title: A modular segmented-flow platform for 3D cell cultivation.
abstract: In vitro 3D cell cultivation is promised to equate tissue in vivo more realistically than 2D cell cultivation corresponding to cell-cell and cell-matrix interactions. Therefore, a scalable 3D cultivation platform was developed. This platform, called pipe-based bioreactors (pbb), is based on the segmented-flow technology: aqueous droplets are embedded in a water-immiscible carrier fluid. The droplet volumes range from 60 nL to 20 μL and are used as bioreactors lined up in a tubing like pearls on a string. The modular automated platform basically consists of several modules like a fluid management for a high throughput droplet generation for self-assembly or scaffold-based 3D cell cultivation, a storage module for incubation and storage, and an analysis module for monitoring cell aggregation and proliferation basing on microscopy or photometry. In this report, the self-assembly of murine embryonic stem cells (mESCs) to uniformly sized embryoid bodies (EBs), the cell proliferation, the cell viability as well as the influence on the cell differentiation to cardiomyocytes are described. The integration of a dosage module for medium exchange or agent addition will enable pbb as long-term 3D cell cultivation system for studying stem cell differentiation, e.g. cardiac myogenesis or for diagnostic and therapeutic testing in personalized medicine.
authors.affiliation: Department of Bioprocess Engineering, Institute for Bioprocessing and Analytical Measurement Techniques e.V., Rosenhof, D-37308 Heilbad Heiligenstadt, Germany. Electronic address: Karen.Lemke@iba-heiligenstadt.de.
authors.forename: Karen
authors.initials: K
authors.lastname: Lemke
authors.affiliation: Department of Bioprocess Engineering, Institute for Bioprocessing and Analytical Measurement Techniques e.V., Rosenhof, D-37308 Heilbad Heiligenstadt, Germany. Electronic address: Tobias.Foerster@iba-heiligenstadt.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Förster
authors.affiliation: Department of Bioprocess Engineering, Institute for Bioprocessing and Analytical Measurement Techniques e.V., Rosenhof, D-37308 Heilbad Heiligenstadt, Germany. Electronic address: Robert.Roemer@iba-heiligenstadt.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Römer
authors.affiliation: Department of Bioprocess Engineering, Institute for Bioprocessing and Analytical Measurement Techniques e.V., Rosenhof, D-37308 Heilbad Heiligenstadt, Germany; Faculty of Medicine, Technische Universität Dresden, Centre for Translational Bone, Joint and Soft Tissue Research, Fetscherstr. 74, D-01307 Dresden, Germany. Electronic address: mandy.quade@tu-dresden.de.
authors.forename: Mandy
authors.initials: M
authors.lastname: Quade
authors.affiliation: Department of Bioprocess Engineering, Institute for Bioprocessing and Analytical Measurement Techniques e.V., Rosenhof, D-37308 Heilbad Heiligenstadt, Germany. Electronic address: Stefan.Wiedemeier@iba-heiligenstadt.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiedemeier
authors.affiliation: Department of Bioprocess Engineering, Institute for Bioprocessing and Analytical Measurement Techniques e.V., Rosenhof, D-37308 Heilbad Heiligenstadt, Germany. Electronic address: Andreas.Grodrian@iba-heiligenstadt.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Grodrian
authors.affiliation: Department of Bioprocess Engineering, Institute for Bioprocessing and Analytical Measurement Techniques e.V., Rosenhof, D-37308 Heilbad Heiligenstadt, Germany. Electronic address: Gunter.Gastrock@iba-heiligenstadt.de.
authors.forename: Gunter
authors.initials: G
authors.lastname: Gastrock
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D058732:Embryoid Bodies / Q000166:cytology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000378:metabolism*
keywords: Automated modular platform; Droplets; Embryoid body formation; High(er) throughput; Long-term 3D cell cultivation