Development of disposable PDMS micro cell culture analog devices with photopolymerizable hydrogel encapsulating living cells.

Microscale cell culture devices with two or more cell types, such as the micro cell culture analog (microCCA), are promising devices to predict mammalian response to toxic drug and chemical exposure. A polydimethylsiloxane (PDMS) version of such microfluidic devices has been challenging to construct due to the difficulty of patterning multi cell types directly into designated individual cell culture chambers in an oxygen plasma bonded PDMS device. Approaches with micro-valves for flow control are complex, expensive and inconvenient to use. In this study, an alternative approach using polyethylene glycol diacrylate (PEG-DA) for spatially controlled multi-cell type patterning inside a bonded microCCA device is described. We constructed a three-cell type PDMS microCCA following a human physiologically based pharmacokinetic (PBPK) modeling, and applied continuous cell culture medium recirculation within the device as a blood surrogate. A fluorescence microscope based direct pattern writing method was used to form cell/hydrogel microstructures with higher cell viability than the traditional UV lamp based method. The positive effect of mixed molecular weight PDG-DA on hydrogel-encapsulated cell membrane integrity was also studied. This prototype PDMS microCCA device was then tested with Triton X-100 as a model toxicant. The combination of hydrogel photo-patterning and the microfluidic cell culture platform enables the fabrication of simple and low cost multi-cell type biosensors for drug development, toxicity study and clinical diagnosis.