Abstract

Organs-on-Chip by Selective Assembly of Primary Cells Enabled by Dielectrophoresis in Microfluidic Devices

Martin Stelzle, Head of BioMEMS & Sensors Department, NMI at University of Tübingen

Combining microfluidics and dielectrophoresis (DEP) to assemble primary human cells enables the automated in vitro construction of micro-organs mimicking the in vivo structure of organs. Tissue-like features include constant perfusion and physiological cell–matrix and cell–cell interactions. As a unique feature of this organ-on-chip technology, the use of DEP selectively assembles only viable cells. Organ-specific 3D-cell culture chambers are designed and validated by multiphysics simulations and realized by injection molding of cyclic olefin polymer (COP). Proprietary surface functionalization enables selective deposition of extracellular matrix proteins in a simple perfusion process. High resolution optical imaging of micro-organs along with the complete set of staining technologies is possible due to the exceptional optical properties of COP. In addition, perfundates and lysates may be collected for biochemical analysis. Results from liver and blood–brain barrier chips will be shown. In particular, metabolic function and secretion of liver sinusoids comparable to fresh hepatocytes validates their organ-like behavior. Our blood–brain-barrier-on-chip demonstrates a first example of a barrier tissue created by using DEP. In summary, this technology is applicable to the assembly and culture of diverse organ tissues comprising complex arrangement of multiple cell types and extracellular matrix and requiring continuous perfusion.