Microfluidic System for Automated Cell-Based Assays

Microfluidic cell culture is a promising technology for applications in the drug screening industry. Key benefits include improved biological function, higher-quality cell-based data, reduced reagent consumption, and lower cost. In this work, we demonstrate how a microfluidic cell culture design was adapted to be compatible with the standard 96-well plate format. Key design features include the elimination of tubing and connectors, the ability to maintain long-term continuous perfusion cell culture using a passive gravity-driven pump, and direct analysis on the outlet wells of the microfluidic plate. A single microfluidic culture plate contained eight independent flow units, each with 104 cells at a flow rate of 50 μL/day (6 min residence time). The cytotoxicity of the anticancer drug etoposide was measured on HeLa cells cultured in this format, using a commercial lactate dehydrogenase plate reader assay. The integration of microfluidic cell culture methods with commercial automation capabilities offers an exciting opportunity for improved cell-based screening.

[1]  L. Griffith,et al.  A microfabricated array bioreactor for perfused 3D liver culture. , 2002, Biotechnology and bioengineering.

[2]  L. Griffith,et al.  Capturing complex 3D tissue physiology in vitro , 2006, Nature Reviews Molecular Cell Biology.

[3]  Luke P. Lee,et al.  An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. , 2007, Biotechnology and bioengineering.

[4]  D. Beebe,et al.  Microenvironment design considerations for cellular scale studies. , 2004, Lab on a chip.

[5]  Teruo Fujii,et al.  Microfluidic PDMS (Polydimethylsiloxane) Bioreactor for Large‐Scale Culture of Hepatocytes , 2004, Biotechnology progress.

[6]  K. Jensen,et al.  Cells on chips , 2006, Nature.

[7]  G. Whitesides The origins and the future of microfluidics , 2006, Nature.

[8]  Luke P. Lee,et al.  Nanoliter scale microbioreactor array for quantitative cell biology , 2006, Biotechnology and bioengineering.

[9]  A. Folch,et al.  Biology on a chip: microfabrication for studying the behavior of cultured cells. , 2003, Critical reviews in biomedical engineering.

[10]  Ales Prokop,et al.  NanoLiterBioReactor: Long-Term Mammalian Cell Culture at Nanofabricated Scale , 2004, Biomedical microdevices.

[11]  Luke P. Lee,et al.  Microfluidics-based systems biology. , 2006, Molecular bioSystems.

[12]  Luke P. Lee,et al.  Continuous perfusion microfluidic cell culture array for high-throughput cell-based assays. , 2005, Biotechnology and bioengineering.

[13]  Luke P. Lee,et al.  A novel high aspect ratio microfluidic design to provide a stable and uniform microenvironment for cell growth in a high throughput mammalian cell culture array. , 2005, Lab on a chip.

[14]  Shuichi Takayama,et al.  Computerized microfluidic cell culture using elastomeric channels and Braille displays. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[15]  A. Jayaraman,et al.  Dynamic gene expression profiling using a microfabricated living cell array. , 2004, Analytical chemistry.

[16]  T. Park,et al.  Integration of Cell Culture and Microfabrication Technology , 2003, Biotechnology progress.

[17]  Albert Folch,et al.  Differentiation-on-a-chip: a microfluidic platform for long-term cell culture studies. , 2005, Lab on a chip.