Open capillary wave micro-reactor for biopharmaceutical screening applications

液滴培养系统作为独立的反应元件，为生物制药研究中的高通量细胞培养和分析提供了并行化和快速数据生成的机会。与连续流动的微流体相比，固定式液滴方法提高了流体操作的灵活性，减少了操作的工作量。目前的无根液滴培养系统由于缺乏全面的在线传感器和充分的混合，只能将实验吞吐量和信息量相结合。本课题的目标是在第一期资助期研制的毛细管波微生物反应器（cwMBR，反应体积为7 gammaL）的基础上，开发一种具有高度传感器集成度的顶开放式单片微生物反应器（MBR）阵列，用于生物药物筛选的分析工具。它允许使用自动化液体处理系统操作的反应单元（3 x 3 mbr）并行化，以从并行传感器读出（例如，液位控制，共振监测，粘度以及pH， O2，葡萄糖和活细胞密度）创建关键的实验数据。通过将毛细管波的平行微混合与多传感器集成概念相结合，高通量方法的小型化承诺将成为现实。在本项目中，将研究氧化应激对应激敏感模式生物酿酒酵母N34代谢的影响，并监测中国仓鼠卵巢细胞的活力和活力，作为该系统适用性的概念验证。利用熔融二氧化硅的高效飞秒激光直接写入微结构，通过毛细管波实现主动混合技术和集成在线传感器，本项目旨在开发小型新型无底液滴微反应器。集成的多个传感器将提高吞吐量能力，提供大量相关数据，从而使培养系统能够进行生物制药筛选。

Droplet-based cultivation systems as independent reaction elements open up the opportunities for parallelization and rapid data generation for high-throughput cell culture and analysis in biopharmaceutical research. In contrast to microfluidics with continuous flow, sessile droplet approaches enhance the flexibility for fluid manipulation with less operational effort. Due to the absence of comprehensive online sensors and adequate mixing in current sessile droplet cultivations systems, experimental throughput and information content can only be combined deficiently.The aim of this proposal, building on the capillary wave micro-bioreactor (cwMBR, reaction volume of 7 gammaL) manufactured in the first funding period, is to develop a top-open monolithic micro-bioreactor (MBR) array with a high degree of sensor integration for application as analytical tool for biopharmaceutical screening. It allows for parallelization of reaction units (3 x 3 MBRs) operated using an automated Liquid handling system to create crucial experimental data from parallel sensor read outs (e. g., liquid level control, resonance monitoring, viscosity as well as pH, O2, glucose and viable cell density). The promises of miniaturization in high-throughput approaches will come true by combining parallel micro mixing via capillary waves with multi-sensor integration concepts. Within this project, oxidative stress will be investigated on the metabolism of a stress sensitive model organism Saccharomyces cerevisiae N34 as well as viability and vitality of Chinese Hamster Ovary cells will be monitored as a proof-of-concept for the applicability of the system.By means of efficient femtosecond laser direct writing for micro-structuring using fused silica, the implementation of an active mixing technique via capillary waves and integrated online sensors, this project aims to develop novel sessile droplet micro-reactors in small scale. Promoting the throughput capabilities, integrated multiple sensors will provide high amounts of relevant data, what empowers the cultivation system for biopharmaceutical screenings.