Pressure-driven perfusion culture microchamber array for a parallel drug cytotoxicity assay

• Published in: Biotechnology and bioengineering Vol. 100; no. 6; pp. 1156 - 1165
• Main Authors: Sugiura, Shinji, Edahiro, Jun-ichi, Kikuchi, Kyoko, Sumaru, Kimio, Kanamori, Toshiyuki
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.08.2008; Wiley; Wiley Subscription Services, Inc
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Arrays; Biological and medical sciences; Biological Assay; Biotechnology; Cell Count; Cell culture; Cell Culture Techniques - instrumentation; Cell Culture Techniques - methods; Cell Survival - drug effects; Culture Media; Diffusion Chambers, Culture - instrumentation; Diffusion Chambers, Culture - methods; Dimethylpolysiloxanes; drug cytotoxicity assay; Equipment Design; Equipment Failure Analysis; Flow Injection Analysis; Fundamental and applied biological sciences. Psychology; HeLa Cells; Humans; Hydrostatic Pressure; integrated cell-based assay; microchamber array; Microfluidic Analytical Techniques - instrumentation; Microfluidic Analytical Techniques - methods; Microfluidics; Perfusion - instrumentation; perfusion culture; Prescription drugs; Toxicity; Drug; Array; perfusion culture; Perfusion; Cytotoxicity test; integrated cell-based assay; drug cytotoxicity assay; Pressure; Culture; microchamber array
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.21836

This article reports a pressure‐driven perfusion culture chip developed for parallel drug cytotoxicity assay. The device is composed of an 8 × 5 array of cell culture microchambers with independent perfusion microchannels. It is equipped with a simple interface for convenient access by a micropipette and connection to an external pressure source, which enables easy operation without special training. The unique microchamber structure was carefully designed with consideration of hydrodynamic parameters and was fabricated out of a polydimethylsiloxane by using multilayer photolithography and replica molding. The microchamber structure enables uniform cell loading and perfusion culture without cross‐contamination between neighboring microchambers. A parallel cytotoxicity assay was successfully carried out in the 8 × 5 microchamber array to analyze the cytotoxic effects of seven anticancer drugs. The pressure‐driven perfusion culture chip, with its simple interface and well‐designed microfluidic network, will likely become an advantageous platform for future high‐throughput drug screening by microchip. Biotechnol. Bioeng. 2008;100: 1156–1165. © 2008 Wiley Periodicals, Inc.