SBIR Phase II: Continuous Near Infrared Monitor for Pichia Pastoris Bioreactors

这个小企业创新研究（SBIR）二期项目将进一步开发一种完全硬化的、用户友好的ASL毕氏酵母监测器，用于商业蛋白质生产。I期试验证明了连续、实时近红外监测在毕赤酵母蛋白表达过程中追踪代谢物水平和细胞密度的商业可行性。在工业生产或过程开发环境中实现该技术需要对整个系统进行加固，并使其更加用户友好。所有硬件组件将与嵌入式计算机合并成一个单元，采样接口将得到增强，以允许连续监测或离散采样。将建立校准生成和更新的协议，并开发性能诊断以最大化校准鲁棒性。仪器的最终设计将由目前的Pichia用户进行beta测试。这项研究的广泛影响将使生物反应器的精确控制和优化工作成为可能，从而使毕赤酵母高价值蛋白质的产量最大化。ASL连续、实时监测的成功开发将增强毕赤酵母作为蛋白表达平台的吸引力。毕氏菌社区接受这种监测仪将加强开发新的生物制药的努力，缩短药物开发过程。ASL的监测器将通过实现更有效的控制和优化，从而促进毕赤酵母的使用，从而降低医疗成本，使这些生物治疗蛋白更广泛地使用。ASL的核心监测技术将适应更广泛的市场，应用于生物技术、生物医学和临床环境，这些领域目前无法获得可靠的在线传感。

This Small Business Innovation Research (SBIR) Phase II project will further develop a fully hardened, user friendly ASL Pichia monitor for commercial protein production. The Phase I effort demonstrated the commercial feasibility of the continuous, real-time near infrared monitor for tracking metabolite levels and cell density during protein expression with Pichia pastoris. Implementing this technology into an industrial production or process development setting requires the entire system to be hardened and made more user-friendly. All hardware components will be incorporated into a single unit with an embedded computer and the sampling interface will be enhanced to permit continuous monitoring or discrete sampling. Protocols for calibration generation and updating will be established, and performance diagnostics to maximize calibration robustness developed. The final design of the instrumentation will be beta-tested by current Pichia users.The broader impacts of this research will enable accurate control of bioreactors and enhance optimization efforts, resulting in maximum production yields of highly valued proteins from Pichia. Successful development of ASL's continuous, real-time monitor will enhance the attractiveness of Pichia as a protein expression platform. Acceptance of the monitor by the Pichia community will enhance efforts to develop new biopharmaceuticals and shorten the drug development process. ASL's monitor will catalyze the use of Pichia by enabling more effective control and optimization, thereby driving down healthcare costs and making these bio-therapeutic proteins more widely available. ASL's core monitor technology will be adaptable to broader markets with applications in biotechnology, biomedical, and clinical settings, where reliable, on-line sensing is currently unavailable.