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Wafer Scale Integration of Coulomb Blockade-based Nanobiosensors with Microfluidic Channels for Label-free Detection of Cancer Biomarkers

出版	2009
URL	http://books.google.com.hk/books?id=whm9tAEACAAJ&hl=&source=gbs_api

註釋In this thesis we propose and implement the fabrication on 4 inch wafer of a novel type of nanobiosensor capable of high sensitivity detection. The principle of the nanobiosensor is based on the variation of electrical tunnelling conductivity through metal nanoislands due to the quantum phenomenon called “Coulomb blockade”. Nickel nanoislands (~5nm diameter), are placed between interdigitated nanoelectrodes devices (IND) (width~45nm). Hence, the conductivity of these Multiple-Tunnel-Junction (MTJ) devices is modified by the adsorption of biomarkers involved in tumourigenesis. Oncologists have recently isolated and characterised a new conformational single chain variable fragment (scFv) which selectively recognises the active form of RhoA. This potential biomarker has been found overexpressed in various tumours. Antibodies fragments (scFv) are adsorbed through coordinative bonds onto nickel nanoislands. Hence the scFv are capable of recognising specifically the active RhoA conformation. We have investigated this biomarker and validated the nickel nanoilands based chemical construction for label-free biodetection using a quartz crystal microbalance (QCM) before implementing the methodology to our devices. An innovative methodology to realise photoPDMS-based microchannels was also developed. Encapsulation with an etched PDMS-nanocomposite finalised the integration of the devices. The final electrical characterisation of the integrated device was tested in real time and continuous biological flow. The active form of RhoA was discriminated against its inactive conformation. In annexe, I present my epistemological and ethical opinions in nanotechnology.