Method for using nanodiamonds to detect nearby magnetic nanoparticles

• US 9,435,791 B2
• Filed: 06/27/2014
• Issued: 09/06/2016
• Est. Priority Date: 06/27/2014
• Status: Active Grant

• Current Assignee: Google LLC (Alphabet Inc.)
• Original Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Inventors: Acosta, Victor Marcel, Bajaj, Vikram Singh, Thompson, Jason Donald, Peeters, Eric
• Primary Examiner(s): MARTINEZ, REBECCA L
• Application Number:
  US14/318,220
• Publication Number:
  US 20150377865A1
• Time in Patent Office: 802 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. An in vivo imaging agent, comprising:

a plurality of functionalized magnetic nanoparticles, wherein each of the functionalized magnetic nanoparticles is functionalized to selectively interact with an analyte in an environment; and

a plurality of functionalized nanodiamonds, wherein each of the functionalized nanodiamonds contains at least one color center and is functionalized to selectively interact with the analyte in the environment, and wherein the at least one color center is configured to emit light in response to illumination, wherein the emitted light has one or more properties relating to proximity between the at least one color center and individual functionalized magnetic nanoparticles of the plurality of functionalized magnetic nanoparticles.

2. The in vivo imaging agent of claim 1, wherein the color centers comprise negatively-charged nitrogen vacancy centers.

3. The in vivo imaging agent of claim 1, wherein the plurality of functionalized magnetic nanoparticles comprises magnetic nanoparticles comprising superparamagnetic iron oxide.

4. The in vivo imaging agent of claim 1, wherein each of the functionalized magnetic nanoparticles comprises a ferromagnetic material, a paramagnetic material, or a superparamagnetic material.

5. The in vivo imaging agent of claim 1, wherein each of the functionalized magnetic nanoparticles is functionalized with a receptor, protein, antibody, or nucleic acid sequence.

6. The in vivo imaging agent of claim 1, wherein each of the functionalized nanodiamonds is functionalized with a receptor, protein, antibody, or nucleic acid sequence.

7. The in vivo imaging agent of claim 1, wherein the functionalized magnetic nanoparticles and the functionalized nanodiamonds are functionalized to selectively bind to cancer cells.

8. The in vivo imaging agent of claim 1, wherein the environment is a human body and the analyte is a cancer cell.

9. The in vivo imaging agent of claim 1, wherein the emitted light has one or more properties relating to a magnetic field produced or affected by one or more proximate functionalized magnetic nanoparticles.

10. The in vivo imaging agent of claim 1, wherein the at least one color center exhibits optical properties that are related to a magnetic field in an environment of the at least one color center.

11. The in vivo imaging agent of claim 10, wherein the at least one color center has a plurality of spin states, and wherein occupancy of the spin states is affected by the magnetic field in the environment of the at least one color center.

12. The in vivo imaging agent of claim 11, wherein the occupancy of the spin states affects the one or more properties of the emitted light.

13. The in vivo imaging agent of claim 1, further comprising a fluorophore attached to each of the functionalized magnetic nanoparticles.

14. The in vivo imaging agent of claim 1, further comprising a fluorophore attached to each of the functionalized nanodiamonds.

15. The in vivo imaging agent of claim 1, wherein each of the functionalized magnetic nanoparticles is functionalized by covalent attachment of a bioreceptor, wherein the bioreceptor specifically binds with at least a portion of the analyte.

16. The in vivo imaging agent of claim 1, wherein each of the functionalized nanodiamonds is functionalized by covalent attachment of a bioreceptor, wherein the bioreceptor specifically binds with at least a portion of the analyte.

17. The in vivo imaging agent of claim 1, wherein the color centers are silicon vacancy centers.

18. The in vivo imaging agent of claim 1, wherein each instance of the analyte has at least a first binding site and a second binding site, wherein each of the functionalized magnetic nanoparticles is functionalized to bind with the first binding site, and wherein each of the functionalized nanodiamonds is functionalized to bind with the second binding site.

19. The in vivo imaging agent of claim 18, wherein binding of an instance of the analyte to both a functionalized magnetic nanoparticle via the first binding site and a functionalized nanodiamond via the second binding site is detectable by the one or more properties of the emitted light from the at least one color center of the functionalized nanodiamond based on proximity of the functionalized magnetic nanoparticle and the functionalized nanodiamond.

20. The in vivo imaging agent of claim 1, wherein the one or more properties of the emitted light include amplitude, wavelength, degree of polarization, orientation of polarization, or location of the emitted light.