Next Generation Proteomics: Towards High-Throughput Protein Analysis via Microfluidic Integration & Soft Materials

Abstract

While the genomics revolution has had sweeping impact on our understanding of life processes, the arguably more important “proteomics revolution” remains unrealized. Proteins are more directly linked to function than genes, but proteins are also dynamic and more biochemically complex. Consequently, protein analysis often demands multi-stage biochemical assays to measure not one, but multiple physicochemical properties (e.g., Western blot, 2D electrophoresis). Unfortunately, benchtop assays consume significant resources, making the biological sciences protein ‘data limited’. To surmount these challenges and realize an era of high throughput proteomics, innovation in instrumentation is needed.Microfluidic technology has advanced separations science, yet progress in multi-stage separations has lagged. Accepted multi-stage design approaches suffer from inherent information loss owing to strategies that ‘discretize’ first-stage separations by mapping readouts to discrete compartments in a second-stage. At UC Berkeley, we are introducing novel non-discretizing integration strategies. This talk will highlight multi-stage assays uniquely enabled by our ‘μMosaic’ fabrication technique: an approach that allows us to regionally photopattern 2D microchambers with heterogeneous, discrete crosslinked polyacrylamide gels. Our design strategy yields low-dispersion, near lossless electrokinetic material transport between disparate assay stages. In one example, I will summarize our recent progress towards fast, hands-free and perhaps even quantitative Western blotting, employed here for analysis of specimens from clinical sample repositories. Our ultimate goal being to advance the understanding of life processes - including development and disease - through quantitative bioinstrumentation.