CA2167188A1

CA2167188A1 - Chlorine-free multilayered film medical device assemblies

Info

Publication number: CA2167188A1
Application number: CA002167188A
Authority: CA
Inventors: Dan L. Fanselow; Raymond L. Ferguson; Walton J. Hammar; Lester B. Odegaard; Daryl D. Dressler; Jon M. Nornberg; Ching-Long Tsai; John H. Ko; Craig S. Chamberlain; Charlotte M. Palmgren
Original assignee: Individual
Current assignee: 3M Co
Priority date: 1993-08-06
Filing date: 1994-06-30
Publication date: 1995-02-16
Also published as: EP0713445A1; US5712044A; AU7357794A; WO1995004655A2; US6045648A; JPH09501364A; AU4687497A; WO1995004655A3; US5766744A; AU681691B2; AU710301B2

Abstract

A multilayered film having outside and inside surfaces comprising: a) a core layer (22) of at least one chlorinefree first thermoplastic polymer having a flexibility and resilience mimicking or greater that that of medical grade polyvinyl chloride film; b) an outside surface layer of at least one chlorine-free second thermoplastic polymer (24) having a Young's modulus up to about ten times the Young's modulus of the core layer thermoplastic polymer and being capable of non-stick release from a heated surface; and c) an inside surface layer (26) of at least one chlorine-free third thermoplastic polymer having a Young's modulus up to about ten times the Young's modulus of the core layer thermoplastic polymer and being capable of heat self-sealing before the core and outside surface layers become substantially deformed under heat; wherein, the film is capable of being expanded (at least in part) under heat and pressure without failure of film integrity, flexibility and resilience. Also provided is a method of preparing such film and film based medical device.

Description

WO 95/046ss 2 ~ 6 ~ t ~ 8 PCT/US94/07470 CHLORINE-FREE MULTILAYERED FILM MEDICAL DEVICE ASSEMBLIES

Field of the Invention This invention relates to multilayered films and film based assemblies, such as mPAic~l pump c~ccettec~ which are suitable to replace conventional polyvinyl chloride (PVC) films and assemblies, but without the environmental and health ha_ards ~Csoci~tpA with PVC m~teri~l$. Further, this invention also relates to meAic~l devices such as intravenous fluid ~iminictration sets 2o made with PVC-free m~tPri~lc, which may include such film based assemblies along with other col,-ponents.

R-rl~uul~d of the Invention Polyvinyl chloride (PVC) based films and film based assemblies are used in numerous mPAir~l products. However, PVC is viewed as ha_ardous to both the envil~nluent and to ~l~onal health. Incineration of PVC results in the release of hydrochloric acid (HCl), and PVC is viewed as a major contributor to HCl in incinerator flue gases. Also, PVC is suspected of contributing to polychlorin~ted diben70 1ioxin and furan toxins formed during 3 0 incineration. Levels of these toxins are up to three times greater in mPAir~l infectious waste as co-l-pa~d to municir~l waste streams. In addition to incineration concerns, eA~osulc to di-2-ethylhexyl phth~l~tP (DEHP), a common pl~ctici7Pr used with PVC, may present a number of health related concerns, inclu-ling reduced blood platelet efficacy and potential links to liver cancer.
Despite these concerns, PVC-based films and film based assemblies continue to be the m~tPri~l of choice in sçientific and mP~lic~l applications.
See, e.g., Encyclopedia of Polymer-Science and Technology, Vol. 17, pg. 50 (1989). The continued use of PVC m~tPri~lc is due, at least in part, to PVC's wo 95/04655 2 1 b 7 1 8 8 PCT/US94/07470 attractive qu~litiec, including flexibility; toughn~cc; recict~nce to W light, solvents, cuts, scratches, and acids; clarity or opaqueness as required; and lowcost. In ~dition, PVC's charactçrictics can be modified through the addition of various additives, such as pl~ctici7Prs, colorants, and the like. For example, U.S. Patent No. 4,298,714 discloses a modified PVC m~tPri~l with reduced hydrophilicity due to the addition of various thiol-group co,l,po~ ds tothe PVC backbone.
Other thermoplastic polymers have been used to form single-layer films and film based assemblies. For example, low-density polyethylene, high lo density polyethylene, poly~l~ylene, ethylene vinyl acetate, and polybutylene have all been used to form single-layer films and film based assemblies.
Encyclopedia of Polymer Science and Technolo~y, ibid., pp. 50-51. Further, films developed for rPp~ Pm~nt of PVC are often made of polyolefins.
Polyolefins have low surface energies and are often difficult to bond with conventional adhesives or solvents. Consequently, none of these polymer m~teri~ls has been succp~scfully used to provide films and film based assemblies with the advantageous char~cterictics needed to serve as environment~lly col"pa~ible rep~ .,.. ntc for PVC-based m~tPri~lc.
The problem is particularly acute with respect to tubing assemblies 20 with c~ccettes used in conn~tion with infusion pumps for m~tering IV fluids to a living patient. ~C~ttes~ for example as taught in U.S. Patent 4,236,880 to Archib~ld, must be highly flexible so as to deform in the manner of a rolling diaphragm when pressed by a ~ull~ping piston. They must additionally be tough enough to withct~nd repeated deformation for extended periods of 2S time: 72 con~ Qus hours is a typical inctituti~n~l ~ui~ lent among U.S.
hospitals. Such c~Ccel~s are ~l~ed by col"~ ssion blow moltling such that the m~teri~l must be able to form a secure heat bond during the fabrication.
In addition to continued environmP-nt~l inco,l,patibility, these films and film based assemblies tend to d~l~..l;n~te during continuous usage. To avoid d~l~",in~t;on problems, U.S. Patent No. 3,561,493 provides a multilayered film in which the inside and outside layers are welded together by a ~r~unded layer of the two different polymers. However, chlorine-WO gs/04655 2 1 6 7 1 8 8 PcTluss4lo747o cont;Aining polymers, such as PVC, are still considered best for use in such films and film based assemblies.
To date, no films and film based assemblies exist which provide the advant~e4us ChalACle~ ;ctics of PVC mAteriAl.c, and yet are environment~lly col,l~lible upon ~licpos~l The~rolc, there is a need for films and film based assemblies that can be utilized in a wide range of both meAirAl and nonmeAir~l products, and that can serve as replArem~Pntc for PVC-based mat~riAlc There is a need for e1PtnPntC of mPAicAl devices such as IV infusion therapy sets which are envilui-".entAlly col"l)a~ible, and yet capable of satisfying the chAllenging require-mentc Spe~i~r~lly~ there is a need for PVC replAcPrnPnt ~csett~s~ IV
sets and mPAirAl films which are extremely flexible, yet tough enough to endure their intended use. They must be capable of being heat bonded, must be visually tr~n~arent~ as well as solvent and W light resi~nt, and capable of being made for a relatively low cost.

Summary of the Invention The present invention is directed to a multilayered film, a film based m~dir~l device assembly such as a mPAicAl cA~sette and methods for formation of the film and the film based meAi~l device assembly.
The film is the building block colllpollellt for the medical device assembly. The film has at least a core layer, an outside surface layer and an inside surface layer colllposed at least of chlorine-free thermoplastic polymers.
The film has the capability of bonding to itself under heat conditions before the film core can distort s~st~lll;Ally. Further the film is capable of being eYpAnde~ at least in part under heat and l lCS~.Ilc without failure of film in~lily, flpyihility and rPciliPnce In ~lcî~llcd embo~limPntc, an optional divider layer or layers is present within the core layer. In other embo~imentc, the core layer can also act as one of the surface layers.
The core layer is composed of at least one chlorin~free, first the,l.loplastic polymer, or a I~ lulc of such first thermoplastic polymers, or ami~lulc of such first thermoplastic polymers with other substances and wO 95/04655 2 l 6 7 ~ 8 8 PCT/US94/07470 polymers. The outside surface layer is co".posed of at least one chlorine-free, second thermoplastic polymer, or a ",i~lu,c of such second thermoplastic polymers, or a Illixlul~ of such second thermoplastic polymers with other substances and polymers. The inside surface layer is co",l)osed of at least one 5 chlorine-free third thermoplastic polymer, or a ,,,i~lu,c; of such third the.",oplastic polymers, or a ",i~lu,c of such third thermoplastic polymers with other subst~nces or polymers. The additional internal layers may most conveniently be co,,lpos~d at least of one of the first, second and third thermoplastic polymers or a IllLl~lulc; of such thermoplastic polymers alone or 10 with other subst~nces and polymers. Also such ~ ition~l internal layers may be, but preferably are not, composed of halogen cQ~ in~ polymers such as polyvinyl chlorid~ or polyfluorocarbons.
The first thermoplastic polymer has a flexibility that mimics or is greater than that of the polyvinyl chloride used to make mPAic~l grade film.
15 In particular, it has a fl~Yihility ~bs~-t;~lly needed to achieve film functions ranging from a capability to fleY. and recover, to a capability to be ~Yp~n~ed without failure or derol..,ily. More spe~ific~lly~ the first thermoplastic polymer has a fleYibility that is measured as a Young's modulllc that subs~ t;~lly mimics or is less than that of polyvinyl chloride film used for 20 m~Air~l appli~tionc. ~erel~bly, the first th~..,oplastic polymer Young's modlllllc ranges from about 10 to about 60 MPa (megaPascals), more preferably from about 10 to about 50 MPa ecreri~lly preferably from about 15 to about 40 MPa.
The second thermoplastic polymer is tough and has an abrasion 25 re-ci~t~nc~ that 5~5l~nl;~11y mimics that of PVC used for m.oAi~l film. It has a Young's mo~lllluc up to about ten times the Young's modulus of the first thcl.llo~ ctic polymer. Preferably this ratio is up to a maYimum of about seven times, more p ef~ldbly, in a range of from about equal to, up to about three times, the Young's mod~ ls of the first thermoplastic polymer.
30 F..sreri~lly pler~l~bly, this ratio is greater than, up to about three times the Young's modulus of the first thermoplastic polymer. Preferably, the Young's WO 95/04655 2 1 6 7 1 8 8 PCT~Sg4/07470 modulllc of embo~li...P -~ of the second thermoplastic polymer ranges from about lS to about 300 MPa, more preferably from about lS to 150 MPa.
The third thermoplastic polymer is able to form a strong heat seal to itself or like matPrial~ It contain~ ecc~ lly no mP~lic~lly harmful substances s that can be cALldcLcd or l~rhP~ into an aqueous or organic based fluid stream and it will not absorb mP~ir~tion~ It is ~lefellcd that the third thermoplastic polymer is capable of adding to the tensile strength of the CGIllpoSile film. Itis also pr~icllcd that the third thermoplastic polymer has a Young's modulus within the general and pref~lcd ranges given above for the second 10 thermoplastic polymer.
Any thermoplastic polymer having the a~ pliate char~rtPri~tics described above is a~r~liate for use as the first, second or third thermoplastic polymer. t'JPner~lly, the first, second and third thermoplastic polymers have backbones of any configura.*on and chPmiral structure that will 15 ...~inl~;n the îolegoing ch~r~rt~Prictics and thermoplas*city during mul*layered film based assembly form~*on. Backbone configura*ons include but are not limited to linear, random, cross-linked, grafted, block, crystalline-amorphous domains, pseudo-cross-linked and ionomeric. Backbone chemical structures include polyolefin, polyester, polyulelhalle, while specific polyolefins include20 polyethylene/polyvinyl alr~hol, polyethylene/polyvinyl acetate, polyacrylates, poly.~.c!l. ^rylates, and polyvinyl aretatPs~ ~ef~llcd thermoplas~*c polymçrs include the polymers of olefin monomers or copolymers of olefin monomers and s~ JIed olefin monomers. F.~peci~lly ~refellcd olefin monomers include C2 to C4 IllonounsdluldLcd alkenes and ç~speri~lly p~eîell~d substituted25 olefin monomers include C4 to Cl4 monounsaturated alkPnPs, C8 to Cl4 aryl kPnPs, and C2 to C6 monounsdtuld~cd alkenes having moieties SP1~PCt~d from the group co~ ting of acetoxy, carboxy, oxyalkanoyl, and alkoxyc~l,onyl of 1 to 6 carbons in the alkoxy group. The use of such a thermoplastic polymer as a first, second or third thel",.,~lastic polymer depends but is not limited to 30 the percent of subsl;luled olefin monomer present in the polymer, the degree of regular molecular oriçnt~tion achieved by the polymer, the degree of cross-linking, pseudo-cros~linkin~ or ionomericity present, the backbone 2~67t~8 configurations mentioned above, the degree of the three rlimPncional rotation allowed by the chPmir~l backbone structure, the degree of crystallinity and the nature of the monomer conctituting the majority of the polymerized unit in the polymer.
The first thermoplastic polymer is flexible and soft. The second thermoplastic polymer is tough. The third thermoplastic polymer is preferably but not nP~s~.;ly tough. The first thermoplastic polymer provides a film core with conformability and e1~ctirity. The second thermoplastic polymer provides an outside surface layer with abrasion pro~lion and non-stick release. The third thermoplastic polymer provides an inside surface layer with tensile ~ , g~h and heat sealing ability. The thermoplastic polymers for the optional divider layer provide ~imPncional stability and tensile strength. In coope,dtion, the surface and core layers provide a multilayer film and film based assembly that are al?pr~Ai."alely as flexible, elastic, resilient and strong as, and in plcr~.lcd embo~ p~ exceed those charact~Prictics of, PVC films and film based ~c~ ..hliPS. The multilayer film is also as durable and scratch/abrasion resistant as PVC.
The multilayer film can have several configurations inrln~ing three layer, five layer and mrg~mlllti (more than five) layer configurations. In all 20 configurations, the outside surface, inside surface and divider layers are united or contiguously ~tt~rhe~ to the core layer. In the three layer configuration, the core layer is sandwiched between inside and outside surface layers. In the pl~ fe.lcd five layer configuration, the inside, outside and core layers are constructed as in the three layer configuration. In addition, the divider layer 25 is placed in a~ro,~ Ply the middle of the core layer so as to divide the corelayer into two parts. The divider layer in this configuration acts to further stabilize the core laya during formation of an assembly from a film.
In plcrel~cd embo~imPntc, the core layer will be composed of a copolymer of an olefin and a substituted olefin and in particularly prcrellcd 3 o embcYlimPntc, the copolymer can be an ethylene-vinyl acetate copolymer, an ethylene-butene copolymer, an ethylene-methyl acrylate copolymer, a very low modlllllc ion(illlel, and combinations thereof.

WO 95/04655 2 1 ~ I ~ 8 ~ PCT/USg4/07470 In l~lcfe.lcd embo ~imPntc, the outside surface layer will be a non-stick or release olefin copolymer. A copolymer of ethylene and l-octene or of ethylene and methyl acrylate is considered particularly suitable.
In prcÇ~.lcd embo limPnt~, the inside surface layer will be co-llposcd of 5 an ionomeric copolymer. A copolymer of ethylene and mPth~crylic acid-metal cation salt is considered particularly suitable.
The film based assembly according to the invention is usually formed from two sheets of the multilayered film. The assembly is constructed to function in the capacity of, and to have charact~Pri~tics similar to those of, a10 mPAi~l device made of a PVC cG~Ilposi~ion. In a plcfe.lcd embodiment, the film based assembly is a mPAic~l fluid bag, a flexible plastic drug COllt;lincr,or a mPAir~l pump c~ette with molded-in fluid ch~nnPl~ and pumping bubbles. The outside surface layer of the film based assembly provides a tough, pro~;Li~e coating for the assembly while the core layer provides the 15 needed Pl~ticity and fleYihility. The inside surface layer provides not only toughnP-ss but also is particularly ;~ptPA for heat bonding. The optional divider layer provides additional lim~Pn~ion~l stability and high precision formation during heat mol-ling and sealing.
The invention is also dil~lcd to a method of forming a film based 20 assembly. Such a method involves several steps, in-luding forming a film as a sheet m~teri~l by coextruding the first, second and third and optional dividerthe~..,oplaslic polymers as contiguous united layers.
In a scecond step, the molded portion of the assembly is produced by mollling a plurality of the sheets in a col"p~ssion blow mold having at least 25 two mold halves with at least one having intPrn~l cavities. In a prcr~lcd embo~imPnt two sheets of the film are placed between the mold halves with their outside surface layers facing the mold halves and their inside surface layers po~itionPA to touch each other when the mold is closed. The molded portion of the assembly is molded by closing the mold halves and applying 30 pr~s~ulc and heat to the sheets while applying gas ple~urc to the portions of the sheets within the internal cavities.

wo 9s/04655 PCT/US94/07470 The molded portion of the assembly is then optionally bonded to its connective or other pl~rorl,led co,l,~ne~ , which in many cases will be polymeric tubing. In pfef~l~d embo-iimentc, the polymeric tubing will also be fabricated from chlorine-free polymers. This bonding may be done by 5 apl)l~flate adhesives, or may advantageously be pt;lr ,lll,ed by applying a Illi~Lulc of a polymeric binder and susceptor particles to the connective cGI"pon~nls, placing the connective co",ponents and the molded portion of the assembly in contact with each other, and subjecting the combination to electlu",~nPtic radiation. The susceplor particles then absorb the 10 elecllu,..~netic radiation and gP~ P heat. This heat melts the polymeric binder m~tPri~l and bonds the acsembly log~l~l.
When adhesive bonding is pel~l,lled, some otherwise appl~liate adhesives have little green strength, and in such cases, susceptor particles maybe mixed with the adhesive, and the adhesive exposed to electrom~gnPtic 15 radiation to speed the cure and to Pnh~nCp- the green strength.
The invention is also dila ~d to a method for bonding together at least one tube and at least one plastic fluid transporting cûlllpol-en~. The method includes the steps of coating at least a portion of one of the tube and the plastic fluid llanspulLing collll)ol en~ (article) with the polymeric binder with 20 sllsceplor particles wh~lein that portion is an area of the article to be bonded to the other article. The areas of the articles to be bonded together are cont~ctPd Those contacted areas are irradiated with ele.;LIu,,,~gmP-tic tion. The ~lsceptor particles absorb the r~ tion and cause local melting of the adhesive and/or plastic m~tPri~l and hence bonding or sealing together.
25 The ~l~scel)lor particles can be ferrite ~wde.~, metal powders, carbon black,glal~hit~ powdel~, amorphous metal powders or coated particles with optional thermoset polymers. The amorphous metal powders are described in copending and co~si~ene~ U.S. Patent Application Ser. No. 07/800,632. The coated particles can be particles, such as glass fibers, glass bubbles, or mica 30 flakes, coated with a thin, continuous mPt~llic film. Such coated particles are described in copPn~ling and co~ignP~ U.S. Patent Application Ser. No.
07/668,974. Most kinds of thermoplastic polymer can be bonded by this Wo 95/04Css 2 ~ 6 7 T a 8 PcT/uss4/07470 g method Preferably, the method employs a thermoplastic polymer as described in the present application.
The invention is also directed to a method for bonding two - co.,.pon~ . The method inclu~P~s the steps of coating at least a portion of 5 one or both of the co,.,pone"~-with a thermoset adhesive mixed with susceptor particles wherein that portion is an area of the co",ponent to be bonded to the other co",ponent. The areas of the co"")onents to be bonded together are cont~tP~. Those contacted areas are irradiated with el~;tru...~nPtic radiation. The susceptor particles absorb the radiation and 10 enh~n~R greRn strength of the adhesive. Conveniently, the co",ponents may be a tube and a fluid lldns~lling part.
The invention is also directed to a composition of matter, comprising a lu.e of a thPrrnosPt adhesive and susceptor particles. Conveniently the thermoset adhesive is an epoxy adhesive, and the susceptor particles are for 15 ex~mpl~ particles coated with re~ ...~netic or ferrom~gnPtic m~eri~l, particles coated with con~uctive m~t~ri~l, and f~""...~gnPtic amorphous powders. The volume loading of the susceplor particles in the ~ ule is preferably b~lwæn about 1% and about 65 %, and more preferably belween about 1% and about 30%.
The multilayered film and film based mPAic~l device assembly of the present invention are flexible, tough, abrasion resistant and heat formable.
They do not release harmful chPmi~l~ such as hydrogen chloride to the al...o~here when they are burned or otherwise degraded. The multilayered film and film based assembly of the present invention are also safe and 25 effective for use in me~ic~l applications. At least the surface layers of thefilm and assembly contain no pl~tjri7pr or other leachable or extrudable ingredient which could co~ ..;n~t~ pharm~ceutic~l fluids. In particular, at least the surface layers contain no phth~l~tç or citrate esters or other pl~tici7ers or additives which are capable of lP~hing into pharm~ceutical 3 o fluids. The multilayered film and film based assembly also have an ability to avoid absorption of solvents, drugs, pharm~^~uti-~l agents and other m~tPri~
which come in contact with the film and film based assembly. This wo ss/046ss PcT/uss4/07470 char~rtPrictic is e-~pPci~lly desirable when the film and film based assembly are used as meAir~l products. In this application, the film and film based assembly display minim~l or no absorption of drug, pharm~ceutir~l carrier or other pharmarPutir~l liquid. Optionally, the film and film based assembly 5 layers can be co.ll~sed of thermoplastic polymers which will make the layers resistant to acid, solvent, UV light, and will render the film and film based assembly clear or opaque or colored.

Brief Des~ tion of the Drawi~c FIG. l is a cross-sectir,n~l view of a first embodiment of a multilayered film assembly having outside and inside surface layers and a core hyer.
FIG. 2 is a cross-sectional view of a second embodiment of a multilayered film having outside and inside surface layers, a core layer of two parts and a divider layer beLweell the two parts of the core layer.
FIGS. 3A and 3B are top and left side views respe~;Li~ely of an embo~limPnt of a film based assembly according to the invention. The e.llbo-l;. .-nl is a mPAir~l pump r~ette.
FIG. 4 is a mPAir~l IV bag colll~ession mold formed from two sheet 2 o films according to the present invention.
FIG. 5 is a colll~lcte mPAir~l IV tubing assembly.
FIG. 6 is a view of a r~ette forming device.

Detailed D~ )lion of the Invention The multilayered film and film based assembly of the present invention possess physical charart~Pri~tics much like those of polyvinyl r-hloride (PVC) film and film based ~cs~Ptnblips~ In addition, the multilayered film and film based assembly are environ,-,~ ,~lly safe and avoid mPAi~l, pharmaceutical and health-related drawbacks of PVC. The polymeric layers of the multilayered film and film based assembly are made of a core layer of at least one soft, flexible thermoplastic polymer and surface layers of at least one tough, abrasion-resistant thermoplastic polymer. These layers contribute a wo 95/04655 2 1 6 7 1 ~3 ~ PCTIUSg4/07470 composite of their char~t~rictics to the multilayered film and film based assembly. Moreover, the core layer is preferably at least slightly larger in thi-~lrness than either of the two surface layers. In this fashion, the flexibility çhqr~^tericticc of the core layer dominate the cGnlposi~. At least the surface s layers and preferably all layers are free of any additives, p!-q-ctiri7Prs or other co,nponents which could be extracted or could exude or leach into fluids in contact with the layers.

Deffniticns Certain terms and phrases are used to describe the film and film based assembly. Generally, these terms and phrases have the or~lin~y definitions understood by those of skill in the art. Several, however, have particular mFqningc as given below.
The term "Young's modulus" means the amount of force per unit 15 volume of mq,teriql needed to Plongqte the mqtFriql a unit Aist~qnce after the stress has been in;t;~lPd and before the curve of stress against elongation becomes nonlinFqr. The Young's modllh-s is measured in l"F,p~p~cc~lc (MPa).
The term '~cqcsett~ means a device generally formed of a multiple r,u,nber of overlaid plastic sheets. The r~ccette pOCCF Cses intPrnql passages 20 and/or chqmbers and/or bubbles suitable for conducting fluids. The ~qcsFtte may be a pumping r-q-ccette suitable for metFering fluids in connection with an infusion pump.
The term "plastic fluid transporting co",ponF nl" me ns a co---~nent formed at least partially of a polymer and having a lumen for conducting 25 fluid. Non-limitin~ examples include c~c~-ttes, tubing, luer locks, injection sites, bag spikes, filters, check valves, and drip ch~"b~r~.
The term "environmF-ntqlly co,--~atible", me ns capable of being hqnAlf!d or treated by a usual method for disposal of medical devices without the release of harmful, noxious or toxic substances to the environment. Usual 30 methods for such disposal include but are not limited to burning and burying.

wo 9s/04655 2 1 6 7 1 8 8 PcT/uss4/07470 Physical Characteristics Toughnecc and resistance toward abrasion and cuts as well as high flexibility are physical characterictics that are e-s.centi~l for meAic~l film and film based meAir~l device assemblies. The medical film and film based s assembly must survive the long term abrasion forces of such medic~l instruments as infusion pumps and friction fittingc They also must have high flexibility and el~cticity so that internal fluid ch~nnPlc and pumping bubbles will ~ inl; h~ their integrity and operate under repetitive flex conditions.
Tough, abrasion resistant thermoplastic polymers typically are not lo flexible enough for use in m~Air~l films and film based assemblies. Highly flexible thermoplastic polymers typically are not tough enough for use in m~Ait~l films and film based assemblies. Consequently, until the present invention, a non-PVC film had not been developed which exhibited a toughness, abrasion resi~t~nre, flexibility, durability, non-stick release, 15 flexibility and eyp~ncion without failure.
Acco,d,ng to the present invention, a multilayered film of a flexible rhlorine-free thermoplastic polymer core layer and tough, thermoplastic polymer outside and inside surface layers, and a film based m~Aic~l device assembly of at least two u~,lapping, heat and co."pr~ssion joined films have 20 been made which have flexibility, durability, el~cticity~ strength, toughnecs, abrasion recict~nce7 nonstick release and expansion without failure. The multilayered film and film based assembly inco,~l~te at least the following parameters a lh~ugh e and preferably the ~e~ inh~g p~r~met~rS as well.
a. The first thermoplastic polymer has a flexibility mimicking or greater 25 than that of polyvinyl chloride m~dic~l film. More sperifi~lly, the first thermoplastic polymer has a flexibility suffi~ient to enable the film to endure ",P~I~ni~l pump action on an PYp~nd~d bubble formed from the film; i.e.
flexing from a fluid filled, fully expanded bubble, down to a completely flat, unfilled condition where the pumping occurs ~pæ~ lly between two hard 3 o surf~çes. Preferably the flexibility of the first thermoplastic polymer is measured by its Young's modulus which in especi~lly ple~elled embo~imentc is within a range of about 15 to about 40 MPa (megaPascals). Examples of 2~6~t88 PVC meAir~l films acting as reference points for the flexibility mimiç~PA by the first thermoplastic polymer include but are not limited to me~lic~l and general pUl~)OSe PVC films such as PVC film p1~ctiri7eA with 40%
diethylhexyl phth~l~t~ m~nllfactllred by O'SuUivan Col~l~lion of Newton 5 Upper FaUs, MA. Also illustrative of PVC p,opellies in mPAic~l applir~tionc include "Nalgene" brand USP VI grade tubing, commercially available from Nalge Co. of Rocl-e,le~, NY, and "Tygon" brand tubing commercially available from Norton r~.rol,l,allce Plastics of Wayne, NJ. The Young's modnlllc of the PVC's used in such films range from about 17 MPa to about lo 40 MPa.
b. The second thermoplastic polymer and preferably but not nece~ . ;ly the third thermoplastic polymer have a Young's modulus that is not more than about ten times, preferably from about equal to, up to no greater than, about ten times, more plt;f~,~bly within a range of greater than, up to about ten 15 times, the Young's modultls of the first thermoplastic polymer. Fcperi~lly preferably, the Young's modllhls of the second thermoplastic polymer ranges up to no more than about seven times, most preferably up to no more than about three times, the Young's modulus of the first thermoplastic polymer.
~er~,led emho~;...rnt~ have a Young's modulus of the second thermoplastic polymer within a range of from about 15 to 300 MPa, more preferably within a range of from about 15 to 150 MPa.
c. The core of the film provides at least a slight majority of the film thirlrnPcc relative to any other single layer. More sperifi~lly, the thir1~nPcs ratio of the film layers incol~l~tiilg first thermoplastic polymer to the film layers incol~l~ting second, third and additional thermoplastic polymer is about 1:1 to about 10:1, ~ler~l~bly from about 1:1 to about 5:1. This pa,~"elel aUows the flexibility of the film core to do",inate the co",posile fleYihility char~rt~orictics of the multilayered film.
d. The multilayered film through the action of the third thermoplastic 3 0 polymer and the third thermoplastic polymer itself have a capacity to self-heat seal before the core and the outside surface layer become plastic or otherwise deform under heat. Further, the film is capable of being e~Yp~nded through wo 95/046s5 2 t ~ ~ t 8 8 PcT/uss4/07470 pr~sure molding to form expanded structures within the film such as pockets which can repe~qtedly be col.,pressed over a long duration without failure. The expansion also is achieved without failure of film inleglily, flexibility and reciliP,n.-,e.
e. The outside surface layer of the film and in plerclled embo~im~ntc, the multilayered film based assembly itself ~ ft;~dbly exhibit a hot surface releace and an abracion recicPnce that mimic or are greater than that of polyvinyl çhlori~e meAi~ l film. More spe~ifi--qlly, the outside surface layer of the film, and preferably, the multilayered film itself, exhibits an outside lo surface abrasion reci~tqnce having an abrasive index range of at least about 100 as meacured by ASTM test D1630-83, the standard test method for rubber propc.ly - abrasion recictqnce.
f. In addition to the flexibility of the first thermoplastic polymer and the core of the film, the multilayered film itself preferably exhibits a flexibilitythat mimics or is greater than that of polyvinyl clllori~e medical film. More ~f~lably, the multilayered film has a Young's modulus within a range of about 15 to about 60 MPa.
g. The multilayered film preferably exhibits eSSenI;A11Y complete recili~n~y in an eYrqn~ed form and escerl~;Ally no eYpnded wall failure during an endul~ce test as a rolling diaphragm of at least 10,000 cycles Ih~u~h eYpqncion and cG,,l~lcs~ion b~lween a completely filled conrlition and a completely collqpsed condition. The wall should return to its original state to show eccf~nl;Ally complete resiliency. It should not crack or exhibit signs of stress we-q~ ning to show ecc~nl;Ally no wall failure.
The multilayered film and film based assembly are capable of bonding to t~em~-lves and to other plastics through the use of adhesive bonding, radio frequency welding, microwave welding and thermal welding. The multilayered film and film based assembly are st~rili7Ahle through gamma irr~diAtion and ethylene oxide. They preferably do not degrade under such st~rili7ing conditions. The multilayered film and film based assembly resist oxidative and ultraviolet degradation such that in a p~efel,ed embodiment, Wo 95/04655 2 1 ~ 7 1 ~ ~3 PCT/US94/07470 they have a si~nific~ntly long shelf life and do not turn yellow or age like polyvinyl chlori~e.

Core Layer Thermoplastic Polymer The first thermoplastic polymer is used to form the core layer of the film. It includes any soft conformable thermoplastic polymer having the ch~t~--;stics, flexibility and preferably the Young's mod~ as described above. ~f~ d thermoplastics include polymers of a C2 to C4 mono-un~dtuldted alkene, copolymers of a majority of a C2 to C4 monou,-~nl,~ted alkene with a lllinolily of a subslituled olefin monomer such as C4 to C14 mo~o~ .d~ alkene or a C8 to C14 aryl alkene, and copolymers of a majority of a C2 to C4 mono-unsalu-dted alkene with a minority of a ~ub~liluled C2 to C6 mono-unsdluldted alkene having a su~liluent such as Cl to C6 alkoxy carbonyl, c~lJuAylic acid, carb~Y~mide and ca,l,o--ylic ester groups. FY~mp'~s include copolymers of olefins such as ethylene and propylene with ~ubsl;luled olefins such as vinyl acetate (EVA or PVA), N-methyl acrylamide (EAM or PAM), acrylic acid (EAA or PAA), mPth~crylic acid (EMA and PMA), EMA or PMA ionomers (EMAZ, EMAS or PHAZ
with metals such as zinc or sodium) and acrylate and metll~crylic esters having Cl to C6 alkyl groups. In the case of EVA and PVA, the acetate can be partially or wholly hydrolyzed to yield poly(vinyl alcohol) (PEA).
F.~m~ 5 as well include ethylene or propylene copolymers of all hydfoc~l~on s.~bsliluled olefins such as ethylene or propylene and styrene (ES
or PS), ethylene or propylene and butene (EB or PB) and ethylene or propylene and octene (EO or PO). Particular examples include copolymers of ethylene and vinyl acetate, ethylene and butene, ethylene and n-butyi acrylate, and ethylene and ethyl acrylate.
~.PmP~lly, as the amount of ~ubsliluled olefin monomer or alkyl or aryl olefin monomer is increased in such an olefin copolymer, the Young's modulus of the copolymer will decrease. Consequently, the ratio of majority olefin monomer to minority sullsliluled olefin monomer in the copolymer will be S~Pl~P~tP~ so that the copolymer will have the approp-iate Young's modlllus wo 95/04655 ~ t ~ 8 PCTtUS94tO7470 as described above. Preferably, this amount is from about 2% to about 50%, e~eci~lly preferably about 10% to about 40% on a molar basis.
Under certain circumct~nces~ the first thermoplastic polymer can also have char~ct~Pncti( s suitable for one of the surface layers. Film constructions5 of this nature will at least be tri/bilayer film where the core layer is also acting as one of the surface layers.

Outside and Inside Surface Layer Thermoplastic Polymers The second and third thermoplastic polymers include any tough, lo abrasion resistant thermoplastic polymer having the characteristics and the high Young's modllll)s as described above (esperi~lly, the important ~ictin~tivecharactPrictics of non-stick release and self-sealing, respectively). In addition to linear backbone structures providing a high order of intermolec~ r oriPnt~ti(!n~ other desirable backbone structures for the second and third 15 Ll.~ll,loplaslic polymers include those having: cross-linking, backbone b.~.-cl-;~-g, grafting, iQnQmPric linking, a col,lbinalion of crystalline and amorphous dol.lains, hydl~gen bonding and molecul~r nri~P-nt~tion such as through a h~ rh~omp structure that restricts the degrees of three ~imPncif-n~l .-.o~.l.ent of the b~r1rhonp (her~inaltc~, Intermolecul~r ~inking). Generally 20 the second and third thermoplastic polymers have the same char~cterictics butare not n~ec~rily of the same cllemi~l structure. Preferably, the second and third lhclllloplastic polymers include polyolefins, cross-linked polyolefins, olefin-s.~l,sl;lul~ olefin copolymers as well as polyu,~ n~Ps, polyethers, and polyesters. The olefinic monomers used alone or in combination to form the 25 polyolefins can be S~PlP~t~P~ from ~liph~tic and aromatic olefins of two to ~ourt~ ~ c~hbol s such as ethylene, propylene, butene, octene and styrene.
~f~ d polymers and copolymers of such olefins include polyethylene, polyl"u~lene, copolymers of ethylene and butene (EB) and copolymers of ethylene and styrene (ES). In copolymers of olefins, the minor olefin 30 monomer (C4 to C14) pl~f~dbly is present in a range of from about 1% to about 20% on a molar basis.

wo gS/U655 2 1 6 7 1 ~ lUS941~74N

When a copolymer of a C2 to C4 olefin and a substituted olefin is used as a second or third thermoplastic polymer, the substituted olefinic monomers can also be sPl~ted from C2 to C4 monoun~..dted olefins with such - substitu~Pnts as acetoxy, oxyaLkanoyl, carboxyl, carboxamido and other similar 5 polar groups. Examples include acrylic acid, mPthacrylic acid, acrylamide and similar hydr~gen bonding or cross-linkable olefins.
The optional Intermolecular ~ inking in the second and third thermoplastic polymers will be low enough to preserve the thermoplastic character of the polymer but sllffiri~nt to provide the degree of abrasion 10 re~i~t~nce and toughness mP~eting the Young's modulus r~uire"lent described above. Preferably the Intermolecular ~ inking is in the range of from about 0.1% to about 10% espe~i~lly preferably about 0.2 to about 5% on a molar basis. Moreover, as in~ tp~ above, the thermoplastic olefin copolymers are sPl~P~ted according to the guidPlines affecting the Young's modulus. Preferred 15 copolymers include a majority of C2 to C4 olefin monomer and a minority of polar, aprotic ~ubsliluled olefin monomer. Preferably, the amount of minority monG~ r present is from about 2% to about 40%, preferably about 5% to about 30% on a molar basis.

2 o Preferred Polymers for Core and Surface Layer In plefell~d embo~ llen~ the first, second and third chlorinP-free thermoplastic polymers are all olefinic polymers. Examples of prerelled first thermoplastic olefinic polymers include ethylene-vinyl acetate copolymers (EVA), ethylene-methyl acrylate copolymers (EMAC), ethylene alkyl acrylate copolymers such as ethylene n-butyl acrylate copolymers (EBA), ethylene-butene copolymers (EB), and combinations thereof. Other examples include the roregoing blended with ionomers.
Nonlimiting PY~mplPs of second therrnoplastic olefinic polymers include ethylene-octene copolymers (EO) (such as the Attanen' copolymers m~nufactllred by Dow ChP-mi~l Co., Mi~ n~l~ MI), EMAC copolymers (such as are manufactured by Chevron Chemical Corp., of Houston, Texas).

wog5/046ss 2 ~ 67 1 88 ~usg4~07470 Nonlimiting eY~mples of the third thermoplastic olefinic polymers include ionomeric ethylene-...rll.ac.ylic acid copolymer with zinc (EMAZ) or sodium (EMAS) doping, such as the Surlynn' copolymers manufactured by the DuPont Co., Willllinglon, DE.
The first, second and third thermoplastic polymers may also conctitute olefin copolymers of the same two monomers but with differing ratios of those monolll~ls. That tliffering ratio changes the modulus value of the resl-lting copolyma and hence makes the copolymer a first, second and third lhclllloplastic polymer. For eY~mple, the first, second and third thermoplastic polymers can all be obtained from EVA and EBA copolymers by ~ltPring the percent by weight content of vinyl acetate (VA) and n-butyl acrylate (n-BA) monomers, ~cspecli~/ely~ in those EVA and EBA copolymers. EVA and EBA
copolymers with relatively high VA and n-BA contents provide low Young's my3~ )s m~teri~lc suitable for use in the core layer of multilayered film. On the other hand, EVA and EBA copolymers with relatively low VA and n-BA
con~e~lc provide high Young's modlllllc m~teri~lc suitable for use in the outside surface layer and the inside surface layer. For ~Y~mple, when an EBA copolymer CGIll~)OSeS the outside and inside surface layers, its n-BA
content is preferably from about l % to about 20%, more preferably from about 1% to about 15%, and most preferably from about 2% to about 10% on a molar basis. In another eAarl,ple the core layer of a three layer film is an EVA copolymer with a VA content of from about 20% to about 30% VA, while the outside and inside surface layers are EVA copolymer with a VA
content of from about 5% to about 10% VA on a molar basis. ~lt~rn~tive 2 s the outside surface layer of that film can be an EVA copolymer with a VA
content of from about 5% to about 10% VA, while the inside surface layer of that film can be an EVA copolymer with a VA content of from about 10% to about 20% percent VA on a molar basis.

3 o Dimensions The thirlrn~,s of the core and surface layers and of multilayered film and film based assembly will vary dep~n-ling upon the int~nded use, and thus, wo gs/04655 2 1 6 7 1 8 8 PcTtrTss4/07470 can readily be s~lect~ by those skilled in the art. However, in a plcfcllcd embo~lim~-nt/ the outside and inside surface layers are moderately thin layers covering the core laya. In particular, the increased hardness and toughn~s~
of the outer surface layers, and the heat seal requirements of the inner layer, allow them to be coextruded as thinner layers than the core. In particular, these layers function to protect the core from abrasion and pick-up of dirt, serve as a release laya (outside surface) to assist in removing a molded assembly from a mold, and serve as a self-sealing layer (inside surface).
Accordingly, the ratio of the t~ ness of the two surface layers to the core layer is l.lcfcldbly from about 1:1 to about 1:14, more preferably from about 1:2 to about 1:14. For eY~mple, when using the prefer~cd EVA, EO, and EMAZ or EMAS copolymers to form a film and film based assembly according to the present invention, a core laya is preferably from about 125 ~m to about 350 ~m, more preferably from about 200 ~Lm to about 300 ~m, and most preferably from about 200 ~m to about 275 ~m thick, while the outside and inside surface layers are each preferably from about 25 ~m to about 125 ~m, more preferably from about 50 ~m to about 100 ~m.

Thermoplastic ~l~ . Modulus Mez;.ur~.--ellt The ~l;ff~cclflexibility of a given thermoplastic polymer is conveniently measured and c~lessed in terms of the Young's modulus, as c~ cd in mP~p~cc~lc (MPa), for the polyma. A polymer with a low Young's modulus (e.g., from about 6 MPa to about 30 MPa) is soft and flexible while a polyma with higha Young's modulus values (e.g., from about 25 MPa to about 300 MPa) is relatively stiff and infl~Yible. The low Young's modulus polymas also tend to be more easily cut or physically abraded and serve as the first thermoplastic polyma.
Conversely, the high Young's modulus polymers present a relatively hard, tough (i.e., cut and scratch-resistant) surface and serve as the second 3 0 thermoplastic polymers.
The following examples section provides the details for such measurements as applied to multilayered films. The functional and numeric wogs/04655 2 1 67 1 8~ ~usg4~07470 parameters for stiffness and flexibility of the first, second and third thermoplastic polymers used in the multilayered films are related to, and in plcfellcd embo~limPnt~, are in~ q~tp~ by the Young's modulus of these polymers. Those parameters are given above.
The measurement of Young's modulus was pclÇo,med using a l~<q,teriLql Test System (MTS) 880 (MTS Systems Corporation, Eden Prairie, MN) with an MTS Sintech Teslwul~ II Application Software Package, version 2.1.
S-q-mpl~s of film were prcparcd for testing by cutting strips 0.5 inch (1.2 cm) wide by 6 inches (15.24 cm) long. These were then inserted into the gripping jaws of the MTS testing mqchine, and a rate of elongation of 15.24 cm (6 inches) per minute was set. For each film sample, three repli(~qtP~s were run.
For each replicate the following information was co",puled and averaged:
1. Young's modulus, co~"puled as the maximum slope of the stress/strain curve, using a 3% strain segment length (actually the slope at 0%
strain).
2. Load at 50% strain 3. Stress at 50% strain Since stress/strain chq~teli~tics can change over time after extrusion, mea~,u"~nts are ~è~ol~d after at least one month following extrusion unless otherwise stated.

Tie Layer and optional Additives While it is preferable not to utilize a tie layer or layers in the multilayered film to bond the various layers together, there may be multilayered constructions in which such layers are desired. When a tie layer is employed, it can be composed of m~teriqls which provide structural in~,ily to the multilayered constructions, will~oul s-lbst~nti~lly affecting theother desirable chqr~q~-tP-ri~tics of the multilayered film, such as fltoYihility, clarity and en~ilun,~,en~ colnpatibility. The selection of the particular tie layer mqt~riql to be utilized in multilayered film according to the present invention, from the wide variety of available tie layer mqteriql~, is subject tothe particular needs and ple~elences of those skilled in the art. P~e~e,rèd tie Wo 95/04655 PCT/US94/07470 layer polymers include vi~coe1~tiG polymers which have functionalities that are cGI~palible with and bind to the layers to be tied, which in the case of plcrell~d e-.lbo~ may be copolymers of meth;~crylic acids.
To provide ~rerific ~d~iti-~n~l çh~t~^tP.ri~tics to multilayered films of 5 the present invention, any one, or all, of the layers can also contain conventional non-leachable additives, such as antistatic materials, pigmPnt~, dyes, UV absoll,Gl~, nuc1P~ting agents, quçn~hing agents and the like. For eY~mr'e, ultraviolet absoll el~ can be added to one or more of the layers of the multilayered film for applic~tio~ in IV r~ettes used with light-sensitive 10 drugs.

Methods of Preparation The lJlcrelled method of ple~ g multilayered film and film based assembly according to the present invention is through coextrusion.
15 CoeAllu~ion is a polymer l~r~c~Ps~;ng method for bringing diverse polymeric m~teri~l~ together to form a unitary layered structure, such as film and sheets of the film. This allows for unique c~lllbin~lion~ of m~teri~l~, and for structures with mllltirle runclions, such as, to~hnçss, flexibility and environ....~ ;.l c<~...p~lihility.
Co.. ponenl polymeric m~tPri~l~ according to the present invention can be coextruded from the melt state in any shape, according to the intPnded end use thereof. The shape and/or thicl~nPss of the coextruded layers will be depe -dçnl upon the çffici~Pncy of the particular extrusion equipment utili7.ed.Generally, films having a flat continuous sheet construction are the prerelled 2s coextruded structures. The films can be formed by co~AL-usion from linear dies and optional hot c~1PndPring and by coextrusion from circular dies followed by gas pl~,s~ e eYp~n~ion. Where a~roplidle, the multilayered film and film based assembly according to the present invention can be uniaxially, biaxially or mlllti~Yi~lly oriented to further enhance its physical 3 o Ç~ CtPri~ti~S.
For eY~mplP, in a pr~relled construction, a multilayered film according to the present invention is co---posed of a coextruded cast film of a core layer WO 9510465~ 2 1 6 7 1 8 8 PCT/US94/07470 of an EVA copolymer with a VA content of about 28%, an outside surface layer of an EO copolymer (e. g., an EO such as the Attanen' copolymer manufactured by the Dow Chemi~l Co., Midl~nA, MI) and an inside surface layer of an ethylene-meth~crylic acid, zinc or sodium ionomeric copolymer (e.g., an EMAZ or EMAS such as the Surlynn' copolymer manufactured by DuPont Co., Wilmington, DE). A three layered film can be coextruded with the forcgoing technique wherein the outside surface layer is the EO copolymer and the inside surface layer is the EMAZ or EMAS copolymer. Also, a five-layered film in which the outside surface and divider layers are composed of an Attane~ copolymer is ~l~rellcd.
The method for forming a film based assembly in~luA~s several steps.
The first involves forming a film as a sheet m~t~ri~l by coextruding the first, second, third and optional divider thermoplastic polymers as contiguous united layers. In a second step, the molded portion of the assembly is produced by heat bonding two of the sheets in a comprcssion blow mold having at least two mold halves with at least one having intprn~l cavities. Two sheets of the film are placed bl twecn the mold halves with their outside surface layers facing the mold halves and their inside surface layers positioned to touch each other when the mold is closed. The molded portion of the assembly is molded by closing the mold halves and applying pies~u~c and heat to the sheets while applying gas pre~.lle to the portions of the sheets within the int~rn~l cavities.
The self bonding core layers or inside surface layers of the sheet films bond toeach other and the portions of the sheet films within the mold cavities expand to form the desired intPrn~l structure of the molded portion of the assembly.
2 5 The molded portion of the assembly is then bonded to its conn~ e or other ~lcfol~ed parts, which usually is polymeric tubing. In pfcf~lcd c-llbo~ nt~, the polymeric tubing will also be fabricated from clllorin~free polymers as described in copending U.S. Patent Application Serial No.
08/104,256, filed on August 10, 1993 and entitled "Multilayered Tubing".
This bonding may be done by a~r~liate adhesives, or may advantageously be pclrol-llcd by applying a Illib~lUlC of a polymeric binder and susceptor particles to the dp~lldlUS, placing parts of the app~atus~ in contact with each WO 95/04655 PCTtUS94tO7470 other, and subjecting the combination to electromqgnetic radiation. The susceplor particles absorb electromq.~n~tic energy and generate heat. This heats the polymeric binder m,q~teriql and heat welds the co,l~onents together.
- Additional inÇul",a~ion about the plc:felled susceptor bonding technique is described in c~qcci~nP~A. U.S. Patent Applications Serial No. 07/588,591, 07/668,974 and 07/800,632.
Preferred Embodiments FIGS. 1 and 2 show cross-se~tionql illustrations of two ql~ e embo~limPntc of the multilayered films 10 and 20 while FIGS. 3A and 3B
lo show top and left side views of a c~Csette 30 according to the present invention. FIG. 1 shows a first embo~im~nt in which multilayered film 10 having a core layer 12 of a first, chlorine-free, soft, flexible thermoplastic polymer cont~cting an outside surface layer 14 of a second chlorine-free, tough, durable thermoplastic polymer and an inside surface layer 16 of a third clllorin~free~ self-bonding thermoplastic polymer. The first thermoplastic polymer is s~s~ lly softer than the second and third thermoplastic polymers. The surface layers 14 and 16 provide tough, protective co~tin~.c for the softer, aore layer 12. The Young's modulus of the first thermoplastic polymer is less than to within about 250% of that of polyvinyl c~loride used in flexible elastomeric meAi~l app1i~tionc, preferably in the range of about 15 to about 50 MPa (megaPascals). The Young's modnl~ls of the second and third thermoplastic polymers is higher than but not more than about seven, preferably three times the Young's modlllllc of the first thermoplastic polymer,preferably in the range of about 15 to about 150 MPa.
In a particularly pr~fe~ed embo~1;.. ent the core layer of the multilayered film is co".posed of EVA copolymer and/or (ethylene-butylene) EB copolymer known as Exactn' m~mlf^^t-lred by Exxon Corp. Floral Park, NJ. For eY~mple, the core layer of the multilayered film 10 (FIG. 1) can be about 200 ~m to 325 ~m of an EVA copolymer with about a 20-30% VA
30 content or an EB copolymer, while surface layers 14 and 16 l~;~ecli~ely can be 50 to 75 ~m of an EO copolymer such as an Attanen' copolymer manufactured by Dow Ch~mi-~l Co. of Midland, MI and 25 to 100 ~m of an wo gs/04655 ~ 7 1 8 8 PcT/uss4/07470 EMAZ copolymer such as a Surlynn' copolymer manufactured by DuPont Co., Wilmington, DE. No adhesive layer is required to adhere the core and surface layers 12, 14 and 16 of this multilayered film 10 together. Instead, upon hot-melt co~,-L,usion, the core and surface layers readily adhere to one s another to form an integldled three-layered structure. However, if need be, itis also within the scope of the present invention to use an additional ms~tPri~l, such as an adhesive, to adhere the core and surface layers and of multilayered film and film based assembly together.
FIG. 2 shows a second embo~lim~nt of multilayered film and film lo based assembly 20 according to the present invention. As with the e~bo iimpnt illuslldted in FIG. 1, this embo~imrnt inç1udes core layer 22 of a first, chlc-nnr-free, soft flexible thermoplastic polymer cont~rting outside surface layer 24 of a second, çhlorine-free, tough, durable thermoplastic polymer and inside surface layer 26 of the third chlorine-free polymer. In 15 ~A~ition~ this embo liment cont~inc a divider layer 28 in the appro~i.n~P
middle of the core layer 22. The divider layer is composed of the second thermoplastic polymer and acts to increase the stabilization of the core layer during film and film based assembly formation. This embodiment is esperi~lly l,iefe.-~d for use in construction of a film based assembly in which 20 precision of the molded int~rn~l structures is desirable.
Figs. 3A and 3B show a mPAi~l pump r~c~ette embodiment of the film based assembly. The m~Air~l pump c~Ccette is configured and o~,dtes according to tlicr1OSllre provided by U.S. Patent 4,236,880. Sheet films 10 or 20, formed p~Ç~ldbly as depicted in FIGS. 1 and 2, constitute ~ltern~tive 2s work pieces for the molded co,.~ponenl. A first sheet of film 10 (or 20) is bonded to a second sheet of film 10 (or 20). The first sheet of film 10 (or 20) con~ c molded tubes 31 and 36 which form the inlet and outlet of the molded col"ponenl. Tube 31 conne~l~ to bubble 32 which is the first piston pumping reservoir for the c~csette. Bubble 32 is intercol-necteA. to bubble 34 3 0 by in~ -ectin~ molded tube 33. Bubble 34 is the second piston pu~ping reservoir and conn~l~ (via over pres~u~t; rh~mber 35) to outlet molded tube wo 95/04655 2 1 6 7 1 8 8 PCTtUS94/07470 36. MeAir~l fluid polymeric tubing 37 and 38 is respectively bonded to molded tubes 31 and 36 to complete the assembly.
The infusion pump c~csette 30 has a low level of undesirable - extractables. This cAc~l~e has a form and function similar to an PYicting 5 infusion therapy c~ccp~ttp~ ~,c;sel~lly sold by 3M (Figure 3A). This c~csette is the metPring elPmPnt of a complete disposable infusion therapy set which includes tubing, luer locks, spike, drip ch~lhel, cl~mps, etc. In use, it is inscl~d into a mP~h~ni-~l mPtPring pump. It meets high ~lfol"lance re4ui~-..~ , including those in Table 5 of Example 5 below.
lo The C~CCPttP of this invention is made from a multilayer polymeric film (10 or 20) re~ ng pl~ctici7~P~A. PVC. This film can be three layers (FIG. 1) or more (FIG. 2) layers, with individual layers composed of single or blended polymers. The CO...i os;lP film construction (10 and 20) must have a modulus low enough (for FY~mple, 15 to 50 MPa) to produce fluid ch~mbers that will 15 pump and roll-back lel~l~lucibly, a surface on one side that is capable of forming a strong heat seal to at least like m~tPri~lc, and a surface on the other that will release from thermofol",ing molds and/or heat-sealing plates, and serve as an outside pr~tecti-~e layer for the finichP~ c~csette The co",posi~
film (10 and 20) has s~lm~iPnt ~imPncir~n~l stability during the thermofol",ing 20 and heat seal process of forming the c~cce~7 that a minimum of intern~l distortion is built into the C~CcPttP~s internal fluid paths and p~l",ping cl-~...be ~. The film (10 and 20) is also optically clear to allow nurses to seeand remove air bubbles during priming.
FIG. 4 shows a mPAi~ ~l IV bag 40 which is co",pre~ion mold formed 25 from two sheet films acconling to the invention. The sheet films are trilayerconstruction in which the inside surface layer 41 forms the inside surface of the bag while outside surface layer 42 forms the outside surface of the bag.
Core layer 47 and layers 41 and 42 are coextruded such that they are continuously united. Heat seal 43 along the outside perimP~t~pr of bag 40 is 30 caused by self bonding of core layer 41. Needle spike access 44 is epoxy welded to outlet duct 45 formed in the top 46 of bag 40 by jointly forrning the heat seal 43, duct 45 and epoxy welding of access 44.

W O 95/04655 2 1 ~ CT~US94/07470 FIG. 5 shows a complete meAir~l IV tubing assembly 50, including a c~csette 30 as described above in connection with FIGS. 3A and 3B. In prcfcllcd emho~im~Pntc, the other e1~PmPntC which comprise the mPtiic~l IV
tubing assembly 50 will thPmselves be free of polyvinyl chloride in their 5 co,l,poshion. Tubing 52 is provided as a plastic fluid transporting co",ponent, preferably its co"lposilion is a co",l,osile m?teri~l such as that ~iiscuss~ in copending and co~ccigned U.S. Patent Application No. 08/104,256, cited above. Such co"ver,lional elements as the bag spike 54 and the Y-sites 56 may be conveniently made from stiff thermoplastic m~tPri~lc; polycarbonate or 0 ABS (acrylcnitrile-but~lienP-styrene) polymer, are considered particularly suitable. The drip chamber 58 r~quilcs optical clarity for its function, and e.g., polypropylene, polycarbonate or acrylic polymers may be used. Pinch clamps 60 and roller clamps 62 may be provided, and these are conveniently made from high density polyethylene. A slide clamp 64 may be provided, 15 conveniently made from s~inlPcc steel.

Susceptor Particle Bon-lin~
A method for susceptible particle bonding of plastic articles is also conte..,p1~1 by the invention. As described above, two thermoplastic articles 2 0 can be heat sealed toggthPr l}~r~ugh the use of susceplor particles coated at the bonding joint. The SUS~)~Ol particles absorb elecllu.~l~gnPtic radiation and convert it to heat. The heat in turn causes the heat sealing of the thermoplastic articles. These mPth~c have been described in U.S.
Appli~tion Ser. No. 07/588,591, U.S. Patent Application Ser. No.
07l668,974, and U.S. Application Ser. No. 07/800,632. The general methods for fol",ing such a plastic article bond are described in these applications.
GenP~lly, the method involves fol",ing an interlayer of the susceptor particles bel~n the two portions of the plastic articles which are to be bonded together as a joint. The joint is then exposed to electrom~gnetic radiation to 3 0 cause heat sealing.
For the ~ull~oses of the present invention, the susceptor bonding technology for assembling the co"lponents of the sets provides advantages Wo 95/046s5 2 1 6 7 1 8 8 PcT/uss4/07470 over adhesives. The susceptor particles th~mcPlves can be made with very little metal content, and those metals can be chosen to be biologically and enviro~ment~lly col,-p~lible. By proper choice of the polymeric binder, most - thermo~l~ctics can be joined together. Typically, the polymeric binder is 5 comprised of the same m~tPri~lc that the conlpone~ to be joined are comprice~ S~sccl)lor tç~hnology allows one to heat only the bond area of the assembly, the rest of the assembly need not be subjected to heat.
Conventi~n~l adhesives, such as cyanoacrylates, one or two part epoxies or W cure epoxies can contain reactive m~teri~lc that are not meAi~lly suitable, 10 can not bond all m~teri~lc such as polypropylene or polyethylene, and may require heating of the entire assembly to cause or speed the cure of the adhesive.

Utility of the Invention Multilayered film and film based assembly according to the present invention can be utilized in a wide range of both mrAir~l and nonmeAir~l pru~luc~. In the m~ic~l area the multilayer film and film based assembly is suitable for reFl~ing chlorine-con~ ;ng PVC film and film based assembly, such as is utilized with intravenous (IV) fluid ~minictration sets, infusion 20 sets, C~C~tS, blood bags, IV fluid bags, ~II11USCO~Y fluid control systems, cardiovascular systems and blood gas monitoring systems. UV absorbers can be added to one or more of the layers of multilayered film and film based assembly for applir~';on in IV sets used with light-sensitive drugs. This ~arPti~ n of the multilayer film and film based assembly will not absorb drug 2s or m~dir~l fluids and will not co~-~...in~P the drug or meAi~l fluid with additive, pl~ctici7p~r and the like through eYtrarti~ n or l~ching.
These and various other advantages and rtalulcs of the invention are pointed out broadly by the folegoing general s~ ifir~tion. The following CA Fl~ are provided to further illustrate the invention. These examples are 30 not meant to limit the broad scope of the invention, however.

wo gs/04655~ t ~ 7 11 ~ ~ PCT/US94/07470 Example 1 An EVA Core Trilayer Fllm A 375 ~m trilayer film was co-extruded from three polymers: a top layer con~i~ting of a 50 ~m laya of an ultra low density copolymer of ethylene and octene (Dow Attanen' 4602), a 275 ~m core layer of a soft EVA
(28%VA) (Qu~hlulll UE-645-04), and an inside, heat seal layer cnnsi~ting of a 50 ~m layer of an ionomer resin that is a copolymer of ethylene and mPth~crylic acid doped zinc ~Dupont Surlynn' 1702). A 20 cm wide three manifold adjustable vane die was used. The Attane~ 4602 was fed to one of lo the outside manifolds of the die by a 2.5 cm Killionn' single screw extruder using a co"ventional screw (Killion, Inc., Verona, NJ); the Surlynn' was fed to the other outside manifold by a similar extruder; the EVA core was supplied to the middle chamber from a 30 mm co-rotating twin screw extruder co."~under (37:1 L/D) with a Zenith pump for mto.t~-ring.
The t~ alul~e profiles for these three extruders is given in Table 1.
(IJnless otherwise indic~t~ the extruder con-1ition~ for film formation acco~ling to each FY~mpl~ are given in Table 1.) The co-extruded film was cast onto a 30 cm ~ t chrome roll held at a te.~ alu~ of 12C, and then i.. .f~A;~ 1y passed through a nip between this chrome roll and a rubber 2 o roll.
To estim~te the best c~C~ttp forming con~lition~ for this film, a simple laboratory-scale forming device 70 was used. This device (shown in FIG. 6) conci~t~ of two ~ll-n~ u~ blocks (72 and 74) that can be held together by wing nuts 76. The lower block 74 has a small cylintlri~l hole, or well 78, 25 into which the film can be thermoÇol",ed when heat and air ples~ule iS
applied. The top block 72 was fitted with an air ~l~s~ule conne~tion 80. The film layers were placed in the former (cenlelcd over the cylin-lric~l hole 78), with the Surlynn' copolymer sides facing one another, and the Attanen' copolymer sides facing the alun,il,u", blocks. A hole 82 had been cut in the 30 upper film layer to allow ple-s~.l.;7~d air to get be~ .) layers. An O-ring 84 was placed over the film sandwich, centeled over the hole 82 in the film and the hole 78 in the lower block 74. A thermocouple 86 was placed between wo 95/0465s 2 1 6 7 t ~ a PCT/US94l07470 the film layers, and positioned ~dj~r-ent to the O-ring 84. The top block 72 was then placed down over the O-ring 84 and film assembly and tightPnP~
down by wing nuts 76. This formed a p~CSi~UlC seal around the sample above the d~Pfl~ti~.n well 78. The air inlet port 80 of the device was conn~ Pd to 5 cc~ .sEd air. The air p~s..u~e was adjusted to 0.2 kg/cm 2 using an in-line gauge. This assembly was then put into a Desl.~t- h oven set at 121 C and heated until the thermocouple read 93C (18 ...inules). The whole assembly was then i~."..PAi~t.oly i...---~ in room ~e "l)f-~tl~re water to quench the consl,uclion.
This e-l~-;.. -nt was l~"e~d several times, each time with a higher final ("formationn) telll~ldtul~. The details are su.n.~.~.;7P~ in Table 2.
Complete ch~mber formation at 106C and 116C means the film cc Ictely filled the well 78 and took its shape. Partial formation typically means the film formed domes which were smaller than the well 78. The heat 15 seal bGlwæn the layers OC ;ull~d under the O-ring 84, taking es~enli~lly the shape of the O-ring 84. At 106C and 116C, the seal bGlwæn the hyers was strong. When an attempt was made to pull the two halves of these films apart at the heat seal, the film itself tore and appGa~ed to sep~ate intern~
rather than within the seal itself. The film released readily from the 20 ~h~ u~ mold halves (72 and 74). In ~ubseluellt eYpPrimp-nt~ a heat gun was used to heat the assembly 70. Using the heat gun, samples could be heated to 107C within 5 ,..inu~s.
c~Pnes were then made from this trilayer film using a production former. Since the former is 27.6 cm wide, two of the 20.3 cm films were 25 spliced lo~" Ih. r using a thPrm~lly stable polyester srliring tape. The c~ettes were ~lGl)alGd as configured in Fig's. 3A and 3B, and were fabricated by blow mol ling belween two forming plates. The forming plates of the production former were two alu...inu... mold halves which were provided with a 2 by 5 array of cavities each a~l~,iale to the shape of the final desired 30 shape of the top and bottom halves of the c~sPtte ~s~ ely.
These plates were molmted in a hydraulic press, and provision made to heat the plates by cartridge heaters within the ~s~ e platens su~lling the wo g5/046s5 ~ 1 ~` 7 ~ 8 8 PCT/US94/07470 plates. At the completion of the heating phase, cooling water was circulated through the bzc~ing of the plates to quench the thermoformed construction rapidly. The two films were placed over the bottom mold half with their Surlynn' s~lrfq.~Ps in contact with each other, and their Attane~ surfaces facing 5 the mold plates, which were initially at room te~ d~ulc. Two small (1.6 mm liAmPtPr) air tubes were inserted between the edges of the film in a slot cut into the mold, so as to inject air along a pair of air delivery runners cut into the mold halves. The top half of the mold was brought down on the film pair and hydraulic p~S;~UlC of 5500 kg applied. Air pr~s~ure between the films was .~ inP11 at a pl~s~ure above about 0.42 kg/cm2 to force the films into the mold cavities as the ~---pel~tufc of the plates was ramped up. The te...peldtulcs of the top and bottom mold halves were ramped up together.
When the preset final telll~ld~ulc (or "formation" te---peld~urc) was reached, the cartridge heaters were turned off, and cooling water was flushed through the plates to bring them back to a lower ~ Pe~A~ C~ while still ~zin~ ing hydraulic ram ~ U~ and internql air ples~.-lc. Once a ~elllpeldlulc was reached at which the consll.-ction was ~limPncionqlly stable, the molds were s~p~ d and the c~c~ltes were removed.
Two pairs of these films were run on this former. On the first pair, 2 0 the final plate ~ A.~. cs were: 120.5 C top plate / 120C bottom plate; the plates were cooled to 57C before removing. With the second pair, the plates were heated to 107C top plate / 108C bottom plate, and removed at 57C.
In both cases, an air p~s~ c of 41.4 kPa and a hydraulic ram ~lCS~u~ of 59.8 kN was used, with an overall cycle time of S --inules. Flexible 25 cacse~t~s, with well formed, flexible cllzbe~s, open fluid paths and strong heat seals were formed from both e~crPrimPntC
Example 2 An EO Outside Surface Layer Trilayer Film A 375 ~m trilayer film conci~ting of a 50 ~m top layer of Attanen' 4602, a 275 ~m core layer of EVA (28%VA), and a 50 f~m layer of a lower m~~ lc ionol,.er (Dupont Surlynn' AD-8255) was co-extruded using the WO 95/04655 2 1 6 7 1 & 8 PCT/US94/07470 equipment described in Example 1. The extruder conditions which prevailed are noted in Table 1.
FYpPrimellts using the labold~ol~-scale forming device were - pe.r~l.. ,ed which p~r~llPl~ those ~i~cu~P~ in Fy~mple 1. The results are ;~ 11ll5~;~ in Table 3.
Ch~mbers formed were complete, and were more flexible than those from the construction of FY~mple 1. Heat seals were strong: seals did not sep~ale~ even after they were pulled to the point that the films tore.
C~Pttçs were then made from these films, using the pr~uction former describPd in Example 1. Formation t~lll~ldtUl~S were: 115.5C top plate / 116.5C bottom plate; an intçrn~l air plei.~u-c of 0.42 kg/cm2, and a ram p~S~ c of 5500 kg was used; cycle time was 5 minutes. C~SPtt~Ps with well formed ch~...hPI~, open fluid paths and strong heat seals were formed.
The ch~mhers of these c~cs~ ~les were somewhat more flexible than those of FY~mp 1.

Example 3 Third Trilayer Fllm A 375 ~m trilayer film con~i~tin~ of a 50 layer of Attane 4602, a 275 ~m layer of EVA (28%VA) and a 50 ~m layer of Surlyn AD-8255 was co-extruded, using a 30 cm wide die. The center EVA layer was supplied to a Cloeren feed block from a 3.2 cm Brabender Extruder (C.W. Br~hen~çr Insllu....~ , South ~ck~n~ NJ) with a positive displ~cçmçnt pump. The Sudyn and Attane were supplied from 2.5 cm Wayne extruders (Wayne M~chine and Die Co. of Totoya, NJ) with 1.168 cc Zenith PEP pumps. The layered feed was then fed through a 30 cm single manifold extrusion die (Extrusion Dies, Inc. of Chippewa Falls, WI). The co-extruded melt was cast onto a 10 cm ~i~mçt~r chrome roll kept at room te",~laLure, and then run through a nip b~lween a rubber roll and the chrome roll. The run speed was - 30 2 meters/min. Extruder conditions are shown on Table 1.
C~ettes were prepa~d on the production former, as described in Fx~mple 1, except that final formation ~",p~latules on the plates were 99C

wO 95/04655 2 ~ 6 ~ ~ ~ 8 PCT~Sg4/07470 on the top plate and the bottom plate. An array of flexible, appalel-tly well formed c-qCcettes was obtained, that appea~d to have good fluid seals and çhqnn.ol~ belween chambers.
Sqmpl~s of these ~qcs~lles were connected with IV tubing, and then tested for p~lrc"",ance in a 3M AVI 200A IV Infusion Pump. The tubing conn~cted to the inlet of the c-q-ccette was conn~ted through a syringe/luer lock to an IV solution bag, placed 46 cm above the pump. The exit tube from the c-q-csette was run to the top of a 50 ml burette, with the top of the burette level with the bottom of the pump. The c~q-csett~ was primed by first sealing the exit tube with a clamp and then squeezing the air out of the çq.~çtte and filling with fluid from the bag. The c-q-c~ette was inserted in the infusion pump and the door was closed. The pump was set to a volume limit of 49 ml and a pu~ping rate of 500 ml/hour, and then activated. The water delivered by the pump and c~sette combination was coll~t~d in the burette and measured. The pump/cA~ette combination delivered 49 ml and then stopped.
The same c~sette was then endurance tested. A closed loop was made by connP~ g both ends of the tubing to an IV bag. The pump was set to pump at the m~imllm rate (999 ml/hr) and IllA~illllllll pl~s;,.lre and pumped continuou~ly for 72 hours. During that period, the c~c~tt~ a~ed to be fimctioning pelr~;clly and showed no sign of fluid leakage or internAl rupture of seals.

Example 4 Low Modulus EMAZ Trilayer Film A 375 ~m trilayer film con~;cl;,lg of a 50 ~m layer of Attane 4602, a 275 ~m layer of EVA (28% VA) and a 50 ~m layer of a very low modulus iono,l,~r, Dupont Surlyn 8320 was co-extruded, using the 30 cm extruder/die des~-ribed in FYAmrle 3. Extruder conditions are given in Table 1.
C~A~settes were made from these films on the production former, 3 o varying the formation conditions to begin seeking an optimum set of conditiom~ Formation It"-~ldlules of 104C +/- 6C were tried; it was found to be advantageous to remove the samples from the press at wo gs/0465s 2 1 6 7 1 3 8 PcT/uss4/07470 le...~.~l...cs as close to room te~ ~ Al~.c as possible, to minimi7P distortion of the ch~mbers; in all cases, the plates were chilled imm~Ai~tely after re~ching the final (formation telllp~ldlulc). S~mplesi were produced that - appca~ed to be well formed and sealed, and had a flexibility appro~-~hing that of c~i~ttes~ made with the p~ ti~i7~A PVC film.
S~mp',es of these c~c~ttes were conn~teA with IV tubing, and then tested for pclr.-l--ance in a 3M AVI 200A IV Infusion Pump in the manner described in EY~mple 3. Some of the samples d~alcd to pump adequately, but contin~ed to drip after the pump was shut off. These samples were cross-s~ctionPA. in the fluid paths between the c-h~mbers, and eY~mineA under an optical co,--p~dtor (Nikon Profile Projector Model V-12, with a Nikon SC-102 digital readout scanner). It was found that there was a slight distortion ofthe films in the corner of the fluid path (Figure 3a, reference numeral 33) in those c~settçs which had not shut off completely. ~e~h~nic~l valves close on these fluid paths and are supposed to press the two films completely together.
However, this slight distortion around the heat seals is enough to prevent the fluid path from being completely closed off with the closing force of the current pump. This defect oc~;ullcd in some but not all of the c-~i~ttesi withina moltling array, and is coll~ldble by tuning the forming l,r~cess, i.e., by making adju~l~"f--,t~ to get ~.nir.,llll sealing telllpcldlu~cs~ seal force, andproper heating rate, and the like.

Example 5 A Five Layer Film and C~ccette In an endeavor to structurally account for the slight intern~l distortion of the films during the forming process, a five-layer modification of Example 4 was made. It is believed that at least some of the distortion described in Example 4 is a result of distortion, or possibly flow-out of the soft EVA in areas adja~nt to the heat seals. To try to reduce this, a single 25 ~m layer of the higher soflening telll~ldlul~ Attane 4602 copolymer was added to the center of the EVA core. Thus a construction of: 50 ~Lm Attane 4602 / 100 ~m EVA (28%VA) / 25 ~m Attane 4602 / 125 ~m EVA (28~ VA) / 75 ~m wo 95/0465~ 2 1 6 7 ~ ~ 8~ PCT/US94/07470 Surlyn 8320 was made. First a trilayer of 50 ~m Attane / 100 ~m EVA / 25 ~m Attane was co-extruded on a 91 cm extruder. A two manifold die was modified to accomplish this. Attane was delivered to the top manifold of the die directly from a 3.2 cm extruder (Killion KLV-125 L/D 30:1, from 5 Killion, Inc. of Verona, Nn using a conventional screw. The EVA was extruded from a 6.4 cm extruder (L/D 30:1 from HPM Col~ld~ion of Mt.
Gilead, OH) through a feed tube and feed block to the lower manifold of the two cl~AIllb~;l co-extrusion die. The lower (25 ~m) Attane layer was added by feeding from a 2.5 cm extruder through a 1.25 cm tap in the bottom of the 10 feed tube to the lower manifold. A pi~m~nt was added to the lower Attane layer to help de~ll.,ine distribution of the S layer, and to distinguish it fromthe other layers in a micf~sc~;c e~A...;nAI;on of the film cross-section. The lower two-col"~nent melt then was joined with the upper Attane layer at the exit to the die. The melt was cast onto a 40 cm chrome roll IllA;liti1ined at 15 room ~.ll~lalul~ and then passed through a nip between a teflon roll and the chrome roll. Run speed was 2 m/minute. The five layer construction was then comp1~t~d by co-extruding a 125 ~Lm EVA/ 75 ~Lm Surlyn layer onto the first trip film, with the Surlyn being supplied from the 3.2 cm extruder and the EVA from the 6.4 cm extruder. Various casting roll lem~.dlul. s were 20 ~ied, but it was found that room te.n~ld~ule on the roll produced an excell~nt film. Second trip run speed was also 2 m/minute. Extruder conditions are given in Table 1. This film was slit to 27.6 cm.
CA~settes were made from this film, using the produt tion former. Two sets of cycle conditions were used, which conditions are s.l"n..~ r~ in Table 25 4.
Sample c~ttes were taken from various plate locations within each i",plc~sion, and from the same location in several i",~r~s.;ons. These were co~ ed into a complete IV set and volllmetric~lly tested. A mo~ifi~tion of the volumetric test of Fy~mple 3 was used. As in Example 3, the IV bag was 3 o 46 cm above the top of the pump; the water was pumped into the top of a 50 ml burette; the top of the burette was 76 cm; below the IV bag. The pump was set to deliver 40 ml and fluid was pu"~ped at a rate of 500 ml/hour. The wO 95/04655 2 1 6 7 1 ~1 ~3 PCT/US94/07470 fluid delivered was then measured in the burette. Following this delivery, the pump autom~ti~lly goes into a very low rate pumping cycle of 1.0 ml/hour, which is called "keep the vein open (KVO)". Its purpose is to continue delivering a small volume of fluid to the vein to prevent occlusion within the 5 needle. The additional fluid delivered during 20 minutes of this cycle was then collected and recorded, and from this, a KVO delivery rate was calculated.
Table 5 is a s~ of the volum~tric ~ccllr~ y of these randomly s~l~ted ~mples The first column lists the actual volumes delivered, when lo the pump had been set to deliver 40 ml. The second column lists the measured rate of delivery during the KVO cycle. (The desired KVO rate is 1.0 ml/hour.) Example 6 A Five-Layer Low Melt Fllm and C~sett~
A five-layer film sample was made in which a dirrt;~ t ethylene/octene copolymer, the lower melt index Dow Attane 4601, was subs~iLuled for the Attane 4602 of P~ 5. The l~u1~ose of this substib~tion was to minimi7P
the t~ndency of the film to fill tiny vent holes in the forming plate, that occurs 2 0 after r~pealed forming with film having a 4602 release layer. This film was extruded on the 20 cm extruder of Example 1, using a two trip process similar to that of FY~mrl~ 5.
Extruder condition~ are listed in Table 1. This film was tested on the laboldloly former, described in Example 1. 0.42 kg/cm2 intern~l p~s;,ul~;
25 was used. When the sample was heated to a final tem~alule of 97C, there was nearly complete cl-~mher form~tion, and a strong heat seal was formed.
There was coll,plete ç~ ..br~ formation at 102C. The film released easily from the ~ ..;nl-... forming plate.

wo 95/04655 ~ 8 8 PCT/US94/07470 Example 7 A Five-Layer EB Film and ~ccette A five-layer film sample was made in which an ethylene-butene copolymer (Exxon Exact 4028) was substituted for the EVA of FYAmrle 5.
5 This film was extruded in the manner of Example 6 (Extruder conditions listed in Table 1), and tested on the labolatol~y former described in Example 1. Tntern~l p~s~u.~ of 0.42 kg/cm2 was used. At a formation te~ At~c of 94C, there was nearly complete formation, with good heat seals. At a formation ~ d~ of 102C, there was complete formation with good heat lo seals.
F.Y~nlP~ 8 Comparative Sin~ Layer Fllm A 375 ~m film of pure EVA (28%VA) (Qu~tul-l UE-645-04) was extruded from the 30 cm extruder setup of FY~mple 3 (using only the 15 Br~he-nder Extruder). CAccettec were made on the production former, using formation ~..l~;dm~s ranging from 64-70C, and a total cycle time of 2.5 to 3.5 ...;n~t~ S (Table 1). ~Ccettes were formed that exhibited meAillm to low seal strength (1.8 kg tensile at 70C forming ~ Am.c; 0.70 kg tensile at 64C fo l~ling te~ e). They had a high adhesion to the mold, and had a 2 o somewhat tacky surface feel.

Example 9 C~ ya~ e Sin~ Layer Fllm A 375 ~Lm film was made of an ethylene / butene copolymer (Exxon Exact 4024) from a single chamber of the 20 cm extruder of FYAmrle 1.
(Con-litinnc Table 1.) These films were tested on the laboratory former to de~.llline the best formation telll~.dtu-e. Results of these tests are s... ~ d in Table 6.
Films were spliced together in the manner of Example 1 and an 30 attempt was made to form cAcsettes on the production former, with three diîrelcl~t formation te~..l~AIu.~es. The results are sl-mm~ri7ed in Table 7.
Under these conditions, c~mber formation varied across a single plate from WO 95/04655 2 1 ~ ~ ~ 8 8 ~cT/uss4/07470 partial formation (dome) to complete formation with bases broken off ~ ent to the heat seals. Heat seals between the films were very strong at the highest formation ~lllpc~alures; the films showed modpr~t~p adhesion to the forming plate.
FY~nlrl~ 10 Comparati~e Si~l~ Layer Fllm A 375 ~m film was made of an ethylene-methyl acrylate copolymer (EMAC 2205, cG"""er~ially available from Chevron ~hPmi~l Co. of Houston, TX), using the center manifold of the 20 cm extruder of FY~mp~
10 Extruder con~lition~ are listed in Table 1. Laboratory tests were run on thisfilm, using the mPthods described in FY~mple 1. In all tests, 0.42 kg/CM2 internal pressule was used. Complete formation occurred at 77C, with a thin but intact cl-a-l-b~r formed. However, there was considerable flow out in the area under the O-ring (the "heat seal area"). In this area, only a thin film was15 left. At 85C a similar formation oc~ulled, with a very thin layer left in the heat seal area, and a slightly thinner bottom on the chamber. At 96C, the heat seal area had broken through entirely, and the ch~mber sepalated completely from the rest of the film. Adhesion to the mold was low in all three cases. Two of these films were spliced together as described previously, 20 and tested on the production former. With final formation telll~ldlu~s of:
bottom plate: 86C, top plate: 90C, partial formation occurred. There was separation of the "chambers~ (actually domes? at their bases on some of the C on~ There appealc;d to be strong heat sealing of the two films in all areas of the plate. The s~mples came out of the mold with low ~hPsion.
E~ample 11 C'Q~np~rative Sinpl~ Layer Fllm A 375 ~m film was made of another ethylene-methyl acrylate copolymer (EMAC 2260, commercially available from Chevron ChP-mi~l Co.
30 of Houston, TX) using the center manifold of the 20 cm extruder of Example 1. Extruder conditions are listed in Table l. Laboratory tests showed that there was partial formation at 88C and 0.42 kg/cm2 pressule with a good Wo 95/046ss ~ 1 6 7 1 8 8 PCT/US94/07470 heat seal. The dome that formed was stiff, co~ alcd to the EMAC 2205.
A~lhP~ion to the mold was low.

FY~mp'~ 12 A Tri-Layer Film A tri-layer film was formed under circum~t~nces wherein the core layer also acted as an inside surface layer. In this case, the first thermoplastic polymer used also had appr~pliatc self-bonding and tensile al~`cngl}l char~ct~ri~tics The film included a 50 ~m layer of Attane 4602 and an 275 ~Lm layer of an ethylene-butene copolymer (and EB copolymer of the t~den~m~- Exact 4024). The film was made on the 30 cm extruder by the process des~-rihed in Example 3, with the third extruder that supplied the Surlyn turned off. The film was soft and flexible, and formed c~settes using a formation ~ ..e of 102C. Unlike the single layer Exact 4024 film of 5 FY~mpl- 9, this ~i/bi-layer film did not adhere to the ~ umold. The Attane 4602 at these fol",alion lc"~y~lalul~s, acted as a "mold-release", and did not appear to adversely affect the ability of the softer and tackier EB to take the shape of the mold. Extruder conditions are listed in Table 1.
Sqmples of this film were tested on the labGldtoly former. A formation lelll~dlulc of 102C was used with 0.42 kg/cm2 of internal plcsa.rc.
Complete form~tion occurred, with strong heat seals, not only under the O-ring, where yl~,saulc was applied, but wherever the films came in contact.
The rl-~.llb~ formed looked quite uniform, and was quite optically clear.

FY~mple 13 An EMAC Tri/Bi-Layer Film and C~csette A trilayer film was formed under circum~t~nr~s where the core layer also acted as an outside surface layer. In this case, the first thermoplastic polymer used also had appropliate mold release and abrasion reci~t~nce char~et~ri~tics~ The film inçluded 275 ~m of ethylene-methyl acrylate copolymer (EMAC 2205) and 100 ~L~m Surlyn (EMAZ 8320). The film was made on the 30 cm extruder of Example 3. Extruder conditions are listed in ,1 Wo 95/04655 2 1 6 7 ~ ~ 8 PCT/USg4/07470 Table 1. Samples of this film were tested on the laboldtoly former. Samples were formed at 77C and 0.42 kg/cm2 of intern~ Ulc. Chamber and seal formation were CG r1ete. The addition of Surlyn 8320 appea,~ to have sl-cnglllened the film in both the chamber and heat seal areas, co",p~cd to 5 c~ttes made from EMAC alone, see Example 10.
The Surlyn adds both a degree of toughness and lim~nsional stability to the film without greatly increasing its stiffness. The EMAC 2205 softens at 59C and melts at 83C. The Surlyn 8320 seals at 72C. Thus this co",bil dlion makes it possible to use a lower formation te~ e (77C) lo than in the previous FY~mrles (92C) . Further, in this Example, the overall film sor~, ing and sealing lcml)el~dlurcs are closer together than in the previous FY~mples Note that the EMAC in this m~tPri~l is acting as both core and outer surface/release layer.

FYsnlp~e 14 An EMAC/Blended EVA Trilayer Fllm A trilayer film of 50 ~m EMAC 2205, 225 of a blend of 75% EVA
(28% VA)/25% EVA (19% VA), and 100 of Surlyn 8320 was made on the 30 cm extruder of F~...l le 3. The two EVA resins were blended by hand, and 20 then added to the hopper of the center layer Bra~e-n~er extruder. The extruder con~litions are listed in Table 1. Samples of this film were tested on the laboldtol~-scale former with a lelll~ldlulc of 74C and a pres~.llc of 0.42 kg/cm2. Co",l)letc formation oc;ul,~d, with strong heat seals. The film assembly released readily from the alll"linu"l plates.
Example 15 An EO Trilayer Film An ABC trilayer film was made from Attane 4602 (A) (50 ~m), ethylene-methyl acrylate copolymer (EMAC 2205) (B) (225 ~m), and Surlyn 3 o AD-8255 (C) (50 ~m), using the 20 cm extruder described in Example 1.
Extruder con~litio~ are listed in Table 1. Laboratory-scale tests were run on this film, using the m~tho~s of Example 1. At a formation telll~ldlul~ of wo gs/04655 PcT/uss4/07470 ~0-96C, there was nearly complete formation with excellent heat seals. At 102C, there was co,l,plete formation with excellent heat seals. Two of these films were spliced together as des-^rihed previously, and tested on the production former. 0.42 kg/cm2 of intem,^l p~s;~ule was used. Forr.^.-^tion ~Illpe~dlul~s were: bottom plate 113C / top plate 108C. Partial formation occurred, but there was no sign of the we, k~nP~ ch, mh~r bases found in FY^mple 10 with the EMAC alone. Strong heat sealing occurred only in the areas where heat sealing is e~pe~ed i.e., the fluid seals on the ~ ;...ele~ of the çhA~mbers and co, n~ting fluid paths.

Example 16 Adhesive Bon~lin~ of Tubin~ and C~scette Tubing made a cording to Fl~mple 8 of U.S. Patent Applir-tion Serial No. 08/104,256 cited above, was bonded to a c~ccPtte prep~t;d according to 15 Fy^mpl^ S above. The two cG".pollenls of a two-part epoxy adhesive commercially available as TRA-BOND FDA-2 from Tra-Con, Inc. of Medford, MA, were mixed and a small amount was applied to one end of the tube. This treated end was inserted into one of the molded tubes in the c~Csette~ and the assembly allowed to cure for 15 -.inu~s at 65C, and then 2 o for 12 hours at 25C.
Example 17 T~in~p of A~sembly The assembly of FY~mple 16 was tested for bond strength and integlily by filling the lumen of the tube and the c~ccette with air, and subjecting the 2s air to a pl~Ul~ of 68.9 kPa. The bond was submerged in water and t T~lll;ned visually for leaks revealed by emitted bubbles. After the visual inspection, the p~ e was rel~ced, and an 3.6 kg weight was hung from the _c~mbly so as to stress the bond. The assembly was visually inspe~ted for signs of bond se~tion. Then the lumen of the tube and the c~C~ette was 30 ~ c~u-;7,d with air to a pl~,S~Urt: of 68.9 kPa. Again, the bond was submerged and e~..-in~d visually for leaks. Ro, dçd constructions according wo gs/046ss 2 1 6 7 1 8 8 PcTluss4/o747o to Fc~mrl~ 16 were able to succ~ssfully pass the three aspects of this test, andwere thus cl~med to be suitable for use in medical tubing assemblies.

Example 18 TriLayer EMAC/SURLYN Blend Film and C~ccette A tri-layer film sample of 50 ~m of EMAC 2205, 225 of a blend of 70% EMAC 2205/30% Surlyn 8320, and 100 ~m of Surlyn 8320 was made on the 30 cm extruder setup according to Example 3. The EMAC and Surlyn resins were bl~on~l~ by hand and then added to the hopper of the center layer Br~hender Extruder. Extrusion conditions are described in Table 1. The film was tested on the laboldto~y-scale former according to Example 1, with an intern~l pl~s~,ule of 0.42 kg/cm2 and a te",l)e~ ie of 77C being used.
Complete formation oc-;u-led with strong heat seals, and a ready release from the plate.
Example 19 Tri/Bilayer Fllm and C~csette A tri/bilayer film sample of 50 ~m of EMAC 2205 and 325 ~m of Surlyn 8320 was made on the 30 cm extruder setup according to Example 3.
Extrusion conditinn~ are ~esçrihe~ in Table 1. The film was tested on the labo.dlo ~-scale former according to Example 1, with an internal p~s~u-e of 0.42 kg/cm2 and a te~ u~e of 79C being used. Complete formation occurred with strong heat seals. The c~ette was quite flexible, and alJ~ed to spring back readily after being co."plessed by hand.

Example 20 TriLayer EVA Film and C~ccette A trilayer film sample of 50 ~m of EMAC 2205, 225 of EVA (28%
VA), and 100 ~um of Surlyn 8320 was made on the 30 cm extruder setup according to F~ f 3. Extrusion conditions are described in Table 1. The film was tested on the labo.d~ol~-scale former according to Example 1, with an intern~l pl~,i.;~Ui~ of 0.42 kg/cm2 and a te~ dlu~ of 77C being used.

wo 95/04655 2 1 6 7 1 ~ ~ PcTtuss4/07470 Complete formation occurred with strong heat seals, and the films released readily from the plate.

FY~n~p'- 21 Adhesive Br~ndin~ of Tubiry and Csssette Tubing and a c~tte according to Example 16 above were bonded to each other, but this time with a cyanoacrylate adhesive commercially available as P~l"abond from National starch and Chemic~l Co.~ldlion of Englewood, NJ. A small amount of the adhesive was applied to one end of the tube, and lo the treated end was inserted into one of the molded tubes in the c~sette. The construction was then allowed to complete the cure for 12 hours at 25C.
The bond was then tested in the fashion described in Example 17, and found to have bond strength and integ~ily and adequate for its pul~ose in m~oAi~
tubing assemblies.
EAamPIe 22 Epoxy Bondin~ of Tubi~ and C~ssette Tubing and a ~C~tte acco~ing to FY~mple 16 above were bonded to each other, but this time with a W curing epoxy adhesive commercially available as W6010 from Polychem Corp. of Cranston, RI. A small amount of the adhesive was applied to one end of the tube, and the treated end was in~l~d into one of the molded tubes in the c~sette. The treated area was then subjected to high inten~ily W light shown through the wall of the c~e~ for one second. The assembly was then allowed to complete the cure for 12 hours at 25C. The bond was then tested in the fashion described in Fx~mrlc 17, and found to have bond strength and integlily and adequate for its ~Ul~)O!;e in mPAi~l tubing assemblies.

E:xample 23 Second Epoxy Bondi~
Tubing and a r~ette were bonded according to Example 19, with the exception that the W curing epoxy adhesive was instead one commercially 216~188 Wo 95/04655 pcTluss4lo747o - ~3-available as L-4240 from ICI of Wilmington, DE. Adequate bond strength and integlily was achieved.

FY~-nP~
.~usceptor Particle Bnntlin~ of Tub;n~ and Drip Chamber 1. 6 mm glass fibers col"",el~ially available as 739 DD from Corning Co. of Corning, New York were coated with a thin layer of st~inll~ss steel as described in U.S. Patent Application Serial No. 07/668,974 to form susceptor particles. These fibers were mixed into an ionomer commercially available as lo Surlyn AD 8255 from E.I. Dupont and Nemours of Wilmington, DE at a volume loading of 20%. A Haake Rheoconl System Model 600, col....lerc;ally available from Haake of S~ le~rook, NJ, was used to make this co,.,l)os;t~. A small amount of blue pigment concenllate in low density polyethylene was also used to give the co-l,l)osile a blue color. This cc",~;,i~ is the suscep~or particle filled bonding m~tPri~l.
A strip of this susceplor particle filled bonding m~t~ri~l which was about 0.25 mm thick and 3 millim~ters wide was placed around the tip of a pol~r~p~lene drip çh~ll.b~ cG"""e~c;ally available from M~AIon of Burbank, CA. Tubing made according to Example 46 of U.S. Patent Application Serial No. 08/104,256 cited above, e.g., a three layer tubing with Surlyn AD 8255 on the inside and outside surfaces and Quantu", UE645 EVA in the core, was slipped over this.
This assembly was placed in a small coil of a Lepel T-2.5-1-MC-B3W(T~ induction heater, co"""~.cially available from Lepel, of Edgewood, NY, set to the 5 to 8 MHz frequency range. The induction heater had a grid control setting of 66, plate current of .50 amps, and grid current of 142 milli~mps The coil was oval in shape with 4 turns of 3.2 mm outside r tubing with inside opening of 3.8 cm wide by 2.2 cm high by 1.6 cm deep. Power to the induction heater coil was turned on for 2.25 secon-ls.
This melted the susceptor particle filled bonding m~tPri~l and the su~ces of the tubing and drip c~mber, forming a good bond. This bond then passed wo 95/046~5 ~ I ~t ~ PcT/uss4/07470 subsequent testing as described in Example 17 for bond strength and leak ,n~lily.

F.Y~P'~ 25 S~. scrptor Particle Bl)n-l;n-~ of Tubin~ and Luer Lock Glass fibers coated with a thin layer of st~inl~ss steel as described in Fy~mple 24 were incol~ ated into a hot melt adhesive commercially available as Euremelt 2140 from Schering-Berlin of T~kt-l~nd, FL, at a volume loading of 20%. A strip of this ~.-sceplor particle filled bonding m~t~ri~l which was lo about 0.25 mm thick and 3 millimPtçrs wide was placed around the end of a piece of the trilayer tubing described in Example 24. This tubing with bonding m~t~ri~l was slipped into a luer lock made of ABS. This was placed in the induction heater coil described above and power was applied to the coil for 2.5 s~on~lc. This heated the susce~)lol particle filled bonding m~tPri~l andbonded the tubing to the luer lock. This bond then passed subsequent testing according to PY~mp'^ 17 for bond strength and leak integlily.

Example 26 Susceptor Particle Bnntlin~ of Tubinp and Drip Chamber Glass fibers coated with a thin layer of st~inl~-s~ steel as desçrihe~d in FY~mplP 24 were incol~oldted into a hot melt adhesive commercially available as JetMelt 3748 from the 3M Company of St. Paul, MN., at a volume loading of 20%.
A strip of this suseeplor particle filled bonding m~t~ri~l which was about 0.25 mm thick and 3 millimeters wide was placed around the tip of a polyyr~lene drip ch~mber commercially available from Medlon of Burbank, CA. Tubing made according to Example 8 of U.S. Patent Application Serial No. 08/104,256 cited above, e.g., a trilayer tubing with Surlyn 8320 on the inside and outside s~rfares and Exact 4028 EB in the core, was slipped over 3 0 this.
A model 2274A microwave gentl~tol commercially available from Litton of Memphis, TN was set to deliver 700 watts at a frequency of 2.45 2167~88 Wo ss/046s5 PCT/US94/07470 gig~P~t7 for 60 seconds. The bond thus created then passed subsequent testing according to Example 17 for bond strength and leak integlily.

EYample 27 SYcc~ptor ~-licle Bonlli~ of Tubin~p and C~sce~te A susceplor particle bonded assembly was ple~ d as in Example 24, except that the tubing was bonded to a c~ettP made according to Ex~..ple 16. This bond then passed ~ubs~uent testing according to FY~mple 17 for bond strength and leak inl~ily.

FY~mple 28 S~c~pto~ Particle Bon-lin~ of Tubin~ and Chamber 10---~n~-!;C amorphous powders were been produced as described in U.S. Patent App1i~tion Serial No. 07/800,632 to form susceptor particles.
The s~lsceptor particles had an alloy co".posilion of Fe685Cr85P,5C5B3 (in atomic ~r~nlage). These powders have a Curie len-p~latu-e of z 130C
and particle sizes below 44 micron (or below 325 mesh). These po~d~,~
were mixed into Q~lul~ UE645 EVA at a volume lo~in~ of 8%. A small amount of green pigmPnt concentlale in low density polyethylene was also 20 used to give the final co---l~osile a green color. This i~lu,e was cG~I~pounded in a two rolls ruWer mill manufactured by S. Bolling, Cleveland, OH, and extruded into tubings having app~i--,ately a 0.25 mm wall thickness, and 3.8 mm outside ~i~mPt~r. These tubings become the amorphous powders filled bonding m~tPri~l~
A piece of this bonding m~tPri~l which was about 3 milli~ le.~ long was placed into the tip of a pol~ p~lene drip chamber as described in FY'~ 23. Tubing made according to Example 46 of U.S. application Serial No. 08/104,256, cited above, e.g. a trilayer tubing with Surlyn AD
8255 on the inner and outer sl~rf~es and QuanLulll UE645 EVA in the core, 3 o was slipped over this.
A doæn samples of this assembly were placed in a rectangular coil of an Emabond P-005-09 induction heater set. This Emabond system has a five wo gs/04655 ~ 8~8 PCT/US94/07470 kilowatt power supply in the 3 to 7 MHz frequency range. The coil is rectangular shape with 3 turns of 15.24 cm x 5.08 cm. Power to the induction heater coil was energized for about 30 seconds. This melted the bonding m~t~ri~l~ and the surfaces to the tubing and drip chamber, forming a 5 good bonding. This bond passed subsequent testing as described in Example 17 for bond strength and leak inte~lity.

Example 29 Sl~sceptor Particle Bondi~ of Tub;nf~ and C~ccette Ferrom~gnPti~ powders as described in Example 28 were mixed into an ionomer commercially available as Surlyn 1702 from E.I. Dupont and Nemours of Wilmington, DE at a volume loading of 8%. A C. W. BMbender model 5000 mixer was used to make this CGIllpoSite. Portion of this CGIll~ , was then hot pressed by using a Carver Laboratory Press model 15 2699 cG~ "crcially available from F. S. Carver of Wabash, IN into a thin sheet of about 0.25 mm thi~nPs~. This sheet of co,l.pGsile is the susceptor powder filled bonding m~tPri~
A strip of this fcllu~ gnP,tic amorphous powder filled bonding m~tPri~l which was about 0.25 mm thick and 3 millimeter wide was placed around the 20 tubing which was made according to FY~mr1e 10 of US application Serial No.
08/104,256 cited above, e.g. a three layer tubing with Surlyn 9320 on the inner and outer s~ s and Exact 4028 the core. This tubing with the bonding m~tPri~l was slipped into an c~ette which was made according to Example 5 above. Several of these assemblies were placed in the induction 25 heater as describe~ in Example 28 for 30 seconds. This melted the bonding m~teri~l~ and the surfaces to the tubing and c~sette, forming a good bonding.
This bond passed s~sequent testing as described in Example 17 for bond ny,lh and leak ih~teglily.

Example 30 Sl~cceptQr Y~l licle Bon-lin~ Tubin~ and Ceccette A bond assembly was p~ cd according to the procedure of Example 28, except that the tubing was bonded to a c~ tte pl~ed according to FY~mple 5 above. This bond passed subsequent testing as described in FY.~mplc 17 for bond strength and leak intcglily.

Example 31 S~ tor Particle B^ndin~ of Tubin~ and Chal.-l~e.
0 A bonded assembly was p~ d a Example 29, except that the tubing was bonded to a drip çh~mher as described in FY~mrle 28. This bond passed sul)s~uent testing as desrrihed in Example 17 for bond strength and leak h~eglily.

E~xample 32 ~sceptl, Particle Bondinp of Tubin~p and Luer Lock A bonded assembly was pre~a-cd according to the procedure of FY~mp1^ 28, except the tubing was bonded to a luer lock. This bond passed subse luent testing as described in E~,lplc 17 for bond strength and leak integlily.
Example 33 S~sceptor Particle Bon-lin~ of lbbinp and Luer Lock A bond assembly was plc~cd as in Example 29, except that the tubing was bonded to a luer lock fabricated from ABS polymer. This bond passed s~3~ucnl testing as desc-ribe~ in FY~mple 17 for bond strength and leak inl~lily.
E~ample 34 P~rlicle B~ of S;~ Layer Tubin~ to Drip Chamber Suzorite mica flakes, from Suzorite Mica Products, Inc. in Hunt Valley, MD, were coated with a thin layer of st~inless steel as described in U.S. Patent Application Serial No. 07/668,974 cited above. These coated mica flakes were then mixed into Qualllulll UE645 EVA (28% vinyl acetate) WO 9~/04655 2 ~ 6 7 ~ PCT/US94/07470 at a volume loading of 10%. Red pigment and titanium dioxide were added to the col..posite to impart a red color. A thin layer of this coated particle susceptor bonding material was placed in the bond area of a drip chamber made from Rexene 1903 EVA (9% vinyl acetate). Tubing made from 5 Quanlul~ UE645 EVA was placed over this. This assembled coponent was placed in the coil of the LEPEL inductiQn heater for 2.25 seconds. The coil was made with 3 mm OD copper tubing. It had S turns, the inner ~ mPter of the coil was 13 mm, the length of the coil was 22 mm. The setting~ on the LEPEL were Grid Control 76, plate current .48 amps, grid current 120 milli~mps The susceptor filled bonding m~teri~l heated and bonded the two co.... ...~onents together, so that it passed the test described in Example 17.

Fyq~I~l~ 35 Flve-Layer Fllm and C~c~ette A five-layer film sample was made according to FY~mrle 5, except that zinc-doped, low modnllJs Surlyn 9320 was ~ubsliluled for the Surlyn 8320. Extrusion conditinn~ are described in Table 1. The film was tested on the laboratory-scale former according to Fy~mple 1, with an intern~l ple~ e of 0.42 kg/cm2 being used. At a forrnation te---pelatu~ of 94C, there was partial formation; at a formation lelll~latu~ of 101C, there was col--plete formation with good heat seals.

Example 36 EMAC TriLayer Film and C~ccette A trilayer film sample of 50 ~m of Attane 4601, 275 of EMAC 2260 and 50 ~m of Surlyn AD 8255 was made on the 30 cm extruder setup according to Example 3. Extrusion con-litions are described in Table 1. The film was tested on the labol~to,y-scale former according to Example 1, with an internal p,es~ul~ of 0.42 kg/cm2 and a te",~,dlu,e of 99C being used.
Complete formation occu~d with strong heat seals, ~Y~cPll~nt release from the plate, and eY~pll~nt clarity.

wo 95/046~ 2 1 6 7 1 8 ~ PcT~ss4/07470 ~9 Example 37 S ~cceptor Particle Fnll~n~ed Curinp of Epoxv Glass fibers coated with a thin layer of stA~inless steel were made according to FYA~mrlA 21 above foll. ing susce~lol particles which were mixed 5 into TRA-BOND FDA-2 epoxy, ~ cu~ in FYA~mple 16 above, at a loading of 20%. This loaded epoxy was applied to the ends of tubing made according to Example 8 of U.S. Patent ~p~lir~tion Serial No. 08/104,256 cited above, and these ends were inserted into a Y-sites fabricated from ABS polymer.
Care was taken to keep the thi~nes.~ of the epoxy l~ ur~ on the tubing 10 uniforl--. These constructions were placed in the coil of the LEPEL jnduGtionheater described above in F~mpl~A 24, and the heater was energized for 25 seconds. This heated the epoxy/coated fiber Illi~lule enough to cure it slightly. The green strength in these treated samples was greater than control .~mrleS made without the use of sus~ptol particles.

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EHAC SLlRLrNEHAC 2205 EVA SLRL~N
2205 8320 (Z8S VAI 8320 ~ATERl~u 1 0 E%TRUOE; 8ARREL
ZONE 1 TEHP 160 160 160 1~0 160 20NE ~ TEHP -- -- -- 185 --20NE 5 TEHP 185 ` 185 1B5 185 185 Igatel Igate) ~gate) CAST ROLL TEHP R.T.
SCREU RPH
LINE SPEED 0.91 0.91 M/HIN H/YIH
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WO 95/046SS 2 1 6 7 ~ ~8 pcTluss4lo747o Table 2 for F.Y~mI~le 1 Time to reach Degree of T~ _ c I . ~ Pressure chamber Degree of seal (C) (min.) (kg/cm2) r~ r 93 18 0.21 partial partial 96 25 0.21 partial partial 97 13 0.21 partial partial 106 16 0.21 to 0.27 complete 1 0 106 16 0.42 ~ ~ , ' c , ' 116 25 0.21 to 0.24 ~ cha~nber formed, but coll p~ d Table 3 for FT;~ 2 Time to reach Degree of T~ [c; t , ci Pressure chamber Degree of seal (oCj (min.) ~cg/cm2) Çi ~-93 18 0.21 2 0 96 25 0.21 97 13 0.21 pa tial partial 106 16 0.21 partial partial 106 25 0.24 complete cc . ' 116 4 0.21 Table 4 for Example 5 C~ette forming con-lition~
Process Attribute Cf ' ~'nn set #1 C nAifit~n set #2 Starting I . ~i (C) 38 49 Formation (highest) t~ ~. e (C) 91.7 91.1 Low air pressure (kg/cm~ 9,14 0.21 Plate h,~ ~ where low air pressure 40.6 51.7 was initiated (C) High air pressure (kg/cm~) 0.91 0.91 Plate t~ ~ O where high air pressure 7300 57 was initiated (C) Hydraulic rampressure ~g) 4:56 4:22 Cyc1e time (min.) >77 >77 Seal t~ G ra~ge (C) > 88 > 88 F~ Te~ ~i Range (C) > 88 > 88 Seal strength (Icg) 4.5 4.5 WO 95/04655 2 1 ~ 7 t 8 ~ PCT/US94/07470 Table 5 for F.Y~mrle 5 Vf ~ f~tri~`s test on c~ cassettes C " set Volume deli~ d during Volume deli~,.f~ during "KVO"
regular pumping (40 mL pumping (in mL/hour, 1.0 mL/hr e~cpected) expected) 1 40.9 1.1 42.7 2.2 42.8 5.9 44.0 11.1 40.2 3.0 2 41.5 1.4 2 43.0 3.0 2 42.9 8.2 2 41.8 4.7 2 44.0 2.7 2 45.7 1.1 2 42.9 1.8 2 39.8 not done Table 6 for F~;3."~ . 9 F~ - Te . - .i (C) Pressure ~g/cm2) Degree of Chamber ru 74 0.42 Partial (Dome) 80.5 0.42 C- .1 't (thin walls) 88 0.42 Chamber c~ rs~l Table 7 for FY~r-'- g T: . rc ûf top Ts_ r ' C of bottom Degree of Chamber plate (C) plate (C) ru .
3 75 75 Partial 79.5 83 80.5 84 C~ . ' k, but with thin walls in some ~ f . ~

Wo 95/04655 2 1 6 7 1 8 8 PCT/USg4/07470 While a descliplion of the prerelled weight fractions, proces~in~
con~ition~, and product usages have been provided by the cY~mrles, the scope of the invention is not to be limited thereto or thereby. Various m~ifi~tions - and alterations of the present invention will be appar~,lt to those skilled in the 5 art without departing from the scope and spirit of the present invention. The examples dçs~rihed in this application are illustrative of the possibilities of v~ying the amounts and types of polymeric m~teri~l~ in the multilayered tubings and films to achieve c~-~cteri~ti~s for spe~ific pul~oses.
Cons~uently, for an underst~n~lin~ of the scope of the present lo invention, reference is made to the following claims.

Claims

1. A multilayered film having outside and inside surfaces comprising:
a) a core layer of at least one chlorine-free first thermoplastic polymer having a flexibility, measured by its Young's modulus, less than about 60 megaPascals;
b) an outside surface layer of at least one chlorine-free second thermoplastic polymer having a Young's modulus up to about ten times the Young's modulus of the core layer thermoplastic polymer and being capable of non-stick release from a heated surface; and c) an inside surface layer of at least one chlorine-free third thermoplastic polymer having a Young's modulus up to about ten times the Young's modulus of the core layer thermoplastic polymer and being capable of heat self-sealing before the core and outside surface layers become substantially deformed under heat;
wherein, the film is capable of being expanded at least in part under heat and pressure without failure of film integrity, flexibility and resilience.

2. A film based assembly comprising:
a molded structure having two sides, each side being comprised of a film according to claim 1 and at least one of the sides being at least in part expanded.

3. A process for making a multilayered film having outside and inside surfaces and at least a core layer and outside and inside surface layers,comprising: coextruding at least one flexible, chlorine-free first thermoplasticpolymer as at least the core layer along with at least one chlorine-free second thermoplastic polymer having hot surface release capability as at least the outside surface layer and at least one chlorine-free third thermoplastic polymerhaving self-sealing capability as the inside surface layer, wherein coextrusion conditions of pressure and heat cause the thermoplastic polymers to become melts, the first thermoplastic polymer has a flexibility, measured by its Young's modulus, less than about 60 megaPascals and the second and third thermoplastic polymers have Young's moduli that are up to about ten times greater than the modulus of the first thermoplastic polymer, thereby providing the multilayered film.

4. A method of forming a film based structure comprising:
placing two sheets of a film of claim 1 between mold halves of a compression blow mold, at least one of the haves having internal cavities so that the outside surface layers of the sheets face the mold halves and the inside surface layers are positioned to contact each other when the mold is closed; andapplying pressure and heat to the sheets in the closed mold while applying gas pressure to the portion of the sheets within the internal cavities of the mold to produce the film based structure.

5. The multilayered film, film based assembly, or method of any preceding claim, wherein the Young's moduli of the second and third thermoplastic polymers are about equal to or are greater than the Young's modulus of the first thermoplastic polymer.

6. The multilayered film, film based assembly, or method of any preceding claim, wherein the Young's moduli of the second and third thermoplastic polymers are up to about seven times the Young's modulus of the first thermoplastic polymer.

7. The multilayered film, film based assembly, or method of any preceding claim, wherein the flexibility of the first thermoplastic polymer is measured by its Young's modulus within a range of about 10 to about 60 megaPascals and wherein the Young's moduli of the second and third thermoplastic polymers are within a range of from about 15 to 300 megaPascals.

8. The multilayered film, film based assembly, or method of any preceding claim, having a flexibility that mimics or is greater than that of polyvinyl chloride medical film and having an abrasion resistance that mimics or is greater than that of polyvinyl chloride medical film

9. The multilayered film, film based assembly, or method of any preceding claim, having an outside surface abrasion resistance having an abrasive index range of at least about 100 as measured by ASTM test D1630-83.

10. The multilayered film, film based assembly, or method of any preceding claim, which after at least partial expansion to provide a raised portion relative to the unexpanded portion of the film exhibits an essentially complete resilience of the expanded portion and essentially no film failure of the expanded portion throughout an endurance test of at least 10,000 cycles of the expanded portion as a rolling diaphragm through expansion and compression between a completely filled condition and a completely collapsed condition.

11. The multilayered film, film based assembly, or method of any preceding claim, which contains at least in its inside surface layer essentiallyno medically harmful substance capable of leaching into an aqueous based or organic based fluid in contact with the inside surface of the film.

12. The multilayered film, film based assembly, or method of any preceding claim, having additional layers between the outside and inside surface layers, those additional layers being comprised of at least one of the first, second and third thermoplastic polymers.

13. The multilayered film, film based assembly, or method of any preceding claim, wherein the first, second and third thermoplastic polymers are polymers of olefin monomers or are copolymers of olefin monomer and substituted olefin monomers.

14. A multilayered film, film based assembly or method according to claim 13 wherein the substituted olefin monomer is a C4 to C14 mono-unsaturated alkene, a C8 to C14 aryl alkene, or a C2 to C6 mono-unsaturated alkene having a moiety selected from the group consisting of acetoxy, carboxy, oxyalkanoyl, and alkoxycarbonyl of 1 to 6 carbons in the alkoxy group, and wherein the thickness ratio of the outside surface layer to the core layer to inside surface layer is about 1:1:1 to about 1:30:1.

15. The multilayered film, film based assembly or method of any preceding claim, wherein at least one of said second thermoplastic polymer and said third thermoplastic polymer is the same as said first thermoplastic polymer and wherein said multilayered film is a two-layered film.

16. The multilayered film, film based assembly, or method of any preceding claim, further comprising a divider layer of the second thermoplastic polymer positioned within the core layer.

17. A film based assembly according to any preceding claim, wherein the molded structure is a cassette having molded-in fluid channels and pumping bubbles therein.

18. A film based assembly according to any preceding claim, wherein the molded structure is an intravenous fluid bag.

19. A method for forming a film based assembly comprising:
bonding a structure formed according to claim 4 to a plastic fluid transporting component.

20. A method for forming a film based assembly according to claim 19 wherein the bonding is accomplished by applying a mixture of a polymeric binder and susceptor particles to the structure or component or both, contacting the structure and component together to form a joint at the location of bonding, and subjecting the joint to electromagnetic radiation

21. A method for forming a film based assembly according to claim 19 wherein the bonding is performed by adhesive bonding.

22. A method for forming a film based assembly according to claim 21 wherein the adhesive used in the adhesive bonding contains susceptor particles, and further wherein the bonding step comprises subjecting the adhesive to electromagnetic radiation to enhance green strength of the adhesive.

23. A method for forming a medical device, comprising:
providing at least one tube and at least one plastic fluid transporting component, applying a mixture of a polymeric binder and susceptor particles to the tube or component or both, contacting the tube and component together to form a joint at the location of bonding, and subjecting the joint to electromagnetic radiation.

24. A method according to claim 23, wherein the susceptor particles are selected from the group consisting of particles coated with ferromagnetic or ferromagnetic material, particles coated with conductive material, and ferromagnetic amorphous powders, and wherein at least one of the tube or the plastic fluid transporting component is made from chlorine-free materials.

25. A method for bonding two components, comprising the steps of:

providing a first and a second component, applying a mixture of a thermoset adhesive and susceptor particles to the first component, the second component or both, contacting the first and second components together to form a joint at the location of bonding and subjecting the joint to electromagnetic radiation to enhance green strength of the adhesive.

26. A method according to claim 25, wherein the first component is a tube and the second component is a fluid transporting part.

27. A method according to claim 26, wherein at least one of the tube and the plastic fluid transporting component is made from chlorine-free materials.

28. A method according to claim 25, wherein the susceptor particles are selected from the group consisting of particles coated with ferromagnetic or ferromagnetic material, particles coated with conductive material, and ferromagnetic amorphous powders.

29. A composition of matter comprising a mixture of a thermoset adhesive and susceptor particles.

30. A composition of matter according to claim 29, wherein the thermoset adhesive is an epoxy adhesive, wherein the susceptor particles are selected from the group consisting of particles coated with ferromagnetic or ferromagnetic material, particles coated with conductive material, and ferromagnetic amorphous powders, and wherein the volume loading of susceptor particles in the mixture is between about 1% and about 65%