Fiber-optic physiological probes

• US 4,925,268 A
• Filed: 07/25/1988
• Issued: 05/15/1990
• Est. Priority Date: 07/25/1988
• Status: Expired due to Term

• Current Assignee: Hospira Incorporated (Pfizer Inc.)
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Iyer, Lokanathan M., Lyon, Kenneth S., Yim, Jeffrey B.
• Primary Examiner(s): Sikes, William L.
• Assistant Examiner(s): Ullah, Akm E.
• Application Number:
  US07/224,620
• Time in Patent Office: 659 Days
• Field of Search: 350/96.15, 350/96.29, 350/96.30, 350/96.31, 350/96.34, 128/634
• US Class Current: 385/12
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: G01N 2021/0385 Diffusing membrane; Semipermeable membrane
• CPC Class Codes: G01N 2021/6434 Optrodes
• CPC Class Codes: G01N 2021/772 Tip coated light guide
• CPC Class Codes: G01N 2021/7786 Fluorescence
• 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 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
• CPC Class Codes: G01N 21/783 for analysing gases
• CPC Class Codes: G01N 21/80 Indicating pH value
• CPC Class Codes: G01N 21/8507 Probe photometers, i.e. with optical measuring part dipped into fluid sample

Abstract

Fiber-optic sensors suitable for monitoring physiological analyte concentration. An analyte-permeable matrix is disposed in the light path defined by the axial core at one end of an optical fiber segment. The matrix contains an indicator molecule covalently linked to a polymer, preferably methyl methacrylate/methacrylamidopropyltrimethylammonium chloride, N-vinylpyrrolidone/p-aminostyrene, methyl methacrylate/hydroxymethyl methacrylate, methyl methacrylate/N-vinylpyrrolidone, or methyl methacrylate/acrylic acid. In representative embodiments, the polymer is approximately 94:6 mole/mole percent of either methyl methacrylate/methacrylamidopropyltrimethylammonium chloride or N-vinylpyrrolidone/p-aminostyrene copolymer. Drift-free performance is obtained with such sensors having analyte-permeable matrices of significantly less than about 70 microns in thickness. The indicator molecule may be covalently linked to the polymer through an aminoarylalkylamine, such as 4-(aminophenyl)-ethylamine or 4-(aminophenyl)-propylamine.

Claims

1. A fiber-optic sensor suitable for monitoring physiological analyte concentration, comprising an analyte-permeable matrix disposed in the light path defined by the axial core at one end of an optical fiber segment the analyte-permeable matrix comprising an indicator molecule covalently linked to a polymer, the indicator molecule capable of responding to the analyte in an optically detectable manner, and the polymer selected from the group consisting of methyl methacrylate/methacrylamidopropyltrimethylammonium chloride, N-vinylpyrrolidone/p-aminostyrene, methyl methacrylate/hydroxymethyl methacrylate, methyl methacrylate/N-vinylpyrrolidone, and methyl methacrylate/acrylic acid.

2. The fiber-optic sensor of claim 1, wherein the polymer is formulated in the range of from about 60:

40 to about 80;

20 wt/wt percent.

3. The fiber-optic sensor of claim 1, wherein the polymer comprises approximately 94:

6 mole/mole percent of either methyl methacrylate/methacrylamidopropyltrimethylammonium chloride or N-vinylpyrrolidone/p-aminostyrene copolymer.

4. The fiber-optic sensor of claim 1, wherein the analyte-permeable matrix has a thickness of less than about 70 microns.

5. The fiber-optic sensor of claim 1, wherein the optical fiber segment has a diameter of approximately 250 microns or less.

6. The fiber-optic sensor of claim 1, wherein the indicator molecule is covalently linked to the polymer through an aminoarylalkylamine.

7. The fiber-optic sensor of claim 6, wherein the aminoarylalkylamine is selected from the group consisting of 4-(aminophenyl)-ethylamine and 4-(aminophenyl)-propylamine.

8. The fiber-optic sensor of claim 7, wherein the indicator molecule is covalently linked to the polymer through 4-(aminophenyl)-ethylamine.

9. The fiber-optic sensor of claim 1, wherein the indicator molecule is an absorptive molecule.

10. The fiber-optic sensor of claim 9, wherein the analyte is hydrogen ion.

11. The fiber-optic sensor of claim 10, wherein the indicator molecule is selected from the group consisting of phenol red and carboxynaphthophthalein.

12. The fiber-optic sensor of claim 11, wherein the indicator molecule is covalently linked to the polymer through either an azo-amide or an amidyl-amide linkage.

13. The fiber-optic sensor of claim 1, wherein the indicator molecule is a luminescent molecule.

14. The fiber-optic sensor of claim 13, wherein the analyte is hydrogen ion.

15. The fiber-optic sensor of claim 14, wherein the indicator molecule comprises carboxynaphthofluorescein.

16. The fiber-optic sensor of claim 13, wherein the analyte is oxygen.

17. The fiber-optic sensor of claim 1, further comprising reflector means disposed in the light path distal with respect to the optical fiber segment to the analyte-permeable matrix.

18. The fiber-optic sensor of claim 17, wherein the reflector means comprises gold foil.

19. The fiber-optic sensor of claim 17, wherein the reflector means comprises one or more of the group consisting of titanium dioxide, zinc oxide, and barium sulfate.

20. The fiber-optic sensor of claim 17, wherein the reflector means is impermeable to the analyte.

21. The fiber-optic sensor of claim 20, wherein the analyte-permeable membrane has a thickness of from about 15 to about 30 μ

m.

22. The fiber-optic sensor of claim 1, further comprising a gas-permeable but ion-impermeable membrane encapsulating the analyte-permeable matrix, the analyte-permeable matrix comprising a base having a pKa ranging from about 6.0 to about 7.8.

23. The fiber-optic sensor of claim 22, wherein the base has a pKa ranging from about 7.0 to about 7.4.

24. The fiber-optic sensor of claim 22, wherein the gas-permeable but ion-impermeable membrane comprises a resin selected from the group consisting of silicones, polycarbonates, and urethanes.

25. The fiber-optic sensor of claim 22, wherein the base comprises an inorganic salt and wherein the analyte-permeable matrix further comprises an antioxidant.

27. The fiber-optic sensor of claim 25, wherein the antioxidant comprises 1,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzene.

28. The fiber-optic sensor of claim 22, wherein the base comprises a polymeric base.

29. The fiber-optic sensor of claim 28, wherein the polymeric base is selected from the group consisting of monomers, homopolymers, and copolymers of 2-vinylpyridine, 4-vinylpyridine, 1-vinylimidazole, and 4-vinylimidizole.

30. The fiber-optic sensor of claim 28, wherein the polymeric base is covalently linked to the analyte-permeable matrix.

31. The fiber-optic sensor of claim 30, wherein the polymeric base is selected from one or more of the group consisting of 2-vinylpyridine, 4-vinylpyridine, histamine, 1-vinylimidazole, and 4-vinylimadazole.

32. The fiber-optic sensor of claim 22, wherein the analyte-permeable matrix comprises one or more of the group consisting of poly-N-vinylpyrrolidone, polyethylene glycol, and polyethylene oxide.

33. The fiber-optic sensor of claim 22, wherein the analyte-permeable matrix comprises approximately 80:

20 wt/wt percent [(methyl methacrylate/methacrylamidopropyltrimethylammonium chloride) 94;

6/polyethylene glycol 600K].

34. A disposable sensor suitable for monitoring physiological analyte concentration, comprising the fiber-optic sensor of claim 1 in a sterile packet.

35. A multi-variable probe, comprising a plurality of fiber-optic sensors according to claims 1, 10, 14, 16, or 22, the analyte-permeable matrices of said sensors being disposed in substantially coterminal array.

36. The multi-variable probe of claim 35, further comprising a thermocouple wire.

37. The multi-variable probe of claim 35, comprising a pCO₂ sensor according to claim 22 disposed distally to pH and pO₂ sensors in substantially colinear array, the pH sensor according to claims 10 or 14, and the pO₂ sensor comprising an oxygen-permeable matrix disposed in the light path defined by the axial core at one end of an optical fiber segment, the matrix comprising a luminescent indicator molecule admixed with or covalently linked to a polymer, the indicator molecule capable of responding to oxygen in an optically detectable manner.

26. The fiber-optic sensor of claim 26, wherein the inorganic salt comprises a bicarbonate.