Cell therapeutics promise to completely transform the treatment of a wide range of diseases such as cancer, neurodegenerative disorders and autoimmune disorders by enabling sophisticated modes of action. This promise comes with challenges in the reproducible manufacturing of cells that are to be administered to thousands of patients. Electroporation-based cell transfection is an appealing technology to achieve high transfection efficiencies for non-viral genetic modification of cells [1]. In decentralized manufacturing with patient-specific cell material, however, both transfection efficiency and cell viability need to be extremely high as the cell source is very limited. Chip-based solutions implementing microscale electroporation might offer the throughput and yield needed for personalized cell therapies due to high and controllable electric field in microfluidic structures. This master thesis will explore in-flow single cell electroporation with integrated electrodes in microfluidic channels. After literature study, the project will start with building the analytical equivalent circuit model for cells in physiological medium based on prior knowledge at imec. Afterward, a coupled electrical and fluidic dynamics model will be developed to study the spatial and temporal electric field characteristics. With this model we would like to understand the dependency of cell electroporation (e.g. pore size, density) on a number of parameters such as materials, electric field strength/frequency, fluid configuration and flow settings. Once the model is verified (e.g. by literature data), we would like to develop optimal device design as well as operation settings for high speed, controllable electroporation. Depending on the device structure of the optimal design, microfluidic electroporation devices can be fabricated and tested. This thesis will consist of 10% literature study, 40-60% modelling, 20%-40% experimentation and 10% reporting/writing. [1] Aijaz et al Nat. Biomed. Eng., 2018

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