Silicon-vacancy-doped nanodiamonds for molecular and cellular imaging

Patent metadata

Field	Value
Publication number	US-9486163-B2
Application number	US-201414186937-A
Country	US
Kind code	B2
Filing date	Feb 21, 2014
Priority date	Feb 21, 2014
Publication date	Nov 8, 2016
Grant date	Nov 8, 2016

Abstract

An imaging agent for detecting analytes in a biological environment includes functionalized, silicon vacancy center-containing nanodiamonds. Individual nanodiamonds of the imaging agent include at least one silicon vacancy center. The at least one silicon vacancy center can emit light having a wavelength in a narrow band in response to illumination having any wavelength in a wide range of wavelengths. The nanodiamonds are functionalized to selectively interact with an analyte of interest. The nanodiamonds can additionally include other color centers, and the imaging agent can include a plurality of sets of nanodiamonds having detectably unique ratios of silicon vacancy centers to other color centers. The silicon vacancy centers in the nanodiamonds can have a preferred orientation enabling orientation tracking of individual nanodiamonds or other applications. A method for detecting properties of the analyte of interest by interacting with the imaging agent is also provided.

First claim

What is claimed is:

1. A method comprising:
exposing a biological environment to illumination from a light source in a wearable device, wherein the illumination comprises excitation light having a wavelength between 1050 and 1200 nanometers, wherein silicon-vacancy nanodiamonds have been introduced into the biological environment, wherein each of the silicon-vacancy nanodiamonds has at least one silicon vacancy center and is functionalized to selectively interact with an analyte in the biological environment, and wherein the excitation light is absorbed by the silicon vacancy centers through two-photon absorption and causes the silicon vacancy centers to emit light in a band of wavelengths centered at approximately 738 nanometers and having a full width at half-maximum of less than 15 nanometers; and
detecting, by a light sensor in the wearable device, one or more properties of the light emitted by the silicon vacancy centers in response to the excitation light.

2. The method of claim 1 , wherein the biological environment is a portion of subsurface vasculature.

3. The method of claim 1 , wherein the analyte is a cell.

4. The method of claim 1 , further comprising introducing the silicon-vacancy nanodiamonds into the biological environment.

5. The method of claim 1 , further comprising:
determining one or more properties of the silicon-vacancy nanodiamonds in the biological environment based on the detected one or more properties of the light emitted by the silicon vacancy centers; and
determining a property of the analyte based on the determined one or more properties of the silicon-vacancy nanodiamonds.

6. The method of claim 1 , wherein the silicon vacancy centers have a preferred orientation, wherein detecting one or more properties of the light emitted by the silicon vacancy centers comprises detecting a polarization of the emitted light, further comprising:
detecting binding of a silicon-vacancy nanodiamond to the analyte based on at least the detected one or more properties of the emitted light.

7. The method of claim 1 , wherein the silicon vacancy centers have a preferred orientation, wherein the illumination has a specified polarization, further comprising:
detecting binding of a silicon-vacancy nanodiamond to the analyte based on at least the specified polarization and the detected one or more properties of the emitted light.

8. The method of claim 1 , wherein nitrogen-vacancy nanodiamonds have been introduced into the biological environment, and wherein each of the nitrogen-vacancy nanodiamonds has at least one nitrogen vacancy center and is functionalized to selectively interact with a second analyte in the biological environment, further comprising:
exposing the biological environment to additional illumination, and wherein the additional illumination causes the nitrogen vacancy centers to emit light;
detecting one or more properties of the light emitted by the nitrogen vacancy centers in response to the additional illumination; and
determining whether a nanodiamond in the biological environment was a silicon-vacancy nanodiamond or a nitrogen-vacancy nanodiamond based on at least the detected one or more properties of the light emitted by the silicon vacancy centers and the detected one or more properties of the light emitted by the nitrogen vacancy centers.

9. The method of claim 8 , wherein each of the silicon-vacancy nanodiamonds has at least one nitrogen vacancy center, wherein the ratio of the concentration of silicon vacancy centers to the concentration of nitrogen vacancy centers in the silicon-vacancy nanodiamonds is a first ratio, wherein each of the nitrogen-vacancy nanodiamonds has at least one silicon vacancy center, wherein the ratio of the concentration of silicon vacancy centers to the concentration of nitrogen vacancy centers in the nitrogen-vacancy nanodiamonds is a second ratio, wherein the first and second ratios are different.

10. A wearable device comprising:
a light source that can direct excitation light having a wavelength between 1050 and 1200 nanometers to a biological environment into which silicon-vacancy nanodiamonds have been introduced, wherein each silicon-vacancy nanodiamond has at least one silicon vacancy center and is functionalized to selectively interact with an analyte in the biological environment, and wherein the excitation light is absorbed by the silicon vacancy centers through two-photon absorption and causes the silicon vacancy centers to emit light in a band of wavelengths centered at approximately 738 nanometers and having a full width at half-maximum of less than 15 nanometers; and
a light sensor that can detect one or more properties of the light emitted by the silicon vacancy centers in response to the excitation light.

11. The wearable device of claim 10 , wherein the biological environment is a portion of subsurface vasculature.

12. The wearable device of claim 11 , wherein the device further comprises:
a housing, wherein the light source and light sensor are disposed in the housing; and
a mount, wherein the mount is configured to mount the housing to an external surface proximate the portion of subsurface vasculature such that the light source can illuminate the silicon-vacancy nanodiamonds in the portion of subsurface vasculature and the light sensor can detect the one or more properties of the light emitted by the silicon vacancy centers.

13. The wearable device of claim 10 , further comprising a controller, wherein the controller is configured to:
operate the light source to illuminate the biological environment,
operate the light sensor to detect the one or more properties of light emitted by the silicon vacancy centers,
determine one or more properties of the silicon-vacancy nanodiamonds in the biological environment based on the detected one or more properties of the emitted light; and
determine a property of the analyte based on the determined one or more properties of the silicon-vacancy nanodiamonds.

14. The wearable device of claim 10 , wherein the silicon vacancy centers have a preferred orientation, wherein detecting one or more properties of the light emitted by the silicon vacancy centers comprises detecting a polarization of the emitted light, and further comprising a controller configured to:
operate the light source to illuminate the biological environment,
operate the light sensor to detect one or more properties of the light emitted by the silicon vacancy centers,
detect binding of a silicon-vacancy nanodiamond to the analyte based on at least the detected one or more properties of the emitted light.

15. The wearable device of claim 10 , wherein each of the silicon-vacancy nanodiamonds has at least one nitrogen vacancy center, wherein each of the silicon-vacancy nanodiamonds has a ratio of the concentration of silicon vacancy centers to the concentration of nitrogen vacancy centers, wherein the light source is configured to expose the biological environment to additional illumination, wherein the additional illumination causes the nitrogen vacancy centers to emit light, wherein the light sensor is configured to detect one or more properties of the light emitted by the nitrogen vacancy centers in response to the additional illumination, and wherein the ratio of the concentration of silicon vacancy centers to the concentration of nitrogen vacancy centers can be determined based on the detected one or more properties of the light emitted by the nitrogen vacancy centers and the detected one or more properties of the light emitted by the silicon vacancy centers.

Assignees

• Verily Life Sciences Llc

Inventors

• Acosta Victor Marcel
• Bajaj Vikram Singh
• Homyk Andrew
• Peeters Eric
• Thompson Jason Donald

Classifications

• A61B5/1459 Primary

  invasive, e.g. introduced into the body by a catheter · CPC title

• G01N21/6428

  Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53) · CPC title

• A61K49/0019

  characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules · CPC title

• A61B5/742

  using visual displays (displays for heart-related electrical signals, e.g. ECG, A61B5/339) · CPC title

• A61B5/7475

  User input or interface means, e.g. keyboard, pointing device, joystick · CPC title