Internal biochemical sensing device

• US 20030171666A1
• Filed: 10/02/2002
• Published: 09/11/2003
• Est. Priority Date: 10/02/2001
• Status: Active Grant

• Current Assignee: University of Southern California
• Original Assignee: Alfred E MANN Institute For Biomedical Engineering At The University of Southern California
• Inventors: Loeb, Gerald E., George, Thomas
• Granted Patent: US 7,096,053 B2
• Time in Patent Office: Days
• US Class Current: 600/407
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: G01N 2021/6432 Quenching
• CPC Class Codes: G01N 2021/772 Tip coated light guide
• CPC Class Codes: G01N 2021/7723 Swelling part, also for adsorption sensor, i.e. without chemical reaction
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B

Abstract

A biosensing device for detecting biological analytes, and methods of use and manufacture, are disclosed. The device includes a biosensing element that can remain implanted for extended periods of time. The biosensing element is connected to an optical fiber terminating outside of the body. The optical fiber is also connected to an information analyzer. The information analyzer directs light through the optical fiber into the biosensing element. The light excites fluorophores, created by a chemical reaction between analytes and biosensing material within the biosensing element. Emitted fluorescent light is redirected through the optical fiber to the information analyzer. Optical gratings within the filtering member of the information analyzer selectively deflect fluorescent emissions into a cladding layer. Detectors attached to the cladding layer detect the deflected fluorescent emissions and, according to their determined wavelength, report the presence or quantity of specific analytes to the patient on an external display.

Claims

1. A compact and portable biosensing device for detecting an analyte from within a patient'"'"'s body, comprising:

a. a biosensing element including a biosensing material;

b. an elongated transmitting member having a first end and a second end, and being optically aligned with the biosensing element at the first end; and

c. a portable information analyzer connected to the second end of the elongated transmitting member and sized and configured to be easily carried by the patient.

2. The compact and portable biosensing device of claim 1 wherein the first end of the elongated transmitting member is connected to the biosensing element.

3. The compact and portable biosensing device of claim 1 wherein the biosensing material is enclosed within a containment matrix.

4. The compact and portable biosensing device of claim 3 wherein the containment matrix is connected to the first end of the elongated transmitting member.

5. The compact and portable biosensing device of claim 1 wherein the biosensing material forms a fluorescing molecule when it reacts with the analyte and wherein the portable information analyzer is configured to detect a fluorescent emission from fluorescing molecule when the fluorescing molecule is exposed to light.

6. The compact and portable biosensing device of claim 2 wherein the first end of the elongated transmitting member is connected to the biosensing element by a seal formed between the containment matrix and an outer surface of the first end of the elongated transmitting member.

7. The compact and portable biosensing device of claim 6 wherein the seal comprises an adhesive material.

8. The compact and portable biosensing device of claim 1 wherein the portable information analyzer comprises:

a. a connector adapted to receive the second end of the elongated transmitting member;

b. an elongated filtering member having a cladding layer extending substantially along its length and further having a first end connected to the connector and a second end connected to a light source;

c. the elongated filtering member further including a wavelength specific grating region configured to deflect light of the specific wavelength into the cladding layer; and

d. a processor operatively connected to the cladding layer for detecting the deflected light.

9. The compact and portable biosensing device of claim 8 wherein the connector causes the elongated transmitting member and the elongated filtering member to be optically coupled.

10. The compact and portable biosensing device of claim 9 wherein a photodiode is operatively connected between the cladding layer and the processor and is adjacent to the wavelength specific grating region.

11. The compact and portable biosensing device of claim 10 wherein the biosensing element is subjected to application of a condition selected from a group consisting of:

an electrical current, a potential change, a temperature change, and a bioactive chemical.

12. An information analyzer for sensing an analyte detected from within a patient'"'"'s body, comprising:

a. an elongated filtering member configured to propagate light and having a cladding layer along its length and having a first end and a second end;

b. the elongated filtering member further comprising a wavelength specific grating region configured to deflect a portion of the propagated light having the specific wavelength into the cladding layer;

c. a connector operatively connected to the first end of the elongated filtering member and adapted to receive an optical fiber and form an optical connection therewith;

d. a light source operatively connected to the second end of the elongated filtering member and configured to direct light therethrough; and

e. a processor operatively connected to the cladding layer for detecting the deflected light.

13. The information analyzer of claim 12 further comprising a photodiode operatively connected between the processor and the cladding layer and adjacent to the wavelength specific grating region.

14. The information analyzer of claim 12 further comprising a user interface operatively connected to the processor and including a display for conveying information to a user about the detected deflected light.

15. A method of using a compact and portable biosensing device, comprising:

a. inserting a biosensing element and a first end of an elongated transmitting member into a patient'"'"'s body such that the first end of the elongated transmitting member is optically aligned with the biosensing element, and a second end of the elongated transmitting member remains outside of the patient'"'"'s body;

b. optically coupling the second end of the elongated transmitting member to a portable information analyzer;

c. directing light from a light source through an elongated filtering member within the information analyzer and through the elongated transmitting member to the biosensing element;

d. directing fluorescent energy from the biosensing element and activated by the directed light through the elongated transmitting member and through at least a part of the elongated filtering member;

e. deflecting at least a portion of the fluorescent energy to a cladding layer adjacent to the elongated filtering member; and

f. detecting the deflected fluorescent energy.

16. The method of claim 15 wherein the biosensing element is subjected to application of a condition selected from a group consisting of:

an electrical current, a potential change, a temperature change, and a bioactive chemical.

17. The method of claim 15 wherein the biosensing element is connected to the first end of the elongated transmitting member.

18. The method of claim 15 wherein the deflecting is accomplished with a wavelength specific grating region within the elongated filtering member, and the deflected fluorescent energy has the specific wavelength.

19. The method of claim 18 further comprising:

a. deflecting an additional portion of the fluorescent energy to the cladding layer, suing a second wavelength specific grating region; and

b. detecting at least some of the additional deflected portion of the fluorescent energy.

20. The method of claim 15 wherein the detecting of the deflected fluorescent energy comprises:

a. directing the deflected fluorescent energy to a photodiode; and

b. detecting a signal produced by the photodiode.

21. The method of claim 15 further comprising displaying information about the deflected fluorescent energy to the patient.

22. The method of claim 15 wherein the biosensing element is inserted in a subcutaneous region of the patient'"'"'s body.

23. An adaptive system of biosensors for sensing a plurality of analytes, comprising:

a. a first biosensor device comprising a first biosensing element and a first elongated transmitting member;

b. a second biosensor device comprising second biosensing element and a second elongated transmitting member;

c. a first end of each of the first and second elongated transmitting members being optically connectable to a portable information analyzer;

d. wherein the first biosensing element contains a first biosensing material that is different from a second biosensing material contained within the second biosensing element, and the first and second biosensing materials react with different ones of the plurality of analytes.

24. The adaptive system of biosensors of claim 23 wherein the first biosensing element is connected to a second end of the first elongated transmitting member and the second biosensing element is connected to a second end of the second elongated transmitting member.

25. The adaptive system of biosensors of claim 23 wherein the portable information analyzer comprises an elongated filtering member and a detection mechanism;

wherein and the optical connection is formed between the second end of either the first or the second elongated transmitting member and the elongated filtering member; and

wherein the elongated filtering member includes at least a first wavelength specific grating region configured to deflect light of the first specific wavelength to the detection mechanism.

26. The adaptive system of biosensors of claim 25 wherein the elongated filtering member includes a second wavelength specific grating region configured to deflect light of the second specific wavelength to the detection mechanism;

and

wherein a reaction between a first one of the plurality of analytes and the first biosensing material produces a molecule that fluoresces at the first specific wavelength and a reaction between a second one of the plurality of analytes and the second biosensing material produces a molecule that fluoresces at the second specific wavelength.

27. A method of manufacturing a compact and portable biosensing device, comprising:

a. encapsulating a biosensing material within a region substantially adjacent to a first end of an elongated transmitting member by attaching a containment matrix to the first end of the elongated transmitting member such that it surrounds the biosensing material;

b. providing a connector that will align a second end of the elongated transmitting member with a first end of an elongated filtering member such that they are optically connected;

c. creating a wavelength specific optical grating in a portion of the elongated filtering member; and

d. connecting a light detector to the elongated filtering member adjacent to the wavelength specific optical grating.

28. The method of claim 27 wherein the elongated filtering member comprises a silicon optical fiber and wherein the wavelength specific optical grating is created by performing the steps of:

a. replacing a portion of the silicon with germanium; and

b. exposing the silicon optical fiber to illumination containing an optical pattern.

29. The method of claim 27 wherein the wavelength specific optical grating is a first wavelength specific optical grating and the light detector is a first light detector, the method further comprising:

a. creating a second wavelength specific optical grating in a different portion of the elongated filtering member that does not include the first wavelength specific optical grating; and

b. connecting a second light detector to the elongated filtering member adjacent to the second wavelength specific optical grating.

30. The method of claim 27 wherein the light detector is a photodiode.

31. The method of claim 27 wherein the light detector is connected to a cladding layer that extends substantially along the outer surface of the wavelength specific optical grating portion of the filtering member.

32. A compact and portable biosensing device for detecting an analyte from within a patient'"'"'s body, comprising:

a. a biosensing element for implantation in a patient'"'"'s body including one or more biosensing materials for selective interaction with an analyte, wherein the binding of the analyte to the biosensing material results in a detectable state change within the biosensing element;

b. a transmitting member having a first end and a second end and a transmitting member outer surface, and the first end being implanted within a patient'"'"'s body and in proximity with the biosensing element; and

c. an information analyzer connected to the second end of the transmitting member configured for location outside the patient'"'"'s body.

33. The device of claim 32, wherein at least a portion of the transmitting member outer surface includes coating layer including materials selected from the group of:

proteins and silanes.

34. The device of claim 32, wherein the biosensing element comprises a biosensing material immobilized on a polymer matrix.

35. The device of claim 32, wherein the biosensing element comprises mammalian cells expressing at least one analyte-specific biosensing material.

36. The device of claim 35, wherein the mammalian cells include an expression vector for expressing reporter molecules, and wherein the biosensing material is a transcription factor for the vector.

37. The device of claim 35, wherein the biosensing material is a transmembrane receptor and wherein binding of the analyte to the transmembrane receptor alters the membrane permeability of the mammalian cells resulting in a state change detectable by the information analyzer.

38. The device of claim 35, wherein the biosensing material is an antibody coupled to a fluorescent dye and wherein binding of the analyte to the antibody changes the intensity of fluorescence of the fluorescent, the intensity change being detectable by the information analyzer.

39. The device of claim 32 wherein the biosensor element further includes a containment matrix around at least a portion of the biosensing material, and wherein the containment matrix is permeable to the analyte.

40. A compact and portable biosensing device for detecting an analyte from within a patient'"'"'s body, comprising:

a. a biosensing element for implantation in a patient'"'"'s body including one or more biosensing materials for selective interaction with an analyte, wherein the binding of the analyte to the biosensing material results in a detectable state change within the biosensing element, and wherein the biosensing material is enclosed in a containment matrix permeable to the analyte;

b. a transmitting member having a first end and a second end and a transmitting member outer surface, wherein at least a portion of the transmitting member outer surface is coated to promote cell adhesion, and the first end being implanted within a patient'"'"'s body and in contact with the biosensing element; and

c. an information analyzer connected to the second end of the transmitting member configured for location outside the patient'"'"'s body.

41. The method of manufacturing a component for use in a biosensing device for detecting one or more analytes, including:

a. providing a transmitting member having a first end and a second end, the second end being configured for operably coupling to an information analyzer;

b. applying a biosensing element having one or more biosensing materials to the transmitting member first end; and

c. applying a containment matrix to the transmitting member first end wherein the containment matrix substantially surrounds the biosensing materials and wherein the containment matrix is permeable to an analyte to be detected.

42. The method of claim 41, further comprising immobilizing the biosensing materials on a hydrogel polymer.

43. The method of claim 41, further comprising expressing biosensing materials in mammalian cells.

44. The method of claim 41 wherein the transmitting member comprises at least a capillary tube having a lumen and an optical fiber, and wherein the biosensing materials are applied to the transmitting member first end by injection of the biosensing materials to a capillary tube first and through the lumen to the capillary tube second end.

45. The method of claim 41, further comprising applying a containment matrix to the transmitting member first end by vapor deposition.

46. The method of claim 45, wherein the containment matrix comprises a xylylene polymer.

47. The method of claim 41, further including applying a coating to the transmitting member outer surface.