Super, ASM; (2014) Oxygen monitoring in a microfluidic culture device for stem cell bioprocess development. Doctoral thesis , UCL (University College London).

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Abstract

In this thesis, an online oxygen monitoring system has been presented to quantify the dissolved oxygen concentration levels in a microfluidic device for the adherent culture of pluripotent stem cells. Oxygen is a critical environmental cue regulating stem cell fate. Therefore an online monitoring system, combined with the greater control over the soluble microenvironment provided by microfluidic systems, is of interest to assist the development of robust bioprocessing approaches for regenerative medicine therapies. An oxygen monitoring system consisting of optical sensors have been designed and integrated with the microfabricated modular culture device technology previously established by the Szita Group. The monitoring system enables non-invasive measurements of bulk and peri-cellular oxygen concentration levels in an adherent culture device. A platform for the operation of the device and monitoring system has been established to meet the requirements for adherent stem cell culture. It supports the adherent culture of mouse embryonic stem cells for up to one week under continuous perfusion and integrates automated monitoring systems for dissolved oxygen and culture confluency. Standard operating procedures for the microfluidic culture have been defined to ensure the robustness and repeatability of the process. The seamless integration of online oxygen monitoring with confluency monitoring has enabled for the first time to quantify non-invasively oxygen uptake rates of adherent stem cell cultures.

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