Developing electrokinetic cantilever biosensors
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Device-based approaches are being developed to measure biological particles such as cells, viruses, proteins, and DNA in dilute samples in situ, on site, or in real time. In many applications, device-based approaches are far more practical or feasible than method-based approaches, which are typically based on microbiological culture or the enzyme-linked immunosorbent assay, because device-based approaches, unlike method-based approaches, are portable, automated, and rapid. At the heart of device-based approaches is the biosensor, which is an analytical device that integrates a biological recognition element with a transduction element. Dynamic-mode cantilevers are an attractive technology for biosensors because they are highly sensitive, label-free, and can be mass-produced cheaply. Microelectrodes that generate electrokinetic effects are also an attractive technology for biosensors, because they can greatly accelerate the capture of biological particles suspended in liquid. In this context, we develop microelectromechanical devices, which we call electrokinetic cantilever biosensors, that combine the high sensitivity of dynamic-mode cantilevers with the rapid capture of biological particles with electrokinetics using standard micromachining fabrication processes. We make the following contributions to the field of device-based biosensing. We develop a thermal ablation method to remove biological material from the surface of silicon biosensors so that biosensors can be conveniently reused during prototyping. We find that piezoelectric actuation is more suitable than electrothermal actuation and we find that electrode configurations with a small electrode gap (≤ 3μm) are best suited for electrokinetics. We perform real-time measurements of E. coli in samples with concentrations as low as 10^2 cells/ml, which approach the infectious dose of E. coli (≈10 cells/ml). We also develop a gap method, which is based on stiffness-change instead of mass-change, to greatly increase the sensitivity of dynamic-mode cantilever biosensors. In this thesis, we conclude that electrokinetic cantilever biosensors are strong candidates for further research. We recommend conducting further work to study the gap method in liquid and to integrate sandwich electrodes with existing, highly sensitive cantilever biosensor designs.