Nanopore-based DNA analysis is a new single-molecule technique that involves monitoring the flow of ions through a narrow pore, and detecting changes in this flow as DNA molecules also pass through the pore. It has the potential to carry out a range of laboratory and medical DNA analyses, orders of magnitude faster than current methods. Initial experiments used a protein channel for its pre-defined, precise structure, but since then several approaches for the fabrication of solid-state pores have been developed. These aim to match the capabilities of biochannels, while also providing increased durability, control over pore geometry and compatibility with semiconductor and microfluidics fabrication techniques. This review summarizes each solid-state nanopore fabrication technique reported to date, and compares their advantages and disadvantages. Methods and applications for nanopore surface modification are also presented, followed by a discussion of approaches used to measure pore size, geometry and surface properties. The review concludes with an outlook on the future of solid-state nanopores.
We observe single nanoparticle translocation events via resistive pulse sensing using silicon nitride pores described by a range of lengths and diameters. Pores are prepared by focused ion beam milling in 50 nm-, 100 nm-, and 500 nm-thick silicon nitride membranes with diameters fabricated to accommodate spherical silica nanoparticles with sizes chosen to mimic that of virus particles. In this manner, we are able to characterize the role of pore geometry in three key components of the detection scheme, namely, event magnitude, event duration, and event frequency. We find that the electric field created by the applied voltage and the pore's geometry is a critical factor. We develop approximations to describe this field, which are verified with computer simulations, and interactions between particles and this field. In so doing, we formulate what we believe to be the first approximation for the magnitude of ionic current blockage that explicitly addresses the invariance of access resistance of solid-state pores during particle translocation. These approximations also provide a suitable foundation for estimating the zeta potential of the particles and/or pore surface when studied in conjunction with event durations. We also verify that translocation achieved by electro-osmostic transport is an effective means of slowing translocation velocities of highly charged particles without compromising particle capture rate as compared to more traditional approaches based on electrophoretic transport.
In this article, we report resistive-pulse sensing experiments with cylindrical track-etched PET pores, which reveal that the diameters of these pores fluctuate along their length. The resistive pulses generated by polymer spheres passing through these pores have a repeatable pattern of large variations corresponding to these diameter changes. We show that this pattern of
This paper describes the development towards a miniaturized analytical system that can perform the major key functions of a flow cytometer. The development aims at diagnostic applications for cell counting and sorting with the ultimate goal of a low-cost portable instrument for point of care diagnosis. The present systems configuration consists of a disposable microfluidic device, that enables injection, single file cell flow through a miniaturized laser induced fluorescence detection system as well as sorting of identified samples. The microfluidic devices were fabricated by means of rapid prototyping technologies based on thick film photo-polymers. This paper reports various approaches on cell sorting and demonstrates sorting of single cells by means of an off-chip valve switching technique. The miniaturized fluorescence detection system employs active and passive micro-optical components, including semiconductor laser and ultra bright LED sources, highly sensitive avalanche photodiodes as well as micro-prism, holographic diffraction gratings and fibre optics for transmission and collection of light. Furthermore we demonstrate the feasibility of integrating solid-state components as part of an on-chip detection system.
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