Modulation of a response signal to distinguish between analyte and background signals

• US 10,542,918 B2
• Filed: 10/23/2013
• Issued: 01/28/2020
• Est. Priority Date: 10/23/2013
• Status: Active Grant

• Current Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Original Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Inventors: Conrad, Andrew, Peeters, Eric, Bajaj, Vikram Singh, Thompson, Jason, Askew, Mark
• Primary Examiner(s): Hoffman, Joanne M
• Application Number:
  US14/061,251
• Publication Number:
  US 20150110721A1
• Time in Patent Office: 2,288 Days
• Field of Search: None
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• 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 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/681 Wristwatch-type devices
• CPC Class Codes: A61B 5/7203 for noise prevention, reduction or removal
• CPC Class Codes: A61B 5/742 using visual displays A61B5/339 takes precedence

Abstract

A method for modulating a response signal includes introducing functionalized particles into a lumen of subsurface vasculature, wherein the functionalized particles are configured to interact with one or more target analytes present in blood circulating in the subsurface vasculature; and non-invasively detecting the one or more target analytes. A response signal, which may include a background signal and an analyte response signal related to interaction of the functionalized particles with the one or more target analytes, is transmitted from the subsurface vasculature. A modulation configured to alter the response signal such that the analyte response signal is affected differently than the background signal may be applied to a portion of subsurface vasculature. Analyte detection may be achieved by differentiating the analyte response signal from the background signal.

Claims

1. A method, comprising:

detecting an analyte response signal transmitted from within a lumen of subsurface vasculature inside a body, wherein the analyte response signal is indicative of interaction of functionalized particles with one or more target analytes present in blood circulating in the subsurface vasculature, wherein the functionalized particles each comprise an antibody covalently attached to a nanoparticle;

detecting an unbound particle signal transmitted from within the lumen of subsurface vasculature, wherein the unbound particle signal is indicative of functionalized particles that are not interacting with the one or more target analytes;

detecting a background signal;

applying a modulation to a portion of the subsurface vasculature, wherein the modulation alters the analyte response signal and the unbound particle signal, such that the analyte response signal is affected differently than the unbound particle signal and the background signal; and

differentiating the analyte response signal from the unbound particle signal and the background signal based, at least in part, on the modulation.

2. The method of claim 1, further comprising introducing the functionalized particles into the lumen of subsurface vasculature by injection, ingestion, inhalation, or transdermally.

3. The method of claim 1, further comprising:

directing an interrogating signal into the subsurface vasculature; and

detecting the analyte response signal transmitted from the subsurface vasculature in response to the interrogating signal.

4. The method of claim 1, wherein the modulation alters the analyte response signal by spatially modulating the functionalized particles that are interacting with the one or more target analytes.

5. The method of claim 1, wherein the modulation alters one or more properties of the functionalized particles that are interacting with the one or more target analytes.

6. The method of claim 5, wherein the one or more properties of the functionalized particles comprises one or more of:

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

7. A method, comprising:

detecting an analyte response signal transmitted from an environment, wherein the analyte response signal is indicative of interaction of functionalized particles with one or more target analytes, wherein the functionalized particles each comprise an antibody covalently attached to a nanoparticle;

detecting an unbound particle signal transmitted from the environment, wherein the unbound particle signal is indicative of functionalized particles that are not interacting with the one or more target analytes;

detecting a background signal;

applying a modulation to a portion of the environment, wherein the modulation alters the analyte response signal and unbound particle signal, such that the analyte response signal is affected differently than the unbound particle signal and background signal; and

differentiating the analyte response signal from the unbound particle signal and the background signal based, at least in part, on the modulation.

8. The method of claim 7, 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.

9. The method of claim 7, wherein the environment comprises a fluid conduit.

10. The method of claim 7, wherein the environment comprises a fluid reservoir.

11. The method of claim 7, wherein the environment comprises a living body.

12. The method of claim 11, wherein the functionalized particles interact with one or more target analytes present in the living body.

13. The method of claim 11, wherein the functionalized particles are embedded in skin or tissue of the living body.

14. The method of claim 13, wherein the functionalized particles interact with one or more target analytes present in the skin or tissue of the living body.

15. The method of claim 11, wherein the functionalized particles are introduced into a body fluid comprising blood, tear fluid, urine, lymph, cerebrospinal fluid, or mucus.

16. The method of claim 15, wherein the functionalized particles interact with one or more target analytes present in the body fluid.

25. The method of claim 11, further comprising:

introducing the functionalized particles into the living body by injection, ingestion, inhalation, or transdermally.

17. A device, comprising:

a detector that detects;

an analyte response signal transmitted from an environment, wherein the analyte response signal is indicative of interaction of one or more target analytes with functionalized particles present in the environment, wherein the functionalized particles each comprise an antibody covalently attached to a nanoparticle;

an unbound particle signal transmitted from the environment, wherein the unbound particle signal is indicative of functionalized particles that are not interacting with the one or more target analytes; and

a background signal;

a modulation source that alters the analyte response signal and the unbound particle signal, such that the analyte response signal is affected differently than the unbound particle signal and background signal; and

a processor that non-invasively detects the one or more target analytes by differentiating the analyte response signal from the unbound particle signal and the background signal based, at least in part, on the modulation.

18. The device of claim 17, further comprising a wearable device mountable to an external surface of the environment, wherein the detector is mounted on the wearable device.

19. The device of claim 18, wherein at least a portion of the modulation source is mounted on said wearable device.

20. The device of claim 17, wherein said modulation source alters the analyte response signal differently than the background signal.

21. The device of claim 17, further comprising an interrogating signal source that directs an interrogation signal source into the environment, the analyte response signal being transmitted in response to the interrogating signal.

22. The device of claim 17, wherein the environment comprises a fluid conduit.

23. The device of claim 17, wherein the environment comprises a fluid reservoir.

24. The device of claim 17, wherein the environment comprises a living body.