Fiber optic sensor for in vivo measurement of nitric oxide

• US 5,582,170 A
• Filed: 12/01/1994
• Issued: 12/10/1996
• Est. Priority Date: 12/01/1994
• Status: Expired due to Fees

• Current Assignee: University Of Massachusetts
• Original Assignee: University Of Massachusetts
• Inventors: Soller, Babs R.
• Primary Examiner(s): Sykes, Angela D.
• Assistant Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US08/347,875
• Time in Patent Office: 740 Days
• Field of Search: 128/634, 385/12, 356/39, 250/458.1, 422/82.05, 422/82.09, 436/68, 436/116, 436/118
• US Class Current: 600/322
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: G01N 2021/7706 Reagent provision
• 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 fiber optic sensor for measurement of in vivo nitric oxide concentrations in a subject. The sensor contains a nitric oxide-sensing compound in a polymer matrix attached to an optical fiber. The sensor may be placed in any blood vessel, including one within the heart of a subject for continuous measurement of nitric oxide concentrations in blood.

Claims

1. A device for measuring an in vivo amount of nitric oxide, comprising:

a nitric oxide-sensing compound; and

an optical system comprising optical fibers arranged to deliver light to and collect light from said nitric oxide-sensing compound;

wherein said nitric oxide-sensing compound reacts with nitric oxide in vivo to induce a change in an optical property of said nitric oxide-sensing compound by an amount proportional to the in vivo amount of said nitric oxide.

2. The device of claim 1, wherein said nitric oxide-sensing compound is a metal-containing compound.

3. The device of claim 2, wherein said metal-containing compound contains iron, manganese, cobalt, platinum, osmium, or ruthenium.

4. The device of claim 1, wherein said nitric oxide-sensing compound is oxyhemoglobin.

5. The device of claim 1, wherein said nitric oxide-sensing compound is cytochrome c.

6. The device of claim 1, wherein said nitric oxide-sensing compound is hemin.

7. The device of claim 1, wherein said nitric oxide-sensing compound is myoglobin.

8. The device of claim 1, wherein said device further comprises a light source for delivering light through said optical system to said nitric oxide-sensing compound, and a light detector for generating an electrical signal in response to light which passes through said nitric oxide-sensing compound or is emitted from said nitric oxide-sensing compound.

9. The device of claim 8, further comprising a processor for analyzing the electrical signal to determine the in vivo amount of nitric oxide.

10. The device of claim 1, wherein said optical system comprises a first optical fiber for delivering radiation to said nitric oxide-sensing compound, and a second optical fiber for collecting radiation which passes through said nitric oxide-sensing compound.

11. The device of claim 10, wherein said second optical fiber contains first and second portions which are separated to form an opening.

12. The device of claim 11, wherein said nitric oxide-sensing compound is disposed in said opening.

13. The device of claim 10, wherein said first and second optical fibers each comprise distal ends, said distal ends each comprising an angled surface coated with a reflecting material.

14. The device of claim 13, wherein said first and second fibers are positioned so that light exits said distal end of said first optical fiber and enters said distal end of said second optical fiber.

15. The device of claim 1, wherein said device further comprises a housing which can be inserted into an artery of a living subject for in vivo measurement of nitric oxide.

16. The device of claim 1, wherein said nitric oxide-sensing compound is embedded in a polymeric material.

17. The device of claim 16, wherein said polymeric material is a fluorinated polymeric material permeable to nitric oxide.

18. The device of claim 1, wherein said device detects nitric oxide in vivo in the range of 0.001 μ

M to 10.0 μ

M.

19. A method of measuring an in vivo amount of nitric oxide in a subject, comprising calibrating the device of claim 1 with known concentrations of nitric oxide to generate a calibration equation, placing the device in a blood vessel of the subject, delivering light to the device, detecting light transmitted through the nitric oxide-sensing compound to generate an electrical signal, and processing the electrical signal with the calibration equation to calculate an in vivo amount of nitric oxide.

20. A device for measuring an in vivo amount of nitric oxide, comprising:

a housing;

a first optical fiber partially contained within said housing, said first optical fiber having distal and proximal ends, wherein said distal end of said first optical fiber comprises an angled surface comprising a reflective coating for delivering light;

a second optical fiber partially contained within said housing and positioned adjacent to said first optical fiber, said second optical fiber comprising an opening and having distal and proximal ends, wherein said distal end of said second optical fiber comprises an angled surface comprising a reflective coating for receiving light from said first optical fiber; and

a nitric oxide-sensing compound, embedded in a polymer matrix in said opening of said second fiber, and positioned to receive light reflected by the reflective coating on the distal end of the second optical fiber.

21. The device of claim 20, wherein said first fiber comprises an opening containing a reference compound comprising a polymeric material.

22. The device of claim 21, wherein said polymeric material is light transparent.

23. The device of claim 21, wherein said polymeric material emits light.

24. A method for determining an in vivo amount of nitric oxide, comprising:

inducing a change in an optical property of a nitric oxide-sensing compound with in vivo nitric oxide; and

detecting the change in the optical property to determine the in vivo amount of nitric oxide.

25. The method of claim 24, wherein said inducing step comprises delivering light to the nitric oxide-sensing compound;

and said detecting step comprises collecting a portion of light that passes through the nitric oxide-sensing compound and analyzing the collected portion of light to determine the in vivo amount of nitric oxide.

26. The method of claim 24, wherein the inducing step includes inducing a change in the absorption spectrum of the nitric oxide-sensing compound.

27. The method of claim 26, wherein the change in the absorption spectrum is related to the in vivo amount of nitric oxide.