Method and compositions for manufacture of chemical sensors

• US 5,326,585 A
• Filed: 08/17/1993
• Issued: 07/05/1994
• Est. Priority Date: 04/27/1992
• Status: Expired due to Fees

• Current Assignee: Puritan Bennett Corp. (Medtronic Plc)
• Original Assignee: Puritan Bennett Corp. (Medtronic Plc)
• Inventors: Soikowski, Carmen L., Nelson, Alan M.
• Primary Examiner(s): Beck, Shrive
• Assistant Examiner(s): Dudash, Diana L.
• Application Number:
  US08/108,108
• Time in Patent Office: 322 Days
• Field of Search: 427/2, 427/163, 427/407.2, 427/379, 427/293, 356/39, 436/68, 436/167, 436/172, 65/3, 65/11, 385/128, 385/145, 422/82, 422/82.05, 422/82.06, 422/82.07, 422/82.08, 422/82.09, 422/58
• US Class Current: 427/163.2
• CPC Class Codes: G01N 2021/773 Porous polymer jacket; Polymer matrix with indicator
• CPC Class Codes: G01N 2021/7786 Fluorescence
• 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

The method for making an optical fiber microsensor involves applying an uncured analyte sensing matrix to an optical fiber and crosslinking the sensing matrix in situ on the optical fiber to yield an ion permeable microsensor which can be used intravascularly to monitor pH, or partial pressures of oxygen or carbon dioxide in blood. The liquid form of the sensing matrix contains a crosslinking agent and a crosslinking inhibitor which can be removed by exposure to elevated temperatures to allow the sensing matrix to crosslink and cure as desired, in situ, on the surface of the optical fiber. A liquid crosslinking overcoat layer containing a crosslinking agent and a crosslinking inhibitor which can be removed by exposure to heat can also be applied over the cured sensing matrix.

Claims

1. A method of making an analyte sensor including an optical fiber having a surface portion covered with a polymeric analyte sensing matrix including a dye indicator material, comprising the steps of:

preparing an analyte permeable polymer with an analyte sensitive indicator dye covalently bonded to the analyte permeable polymer to form a liquid polymeric analyte sensing matrix;

forming a liquid mixture of said liquid polymeric analyte sensing matrix with a crosslinking agent and a crosslinking inhibitor which can be removed by exposure to heat;

coating said optical fiber surface portion with said liquid mixture; and

heating said liquid mixture on said optical fiber surface portion for a sufficient period of time to remove said crosslinking inhibitor from said liquid mixture, whereby said crosslinking agent crosslinks said liquid polymeric analyte sensing matrix in situ on said optical fiber surface portion thereby producing a cured sensing matrix.

2. The method of claim 1, wherein said crosslinking agent comprises a blocked polyether isocyanate incorporating said crosslinking inhibitor selected from the group consisting of ethanol, o-nitrophenol, resorcinol, benzenethiol, acetyl acetone, 2-methyl-2-propanol, p-chlorophenol, phloroglucinol, ethyl acetoacetate, acetone oxime, methyl ethyl ketone oxime, m-cresol, guaiacol, 1-dodecanthiol, diethyl malonate, diphenyl amine, phenol caprolactam, 2, 4-diisobutylphenol, monomethylaniline, and isoocytylphenol.

3. The method of claim 2, wherein said crosslinking inhibitor is acetone oxime.

4. The method of claim 2, wherein said liquid polymeric analyte sensing matrix comprises a copolymer of hydroxyethyl methacrylate and N-(3-aminopropyl) methacrylate hydrochloride.

5. The method of claim 4, wherein said dye indicator material comprises 8-hydroxy-1, 3, 6 pyrenetrisulfonic acid.

6. The method of claim 1, wherein said liquid polymeric analyte sensing matrix comprises a crosslinkable vinyl terminated organosiloxane, said crosslinking agent comprises a catalyst and said crosslinking inhibitor comprises a vinyl terminated dimethylsiloxane.

7. The method of claim 6, wherein said crosslinking inhibitor has the chemical structure ##STR4##

8. The method of claim 6, wherein said crosslinking inhibitor is divinyl tetramethyldisiloxane.

9. The method of claim 6, wherein said dye indicator material is selected from the group consisting of fluorescein and 8-hydroxy-1, 3, 6 pyrenetrisulfonic acid.

10. The method of claim 9, wherein said dye indicator material is covalently bonded with a copolymer selected from the group consisting of acrylamide, hydroxyethyl methacrylate, and a copolymer of hydroxyethyl methacrylate and N-(3-aminopropyl) methacrylate hydrochloride.

11. The method of claim 6, wherein said dye indicator material is selected from the group consisting of coronene and decacyclene, and a combination thereof.

12. The method of claim 9, wherein said liquid polymeric analyte sensing matrix comprises methylhydrodimethylsiloxane copolymer.

13. The method of claim 6, wherein said dye indicator material comprises a polynuclear aromatic dye covalently linked to the organosiloxane copolymer.

14. The method of claim 1, wherein said liquid mixture on said optical fiber surface portion is heated to a temperature exceeding the boiling point or temperature of decomposition of said crosslinking inhibitor.

15. The method of claim 1, wherein said liquid mixture on said optical fiber surface portion is exposed to a temperature of from about 140°

to about 240°

C. for approximately 10-60 seconds.

16. The method of claim 1, wherein said liquid mixture on said optical fiber surface portion is exposed to a temperature of about 220°

C. for approximately 15 seconds.

17. The method of claim 1, wherein said liquid mixture on said optical fiber surface portion is exposed to a temperature of about 175°

for approximately 20 seconds.

18. The method of claim 1, further including the step of applying a layer of an uncured overcoat mixture comprising a second crosslinking agent and a second crosslinking inhibitor which can be removed by exposure to elevated temperature over said liquid polymeric analyte sensing matrix following said step of heating said liquid mixture;

and

heating said uncured overcoat mixture on said optical fiber surface portion for a sufficient period of time to remove said second crosslinking inhibitor from said uncured overcoat mixture, whereby said second crosslinking agent crosslinks said overcoat mixture in situ over said cured sensing matrix.

19. The method of claim 18, wherein said overcoat mixture includes titanium dioxide.

20. The method of claim 18, wherein said overcoat second crosslinking agent comprises a blocked form of a polyether isocyanate incorporating said second crosslinking inhibitor, and said second crosslinking inhibitor is selected from the group consisting of ethanol, o-nitrophenol, resorcinol, benzenethiol, acetyl acetone, 2-methyl-2-propanol, p-chlorophenol, phloroglucinol, ethyl acetoacetate, acetone oxime, m-cresol, guaiacol, 1-dodecanthiol, diethyl malonate, diphenyl amine, phenol caprolactam, 2,4-diisobutylphenol, monomethylaniline, and isooctylphenol.

21. The method of claim 18, wherein said overcoat second crosslinking inhibitor comprises acetone oxime.

22. The method of claim 18, wherein said overcoat second crosslinking agent comprises a crosslinkable vinyl terminated organosiloxane and a catalyst, and said second crosslinking inhibitor comprises a vinyl terminated dimethylsiloxane.

23. The method of claim 22, wherein said second crosslinking inhibitor has the chemical structure ##STR5##

24. The method of claim 22, wherein said second crosslinking inhibitor is divinyl tetramethyldisiloxane.

25. The method of claim 22, wherein said overcoat mixture comprises methylhydrodimethylsiloxane copolymer.

26. The method of claim 18, wherein said uncured overcoat mixture on said cured sensing matrix is heated to a temperature exceeding the boiling point or temperature of decomposition of said second crosslinking inhibitor.

27. The method of claim 18, wherein said uncured overcoat mixture on said cured sensing matrix is exposed to a temperature of from about 140°

to about 220°

C.

28. The method of claim 18, wherein said uncured overcoat mixture on said cured sensing matrix is exposed to a temperature of from about 140°

to about 220°

C. for approximately 10 to 60 seconds.

29. The method of claim 18, wherein said uncured overcoat mixture on said cured sensing matrix is exposed to a temperature of about 175°

for approximately 30 seconds.

30. The method of claim 1, further including the step of priming said optical fiber surface portion by applying a silanizing agent selected from the group consisting of isocyanatopropyltriethoxysilane and vinyltriethoxysilane to said optical fiber surface portion prior to said step of coating said optical fiber surface portion with said liquid mixture.