SBIR Phase I: Continuous Near Infrared Monitor for Pichia Pastoris Bioreactors

This Small Business Innovation Research (SBIR) Phase I project will develop sensing technology capable of continuously monitoring concentrations of critical metabolites during protein expression with the yeast Pichia pastoris. Presently, continuous monitoring is unavailable and this process is controlled using time consuming and labor intensive off-line analyses. This sensing technology uses near infrared absorption spectra of bioreactor growth medium collected continuously to monitor analyte concentrations and changes in biomass throughout the fermentation process. Preliminary results demonstrate the ability to make accurate and continuous analytical measurements and to actively control metabolite concentrations. This success is attributed to ASL innovations that include using a solid-state spectrometer, restricting the measurement spectral range, and implementing a calibration strategy based on analyte-specific chemical information. This Phase I effort will establish the commercial feasibility of this monitoring approach by developing a robust, practical calibration system for routine operation and by designing a means to continuously and non-destructively collect analytical spectra. The broader impacts of this research will be to enable accurate feedback control of bioreactors, thereby enhancing optimization
efforts and maximizing production yields of high commodity proteins. Successful development of a continuous, real-time monitor for Pichia pastoris will enhance its attractiveness as a protein expression platform. The proposed monitor will overcome the limitations of off-line analyses by providing an effective means to follow metabolite concentrations and cell density changes non-destructively during the course of a fermentation process. This sensing technology will fill a void in the general protein expression market where reliable, on-line sensing is unavailable. This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).