Session F47: Invited Session: Solid-State Nanopores: Translocation and Applications

The time distribution of charged biopolymers translocation through voltage-biased solid-state nanopores

When a charged DNA or protein molecule is passing through a voltage biased solid-state nanopore in an ionic solution, it generates a current blockage signal characterized by its amplitude and time duration (or translocation time). Many parameters such as solution viscosity, applied voltage, the size, conformation, charge, and the charge sequence of the molecule could all contribute to the translocation time and its distribution. By fitting the translocation times to the solution of a Smoluchowski-type equation for 1D-biased diffusion and using the Einstein relation, the viscous drag force on uniformly charged DNA molecules and the uncertainty in determining the DNA chain length due to the contribution of Brownian motion can be evaluated. Furthermore, the time distribution of globular shaped particles and not uniformly charged unfolded protein molecules will also be discussed.\\[4pt] [1] Li, J. and D.S. Talaga, \textit{The distribution of DNA translocation times in solid-state nanopores.} J. Phys. Condens. Matter 2010. \textbf{22}: p. 454129 (8pp).\\[0pt] [2] Ling, D. and X. Ling, \textit{First-passage-time analysis of DNA translocation in solid-state nanopores}, in \textit{APS March Meeting 2012 }2012: Boston, Massachusetts.\\[0pt] [3] Ledden, B., D. Fologea, D.S. Talaga and J. Li, \textit{Sensing Single Protein Molecules with Solid-state Nanopores}, in \textit{Nanopores: Sensing and Fundamental Biological Interactions}, S.M. Iqbal and R. Bashir, Editors. 2011, Springer: New York. p. 129-150.   

Controlling DNA Translocation Speed through Solid-State Nanopores by Surface Charge Modulation

The Nanopore method is an emerging technique, which extends gel-electrophoresis to the single-molecule level and allows the analysis of DNAs, RNAs and DNA-protein complexes. The strength of the technique stems from two fundamental facts: First, nanopores due to their nanoscale size can be used to uncoil biopolymers, such as DNA or RNA and slide them in a single file manner that allows scanning their properties. Consequently, the method can be used to probe short as well as extremely long biopolymers, such as genomic DNA with high efficiency. Second, electrostatic focusing of charged biopolymers into the nanopore overcomes thermally driven diffusion, thus facilitating an extremely efficient end-threading (or capture) of DNA. Thus, nanopores can be used to detect minute DNA copy numbers, circumventing costly molecular amplification such as Polymerase Chain Reaction. A critical factor, which determines the ability of nanopore to distinguish fine properties within biopolymers, such as the location of bound small-molecules, proteins, or even the nucleic acid's sequence, is the speed at which molecules are translocated through the pore. When the translocation speed is too high the electrical noise masks the desired signal, thus limiting the utility of the method. Here I will discuss new experimental results showing that modulating the surface charge inside the pore can effectively reduce the translocation speed through solid-state nanopores fabricated in thin silicon nitride membranes. I will present a simple physical model to account for these results.   

Advanced Solid State Nanopores Architectures: From Early Cancer Detection to Nano-electrochemistry

Solid-state nanopores (ssNPs) are potentially low-cost and highly scalable technologies for rapid and reliable se-quencing of the human diploid genome for under {\$}1,000. The ssNPs detect ionic current changes while molecules translocate through the pore. Several key challenges must be overcome in order for ssNPs to become ubiquitous in the fields of medical diagnostics and personalized healthcare. One major challenge is to reduce the speed at which DNA translocates through the nanopore from microseconds to milliseconds per nucleotide, enabling reliable identification of single nucleotides. The other major challenge is to improve the sensitivity of the approach requiring new sensing modalities and novel device architectures. In this paper, we review our recent efforts to (i) develop ssNPs for early cancer detection, (ii) to embed graphene electrodes in dielectric nanolaminates to form 3 and 4 terminal nanopore devices, and (iii) we demonstrate a nanopore based structure consisting of stacked graphene and Al$_{2}$O$_{3}$ dielectric layers to study electrochemical activity at graphene edges. The electrochemical signal corresponding to the atomically thin graphene layer could also provide a pathway to DNA sequencing.   

Nonlinear transport of fd virus particles through a solid-state nanopore

In this talk I will discuss our recent experiments on fd virus particles. The fd particles provide an interesting model system for testing the first-passage time theory of electric-field-driven translocation. We find that the distribution of translocation time can be understood using Schrodinger's first-passage time distribution function. The extracted diffusion constant for fd is significantly larger than the expected value from the Stokes-Einstein relation. We also find that the extracted translocation velocity is a nonlinear function of the electric field. We attribute the large effective diffusion constant to a Taylor dispersion effect in the electroosmotic flow profile in the nanopore and the nonlinear electrophoretic mobility to a Stotz-Wien effect.   

Nanopore Graphene-based Electronic Devices

Graphene is an exceptional material for high-speed electronics, as well as a revolutionary membrane material due to its strength and atomic thickness. Nanopores in suspended graphene membranes are currently regarded as candidates for ultrafast DNA sequencing. When a single DNA molecule passes through a nanopore, it blocks the field-driven ions passing through the pore and is detected by measuring the ion current reduction. Due to the thin nature of graphene membranes and reduced pore resistance, we observe larger current signals than in the case of traditional solid-state nanopores. Use of graphene as a membrane material opens the door to a new class of nanopore devices in which electronic sensing and control are performed directly at the pore.