A new microfluidic tool for rapid analysis of protein stability and integrity in bioprocesses

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Analysis of protein stability is currently too slow and requires too much of an exceedingly valuable biopharmaceutical to be useful in guiding bioprocess development or control. Introducing the first microfluidic method for protein stability testing will reduce sample use and cost of analysis by up to 108-fold over microwell-based analysis. Combined expertise from biochemical engineering and the London Centre for Nanotechnology will enable this analysis with parallelism for up to 1000 samples per day. The new generation of protein-based medicines has rapidly become a $30billion-a-year industry addressing previously untreatable diseases. They have the potential for much further growth but a principal constraint is the high cost of the manufacturing methods required to preserve the structural integrity of proteins with limited stability. The ability to perform rapid and parallel protein stability characterisation experiments, at the microfluidic scale, is essential to enable: a) the rapid optimisation of therapeutic protein formulations; and b) the real-time monitoring of protein product quality in process-, microwell- and microfluidic scale bioprocess development experiments. Our preliminary research has demonstrated protein stability determination using fluorescence measurements at the microwell scale (Aucamp et al., 2005). The aims of this proposal are to a) explore the fundamentals that impact on measurement accuracy and sensitivity at the microfluidic scale, so as to significantly decrease the sample volumes required for protein stability measurement; b) establish a microfluidic denaturation technique; c) overcome the challenges that will enable broad application to bioprocessing and formulation of biopharmaceutical protein products.