Silicon-vacancy-doped nanodiamonds for molecular and cellular imaging

• US 9,486,163 B2
• Filed: 02/21/2014
• Issued: 11/08/2016
• Est. Priority Date: 02/21/2014
• Status: Active Grant

• Current Assignee: Google LLC (Alphabet Inc.)
• Original Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Inventors: Acosta, Victor Marcel, Bajaj, Vikram Singh, Homyk, Andrew, Peeters, Eric, Thompson, Jason Donald
• Primary Examiner(s): Chen, Tse
• Assistant Examiner(s): HOFFMAN, JOANNE M
• Application Number:
  US14/186,937
• Publication Number:
  US 20150238125A1
• Time in Patent Office: 991 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61B 5/0022 Monitoring a patient using a global network, e.g. telephone networks, internet
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/14558 by polarisation
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/1468 using chemical or electrochemical methods, e.g. by polarographic means A61B5/1486 takes precedence
• CPC Class Codes: A61B 5/1477 non-invasive
• CPC Class Codes: A61B 5/4848 Monitoring or testing the effects of treatment, e.g. of medication
• CPC Class Codes: A61B 5/681 Wristwatch-type devices
• CPC Class Codes: A61B 5/7282 Event detection, e.g. detecting unique waveforms indicative of a medical condition A61B5/4094, A61B5/4818, A61B5/349, A61B5/0823 take precedence
• CPC Class Codes: A61B 5/742 using visual displays A61B5/339 takes precedence
• CPC Class Codes: A61B 5/746 Alarms related to a physiological condition, e.g. details of setting alarm thresholds or avoiding false alarms alarms per se G08B
• CPC Class Codes: A61B 5/7475 User input or interface means, e.g. keyboard, pointing device, joystick
• CPC Class Codes: A61K 49/0013 Luminescence
• CPC Class Codes: A61K 49/0019 characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
• CPC Class Codes: A61K 49/0093 Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C09K 11/59 : containing silicon
• CPC Class Codes: C23C 16/27 : Diamond only
• CPC Class Codes: G01N 2021/1746 : Method using tracers
• CPC Class Codes: G01N 2021/6439 : with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 21/6428 : 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 Class Codes: G01N 21/6458 : Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G01R 33/281 : Means for the use of in vitro contrast agents G01R33/282 takes precedence; involving use of a contrast agent in MR imaging G01R33/5601; in vivo contrast agents A61K49/0002
• 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
• CPC Class Codes: G02B 21/00 : Microscopes

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.

Claims

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.