University of Twente Student Theses


Multiplexed and automated parallelization of organ-on-chip technology

Winter, S. de (2022) Multiplexed and automated parallelization of organ-on-chip technology.

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Abstract:Microfluidic organ-on-chip (OoC) systems recapitulate the human physiology by advanced 3-dimensional (3D) cell culture, but lack in parallelization and automation and are consequently barely used for pharmakinetic analysis or high-throughput screening. At the same time, existing parallelized microfluidic cell culture platforms enable automated control over the cell culture conditions, but are limited to straightforward 2D cell culture due to the use photolithography based wafer molds. These wafer molds are expensive and time-consuming to make which obstructs the translation towards multiplexed OoC systems. Therefore, this study presents a parallelized microfluidic chip with a modular build-up consisting of a standardized fluid routing system and a customizable cell culture layer. The polydimethylsiloxane (PDMS) based chip is fabricated by multilayer soft-lithography and injection molding. The larger and more complex 3D cell culture compartments can be rapidly prototyped by micro-milling, which enables fast and easy redesign of the microfluidic chip. The fluid routing layer consists of a dense network of channels and microfluidic large-scale integration of push-down valves. This facilitates tight and spatiotemporal control over each of the individual cell culture compartments. A wide range of push-down valve geometries were characterized, which showed that the quality highly depends on the height and width of the channel, and on the thickness and elasticity of the membrane fabricated by a well- established protocol. In the end, a 16-chamber microfluidic chip was successfully fabricated and operating. All layers were aligned and leak-free bonded, and both a vessel-on-chip and engineered heart tissue model were integrated into the platform. It was demonstrated that cell culture chambers of 0.9 µl were filled with a f low rate of 2.7 µl/s. Finally, human umbilical vein endothelial cells (HUVECs) were initially cultured and maintained for at least three days as first proof-of-concept experiment. It was observed that the success rate was depending on the cell culture density. In the future many other types of applications could be integrated into the platform. All in all, the presented modular chip design is paving the way towards the implementation of OoCs in high-throughput pharmakinetic analysis and multiparameter screening.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Subject:42 biology, 44 medicine
Programme:Biomedical Engineering MSc (66226)
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