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

这个小企业创新研究第一阶段项目将开发一种光纤光耦合原位探针，利用超发光二极管（SLD）光源监测生物反应器发酵与ASL？的生物反应器监视器。目前的ASL监视器使用传统的热光源，这是固有的低亮度，将显着减少仪器？的吞吐量和信噪比时，耦合到有限孔径光纤。然而，SLD的小发射面积非常适合光纤耦合，并且在吞吐量方面具有显著优势，允许在高度浑浊的溶液中进行精确测量。在这项工作中，SLD设备将被制造和耦合到光纤测试组件。将在活发酵工艺期间评价其分析性能。对于一个商业原位探针，利用SLD是可行的，它必须能够获得高品质的光谱与信噪比等于或优于目前的ASL monitor.The更广泛/商业的影响，这项研究将提高目前的ASL生物反应器监测器的性能，并使原位采样，这是非常可取的潜在用户的这项技术。在巴斯德毕赤酵母和E. coli提供了一种主动反馈控制的方法，有助于优化生产产量并有助于保持质量控制。更好的质量控制将降低劳动力和生产成本，最终减少候选药物的上市时间，降低消费者的成本。

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.