SBIR-STTR Award

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

This Small Business Innovation Research (SBIR) Phase II project proposes to develop an on-line, probe-based monitor for the real-time, continuous measurement of key analytes in protein expression bioreactors. This directly addresses the need for improved biopharmaceutical production monitoring. The current manual sampling and off-line analysis methods have significant limitations including contamination risks and inherent time delays that severely limit process control. The primary objectives of this effort include the optimization of a high brightness super luminescent diode (SLD) light source and the accompanying optical probe. The SLD provides the light throughput that is required for quantitative in situ measurements, and is perfectly suited for light coupling to an optical-fiber probe. This approach has the added advantage of multiplexing, thereby enabling a single monitor system to simultaneously track analyte concentrations in multiple bioreactors. Both the probe and SLD will be rigorously tested through a series of benchtop and live fermentation evaluations. The ultimate outcome of this effort will be a market-ready, probe-based bioreactor monitor compatible with the major expression platforms in the biopharmaceutical industry.The broader impact/commercial potential of this proposed project, if successful, will be to enable the fast-growing biopharmaceutical industry to make game-changing advances in the development and production of critically important drugs. By replacing current manual chemical measurement methods performed during the production of biopharmaceuticals with automated and continuous monitoring, this real-time probe-based monitor will enable needed improvements in process efficiency, lead to reduced development costs, and accelerate the time to market for state-of-the-art drugs. Because of the high value of these medications, and the driving market need, the commercial potential for this real-time monitor is significant with a specific market niche estimated at $510 million in the U.S. alone, residing in the larger global biologics market estimated at $239 billion by 2015. Ultimately, these advantages will translate to lower costs and greater access for consumers to life-changing medicines.