Impedance spectroscopy for cellular and biomolecular analysis

The application of microfabrication technology to molecular and cell biology has motivated the rapid development of a novel class of microdevices collectively known as ‘Lab On a Chip’ devices. Impedance spectroscopy is a non-invasive, label-free, analytical technique that is amenable to miniaturization, electronic integration, automation, and scalability within ‘LOC’ devices. This thesis describes a microfabricated device for performing continuous impedance analysis of individual cells held in an array of hydrodynamic traps. This device enables continuous long-term analysis of cells and time-dependent measurement of changes elicited by cytotoxic agents and drug compounds. Finite element models are employed to predict the response to changes in the captured single cells (cell position in the trap, cell size, membrane conductivity). The system is used to assay the response of HeLa cells to the effects of the surfactant Tween 20 and Streptolysin-O, a bacterial pore-forming toxin. Novel electrode materials that reduce the parasitic effect of electrode polarisation are described and characterised. These are iridium oxide and PPy/PSS (polypyrrole/poly(styrenesulphonate)). Impedance data is analysed in terms of equivalent circuit models. The findings presented suggest that iridium oxide and PPy/PSS could be used as alternative materials to platinum black and plain platinum. PPy/PSS electrodes offer the highest electrode/electrolyte interface area and least variation with time. Finally, a silicon-based capacitive sensor with nanometric plate separation (nanogap capacitor), is characterized by impedance spectroscopy, and used to explore the behaviour of double layers constrained in cavities of dimensions comparable to the Debye length.