(114a) Bioprocess-on-a-Chip

Optimizatin of bioprocess involves large numbers of parameters associated with choice of media, cell line, expression vector design, and mode of operation. Small scale bioreactors are relatively expensive to purchase and operate limiting the number of parallel studies that can be conducted. Several forms of microreactors have been suggested, and these reactors provide information on potential product yields. However, product quality is a critical issue and not addressed in current systems. We describe an approach to microscale systems using animal cell cultures producing extracellular protein products. This system consists of three elements: microreactor, protein separation, and chemical characterization of the protein product to determine the sialic acid to protein ratio as a measure of completeness of N-linked glycosylation. Each individual component has been fabricated in polystyrene and tested. These components and their performance have been characterized using insect cell line Sf-21 for cellular response, SEAP (human secrected alkaline phosphatase) for product yield, and human immunoglobulin for sialic acid content characterization. The microscale components in this system are autonomous in the sense that no external pumps or reservoirs are needed.