High throughput characterization of individual magnetic nanoparticles

Patent metadata

Field	Value
Publication number	US-10875766-B2
Application number	US-201716343590-A
Country	US
Kind code	B2
Filing date	Oct 27, 2017
Priority date	Oct 28, 2016
Publication date	Dec 29, 2020
Grant date	Dec 29, 2020

Abstract

Technologies related to parallel characterization of individual MNPs are disclosed. A diamond chip with MNPs distributed thereon may be used with an epifluorescence microscope and camera to generate multiple different images of multiple individual MNPs. The multiple images are recorded at different microwave frequencies and under different external magnetic field strengths. The multiple images are then used to determine properties of the multiple individual MNPs.

First claim

The invention claimed is:

1. An apparatus for high throughput characterization of individual Magnetic Nanoparticles (MNPs), the apparatus comprising:
a diamond chip doped with a layer of nitrogen vacancy (NV) color centers;
one thousand or more MNPs, wherein the MNPs are distributed either on the diamond chip or on a substrate layer on the diamond chip;
a laser generator to direct a laser beam at the diamond chip;
a controllable-frequency microwave antenna positioned proximal to the MNPs;
a controllable-strength magnetic field generator positioned to generate a magnetic field at the MNPs;
a camera to record fluorescence images, of fluorescence generated by the NV color centers in response to stimulation by the laser beam, wherein the fluorescence recorded in a fluorescence image is modulated by magnetic resonance of the MNPs, and wherein the magnetic resonance is responsive to stimulation by the controllable-frequency microwave antenna under the magnetic field generated by the controllable-strength magnetic field generator, with the controllable-strength magnetic field generator arranged to modify a magnetic field strength at the MNPs with the camera operable to record additional fluorescence images in response to the modifying of the magnetic field strength; and
a computer having computer readable instructions to perform operations, the operations including operations to use the fluorescence images and the additional fluorescence images to form magnetization curves for at least a first individual MNP and a second individual MNP.

2. The apparatus of claim 1 , wherein the camera comprises a sCMOS camera.

3. The apparatus of claim 1 , wherein the laser beam comprises a laser beam with a wavelength in the range of 500-600 nanometers.

4. The apparatus of claim 1 , wherein the laser beam is directed at a side of the diamond chip at a glancing angle.

5. The apparatus of claim 1 , wherein the controllable-strength magnetic field generator is adapted to generate a magnetic field between ±200 mT.

6. The apparatus of claim 1 , wherein the layer of NV color centers is about 200 nanometers thick.

7. An apparatus for high throughput characterization of individual Magnetic Nanoparticles (MNPs), the apparatus comprising:
a diamond chip doped with a layer of nitrogen vacancy (NV) color centers;
protective layers of silver and sapphire deposited on the diamond chip;
one thousand or more MNPs, wherein the MNPs are distributed either on the diamond chip or on a substrate layer on the diamond chip;
a laser generator to direct a laser beam at the diamond chip;
a controllable-frequency microwave antenna positioned proximal to the MNPs;
a controllable-strength magnetic field generator positioned to generate a magnetic field at the MNPs;
a camera to record fluorescence images, of fluorescence generated by the NV color centers in response to stimulation by the laser beam, wherein the fluorescence recorded in a fluorescence image is modulated by magnetic resonance of the MNPs, and wherein the magnetic resonance is responsive to stimulation by the controllable-frequency microwave antenna under the magnetic field generated by the controllable-strength magnetic field generator.

8. A method for high throughput characterization of individual Magnetic Nanoparticles (MNPs), comprising:
distributing one thousand or more MNPs on a diamond chip or on a substrate layer positionable on the diamond chip, wherein the diamond chip is doped with a layer of nitrogen vacancy (NV) color centers;
positioning the diamond chip and MNPs, or the substrate layer and MNPs, in an epifluorescence microscope, wherein the epifluorescence microscope comprises a camera or is coupled with a camera; and
recording, by the camera, fluorescence images at multiple different microwave frequencies, wherein the fluorescence images record fluorescence modulated by magnetic resonance of the MNPs, wherein each fluorescence image comprises multiple pixels, and wherein at least a first pixel in each fluorescence image records fluorescence modulated by magnetic resonance of a first individual MNP, and wherein at least a second pixel in each fluorescence image records fluorescence modulated by magnetic resonance of a second individual MNP;
modifying a magnetic field strength at the MNPs;
recording additional fluorescence images in response to modifying the magnetic field strength; and
using the fluorescence images and the additional fluorescence images to form magnetization curves for at least the first individual MNP and the second individual MNP.

9. The method of claim 8 , further comprising setting a magnetic field strength for the fluorescence images.

10. The method of claim 8 , further comprising calculating a resonant microwave frequency, and wherein the multiple different microwave frequencies comprise microwave frequencies above and below the resonant microwave frequency.

11. The method of claim 8 , further comprising creating a magnetic field map from the fluorescence images.

12. The method of claim 11 , further comprising identifying isolated magnetic features in the magnetic field map in order to identify individual MNPs.

13. The method of claim 8 , wherein modifying the magnetic field strength includes sweeping a magnetic field in small increments between a negative of a maximum value and the maximum value.

14. The method of claim 8 , further comprising using the magnetization curves to populate a histogram of coercivity, remanent magnetization, or saturation magnetization of the first individual MNP or the second individual MNP.

15. The method of claim 8 , further comprising mechanically sorting the first individual MNP and the second individual MNP into different groups according to properties characterized by the magnetization curves.

16. The method of claim 8 , wherein the fluorescence images comprise a field of view of about 200×200 micrometers.

17. A method for high throughput characterization of individual Magnetic Nanoparticles (MNPs), comprising:
distributing one thousand or more MNPs on a diamond chip or on a substrate layer positionable on the diamond chip, wherein the diamond chip is doped with a layer of nitrogen vacancy (NV) color; centers, wherein distributing the MNPs comprises:
drop casting a dilute MNP suspension in polymethylmethacrylate (PMMA);
spin coating a dilute MNP suspension in a polymer matrix; or
lithographically defining an array of holes in a mask, dispersing MNPs over the mask, and removing the mask;

positioning the diamond chip and MNPs, or the substrate layer and MNPs, in an epifluorescence microscope, wherein the epifluorescence microscope comprises a camera or is coupled with a camera; and
recording, by the camera, fluorescence images at multiple different microwave frequencies, wherein the fluorescence images record fluorescence modulated by magnetic resonance of the MNPs, wherein each fluorescence image comprises multiple pixels, and wherein at least a first pixel in each fluorescence image records fluorescence modulated by magnetic resonance of a first individual MNP, and wherein at least a second pixel in each fluorescence image records fluorescence modulated by magnetic resonance of a second individual MNP.

Assignees

• Stc Unm

Inventors

• Acosta Victor
• Jarmola Andrejs

Classifications

• B82B3/009 Primary

  Characterizing nanostructures, i.e. measuring and identifying electrical or mechanical constants · CPC title

• B82Y35/00 Primary

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

• G01R33/1276

  of magnetic particles, e.g. imaging of magnetic nanoparticles (G01R33/1269 takes precedence) · CPC title

• G01R33/12

  Measuring magnetic properties of articles or specimens of solids or fluids (involving magnetic resonance G01R33/20) · CPC title

• G01R33/1223 Primary

  Measuring permeability, i.e. permeameters (G01R33/14 takes precedence) · CPC title