DK2313487T3 - Organimiterende anordning med mikrokanaler og anvendelsesfremgangsmåder - Google Patents
Organimiterende anordning med mikrokanaler og anvendelsesfremgangsmåder Download PDFInfo
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- DK2313487T3 DK2313487T3 DK09790529.3T DK09790529T DK2313487T3 DK 2313487 T3 DK2313487 T3 DK 2313487T3 DK 09790529 T DK09790529 T DK 09790529T DK 2313487 T3 DK2313487 T3 DK 2313487T3
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Claims (15)
1. Organimiterende anordning, der omfatter: et legeme med en central mikrokanal (250) deri og en mindst delvist porøs og mindst delvist fleksibel membran (208) placeret inde i den centrale mikrokanal og langs et plan, hvilken membran er konfigureret til at adskille den centrale mikrokanal for at danne en første central mikrokanal (250A) og en anden central mikrokanal (250B), hvor et første fluid tilføres gennem den første centrale mikrokanal og et andet fluid tilføres gennem den anden centrale mikrokanal, hvilken membraner er coatet med mindst ét bindingsmolekyle, der understøtter klæbning af en flerhed af levende celler; og en første funktionskanal (252) adskilt fra den første og den anden centrale mikrokanal af en første mikrokanalvæg (234, 244), hvor membranen er monteret på den første mikrokanalvæg, og når et tryk påføres den første funktionskanal, bevirker det, at membranen bøjes i en første ønsket retning for at ekspandere eller sammentrækkes langs planet inde i den første og den anden centrale mikrokanal.
2. Anordning ifølge krav 1, der endvidere omfatter: en anden funktionskanal (252) adskilt fra den første og den anden centrale mikrokanal af en anden mikrokanalvæg (234, 244), hvor en modsat ende af membranen er monteret på den anden mikrokanalvæg, og når et tryk påføres den anden funktionskanal, bevirker det, at membranen afbøjes i en anden ønsket retning for at ekspandere eller sammentrækkes langs planet inde i den første og den anden centrale mikrokanal.
3. Anordning ifølge krav 1 eller krav 2, der endvidere omfatter: en første membran (806A; 906A) og en anden membran (806B; 906B) placeret inde i den centrale mikrokanal, hvor den anden membran er orienteret parallelt med den første membran for at danne en tredje central mikrokanal derimellem; eller en flerhed af membraner (806A, 806B; 906A, 906B), der er placeret langs parallelle planer i den centrale mikrokanal, hvor mindst én af flerheden af membraner er mindst delvist porøs, hvilken flerhed af membraner er konfigureret til at opdele den centrale mikrokanal i en flerhed af centrale mikrokanaler.
4. Fremgangsmåde, der omfatter: tilvejebringelse af en organimiterende anordning med et legeme, hvilket legeme indbefatter en mindst delvist porøs og mindst delvist elastisk membran (208) placeret langs et plan inde i en central mikrokanal for at opdele den centrale mikrokanal i en første central mikrokanal (250A) og en anden central mikrokanal (250B), hvor membranen er coatet med mindst ét bindingsmolekyle, der understøtter klæbning af en flerhed af levende celler, og mindst én funktionskanal (252), der er adskilt fra den første og den anden centrale mikrokanal af en mikrokanalvæg (234, 244), hvor membranen er monteret på mikrokanalvæggen; tilførsel af et første fluid, der eventuelt omfatter hvide blodlegemer, gennem den første centrale mikrokanal; tilførsel af et andet fluid gennem den anden centrale mikrokanal; påføring af et tryk på den mindst ene funktionskanal for at bevirke, at membranen afbøjer i en ønsket retning for at ekspandere eller sammentrækkes langs planet inde i den første og den anden mikrokanal; og overvågning af cellers adfærd i forhold til membranen mellem den første og den anden centrale mikrokanal.
5. Fremgangsmåde ifølge krav 4, hvor påføring af et tryk endvidere omfatter: øgning af trykket, således at én eller flere sider af membranen bevæger sig i ønskede retninger langs planet; og sænkning af trykket, således at den ene eller flere sider af membranen bevæger sig i en modsat retning langs planet.
6. Anordning ifølge et hvilket som helst af kravene 1-3, hvor mindst én poreåbning i membranen er mellem ,5 og 20 mikron i en breddedimension, og/eller hvor membranen er coatet med ét eller flere cellelag, hvor det ene eller flere cellelag er påført en overflade af membranen.
7. Fremgangsmåde ifølge et hvilket som helst af kravene 4 eller 5, hvor membranen er coatet med ét eller flere cellelag, hvor det ene eller flere cellelag påføres en overflade af membranen og/eller mindst én poreåbning i membranen er mellem ,5 og 20 mikron i en breddedimension, og/eller hvor én eller begge sider af membranen behandles med ét eller flere cellelag (608, 610), hvor det ene eller flere cellelag omfatter celler udvalgt fra en gruppe, der er udvalgt fra metazo-, pattedyre- og humane celler; fortrinsvis hvor cellerne er udvalgt fra en gruppe, der er udvalgt fra epitel-, endotel-, mesenkymale, muskel-, immun-, nerve- og hæmatopoietiske celler; eller hvor én side af membranen behandles med epitelceller og den anden side af membranen behandles med endotelceller.
8. Anordning ifølge et hvilket som helst af kravene 1-3 eller 6, hvor én eller begge sider af membranen behandles med ét eller flere cellelag (608, 610), hvor det ene eller flere cellelag omfatter celler udvalgt fra en gruppe, der er udvalgt fra metazo-, pattedyre- og humane celler; fortrinsvis hvor cellerne er udvalgt fra en gruppe, der er udvalgt fra epitel-, endotel-, mesenkymale, muskel-, immun-, nerve- og hæmatopoietiske celler; eller hvor én side af membranen behandles med epitelceller og den anden side af membranen behandles med endotelceller.
9. Anordning ifølge krav 8, hvor anordningens legeme og membranen er fremstillet af et biokompatibelt eller bionedbrydeligt materiale; og/eller hvor membranen er coatet med et biokompatibelt middel, der letter binding af det mindst ene cellelag på membranen.
10. Anordning ifølge krav 9, hvor det biokompatible middel er en ekstracellulær matrix, der omfatter collagen, fibronectin og/eller laminin; eller hvor det biokompatible materiale er udvalgt fra en gruppe, der er udvalgt fra collagen, laminin, proteoglycan, vitronectin, fibronectin, poly-D-lysin og polysaccharid.
11. Fremgangsmåde ifølge et hvilket som helst af kravene 4, 5 eller 7, der endvidere omfatter: etablering af kontakt mellem membranen og mindst ét lag af celler (608) på en første side af membranen og mindst ét lag af celler (610) på en anden side af membranen, hvorved der dannes en vævs struktur, der omfatter mindst to forskellige celletyper; etablering af kontakt mellem vævsstrukturen, der omfatter mindst to forskellige celletyper, og mindst ét middel i et anvendeligt celledyrkningsmedium; og måling af et respons fra cellerne i vævsstrukturen, der omfatter mindst to forskellige celletyper, for at bestemme effekten af det mindst ene middel på cellerne; fortrinsvis hvor det anvendelige celledyrkningsmedium tilføres hvide blodlegemer; og/eller hvor midlet er udvalgt fra en gruppe, der er udvalgt fra nanopartikler, miljømæssige toksiner eller forureningskilder, cigaretrøg, kemikalier eller partikler anvendt i kosmetiske produkter, lægemidler eller lægemiddelkandidater, aerosoler, naturligt forekommende partikler indbefattende pollen, kemiske våben, enkelt- eller dobbeltstrengede nukleinsyrer, vira, bakterier og encellede organismer.
12. Fremgangsmåde ifølge krav 11, hvor vævsstrukturen, der omfatter mindst to forskellige celletyper, omfatter alveolære epitelceller på den første side af den porøse membran og pulmonale mikrovaskulære celler på den anden side af den porøse membran.
13. Fremgangsmåde ifølge krav 11 eller krav 12, hvor målingen af responset udføres ved måling af ekspression af reaktive oxygenarter; eller ved anvendelse af vævsfarvning; eller hvor målingen af responset udføres fra en prøve af celledyrkningsmediet i kontakt med den første eller den anden eller begge sider af membranen omfattende vævs struktur, der omfatter mindst to forskellige celletyper.
14. Fremgangsmåde ifølge et hvilket som helst af kravene 11 til 13, der endvidere omfatter før måling af effekten af midlet, udtagning af en biopsi af membranen omfattende vævsstruktur, der omfatter mindst to forskellige celletyper, hvor biopsien farves.
15. Fremgangsmåde ifølge et hvilket som helst af kravene 11 til 14, der endvidere omfatter: sammenligning af effekten af midlet med et andet middel eller en kontrol uden midlet i et tilsvarende parallelt anordnings system; eller et trin med etablering af kontakt mellem membranen og mindst to midler, hvor der først etableres kontakt med det første middel for at bevirke en effekt på vævsstrukturen, der omfatter mindst to forskellige celletyper, og der etableres kontakt med det mindst andet middel efter et tidsrum for at teste effekten af det andet middel på vævsstrukturen, der omfatter mindst to forskellige celletyper, der påvirkes af det første middel.
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