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

这个小型企业创新研究一期项目将开发一种光纤耦合原位探头，利用超辐射二极管(SLD)光源，使用ASL？S生物反应器监测仪监测生物反应器发酵。目前的ASL监视器使用的是传统的热光源，这种光源固有的低亮度，当与有限孔径光纤耦合时，将显著降低仪器的吞吐量和信噪比。然而，SLD的发射面积很小，非常适合光纤耦合，在吞吐量方面具有显著优势，可以在高度混浊的解决方案中进行准确测量。在这项工作中，SLD设备将被制造并耦合到光纤测试组件上。它们的分析性能将在现场发酵过程中进行评估。要使利用SLD的商业原位探测器可行，它必须能够获得高质量的光谱，信噪比等于或高于目前的ASL监测器。这项研究的更广泛/商业影响将改善当前ASL生物反应器监测器的性能，并实现原位采样，这是这项技术的潜在用户非常希望的。在毕赤酵母和大肠杆菌表达蛋白质的过程中，ASL监测仪提供了关键分析物的连续在线测量，这为主动反馈控制提供了一种手段，有助于优化生产产量和帮助维持质量控制。更好的质量控制将减少劳动力和生产成本，最终缩短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.