10. The nuclear magnetic resonance microscope of claim 9 , wherein the nuclear magnetic resonance microscope includes a laser to illuminate the nitrogen vacancy color centers.

11. The nuclear magnetic resonance microscope of claim 10 , wherein the laser generates green laser light.

12. The nuclear magnetic resonance microscope of claim 9 , wherein the magneto-fluorescent diamond film is structured with a diamond nanograting.

13. The nuclear magnetic resonance microscope of claim 12 , wherein the diamond nanograting has sidewalls with the sidewalls doped with the nitrogen vacancy color centers.

14. The nuclear magnetic resonance microscope of claim 9 , wherein the two microwave striplines are operable to excite the analytes proximal to the nitrogen vacancy color centers to facilitate polarization transfer via solid effect; Hartmann-Hahn protocol; resonant cross-relaxation, or a combination thereof.

15. The nuclear magnetic resonance microscope of claim 9 , wherein the nuclear magnetic resonance microscope includes a switch for activating and deactivating the nuclear magnetic resonance measurement.

16. The nuclear magnetic resonance microscope of claim 9 ; wherein the nuclear magnetic resonance microscope includes a memory to record an optical image of the analytes along with nuclear magnetic resonance spectra from the analytes.

17. A measurement method comprising:
illuminating, using electromagnetic radiation having a wavelength within a range of wavelengths, a detection region on a coverslip at which a film is embedded in the coverslip with the film doped with reactive centers that undergo stable fluorescence;
providing a magnetic field to analytes disposed proximal to the reactive centers of the film for nuclear magnetic resonance measurement of the analytes;
generating microwave fields, from two microwave striplines on the coverslip, to irradiate the analytes for the nuclear magnetic resonance measurement; and
detecting fluorescence of the reactive centers, at a photodetector, in response to resonance of the analytes in the nuclear magnetic resonance measurement with the reactive centers illuminated by the electromagnetic radiation.

18. The measurement method of claim 17 , wherein the method includes imaging analytes from detecting the fluorescence of the reactive centers.

19. The measurement method of claim 17 , wherein the method includes, in the nuclear magnetic resonance measurement, using a sensing sequence that samples nuclear precession and converts final nuclear phase into longitudinal magnetization with the longitudinal magnetization detected using electron-nuclear double resonance sequences tailored for the reactive centers.

20. The measurement method of claim 19 , wherein the reactive centers are nitrogen vacancy color centers.

21. The measurement method of claim 17 , wherein the film is a magneto-fluorescent diamond film with the reactive centers being nitrogen vacancy color centers.

22. The measurement method of claim 21 , wherein the magneto-fluorescent diamond film includes a diamond nanograting having sidewalls with the sidewalls doped with the nitrogen vacancy color centers.

23. The measurement method of claim 17 , wherein illuminating using electromagnetic radiation includes illuminating using a laser that generates green laser light.

24. The measurement method of claim 17 , wherein generating microwave fields from two microwave striplines includes generating the microwave fields at frequencies to excite the analytes proximal to the reactive centers of the film, to facilitate polarization transfer via solid effect, Hartmann-Hahn protocol, resonant cross-relaxation, or a combination thereof in the nuclear magnetic resonance measurement.

25. The measurement method of claim 17 , wherein the method includes performing label-free nuclear magnetic resonance imaging at sub-cellular length scales with single organelle resolution.

26. The measurement method of claim 17 , wherein the method includes nuclear magnetic resonance imaging of metabolic compositions of individual cells.

27. The measurement method of claim 17 , wherein the method includes monitoring adenosine triphosphate (ATP) production in mitochondria.

28. The measurement method of claim 17 , wherein the method includes monitoring of evolution of pyruvate-lactate conversion in cancer cells.

29. The measurement method of claim 17 , wherein the method includes monitoring diffusion of fluids through cell membranes.

30. The measurement method of claim 17 , wherein the method includes monitoring dynamics of metabolites within cell cultures.

Assignees

• Unm Rainforest Innovations
• Acosta Victor Marcel
• Jarmola Andrejs

Inventors

• Acosta Victor Marcel
• Jarmola Andrejs

Classifications

• G01R33/282

  Means specially adapted for hyperpolarisation or for hyperpolarised contrast agents, e.g. for the generation of hyperpolarised gases using optical pumping cells, for storing hyperpolarised contrast agents or for the determination of the polarisation of a hyperpolarised contrast agent · CPC title

• G01R33/243

  Spatial mapping of the polarizing magnetic field · CPC title

• B82Y35/00

  Methods or apparatus for measurement or analysis of nanostructures · CPC title

• G01R33/323 Primary

  Detection of MR without the use of RF or microwaves, e.g. force-detected MR, thermally detected MR, MR detection via electrical conductivity, optically detected MR · CPC title

• G01N24/08 Primary

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