Single Solid-state Nanopores Research Articles

Electrophoretic Translocation of Star-Shaped Polymers through Single Solid-State Nanopores

Electrophoretic Translocation of Star-Shaped Polymers through Single Solid-State Nanopores

Characterization of Nanopipet-Supported ITIES Tips for Scanning Electrochemical Microscopy of Single Solid-State Nanopores.

Nanoscale scanning electrochemical microscopy (SECM) is a powerful scanning probe technique that enables high-resolution imaging of chemical processes at single nanometer-sized objects. However, it has been a challenging task to quantitatively understand nanoscale SECM images, which requires accurate characterization of the size and geometry of nanoelectrode tips. Herein, we address this challenge through transmission electron microscopy (TEM) of quartz nanopipets for SECM imaging of single solid-state nanopores by using nanopipet-supported interfaces between two immiscible electrolyte solutions (ITIES) as tips. We take advantage of the high resolution of TEM to demonstrate that laser-pulled quartz nanopipets reproducibly yield not only an extremely small tip diameter of ∼30 nm, but also a substantial tip roughness of ∼5 nm. The size and roughness of a nanopipet can be reliably determined by optimizing the intensity of the electron beam not to melt or deform the quartz nanotip without a metal coating. Electrochemically, the nanoscale ITIES supported by a rough nanotip gives higher amperometric responses to tetrabutylammonium than expected for a 30 nm diameter disc tip. The finite element simulation of sphere-cap ITIES tips accounts for the high current responses and also reveals that the SECM images of 100 nm diameter Si3N4 nanopores are enlarged along the direction of the tip scan. Nevertheless, spatial resolution is not significantly compromised by a sphere-cap tip, which can be scanned in closer proximity to the substrate. This finding augments the utility of a protruded tip, which can be fabricated and miniaturized more readily to facilitate nanoscale SECM imaging.

Molecular Dynamics Simulations of Colloids in Single Solid-State Nanopores

The transport of biomolecules and small particles such as viruses through constrained geometries is critical to understand for efficient molecular separations, detection and selective binding for biomedical and biodefense applications. To develop improved capabilities for isolating and controlling both particles and molecules, there is a need for models developed by computational techniques and matched by well-integrated experiments. Here, we use molecular dynamics simulations to study the flow of colloidal silica particles (diameter ∼50-100 nm) through cylindrical nanopores with diameter 200nm, and lengths 50-100 nm. Particle translocation is investigated in the presence of an applied electric field. We demonstrate the molecular origin of the pore resistance change that occurs once the colloid is inside the pore. The rate at which particles transit the nanopore is highly dependent on the dispersion forces and the electric field, which is in turn a function of both the applied voltage and the pore geometry. Models are supported by experimental findings obtained with resistive pulse sensing.This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344, LLNL-ABS-644260.

Theoretical models for electrochemical impedance spectroscopy and local ζ-potential of unfolded proteins in nanopores

Single solid-state nanopores find increasing use for electrical detection and/or manipulation of macromolecules. These applications exploit the changes in signals due to the geometry and electrical properties of the molecular species found within the nanopore. The sensitivity and resolution of such measurements are also influenced by the geometric and electrical properties of the nanopore. This paper continues the development of an analytical theory to predict the electrochemical impedance spectra of nanopores by including the influence of the presence of an unfolded protein using the variable topology finite Warburg impedance model previously published by the authors. The local excluded volume of, and charges present on, the segment of protein sampled by the nanopore are shown to influence the shape and peak frequency of the electrochemical impedance spectrum. An analytical theory is used to relate the capacitive response of the electrical double layer at the surface of the protein to both the charge density at the protein surface and the more commonly measured zeta potential. Illustrative examples show how the theory predicts that the varying sequential regions of surface charge density and excluded volume dictated by the protein primary structure may allow for an impedance-based approach to identifying unfolded proteins.

Dynamics of Colloids in Single Solid-State Nanopores

We use solid-state nanopores to study the dynamics of single electrically charged colloids through nanopores as a function of applied voltage. We show that the presence of a single colloid inside of the pore changes the pore resistance, in agreement with theory. The normalized ionic current blockade increases with the applied voltage and remains constant when the electrical force increases even more. We observe short and long events of current blockades. Their durations are associated, respectively, with low and high current variation. The ratio of long events increases with the electrical force. The events frequency increases exponentially as a function of applied voltage and saturates at high voltage. The dwelling time decreases exponentially at low and medium voltages when the electrical force increases. At large voltages, this time decreases inversely proportionally to the applied voltage. The long events are associated with translocation events. We show that the dynamics of colloids through the nanopore is governed mainly by two mechanisms, by the free-energy barrier at relatively low and medium voltages and by the electrophoresis mechanism at high voltage.

Solid-State Nanopore Translocation of Idealized Helical Repeat Proteins

We report on the translocation of consensus tetratricopeptide repeat (CTPR) proteins with 10 and 20 repeats through single solid-state nanopores formed in a free standing silicon nitride membrane. The translocation of CTPR proteins was measured in KCl solution at pH below and above its isoelectric point (pI), as well as with and without denaturing agent, Guanidine HCl. When a CTPR protein molecule transits through a nanopore driven by an applied voltage, it partially blocks the ions (K+ and Cl-) flow in the nanopore and generates a characteristic electric current blockage signal. The current blockage signal reveals information about the size, conformation, and primary sequence of the CTPR protein molecule. Previous translocation studies carried out with DNA have established that higher bias voltages result in shorter duration current blockages indicating that DNA translocates faster at a stronger electric field. However, CTPR translocation studies presented here show that longer duration current blockades were observed at higher bias voltages. We explain this surprising result by theoretical analysis of CTPR protein translocation in solid state nanopores. We discuss how the inhomogeneous distribution of the primary charge sequence of the CTPR proteins predicts translocation barriers that are proportional to the bias voltage. Larger barriers at higher bias voltages will result in longer translocation times, consistent with our experimental results.

Ionic Transport Through Single Solid‐State Nanopores Controlled with Thermally Nanoactuated Macromolecular Gates

Single solid-state nanopores modified with poly-N-isopropylacrylamide (NIPAM) brushes display thermally controlled gating properties. Below the lower critical solubility temperature (LCST) NIPAM brushes are swollen and, consequently, dramatically reduce the effective cross section of the nanopores (see image). Conversely, above the LCST the brushes dehydrate and suffer a transition into a collapsed state, which promotes the widening of the nanopore and enables a substantial flow of ions.