Spatial modulation of magnetic particles in vasculature by external magnetic field

• US 9,504,405 B2
• Filed: 10/23/2013
• Issued: 11/29/2016
• Est. Priority Date: 10/23/2013
• Status: Active Grant

• Current Assignee: Google 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): Chen, Tse
• Assistant Examiner(s): HOFFMAN, JOANNE M
• Application Number:
  US14/061,334
• Publication Number:
  US 20150112168A1
• Time in Patent Office: 1,133 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 5/0059 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 5/01 Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue clinical contact thermometers G01K13/20
• CPC Class Codes: A61B 5/02055 Simultaneously evaluating both cardiovascular condition and temperature
• CPC Class Codes: A61B 5/021 Measuring pressure in heart or blood vessels A61B5/0205 takes precedence
• CPC Class Codes: A61B 5/024 Detecting, measuring or recording pulse rate or heart rate A61B5/0205, A61B5/021 take precedence
• 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 5/0515 Magnetic particle imaging
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• 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 5/681 Wristwatch-type devices
• CPC Class Codes: A61B 5/7228 Signal modulation applied to the input signal sent to patient or subject; demodulation to recover the physiological signal modulation H03C
• CPC Class Codes: G01R 33/24 for measuring direction or magnitude of magnetic fields or magnetic flux
• CPC Class Codes: G01R 33/44 using nuclear magnetic resonance [NMR] G01R33/24, G01R33/62 take precedence
• CPC Class Codes: G16H 40/63 for local operation

Abstract

A method for modulating a response signal includes introducing functionalized magnetic particles configured to interact with target analytes into the body, applying a magnetic field sufficient to draw the functionalized magnetic particles towards a surface of the lumen of subsurface vasculature closest to an internally or externally applied mask having a spatial arrangement, and detecting a response signal, which includes a background signal and an analyte response signal, transmitted from the subsurface vasculature. The analyte response signal related to interaction of the functionalized magnetic particles with the target analytes and is modulated with respect to the background signal due, at least in part, to the spatial arrangement of the mask. The target analytes may be non-invasively detected by differentiating the analyte response signal from the background signal due, at least in part, to the modulation of the analyte response signal.

Claims

1. A method, comprising:

applying a magnetic field sufficient to distribute magnetic particles present in a body into a mask having a spatial arrangement in a lumen of subsurface vasculature;

detecting a response signal transmitted from the subsurface vasculature, wherein the response signal includes a background signal and an analyte response signal indicative of interaction of functionalized particles present in the body with the one or more target analytes, wherein the spatial arrangement of the mask formed by the magnetic particles modulates the analyte response signal with respect to the background signal as the functionalized particles in the body flow past the spatial arrangement of the mask, such that a period of the unmodulated analyte response signal is different than a period of the modulated analyte response signal as detected, and such that the period of the modulated analyte response signal as detected is different than a period of the background signal as detected; and

non-invasively detecting the one or more target analytes by differentiating the analyte response signal from the background signal due, at least in part, to the modulation of the analyte response signal.

2. The method of claim 1, further comprising introducing functionalized particles into the subsurface vasculature, wherein the functionalized particles interact with one or more target analytes present in blood circulating in the subsurface vasculature.

3. The method of claim 1, further comprising introducing magnetic particles into the subsurface vasculature.

4. The method of claim 1, wherein the response signal further includes an unbound particle signal indicative of functionalized particles that are not interacting with the one or more target analytes.

5. The method of claim 4, further comprising non-invasively detecting the one or more target analytes by differentiating the analyte response signal from the background signal and the unbound particle signal, due, at least in part, to the modulation of the analyte response signal.

6. The method of claim 5, wherein the analyte response signal is modulated differently than the background signal.

7. The method of claim 6, wherein the analyte response signal is modulated differently than the background signal due, at least in part, to the velocity of the functionalized particles in the blood circulating in the subsurface vasculature.

8. The method of claim 5, wherein the analyte response signal is modulated differently than the unbound particle signal.

9. The method of claim 8, wherein the analyte response signal is modulated differently than the unbound particle signal due, at least in part, to a difference in the velocity of the functionalized particles in the blood circulating in the subsurface vasculature that are interacting with the one or more target analytes and the velocity of the functionalized particles in the blood circulating in the subsurface vasculature that are not interacting with the one or more target analytes.

10. The method of claim 1, further comprising:

directing an interrogating signal into the subsurface vasculature; and

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

11. A method, comprising:

applying a mask having a spatial arrangement, externally to a portion of subsurface vasculature in a body, wherein the mask is positioned between the subsurface vasculature and a detector;

applying a magnetic field sufficient to draw functionalized magnetic particles present in the body towards a surface of a lumen of subsurface vasculature closest to the mask;

detecting, with the detector, a response signal transmitted from the subsurface vasculature, wherein the response signal includes a background signal and an analyte response signal indicative of interaction of the functionalized magnetic particles with the one or more target analytes, wherein the spatial arrangement of the mask formed by the magnetic particles modulates the analyte response signal with respect to the background signal as the functionalized particles in the body flow past the spatial arrangement of the mask, such that a period of the unmodulated analyte response signal is different than a period of the modulated analyte response signal as detected, and such that the period of the modulated analyte response signal as detected is different than a period of the background signal as detected; and

non-invasively detecting the one or more target analytes by differentiating the analyte response signal from the background signal due, at least in part, to the modulation of the analyte response signal.

12. The method of claim 11, further comprising introducing functionalized magnetic particles into the subsurface vasculature, wherein the functionalized particles interact with one or more target analytes present in blood circulating in the subsurface vasculature.

13. The method of claim 11, wherein the response signal further includes an unbound particle signal indicative of functionalized particles that are not interacting with the one or more target analytes.

14. The method of claim 13, further comprising non-invasively detecting the one or more target analytes by differentiating the analyte response signal from the background signal and the unbound particle signal, due, at least in part, to the modulation of the analyte response signal.

15. The method of claim 11, wherein the analyte response signal is modulated differently than the background signal.

16. The method of claim 11, wherein the analyte response signal is modulated differently than the unbound particle signal.

17. The method of claim 11, wherein the magnetic field is applied at a first location with respect to the subsurface vasculature and wherein the mask is applied at a second location with respect to the subsurface vasculature, said second location being downstream from the first location in the direction of the flow of blood circulating in the subsurface vasculature.

18. The method of claim 17, further comprising:

deactivating the magnetic field; and

detecting a response signal transmitted from the subsurface vasculature at the second location.

19. The method of claim 11, further comprising:

directing an interrogating signal into the subsurface vasculature; and

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

20. A device comprising:

a detector that can detect an analyte response signal transmitted from a body, wherein the analyte response signal is indicative of the interaction of the one or more target analytes with functionalized particles present in the body;

a modulation source comprising a magnetic field source that applies a magnetic field sufficient to distribute magnetic particles present in the body into a mask having a spatial arrangement in a lumen of subsurface vasculature, wherein the spatial arrangement of the mask formed by the magnetic particles modulates the analyte response signal with respect to a background signal as the as functionalized particles in the body flow past the spatial arrangement of the mask, such that a period of the unmodulated analyte response signal is different than a period of the modulated analyte response signal as detected, and such that the period of the modulated analyte response signal as detected is different than a period of the background signal as detected; and

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