Open capillary wave micro-reactor for biopharmaceutical screening applications

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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.