Electrical impedance tomography for real-time 3D tissue culture monitoring

Electrical impedance tomography (EIT) is an emerging image technique that can image the spatial conductivity distribution in the sensing area by generating an electric field and measuring the induced boundary voltages. With the advantages of low-cost, high-temporal resolution, non-destructive and non-radiative, EIT has been developed for the clinical applications, including thorax imaging, lung ventilation monitoring, breast cancer screening and functional brain imaging. Its feasibility for monitoring the motion and conductivity change of the human tissues has been well investigated. It, therefore, shows enormous potential in the in-vitro cellular characterisation, where samples have the same electrical properties as in-vivo human tissues. Since conventional biological imaging techniques are mainly optimised for the monolayer cell culture, their performance is limited when processing the dense, highly scattering tissues, which can better mimic the in vivo situation than 2D cultured cells. Utilising EIT as a novel method to monitor these 3D samples may help to overcome the difficulties and improve the temporal resolution of the data. This thesis aims to evaluate the feasibility of miniature EIT for 3D sample imaging and improve its performance for real-time 3D tissue culture monitoring. Phantom studies were first carried out to evaluate the challenges of EIT imaging when performing in the sensors in the millimetre scale. Different imaging settings, including imaging modality and measuring frequency, were compared, and a combined regularisation method is proposed to improve the image quality. Besides, a physical model for 3D biological tissue was developed to estimate its equivalent conductivity through the electrical properties and volume fraction of cells. The spatial resolution of EIT for tissue culture imaging was examined based on the model. In addition, the protocols of time-difference and frequency-difference EIT for 3D tissue culture monitoring in tightly packed spheroids and sparsely distributed bioscaffolds have been developed and verified through the experiments utilising MCF-7 breast cancer cells. Moreover, equivalent circuit models were developed for the EIT measurement, and a joint simulation method combining the finite element model and equivalent circuit analysis was developed to analyse the measurement error in frequency-difference EIT. Finally, a calibration method was developed to eliminate the circuitry errors in frequency-difference EIT so that it can be applied for the long-term monitoring in biological applications. In summary, this thesis presents the research works on improving the robustness of miniature EIT to the measuring noise and the background disturbance through the optimization of experimental protocols, measuring methods and imaging settings. It shows the potential to be applied in biological research using 3D cell culture, including drug discovery and tissue engineering