Solid-state nanopores : fabrication and applications

Abstract: Nanopores are of great interest in study of DNA sequencing, protein profiling and power generation. Among them, solid-state nanopores show obvious advantages over their biological counterparts in terms of high chemical stability and reusability as well as compatibility with the existing CMOS fabrication techniques. Nanopore sensing is most frequently based on measuring ionic current through a nanopore while applying a voltage across it. When an analyte passes through the pore, the ionic current temporarily changes, providing information of the analyte such as its size, shape and surface charge. Although many magnificent reports on using solid-state nanopores have appeared in the literature, several challenges still remain for their wider applications, which include improvement of fabrication reproducibility for mass production of ultra-small nanopores and minimization of measurement instability as well as control of translocation speed and reduction of background noise. This thesis work explores different techniques to achieve robust and high throughput fabrication of sub-10 nm nanopores for different applications.The thesis starts with presenting various fabrication techniques explored during my PhD studies. Focused ion beam method was firstly employed to drill nanopores in free-standing SiNx membranes. Sub-10 nm nanopores could be obtained with a focused helium ion beam. But the fabrication throughput was limited with this technique. A new fabrication process combing electron beam lithography (EBL) with reactive ion etching/ion beam etching, which is compatible with the existing CMOS fabrication technology, was developed to realize a high throughput, mass production of nanopores in free-standing SiNx membranes. However, the smallest size that could be controllably achieved with this process was around 40 nm, which is still far from sub-10 nm in size required for, e.g., DNA sequencing. Finally, by using anisotropic etching of single-crystal silicon in KOH solution, sub-5 nm truncated pyramidal nanopores were mass produced with good process controllability in a silicon-on-insulator (SOI) substrate. In addition, nanopore arrays were also successfully fabricated using a modified EBL based fabrication process.Then, several sensing application examples using either single nanopores or nanopore arrays were investigated. Translocation of nanoparticles, DNA and proteins were demonstrated using the fabricated single nanopores or nanopore arrays in a single freestanding membrane. Moreover, the kinetics and mechanism of the lipid bilayer formation in nanopore array, aiming to prevent non-specific adsorption, were studied using ionic current measurements. In addition, individual addressability of a solid-state nanopore array on separated freestanding membranes was realized by integrating microfluidics and a customized multiplexer.