System, device and method for determining the concentration of an analyte

• US 7,236,812 B1
• Filed: 08/27/2004
• Issued: 06/26/2007
• Est. Priority Date: 09/02/2003
• Status: Expired due to Fees

• Current Assignee: BioTex Incorporated
• Original Assignee: BioTex Incorporated
• Inventors: Gowda, Ashok, McNichols, Roger, Ballerstadt, Ralph
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US10/929,056
• Time in Patent Office: 1,033 Days
• Field of Search: 600/312, 600/317, 600/322, 600/341, 600/342, 600/310, 422/82.05, 422/82.06, 436/95, 436/805
• US Class Current: 600/316
• 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 2021/1787 Tomographic, i.e. computerised reconstruction from projective measurements
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 2201/06193 Secundary in-situ sources, e.g. fluorescent particles
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

There are many inventions described and illustrated herein. In one aspect, the present invention is a system, a device and a method for sensing the concentration of an analyte in a fluid (for example, a fluid sample) or matrix. The analyte may be glucose or other chemical of interest. The fluid or matrix may be, for example, the fluid or matrix in the body of an animal (for example, human), or any other suitable fluid or matrix in which it is desired to know the concentration of an analyte. In one embodiment, the invention is a system and/or device that includes one or more layers having a plurality of analyte-equivalents and mobile or fixed receptor molecules with specific binding sites for the analyte-equivalents and analytes under analysis (for example, glucose). The receptor molecules, when exposed to or in the presence of analyte (that resides, for example, in a fluid in an animal), bind with the analyte (or vice versa). As such, some or all (or substantially all) of the receptor molecules within a given layer may bind with the analyte, which results in a change in the optical properties of one or more of the layers. These layer(s) may be examined or interrogated, via optical techniques, whereby the optical response of the layers and/or, in particular, the substance within the layer(s), may be measured, evaluated and/or analyzed.

Claims

1. An analyte sensing device for sensing a concentration of analyte in a fluid, the analyte sensing device comprising:

a first sensor layer having at least one optical property that is responsive to the concentration of analyte in communication therewith, the first sensor layer including;

a matrix having a plurality of first analyte equivalent residues disposed therein; and

a plurality of first analyte binding receptor molecules, wherein the first analyte binding receptor molecules are capable of reversibly binding with the first analyte equivalent residues and the analyte; and

wherein the at least one optical property includes a scattering of optical radiation incident on the first sensor layer.

2. The analyte sensing device of claim 1 further including a housing wherein the first sensor layer is contained within the housing and wherein a portion of the housing is permeable to the analyte and non-permeable to the first sensor layer and wherein the first sensor layer further includes a plurality of nanoparticles.

3. The analyte sensing device of claim 1 further including a housing wherein the first sensor layer is contained within the housing and wherein a portion of the housing is permeable to the analyte and non-permeable to the first sensor layer.

4. The analyte sensing device of claim 3 wherein the first sensor layer further includes at least one extra-matrix space disposed between the matrix and the housing.

5. The analyte sensing device of claim 3 wherein the housing further includes a portion that is non-permeable to the analyte.

6. The analyte sensing device of claim 1 further including a second sensor layer having at least one optical property that is responsive to the concentration of analyte in communication therewith, the second sensor layer including:

a matrix having a plurality of second analyte equivalent residues disposed therein; and

a plurality of second analyte binding receptor molecules, wherein the second analyte binding receptor molecules are capable of reversibly binding with the second analyte equivalent residues and the analyte.

7. The analyte sensing device of claim 1 further including a first target arranged to be disposed within a path of optical radiation when the path of optical radiation illuminates the first sensor layer.

8. The analyte sensing device of claim 7 further including a second target wherein the second target is not disposed within the path of optical radiation.

9. The analyte sensing device of claim 7 wherein the first target is a reflective target.

10. The analyte sensing device of claim 7 wherein the first target is a fluorescent target.

11. The analyte sensing device of claim 1 wherein the first analyte equivalent residues are confined within the matrix and the first analyte binding receptor molecules are capable of migrating outside of the matrix.

12. The analyte sensing device of claim 1 wherein the first analyte binding receptor molecules are confined within the matrix and the first analyte equivalent residues are capable of migrating outside of the matrix.

13. The analyte sensing device of claim 1 wherein the first sensor layer further includes a plurality of nanoparticles.

14. The analyte sensing device of claim 13 wherein the nanoparticles are attached to the first analyte binding receptor molecule.

15. The analyte sensing device of claim 13 wherein the nanoparticles are attached to the first analyte equivalent residues.

16. The analyte sensing device of claim 1 wherein the first sensor layer is disposed around at least one fiber optic which is capable of providing radiation to and/or receiving radiation from the first sensor layer.

17. An analyte sensing device for sensing a concentration of analyte in a fluid of an animal body, the analyte sensing device capable of being implanted in the animal body such that it is in communication with the fluid, the analyte sensing device comprising:

a housing; and

a sensor layer disposed within the housing, wherein the sensor layer having at least one optical property that is responsive to the concentration of analyte in communication therewith, the sensor layer includes;

a matrix having a plurality of analyte equivalent residues disposed therein;

at least one extra-matrix space disposed between the matrix and the housing; and

a plurality of analyte binding receptor molecules, wherein the analyte binding receptor molecules are capable of reversibly binding with the analyte equivalent residues and the analyte; and

wherein the housing includes a permeable membrane that is permeable to analyte and non-permeable to the sensor layer and wherein the at least one optical property includes a scattering of optical radiation incident on the sensor layer.

18. The analyte sensing device of claim 17 wherein the analyte equivalent residues are confined within the matrix and the analyte binding receptor molecules are capable of migrating outside of the matrix.

19. The analyte sensing device of claim 17 wherein the analyte binding receptor molecules are confined within the matrix and the analyte equivalent residues are capable of migrating outside of the matrix.

20. The analyte sensing device of claim 17 wherein the at analyte is glucose.

21. A method to detect the concentration of an analyte in a fluid using an analyte sensing device comprising a sensor layer disposed within the housing, wherein the sensor layer exhibits at least one optical property that is responsive to the concentration of analyte in communication therewith, the sensor layer including a matrix having a plurality of analyte equivalent residues disposed therein, and a plurality of analyte binding receptor molecules, wherein the analyte binding receptor molecules are capable of reversibly binding with the analyte equivalent residues and the analyte, the method comprising:

placing an analyte sensing device in communication with the fluid;

providing incident optical radiation to the analyte sensing device;

receiving responsive optical radiation from the analyte sensing device;

determining the concentration of analyte by using the responsive optical radiation to measure a change in scattering of optical radiation by the sensor layer; and

outputting data which is representative of the concentration of analyte.

22. The method of claim 21 further including analyzing the responsive optical radiation to detect fluorescence which depends at least partially on analyte dependent optical properties.

23. The method of claim 21 wherein providing incident optical radiation to the analyte sensing device includes providing incident optical radiation to the analyte sensing device using an optical coherence tomography instrument.

24. The method of claim 21 further including analyzing the responsive optical radiation to determine a change in scattering of optical radiation by the sensor layer and wherein analyzing the responsive optical radiation includes using a mathematical analysis of one or more optical coherence tomography return signals of the responsive optical radiation.

25. The method of claim 21 wherein analyzing the responsive optical radiation to measure a change in scattering of optical radiation by the sensor layer includes measuring the transmission of optical radiation incident on the sensor layer to determine the scattering of optical radiation incident on the sensor layer.

26. An analyte sensing system comprising:

analyte sensing device to sense a concentration of analyte in a fluid, the analyte sensing device including;

a first sensor layer having at least one optical property that is responsive to the concentration of analyte in communication therewith, the first sensor layer including;

a matrix having a plurality of first analyte equivalent residues disposed therein; and

a plurality of first analyte binding receptor molecules, wherein the first analyte binding receptor molecules are capable of reversibly binding with the first analyte equivalent residues and the analyte;

wherein the at least one optical property includes a scattering of optical radiation incident on the first sensor layer; and

means for measuring the at least one optical property to determine the concentration of analyte in communication with the first sensor layer.

27. The analyte sensing system of claim 26 wherein the means for measuring the at least one optical property is (1) a spectrophotometer or (2) a system using (i) optical coherence tomography, (ii) optical coherence domain reflectometry, or (iii) optical time-domain reflectometry.

28. The analyte sensing system of claim 26 further including a housing wherein the first sensor layer is contained within the housing and wherein a portion of the housing is permeable to the analyte and non-permeable to the first sensor layer.

29. The analyte sensing system of claim 28 wherein the first sensor layer further includes at least one extra-matrix space disposed between the matrix and the housing.

30. The analyte sensing system of claim 28 wherein the housing further includes a portion that is non-permeable to the analyte.

31. The analyte sensing system of claim 26 further including a second sensor layer having at least one optical property that is responsive to the concentration of analyte in communication therewith, the second sensor layer including:

a matrix having a plurality of second analyte equivalent residues disposed therein; and

a plurality of second analyte binding receptor molecules, wherein the second analyte binding receptor molecules are capable of reversibly binding with the second analyte equivalent residues and the analyte.

32. The analyte sensing system of claim 26 further including a first target arranged to be disposed within a path of optical radiation when the path of optical radiation illuminates the first sensor layer.

33. The analyte sensing system of claim 32 further including a second target wherein the second target is not disposed within the path of optical radiation.

34. The analyte sensing system of claim 32 wherein the first target is a reflective target.

35. The analyte sensing system of claim 32 wherein the first target is a fluorescent target.

36. The analyte sensing system of claim 26 wherein the first analyte equivalent residues are confined within the matrix and the first analyte binding receptor molecules are capable of migrating outside of the matrix.

37. The analyte sensing system of claim 26 wherein the first analyte binding receptor molecules are confined within the matrix and the first analyte equivalent residues are capable of migrating outside of the matrix.

38. The analyte sensing system of claim 26 wherein the first sensor layer further includes a plurality of nanoparticles which are attached to the first analyte binding receptor molecule.

39. The analyte sensing system of claim 38 wherein the first sensor layer further includes a plurality of nanoparticles which are attached to the first analyte equivalent residues.

40. The analyte sensing system of claim 26 wherein the means for measuring the at least one optical property uses changes in transmission of optical radiation incident on the first sensor layer to determine the scattering of optical radiation incident on the first sensor layer.

41. An analyte sensing system comprising:

an analyte sensing device, capable of being implanted in an animal body such that it is in communication with a fluid in the animal body, the analyte sensing device comprising;

a housing; and

a sensor layer disposed within the housing, wherein the sensor layer having at least one optical property that is responsive to the concentration of analyte in communication therewith, the sensor layer includes;

a matrix having a plurality of analyte equivalent residues disposed therein;

at least one extra-matrix space disposed between the matrix and the housing; and

a plurality of analyte binding receptor molecules, wherein the analyte binding receptor molecules are capable of reversibly binding with the analyte equivalent residues and the analyte; and

wherein the housing includes a permeable membrane that is permeable to analyte and non-permeable to the sensor layer and wherein the at least one optical property includes a scattering of optical radiation incident on the sensor layer; and

means for measuring the at least one optical property to determine the concentration of analyte in communication with the sensor layer.

42. The analyte sensing system of claim 41 wherein the analyte equivalent residues are confined within the matrix and the analyte binding receptor molecules are capable of migrating outside of the matrix.

43. The analyte sensing system of claim 41 wherein the analyte binding receptor molecules are confined within the matrix and the sensor layer includes an analyte analogue which is capable of migrating outside of the matrix.

44. The analyte sensing system of claim 43 wherein the analyte analogue is dextran.

45. The analyte sensing system of claim 44 wherein the dextran is conjugated with one or a plurality of nanoparticles.

46. The analyte sensing system of claim 41 wherein the analyte is glucose.

47. The analyte sensing system of claim 41 wherein the means for measuring the at least one optical property uses the transmission of optical radiation incident on the sensor layer to determine the scattering of optical radiation incident on the sensor layer.

48. The analyte sensing system of claim 41 wherein the means for measuring the at least one optical property is (1) a spectrophotometer or (2) a system using (i) optical coherence tomography, (ii) optical coherence domain reflectometry, or (iii) optical time-domain reflectometry.