Terry Gaige

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.

Microfluidic Tissue Model for Live Cell Screening

We have developed a microfluidic platform modeled after the physiologic microcirculation for multiplexed tissue‐like culture and high‐throughput analysis. Each microfabricated culture unit consisted of three functional components: a 50 μm wide cell culture pocket, an artificial endothelial barrier with 2 μm pores, and a nutrient transport channel. This configuration enabled a high density of cancer cells to be maintained for over 1 week in a solid tumor‐like morphology when fed with continuous flow. The microfluidic chip contained 16 parallel units for “flow cell” based experiments where live cells were exposed to a soluble factor and analyzed via fluorescence microscopy or flow‐through biochemistry. Each fluidically independent tissue unit contained ∼500 cells fed with a continuous flow of 10 nL/min. As a demonstration, the toxicity profile of the anti‐cancer drug paclitaxel was collected on HeLa cells cultured in the microfluidic format and compared with a 384‐well dish for up to 5 days of continuous drug exposure.

Microfluidic systems for live cell imaging.

Microfluidic systems provide many advantages for live cell imaging, including improved cell culture micro-environments, control of flows and dynamic exposure profiles, and compatibility with existing high resolution microscopes. Here, we will discuss our approach for design and engineering of microfluidic cell culture environments as well as interfacing with standard laboratory tools and protocols. We focus on an application specific design concept, whereby a shared fabrication process is used to deliver multiple products for different biological applications. As adoption of advanced in vitro models increases, we envision the use of microfluidic cell culture technology to become commonplace.