Organ-on-a-Chip: Methods and Protocols

322 Pages·2021·10.055 MB·English

by  Marco Rasponi

Methods in
Molecular Biology 2373
Marco Rasponi Editor
Organ-
on-a-Chip
Methods and Protocols
M M B
ETHODS IN OLECULAR IO LO GY
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University ofHertfordshire
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Organ-on-a-Chip
Methods and Protocols
Edited by
Marco Rasponi
Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milano, Italy
Editor
MarcoRasponi
DepartmentofElectronics,Information
andBioengineering
PolitecnicodiMilano
Milano,Italy
ISSN1064-3745 ISSN1940-6029 (electronic)
MethodsinMolecularBiology
ISBN978-1-0716-1692-5 ISBN978-1-0716-1693-2 (eBook)
https://doi.org/10.1007/978-1-0716-1693-2
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Preface
Inthelastfewdecades,microfluidicshasbeenestablishedasapromisingtoolfordeveloping
anewsetofminiaturizeddevices,particularlyrelevantinthebiologicalfield.Latestadvance-
ments in microfabrication techniques allowed the recapitulation of physiologically relevant
cell microenvironments within microdevices, establishing a series of microphysiological
systems. Building upon the combination of microfluidics, 3D microarchitectures, and cell
cultures,organ-on-a-chip(OoC)emergedasatechnologyabletooutperformconventional
in vitro models in providing a patho-physiologically relevant setting for comprehensive
investigationsofhumanphysiologyanddiseasestates.
The ability of OoC to mimic the target human organ functions, together with the
inherentadvantagesofminiaturization,e.g.,highcontroloverthemasstransportphenom-
enaandtheneedofextremelylowamountsofcellsandreagents,iscontributingtotheidea
of using such advanced biological models in the drug development process (DDP) to
improvethescreeningofdrugcandidatesprior toinvivotesting.
Inthisbook,acollectionofmicrophysiologicalsystemsemployedforchemicals/drugs
screeningtogetherwiththestrategiesemployedtomimicvariousphysiologicalconditionsis
presented.Inparticular,modelsatincreasingcomplexitiesareshown,frommicrofluidiccell
monolayers, to multi-compartmentalized cultures, to physiologic barriers and 3D cell
microtissues.
OoC platforms here described include liver, intestine, blood-brain barrier, kidney,
vessels, cardiac and skeletal muscles, articular joint, and human fat. Additionally, the first
three chapters of the book provide a comprehensive overview of the microfabrication
technologies used to fabricate OoC devices, namely (1) standard photolithography and
softlithography,(2)techniquestofabricatemembranesinOoCmodels,and(3)industrial-
orientedfabricationmethodswhichmaybeusedtomovetheOoCsectorfromacademiato
themarket.
I hope that this volume on Organ-on-a-Chip will be useful to a wide readership of
scientists working in the fields of biology, pharmacology, bioengineering, and tissue engi-
neering. The protocols here described have been tuned and optimized for the specific
applications described in the corresponding chapters. They can be strictly followed to
reproduce the experiments therein described or serve as general guidelines to establish
neworgan-on-a-chipmodels.
Milano,Italy MarcoRasponi
v
Contents
Preface ..................................................................... v
Contributors................................................................. ix
1 PhotoandSoftLithographyforOrgan-on-ChipApplications ................ 1
ErikaFerrari,FedericoNebuloni,MarcoRasponi,
andPaolaOcchetta
2 Organ-on-ChipsforStudyingTissueBarriers:StandardTechniques
andaNovelMethodforIncludingPorousMembranesWithin
MicrofluidicDevices..................................................... 21
MattiaBallerini,MohammadJouybar,AndreaMainardi,
MarcoRasponi,andGiovanniStefanoUgolini
3 ThermoplasticMicrofluidics.............................................. 39
PerMagnusKristiansen,AgnieszkaKarpik,JeromeWerder,
MarcoGuilherme,andMichaelGrob
4 BileDuct-on-a-Chip .................................................... 57
YuDu,WilliamJ.Polacheck,andRebeccaG.Wells
5 EstablishmentofaModularAnaerobicHumanIntestineChip ............... 69
SasanJalili-Firoozinezhad,AmirBein,FrancescaS.Gazzaniga,
CicelyW.Fadel,RichardNovak,andDonaldE.Ingber
6 IntestinalEpitheliumTubulesonaChip................................... 87
KingaKosim,IrisSchilt,Henri¨etteL.Lanz,PaulVulto,
andDorotaKurek
7 AHumanNeurovascularUnitOn-a-Chip ................................. 107
SharonWeiLingLee,RenatoRogosic,ClaudiaVenturi,
ManuelaTeresaRaimondi,AndreaPavesi,
andGiuliaAdriani
8 GenerationofaGlomerularFiltrationBarrieronaGlomerulus-on-a-Chip
Platform ............................................................... 121
LauraPerinandStefanoDaSacco
9 ElectromechanicalStimulationof3DCardiacMicrotissues
inaHeart-on-ChipModel............................................... 133
RobertaVisone,PaolaOcchetta,andMarcoRasponi
10 MiniaturizedVascularizedBleedingModelofHemostasis ................... 159
ElaissaTrybusHardy,YumikoSakurai,andWilburA.Lam
11 FabricationandUseofaPumplessMicrofluidicLymphaticVesselChip ....... 177
ParinazFathiandMandyB.Esch
12 On-ChipPlateletActivationAssessment:MicrofluidicEmulation
ofShearStressProfilesInducedbyMechanicalCirculatory
SupportDevices........................................................ 201
TatianaMencarini,SilviaBozzi,andAlbertoRedaelli
vii
viii Contents
13 Biofabricationof3DHumanMuscleModelwithVascularization
andEndomysium....................................................... 213
SimoneBersini,RiccardoFrancescato,andMatteoMoretti
14 MechanicalInductionofOsteoarthritisTraits
inaCartilage-on-a-ChipModel .......................................... 231
AndreaMainardi,PaolaOcchetta,andMarcoRasponi
15 DetailedMethodologytoEstablishaSynovium/Cartilage-on-a-ChipModel
toInvestigatetheProcessofMonocyteExtravasation ....................... 253
SilviaPalombella,ShimaSalehi,CarlottaMondadori,GiuseppeTalo`,
ValerioSansone,MatteoMoretti,andSilviaLopa
16 AMesoscale3DCultureSystemforNativeandEngineered
BiphasicTissues:ApplicationtotheOsteochondralUnit .................... 267
IreneChiesa,RobertoDiGesu`,KalonJ.Overholt,
andRiccardoGottardi
17 3DBiofabricatedInVitroModelsofVascularizedandMineralized
BoneTissues ........................................................... 283
MariaVittoriaColombo,SimoneBersini,ChiaraArrigoni,
andMatteoMoretti
18 Isolation,Integration,andCultureofHumanMature
AdipocytesLeveragingOrgan-on-ChipTechnology......................... 297
JuliaRogal,JuliaRoosz,andPeterLoskill
Index ...................................................................... 315
Contributors
GIULIAADRIANI • SingaporeImmunologyNetwork(SIgN),BiomedicalSciencesInstitute,
AgencyforScience,Technology,andResearch(A*STAR),Singapore,Singapore
CHIARAARRIGONI • RegenerativeMedicineTechnologiesLaboratory,EnteOspedaliero
Cantonale,Lugano,Switzerland
MATTIABALLERINI • DepartmentofElectronics,InformationandBioengineering,Politecnico
diMilano,Milan,Italy
AMIRBEIN • WyssInstituteforBiologicallyInspiredEngineering,HarvardUniversity,
Boston,MA,USA
SIMONEBERSINI • RegenerativeMedicineTechnologiesLaboratory,EnteOspedaliero
Cantonale,Lugano,Switzerland
SILVIABOZZI • DepartmentofElectronics,InformationandBioengineering,Politecnicodi
Milano,Milan,Italy
IRENE CHIESA • ResearchCenter‘E.Piaggio’,UniversityofPisa,Pisa,Italy;Departmentof
InformationEngineering,UniversityofPisa,Pisa,Italy;DepartmentofPediatrics,
DivisionofPulmonaryMedicine,TheChildren’sHospitalofPhiladelphiaandThe
UniversityofPennsylvania,Philadelphia,PA,USA;Center forCellularandMolecular
Engineering,DepartmentofOrthopaedicSurgery,SchoolofMedicine,Universityof
Pittsburgh,Pittsburgh,PA,USA
MARIAVITTORIACOLOMBO • RegenerativeMedicineTechnologiesLaboratory,Ente
OspedalieroCantonale,Lugano,Switzerland;DepartmentofChemistry,Materialsand
ChemicalEngineering(CMIC)“GiulioNatta”,PolitecnicodiMilano,Milan,Italy
STEFANO DASACCO • ChildrenHospitalLosAngeles,LosAngeles,CA,USA
ROBERTODIGESU` • DepartmentofPediatrics,DivisionofPulmonaryMedicine,The
Children’sHospitalofPhiladelphiaandTheUniversityofPennsylvania,Philadelphia,PA,
USA;Center forCellularandMolecularEngineering,DepartmentofOrthopaedic
Surgery,SchoolofMedicine,UniversityofPittsburgh,Pittsburgh,PA,USA;FondazioneRi.
MED,Palermo,Italy
YUDU • DivisionofGastroenterology,DepartmentofMedicine,PerelmanSchoolofMedicine
attheUniversityofPennsylvania,Philadelphia,PA,USA;Center forEngineering
MechanoBiology,TheUniversityofPennsylvania,Philadelphia,PA,USA
MANDYB.ESCH • BiophysicalandBiomedicalMeasurementGroup,Microsystemsand
NanotechnologyDivision,PhysicalMeasurementLaboratory,NationalInstituteof
StandardsandTechnology,Gaithersburg,MD,USA
CICELYW.FADEL • WyssInstituteforBiologicallyInspiredEngineering,HarvardUniversity,
Boston,MA,USA;DepartmentofNeonatology,BethIsraelDeaconessMedicalCenter,
Boston,MA,USA;DepartmentofPediatrics,HarvardMedicalSchool,Boston,MA,USA
PARINAZFATHI • DepartmentsofBioengineering,MaterialsScienceandEngineering,and
BeckmanInstitute,UniversityofIllinoisatUrbana-Champaign,Urbana,IL,USA
ERIKAFERRARI • DepartmentofElectronics,InformationandBioengineering,Politecnicodi
Milano,Milan,Italy
RICCARDOFRANCESCATO • RegenerativeMedicineTechnologiesLaboratory,EnteOspedaliero
Cantonale,Lugano,Switzerland;DepartmentofElectronics,Informationand
Bioengineering,PolitecnicodiMilano,Milano,Italy
ix
x Contributors
FRANCESCAS.GAZZANIGA • WyssInstituteforBiologicallyInspiredEngineering,Harvard
University,Boston,MA,USA;DepartmentofImmunology,HarvardMedicalSchool,
Boston,MA,USA
RICCARDOGOTTARDI • DepartmentofPediatrics,DivisionofPulmonaryMedicine,The
Children’sHospitalofPhiladelphiaandTheUniversityofPennsylvania,Philadelphia,PA,
USA;Center forCellularandMolecularEngineering,DepartmentofOrthopaedic
Surgery,SchoolofMedicine,UniversityofPittsburgh,Pittsburgh,PA,USA;FondazioneRi.
MED,Palermo,Italy
MICHAELGROB • FHNWUniversityofAppliedSciencesandArtsNorthwesternSwitzerland,
SchoolofEngineering,InstituteofPolymerNanotechnology(INKA),Windisch,
Switzerland
MARCOGUILHERME • FHNWUniversityofAppliedSciencesandArtsNorthwestern
Switzerland,SchoolofEngineering,InstituteofProductandProductionEngineering
(IPPE),Windisch,Switzerland
ELAISSATRYBUSHARDY • WallaceH.CoulterDepartmentofBiomedicalEngineering,
GeorgiaInstituteofTechnologyandEmoryUniversity,Atlanta,GA,USA;Departmentof
Pediatrics,DivisionofPediatricHematology/Oncology,EmoryUniversitySchoolof
Medicine,Atlanta,GA,USA;AflacCancerandBloodDisordersCenterofChildren’s
HealthcareofAtlanta,Atlanta,GA,USA
DONALD E.INGBER • WyssInstituteforBiologicallyInspiredEngineering,Harvard
University,Boston,MA,USA;VascularBiologyProgramandDepartmentofSurgery,
BostonChildren’sHospitalandHarvardMedicalSchool,Boston,MA,USA;HarvardJohn
A.PaulsonSchoolofEngineeringandAppliedSciences,Cambridge,MA,USA
SASANJALILI-FIROOZINEZHAD • KochInstituteforIntegrativeCancerResearch,
MassachusettsInstituteofTechnology,Cambridge,MA,USA
MOHAMMADJOUYBAR • Microsystems,EindhovenUniversityofTechnology,Eindhoven,The
Netherland;InstituteforComplexMolecularSystems,EindhovenUniversityofTechnology,
Eindhoven,TheNetherland
AGNIESZKAKARPIK • FHNWUniversityofAppliedSciencesandArtsNorthwestern
Switzerland,SchoolofEngineering,InstituteofPolymerNanotechnology(INKA),
Windisch,Switzerland;LaboratoryofMicro-andNanotechnology(LMN),PaulScherrer
Institute(PSI),Villigen-PSI,Switzerland
KINGAKOSIM • MimetasBV,Leiden,TheNetherlands
PERMAGNUSKRISTIANSEN • FHNWUniversityofAppliedSciencesandArtsNorthwestern
Switzerland,SchoolofEngineering,InstituteofPolymerNanotechnology(INKA),
Windisch,Switzerland;LaboratoryofMicro-andNanotechnology(LMN),PaulScherrer
Institute(PSI),Villigen-PSI,Switzerland;SchoolofMechanicalandMaterial
Engineering,UniversityCollegeDublin,Belfield,Dublin4,Ireland
DOROTAKUREK • MimetasBV,Leiden,TheNetherlands
WILBURA.LAM • WallaceH.CoulterDepartmentofBiomedicalEngineering,Georgia
InstituteofTechnologyandEmoryUniversity,Atlanta,GA,USA;Departmentof
Pediatrics,DivisionofPediatricHematology/Oncology,EmoryUniversitySchoolof
Medicine,Atlanta,GA,USA;AflacCancerandBloodDisordersCenterofChildren’s
HealthcareofAtlanta,Atlanta,GA,USA
HENRIE¨TTEL.LANZ • MimetasBV,Leiden,TheNetherlands
SHARONWEILINGLEE • SingaporeImmunologyNetwork(SIgN),BiomedicalSciences
Institute,AgencyforScience,Technology,andResearch(A*STAR),Singapore,Singapore;