CA1203742A - Indicators for ethylene oxide - Google Patents

Abstract

INDICATORS FOR ETHYLENE OXIDE
ABSTRACT OF THE DISCLOSURE
A device for giving a visual indication of the amount of residual ethylene oxide present in ethylene oxide treated solid hospital articles and other health devices. The amount of residual ethylene oxide is indicated by the difference in color exhibited by different sensitized areas of the device in the form of an opaque dark colored support member having bonded to its surface a thin film of a cholesteric liquid crystal composition in a solid film-forming binder. The film is made by laying down on the surface of the support member a solution or dispersion of liquid crystals which exhibits a change in color when in contact with ethylene oxide at a temper-ature from 60° to 100°F in a solution of the solid binder, then evaporating the solvent. As prepared, the film is in a form adapted to be packaged with goods to be subjected to sterilization with ethylene oxide, a portion of the film being sealed within a transparent enclosure the walls of which possess a permeability to ethylene oxide no greater than that of the material of the treated goods.

Description

BACKGRC)UND OF TIIE INVENTION

lllis inventiorl relates to novel inclicator devices for det~rminin~3 the arnoullt o~ e~hylene oxi~e a~sorbed ~uring th~
ethylene oxide sterilization o~ hospital supplies and related health care materials. The invention is useful in determining when a level o ethylene oxicle is reached, upon aeration, which is no longer a health hazard should the sterili~ation items come into contact with the human body.
Items sterilized with ethylene oxide l~iocidal gas must be ploperly aera~ed so that the release cf residual gas during ]0 use of the treatecl item will not cause hemolysis, erythema, and edema o the tissues, or otllerwise harm the body. It i~ esti-mated that more than 10~00() ethylene oxide sterilization units are installed in U.S. hospitals~ Such sterilizers are normally operated at 50-60C and steam is introduced during the bio-cidal or sterilization cycle to provide the humidity requiredfor the process. 'I'his processing results in the breakdown ~f some of the ethylene oxide to give ethylene glycol and 2-chloro-et~,anol. The latter may be formed durincJ ethylene oxide steri-lization when there is a source of chloride as in polyvinyl chloride. Water may react with ethylene oxide to produce ethylene glycol duriny sterilization.
The Federal Kegister Vol.43,No.122,p.27482 contains rules (proposed by the Depclrtment of Health, Educa~ion, and Wel-fare) that devices contaetin~ blood or large implants shall not contain more than 25 parts per million oE ethylene oxide and devi(es contactit~ skin shall not cc-ntain more than 250 part~ per million oE ethylene oxi~e. The laboratory analysis fol- eti~ylelle oxide is complex, expensive, and time consuming.
There~ore, hospitals have relied on a~rating for excessively 3() lon(l ~rio(ls of ~:ime to ens~lre hclVinC~ reached a sa~e level of r(si(l~ yLene c>xide l~iocidaL (]lS Resulting time delays C--lnSf:' shor~ l(?ci of av(~ li)le materials Eor hospLtal oper~tions --2- ~

3~

excessive stockpiling of hospital items, and often the unknow-ing use o~ s~erilized items whicll contain concentrations of ethylene oxicle hazardous to health. There exist indicator strips or taqs which underc30 a permanent color change on exposure to ethylelle oxide. These, however, do not show the amount of effective exposure o~ the items being sterilized. No simple indicators are available which attest to the adequacy of the item~ being sterilized. No simple inclicators are available which attest to the adequacy of ethylene oxide exposure or which give the residual ethylene oxide remaining after exposure.
The Canadian Government has recogni~ed an urc3ent need for the type of device described in this invention and has granted approximat~ly 250 thousand dollars to support the development of the product of this invention.

THE STATE OF THE ART
Liquid crystals and their properties are well known and the many technical articles including review articles pub-lished provide general information on liquid crystals and their properties. See for example G~ H. srown and W. ~,. Shaw, Chemical Reviews, Vol. 57, No. 6, Dec. 1957, p.l,O49 titled "The Mesomorphic State -Liquid Crystals", Glenn H. Brvwn, Analytical Chemistry Vol. 41, No.13, November 1969, p.26A titled "Liquid Crystals and Some o~ Their Applications in Chemistry" and L. Melamed and D. R~lbin, Applied Optics, Vol. lO,NoO5, May 1971 p. 1103 titled "S~lecte~d Optical Properties of Mixtures of C'holesteric Liq-lid Crystals".
I.iquid crystallirle materials have properties inter-mecliate ~etween t~lose o~ a true liqllid and a true crystal, having both an ordered structure and fluidity. The structure of cholesteric materials is markedly different from that of other liquid crystal structures. 1'he differences of the chol-esteric structure include optical negativity compared with op-tical positivity of the other structLlres. The cholestericstructure is optically active arld shows a strong optical rota-tory power, and the cholesteric phase scatters white light selectively to give vivid colors. ~he cholesteric phase can selectively rotate circularly polarized light either clockwise or counterclockwise and the mean wave len~th of the reflection band from the cholesteric phase depends upon the angle of in-cidence of the beam.
The detection of ~3ases and other impurities by choles-teric liquicl crystals has been reported in the above references and in others. Fergason~ ~.S. Patent No.3,409,404 describes the use of cholesteric liquid crystal~ to iderltify unknown gases and other materials. No reference is made in published liter-ature to the identification of the quantity o~ ethylene oxide present in a material or as to the use of cholesteric liquid crystals an indicator system for ethylene c>xide sterilization, despite the urgent need for such an indicator as a means or insuring against health hazards caused by exposure to ethylene oxide. The technology as known will not of and by itself pro-vide the functions of the indicator device described in this invention. No prior art indicator is operable over the wide range of tem~eratures normally encounterecl in the hospitals.
Ferc~asorl clearly states that the cholesteric liquid crystals oF his invr?lltion are tem~erature sensitive and that analyses must t~e con~lLIc-e(l at a known calibrated temperature.

30 Such Lern~r r-atllre depe1-ldr?rlcy is a recogrli~ed characteristic o~
liq~li(l cr-ystaLs. A seconcl well known property oE cholesteric 3~

liquid crystals is the dependence of color response on the purity of liquid crystal or o a mixture of liquid crystals being used. Purification of the liquid crystals is both ~if-ficult and e~pensive. It is an important Eeature of the present invention that a high de~ree oE chemical puri-ty is not required for proper practice of this inventiorl. Cholesteric liquid crystals deteriorate on exposure to light, oxidation, and through contact with atmospheric impurities on aging. Such de-terioration changes the response to temperature and to exposùre to the agents whLch are being analyzed or assayed. Dixon et al. U.S. Patent No. 3,656,909 recognized these instabilities as a disadvantage of the above cited Fergason teaching and attempted to minimize the problem by addition of UV radiation stabilizers consisting of aroma-tic azo or aromatic azoxy com-pounds.
The effect of aging i~ minimized in the indicator of the present invention. The degradation products obtained during the sterilization cycle with ethylene oxide, eg ethylene glycol will remain after aeration, and act ~o change the color response of the liquid crystal syste~s kno~l in the art. The present invention compensates Eor the residual non-volatile materials remaining ~fter aeration. A color blind person could not distinc~uisil the color changes occuring in the cholesteric liquid crystal systems oE the prior art. In contrast, a person does not have to perceive color to use the indicator article of the present invention.

_r)--SUMMARY OF T~E INVEN~`ION
According to one aspect of the present invention there is provided an indicator assembly for providing a visual indication of relative eoneentra-tional levels of an alkylene oxide biocidal gas present in an artiele treated wi-th such a biocidal gas, said assembly comprising a sheet-like supporting substrate, a film-like coa-ti.ng carried by said substrate, said eoating ineluding a eholesterie liquid erystal eomposition res-ponsive to bioeidal gas reaeting therewith to undergo eolor ehange, as a fune-: 10 tion of bioeidal gas eoncentrations present, a transparent cover sheet overlying said coating, said eover sheet being permeable to permit transport of bioeidal gas therethrough, means defining a viewable reference zone of said coating, said ref-erenee zone being covered by and sealed to said cover sheet and separated thereby from an ambient system, said reference zone being distinc-t from a vis-ible comparison area of said coating, and said eomparison area being eovered by said eover sheet in a non-isolating manner to be direetly exposed to the same ambient system.
According to another aspect of the presen-t invention there is provi-ded the method of fabricating an indicating device for providing a visual rep-resentation of relative eoncentrational levels of an alkylene oxide biocidal gas present in an article treated with such a biocidal gas, said me-thod eom-prising -the steps of preparing a cholesteric liquid crystal, coating eomposition, applying said co-ating composition as a fluid film on a supporting substrate, evc~porating said solvent from said s~lbstrate at a temperature below about 250F to provide a coating bonded to said substrate, superimposin~ on at least a portion of said coatincJ a transparent cover sheet permeable to the biocidal gas ancl having a thic~ness correlateA

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with an effec-tive thickness oE an article to be permeated by the biocidal gas, bcnding said cover sheet to said coating to define a reference zone and a comparison area of said coating, said reference zone being in biocidal gas flow communication with an ambient system through said cover sheet, said comparison area being in direct communication with the ambient system, and said reference zone and said comparison area being viewable through said cover sheet superimposed thereon.
According to a further aspect of the present invention there is pro-vided the method for indicating the amount of residual alkylene oxide present in an alkylene oxide -treated article by using a gas indicating device having a gas-sensitive cholesteric liquid crystal composition applied as a coating on a supporting substrate/
a mechanically isola-ted zone of said coating being sealed from dir-ect exposure to an ambient system, and a transparent, gas-permeable cover sheet covering said isolated zone of said coating, and said zone being view-able through sai.d cover sheet, said method comprising the steps of exposing said indicating device to an alkylene oxide biocidal gas, diEfusing a biocidal gas through said cover sheet to contact said zone oE said coa-ting, visually noting any color change occurring in said zone, aerating said indicating device, and again visually noting any color change in said zone of said coating ana comparing the color of said zone wi.th that of an area exposed directly to the a~bient system, the steps of said method being carried out in the presence of an article whereby the gas indicating device and the article are simultaneously exposed to said s-teps.
~ ccording to another aspect of the present invention -there is provi-ded an indicator assembly for providing a visual indica-tor having two differ-ent visually di.scernihle degrees o:E sensitivity to alkylene oxide biocidal gas in effecti.ng color chanc3e as a function oE concentrations of alkylene oxide biocidal gas present, said assel~ly comprising -6a-a base subs-trate, a film-like coating applied -to said substrate, said coating including a cholesteric liquid crystal component res-ponsive to biocidal gas reacting therewith to undergo and to exhibit color chancle as a function of concentration of biocidal gas present, first and second laterally spaced demarked areal zones of said coat-ing exhibiting visual dis-tinguishable marginal contours, first and second cover sheets overlying respective said first and second zones and sealed to said film-like coating, said first and second cover sheets being characterized in that -they exhibit different degrees of permeability to biocidal gas upon exposure there-to, said zones undergoing color changes a-t different rates upon exposure of said zones to biocidal gas and upon removal of biocidal gas from said zones.
The present invention provides a practical, highly effective, inex-pensive and sensitive ethylene oxide indicating device which may be incorpora-ted into a package along with hospital or surgical goods to be sterilized by ethylene oxide treatment. Upon exposure of the treated article to aeration, by user, to eliminate retained or absorbed ethylene oxide before use on the body, the device of the inven-tion provides a rapid and sensitive indication oE
the effectiveness of the aeration. Specifically, the device undergoes a change in reflective color so that the exposed control and test areas of the device can be compared to determine when the amount of residual ethylene oxide in the sterilized items has reached a saEe reduced level.
In accordance with the invention the sensi-tized layer in the con-trol and test careas i9 a cho:Lesteric liquid crystal coating. No manipulation of the indicator device is required c~nd no technical 5kill is needed for its use.
Since the test area ancl the control go through the same aging processes, the same exposure to light, and -the same retention of the ethylene glycol and other degradation products of ethylene oxide cluring the s-terilization cycles, the resu]ts or efEects oE these factors or variables are co~pensated. Thus, -6h -the difEerential in color between the test and control areas is a representa-tion of the concentration of ethylene oxide in the tes-t area. Since the sen-sitized layer consisting of cholesteric liquid crystals is the same in the control and test areas, the ].iquid crystals do not have to be extremely pure to have the color differentials representative of the amount of retained e-thyl-ene oxide in the -6c-test section. Durin~ t:he aeration process, the control area loses its ethylene oxide rapidly to reach a near zero level of ethylene oxide while the test area representing the sterilized item will lose its ethylene oxide content at approximately the same rate as the sterili~ed item. The same device may be used to indicate the amount of ethylene oxide absorbed during the sterilization process. In thi~ case, the control area will rapidly reach saturation with ethylene oxide and the color formed compared to the test area will show how much ethylene oxide has been absorbed by the item being sterili~ed.

DESCRIPTION OF PREFERRED EMBODIMENT~
One embodiment of the invention comprises an opaque dark-colored support member having on its surface a thin coating or film consisting essentially of a choleskeric liquid crystal composition exhibi}ing a color change in reflective light when exposed to ethylene oxicle at a temperature from 60 to lOO~F, the liquid crystals being dispersed in a solid non-tacky film-formin~ binder. The coatinq or fil~ i5 formed by applying to the surface of the support member a solution o~ th~ binder in a liquid solvent. The solution also contains the desired liquid crystal composition which can be either dispersed in the form of small droplets as the inner or disperse phase of a two-phase system, or di,ssolved in the solvent along with the binder to form a single phase system. Th2 solvent is then eva-porate~ to provide a solid coatin~ o~ film bonded to the supportmember and in the form oF a sincJle or two-phase system corres-ponding to the phast?s of the liquid coatincJ composition.

~7--In one preferred embocliment a portion of the coating or film is sealed within an enclosure formed of plasticized polyvinyl chloride. Most hospital and surgical goods packaged for sterilization with ethylene oxide constitute textile fabrics, rubber or various syntlletic plastics compositions. It has been found that oE all these materials usually present in such pack-ages, items made of plasticized polyvinyl chloride retain ethyl-ene oxide most tenaclously. By providing a portion of the indi-cator coating or film sealed within an enclosure, the walls of which possess a permeability to ethylene oxide no greater than that of plasticized polyvinyl chloride, or in any event, no greater than that of whatever goods are present in the package, and by providing another portiun of tlle coating or film in the indicator device which is exposed to the atmosphere and from which residual ethylene oxide is consequen-tly eliminated very rapidly upon aeration, the indicator makes possible a direct color comparison of two adjacent zones of the same coating.
This technique automatically eliminates possible error~ caused by temperature differences betwe~n ~he indicator coating or film 20 ?~s~d a color sta!~dard used ~or com::p3rison, any ef ect of residual ethylene cllycol due to degradation ~f ethylene oxide, any dif-ferences in aginy between film in the indicator and in the color standard. Also minimized is ~he need for close quality control o~ separate coatings made ~rom di~erent batches of liquid Z5 crystals.
I'he support rnember may be any solid material either rigid or flexible which does not react chemically with the liquid crysta 1 50 as to interfere with its optical capabilities. The suE~port melllber also mu~t allow permeLltiorl of ethylene oxide at 3() a rate e(l~lal to or faster than the enclosure material. Sub--n--~3~

strates wi-th devices using polyvinyl chloride as the enclosure material may be, for example, unplasticized polyvinyl chloride, cardboard, polyethylene, polypropylene, etc., but not imper~ious materials such as slass, metals, or ceramics. It is preferred to use support members which are as thin as possible while still pro~iding the requisite strength.
The cholesteric liquid crystal composition employed can be any such material or mixture of materials which provides a visual indication, i.e., a reversible change in color by re-flective light when exposed to ethylene oxide. For best results,that is, Eor readily observable color changes throughout a tem-peratuve range, from ~0~ to 100F., it is preferred to employ a mixture of three different types of cholesteric liquid crystals.
The mixture includes 30% to 80% by weight of a cholesteryl ester of a fatty acid having from 6 to 20 carbon atoms, ~rom 5% to 40%
of a member selected from the group consisting of cholesteryl oleyl carbonate and cholesteryl 2-(2-alkoxyethoxy) ethyl car-bonates in which the alkoxy ~roup has from 1 to 4 carbon a-toms, and from 0.5% to ~0% of a member selected from the group con-sisting of cholesteryl benzoate, cholesteryl cinnamate, choles-teryl furfuryl carbonate, cholesteryl allyl carbona-te, choles-teryl bromide, cholesteryl nitrate, choles-teryl cinnamyl car bonate, and cholesteryl methallyl carbonate. In other composi-tions, a mixture containing two or more components from the same "group" may be used.
The minimum amoun-t and maximum amount of each af the three -types used varies dependlng upon -the identity of the member of each type which is used and can readily be determined by simple experiments. In general, the propor-tions of each lie within the limi-ts se-t for-th abo~e.

9_ AmoncJ cholesteryl esters of Eatty acids which can be used are cholesteryl hexanoate, cholesteryl octanoate, choles teryl nonanoate, cholesteryl clecanoate, cholesteryl dodecanoate, cholesteryl laurate, cholesteryl myristate, cholesteryl palmitate and cholesteryl oleate, of these the nonanoa-te is preferre~
for convenience and commercial availability. The mixed carbonate esters of the second type include cholesteryl 2 (2-methoxyethoxy) ethyl carbonate, cholesteryl 2-(2-ethoxyethoxy) ethyl carbonate,

2-(2 propoxyethoxy) ethyl carbonate and cholesteryl 2-(2-butoxy-ethoxy) ethyl carbonate~
The binder can be any non-tacky film-forming solid material preferably an organic polymer, which does not re~ct chemically with the cholesteric liquid crystal and does not interfere with its sensitivity to e~hylene oxide and which is lS soluble in a solvent which can be removed by evaporation at a temperature at which the binder and cholesteric liquid crystals are not substantially degraded or decomposed, i.e., at a ~emper-ature Up to about 250F. The binder serves to protect the liquid crystal from ~ir oxidation~ modifies the sensitivity range of the liquid crystal mixture and a.lso provides durability by preventing smearing or remo~al of the liquid crystal material if it is accidentally broucJht into contact with another surface.
The solvent is any liquid capable of dissolving the selected binder to form a solution containing at least 20% by weight of ~index and which does not react chemically with the binder or with the liquid crystal. In the preferred embodiment, the solvent is also capahle oE dissolving the cholesteric liquid crystal to rorm a solution containin(l at least 10~ by weight oE
liquid crystal, :itl which case the mixecl oslution is in t}le form o~ a sin~Jle ~l~ase system or lacquer.

.~ ~va~ a ~

A suitable birlder is any of a ~ide variety of synthetic p~astic materials inc]uding polyvinyl acetate, acetal homopoly-mers and copolymers, cellulose esters such as cellulose acetate or butyrate, polyester resins, acrylic resins including polymers and copolymers of acrylic and methacrylic esters, styrene polymer;
and copolymers, and the like. ~ variety of readily available liquid oryanic solvents boiling at temperatures up to 250F.can be used for the foregoing binders to form single-phase systems.
Typical solvents include any of the commonly us~d alcohols, ketones, esters, or hydrocarbons, either aromatic or aliphatic, most of which readily dissolve the cholesteric liquid crystal.
Evaporation of the solvent from such solutions leads to the formation of a solid single phase sys~em, i.e., a solution dis-persion.

It is also possible to employ, for certain binders, a liquid solvent which is incapable of dissolving the cholesteric liquid crystal, in which case the li9uid crystal is dispersed in the solution of ~inder to form a two-phase system or dis-persion in which the binder is in the con-tinuous phase and the liquid crystal is in the dispe~dor lnner phase. The most convenient and satisfactc)ry solvent for forming such two-pha~e systems is water. One may use with the water solvent a variety oE film Eorming non~tacky water-soluble binders such as polyvinyl alcohol, polyvinyl pyrrolidone, gelatin, starch, casein, poly-acrylic acid, and copolymers of styrene or ethylene with maleicanhydride wl~ich can be dissolved in water with the aid of ammonia.
Evaporatioll of water Erom such two-phase systems leads to the ~ormation oE ~ solid two-pln~se sy~;t~m in which the droplets of liquid crystal ~re clisperse(l thro~l<lllollt the mass of solid binder.

_ l ~

~2~'7~2 An alternative two-phase system may be prepared by dispersing microcapsules oE liquicl crystals obtained by common processes well known in the art in either a water or solvent base solution of the previously mentloned binders and forming a film which upon drying contains the microcapsules as one phase dispersed in a dry film of the binder as the second.
The ratio of cholesteric liquid crystal to binder can vary from l:lO to l:l by weight, althou~h a ratio in the range from l:4 to l:2 by weiclht is generally preferred. It has been found that in the case of both systems, the color intensity of the coating vr film increases in proportion to the amount of 1icluid crystal present. It has also been ound, surprisingly and quite unexpectedly, that the color change temperature range is higher for single-phase systems than for two-phase systems, ofering the advantage that coatings or films which are single-phase systems are less affected by temperature fluctuation with;n the 60 to 100F. range norma'Lly encountered during aera-tion of the package. Coatings or films having the single-phase system are more uniform, smoother ancl harder than are the coating~
or Eilms having two-phase systems. The increase in color re-sponse temperature range for single-phase systems over two-phase systems (as well as over the pure liquid crystal without binder1 indicates the interaction between binder and liquid crystal, the precise extent oE wh:Lch depencls upon the identity of the speci~ic binder employec1.
~ Ihe amo~lnt of soLvent usecl is not critical; it is de-sired o~ course, tha~ the solution be sufficiently fluid so that it can rea(lily bc formed int:o a coating or film on the support member. [t is ~Indesirab1e, however, to use excessiv~ly large quantities of sol.verlt because o~ increased cost and extended drying times durinq processinq. When the solvent is incapable oE dissolving the choleste~ic li(.~uid crystal, it is preferred to form a dispersi.on of the liquid crystal in a solution of the binder without the aid of wettin~ or dispersinc3 agents, these tencling to interfere w.ith the properties and characteristics of the liquid crystal. It is prefera~le to rely simply upon mechanical dispersion or st.irrinq of the ingredients. In general, it i5 desirable -that the solùtion should contain at least 10%
by weight o:E binders; solutions containing larger concentration up to 50% by welc3ht or even more may also be usedO
In manu~actur.ing the indicators of the present inven-tion, the soluti.on or dispersion of liquid crystal in binder solution is simply layed down on the surface of the support member to form a coating or fil.m. Then the solvent is evaporated either ~t room tcmperature or at elevated temperatures up to ~50F. to form a solid coating or film bonded to the sùpport member. The solid film or coating thus formed can vary greatly i.n thickness although a thickness of at leas~ 0.3 mil is usually clesired to en.sure sufficiently conspicuous color ch~nges upon e~posure to ethylene oxide in order to pro~ide an indicator of the desirecl sensitivity when observed by the naked eye.

13RII~F DE.SCI~IPTION OF T}IE: DRAr~IN(~S
In the appendecl clrawincJs:
F~TGURF l is a perspective~ enlarcJed view of a preferred em~o-~iment o~ the invention showinc3 the components thereof;
l~lflUR~ 2 is a cross-sectional view taken along lines 2-2 of l~ ;UR~ l;
I'T~[1RI;~ 3 :i].lustrates an embodiment of the v.isual indicator c~ the invcntiorl, which is meanincJ~ully readable c~ven l,y ~l ~olor blind l~erL;on; an~

~ f~ ~li~ Al ~rD
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FIGU~E 4 is a ~raphic representation of the color dif~erentials achieved with various useful formulae, according to the invention~
In the drawing, there is shown for illustrative pur-poses, an indicator comprising a support member 10 in the form of a flexible support sheet or film of unplasticized high mole-cular weight polyvinyl chloride approximately 3 mils thick.
Carbon black pigment i8 dispersed in the film to render it opaque and black. Such a support member allows ethylene oxide to diffuse rapidly through any overlying film both during the sterilization and the aeration processes. On the upper face of the support member 10 is a solid intermediate coating or film 12 preferably in a range from 0.3 to 1~5 mils thick formed by applying to the surface of the support sheet 10 a composition consisting of a chole~teric liquid crystal material in a solu tion of a normally solid binder, and then evaporating the solvent.
The evaporation is conveniently carried out by allowing the coating to dry overniqht at room temrperature, and then heating the coated sheet 10 for two hotrs at 200F.

Superimposed on the surace of the coa-ting 12 is a ~
mil thick, high moleculax weight polyvinyl chloxide cover sheet 14 plastici~ed with dioctylphthal~tte a plasticizer commonly employed in hospital and surgical goods made of polyvinyl chlor~
ide. Conveniently, the thickness of the cover sheet 14 is chosen to correspond, for example, to the wall thickness of commercially used polyvinyl chlor:icle tubing. The sheet thickness may be varied to match or to correlate with the bulk or thickness of the~ hospital articles or .supplies beincJ teste~, if desired.

37~a~

The composite assembly is heat sealed in an annular path 16 to defirle a central zone 18 of film 12 hermetically enclosed w.ithin and visible through the cover sheet 14. Both the exposed marginal area 14a of sheet 14 and the sealed zone 18 are identi-cal in composition, color and appearance.
In use, the indlcator of the invention .is placed within a package along with the products to be sterilized and exposed to a mixture o~ ethylene oxide and freon for example ~12:88), conventionally used for sterilization purposes. During this period, both the exposed area o coating or film 12 and the sealed zone 18 change in color as viewed in reflected white ligh~
The difference in color between film 12 and the sealed portion 18 indicates the amount of ethylene oxide absorbed by the plasticized polyvinyl chloride co~er sheet 14 which directly corresponds to that absorbed by the articles of polyvinyl chloride being sterilized.
When the treated package is to be used, it i5 allowed to aerate either at ambient conditions or at room temperature or elevated ternperatures c.125F in an atmosphere of circulating forced ai.r. The exposed area of coating or film 1~ changes back to its original color after a few minu-tes exposure to the atmosphere iP the liquid crystal film has a sensitivity to ethylene oxide at only relatively high concentrations (c.250 ~
parts/ million). When the color of the sealed zone 18 matches that of the exposed area oE coating 12, the plasticized poly-vinyl chlori.de sheet 14 and the items in the package have reached the minimum concentration o~ absorbed ethylene oxide, within the limit:s of sen~itivity of the liquid crystal Pilm coating l.2. I,iquid crystal Eilms 12 of higher sensitivity eg.

l5-~5 p~rts/million very often will not return to -the original color, presumably due to the pxesence of degradation products, SUC}l as cthylene g:Lycol, formed durinc3 the sterilization and aeration processes. In such cases, the concentration of ethylene oxide in the plasticized polyvinyl chloride sheet 14 and the polyvinyl chloride items b~ing aeratecl have reached the level of the minimum sensitivity of the liquid crystal film 12, c. 25 parts/million when the sealed test zone 18 reaches the same co]or as liquid crys-tal film 12. Liquid crystal film 12 may have a sensitivity to amounts of ethylene oxide less than 25 parts/million. In this case, the safety level of 25 parts/
million is indicated by the difference in color between liquid crystal film 12 and the sealed zone 18.
In preparing the coating solution to be applied to the support member 10 in the case of -the single phase system, the components making up the liquid crystal formulation are weighed out, then thoroughly mixed im the molten state and added hot to the binder 501ution~ The resulting mixture is Stirred until it becomes homogeneous. Some solutions are perfectly clear while others de~elop a haze orclvudiness. The mixed solution is applied to a support, eg. black unplasticized 3 mil polyvinyl chloride by conventional draw~down t,echniques, the thickness of the coating to be applied bein~ selected to provide the de-sired thickness of the inal dried coating or film after evapora-tion of the solvent. The coating is allowed to dry by exposureto air at ambient temperature~
In the case of a two-phase system, -the components of the liquicl crystal Formulation, after weic~hin~, are melted and sti,rred t:o Forlll a clcar mixture or mclt at a temperature of about _ L ~, .

3~

200 to 250F. The hot melt is added dropwise to a water solu-tion of the binder maintained at a temperature of 180 to 200F.
with high speed stirring to ensure the formation of a uniform, fine-particle emulsion. The emulsion is allowed to cool, and any foam is removed from the surface. The cooled emulsion is applied by conventional draw-down procedures onto a support member as described above, and then dried by exposure to air at room temperature.
After drying for several hours at room temperature, the coated sheet is heated in an oven at 200~. for two hours to ensure complete removal of solvent. The dry sheet is cut into pieces of appropriate size, about one inch by three inches. A
piece of one-inch square, 9 mil thick clear, transparent poly-vinyl chloride plasticized with dioctylphthalate or equivalent plasticizer is then heat sealed to the coated side of the support member by means of a heated iron or platen.
In evaluating the indicators by exposing them to ethyl-ene oxide and then aerating, standard samples of polyvinyl chloride plasticized with dioctylphtalate in the form of 9 mil ~ilm are exposed and aerated along with the indicator articles, under -the same conditions. Changes in colors of the indicators are re-corded at intervals during exposure and aeration. At the same -time, samples of the standard ~ilm are removed and assayed Eor ethylene oxide by gas chroma-tography. By this procedure i-t has been demons-trated tha-t indicators of the present invention are capable of indica-ting by color change the presence of as lit-tle as 25 parts/million or less of residual ethylene oxicle in the film.

The following tabu]ations give examples of various liquid crys~al mixture~ in terms of parts by we.ight useful in the present invention.
Example 1 5S.47 cholesteryl nonanoate 14~93 cholesteryl benzoate 24.60 cholesteryl oleyl carbonate 5~00 cholesteryl 2-(2-ethoxyethoxy1 ethyl carbonate Example 2 55.47 cholesteryl nonanoate 14.93 cholesteryl benzoate 24.60 cholesteryl oleyl carbonate 5.00 cholesteryl 2-(2-butoxyethoxy) ethyl carbonate Example 3 1.5 55.47 cholesteryl nonanoate 14.93 cholesteryl benzoate 24.60 cholesteryl oleyl carbonate 5.00 cholesteryl 2-(2-methoxyethoxy~ ethyl carbonate Example 4 61.3 cholesteryl nonanoate 17.6 cholesteryl benzoate 21.1 cholesteryl cinnamyl carbon~te Example 5 55.47 cholesteryl nonanoate 14.93 chole~teryl bellzoate 24.60 cholesteryl oLeyl carbonate 5.00 cholesteryl methallyl carbonate ~2~3~4~

Example 6 55.12 cholesteryl nonanoate 14.56 cholesteryl benzoate 29.52 cholesteryl oleyl carbonate .80 cholesteryl fuxfuryl carbonate Example 7 52.75 cholesteryl nonanoate 29.75 cholesteryl oleyl carbonate 17.50 chol~steryl benæoate Example 8 57.62 cholestexyl nonanoate 3203B cholesteryl oleyl carbonate 10.0 cholesteryl benzoate The liquid crystal ormulations of Examples 1-6 were mixed with a resin lacquer solution to form a single phase system, as described above, th~ ratio of liquid crystal to resin being in each case 1:4 by weight. The liquid crystals of Examples 7 and 8 were dispersed in an aqueous solution of polyvinyl alcohol ~ 6g by weight) sold under the tr~de name ELVANOL 52-22 to form a two-phase system as described above, the weight ratio of liquid crystal to polyvinyl alcohol being 1:4. The following tabulation summarize~ the coat.ing solutions ox dispersions thus prepared.
Tahula-tion Binder Solution Liquid Crystal Formulation 25 a) DeSoto E 31n Ex. 1,2,5,6 I)) Monsanto 26A Ex. 1,2,3,5,6 c) Bakelit.e ~crylic 203 Ex. 1,3,4,5,6 d~ DeSoto E 3nB Ex. 2,6 e~ A~hland EP-8911-7-7 Ex. 2,4,6 f) Stein-llall 1560 Ex. 2,3,5,6 c~) ~cryloid ~66 (50~) E'x. 6 h) D~Soto ~ ln6 F.x. 6 i) National Starch 33~2 Ex. 6 j) ReicllhoLcl ~.Sl,-2294 Ex. 6 35 k) Reichll()kl ESL-210B Ex. 6 I) Aclueous solutiorl 6~ of El.V~NOI. 52-22 Ex. 7,8 3~4;~

The foregoinq liquid solutions or dispersions were applied to a support member as dcscribed above and made up into indicators as shown in FI~,UR~ 1. In each case, in the absence of ethylene oxide, a characteristic initial color of the indi-cator by reflected white light i5 obtained at any given temper-ature in the range from 60 to 100F., and in each ca~e, the indicator displayed a diStinctive change in color in the pre~ence of small quantities of ethylene oxide. The initial color and the color in the presence of ethylene oxide occuring at room ~emperature (72F) are shown in Table 1:

Table 1 Liquid C~ystal Color Induced by Formulation and Bi.nder Initial Color Ethylene Oxide Ex.l 15 a Ochre-brown Blue-~ black b Rose-brown Purple c Red-blue-green Purple Ex.2 b Black Blue-~purple 20 d Yellow-brown Green--~ red--~purple e Blue Purple-~black f Black Red-~blue~purple Ex.3 a Green Blue-~purple-~green 25 b Rose Blue-~purple c Red-green Blue--~purple f Blue-qreen Purple black ~x.4 c Black Brown-~reen-~blue 30 e Black Blue-~green Ex.5 a Green E31ue ->black b T3rown-green Blue 3purple c Green Purple 35 f Yellow-green Purple Ex.6 a Black Red -~purple b Black Green-~purple c Black Blue -~purple 40(~ Black Red--~blue e Blac)c Red~-~Jreen-~purple f Black Rlue -~purple cl 13lack Red ~green 1) Black T31ue-~ purple i T3lack T31ue--~purple j n~ ck Blue -~purple k Dl.ack Blue-~ purple .x.7 ï ~ed Blue-~purple Ex.8 r Black Green-~Blue -~purple In many cases the color oF the indicator undergoes a series of changes with inCreaSlnCJ exposure or loss of ethylene oxide and in some cases the final color after aeration to remove ethylene oxide is not identical to the original color, although usually close to it.

F'ormula Indicating level of ET0 Ex. l b) ~,400 ppm (48 hrs.) d) I~
i~ ,~ 230 ppm (144 hrs.) Ex.2 d) ~, 400 ppm (48 hrs.) h) ~v360 ppm (72 hrs.) Ex.3 a) C~;780 ppm tover 144 hrs.) cJ ., e) ~ 4~0 ppm (48 hrs.) g) f~280 ppm (194 hrs.) i) ~400 ppm (48 hrs.

Ex.4 -~r ~v'l40 ppm ~168 hrsO) e) ,~l040 ppm ~24 hrs.) Ex.5 b~ 60 ppm (216 hrs.) f) f_380 ppm ~192 hrs.) Ex.6 e) _~480 ppm (96 hrs.) f) rJ480 ppm t96 hrs.~
These examples show the selection of particular liquid crys-tal compositions in combination with different binders can be used to provide desired ~ensitivity levels of ethylene oxide and color play temperature rancJes.
Table 2 shows the temperature color play ran~e of the examples. rn some cases Ex. L a, b, ~x. 2 d, Ex. 3 a, c,e,g, i, Ex. ~ c, an(l ~,x~mple 5 b, F, the li(luid crystal coatings exhibit colors at lelllperatllres l>elow room tempcrature (72 F). The ~L2~3~

remainder are black at room ~emperature and do not show colors until warmed above 72F. Table 2 shows that a broad range of color play tem~eratures is possible, from which the investiga-tor may choose the condit-ions which fit desired conditions.
Table 3 shows the response of the various indicator examples to difEerent exposure time~ to ethylene oxide sterili-zation where color differential can be used to tell the ETO
level which has been reached.
Table 4 illustrates the use of the indicator device to establish concentration levels of residual ETO reached during different time Feriods of aeration. Table 2 may be analyzed in the following manner depending on whe~ the color of the ex-posed area matches that of the sealed area.
Table 15I,iquid Crystal Original Color Formulation & Binder (72F) Red Green ~ ue Purple Black Ex.l b) Red~72F <80F <80~F 87F 102F
~) Red<72 ~80 ~80 <80 98 20i) Black 88 90 92 95 ll0 Ex.2 d) Red~72 C80 C80 84 96 h) E31ack C80 ~80 ~80 83 93 Ex.3 25a) Red-G,reen ~72 C80 ~80 <80 98 c) ~ed <72 ~80 ~80 ~80 96 e) ~reen <72 ~80 <80 ~80 96 g) Yello~ Bronze -clreen C72 C80 ~80 CE30 107 (~reen <72 <72 ~80 ~80 95 Ex.4 c) Black ~ 72 C80 90 105 l45 e) Black <80 84 92 104 150 Ex.5 ~)l3rown-qreen C72<72 ~80 ~80 90 f) Yellow-~lre~en~72 <80 ~80 ~80 94 Ex.G
e) E31ack ~E30 ~80 ~80 80 94 ~) slack ~80 CE)0 ~80 87 92 TABLE 3 (Sealed Area~
Time of Ethylene Oxide Exposure xposed Are Original15 Min. 30 Min. 1 Hr. 2 Hr. 4 Hr. 6 Hr. 8 Hr.
Formulation Color(140pPm/ETo)(220ppm/ETG)(340ppm/ETO) ~460ppm/ETO) ~620ppm/ETO) (1160ppm/ETO) (1100ppm/ETO~
Ex. 1 c) Red Sl.red NC Red NC NC NC NC
Blue NC NC Blue-purple Purple NC NC
d) Red Red NC NC NC NC NC NC
Blue Purple NC Ft, Purple Black NC NC
i) Black Green Blue-purple NC NC Blue NC NC
~ Black NC NC NC NC NC NC
Ex. 2 c) Red Red NC NC NC NC NC NC ~
Black NC NC NC NC NC NC
h) Black Red NC NC NC NC NC NC
Blue Blue-purple Black NC NC NC NC
Ex. 3 a Red-green Red Green NC NCBlue NC NC
Purple NC Purple-black NCNC NC NC
c Red Red Green NC NCNC Blue-green NC
Blue-green Purple NC NCPurple-black NC NC
e Green Red Green NC NCNC NC NC
Purple NC NC NCPurple-black NC NC
g -~reen Red Green NC NCNC NC NC
Blue-Purple Purple-black NC NC NC NC NC
i Green Red NC Red-green NCNC Green NC
Purple NC NC NC NC NC NC

T~BLE 3 (Cont'd) ~Sealed Area Time of Ethylene O~ide Exposure~Exposed AreaJ
Original15 Min 30 Min. 1 Hr. 2 Hr. 4 Hr. 8 Hr. 24 Hr.
Formulation Color (160ppm/ETO~ (300ppm/ETO) (400ppm/ETO) (640ppm¢ETO) (lOOOppm/ETO) (1500ppm/ETO) (2880ppm/ETO~
Ex.4 c) Black Black Red-brown Red NC NC NC Red-brown Red-browm GreenBlue-Green NC Blue NC NC
e) Black Red NC NC NC NC NC Red-brown Red-green GreenBlue-Green Blue Dk.blue NC NC
Ex.5 b~Bro~-greenGreen Blue NC NC NC NC NC
Blue-purple Purple Purple-black NC NC NC NC ~a f)Yellow-greenGreenBlue-green Bronze-green NC NC NC NC
Blue-purple Purple NCNC NC Dk.purple NC
15 Min. 30 Min. 1 Hr. 2 Hr. 4 Hr.30 Hr.
(160ppm/ETO) (260ppm/ETO) (420ppm/ETO) (560ppm/ETO) (950ppm/ETO~ (4800ppm/ETO) Ex.6 e) Black Blue Red-blue NC Black NC NC
Dk.blue Purple Purple-black NC NC NC
f) Black Black NC Blue Red-blue NC Ft.Blue Blue NC NC NC Blue-purplePurple T.~BLE 4 ~Sealed Area Time Aeration (Ambient 72F~ ~Exposed AreaJ
24 Hrs. 48 Hrs. 72 ~rs. 144 Hrs.
Formula(800ppm/ETO) (4QOppm/ETO)(36GpPm/ETO)(280ppm~ETO) Ex. 1 b) Red Tan Ft. Red Sl,Rust Green Tan Ft. Red Sl.Rust d) Red Red NC NC
Purple Red NC NC
i) Blue Green Red-green Black Black Black NC Black ~x. 2 Red Red NC NC
Blue Ft. Red NC NC
h) Red Red Ft. Red Black Blue-green Ft. Red Ft. Red Black a~
~x. 3 a) Green Red-green Red-green NC
Dk. Blue NC Blue Blue-green c) Green Green Blue-green Blue Blue Red-blue Red Red-purple e) Green Rust Olive-green Ft. Rust Blue Rust Olive-green Ft. Rust g) Green Red Red-green Bronze-red Purple Red-blue Green-blue Bronze-red i) Green Red ~ Green Bronze-green Blue-purple Red Green Bronze-green TAB-~E 4 (Cont'd) ~Sealed Area~
Time Aeration (Ambient 72F) ~E~posed AreaJ
8 Hrs. 24 Hrs. 72 Hrs. 120 Hrs. 168 Hrs.192 Hrs. 216 Hrs.
Formula(1540p~m/ET0) (lG40ppm/ETO)~34Gppm/ETO) ~460ppm/ETO) (440ppm/ET0) (380ppm/ET0) (360pDm/ET0) Ex. 4 c) Blue-purple Purple-brown NC NC Dark B~o-~-.NC NC
Brown NC NC Dark Brown Dark BrownNC NC
e) 31ue Brown NC Brown-black NC NC NC
3rown Brown NC Brown-black NC NC NC
Ex 5Blue-green NC Bronze-green NC NC NC NC
Red Bronze-red NC Yellow-green NC NC Bronze-green r' ) Green NC NC NC NCYellow-green NC
Red Bronze-red NC NC Yellow-green Yellow-green NC

8 Hrs. 24 Hrs. 96 Hrs. 120 Hrs. 168 Hrs.
~2000ppm/ET0)(1600Ppm/ET0)(480ppm/ET0) (460ppm/ET0)(.4ûûppm/ETO) _x. 6 e) Red-green Green-blue Black NC NC
Blue Ft. Blue Black NC NC
f) Ft. Blue Blue-PurpleFt. Purple NC NC
Black NC Ft. Purple NC NC

DETERMINATION OF RESIDUAL E~O E~Y COLOR DIFFERENCE

In addition to matching the color of the exposed vs sealed areas of the indicator de~ice to determine safe r~sidual ETO levels in the hospital devices, the difference in color between the exposed and sealed areas can be used to det~rmine progress Orc aeration. The following i5 an example of how thi~
~echnique works. A color scale i5 deYeloped for use in moni-toring the level~ oE ETO. A graph is prepared for each formu-lation used. The levc?l of ETO can then bc determined by UsincJ
the number differences between the expo.sed and sealed areas and locating the position on the graph to determine? the residual ETO. The following color scale key indicates how the method may be used.
Color Scal~ Number Bl~ck o Dark Brown Brown 2 Bronze 3 Brownish Green 4 Green Blui~h Green 6 .reenish Blue 7 ~lue 8 uluish Rurple 9 Purple 10 Dark Purple 11 A series of coating~ were prepared using the formulations ~escribed i.n the following paragraphs.
I l~'xample 1 .TI ExamE)le 1 -~ 5~ MBn~
III ~'hol(?!;teryl nonar)oate 7r~%
C~lo l es teryl chl oriclc 1 C'holesteryl oleyl car~onate 10 IV III -~ ~ M~A
'I'lu~ie Form~llativrls were d:ispersecl in ~cryloid B44 acrylic resin .It a ratio of 1 part liyuicl crystal to 4 parts soli(l rcsirl with 12 par~s tol~lene as svlvent. They were coat~?d in the usual manner on black PVC to give a dry film thickness of 0.7 - 0.9 mil. These were covered with 3 mil clear plasti-ci~ed polyvinyl chk~ride (PVC) to give the indicator shown in FI~,~lRE 1. These indicator3 were sterili2ed ~or three hourc at 140F and then mechanically aerated. The qraph (FIGURE 4) give~
the cOnct3n~ratiOnF~ of ETO at numerical figures representing color difference between axposed and sealed area~. The level o residual ETO in ppm i~ also indicated on the graph.
PROTOTYPES FOQ FIELD EVALUATION
It is necessary to identify and evaluate a number of ~i~nificant factors before deve1Oping indicator devic~
prototypes for actual field testing.

1. Aeration The residual ethylene oxide ~ETO) can be removed after sterili2ation,.by a number of method~. The ~terilized i~ems may be s~ored on open shelve~ (naturalj to allow the ETO
to evaporate or dif~use into the aurrounding atmosphere. Thi3 procedure requires an ~xces~ive p~riod o~ time and also po~es an environmental health hazardO Commercial mechanical aerator~
(mechanical3 are available which use forced air a~ elevated tem~eratures ~120~ to 130~F) to remove the ETO much faster.
~lospitals u9e a combination of the natural and mechan.ical (hospital). Mechanical aeration .i~ carried out for approxi-mately 12 hours and the medica1 i~em0 are then ramoved, placed on shelve3, clnd allowed to aerate naturally. U~ing 3 mil r~lasticize(l IPVC to represent the wor~t case~ the three above-descrjbe(l metho(ls were com~are~ and residual ETO was determined at different time interval~. Table 5 ~umm~ri~es the firltlings.

~37~

Time (Hours) o 16 40 90 200 Aeration Mode ETO Concentration (ppm) Mechanical llO0 320 180 90 47 Hospi~al llO0 460 350 250 ~3atural 1100 900 580 430 In order ~o ensure a ~afe level of les~ than 250 ppm xesidual ETO in non-implants, mechanical treatment require~
30 - 40 hours, and the hospital proces3 requires 90 - lO0 hours.

For a safe level of less than 25 ppm in implants, mechanical treatment requires 4Q0 ~ S00 hours and hospital treatment about 2000 hours. The indicator devices gave results properly indi-cating EI'O 1evels using each o~ the above processes.
2. Coating thickness Bird applicators were used initially to apply the liquid crystal films at various thicknesses. It was generally found that color response v~ried d~le to ncn-uniformity of the applied coatin~. A doctor blade pilot coater was developed which applies very uniform coatings at the desired film thick-nesses. A ~ower dryer was used to evaporate the solvent during coating operations. This equipment has been used to prepare the coated substrates for field evaluation. The film thickne~s of the liquid crystal film is critical. Very thin films are black ancl thicker films show no color difference betwee~ the exposed and covered areas during steri1i~ation. Useful film thickn~sses ~re bc-~tween 0.3 and l.5 mils with 0.4 mil to 0.9 mi I bein(3 the preferred rancJe.

3. Resin binders ~rlle resin binders afEect the performance of the indi-cator devices in a number of ways. A binder must be chosen which adheres properly to the substrate being used. Solvents in some binder systems will cause certain substrate films to curl. The eEfect on sensitivity and color play temperature has been shown in earlier examples. Compatibility of the resin with the liquid crystal formulation a~fects the clarity and color intensity or brightnes~ of the indicator film. It should be understood that the choice of resin is experimentally de-termined and is dependent on the compositions of the indicator componentsO Particularly useEul re!sins are the polymers and copolymers of acrylic ~sters, acrylonitrile, and ~inyl esters.

4. Purity oE liquicl crystal~ and use of additives~
It has been mentioned earlier that since this is a comparative or differential indicator system, purity of coating compositions is compensated or"zeroed out" since the same film is used in both æones of comparison. Some liquid crystals were purified by xecrystalliæation~ There was no apparent difference in the bric3htness o~ the colors obtained from purified liquid crystal films when comparecd to the unpurified materials normally usecl. All materials evaluated have been ohtained Prom commercial sources and none was chemically pure. The primary cliEference between the E~ure arld technical liquid cry~tal products is the color play ternperature, which depends on the mesomorphic range of the licluid crystal beinq used. Aclditives such as n-(p-methoxy~enzylidene)-p~ butylaniline (MBBA) and phenyl-azopherlol cholestcryl car~onate were used to shift the color play ranqe to ]ower temE>erat-lres and to improve resistance to de~raclation oE the li(3uid crystals by licJht.

.. 1 1)

5. Structures Structures other than shown in FIGURE 1 can be used and still be within -the scope of the invention. For example, instead of heat sealing the cover film 14 to the liquid crystal film 12 to form the annular zone 16, the two films may be joined by using a two-side pressure sensitive adhesive tape with the annular zone 16 cut out. A second liquid crystal coating of a composition the same as or differing from the com-position of liquid crystal film 12 can be applied to the top surface of cover film 14. I have found that the sensitivity range can b~ changed and a more varied color response can be obtained by using such structures. The dimen~ions of the in-dicator device or the size~ or shapes of the annular ~one 16 are not limited.

HOSPIq'AL FIELD EVALUATION

Trials were conducted at a Canadian general hospital using the following indicator sy~tems 1 Indicator type comparable to FIGURE 1 A. Liquid crystal Formulation:

Cholesteryl nonanoate 58.38%
Cholesteryl benzoate 15.76 Cholesteryl cinnamyl carbonate 20.l0 Phenylazophenol chol~steryl carb~nate 4.76 L. Coating Formulation: (parts by weight) L.iquid crystal formulation (above) ~cryloid ~4~l resin (acrylic ester ~rom Rohm & Haas) Toluene 12 -3l-The above coating was applied to black coated Fasson~ micropore pressure sensitive tape at a dry film -thickness of 0.7 mil. A
clear 7.5 mil PVC film was heat-sea]ed to the liquid crystal/
resin layer. The adhesive backing of the indicator device was used to attach the indicator device to the medical device.
Areas of the indicator which are not attached to the medical device are completely exposed to ethylene oxide during sterili-zation and the ~b~orbed gas is rapidly lost during aeration.
~he color of the liquid crystal area sealed under the PVC
cover and in contact with the medical device is dependent on .
the amount of ethylene oxide which penetrates through the medical c1evice to the liquid crystal coating. During aeration, ethylene oxide is lost Erom the de~ice and the color of *he PVC covered liquid crystals reverts to the color of the exposed liquid crystal areas. The indicators prepared as described above were attached to a number of medical devices and evalu-ated. Sterilization conditions were 2.5 hours exposure at 120F followed by 12 hours of mechanical aeration. The colors of the indicators were noted after aeration periods, as shown in Table 6.
*

TABLF 6 GOLCR O~ TAP~ - TYP~ INDICATORS

lndicator Color ~xpoæed/Covered) Aeration S~mple 12 Hours 44 hours 162 Hours 1. Indotrachael tube green/green-blue brown/brown-green brown/green-brown 2. Red rubber catheter green-blue/blue brownfgreen-blue brown/green-brown 3. Wooden tongue depresscrs blue-green/blue-green* brown/brown 4. Glass Syringe blue-green/green blue brown/brown-green brown/brown~:
5. Plastic airway blue-green/green-blue brown/brown*

6. Rubber anaesthesia mask blue-green/blue-green' brown/brown

7. Plastic trach tube green-blue/blue green-brown,/green-blue brown/brown-green

8. Scalpel blades blue-green/blue-green'c brown/brown

9. Telfa & gauze dressing blue-green/blue-green~'- brown/brown

10. Rubber anaesthesia tubing blue-green/blue-green* brown/brown * Color match indicates little or no ethylene oxide remains in sample.

~Ç~

II Yes - no type indicators It would be very di~flcult for a color blind person to evaluate the above clescribed indiccators. This problem can be overcome by using a li~uid crystal formulation which is sensi-tive to ethylene oxide (i.e., exhibi-ts color chancJe with ETO) but whose color play temperature range is above room tempera-ture. Since the liq~id crystal formulation does not exhibit color at room temperature, a symbol produced using this formu-lation appears ir.vi~i~le if attached to a black su~strate. On exposure to ethylene oxide the letters or symbols would appear in scme color which is ~ependent on the ethylene oxide concen-tration. With loss oE ethylene oxide the symbol or letters would disappear on the black background.
A liquid crystal formulation whose color play range from black to brown throucJh the visual spectrum to purple occur-ring in the temperature range 33'~ to 51C was used to cocat a black substrate, Fasson micropore pressu~e sensitive adhesive tape. ~t temperatures below 33C the liquid crystal film was hlack. Circular 30 and triang~llar 32 shapes w~re cut from this liquid crystal film substrate and adhesively applied to a black PVC support 3~. One of the shapes ~0 was covered with 3 mil clear plasticized PVC 40 (a "worst case" material3 while the second shape 32 wa5 covered with 5 mil clear polyethylene 42 ~representing those medical devices which do not retain ETO

tenaciously). The covers 40 ancl 42 were sealed to the black PVC 36 to erlclose the symbols 30 and 32. This is illustrated in FIGURE 3. Initially, the entire in(licator device appeared black. S~erilization exL)osure to ethylene oxicle caused the liq~lid crystal c~)ate(l shapes 30 an(l 32 to exhi~it color~ On aeration t~le ~haE)e 32 Leneath the polyethylene 4~ became ~lack -3~-~v~ ~

indicating medical relatively impervious devices such as scal-pels ~lass syringes and other materials whic11 do not retain ETO tendcio-1sly were safe to use. The other symbol 30 remained colored ancl di~ not returr1 to black until the loss of absorbecl ETO in the clear PVC film 40 was at a safe level indicating that medical devices of the type which tenaciously retain ETO
were safe to use. The shapes which appear different shades of ~ray to color blind people became invisible when the actual color returned to ~lack.
The foreqoing examples are merely illustrative to teach the produc~s and the working of the present invention.
Many other compositions which use different liquid crystals, resin binders, and which vary in the ratios of components were evaluated and further demonstrate the principles and the functionin~ of this invention. 13ased on the clear teaching o~ the invention others skilled in the art can also prepare still other working examples using components and methods not specifi-cally identified in the examples but described cJenerally or effectively ~uygested in the specifications. For example, in the embodiment of FIGURE 3, it would be feasible optionally to vary the roles of the shaped elements 30 32 and the cover sheets 40, 42, and still achieve the aims of the invention --all with-out deviating from the inventive concepts taught herein. The resulting indicator devices would clearly fall within the scope oE the invention, as defined in the appended claims.

Claims (12)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. An indicator assembly for providing a visual indication of relative concentrational levels of an alkylene oxide biocidal gas present in an article treated with such a biocidal gas, said assembly comprising a sheet-like supporting substrate, a film-like coating carried by said substrate, said coating including a cholesteric liquid crystal composition res-ponsive to biocidal gas reacting therewith to undergo color change, as a func-tion of biocidal gas concentrations present, a transparent cover sheet overlying said coating, said cover sheet being permeable to permit transport of biocidal gas therethrough, means defining a viewable reference zone of said coating, said ref-erence zone being covered by and sealed to said cover sheet and separated thereby from an ambient system, said reference zone being distinct from a vis-ible comparison area of said coating, and said comparison area being covered by said cover sheet in a non-isolating manner to be directly exposed to the same ambient system.

2. The indicator device as set forth in claim 1 wherein said liquid crystal composition includes a mixture of three types of cholesteric liquid crystals, said mixture comprising about 30% to about 80% by weight of a choles-teryl ester of fatty acid having from 6 to 20 carbon atoms, from about 5% to about 40% by weight of a member selected from the group consisting of choles-teryl oleyl carbonate and cholesteryl 2-(2-alkoxyethoxy)ethyl carbonates in which the alkoxy group has from 1 to 4 carbon atoms, and mixtures thereof, and from about 0.5% to about 40% by weight of a member selected from the group con-sisting of cholesteryl benzoate, cholesteryl cinnamate, cholesteryl furfuryl carbonate, cholesteryl allyl carbonate, cholesteryl bromide, cholesteryl nit-rate, cholesteryl cinnamyl carbonate, cholesteryl methallyl carbonate, and mix-tures thereof.

3. The indicator device as set forth in claim 1 wherein said liquid crystal composition comprises from about 30% to about 80% by weight of a chol-esteryl ester of a fatty acid having from 6 to 20 carbon atoms, and from about 0.5% to about 40% by weight of a member selected from the group consisting of cholesteryl benzoate, cholesteryl cinnamate, cholesteryl furfuryl carbonate, cholesteryl allyl carbonate, cholesteryl bromide, cholesteryl nitrate, choles-teryl cinnamyl carbonate, cholesteryl methallyl carbonate, and mixtures there-of.

4. The indicator device as set forth in claim 1 wherein said liquid crystal composition includes a cholesteric liquid crystal, a solid non-tacky film-forming binder and a solvent for said binder chemically inert to said bin-der and removable by evaporation at a temperature below about 250°F; whereby evaporation of said solvent provides a dispersion in which said binder is in a continuous phase and said liquid crystal is in a dispersed phase.

5. The indicator device as set forth in claim 4 wherein said solvent is water and wherein said liquid crystal is dispersed as droplets throughout a mass of solid binder.

6. The indicator device as set forth in claim 4 wherein said solvent is a solvent also for said cholesteric liquid crystal, whereby evaporation of said solvent yields a single solid phase system.

7. The method of fabricating an indicating device for providing a vis-ual representation of relative concentrational levels of an alkylene oxide biocidal gas present in an article treated with such a biocidal gas, said met-hod comprising the steps of preparing a cholesteric liquid crystal, coating composition, applying said coating composition as a fluid film on a supporting substrate, evaporating said solvent from said substrate at a temperature below about 250°F to provide a coating bonded to said substrate, superimposing on at least a portion of said coating a transparent cover sheet permeable to the biocidal gas and having a thickness correlated with an effective thickness of an article to be permeated by the biocidal gas, bonding said cover sheet to said coating to define a reference zone and a comparison area of said coating, said reference zone being in biocidal gas flow communication with an ambient system through said cover sheet, said comparison area being in direct communication with the ambient system, and said reference zone and said comparison area being viewable through said cover sheet superimposed thereon.

8. The method as set forth in claim 7 and further comprising the steps of exposing said indicating device to an alkylene oxide biocidal gas, diffus-ing said biocidal gas through said cover sheet to contact said zone of said coating, visually noting any color change occurring in said zone, aerating said indicating device and again visually noting any color change in said zone of said coating.

9. The method for indicating the amount of residual alkylene oxide present in an alkylene oxide treated article by using a gas indicating device having a gas-sensitive cholesteric liquid crystal composition applied as a coating on a supporting substrate, a mechanically isolated zone of said coating being sealed from dir-ect exposure to an ambient system, and a transparent, gas-permeable cover sheet covering said isolated zone of said coating, and said zone being view-able through said cover sheet, said method comprising the steps of exposing said indicating device to an alkylene oxide biocidal gas, diffusing a biocidal gas through said cover sheet to contact said zone of said coating, visually noting any color change occurring in said zone, aerating said indicating device, and again visually noting any color change in said zone of said coating and comparing the color of said zone with that of an area exposed directly to the ambient system, the steps of said method being carried out in the presence of an article whereby the gas indicating device and the article are simultaneously exposed to said steps.

10. The method as set forth in claim 9 and further comprising the steps of exposing said indicating device to the biocidal gas and aerating said indi-cating device in the presence of an article treated with the biocidal gas.

11. The indicator device as set forth in claim 1 wherein said liquid crystal composition comprises from about 30% to about 80% by weight of a chol-esteryl ester of a fatty acid and having from 6 to 20 carbon atoms, and from about 0.5% to about 40% by weight of a member selected from the group consist-ing of cholesteryl benzoate, cholesteryl cinnamate, cholesteryl furfuryl car-bonate, cholesteryl allyl carbonate, cholesteryl bromide, cholesteryl nitrate, cholesteryl cinnamyl carbonate, cholesteryl methallyl carbonate, and mixtures thereof.

12. An indicator assembly for providing a visual indicator having two different visually discernible degrees of sensitivity to alkylene oxide bioci-dal gas in effecting color change as a function of concentrations of alkylene oxide biocidal gas present, said assembly comprising a base substrate, a film-like coating applied to said substrate, said coating including a cholesteric liquid crystal component res-ponsive to biocidal gas reacting therewith to undergo and to exhibit color change as a function of concentration of biocidal gas present, first and second laterally spaced demarked areal zones of said coat-ing exhibiting visual distinguishable marginal contours, first and second cover sheets overlying respective said first and second zones and sealed to said film-like coating, said first and second cover sheets being characterized in that they exhibit different degrees of permeability to biocidal gas upon exposure there-to, said zones undergoing color changes at different rates upon exposure of said zones to biocidal gas and upon removal of biocidal gas from said zones.