SBIR Phase I: In Situ Optical Probe for Real-time Monitoring of Protein Expression Bioreactors

This Small Business Innovation Research Phase I project will develop a fiber optically coupled in situ probe utilizing a superluminescent diode (SLD) optical source for monitoring bioreactor fermentations with ASL?s bioreactor monitor. The current ASL monitor uses a conventional, thermal light source, which is inherently low-brightness and will significantly reduce the instrument?s throughput and SNR when coupled to a limited-aperture fiber. The small emitting area of the SLD, however, is perfectly suited to fiber coupling, and presents a significant advantage in throughput, allowing for accurate measurements in highly turbid solutions. During this effort, SLD devices will be fabricated and coupled to a fiber-optic test assembly. Their analytical performance will be evaluated during live fermentation processes. For a commercial in situ probe that utilizes an SLD to be feasible, it must be capable of obtaining high-quality spectra with an SNR equivalent to or better than the present ASL monitor. The broader/commercial impacts of this research will both improve the performance of the current ASL bioreactor monitor and enable in situ sampling, which is highly desirable by potential users of this technology. The availability of continuous on-line measurements of key analytes provided by the ASL monitor during protein expression with Pichia pastoris and E. coli supplies a means for active feedback control, aiding in optimization of production yields and helping maintain quality control. Better quality control will reduce labor and production costs and ultimately, reduce the time to market for drug candidates and lower costs to consumers.