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

这个小型企业创新研究（SBIR）第二阶段项目提出开发一种在线的，基于探针的监测器，用于实时，连续测量蛋白质表达生物反应器中的关键分析物。这直接解决了对改进的生物制药生产监控的需求。 目前的手动取样和离线分析方法具有显著的局限性，包括污染风险和固有的时间延迟，这严重限制了过程控制。 这项工作的主要目标包括高亮度超发光二极管（SLD）光源和伴随的光学探头的优化。 SLD提供定量原位测量所需的光通量，并且非常适合光耦合到光纤探头。 这种方法具有多路复用的额外优点，从而使单个监测系统能够同时跟踪多个生物反应器中的分析物浓度。 探针和SLD都将通过一系列实验台和现场发酵评估进行严格测试。 这一努力的最终成果将是一个市场就绪的，基于探针的生物反应器监测器，与生物制药行业的主要表达平台兼容。如果成功，这个拟议项目的更广泛的影响/商业潜力将使快速增长的生物制药行业在开发和生产至关重要的药物方面取得改变游戏规则的进展。 通过用自动化和连续监测取代目前在生物制药生产过程中执行的手动化学测量方法，这种基于探针的实时监测器将能够实现所需的过程效率改进，从而降低开发成本，并加快最先进药物的上市时间。 由于这些药物的高价值和推动市场需求，这种实时监测器的商业潜力很大，仅在美国就有5.1亿美元的特定市场利基，到2015年，全球生物制剂市场估计为2390亿美元。 最终，这些优势将转化为更低的成本，并使消费者更容易获得改变生活的药物。

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.