CA2131379A1

CA2131379A1 - Cross-linked gas-permeable membrane of a cured perfluorinated urethane polymer, and optical gas sensors fabricated therewith

Info

Publication number: CA2131379A1
Application number: CA002131379A
Authority: CA
Inventors: Alan Olstein
Original assignee: Individual
Current assignee: Optical Sensors Inc
Priority date: 1992-03-09
Filing date: 1993-02-26
Publication date: 1993-09-16
Also published as: EP0630469A4; JPH07507136A; AU3783193A; AU669515B2; WO1993018391A1; US5453248A; US5631340A; EP0630469A1

Abstract

An optical sensor (11) is provided for measuring dissolved gases such as O2 or CO2 in a fluid sample. The sensor (11) is formulated so as to contain a gas permeable membrane (17) of a cured perfluorinated urethane polymer and, incorporated therein, a gas-sensitive indicator component (22). Methods for making and using the membrane (17) and sensor (11) are provided as well.

Description

W093/1~91 ~ ~ 3 L 3 7 ~ PCT/US93/01827 CROSS-LI~XED GAS-PERMEA~LF MENBRANE OF A CURED
PERFLUORI~ATED URETHA~E POLYMER. AND OPTICAL
GAS SENSORS ~ABRICA~ED THEREWITH

Cross-Reference to Related AP~1~CatiOn ~0 This application is a continu~tion-in-part of V.S. Patent Application Serial No. 0~/848,627, filed March 9, 1992.

~echnical Field The present invention relates generally to optical sensors for measuring dissclved gases in a fluid, and more particularly relates to a novel optical sensor - sy~tem cont~ining a gas perm~able membrane of a cured perfluorinated urethane polyr.er.

Backarsund Y
Chemical sensors are generally ~nown for use in ~ wide variety of areas such as medicine, scientific rese~rch, indus$rial applications and the like. Fiber optic and electrochemical approaches are generally known for use in ~ituations where it is desired to detect and/or measure th~ concentration of a parameter at a remote location without requiring electrical communi-cation with the remote location. Structures, properties, functions and operational details of fiber optic chemical sensors can be found in United States Patent No.
4,577,109 to ~irschfeld, U.S. Patent No. ~,~85,814 to Xane, and U.S. Patent No. 4,842,783 t~ ~laylock, as well as Seitz, "Chemical Sensors Based on Fiber optics,"
AnalYtical Chemistrv, Vol. 56, No. l, January 1984, each of which is incorporated by reference herein.

WO g3/183gl PCr/USg3/01827 ~ 7 9 -2-Publications such as these generally illustrate that i~ $t known to incorporate a chemical sensor into fiber optic wavequide, an electrochemical qas sensor or the like, in a manner such that the chemical sensor will interact with the analyte. ~his interaction results in a change in opt$cal pr~perties, which change ~ probed and detected throuqb the fiber optic w~veguide or the like.
Tbese optical properties of chemical sensor compositions typically involve change~ in colors or in color intensit~e~. In these types of systems, it is possible to detect particularly minute changes in the parameter or parameter~ being monitored in order to tbereby provide especially ~ensitive remote monitoring capabilities.
Chemical sensor composition~ that are incorporated at the distal end of fiber optic sensors are often configured as membrane~ that are secured at the distal tip end of the waveguide device or optrode.
Cas sensor~ o~ this general type are usefu~ in monitoring qas concentrations such as oxygen and carbon dioxide in bloodstreams and tbe like. Also, it i~
~ometimes desirable to provide sensors that monitor other parameters such as pH. Ion concentrations can also be detected, such as potassium, sodium, calcium and metal ion~.
A typical ~as sensor device positions thè
sensor material at a generally distal lccation with the assistance of ~arious different support means. Support means must be such as to permit interaction between the gas indicator and the substance being subjected to monitoring, measurement and/or detection. Known approaches in this regard include the use of permeable membranes and composites incorporating micro-encapsu-lation. With certain arrangements, it is desirable to incorporate membrane components into these types of devices. These membrane components must possess certain WO93/1~91 ~1 ~13 7 9 PCT/US93/01827 properties in order to be particularly advantageous.
Many membr~ne ~terials have some ~dvant~geous properties but a1RO have shortcominqs. Generally speaking, the materi~ls must be biocompatible, they must be permeable to the gas being monitored, and they must be capable of supporting the qas-sensitive indicator, wbile at the same time possessing the strength adeguate to permit maneuvering of the dev~ce without concern about damage to the ga~ sensor. It is also desirable to have these material~ be photocurable in order to facilitate locating the ga~ sensor composite on the devlce.
In sum~ary, the present invention is addressed to novel polymer composit~ons which have been found to be particularly ~uit~ble for use as membrane~ and membrane-like components which incorporate gas-censitive indicators to form the active qas sensor component of a qa~ ~ensor device. The polymer compo~ition~ are ~
particularly useful in fiber optic sensors for measuring di~solved qases, particularly 2 or CO2, in a fluid. The polymer composit~ons are cured perfluorinated urethane polymers formed by cross-linking a perfluorinated urethane precursor using a suitable cross-linking agent.
Relat~ve to previously known and used qas sensors, the present polymer compositions provide for gas ~ensors of superior sensitivity, resolution, solvent resistance ~nd photostability. ~n addition, qas sensors fabricated with the p~esent polymer comp~sitions displ~y increased resistance to fluid flow and shear, because of increased ~dhesion of the polymer c~mposition to the fiber substrate. Also, the polymer compositions described herein generally require a lower level of cross-linking agent, ~nd will typically contain very little or no residual monomer after cure. ~inally, the present polymer compositions have been found to increase the life of the gas sensor by eight- to ten-fold.

~ 3 7 9 PCT/US93/01827 Overview of Related Art The following references relate to one or more aspects of the present inventlon:
U.S. Patent No. 3,671,497 to Low et al.
describes a polyurethane resin derived from a hydroxy-ter,minated perfluoroether.
U.S. P~tent No. 4,549,012 to Sharma describes perfluoroacyl modified cellulose ~cetate polymers which ~re stated to be useful in formin~ thin gas-permeable membrane~.
U.S. Patent No. 4,~85,814 to Kane describes an optical probe useful for measurinq pH and oxygen and blood. The device includes ~ membrane constructed of hydrophilic porous material containing a p~-sensitive dye.
U.S. ~atent No. 4,842,783 to 81aylock describes a fiber optic chemical sensor which, at the distal çnd of the optical fiber, is provided with a photocrosslinked polymeric gel havinq ~ dye adsorbed therein.
V.S. Patent No. 4,935,480 to Zdrahala et al.
relates to fluorinated polyether urethanes,and ~edical devices (e.q., catheters) fabricated therefrom.
U.S. Patent No. 5,032,666 shows a thermoplastic fluorinated polyurethaneurea having free amino groups, and disclose~ the use of 5UC~ polymers in forming ~, ~ntithrombo~enic urfaces in medical de~ices.
PCT Publication No. W088/05533, inventors Klainer et ~1., describes a fiber optic sensing de~ice for measur~ng a chemical or physiological parameter of a body fluid or tissue, in which a polymer containing photoactive m~ieties is directly bound to the fiber optic tip.
European Patent Publication No. 224,201, inventors Caporiccio et al., describes a process for conversion of high molecular weight perfluoropolyether~

W093/1~91 ~i 3 1 3 7 9 PCT/US93/01827 to provide lower molecular weight, neutral perfluoropolyetber~.
European Patent ~ublication No. 322,624, inventor~ 8irkie et al., describes per~luorinated polyether~ useful ~n electrical applications.
V.X. Patent Application No. 2,132,348 to Bacon et al. describes an oxy~en sensor $n which the ga~
sen~it~ve indicator component is a luminescent organomet~lllc complex.
H.J. Hageman et al., "Photoinitiators and Photocatalysts for Various Polymerisation and Cros~link~ng P~oce~es," in R~diation Curin~ of Polvmers ~1, ed. D.R. R~nd-ll (The Royal Society o~ Chemistry, 1991), at pp. 46-53, identify a nu~er of materials which will act to catalyze radiation curing of multifunctional monomer~ or oligomer~.

~mary o~ the Invention Accordi~gly, it is a prir.ary object of the invent~on to address the above-mentioned needs in the art, by providing an optical sensor for measuring dissolved gases in a fluid, wherein the sensor has improved sensitivity, resolution, solvent resistance, photostability, and resistance to shear.
It i~ anotber object of the invention to ~ddress these needs by providing an optical gas sensor which includes a membrane of a cured perfluorinated urethane polymer ~nd a gas-sensiti~e indicator component.
It is still another object of the invention to provide such a sensor in which the prefluorinated urethane polymer comprises a perfluorinated polyurethane ~crylate.
It is yet another object of the invention to provide a gas permeable mem~rane for use in such a sensor, which comprises a polymeric matrix of a cured W093/1~91 ~ i3~ PCT/US93/01827 perfluorinated urethane polymer, and, incorporated therein, ~ qas-sensitive indicator component.
It is ~ further ob~ect of the invention to provide such a membrane in which the pesfluorinated urethane polymer comprises a perfluorinated polyuretbane acrylat~.
It is still a further ob~ect of the invention to provido ~ method of making an optical ga~ sensor by polymerizinq ~ precursor to a perfluorinated urethane poly~er on a fiber optic tip.
~ t is yet a further o~ect of the invention to provid~ ~ method of ~aking an optical gas ensor by polymerizing a photocurabl~ polymeric precursor on a fiber optic tip by irradiating the precursor through tbe fiber.
Additional ob~ects, advantages and novel feature~ of the invention will be set forth in par~ in th~ description which follows, ~nd in part will become apparent to those skilled in the art upon examination of the following, or ~ay be learned by practice of the invention.
In one aspect, a cross-linked gas permeable membrane useful in optical gas sensors is provided, wherein the membrane comprises a polymeric matrix of a cured perfluorinated urethane polymer, and, incorporated therein, a gas-sensitive indicator component as will be described in detail herein. In a preferred embodiment, the perfluorinated urethane polymer is a perfluorinated polyurethane acrylate which comprises a perfluorinated polyurethane acrylate precursor cross-linked with cross-linking agent.
In another aspect, an optical sensor is provided for ~easuring dissolved gases such as 2 or C02, which comprises an optical waveguide having ~ distal end portion for monitoring a gas component wit~in a fluid, ~" , 7 g WO93/1~g1 PCT/US93/01827 e.g., ~ bloodstream or the like, and a proximal end portion for com~unication with means for receiving a signal from the distal end portion, and wherein the dist~l end portion has a gas sens~r means comprising a S cross-linked gas permeable membrane as ~ummarized above and a~ will be ~escribed in detail below.
In ~t~ll anotber aspect, a method is proviaed for ma~ing the aforementioned optical ~ensor. In ~
pr-ferred embodi~ent, the method involves polymerization of ~ photocurable polymeric precuxsor on the fiber optic tip, by irradiating the precursor-coated tip through the opt~o~l f~ber. ~n another embodiment, polymerization of perfluorinated urethane polymer precursor may be effected by contac$~ng the precursor-coated tip with a cro~-linkinq agent in solution or the like.
In yet another aspect, a cured perfluorinated urcthane polymer i~ provided which is useful in the abo~e-mentioned contexts.

~x~ef Descriptlon of the Drawinas In the course of this description, reference will be made to the attached drawings, wherein:
Figure l is a generally schematic view of a chemical sensor de~ice according to the present invention whic~ is incorporated in a fiber optic gas sensor device;
Figure 2 is ~n enlarged, detail and generally schematic view of the distal end portion of a qas sensor device generally in accordance with Figure l ~nd incorporating a monolithic cross-linked fluorocarbon po~ymer ~ccording to the present invention; and Figure 3 is a view similar to Figure 2 but illustrating a composite membrane arranqement.

WO 93/18391 PCI'/USg3/01827 ~31~7g -8-Detailed Description of the Invention Before the present compositions, membranes, sensors and methods of manufactur~ are disclosea and described, it is to be understood tbat thi~ invention i~
not limited to specific sensor formats, spec$fic membrane composition~, or particular cross-linking agents or curing processes, as such may, of course, vary. It is ~l~o to be under~tood that the terminology used herein i~
~or th~ purpose of describing p~rticular embodiments only and i~ not intended to be limiting.
It must be noted that, as used in the ~pecification and the appended claim~, the ~ingular form~
~a,~ nan~ and "the" include plural referents unless the context clearly dictates otherwi~e. Thus, for example, ~5 re~erence to ~a pesfluorinated ureth~ne poly~er" includes mixturcs of such polymers, reference to "a perfluorinated urethane polymer precursor" include~ mixtures of t~o or mor~ ~uch polymer~, reference to "a cross-linking agent"
include~ reference to two or more cross-linking agent~, and tbe like.
In describing and cl~iming the present invention, the following terminology will be used in accordance with the definitions set out below.
The term ~polymer" as used herein is intended to include both oligomeric and polymeric materials, i.e., compounds which include two or more monomeric units.
Similarly, the term "perfluorinated polyether" linkage is intended to mean a linkage containing at least two perfluorinated ether mer units, i.e., ether mer units in which each hydrogen atom normally present has been replaced by a fluorine atom.
The term "urethane" is used herein in its conventional sense to denote organic compounds containing a recurring -0-(C0)-~H-linkage. The term "urethane acrylat~ polymer" is intended to mean a urethane polymer WO93/18391 ~1 3 1 3 i 9 PCT/US93/01827 _g_ derived fro~ polymeriz~tion of a urethane oligomer having acrylate termini -O-(C0)-CH-CH2.
The term "precursor" is used herein to mean a c~mpound which when polymerized and/or cross-linked will S give rise to a desired poly~er. For example, the term ~perfluorinatcd urethan~ polymer precursor" denotes a compound which when treated with, for exampls, moisture, radiation, cross-link~ng agents, or combinations thereof, will qive rise to the desirea "perfluorinated uretbane 0 polymer" a8 will be described in qreater detail bclow.
In describing chemical compounds herein, the term nlower alkyl" is used in its conventional sense to mean an alkyl group of l to 6 carbon atoms, e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, and the like. "Lower alkylene" refers to a difunctional saturated branched or unbranched hydrocarbon chain contalning from l to 6 carbon atoms, and includes, for example, methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2-CH2-CH2-), and the like. The term ~alkylarylene" refers to ~ difunctional hydrocarbon mo~ety containing l or 2 monocyclic aromatic moieties, either unsubstituted phenyl rings or containing one to four cubstituents such as lower alkyl, halo~en, nitro, or the like. "Alkylarylene" linking groups may also contain 2S lower alkylene spacers adjacent the aromatic ring~, in which some or all of the hydro~en atoms normally present may be replaced with fluorine atoms.
The polymeric compositions which are used to formulate the gas permeable membrane of the invention are cured pérfluorinated urethane polymers; the membrane itself comprises a matrix of such a polymer and, incorporated in the matrix, a gas-sensitive indicator.
The cured perfluorinated urethane polymers are typically perfluorinated urethane polymer precursors cross-linked W093/18391 PCT/US93/Ot827 7 ~ -lo-with a cross-linking agent. Generally, sucb precursors have the structur~l formul~

OCN-As-~lH- O-X~ NH~-A~-NCO

wherein Ar is a monocyclic aromat~c moiety and X is a p-rfluorinated polyether linXage containing approximately 2 to 100, preferably 10 to 50, mo~t preferably 15 to 25, recurring perfluorinated mer units having the structure ~CF20t~ ~CF2cF20t~ or combinations thereof. Preferably, Ar ls pbenyl, either unsubstituted or substituted with one to four substituents wh~ch ar~ selectea so ~s not to interfere with polymerization or use of the cured iolymer ~n the gas sensor such substituents include, for example, lower alkyl (Cl-C6), halogen, nitro, and the like.
The precursor of Formula (I) may be cross-linked using water or an organic diol HO-R-OH wherein R
is a hydrocarbon substituent of about 2 to 20 carbon atoms, and in wh~ch some or ~11 of the hydrogen atoms normally present have been replaced with fluorine atoms.
Preferably, R is an alkylene linking group, i.e., an alky~ene linking group containing from a~out 1 to 6 carbon atoms, or an alkylarylene linking group containing one or~two monocyclic ~romatic moietieC and, depending on the number of aromatic moieties, two or three lower alkylene spacer qroups, again, in whi~h some or all of the hydrogen at~ms normally present have been replaced with fluorine atoms. Exemplary organic diols include bisphenol A ~nd hexafluorobisphenol A.

~ ~t~.J~ fr,~S~r~ ,r~ L~ r~ J~rJ~ ~,~r.rs WO93/1~91 ~ 3 7 9 PCT/US93/01827 ~ n a preferred embodiment, the precursor of Formula (I) is convertcd to a perfluorin~ted urethane acrylate precursor prior to curing, by replacing the terminal isocyanate moieties -N-C~0 with acrylate termin~
S -N~-COO-(CH2)n-(CO)-CH-CH2 wbere n is typically in the range o~ l to about 6. This may be effected by reacting the d~isocyanate precursor (I) with, for example, hydroxymethylmethacrylate (in whicb case n is l), hydroxyethylmethacrylate (in whicb case n is 2), or tbe like. The perfluorinated urethane acrylate precursor so pro~id-d, h~vinq the structural formula ~ C O (CH2kO-C-~H-A~-NH C-0-X-C-~1H-A~-N1H-C-0-(CH2)-0-C

- (II) may then be cured in the presence of a suitable photoinitiator or photocatalyst using radiation. In a ~ariation on this embodiment, the diisocyanate-terminated precursor of Formula (I) may be reacted with virtually any compound having a hydroxy terminus and a vinyl terminus, typically containing about 2 to lO carbon atomg, to provide a ~inyl-terminated precursor and to enable cross-linking.
Suitable photoinitiators for carrying out the cross-linking in the aforementioned case, i~e., to cure the perfluorinated urethane acrylate precursor of Formula (II), are radical photoinitiators that are well-known to those skilled in the art. Examples of such photoinitiators include ~-alkoxy deoxybenzoins, ~ dialkoxy deoxybenzoins, ~ dialkoxy acetophenones, 3S benzophenones, thioxanthones, benzils, and other W093/1~91 ~;13 i ~ 7 9 PCT/US93/01827 compounds identified by H.J. Hageman et al., ~Photoinitiators and P~otocatalysts for Various Polymerisation and CrosslinXing Processes," in Radiation Curina of Polymers II, ed. D.R. Randell ~The Royal Society of Chemistry, l99l), at pp. 46-53, cited supra.
The disclosure of the aforementioned reference is incorporatea by reference herein.
In another embodi~ent, the diisocyanate-terminated precursor of Formula (I) ~s converted to an epoxy-terminatea precur~or having the formula ~ CH2~ O~ C~ O-X-C-~'H-A~-~H-C-O-(CH2) (III) whereln Ar, X, and n are as defined a~ove. This conversion may be readily effected by reaction of the precur~or of Formul~ ~I) with two equivalents of compound having the structural formula ~(CH2)~0H

2~ ~i.e., glycidol when n is l). This epoxy-terminated compound ~ay then be cured with radiation in the presence of a cationic photoinitiator, e.g., a sulfonium salt, an organometallic complex such as that manufactured under the name Irgacure~ by Ciba-Geigy Corporation, or the like.
One of the advantages of fabricating optical gas ~ensors with the aforementioned polymer compositions ~s t~at relatively low levels of cross-linking agent are required. Conventional systems typically require a very high le~ l of cross-linking agent, on the order of W093/1~91 ~i 3 7 3 PCT/USg3/01827 20 wt.% of the total polymeric composition. The present perfluorinated urethanes, however, typically reguire only ~bout 0.5 to 5 wt.% cross-linking agent, more typic~lly about 0.5 to 1 wt.~, to provide dimens~onal stability.
S In formulating the gas permeable ~embrane, it i~ preferred tbat tbe above-described cross-linking re~ction occur ~n th~ presence of the qas-sensitiv~
indicator component which will then be incorporated into th~ poly~eric ~trix which serves as the membrane. the gas-sensitive indic~tor will generally be physically entrapped within the polymeric matrix, but it may also be covalently bound thereto. The gas-sensitive indicator is typic~lly an inorganic complex which is a luminescent matcrial gu-nchable by the oxygen, carbon dioxide, or the l~ke, i.e., the dissolved gas which is undergoing measurement. Examples of suitable gas-sensit~ve indicators useful for 2 determination may be four.d in V.X. ~atent No. 2,132,348, cited supra, and include complexe~ of rutheniu~ (I~), osmium (II), iridium (III), rhodium, rhenium, ~nd chromium (III) with 2,2'-bipyridine, l,lO-phenantbroline, 4,7-diphenyl~l,lO-phenanthroline), 4,7-dimethyl-l,lO-phenanthroline, 4,7-disulfon~ted--diphenyl-l,lO-phenanthroline, 2,2'-bi-2-thiazoline, 2,2'-bithiazole, 5-bromo-l,lO-phenanthroline, 25- and 5-chloro-l,lO-phenanthroline, and complexes of VO (II), Cu (II), plat~num (II), and zinc (~I) with porphin etioporphorin tetraphenylporphyrin, mesoporphyrin IX dimet~ylester, protoporphyrin IX dimethylester and octaethylporphyrin. Preferred gas-sensitive indicators for fabricating oxygen sensors are ruthenium complexes.
For C02 sensors, virtually any pH-sensitive fluorescent or ~bsorbent dye can be usedl although preferred indicators include fluorescein and fluorescein derivatives such as carboxyfluorescein, seminaph-thorhodafluor, ~eminaphthofluorescein, naphtho-WO93/1~91 ~ PCT/US93/01827 fluorescein, hydroxypyrene trisulfonic ~cid, dichlorofluorescein, and t~e like.
The cross-linking reactions which give rise to tbe gas permeable membrane are preferably carried out on the fiber substrate. ln a preferred embodiment, tbe precur~or i~ pbotocurable and is cros~-linked on the fiber ~ubstr~te using radiation transmitted through the fiber. Alternatively, tbe membrane may be prepared ~eparately and deposited on the surface of the optical fiber; in ~uch instances, it i~ typically necess~ry to prime tbe Siber ~urface prior to deposition of the sensing membrane thereonto. An example of ~ suit~ble qlass primer i~ ~-meth~cryloxypropyl trimethoxysilane.
Alternativ-ly, the distal tip of the fiber may be dippea ~nto ~ ~olution of the precursor and the gAs-sensitive indicator and taking suit~ble 6teps to cure and cross-link the ~olution. Once cured, the gas sensor thu~
for~-d i~ cleaned of residual unreacted monomer by rinsinq with a ~olvent such ~s acetone. The present invention, however, minimize~ the potenti~l for unre~cted monomer and rinsinq may be a superfluous step.
The polymer composition--i.e., the cross-linked perfluorinated urethane polymer--will typically represent on the order of 80 to 99 wt.% of the ~as permeable membrane, more typically 95 to 99 wt.% of the mem~rane.
- Any photoinitiator used will be present at customary catalytic levels, typically substantially below 1 wt.% of the membrane. Gas-sensitive indicator will generally represent on the order of 0.05 to ~.0 wt.% of the ~embrane.
Figure 1 shows a typical fiber optic gas sensor arr~ngement. The illustrated device 11 includes a liqht source 12 for directing probe radiation into the device, ~ well a~ a light detector 13 for sensing and detecting radiation from the device. Device 11 includes one or W093/18391 ~ 3 t ~ 7 9 PCT/US93/01827 more optical ~ibers 14 that are joined to light source 123 and to light detector 13 throuqh a suitable junction assembly 15 at a location which is proximal of the distal end portion 16 of the optical fiber 14. As is generally known, eacb optical fiber 14 includes a core surrounded ~y a cladding or cover~ng.
Distal end portion 16 has a distal tip ~7 which is a membrane of ~ cross-linked perfluorinated urethane polymer m~trix, and, incorporated therein, a gas-sensitive indicator as described above. ~he gas-sensitive indicator enables the matrix to underqo a known ch~nge ~n color, color intensity or other property, which change is observed by the light detector 13 in a manner ~enerally known in.the art.
With the embodiment illustrated in Figure 3, a di~tal end portion 16' has a distal tip 17'. ~he tip 17' is ~ composite membrane suitable for multifunctiona~
monitoring, such ~s for monitoring pH conditions or the like and gas concentrations. Microparticles 21 of a polymer matrix comprising a perfluorinated urethane polymer and ~ gas-sensitive indicator are included within the composite membrane at the distal tip 17'. Also included ~re other indicator components 22 such as fluorescent pH indicators. Both the ~as sensor microparticles 21 and the other indicators 22 are -encapsulated within a known type of ~as and ion permea~le hydrophilic polymer 23 which provide needed support for the microparticles therewithin.
As noted earlier, the primary utility of the present invention is in the detection and measurement of dissol~ed gases such as 2 and C02 in the bloodstream.
However, the membrane and sensor of the invention may also be used in a variety of other coptexts, e.g., for on-line sensing in a flowing fluid stream.
- ---_____-________________ W093/1~91 PCT/US93/01827 ~ i3 i3 7 ~ -16- ~
It is to be understood tbat while the invention has been described in conjunction with preferred specific embodiments thereof, the foregoinq description, as well ~s the examples whicb follow, are intended to illustrate ~nd not limit the scope of the invention. Other aspects, advantages and modif~cations within th~ scope of the invention will be apparent to those skilled in the ~rt to which the invention pertains.

Exam~le 1 ~ he ob~ective of thig example was to prepare radiation curable fluoropolyurethane for fabricat~ng ~n H20 and H~ impermeable membrane with good elastomeric propertie~. A difunctional, isocyanate-terminated fluorinated polyether having an equivalent weight of approxim~tely 1500 ~Fluorolink B, obtaineB from Ausi~ont, Morri~town, New Jersey) was used as the polymeric precur~or. The reactions which were carr~ed out (1) replaced the diisocyanate termini of the precur~or with acrylate moieties, thereby providing a photocurable compound, and (2) cured this latter 2crylate-terminated compound, as follows.
Five g of Fluorolink B was weighed out and 0.43 g dry hydroxymethacrylate (HENA) (obtained from 25- Aldrich Chemical, Milwaukee WI) was added over a 4-A
molecular ~ieve. The reaction was permitted to proceed at room temperature uncataly2ed. After 1 hour, no apparent exotherm occurred. ~he reaction was incubated at approximately 20C for 18 hours. At that time, it was found that the preparation had not cured; accordingly, 5 yl dibutyltin laurate (o~tained from Air Products and Chemicals under the name ~-12) catalyst was added, and the preparation bubbled slightly.
~he acrylate urethane was found to be soluble in Freon 113 trichlorotri~luoroethane; 5 ~1 of the WO93t18391 ~ 1 3 1 3 7 9 PCT/US93/01827 cationic photoinitiator Irgacure 500 ~Ciba-Geigy) wa~
added, and the polymer solution was thus cured under a stream of N2. The ~tructure of the polymer was verified using infrared spectroscopy.

ExamDle 2 ~ he objective of th~s example was to prepare an 2 ~ensor by dissolving an 02-sensitive indicator in ~
cros~-linkable, curable polymer matrix that is permeable to 2 As in Example l, Fluorolink B was used as the precursor to the cured perfluorinated urethane acrylate polymer whicb ~erves as the primary component of the polymer matrix. In this example, cure was effected with moisture.
l.9 mg tris(diphenyl phenanthroline) Ru HCl2 (obtained from Florida International University) wa~
selected as the 2 ~ensitive indicator, dissolved in O.l ml CH2Cl2, and miscibilized in l.0 g of the perfluorinated prepolymer Fluorolink B. ~he sensor (Ensign Bickford glass-on-glass, llO ~, numerical ~perture 0.39) was dipped in the polymer/qas indicator preparation and cured at ~0C in a humidified forced air oven for 18 hours.
The following day the sens~r was tested in a 39C tcnometer using 100% He and 100% 2 The siqnal ~alues at 70% lamp intensi~y were 6000 at 100% He and 200 at 100% 2 Therefore, there is greater than a 90% loss of signal at ~60 mm 2 Also, no substantial "burn-in' effect was observed.

WO93/1~91 PCT/US93/01827 ExamDle 3 In thi~ example, an 2 sensor wa8 prepared using the radiation-curable perfluorinated polyurethane acrylate, as follows.
1.5 mg tri~(diphenyl phenanthroline) Ru HCl2 was dissolved in O.l ~l CN2Cl2 and m~scibilized in l.5 g of tbe uncured polymer prepared in Exampl~ l. 90 mg Irqacure- 500 wa~ added and ~ cleaned ll0 ~ EB
connector~zed fiber was dipped in th~ solution to coat the dist~l end. ~he fiber wa~ placed in ~ test tube under argon and exposed to an external ~ource of ultraviolet radiation ~3.4 mW) to cur~ for 60 seconds.
The fiber was coupled to an OSR-l (Optical Sensor~ Consultant~, Inc., San Carlos CA) ana the distal lS end placed in a tonometer at 37-C. Under 100% Ar sparge, a 603 n~ emi~sion w~s observed (~500 Cp5) ~ under l00~ 2 sparge, signal los~ was greater than about 90% ~with ob~erved value ~t approximately 250 cps). Response time was very rapid, less than about 30 seconds. Very little signal loss was observed over the 90 minute experiment.

ExamDle 4 2 sensors were prepared using different polymer~. In the following tables, the polyurethane/urea ~aterial was prepared as described in Example l, and tbe procedure of Example 2 was used to make the sensors, except for sensor nu~bers 7, 8 and 9 which were prepared using the procedure of Example 3. "S.V.k" represents the Stern-Vollmer constant; as may be seen from tbe S.V.k data, the polyurethane/urea-based sensor displays a sensitivity approximately two-fold greater tban that of the commercially available sensors.

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W093/l~gl `~ PCT/US93/01827 ~I ~i37~ -20-Exam~le 5 ~n opt~cal carbon dioxide sensor may be prcpared using the methods and materials of the invention, as follows:
S Three mg flu~rescein disodium s~lt (Aldrich) are di~solv-d in 0.01 M ~odium bicarbonate buffer containing 0.9% NaCl. ~his buffered fluorescein solution (0.15 g) i~ then dispersed and emulsified in a solution o~ 1.0 g perfluorinated polyurethane dimethacrylate ~80~ ~olid~, 20% ethyl acetate), and photocured on the di~tal end of ~ pretreated reactive fiber optic. The fiber optic carbon dioxide sensor so prepared has a 485 nm ~ign~l 4507, ~ 455 nm ciqnal 1237 ~ratio~3.64) ~ 1% C02; the sensor ha~ a 485 nm ~ignal 3772, and a 455 nm ~ign~l 1111 (ratio~3.39) ~ 10% C02. Carbon dioxide ~ensors ~ay be made to have enhanced ~ignal change by buffering in ~ medium closer to the pKa of the indicator, i.e., 6.8.

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Claims

Claims:

1. A cross-linked gas permeable membrane useful in optical gas sensors for measuring O2 or CO2 in a fluid, comprising a polymeric matrix of a cured perfluorinated urethane polymer, and, incorporated therein, a gas-sensitive indicator component.

2. The membrane of claim 1, wherein the cured perfluorinated urethane polymer comprises a perfluorinated urethane polymer precursor cross-linked with a cross-linking agent.

3. The membrane of claim 2, wherein the perfluorinated urethane polymer precursor has the structural formula (I) wherein Ar is a monocyclic aromatic moiety and X is a perfluorinated polyether linkage containing approximately 2 to 100 recurring perfluorinated mer units having the structure ?CF2O?, ?CF2CF2O?, or combinations thereof.

4. The membrane of claim 3, wherein the cross-linking agent is water.

5. The membrane of claim 3, wherein the cross-linking agent is a diol.

6. The membrane of claim 5, wherein the diol is selected from the group consisting of bisphenol A and hexafluorobisphenol A.

7. The membrane of claim 1, wherein the cured perfluorinated urethane polymer comprises a perfluorinated urethane polymer precursor having the structural formula (II) wherein Ar is a monocyclic aromatic moiety, X is a perfluorinated polyether linkage containing approximately 2 to 100 recurring perfluorinated mer units having the structure ?CF2O?, ?CF2CF2O?, or combinations thereof, and n is an integer in the range of 0 to 6 inclusive, wherein the precursor is cured with a photoinitiator in the presence of radiation.

8. The membrane of claim 1, wherein the cured perfluorinated urethane polymer comprises an epoxy-terminated precursor having the structural formula (III) wherein Ar is a monocyclic aromatic moiety, X is a perfluorinated polyether linkage containing approximately 2 to 100 recurring perfluorinated mer units having the structure ?CF2O?, ?CF2CF2O?, or combinations thereof, and n is an integer in the range of 0 to 6 inclusive, cured with a photoinitiator in the presence of radiation.

9. The membrane of claim 2, wherein the polymeric matrix comprises approximately 95 wt.% to 99.5 wt.% perfluorinated polyurethane acrylate precursor and approximately 0.5 wt.% to 5 wt.% cross-linking agent.

10. The membrane of claim 1, wherein the gas-sensitive indicator is selected from the group consisting of complexes of ruthenium (II), osmium (II), iridium (III), rhodium, rhenium, and chromium (III) with 2,2'-bipyridine, 1,10-phenanthroline, 4,7-diphenyl(1,10-phenanthroline), 4,7-dimethyl-1,10-phenanthroline, 4,7-disulfonated-diphenyl-1,10-phenanthroline, 2,2'-bi-2-thiazoline, 2,2'-bithiazole, 5-bromo-1,10-phenanthroline, and 5-chloro-1,10-phenanthroline, and complexes of VO (II), Cu (II), platinum (II), and zinc (II) with porphin etioporphorin tetraphenylporphyrin, mesoporphyrin IX dimethylester, protoporphyrin IX dimethylester and octaethylporphyrin.

11. The membrane of claim 1, wherein the gas-sensitive indicator is selected from the group consisting of fluorescein, carboxyfluorescein, seminaphthorhoda-fluor, seminaphthofluorescein, naphthofluorescein, hydroxypyrene trisulfonic acid and dichlorofluorescein.

12. The membrane of claim 10, wherein the gas-sensitive indicator is physically entrapped within the polymer matrix.

13. The membrane of claim 10, wherein the gas-sensitive indicator is covalently bound to the polymer matrix.

14. An optical gas sensor for measuring O2 or CO2 in a fluid, comprising:
an optical waveguide having a distal end portion for monitoring a gas component within a fluid, and a proximal end portion for communication with means for receiving a signal from the distal end portion, and wherein the distal end portion has a gas sensor means comprising a cross-linked gas permeable membrane comprising a polymeric matrix of a cured perfluorinated urethane polymer and, incorporated therein, a gas-sensitive indicator component.

15. The optical sensor of claim 14, wherein the cured perfluorinated polyurethane acrylate comprises a perfluorinated urethane polymer precursor cross-linked with a cross-linking agent.

16. The optical sensor of claim 15, wherein the perfluorinated urethane polymer precursor has the structural formula (I) wherein Ar is a monocyclic aromatic moiety, X is a perfluorinated polyether linkage containing approximately 2 to 100 recurring perfluorinated mer units having the structure ?CF2O?, ?CF2CF2O?, or combinations thereof, and n is an integer in the range of 0 to 6 inclusive.

17. The optical sensor of claim 16, wherein the cross-linking agent is water.

18. The optical sensor of claim 16, wherein the cross-linking agent is a diol.

19. The optical sensor of claim 18, wherein the diol is selected from the group consisting of bisphenol A or hexafluorobisphenol A.

20. The optical sensor of claim 15, wherein the cured perfluorinated urethane polymer comprises a perfluorinated urethane polymer precursor having the structural formula (II) wherein Ar is a monocyclic aromatic moiety and X is a perfluorinated polyether linkage containing approximately 2 to 100 recurring perfluorinated mer units having the structure ?CF2O?, ?CF2CF2O?, or combinations thereof, and n is an integer in the range of 0 to 6 inclusive, cured with a photoinitiator in the presence of radiation.

21. The optical sensor of claim 15, wherein the cured perfluorinated urethane polymer comprises an epoxy-terminated precursor having the structural formula (III) wherein Ar is a monocyclic aromatic moiety, X is a perfluorinated polyether linkage containing approximately 2 to 100 recurring perfluorinated mer units having the structure ?CF2O?, ?CF2CF2O?, or combinations thereof, and n is an integer in the range of 0 to 6 inclusive, cured with photoinitiator in the presence of radiation.

22. The optical sensor of claim 14, wherein the sensor is a O2 sensor and the gas-sensitive indicator is selected from the group consisting of complexes of ruthenium (II), osmium (II), iridium (III), rhodium, rhenium, and chromium (III) with 2,2'-bipyridine, 1,10-phenanthroline, 4,7-diphenyl(1,10-phenanthroline), 4,7-dimethyl-1,10-phenanthroline, 4,7-disulfonated-diphenyl-1,10-phenanthroline, 2,2'-bi-2-thiazoline, 2,2'-bithiazole, 5-bromo-1,10-phenanthroline, and 5-chloro-1,10-phenanthroline, and complexes of VO (II), Cu (II), platinum (II), and zinc (II) with porphin etioporphorin tetraphenylporphyrin, mesoporphyrin IX
dimethylester, protoporphyrin IX dimethylester and octaethylporphyrin.

23. The optical sensor of claim 14, wherein the sensor is a CO2 sensor and the gas-sensitive indicator is selected from the group consisting of fluorescein, carboxyfluorescein, seminaphthorhodafluor, seminaphthofluorescein, naphthofluorescein, hydroxypyrene trisulfonic acid and dichlorofluorescein.

24. A method for making an optical gas sensor for measuring O2 or CO2 in a fluid, comprising the steps of:
(a) providing an optical waveguide having a distal end portion for monitoring a gas component within a fluid, and a proximal end portion for communication with means for receiving a signal from said distal end portion;
(b) coating said distal end portion with a solution containing a photocurable polymeric precursor and a gas-sensitive indicator component; and (c) effecting cross-linking of the precursor by irradiating the distal end portion through the optical waveguide using radiation of a wavelength effective to cure the precursor.

25. A method for making an optical sensor for measuring O2 or CO2 in a fluid, comprising the steps of:
(a) providing an optical waveguide having a distal end portion for monitoring a gas component within a fluid, and a proximal end portion for communication with means for receiving a signal from said distal end portion;
(b) coating said distal end portion with a solution containing, a perfluorinated urethane polymer precursor and a gas-sensitive indicator component, to provide a precursor-coated tip; and (c) effecting cross-linking of said precursor, thereby providing at the distal end portion a gas sensor means comprising a cross-linked gas permeable membrane of a cured perfluorinated urethane polymer and, incorporated therein, the gas-sensitive indicator component.

26. The method of claim 25, wherein cross-linking is carried out by contacting the precursor-coated tip with a cross-linking agent.

27. The method of claim 25, wherein cross-linking is carried out by contacting the precursor-coated tip with a cross-linking agent in the presence of radiation.

28. The method of claim 25, wherein cross-linking is carried out by irradiating the distal end portion of the optical waveguide.

29. The method of claim 25, wherein the irradiating is effected through the optical waveguide.

30. A cured perfluorinated urethane polymer prepared by the process which comprises cross-linking a perfluorinated urethane polymer precursor having the structural formula (I) wherein Ar is a monocyclic aromatic moiety and X is a perfluorinated polyether linkage containing approximately 2 to 100 recurring perfluorinated mer units having the structure ?CF2O?, ?CF2CF2O?, or combinations thereof, with a cross-linking agent.

31. The cured perfluorinated urethane polymer of claim 30, wherein the cross-linking agent is water.

32. The cured perfluorinated urethane polymer of claim 30, wherein the cross-linking agent is a diol.

33. The cured perfluorinated urethane polymer of claim 32, wherein the cross-linking agent is selected from the group consisting of bisphenol A or hexafluoro bisphenol A.

34. A cured perfluorinated urethane polymer prepared by the process which comprises treating a perfluorinated urethane polymer precursor having the structural formula (II) wherein Ar is a monocyclic aromatic moiety, X is a perfluorinated polyether linkage containing approximately 2 to 100 recurring perfluorinated mer units having the structure ?CF2O?, ?CF2CF2O?, and n is an integer in the range of 0 to 6 inclusive, with radiation in the presence of a catalytic amount of a photoinitiator.

35. A cured perfluorinated urethane polymer prepared by the process which comprises treating a perfluorinated urethane polymer precursor having the structural formula (III) wherein Ar is a monocyclic aromatic moiety, X is a perfluorinated polyether linkage containing approximately 2 to 100 recurring perfluorinated mer units having the structure ?CF2O?, ?CF2CF2O?, or combinations thereof, and n is an integer in the range of 0 to 6 inclusive, with approximately two equivalents of a compound having the structural formula, followed by polymerization catalyzed by a cationic photoinitiator.