| Semiconductor nanowires represent an important class of nanostructured materials with the potential to impact applications from nanoscale electronics to biotechnology. This thesis presents a general strategy for the fabrication of silicon nanowires (SiNW) into SiNW field-effect transistors, the conversion of SiNW field-effect transistors into SiNW sensors, and the development of SiNW sensors for drug discovery and medical diagnostics.; Individual SiNWs grown via nanocluster-catalyzed vapor-liquid-solid mechanism can be fabricated into SiNW field-effect transistors (FETs) by electron beam lithography followed by vacuum evaporation of contact metals. Ti and Ni are ideal metals to make Ohmic contacts with p-type SiNWs after high temperature annealing and the SiNW FETs exhibit, through electrical transport measurements, characteristics exceeding that of conventional planar devices. Furthermore, SiNW FET devices can be configured into SiNW sensors with appropriate surface functionalization methodology to tether molecular receptors onto SiNW.; The biological application of SiNW FET sensors is first demonstrated for real-time, label-free, electrically-based sensing of cancer marker proteins by covalently immobilizing monoclonal antibody receptors onto the SiNW surface via aldehyde-silane condensation reactions. Free prostate specific antigens (fPSA), complexed prostate specific antigens (cPSA), and carcinoembryonic antigens (CEA) are detected in concentration-dependent manner with a sensitivity limit reaching sub-femtomolar range. Multiplex detection of several cancer marker proteins suggests the feasibility of assembling at least three SiNWs for simultaneous and independent quantification of multiple biological species.; The combination of ultrahigh sensitivity and label-free detection scheme makes SiNW sensors especially attractive for probing small molecule-protein interactions. By modifying the SiNW surface with Abl tyrosine kinase, ATP binding to the Abl proteins and the inhibition of ATP binding by small molecule inhibitors can be detected. The inhibition profiles of small molecule inhibitors obtained from the experiments are consistent with reported literature. SiNW sensors therefore represent a novel approach that has significantly overcome many limitations of conventional techniques for investigating small molecule-protein interactions in chemical genetics and drug discovery.; Lastly, the possibility of single molecule detection using SiNW sensors is briefly explored with PSA and CEA sensing. |
