Published January 18, 2021 | Version v1
Journal article Open

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

  • 1. Fraunhofer Institute for Biomedical Engineering IBMT; Joseph-von-Fraunhofer-Weg 1, Sulzbach 66280, Germany; E-mail: thorsten.knoll@ibmt.fraunhofer.de
  • 2. Tyndall National Institute, University College Cork; Dyke Parade, Cork T12 R5CP, Ireland
  • 3. Institute of Thermofluids, School of Mechanical Engineering, University of Leeds; Leeds LS2 9JT, UK
  • 4. NILU-Norwegian Institute for Air Research, Department for Environmental Chemistry, Health Effects Laboratory; Instituttveien 18, Kjeller 2007, Norway; Faculty of Medicine, Institute of Basic Medical Sciences, Department of Molecular Medicine, University of Oslo; Sognsvannsveien 9, Oslo 0372, Norway
  • 5. Department of Nanobiology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences; Dubravska cesta 9, Bratislava 84505, Slovakia
  • 6. Institut Català de Nanociència i Nanotecnologia (ICN2), CSIC and BIST; Campus UAB, Bellaterra 08193, Barcelona, Spain; Universitat Autònoma de Barcelona (UAB); Campus UAB, Bellaterra, 08193, Barcelona, Spain
  • 7. Institut Català de Nanociència i Nanotecnologia (ICN2) CSIC and BIST Campus UAB, Bellaterra 08193, Barcelona, Spain
  • 8. Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology SUT; Radlinskeho 9, Bratislava 812 37, Slovakia
  • 9. NILU-Norwegian Institute for Air Research, Department for Environmental Chemistry, Health Effects Laboratory; Instituttveien 18, Kjeller 2007, Norway
  • 10. Institut Català de Nanociència i Nanotecnologia (ICN2) CSIC and BIST Campus UAB, Bellaterra 08193, Barcelona, Spain; Vall d'Hebron Institut de Recerca (VHIR); Barcelona 08193, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA); Barcelona 08193, Spain
  • 11. School of Chemistry, University of Leeds; Leeds LS2 9JT, UK

Description

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 labelfree 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.

Notes

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). Open access funding enabled and organized by Projekt DEAL.

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