N. Gaio1 – M.L.H. Vlaming2 – T. van Weelden3 – P. Nacken2 – S. Braam2 – E. Boschman3 – R. Dekker1,4 1Department of Microelectronics, Delft University of Technology, Feldmannweg 17, 2628CT Delft, The Netherland
2Pluriomics B.V., Biopartner building 3, Galileiweg 8, 2333 BD Leiden, The Netherlands 3Boschman Technologies/APC, Stenograaf 3, 6921EX Duiven, The Netherlands
4Philips Innovation Service, NL-5656 AE Eindhoven, Netherlands
INTRODUCTION
DEVICE DESIGN
BIOCOMPATIBILITY TESTS
Contact: Nikolas Gaio - Email: [email protected]
CYTOSTRETCH DEVICE: A STRETCHABLE MICRO-ELECTRODE ARRAY IN MULTI-WELL PLATE FORMAT.
Delft University of Technology
Cytostretchisamodularpla*ormthatcanbecustomizedfordifferentOrgan-on-Chip(OOC)models.Thisisbasedonconven5onal semiconductormicro-fabrica5on.Thedevicecanbeused tomechanically s5mulatecardiomyocytes invitro.Moreover,Cytostretchisprovidedwithamicro-electrodearray(MEA).Herewepresentthelatestresultstowardsthe industrializaDon of the Cytostretch plaEorm realized in the framework of the European InForMed project. TheproducDon version allows for parallel screening, and is compa5ble with standard readout equipment. Finally, themolded package, fabricated with a film assisted molding technology, comprises the plasDc well where thecardiomyocytes are cultured and it isolates electrically the interconnecDon between the MEA and the PCB duringincubaDon.Thebiocompa5bilityofthenewmoldedpackagewasprovenbyseedingonitiPSC-derivedCardiomyocytes.
Mul5-wellplate- Moldedwells(Epoxy)- Alllowsparallelscreening;- CompaDblewithopDcalinspecDon;- Suitableforinterfacingwithavailableread-outsystems.
Chip-Silicon-basedmicrofabricaDon;-Includecellcultureenvironment;-EquippedwithMEA.
Microelectrodearray- 12TitaniumNitrideelectrodes;- EmbeddedinstretchablePDMSfoil;- Itcanbecombinedwithasetofmicro-groovestoinducecellalignment.
MoldedPackage
PCB
MetalLine
Electrode
Micro-Groove
SiliconSubstrate
PDMSfoil
MOLDED PACKAGING
MicrofabricatedChip
FreshFimIntake FilmVacumForming
PCBLoading MoldClosing
CavityFilling OpeningandUnload
FILMASSISTEDMOLDINGGoal:TestthebiocompaDbilityofnewlydevelopedCytostretchpackagingmaterialswithPluricyte®Cardiomyocytes;Readout:MonitorcellandmonolayerappearancewithlightmicroscopyandverifybeaDngofcardiomyocytesusingcalciumdye.Pluricyte®CardiomyocytesinMolding-compound(G700LTD)precondi5onedmedia:
Lower cell density in the cells culture in precondiDonedmedium. Calcium transients were observed in all condiDonssuggesDngcellsarebeaDng.
ControlPlate Precondi5onedMedium
Lower cell density was observed in the cell culture on the Cytostretch device. While the cardiomyocytesappeared normal, no calcium transients were observed. Future tests will invesDgate the causes (maturity/funcDonality/..).
Pluricyte®CardiomyocytesonCytostretchaRer7days–Moldingcompound:EME-G770HPTypeA
Two different molding compounds have been tested:G700LTDand:EME-G770HPTypeA.