Method for using nanodiamonds to detect nearby magnetic nanoparticles

• US 9,555,131 B2
• Filed: 07/18/2016
• Issued: 01/31/2017
• Est. Priority Date: 06/27/2014
• Status: Active Grant

• Current Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Original Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Inventors: Acosta, Victor Marcel, Bajaj, Vikram Singh, Thompson, Jason Donald, Peeters, Eric
• Primary Examiner(s): MARTINEZ, REBECCA L
• Application Number:
  US15/212,636
• Publication Number:
  US 20160324990A1
• Time in Patent Office: 197 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61B 2576/00 Medical imaging apparatus involving image processing or analysis A61B1/00009, A61B6/52 and A61B8/52 take precedence; image processing per se G06T; details of algorithms for analysing medical images G06T7/0012
• CPC Class Codes: A61B 5/0035 adapted for acquisition of images from more than one imaging mode, e.g. combining MRI and optical tomography
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0507 using microwaves or terahertz waves
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 5/14507 specially adapted for measuring characteristics of body fluids other than blood devices for taking samples of body liquids A61B10/0045
• 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: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/001 Preparation for luminescence or biological staining
• CPC Class Codes: A61K 49/005 characterised by the carrier molecule carrying the fluorescent agent
• CPC Class Codes: A61M 5/007 for contrast media
• CPC Class Codes: G01N 33/5091 for testing the pathological state of an organism
• CPC Class Codes: G01N 33/54333 Modification of conditions of immunological binding reaction, e.g. use of more than one type of particle, use of chemical agents to improve binding, choice of incubation time or application of magnetic field during binding reaction
• CPC Class Codes: G01N 33/54346 Nanoparticles
• CPC Class Codes: G01N 33/544 the carrier being organic
• CPC Class Codes: G01N 33/551 the carrier being inorganic

Abstract

An imaging agent for detecting analytes in an environment includes functionalized nanodiamonds and functionalized magnetic particles that can selectively interact with an analyte. Each functionalized nanodiamond contains at least one color center configured emit light in response to illumination. At least one property of the light emitted by the color centers is related to the proximity of the functionalized magnetic particles to the color centers. This property can be detected to determine that the functionalized nanodiamonds are proximate to the functionalized magnetic particles, to determine that the functionalized nanodiamonds and the functionalized magnetic particles are interacting with the analyte, or other applications. Devices and methods for detecting properties of the analyte by interacting with the functionalized nanodiamonds and functionalized magnetic particles are also provided.

Claims

1. A method comprising:

exposing a portion of vasculature in a human body to illumination, wherein the human body includes an in vivo imaging agent, wherein the in vivo imaging agent comprises functionalized nanodiamonds and functionalized magnetic nanoparticles, wherein each of the functionalized nanodiamonds contains at least one color center and is functionalized to selectively interact with an analyte in the portion of vasculature, wherein each of the magnetic nanoparticles is functionalized to selectively interact with the analyte in the portion of vasculature, and wherein the illumination causes individual color centers to emit light having one or more properties relating to proximity between the individual color centers and the functionalized magnetic nanoparticles;

detecting the one or more properties of the light emitted by the color centers in response to the illumination;

determining that an individual nanodiamond is proximate to at least one magnetic nanoparticle based on the detected one or more properties of the light emitted by the color centers of the individual nanodiamond in response to the illumination; and

determining that the individual nanodiamond and at least one magnetic nanoparticle are bound to the analyte based on the determination that the individual nanodiamond is proximate to the at least one magnetic nanoparticle.

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

3. The method of claim 1, further comprising introducing the in vivo imaging agent into the human body.

4. The method of claim 1, wherein the color centers comprise negatively-charged nitrogen vacancy color centers, wherein exposing the portion of vasculature to illumination comprises exposing the portion of vasculature to light having wavelengths in the range of about 500 nanometers to about 650 nanometers, and wherein detecting the one or more properties of the light emitted by the color centers comprises detecting light having wavelengths in the range of about 650 nanometers to about 800 nanometers.

5. The method of claim 1, wherein exposing the portion of vasculature to illumination comprises illuminating the portion of vasculature with light of a first amplitude during a first period of time and with light of a second amplitude during a second period of time, wherein the first period of time and the second period of time are separated by a latency period having a specified duration, wherein detecting the one or more properties of the light emitted by the color centers comprises detecting the amplitude of the light emitted by the color centers during the second period of time, and further comprising:

determining that an individual nanodiamond is proximate to at least one magnetic nanoparticle based on at least the specified duration of the latency period, the second amplitude, and the detected amplitude of the light emitted by the color centers of the individual nanodiamond in response to the illumination.

6. The method of claim 1, further comprising:

exposing the portion of vasculature to microwave radiation.

7. The method of claim 6, wherein exposing the portion of vasculature to microwave radiation comprises exposing the portion of vasculature to microwave radiation having a first amplitude during a first period of time and having a second amplitude during a second period of time, wherein the first and second amplitudes of microwave radiation are different, wherein the microwave radiation has a specified frequency, wherein exposing the portion of vasculature to illumination comprises exposing the portion of vasculature to illumination having the first amplitude during a first period of time and having a second amplitude during a second period of time, wherein detecting the one or more properties of the light emitted by the color centers comprises detecting the amplitude of the light emitted by the color centers during the first period of time and during the second period of time, and further comprising:

determining that an individual nanodiamond is proximate to at least one magnetic nanoparticle based on at least the first and second amplitudes of the microwave radiation, the first and second amplitudes of the illumination, and the first and second detected amplitudes of the light emitted by the color centers of the individual nanodiamond in response to the illumination during the first and second periods of time, respectively.

8. The method of claim 7, wherein the color centers comprise negatively-charged nitrogen vacancy color centers and wherein the specified frequency of the microwave radiation is about 2.869 gigahertz.

9. The method of claim 6, wherein exposing the portion of vasculature to microwave radiation comprises exposing the portion of vasculature to microwave radiation during at least two time periods, wherein the microwave radiation has a respective specified frequency during each of the at least two time periods, wherein the respective specified frequencies have at least two different values, wherein exposing the portion of vasculature to illumination comprises exposing the portion of vasculature to illumination during the at least two time periods, wherein detecting the one or more properties of the light emitted by the color centers comprises detecting respective amplitudes of the light emitted by the color centers during respective time periods of the at least two time periods, and further comprising:

determining one or more features of a magnetic resonance spectrum of the color centers in the functionalized nanodiamonds using at least the at least two specified frequencies of the microwave radiation and the at least two respective detected amplitudes of the light emitted by the color centers.

10. The method of claim 9, wherein the one or more features of the magnetic resonance spectrum comprise a degree of widening of an absorbance peak of the magnetic resonance spectrum, and further comprising:

determining that an individual nanodiamond is proximate to at least one magnetic nanoparticle based on the determined degree of widening of the absorbance peak of the magnetic resonance spectrum.

11. The method of claim 9, wherein determining one or more features of the magnetic resonance spectrum comprises determining a first center frequency of a first magnetic resonance spectrum corresponding to a first duration of time and determining a second center frequency of a second magnetic resonance spectrum corresponding to a second duration of time, and further comprising:

determining first and second temperatures of an individual nanodiamond during the first and second durations of time, respectively, based on the first and second determined center frequencies, respectively;

exposing the portion of vasculature to an oscillating electromagnetic field such that individual functionalized magnetic nanoparticles in the portion of vasculature heat regions within the portion of vasculature proximate to respective individual functionalized magnetic nanoparticles; and

determining that an individual nanodiamond is proximate to at least one magnetic nanoparticle based on the determined first and second temperatures and one or more properties of the oscillating electromagnetic field.

12. A device comprising:

a light source, wherein light emitted from the light source illuminates a portion of vasculature, wherein the portion of vasculature includes an in vivo imaging agent, wherein the in vivo imaging agent comprises functionalized nanodiamonds and functionalized magnetic nanoparticles, wherein each of the functionalized nanodiamonds contains at least one color center and is functionalized to selectively interact with an analyte in the portion of vasculature, wherein each of the magnetic nanoparticles is functionalized to selectively interact with the analyte in the portion of vasculature, and wherein the illumination causes individual color centers to emit light having one or more properties relating to proximity between the individual color centers and the functionalized magnetic nanoparticles;

a light sensor, wherein the light sensor receives light emitted from the portion of vasculature, wherein the light sensor detects one or more properties of light emitted by the color centers in response to the illumination; and

a controller, wherein the controller comprises at least one processor programmed to;

operate the light source to illuminate the portion of vasculature,

operate the light sensor to detect the one or more properties of light emitted by the color centers,

determine that an individual nanodiamond is proximate to at least one magnetic nanoparticle based on the detected one or more properties of the light emitted by the color centers of the individual nanodiamond in response to the illumination; and

determine that the individual nanodiamond and at least one magnetic nanoparticle are bound to the analyte based on the determination that the individual nanodiamond is proximate to the at least one magnetic nanoparticle.

13. The device of claim 12, further comprising:

a housing, wherein the light source and light sensor are disposed in the housing; and

a mount, wherein the mount can secure the housing to a surface of the human body such that the light source can illuminate the functionalized nanodiamonds in the portion of vasculature and the light sensor can detect the one or more properties of the light emitted by the color centers.

14. The device of claim 12, further comprising an electromagnetic field emitter, wherein the at least one processor is further programmed to:

operate the electromagnetic field emitter to expose the portion of vasculature to microwave radiation having a first amplitude during a first period of time and having a second amplitude during a second period of time, wherein the first and second amplitudes of microwave radiation are different, wherein the microwave radiation has a specified frequency, wherein exposing the portion of vasculature to illumination comprises exposing the portion of vasculature to illumination having a first amplitude during the first period of time and having a second amplitude during the second period of time, wherein detecting the one or more properties of the light emitted by the color centers comprises detecting the amplitude of the light emitted by the color centers during the first period of time and during the second period of time, and further comprising;

determining that an individual nanodiamond is proximate to at least one magnetic nanoparticle based on at least the first and second amplitudes of the microwave radiation, the first and second amplitudes of the illumination, and the first and second detected amplitudes of the light emitted by the color centers of the individual nanodiamond in response to the illumination during the first and second periods of time, respectively.

15. The device of claim 14, wherein the color centers comprise negatively-charged nitrogen vacancy color centers and wherein the specified frequency of the microwave radiation is about 2.869 gigahertz.

16. The device of claim 12, further comprising an electromagnetic field emitter, wherein the at least one processor is further programmed to:

operate the electromagnetic field emitter to expose the portion of vasculature to microwave radiation during at least two time periods, wherein the microwave radiation has a respective specified frequency during each of the at least two time periods, wherein the respective specified frequencies have at least two different values, wherein exposing the portion of vasculature to illumination comprises exposing the portion of vasculature to illumination during the at least two time periods, wherein detecting the one or more properties of the light emitted by the color centers comprises detecting respective amplitudes of the light emitted by the color centers during respective time periods of the at least two time periods; and

determine one or more features of a magnetic resonance spectrum of the color centers in the functionalized nanodiamonds using at least the at least two specified frequencies of the microwave radiation and the at least two respective detected amplitudes of the light emitted by the color centers.

17. The device of claim 16, wherein the one or more features of the magnetic resonance spectrum comprise a degree of widening of an absorbance peak of the magnetic resonance spectrum, and wherein the at least one processor is further programmed to:

determine that an individual nanodiamond is proximate to at least one magnetic nanoparticle based on the determined degree of widening of the absorbance peak of the magnetic resonance spectrum.

18. The device of claim 16, wherein determining one or more features of the magnetic resonance spectrum comprises determining a first center frequency of a first magnetic resonance spectrum corresponding to a first duration of time and determining a second center frequency of a second magnetic resonance spectrum corresponding to a second duration of time, and wherein the at least one processor is further programmed to:

determine first and second temperatures of an individual nanodiamond during the first and second durations of time, respectively, based on the first and second determined center frequencies, respectively;

operate the electromagnetic field emitter to expose the portion of vasculature to an oscillating electromagnetic field such that individual functionalized magnetic nanoparticles in the portion of vasculature heat regions within the portion of vasculature proximate to respective individual functionalized magnetic nanoparticles; and

determine that an individual nanodiamond is proximate to at least one magnetic nanoparticle based on the determined first and second temperatures.