Biosensor based on monitoring ion exchange through living cells using the A1GaN/GaN heterostructure

[Truncated abstract] This work is mainly focused on the development of AlGaN/GaN heterostructure living cell-based biosensors that operate by monitoring ion transport through the cell membrane. This technology can assist in drug development, but also has the potential to lead to low cost diagnostics of disease for the broader community. However, there are a number of issues that should be addressed to create reliable and robust devices. Some of the challenges are in stabilisation of short- and long-term drift of the sensor signal, improvement of ion sensitivity to meet or exceed the benchmark set by glass electrodes, reliable packaging and encapsulation of sensor chips, and lack of equivalent all-solid-state reference electrodes. The semiconductor interface with living cells must be separately addressed. In particular, compatibility between the semiconductor surface and the living cell as well as attachment and morphology at the interface must be understood for accurate interpretation of sensor signals. This thesis contains a number of investigations to address these challenges.

The biocompatibility between the AlGaN/GaN semiconductor surface and living cells was thoroughly investigated with a number of complementary methods. Quantitative flow cytometry data indicated a slight increase in the number of dead cells with increasing Al concentration. However, cells survived on the entire range of AlxGa1- xN/GaN compositions. These results suggest possible optimisation through introduction of a thin GaN capping layer and offer flexibility in the AlGaN/GaN heterostructure design. Also a transmission electron microscopy (TEM) lamina of human embryonic kidney (HEK) cells on AlGaN/GaN was successfully obtained through utilising the nano-scale milling, deposition and imaging capabilities of focused ion beam/scanning electron microscopy (FIB/SEM). This enabled visualisation and analysis of cell morphology and attachment at the interface and is one of the first accounts of living cell and semiconductor interface imaging.