Design, modelling and fabrication of micro-scale electrode arrays (MEAs) for micro-bioimpedance tomography

Abstract

This research involves the design and fabrication of micro-scale electrodes and optimisation of image reconstruction techniques. It aims to explore the use of bioimpedance tomography techniques in extracting some structured information on three-dimensional (3D) cell growth for the purpose of identifying cancer development, such as, cancer cell spheroids. Electrical impedance tomography (EIT) is a non-invasive imaging technique that maps the variation in conductivity of a sample, in the form of two or three dimensions. This technique has been successfully used in many clinical applications, for example, in detection of breast cancer, acute stroke differentiation, detection of bleeding due to traumatic brain injury, and detection of bacterial infection during surgery. The capability of EIT to spatially map biological development process enables it to be used in monitoring cell growth in three-dimensional formation. The work presented in this thesis includes miniaturising the electrode designs from a millimetre-scale on a PCB to a micrometre-scale on a glass substrate, and on a flexible material. Apart from the fabrication and experimental work, sensitivity analysis was performed using COMSOL Multiphysics® modelling. The final electrode design, the flexible micro-scale electrode array (Flex-MEA), is fabricated on a flexible printed circuit board (PCB). The development of Flex-MEA technology with improved imaging reconstruction on micro-scale has produced an improved high-throughput and showed great potential as a research aid in drug discovery. The research has proven that Flex-MEA enables improved electrode arrangement compared with planar Pt electrodes making it a superior choice as a portable, non-invasive technique to image the growth of microbial cultures. Successful measurements of cell growth and proliferation propounded by this research will have a definite potential not only in the biomedical field, example, in therapeutic drug monitoring, but also in bioprocessing technology.