SBIR-STTR Award

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)

This Small Business Innovation Research (SBIR) Phase II project will further develop a fully hardened, user friendly ASL Pichia monitor for commercial protein production. The Phase I effort demonstrated the commercial feasibility of the continuous, real-time near infrared monitor for tracking metabolite levels and cell density during protein expression with Pichia pastoris. Implementing this technology into an industrial production or process development setting requires the entire system to be hardened and made more user-friendly. All hardware components will be incorporated into a single unit with an embedded computer and the sampling interface will be enhanced to permit continuous monitoring or discrete sampling. Protocols for calibration generation and updating will be established, and performance diagnostics to maximize calibration robustness developed. The final design of the instrumentation will be beta-tested by current Pichia users. The broader impacts of this research will enable accurate control of bioreactors and enhance optimization efforts, resulting in maximum production yields of highly valued proteins from Pichia. Successful development of ASL's continuous, real-time monitor will enhance the attractiveness of Pichia as a protein expression platform. Acceptance of the monitor by the Pichia community will enhance efforts to develop new biopharmaceuticals and shorten the drug development process. ASL's monitor will catalyze the use of Pichia by enabling more effective control and optimization, thereby driving down healthcare costs and making these bio-therapeutic proteins more widely available. ASL's core monitor technology will be adaptable to broader markets with applications in biotechnology, biomedical, and clinical settings, where reliable, on-line sensing is currently unavailable.