Readying Miniaturized Reactors for Flow Biocatalysis

项目描述：几乎所有的工程部门都已经成功地从批量加工过渡到连续加工。生物化学工程中连续加工的一个特别有前途的领域是活性药物成分（api）和增值化学品的生物催化合成。然而，大规模连续生产尚未成功证明。连续流生物催化改善了对反应条件的控制，提高了产率和生产率水平。这种效率的提高和随之而来的废物的最小化最终将导致更清洁的过程和更低的总成本。此外，连续的过程可以减少工艺线和设施占地面积，从而减少前期资本投资。为了充分利用连续处理的优势，有必要描述反应器的性能，并了解生物催化剂的限制和反应器运行之间的相互作用。只有这样，才能利用这些过程成功地达到与工业相关的产量。为了实现这一目标，需要能够仔细评估反应器性能和生物催化剂行为的缩小模型。小型连续流反应堆是首选。与传统的批量系统相比，它们的小尺寸允许用更小的体积进行实验，在使用昂贵的底物或酶时显著降低成本。在这些反应器中，便于控制反应参数，并证明了在线净化与产品的回收。此外，由于传质增强，反应时间随之缩短，反应可能会加速。因此，小型化连续流反应器将成为未来快速、高通量获取高质量数据的基础。项目目标-设计、制造和表征一个小型连续流反应器，该反应器具有集成的光学传感器和在线分析工具，用于在线监测化学和物理变量（pH值、温度、氧气和二氧化碳）以及在线反应分析（GC-和LC-MS）。-通过工业相关的生物催化反应验证集成的小型连续流反应器。-比较间歇系统和连续系统中的反应器性能(例如，通过时空产率，(gproduct/（Lreactor.h)和（gproduct/genzyme））在所有尺度上评估工艺稳定性，产品工艺的质量概况和可扩展性。产出与影响该项目与英国工业生物技术领域的战略重点以及EPSRC未来生物制造研究中心保持一致。由于该研究方向的高相关性和及时性，我们预计该项目的每个目标都将导致出版物输出。在整个项目中获得的结果将包括在本科或研究生模块的教学中。

Description of the projectIn almost all engineering sectors there has been a successful transition from batch to continuous processing. One particularly promising area for continuous processing in biochemical engineering is the biocatalytic synthesis of active pharmaceutical ingredients (APIs) and value-added chemicals. However, continuous production at large scale has not yet been successfully demonstrated. Continuous-flow biocatalysis offers an improved control over reaction conditions with benefits in yield and productivity levels. This increase in efficiency and concomitantly minimization of waste will ultimately result in cleaner processes with lower overall costs. Furthermore, continuous processes enable a reduction in process lines and facility footprints which in turn result in less up-front capital investment. To exploit the full benefits of continuous processing, it is necessary to characterise reactor performance, and to understand the interplay between the biocatalysts' constraints and the reactor operation. Only then can these processes be exploited to successfully at industrially relevant volumes.To achieve this aim, scale-down models that enable careful assessment of reactor performance and biocatalysts' behaviour are necessary. Miniaturized continuous-flow reactors are prime candidates. Their small dimensions allow experiments to be performed with much smaller volumes compared to traditional batch systems, offering significant cost reduction when using expensive substrates or enzymes. Within these reactors the control of reaction parameters is facilitated, and in-line purification with recovery of products has been demonstrated. Additionally, reactions can be potentially accelerated due to enhanced mass transfer with a concomitant decrease in reaction time. Therefore, miniaturized continuous-flow reactors will in the future form the basis to acquire high-quality data rapidly and with high throughput. Project Objectives- Design, fabricate, and characterize a miniaturized continuous-flow reactor with integrated optical sensors and at-line analytical tools for the on-line monitoring of chemical and physical variables (pH, temperature, oxygen and CO2) and for at line reaction analytics (GC- and LC-MS). - Validate the integrated miniaturized continuous-flow reactor with industrially relevant biocatalytic reactions. - Compare the reactor performance in batch and continuous systems (e.g. by space-time yields, (gproduct/(Lreactor.h), and (gproduct/genzyme)) at all scales assessing process stability, quality profile of the products process and scalability. Output & ImpactThis project aligns with UK strategic priorities in the area of Industrial Biotechnology and the departmental EPSRC Future Biomanufacturing Research Hub. Due to the high relevance and timeliness of this research direction, we anticipate that each objective of the project will lead to a publication output. The results obtained throughout this project will be included in teaching of undergraduates or postgraduate modules.