Xin Zhu

It is a well-known principle that like charges repel, whether positive or negative. However, experiments on electrically charged matter suspended in liquids have frequently reported the opposite: attraction between like-charged particles, rather than repulsion. Experiments have also shown that the sign of the force at large separations can depend on the sign of the particle charge, e.g., in water negative particles attract, while positives repel as expected, and this trend generally reverses in polar organic solvents such as alcohols. These observations cannot be reconciled with standing theories of the electrostatic interaction that regard the intervening solvent medium as a structureless, featureless dielectric continuum. Recent work has called for the traditional continuum view of the medium to be relinquished, attributing the observed attraction to an “electrosolvation force” – a term that describes interactions bearing electrical signatures that depend on the properties and structuring of the molecular solvent close to an interface. Here we discuss a range of recent experiments that shed light on the mechanistic underpinnings of this previously unanticipated interaction. We also discuss developments on the theoretical front that not only capture the observed attraction between like-charged particles but also recover the canonical monotonic repulsion – a hallmark of standing continuum-dielectric theories. Thus, the traditionally anticipated repulsion represents a distinct and important regime within a general theoretical framework that accounts for the solvent in substantially greater detail. Given the fundamental importance of the forces that drive structure and organization from molecular and particulate building blocks, this emerging discovery is likely to have broad implications across a wide range of fields. Interface-governed properties that generate long-range signatures in fluids may also prove relevant to electrokinetic and electrochemical processes.

This work numerically reveals a novel strategy to modulate two ionic conductance state in a nanochannel via pressure-dependent fluidic motion inside the channel. Steady and transient simulations based on Poisson–Nernst–Planck–Stokes equations demonstrate that the two states with distinct ionic conductance and ion selectivity can be reversibly switched by external pressure, with a characteristic time of ~100 μs. Furthermore, the two conductance states are found to depend on the transversal electric field, which gives rise to two distinct intrachannel fluidic flow patterns, namely laminar flow and vortex flow, respectively. This finding suggests the potential of pressure-controlled ionic conductance switching for applications in nanofluidic ionic circuits, flow-regulated sensing, and integrated micro/nanoscale devices. It also provides insights into nonlinear ionic current–voltage behaviors.

Solid-state nanopores hold substantial potential in single-molecule sensing. Fully wetting the nanopore is a crucial but challenging pre-treatment step for biomolecule sensing. Conventional wetting techniques, including passive wetting, plasma treatment, mechanical pressure, and thermal treatment, and chemical treatment, often suffer from limited effectiveness, high complexity, or incompatibility with certain materials and nanopore geometries. This work proposes a contactless ultrasonic wave-facilitated wetting (UFW) method for rapid nanopore wetting. Our experimental findings demonstrate that UFW enhances the wetting speed by over three orders of magnitude in SiNx nanopores compared to passive wetting, reducing the wetting time to minutes. Improvements are also observed in sandwiched ZnO–SiNx and ITO–SiNx structure nanopores with varying hydrophilicity. This work provides a rapid, real-time, chemical-free, and low-cost wetting method for solid-state nanopores and may also be applicable to other nanostructured systems.

Size and shape are critical discriminators between molecular species and states. We describe a microchip-based high-throughput imaging approach offering rapid and precise determination of molecular properties under native solution conditions. Our method detects differences in molecular weight across at least three orders of magnitude and down to two carbon atoms in small molecules. We quantify the strength of molecular interactions across more than six orders of magnitude in affinity constant and track reactions in real time. Highly parallel measurements on individual molecules serve to characterize sample-state heterogeneity at the highest resolution, offering predictive input to model three-dimensional structure. We further leverage the method’s structural sensitivity for diagnostics, exploiting ligand-induced conformational changes in the insulin receptor to sense insulin concentration in serum at the subnanoliter and subzeptomole scale.

Nanopores that integrate indium-tin-oxide (ITO) electrical gates have previously demonstrated the capability of modulating the DNA folding/knotting configurations in their translocation dwell times in such devices. Four ITO-SiNx nanopore devices are fabricated with their sizes in the 8 ∼ 20 nm range. The current blockage and dwell time characterizations using these nanopores are presented for DNAs entering from both the SiNx and ITO sides of the nanopores with 0 V bias applied at the ITO gate. While the current blockage data show little dependence on nanopore sizes, dwell time appears to be shorter with smaller nanopore sizes. Interestingly, the dwell times of DNAs entering from the ITO side are observed to be shorter than those of the reverse direction, suggesting the DNA translocation process is affected by the asymmetry of the layered nanopore structures. This work proves ITO as a compatible material for DNA translocation and provides a basic research for the velocity studies of DNA translocation in gated nanopores.

We propose and fabricate solid-state nanopore devices that monolithically integrate solution-gated, vertical thin-film transistors (TFTs) inside the nanopores for charge-based sensing of translocating biomolecules. The TFTs consist of zinc oxide semiconductor channels and aluminum oxide gate dielectrics, which are both conformally deposited along the inner surfaces of the nanopores via atomic layer deposition. The resultant TFT channel lengths and nanopore diameters both reach the ∼10 nm range. In translocation experiments using λ-DNAs or bovine serum antibody (BSA) proteins, the TFT–nanopore devices demonstrate concurrent detection of the ion conductance blockade signals and modulation signals in the TFT electrical current. The TFT signals show opposite signs for the negatively charged DNAs and positively charged BSAs as well as staircase signal shapes that correspond to the folding and knotting of λ-DNAs. Further experiments under various electrical biases and solution ionic strengths show that the ion blockade signals and the TFT signals have different dependence upon these experimental conditions. The TFT signals are analyzed to be consistent with the field effect sensing of the biomolecular charge, and the induced mirror charge is estimated from the signal amplitudes. This study could be a step forward to achieve charge-based single-biomolecular technology for basic research as well as for biosensing applications. It may also stimulate the development of TFT technologies for conformal integration of semiconductor electronics at the front end of nanostructures.

Excessively-long translocation events of single DNAs are experimentally observed using a small nanopore. Solid-state Nano pores on SiNx membranes with pore diameters less than 5nm are fabricated via Transmission Electron Microscopy. The translocation testing system is set up based on patch-clamp and Lab-on-Chip, and translocation experiments of Lambda DNAs are conducted. Stable current traces and single molecular translocation events are achieved. Statistical analysis under various cross-membrane voltages shows typical characteristics of SiNx Nano pores, including event rates, threshold voltages, and noise power-spectrum-density. Particularly, excessively-long dwell time (>100ms) events through <5 nm nanopore are observed and attributed to the interaction between DNAs and pore walls. This characteristic is compared against the basic current-blockage model as well as that of a 10 nm nanopore control experiment, demonstrating additional blockage effects.

This experimental work studies the translocation of bovine serum albumin (BSA) proteins through MoS₂ nanopores. A simple method of device fabrication is developed based on dry-transfer of exfoliated MoS₂ membranes and subsequent TEM drilling, yielding MoS₂ nanopores of a few monolayers thick and diameters as small as ∼11 nm. The current-voltage relation and low-frequency current noise of the devices are characterized. Typical BSA translocation signals that possibly correspond to various orientations are observed in the MoS₂ devices, exhibiting enhanced amplitude and similar characteristics when compared to those from a silicon nitride (SiN_x) control. Furthermore, the statistical data of the signal amplitude and dwell time at various biases are analyzed. These results show opportunities of single-molecular protein analysis using MoS₂ nanopores.

This work reveals a counterintuitive but basic process of ionic screening in nanofluidic channels. Steady-state numerical simulations and mathematical analysis show that, under significant longitudinal ionic transport, the screening ionic charges can be locally inverted in the channels: their charge sign becomes the same as that of the channel surface charges. The process is identified to originate from the coupling of ionic electro-diffusion transport and junction two-dimensional electrostatics. This finding may expand our understanding of ionic screening and electrical double layers in nanochannels. Furthermore, the charge inversion process results in a body-force torque on channel fluids, which is a possible mechanism for vortex generation in the channels and their nonlinear current–voltage characteristics.