Microfluidic In Vitro Platform for (Nano)Safety and (Nano)Drug Efficiency Screening

Abstract

(Nano) seguretat; Eficiència dels medicaments; Plataforma de microfluids

(Nano) seguridad; Eficiencia de los fármacos; Plataforma de microfluidos

(Nano)safety; Drug efficiency; Microfluidic platform

Microfluidic technology is a valuable tool for realizing more in vitro models capturing cellular and organ level responses for rapid and animal-free risk assessment of new chemicals and drugs. Microfluidic cell-based devices allow high-throughput screening and flexible automation while lowering costs and reagent consumption due to their miniaturization. There is a growing need for faster and animal-free approaches for drug development and safety assessment of chemicals (Registration, Evaluation, Authorisation and Restriction of Chemical Substances, REACH). The work presented describes a microfluidic platform for in vivo-like in vitro cell cultivation. It is equipped with a wafer-based silicon chip including integrated electrodes and a microcavity. A proof-of-concept using different relevant cell models shows its suitability for label-free assessment of cytotoxic effects. A miniaturized microscope within each module monitors cell morphology and proliferation. Electrodes integrated in the microfluidic channels allow the noninvasive monitoring of barrier integrity followed by a label-free assessment of cytotoxic effects. Each microfluidic cell cultivation module can be operated individually or be interconnected in a flexible way. The interconnection of the different modules aims at simulation of the whole-body exposure and response and can contribute to the replacement of animal testing in risk assessment studies in compliance with the 3Rs to replace, reduce, and refine animal experiments.

T.K. and Y.K. contributed equally to this work. The authors thank Frank Bauerfeld for system assembly and electrical testing, Werner Haberer for assembly of the microfluidic cartridges, Axel Brenner for the fabrication of the silicon micro cavity chips, Hoffman La Roche for providing the Ro 19-8022, NorGenoTech for providing the Fpg enzyme, and Karen Steenson for proofreading. This research was funded by the European Commission under the Horizon2020 programme (HISENTS, Grant Agreement No. 685817 and VISION, Grant Agreement No. 857381); and by the Norwegian Research Council Norway (RCN) via the European Research Area Network (ERA-NET) EuroNanoMed II project INNOCENT (RCN 271075) and the ERA-NET EuroNanoMed III project Graphene-encapsulated magnetic nanoparticles (RCN 246672/O70). K.K. received Short Term Scientific Mission Grant (ID 42926) under COST Action CA 17140 “Cancer Nanomedicine from the Bench to the Bedside” supported by COST (European Cooperation in Science and Technology). E.E. received funding from the Norwegian Research Council (272412/F40). O.H.M. received funding from the Spanish Ministry of Economy and Competitiveness (SEV-2013-0295-17-3).