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

• US 8,364,217 B2
• Filed: 06/08/2007
• Issued: 01/29/2013
• Est. Priority Date: 09/02/2003
• Status: Expired due to Fees

• Current Assignee: BioTex Incorporated
• Original Assignee: BioTex Incorporated
• Inventors: Ballerstadt, Ralph, McNichols, Roger, Gowda, Ashok
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Liu, Chu Chuan (JJ)
• Application Number:
  US11/811,083
• Publication Number:
  US 20070249917A1
• Time in Patent Office: 2,062 Days
• Field of Search: 600/310, 600/316, 600/322, 600/341, 600/365, 600/473, 600/476, 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 housing;

a first layer, disposed in the housing, having a first optical property that is responsive to the concentration of analyte in communication therewith, the first 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

a second layer, disposed in the housing, having at least one optical property that is insensitive to the concentration of analyte in communication therewith;

wherein the first optical property is a scattering of optical radiation incident on the first layer.

2. The analyte sensing device of claim 1 wherein the analyte is glucose.

3. The analyte sensing device of claim 1 wherein the housing includes a first portion that is permeable to the analyte and non-permeable to the first layer.

4. The analyte sensing device of claim 1 wherein the first portion of the housing is a membrane.

5. The analyte sensing device of claim 4 wherein the membrane is cellulose acetate and/or polysulphone.

6. The analyte sensing device of claim 1 wherein the first layer further includes at least one extra-matrix space disposed between the matrix and the housing.

7. The analyte sensing device of claim 1 wherein the housing further includes a reflecting portion disposed distal to a path of optical radiation that is incident on the first layer.

8. The analyte sensing device of claim 1 wherein the housing further includes a reflecting portion disposed distal to a path of optical radiation that is incident on the second layer.

9. The analyte sensing device of claim 1 wherein the housing further includes a reflecting portion disposed distal to a path of optical radiation that is incident on the first and second layers.

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

11. The analyte sensing device of claim 1 wherein the at least one optical property of the second layer provides a reference signal.

12. The analyte sensing device of claim 1 wherein the first layer further includes a plurality of nanoparticles which are attached to a plurality of the first analyte binding receptor molecules.

13. The analyte sensing device of claim 1 wherein the first layer further includes a plurality of nanoparticles which are attached to a plurality of the first analyte equivalent residues.

14. The analyte sensing device of claim 1 wherein the first layer further includes a plurality of nanoparticles which are attached to a plurality of the first analyte binding receptor molecules and a plurality of the first analyte equivalent residues.

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

a housing having;

a first portion that is permeable to the analyte and non-permeable to a first layer; and

a reflecting portion;

the first layer, disposed in the housing, having a first optical property that is responsive to the concentration of analyte in communication therewith wherein the first optical property is a scattering of optical radiation incident on the first layer, the first 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 reflecting portion is disposed distal to a path of optical radiation that is incident on the first layer.

16. The analyte sensing device of claim 15 wherein the analyte is glucose.

17. The analyte sensing device of claim 15 wherein the housing includes a first portion that is permeable to the analyte.

18. The analyte sensing device of claim 17 wherein the first portion of the housing is a membrane.

19. The analyte sensing device of claim 18 wherein the membrane is cellulose acetate and/or polysulphone.

20. The analyte sensing device of claim 15 wherein the first layer further includes at least one extra-matrix space disposed between the matrix and the housing.

21. The analyte sensing device of claim 15 wherein the housing further includes a reflecting portion disposed distal to a path of optical radiation that is incident on the second layer.

22. The analyte sensing device of claim 15 further including a second layer having at least one optical property that is responsive to the concentration of analyte in communication therewith, the second 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.

23. The analyte sensing device of claim 15 wherein the first layer further includes a plurality of nanoparticles which are attached to a plurality of the first analyte binding receptor molecules.

24. The analyte sensing device of claim 15 wherein the first layer further includes a plurality of nanoparticles which are attached to a plurality of the first analyte equivalent residues.

25. The analyte sensing device of claim 15 wherein the first layer further includes a plurality of nanoparticles which are attached to a plurality of the first analyte binding receptor molecules and a plurality of the first analyte equivalent residues.

26. An analyte sensing system for sensing a concentration of analyte in a fluid, the analyte sensing system comprising:

a first device including;

a first layer having a first optical property that is responsive to the concentration of analyte in communication therewith wherein the first optical property is a scattering of optical radiation incident on the first layer, the first 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

a second device including a first layer having at least one optical property that includes a predetermined response to the concentration of analyte in communication therewith.

27. The analyte sensing system of claim 26 wherein the analyte is glucose.

28. The analyte sensing system of claim 26 wherein the first layer of the first device further includes at least one extra-matrix space disposed adjacent to the matrix.

29. The analyte sensing system of claim 26 wherein the first device further includes a housing having a reflecting portion disposed distal to a path of optical radiation that is incident on the first layer of the first device.

30. The analyte sensing system of claim 26 wherein the second device further includes a housing having a reflecting portion disposed distal to a path of optical radiation that is incident on the first layer of the second device.

31. The analyte sensing system of claim 26 wherein the at least one optical property of the first layer of the second device provides a reference signal.

32. The analyte sensing system of claim 26 wherein the at least one optical property of the first layer of the second device includes a predetermined response to the concentration of analyte in communication therewith over a first range of concentrations of analyte.

33. The analyte sensing system of claim 26 wherein the first layer of the first device further includes a plurality of nanoparticles that are attached to a plurality of the first analyte binding receptor molecules.

34. The analyte sensing system of claim 26 wherein the first layer of the first device further includes a plurality of nanoparticles that are attached to a plurality of the first analyte equivalent residues.

35. A method to detect the concentration of an analyte in a fluid using an analyte sensing device comprising (1) a first layer disposed within a housing, wherein the first layer exhibits at least one optical property that is responsive to the concentration of analyte in communication therewith, the first 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, and (2) a second layer, disposed in the housing, having at least one optical property that is insensitive to the concentration of analyte in communication therewith, the method comprising:

placing the 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 (i) the responsive optical radiation to measure a change in scattering of optical radiation by the first layer and (ii) a response to the optical radiation by the second layer; and

outputting data which is representative of the concentration of analyte.

36. The method of claim 35 further including analyzing the responsive optical radiation to detect fluorescence which depends at least partially on analyte-dependent optical properties.

37. The method of claim 35 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.

38. The method of claim 35 further including analyzing the responsive optical radiation to determine a change in scattering of optical radiation by the first 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.

39. The method of claim 35 wherein analyzing the responsive optical radiation to measure a change in scattering of optical radiation by the first layer includes measuring the transmission of optical radiation incident on the first layer to determine the scattering of optical radiation incident on the first layer.

40. The method of claim 35 further including measuring the at least one optical property of the second layer.

41. The method of claim 40 wherein the at least one optical property of the second layer provides a reference signal.