Microfluidic System for Automated Cell-Based Assays

Abstract

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 8 independent flow units, each with 10(4) cells at a flow rate of 50 μl/day (6 minute residence time). The cytotoxicity of the anti-cancer drug etoposide was measured on HeLa cells cultured in this format, using a commercial lactate dehydrogenase (LDH) plate reader assay. The integration of microfluidic cell culture methods with commercial automation capabilities offers an exciting opportunity for improved cell-based screening.

Three-dimensional cell culture: the missing link in drug discovery

“…1e) may also be useful for drug screening (e.g. [43]); however, many of these microfluidic channel-based systems only support 2D cultures that, arguably, do not represent the in vivo environment [44]. Toh et al [39] described a microfluidic system that supports 3D culture.…”

Microfluidic Platforms for Hepatocyte Cell Culture: New Technologies and Applications

“…Majority of current microfluidic-based systems used for in vitro hepatocyte cell culture only partially meet these requirements. 23,26,35,36,45 Over the last decade, several microfluidic-based cell culture systems that posse characteristics required for high throughput toxicity screening have been published. For example, Domansky et al 12 developed a bioreactor that was integrated into multiwell plate format.…”

The Current Status of Alternatives to Animal Testing and Predictive Toxicology Methods Using Liver Microfluidic Biochips

“…Although integration has not yet reached thousands of microfluidic biochips, parallel analyses are possible. 52,86 A review of coupling the microfluidic biochips and a live imaging platform has been proposed by Lee et al 51 To our mind, the key features of this type of microfluidic and live imaging platform should typically be composed of a motorized fluorescence microscope, a CCD camera that captures the images, and a digitizing system that stores the images in a large-capacity computer, with each step controlled by software for image acquisition and analysis. In order to perform parallel assays, the culture set-up should be composed of a ''handling'' unit including the microfluidic.…”