Enhanced Nanoparticle Sensing in a Highly Viscous Nanopore.

Slowing down translocation dynamics is a crucial challenge in nanopore sensing of small molecules and particles. Here, it is reported on nanoparticle motion-mediated local viscosity enhancement of water-organic mixtures in a nanofluidic channel that enables slow translocation speed, enhanced capture efficiency, and improved signal-to-noise ratio by transmembrane voltage control. It is found that higher detection rates of nanoparticles under larger electrophoretic voltage in the highly viscous solvents. Meanwhile, the strongly pulled particles distort the liquid in the pore at high shear rates over 103 s-1 which leads to a counterintuitive phenomenon of slower translocation speed under higher voltage via the induced dilatant viscosity behavior. This mechanism is demonstrated as feasible with a variety of organic molecules, including glycerol, xanthan gum, and polyethylene glycol. The present findings can be useful in resistive pulse analyses of nanoscale objects such as viruses and proteins by allowing a simple and effective way for translocation slowdown, improved detection throughput, and enhanced signal-to-noise ratio.

Regulating Nonlinear Ion Transport through a Solid-State Pore by Partial Surface Coatings.

Using functional nanofluidic devices to manipulate ion transport allows us to explore the nanoscale development of blue energy harvesters and iontronic building blocks. Herein, we report on a method to alter the nonlinear ionic current through a pore by partial dielectric coatings. A variety of dielectric materials are examined on both the inner and outer surfaces of the channel with four different patterns of coated or uncoated surfaces. Through controlling the specific part of the surface charge, the pore can behave like a resistor, diode, and bipolar junction transistor. We use numerical simulations to find out the reason for the asymmetric ion transport in the pore and illustrate the relationship between specifically charged surfaces and electroosmotic flow. These findings help understand the role of the corresponding surface composition in ion transport, which provides a direct approach to modify the electroosmotic-flow-driven ionic current rectification in the channel-based device via dielectric coatings.

Dielectric Coatings for Resistive Pulse Sensing Using Solid-State Pores.

The present study reports on the systematic characterization of the effectiveness of dielectric coating to tailor capture-to-translocation dynamics of single particles in solid-state pores. We covered the surface of SiNx membranes with SiO2, HfO2, Al2O3, TiO2, or ZnO, which allowed us to change the ζ-potential at the pore wall, reflecting the isoelectric points of these coating materials. Resistive pulse measurements of negatively charged polystyrene beads elucidated more facile electrophoretic capture of the particles and slower translocation motions in the channel under more negative electric potential at the oxide surface. These findings provide a guide to engineer pore wall surface for optimizing the translocation dynamics for efficient sensing of particles and molecules.

Effect of Electrolyte Concentration on Cell Sensing by Measuring Ionic Current Waveform through Micropores.

Immunostaining has been widely used in cancer prognosis for the quantitative detection of cancer cells present in the bloodstream. However, conventional detection methods based on the target membrane protein expression exhibit the risk of missing cancer cells owing to variable protein expressions. In this study, the resistive pulse method (RPM) was employed to discriminate between cultured cancer cells (NCI-H1650) and T lymphoblastoid leukemia cells (CCRF-CEM) by measuring the ionic current response of cells flowing through a micro-space. The height and shape of a pulse signal were used for the simultaneous measurement of size, deformability, and surface charge of individual cells. An accurate discrimination of cancer cells could not be obtained using 1.0 × phosphate-buffered saline (PBS) as an electrolyte solution to compare the size measurements by a microscopic observation. However, an accurate discrimination of cancer cells with a discrimination error rate of 4.5 ± 0.5% was achieved using 0.5 × PBS containing 2.77% glucose as the electrolyte solution. The potential application of RPM for the accurate discrimination of cancer cells from leukocytes was demonstrated through the measurement of the individual cell size, deformability, and surface charge in a solution with a low electrolyte concentration.

Application of Micropore Device for Accurate, Easy, and Rapid Discrimination of Saccharomyces pastorianus from Dekkera spp.

Traceability analysis, such as identification and discrimination of yeasts used for fermentation, is important for ensuring manufacturing efficiency and product safety during brewing. However, conventional methods based on morphological and physiological properties have disadvantages such as time consumption and low sensitivity. In this study, the resistive pulse method (RPM) was employed to discriminate between Saccharomyces pastorianus and Dekkera anomala and S. pastorianus and D. bruxellensis by measuring the ionic current response of cells flowing through a microsized pore. The height and shape of the pulse signal were used for the simultaneous measurement of the size, shape, and surface charge of individual cells. Accurate discrimination of S. pastorianus from Dekkera spp. was observed with a recall rate of 96.3 ± 0.8%. Furthermore, budding S. pastorianus was quantitatively detected by evaluating the shape of the waveform of the current ionic blockade. We showed a proof-of-concept demonstration of RPM for the detection of contamination of Dekkera spp. in S. pastorianus and for monitoring the fermentation of S. pastorianus through the quantitative detection of budding cells.

Crucial Role of Out-of-Pore Resistance on Temporal Response of Ionic Current in Nanopore Sensors.

We investigated the temporal resolution of ionic current in solid-state nanopore sensors. Resistive pulses observed upon translocation of single-nanoparticles were found to become blunter as we imposed larger external resistance in series to the pore via the integrated microfluidic channels on the membrane. This was found to occur even when the out-of-pore resistance is more than an order of magnitude smaller than that at the nanopore, which can be understood as a predominant contribution of charging/discharging at the water-touching thin dielectrics to retard the response of the ionic current against ion blockage by a fast-moving object through the sensing zone. Most importantly, our results predict a time resolution of better than 12 ns, irrespective of the nanopore size, by optimizing the membrane capacitance and the external resistance that promises high-speed single-molecule sequencing by the ionic current at 106 base/s.

Dissecting Time-Evolved Conductance Behavior of Single Molecule Junctions by Nonparametric Machine Learning.

Improved understanding of charge transport in single molecules is essential for utilizing their potential as circuit components at the nanosize limit. However, reliable analyses of varying tunneling current acquired by break junction experiments remain an ongoing challenge to find molecular feature structure-property relationships. In this work, we report on an unsupervised learning approach for investigating molecular signatures in conductance traces. Our hybrid machine learning algorithm compares grids of data in conductance-time domains and judges the similarity without any researcher-crafted parameters to identify fine molecular components that may otherwise be obscured by background fluctuations. We demonstrate its ability for classifying Au-alkanedithiol-Au conductance traces acquired with microfabricated mechanically controllable break junctions. The unbiased procedure was able to not only judge the presence or absence of the carbon chains in the electrode gap but also to identify multiple conductance states of the molecular tunneling junctions with different conformations. This finding may offer a useful tool for studying single-molecule properties using break junction methods.

Tailoring Dielectric Surface Charge via Atomic Layer Thickness.

Channel surface property is a crucial factor that affects capture-to-translocation dynamics of single-particles in solid-state pores. Here, we show that atomically-thin dielectrics can be used to finely tune the pore wall surface potential. We isotopically coated alumina of atomically controlled thickness on a Si3N4 micropore. The surface zeta-potential in a buffer was found to decrease sharply by 1 nm thick deposition that served as a water-permeable ultra-thin sheet to modulate the effective charge density of the Al2O3/Si3N4 multilayer structure. Further thickening of the atomic layer enabled to control the zeta potential with a thickness at 3.4 mV/nm resolution. Accordingly, we observed concomitant enhancement in the capture rate and the translocation speed of negatively charged polymeric particles by virtue of the mitigated electroosmotic back flow in the functionalized pore channel. This simple method is widely applicable for tailoring the surface charge properties of essentially any sensors and devices working in aqueous media.

Electroosmosis-Driven Nanofluidic Diodes.

Fundamental understanding of ion transport in a fluidic channel is of critical importance for realizing iontronics. Here we report on asymmetric ion transport in a low thickness-to-diameter aspect ratio nanopore. Under uniform salt concentration conditions, the cross-pore ionic current showed ohmic characteristics with no bias polarity dependence. In stark contrast, despite the weak ion selectivity expected for the relatively large nanopores employed, we observed diode-like behavior when a salt gradient was imposed across the thin membrane. This unexpected result was attributed to the electroosmotic flow that served to modulate the access resistance through dragging the condensed ions into or out of the nanopore orifices. The simple mechanism was also revealed to be effective in fluidic channels of various size from micro- to nanoscale enabling rectification of the property engineering by the pore geometries. The present findings allow for novel designs of artificial ion channel building blocks.

Quasi-Stable Salt Gradient and Resistive Switching in Solid-State Nanopores.

Understanding and control of ion transport in a fluidic channel is of crucial importance for iontronics. The present study reports on quasi-stable ionic current characteristics in a SiNx nanopore under a salinity gradient. An intriguing interplay between electro-osmotic flow and local ion density distributions in a solid-state pore is found to induce highly asymmetric ion transport to negative differential resistance behavior under a 100-fold difference in the cross-membrane salt concentrations. Meanwhile, a subtle change in the salinity gradient profile led to observations of resistive switching. This peculiar characteristic was suggested to stem from quasi-stable local ion density around the channel that can be switched between two distinct states via the electro-osmotic flow under voltage control. The present findings may be useful for neuromorphic devices based on micro- and nanofluidic channels.