Solid-State Nanopores for Sensing : From Theory to Applications

Abstract: Nanopore based sensing technology has been widely studied for a broad range of applications including DNA sequencing, protein profiling, metabolite molecules, and ions detection. The nanopore technology offers an unprecedented technological solution to meeting the demands of precision medicine on rapid, in-field, and low-cost biomolecule analysis. In general, nanopores are categorized in two families: solid-state nanopore (SSNP) and biological nanopore. The former is formed in a solid-state membrane made of SiNx, SiO2, silicon, graphene, MoS2, etc., while the latter represents natural protein ion-channels in cell membranes. Compared to biological pores, SSNPs are mechanically robust and their fabrication is compatible with traditional semiconductor processes, which may pave the way to their large-scale fabrication and high-density integration with standard control electronics. However, challenges remain for SSNPs, including poor stability, low repeatability, and relatively high background noise level. This thesis explores SSNPs from basic physical mechanisms to versatile applications, by entailing a balance between theory and experiment.The thesis starts with theoretical models of nanopores. First, resistance of the open pore state is studied based on the distribution of electric field. An important concept, effective transport length, is introduced to quantify the extent of the high field region. Based on this conductance model, the nanopores size of various geometrical shapes can be extracted from a simple resistance measurement. Second, the physical causality of ionic current rectification of geometrically asymmetrical nanopores is unveiled. Third, the origin of low-frequency noise is identified. The contribution of each noise component at different conditions is compared. Forth, a simple nano-disk model is used to describe the blockage of ionic current caused by DNA translocation. The signal and noise properties are analyzed at system level.Then, nanopore sensing experiments are implemented on cylinder SiNx nanopores and truncated-pyramid silicon nanopores (TPP). Prior to a systematic study, a low noise electrical characterization platform for nanopore devices is established. Signal acquisition guidelines and data processing flow are standardized. The effects of electroosmotic vortex in TPP on protein translocation dynamics are excavated. The autogenic translocation of DNA and proteins driven by the pW-level power generated by an electrolyte concentration gradient is demonstrated. Furthermore, by extending to a multiple pore system, the group translocation behavior of nanoparticles is studied. Various application scenarios, different analyte categories and divergent device structures accompanying with flexible configurations clearly point to the tremendous potential of SSNPs as a versatile sensor.