| Studying the biochemical behavior of a single cell by tracking spatial distribution of a variety of extracellular signal molecules in real time is essential for understanding important cellular processes such as cancer metamorphosis, immune response and neuron transmission. An ideal apparatus for such study is an array of miniaturized chemical sensors and biosensors. These sensors usually require single molecule sensitivity since the concentrations of many extracellular biofactors are extremely low. Currently, fluorescent biodetection methods remain the top choice for such studies. However, fluorescent methods suffer from a number of shortcomings such as protein function alteration due to fluorescent tag labeling, limited multiplexibility due to overlapped spectra between different fluorescent tags and photo bleaching.; In this thesis, we present the concepts of three electrical detection approaches that have the potential for single molecule detection. First approach utilizes a self-assembled monolayer (SAM) of organic semiconductor assembled on insulating substrate to form a field effect device of which the conduction is modulated by the binding of the biomolecules. Second approach uses a nanogap formed by electromigration in a gold nanowire as a platform for inelastic tunneling spectroscopy. Third approach converts biomoleculer binding to a nanoelectrode surface selectively modified with SAM immobilized with capturing ligands for target molecules to a reduced current conduction. We have performed preliminary characterization of these sensors after their construction and we present the characterization results in this thesis. We also describe the technical difficulties encountered during fabrication and characterization. To overcome these difficulties, we propose future research plans.; One feature shared by these sensors is that they have small footprint and are all constructed on a silicon dioxide surface hence they are fully compatible, with the complementary metal oxide semiconductor (CMOS) post process. System-on-chip integration of these sensors and signal processing circuitry can be easily achieved with a few postprocesses following CMOS circuit fabrication. Furthermore, construction of these sensors can fully relies on molecular self-assembly and photolithography which can easily reach <100 nm resolution; therefore, large volume production of these sensors is feasible to significantly lower their fabrication cost. |
