Analyte sensor method and apparatus

• US 8,280,470 B2
• Filed: 11/05/2007
• Issued: 10/02/2012
• Est. Priority Date: 11/03/2006
• Status: Active Grant

• Current Assignee: Volcano Corporation (Koninklijke Philips N.V.)
• Original Assignee: Volcano Corporation (Koninklijke Philips N.V.)
• Inventors: Milner, Thomas E., Kemp, Nathaniel J., Castella, Paul
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Liu, Chu Chuan (JJ)
• Application Number:
  US11/935,265
• Publication Number:
  US 20080119701A1
• Time in Patent Office: 1,793 Days
• Field of Search: 600/309, 600/310, 600/316, 600/322, 600/342, 600/473, 600/476, 356/402, 356/450
• US Class Current: 600/310
• CPC Class Codes: A61B 2562/0285 Nanoscale sensors
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• CPC Class Codes: A61B 5/0066 Optical coherence imaging
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B

Abstract

The invention generally relates to systems, methods, and apparatuses for an analyte sensor. In one aspect, an analyte sensing device comprises a sensor body member including at least one nanopore and an optical conduit in optical communication with the sensor body member. The optical conduit transmits optical energy to the sensor body member and receives reflected optical energy back from the sensor body member. A photodetector is optically coupled to the optical conduit to determine an optical parameter from the reflected optical energy.

Claims

1. An analyte sensing device comprising:

a. a sensor body member including at least one nanopore;

b. an optical conduit in optical communication with the sensor body member, the optical conduit transmits optical energy to the sensor body member and receives reflected optical energy back from the sensor body member; and

c. a photodetector optically coupled to the optical conduit to determine an optical parameter from the reflected optical energy,

wherein the photodetector is optically coupled to an optical coherence tomography instrument and the optical parameter is correlated with a refractive index of the analyte.

2. The analyte sensing device of claim 1, wherein the sensor body member includes a reflective surface at the distal end of the sensor body element in optical communication with the optical conduit and the optical conduit includes a reflective surface at the distal end of the optical conduit.

3. The analyte sensing device of claim 1, wherein the optical coherence tomography instrument comprises:

a. a light source;

b. a polarization maintaining reference path;

c. a polarization maintaining sample path optically aligned with the optical conduit; and

d. a polarization maintaining detection path optically aligned with the photodetector, wherein the detection path, the source path, and the reference path are each optically connected to a path coupler.

4. The analyte sensing device of claim 1, wherein the nanopore is at least 300 nanometers.

5. The analyte sensing device of claim 3, wherein the optical coherence tomography instrument is phase sensitive to measure the change in optical path length.

6. The analyte sensing device of claim 3, wherein the optical coherence tomography instrument is polarization sensitive.

7. The analyte sensing device of claim 3, wherein the sensor body element is optically coupled with at least one faraday rotator and the optical coherence tomography instrument is polarization sensitive to measure circular birefringence.

8. The analyte sensing device of claim 3, wherein the optical coherence tomography is phase and polarization sensitive.

9. The analyte sensing device of claim 1, wherein the sensor body member is operationally coupled to a catheter.

10. The analyte sensing device of claim 1, wherein the sensor body member is substantially coated with a surfactant.

11. The analyte sensing device of claim 1 wherein the at least one nanopore are a plurality of nanopores.

12. The analyte sensing device of claim 11, wherein the nanopores are asymmetrical.

13. The analyte sensing device of claim 11, wherein an optical pathlength of the light reflected from the nanopores and a polarization state of light reflected from the nanopores determine the analyte concentration in the nanopores.

14. The analyte sensing device of claim 11, wherein the nanopores are substantially parallel to one another.

15. A method for obtaining optical measurements of an analyte comprising the steps of:

optically coupling a sensor body element with an optical conduit, the sensor body element includes at least one nanopore and a reflective surface, and the optical conduit is operably associated with a reference reflector;

permitting the diffusion of an analyte into the at least one nanopore;

transmitting optical energy from the optical conduit to the sensor body element;

reflecting optical energy from the sensor body element back to the optical conduit;

measuring the reflected optical energy with a detector optically coupled to an optical coherence tomography instrument; and

determining a refractive index of the analyte from the measured energy.

16. The method for obtaining optical measurements of an analyte of claim 15, wherein the optical conduit and reference reflector are included in the optical coherence tomography system and the method further comprises the steps of:

generating light energy from a light source;

transmitting at least a first portion of the generated light energy onto the reference reflector wherein at least a portion of the transmitted first portion of light energy is reflected by the reference reflector;

transmitting at least a second portion of the generated light energy into the sensor body, wherein at least a portion of the transmitted second portion of light energy contacts an analyte located within the at least one nanopore and wherein at least a portion of the light energy which contacts the analyte is reflected;

receiving the light energy reflected by the reference reflector and the analyte;

combining the received light energy, wherein the combined light energy interferes; and

processing the combined light energy to measure the refractive index of the analyte within the at least one nanopore.

17. The method for obtaining optical measurements of an analyte of claim 15 further comprises measuring the change in optical pathlength to measure the refractive index of the analyte inside the at least one nanopore where the optical coherence tomography instrument is phase sensitive and coupled to an optical clock.

18. The method for obtaining optical measurements of an analyte of claim 15, wherein the at least one nanopore are a plurality of nanopores and the method further comprises measuring a change in form-birefringence to measure an average refractive index of the analyte inside the nanopores where the optical coherence tomography instrument is polarization sensitive and the nanopores are asymmetrical.

19. The method for obtaining optical measurements of an analyte of claim 17 further comprising measuring a polarization state of the light backscattered from the sensor body element;

depicting a trajectory of the polarization state on a Poincare sphere or a complex polarization ratio (Z) plane; and

analyzing the trajectory to estimate the analyte concentration in the nanopore.

20. The method for obtaining optical measurements of an analyte of claim 16 further comprises:

detecting a phase retardation between the orthogonal light oscillations in the sensing body element;

breaking the symmetry due to reflection of light in the sensing body element with at least one Faraday rotator element;

analyzing the trajectory of a Stokes vector on a Poincare sphere corresponding to the light backscattered from the sensing body element for movements orthogonal to displacements due to the linear birefringence;

analyzing the composite trajectory on the Poincare sphere with movements due to linear form birefringence and circular birefringence of the analyte to estimate analyte concentration.

21. The method for obtaining optical measurements of an analyte of claim 16 further comprising estimating the concentration of the analyte with circular birefringence where the optical coherence tomography instrument is polarization sensitive and the sensor body element is coupled to at least on Faraday rotation element.

22. The method for obtaining optical measurements of an analyte of claim 16 further comprising estimating the analyte concentration with circular and form birefringence where the optical coherence tomography instrument is phase and polarization sensitive and the sensor body element is coupled to at least one Faraday rotation element.

23. The method for obtaining optical measurements of an analyte of claim 16 further comprising coupling the sensor body element with a catheter and inserting the catheter into a patient.

24. The method for obtaining optical measurements of an analyte of claim 16, further 10 comprising allowing the analyte to fill the sensor body element;

monitoring the analyte by optical parameters in a time-dependent manner; and

deducing the concentration of the analyte from the time variation of the analyte filling the sensor body element.