DNA Coil Dynamics and Hydrodynamic Gating of Pressure‐Biased Nanopores

Abstract

Nanopores are ideally suited for the analysis of long DNA fragments including chromosomal DNA and synthetic DNA with applications in genome sequencing and DNA data storage, respectively. Hydrodynamic fluid flow has been shown to slow down DNA transit time within the pore, however other influences of hydrodynamic forces have yet to be explored. In this report, a broad analysis of pressure‐biased nanopores and the impact of hydrodynamics on DNA transit time, capture rate, current blockade depth, and DNA folding are conducted. Using a 10 nm pore, it is shown that hydrodynamic flow inhibits the early stages of linearization of DNA and produces predominately folded events which are initiated by folded DNA (2‐strands) entering the pore. Furthermore, utilizing larger pores (30 nm) leads to unique DNA gating behavior in which DNA events can be switched on and off with the application of pressure. A computational model, based on combining electrophoretic drift velocities with fluid velocities, accurately predicts the pore size required to observe DNA gating. Hydrodynamic fluid flow generated by a pressure bias, or potentially more generally by other mechanisms like electroosmotic flow, is shown to have significant effects on DNA sensing and can be useful for DNA sensing technologies.

Enhanced Pulley Effect for Translocation: The Interplay of Electrostatic and Hydrodynamic Forces

“…The pulley effect has been observed by others in experiments and simulations since then. 14,41,42 A challenge in utilizing this mechanism to promote singlefile capture is the dominance of drift over diffusion in stronger flows. In other words, one could increase the pressure difference to have a stronger velocity gradient, thereby enhancing the forces driving the pulley effect, but consequently, the polymer is carried away with the flow and arrives at the pore faster before significant unraveling takes place.…”

“…This imposes a force equivalent to applying a 312.5 mV voltage difference across the nanopore This is close to the range of voltage biases used in experiments. 10,14,21 This configuration was chosen based on the observations from a set of preliminary runs (results not shown here). For those runs, we applied a simpler and less computationally expensive model of a field that varied only in the x-direction.…”

“…The average electrostatic force on a single monomer F e across the pore for λ = 1.25 is −5 pN. This imposes a force equivalent to applying a 312.5 mV voltage difference across the nanopore This is close to the range of voltage biases used in experiments. ,, …”

“…Sharma et al conducted a broad analysis of pressure-biased nanopores beyond only the translocation time and studied the impact of a hydrodynamic force on capture rate, current blockade depth, and DNA folding . In this study, a positive voltage difference was applied across the pore and both positive and negative pressure gradients were investigated.…”

Multiscale simulations of nanofluidics: Recent progress and perspective

“…Biological nanopores were proved emerging as powerful tools for single molecule analysis, sequencing, 2 and DNA sensing. 349 Biomimetic solid-state nanochannels enable new modalities for biosensing which has the capabilities of rapid and sensitive detection. 3,69 Wang et al 4 have constructed a nanodevice for highly sensitive and selective detection of H 2 O 2 by nanochannels decorated with PBAE (4-(phenoxymethyl) benzeneboronic acid pinacol ester) (Figure 11b).…”