Open capillary wave micro-reactor for biopharmaceutical screening applications

用于生物制药筛选应用的开放式毛细管波微反应器

• 批准号: 310619924
• 负责人: Professor Dr. Andreas Dietzel
• 金额: --
• 依托单位: Institut für Bioverfahrenstechnik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/310619924?language=en
• 关键词: Open; capillary; wave; micro; reactor

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.

基于液滴的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。与具有连续流动的微流体相比，固着液滴方法以较少的操作努力增强了流体操纵的灵活性。由于目前的无座液滴培养系统缺乏全面的在线传感器和充分的混合，实验通量和信息量只能不足地结合。（cwMBR，反应体积为7 μ L），在第一个供资期内生产，是开发一种具有高度传感器集成的顶部开放的整体式微生物反应器（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）的并行化，以从并行传感器读出（例如，例如，在一个实施例中，液位控制、共振监测、粘度以及pH、O2、葡萄糖和活细胞密度）。高通量方法中的小型化的承诺将通过将经由毛细管波的并行微混合与多传感器集成概念相结合来实现。本项目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，并监测中国人卵巢细胞的活力和活力，作为系统适用性的概念验证。通过高效的飞秒激光直写技术，利用熔融石英进行微结构化，该项目通过毛细管波和集成在线传感器实现主动混合技术，旨在开发小规模的新型固着液滴微反应器。集成的多个传感器将提高生产能力，提供大量的相关数据，使培养系统能够进行生物制药筛选。