Polyvalent functionalized nanoparticle-based in vivo diagnostic system

• US 9,910,035 B1
• Filed: 07/16/2014
• Issued: 03/06/2018
• Est. Priority Date: 07/16/2014
• Status: Active Grant

• Current Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Original Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Inventors: Schwartz, Jerrod Joseph, Audeh, Mark, Bajaj, Vikram Singh
• Primary Examiner(s): Vu, Jake M
• Assistant Examiner(s): Samala, Jagadishwar R
• Application Number:
  US14/333,155
• Time in Patent Office: 1,329 Days
• CPC Class Codes: A61B 2562/0223 Magnetic field sensors
• CPC Class Codes: A61B 2562/043 in a linear array
• CPC Class Codes: A61B 5/05 Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves impedance plethysmography A61B5/0295; measuring movement of the entire body or parts thereof A61B5/11; detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof A61B5/24
• CPC Class Codes: A61B 5/145 Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissuemeasuring of blood pressure or blood flow A61B5/02; non-radiation detecting or locating of foreign bodies in blood A61B5/06
• 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 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/681 Wristwatch-type devices
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents

Abstract

A system for modulating a response signal includes polyvalent functionalized nanoparticles configured to bind with target analytes located on a surface of a cell, a detector configured to detect an analyte response signal transmitted from the body, a modulation source configured to modulate the analyte response signal, and a processor configured to non-invasively detect the one or more target analytes by differentiating the analyte response signal from a background signal, at least in part, based on the modulation. The analyte response signal is related to the binding interaction of the target analytes on the cell surface with the polyvalent functionalized nanoparticles. In some examples, the system may also include magnetic particles and a magnetic field source sufficient to distribute the magnetic particles into a spatial arrangement in the body. The analyte response signal may be differentiated from the background signal, at least in part, based on modulation of the signals due, at least in part, to the spatial arrangement of the magnetic particles.

Claims

1. A system comprising:

polyvalent functionalized nanoparticles for binding with one or more target analytes on a surface of a cell present in an environment;

a detector for detecting;

an analyte response signal transmitted from the environment, wherein the analyte response signal is related to binding of the one or more target analytes on the cell surface with the polyvalent functionalized nanoparticles; and

an unbound polyvalent functionalized nanoparticle signal transmitted from the environment related to polyvalent functionalized nanoparticles that are not interacting with the one or more target analytes;

a modulation source for modulating the analyte response signal and the unbound nanoparticle signal, such that the analyte response signal is affected differently than the unbound nanoparticle signal; and

a processor for non-invasively detecting the one or more target analytes on the cell surface by differentiating the analyte response signal from the unbound nanoparticle signal, based, at least in part, on the modulation,

wherein the modulation source alters one or more properties of the polyvalent functionalized nanoparticles that are bound to the one or more target analytes on the cell surface and wherein the one or more properties of the polyvalent functionalized nanoparticles comprises one or more of;

optical properties, magnetic properties, electric properties, thermal properties, acoustic properties, chemical properties, and physical properties.

2. The system of claim 1, wherein the environment is a living body and further comprising a wearable device having a mount for mounting the wearable device to an external surface of the living body, wherein the detector is mounted on the wearable device.

3. The system of claim 2, wherein at least a portion of the modulation source is mounted on said wearable device.

4. The system of claim 1, wherein the processor further differentiates the analyte response signal from a background signal and wherein said modulation source modulates the analyte response signal and the background signal, such that the analyte response signal is affected differently than the background signal, or to alter the analyte response signal by spatially modulating the polyvalent functionalized nanoparticles that bind with the one or more target analytes on the cell surface.

5. The system of claim 1, wherein the modulation source alters the analyte response signal by modulating an interrogation signal directed into the body.

6. The system of claim 1, further comprising an interrogating signal source, the analyte response signal being transmitted in response to the interrogating signal.

7. The system of claim 1, wherein the environment comprises a fluid conduit or a fluid reservoir.

8. The system of claim 1, wherein the environment is a living body, wherein the polyvalent functionalized nanoparticles are introduced into the living body to bind with one or more target analytes present on a surface of a cell in a body fluid contained in the living body, and wherein the body fluid comprises blood, tear fluid, urine, lymph, cerebrospinal fluid, stool, or mucus.

9. The system of claim 1, wherein the environment is a living body, wherein the polyvalent functionalized nanoparticles are embedded in skin or tissue of the living body, and wherein the functionalized nanoparticles are introduced into the living body to bind with one or more target analytes present on the surface of a cell in the skin or tissue of the living body.

23. The system according to claim 1, wherein the cells are tumor cells.

26. The system of claim 1, wherein the nanoparticles comprise two or more different binding receptors to detect multiple different target analytes on the cell surface.

10. A system, comprising:

polyvalent functionalized nanoparticles for binding with one or more target analytes on a surface of a cell present in an environment;

a detector for detecting a response signal transmitted from the environment, wherein the response signal includes a background signal and an analyte response signal related to binding of the one or more target analytes with polyvalent functionalized nanoparticles;

magnetic particles;

a magnetic field source sufficient to distribute the magnetic particles into a spatial arrangement in the environment, wherein the spatial arrangement of the magnetic particles modulates the analyte response signal, such that the analyte response signal is affected differently than the background signal; and

a processor for non-invasively detecting the one or more target analytes by differentiating the analyte response signal from the background signal based, at least in part, on modulation of the analyte response signal, wherein the analyte response signal is modulated differently than the background signal or modulated differently than the unbound particle signal.

11. The system of claim 10, wherein the response signal further includes an unbound particle signal related to polyvalent functionalized nanoparticles that are not bound with the one or more target analytes.

12. The system of claim 11, wherein the processor further non-invasively detects the one or more target analytes by differentiating the analyte response signal from the unbound particle signal, at least in part, based on modulation of the signals due, at least in part, to the spatial arrangement of the magnetic particles.

13. The system of claim 10, further comprising an interrogating signal source, the response signal being transmitted in response to the interrogating signal.

14. The system of claim 10, wherein the environment comprises a fluid conduit or fluid reservoir.

15. The system of claim 13, wherein the environment comprises a living body.

16. The system of claim 15, wherein the environment comprises a lumen of subsurface vasculature in the living body.

24. The system according to claim 10, wherein the cells are tumor cells.

17. A method comprising:

introducing polyvalent functionalized nanoparticles into an environment for binding with one or more target analytes on a surface of a cell present in the environment;

detecting an analyte response signal transmitted from the environment, wherein the analyte response signal is related to binding of the one or more target analytes with the polyvalent functionalized nanoparticles and wherein the response signal is modulated;

detecting an unbound polyvalent functionalized nanoparticle signal transmitted from the environment, wherein the unbound nanoparticle signal is related to polyvalent functionalized nanoparticles that are not interacting with the one or more target analytes;

detecting a background signal;

applying a modulation to a portion of the environment for altering the analyte response signal and the unbound nanoparticle signal, such that the analyte response signal is affected differently than the unbound nanoparticle signal and the background signal; and

differentiating the analyte response signal from the unbound nanoparticles signal and the background signal.

18. The method of claim 17, further comprising:

directing an interrogating signal into the environment; and

detecting the analyte response signal transmitted from the environment in response to the interrogating signal.

19. The method of claim 17, wherein the environment comprises a fluid conduit, a fluid reservoir, or a living body.

20. The method of claim 19, wherein the polyvalent functionalized nanoparticles interacts with one or more target analytes present in the living body.

21. The method of claim 20, wherein the polyvalent functionalized nanoparticles are embedded in skin or tissue of the living body.

22. The method of claim 21, wherein the polyvalent functionalized nanoparticles interacts with one or more target analytes present in the skin or tissue of the living body.

25. The method according to claim 17, wherein the cells are tumor cells.