This SBIR Phase I project will establish the feasibility of a new protein analysis system for rapid and precise quality characterization for biologics - protein-based drugs such as antibodies and recombinant proteins. Biologics have achieved remarkable efficacy for many diseases, e.g. cancer, psoriasis, and are the fastest growing drug development segment. However, biologics are highly complex molecules manufactured in living cells, and as a result, frequent quality testing is required for development, regulatory approval, and commercial manufacturing of biologics. Current testing approaches are cumbersome and too slow to provide the required throughput, taking weeks to complete an analysis. This project will utilize microfluidic technology's ability to seamlessly integrate multiple analytical functions to complete a protein characterization analysis in only minutes. The innovative approaches and research resulting from this project will advance the fields of protein separation science and expand the microfluidic technology field. This project will also transform biologic drug development and manufacturing by making the critical testing less cumbersome and faster, and will enable more frequent, comprehensive testing. This will result in profound productivity gains that will translate into a greater number of higher quality drugs developed in less time and with less cost. This project will demonstrate proof-of-concept for a novel quantitative protein analysis platform for biologics that combines optically-monitored, capillary isoelectric focusing (cIEF) and mass spectrometry (MS). This project proposes to develop an innovative microfluidic device that incorporates a novel light guide, which is capable of measuring protein levels while simultaneously performing electrophoretic separation and electrospray ionization. Adding this light guide to this device enables a powerful integration of imaged cIEF and MS techniques, enabling simultaneous quantitation and determination of mass and charge heterogeneity profiling of unlabeled protein samples. This microfluidic device will be the first demonstrated integration of these analytical functions in a robust and rapid system suitable for the bioproduction environment. The goals of this project will be to: 1) design and test chips to identify the most optimal design, 2) identify wall coatings required to modify chip surfaces to enable microfluidic electrophoresis, and 3) develop reagents and assay conditions to enable electrophorectic separation by isoelectric focusing that are compatible with ionization for electrospray delivery to mass spec. Success in Phase I will lead to a Phase II program in which we will develop a commercial microfluidic chip and reagent kit, develop the commercial instrument system, and validate the system performance for GMP compliant use.
