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Open AccessArticle

A Modular, Reconfigurable Microfabricated Assembly Platform for Microfluidic Transport and Multitype Cell Culture and Drug Testing

by Xin Xie 1,2,†, Sushila Maharjan 2,3,†, Sanwei Liu 4, Yu Shrike Zhang 2,* and Carol Livermore 1,*
1
Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA 02115, USA
2
Division of Engineering in Medicine, Brigham and Women’s Hospital, Department of Medicine, Harvard Medical School, Cambridge, MA 02139, USA
3
Research Institute for Bioscience and Biotechnology, Nakkhu-4, Lalitpur 44600, Nepal
4
MEMS Sensors and Actuators Laboratory, Institute for Systems Research, University of Maryland, College Park, MD 20742, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Micromachines 2020, 11(1), 2; https://doi.org/10.3390/mi11010002
Received: 4 December 2019 / Accepted: 11 December 2019 / Published: 18 December 2019
(This article belongs to the Special Issue Microengineering Techniques for Disease Modeling and Drug Discovery)
Modular microfluidics offer the opportunity to combine the precise fluid control, rapid sample processing, low sample and reagent volumes, and relatively lower cost of conventional microfluidics with the flexible reconfigurability needed to accommodate the requirements of target applications such as drug toxicity studies. However, combining the capabilities of fully adaptable modular microelectromechanical systems (MEMS) assembly with the simplicity of conventional microfluidic fabrication remains a challenge. A hybrid polydimethylsiloxane (PDMS)-molding/photolithographic process is demonstrated to rapidly fabricate LEGO®-like modular blocks. The blocks are created with different sizes that interlock via tongue-and-groove joints in the plane and stack via interference fits out of the plane. These miniature strong but reversible connections have a measured resistance to in-plane and out-of-plane forces of up to >6000× and >1000× the weight of the block itself, respectively. The LEGO®-like interference fits enable O-ring-free microfluidic connections that withstand internal fluid pressures of >120 kPa. A single layer of blocks is assembled into LEGO®-like cell culture plates, where the in vitro biocompatibility and drug toxicity to lung epithelial adenocarcinoma cells and hepatocellular carcinoma cells cultured in the modular microwells are measured. A double-layer block structure is then assembled so that a microchannel formed at the interface between layers connects two microwells. Breast tumor cells and hepatocytes cultured in the coupled wells demonstrate interwell migration as well as the simultaneous effects of a single drug on the two cell types. View Full-Text
Keywords: modular microassembly; modular microfluidics; microphysiological system; cell culture; drug toxicity assay modular microassembly; modular microfluidics; microphysiological system; cell culture; drug toxicity assay
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MDPI and ACS Style

Xie, X.; Maharjan, S.; Liu, S.; Zhang, Y.S.; Livermore, C. A Modular, Reconfigurable Microfabricated Assembly Platform for Microfluidic Transport and Multitype Cell Culture and Drug Testing. Micromachines 2020, 11, 2.

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