Abstract

Towards Organs-on-Chip for Drug Testing, Mechanistic Studies, and Personalized Medicine by Selective Assembly of Primary Cells Enabled by Dielectrophoresis in Microfluidic Devices

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

Organs-on-chip are envisioned to provide in vivo-like results in preclinical drug testing by establishing cell cultures mimicking the smallest functional units of an organ. A brief review of prominent international projects will be given. Secondly, we will report on our organs-on-chip technology based on combining microfluidics and dielectrophoresis (DEP) to assemble primary human cells and enabling the automated in vitro construction of micro-organs mimicking the in vivo structure of organs. As a unique feature of this organ-on-chip technology, DEP selectively draws viable cells into 3D assemblies defined by the structure of the microfluidic cell chamber. These organ-specific 3D cell culture chambers are designed and validated by multiphysics simulations and fabricated by injection molding of cyclic olefin polymer (COP). Proprietary surface functionalization enables selective patterning of extracellular matrix proteins in a simple perfusion process. High resolution optical imaging of micro-organs along with the complete set of staining technologies can be applied due to the exceptional optical properties of COP. In addition, perfundates and lysates may be collected for biochemical analysis. Results from liver, blood–brain barrier, and tumor chips will be discussed. In particular, metabolic function and secretion of liver sinusoids comparable to fresh hepatocytes validates their organ-like behavior. Our blood–brain-barrier-on-chip aims at creating a barrier tissue by using DEP. Micro-tumors have been assembled to test anti-cancer drugs. A multiwell plate format in combination with a dedicated periphery system will provide for seamless integration into the drug development workflow. In summary, this technology is applicable to the assembly and culture of diverse organ tissues involving complex arrangement of multiple cell types and extracellular matrix and enables continuous perfusion of these micro-organs. Applications of this technology in drug testing, mechanistic