Channel-length dependence of particle diffusivity in confinement.

Understanding the diffusive behavior of particles and large molecules in channels is of fundamental importance in biological and synthetic systems, such as channel proteins, nanopores, and nanofluidics. Although theoretical and numerical modelings have suggested some solutions, these models have not been fully supported with direct experimental measurements. Here, we demonstrate that experimental diffusion coefficients of particles in finite open-ended channels are always higher than the prediction based on the conventional theoretical model of infinitely long channels. By combining microfluidic experiments, numerical simulations, and analytical modeling, we show that diffusion coefficients are dependent not only on the radius ratio but also on the channel length, the boundary conditions of the neighboring reservoirs, and the compressibility of the medium.

Nonlinear Electrophoresis of Highly Charged Nonpolarizable Particles.

Nonlinear field dependence of electrophoresis in high fields has been investigated theoretically, yet experimental studies have failed to reach consensus on the effect. In this Letter, we present a systematic study on the nonlinear electrophoresis of highly charged submicron particles in applied electric fields of up to several kV/cm. First, the particles are characterized in the low-field regime at different salt concentrations and the surface charge density is estimated. Subsequently, we use microfluidic channels and video tracking to systematically characterize the nonlinear response over a range of field strengths. Using velocity measurements on the single particle level, we prove that nonlinear effects are present at electric fields and surface charge densities that are accessible in practical conditions. Finally, we show that nonlinear behavior leads to unexpected particle trapping in channels.

Density-Dependent Speed-up of Particle Transport in Channels.

Collective transport through channels shows surprising properties under one-dimensional confinement: particles in a single file exhibit subdiffusive behavior, while liquid confinement causes distance-independent correlations between the particles. Such interactions in channels are well studied for passive Brownian motion, but driven transport remains largely unexplored. Here, we demonstrate gating of transport due to a speed-up effect for actively driven particle transport through microfluidic channels. We prove that particle velocity increases with particle density in the channel due to hydrodynamic interactions under electrophoretic and gravitational forces. Numerical models demonstrate that the observed speed-up of transport originates from a hydrodynamic pistonlike effect. Our discovery is fundamentally important for understanding protein channels and transport through porous materials and for designing novel sensors and filters.

QuipuNet: Convolutional Neural Network for Single-Molecule Nanopore Sensing.

Nanopore sensing is a versatile technique for the analysis of molecules on the single-molecule level. However, extracting information from data with established algorithms usually requires time-consuming checks by an experienced researcher due to inherent variability of solid-state nanopores. Here, we develop a convolutional neural network (CNN) for the fully automated extraction of information from the time-series signals obtained by nanopore sensors. In our demonstration, we use a previously published data set on multiplexed single-molecule protein sensing. The neural network learns to classify translocation events with greater accuracy than previously possible, while also increasing the number of analyzable events by a factor of 5. Our results demonstrate that deep learning can achieve significant improvements in single molecule nanopore detection with potential applications in rapid diagnostics.

Nondecaying Hydrodynamic Interactions along Narrow Channels.

Particle-particle interactions are of paramount importance in every multibody system as they determine the collective behavior and coupling strength. Many well-known interactions such as electrostatic, van der Waals, or screened Coulomb interactions, decay exponentially or with negative powers of the particle spacing r. Similarly, hydrodynamic interactions between particles undergoing Brownian motion decay as 1/r in bulk, and are assumed to decay in small channels. Such interactions are ubiquitous in biological and technological systems. Here we confine two particles undergoing Brownian motion in narrow, microfluidic channels and study their coupling through hydrodynamic interactions. Our experiments show that the hydrodynamic particle-particle interactions are distance independent in these channels. This finding is of fundamental importance for the interpretation of experiments where dense mixtures of particles or molecules diffuse through finite length, water-filled channels or pore networks.

Anisotropic diffusion of spherical particles in closely confining microchannels.

We present here the measurement of the diffusivity of spherical particles closely confined by narrow microchannels. Our experiments yield a two-dimensional map of the position-dependent diffusion coefficients parallel and perpendicular to the channel axis with a resolution down to 129 nm. The diffusivity was measured simultaneously in the channel interior, the bulk reservoirs, as well as the channel entrance region. In the channel interior we found strongly anisotropic diffusion. While the perpendicular diffusion coefficient close to the confining walls decreased down to approximately 25% of the value on the channel axis, the parallel diffusion coefficient remained constant throughout the entire channel width. In addition to the experiment, we performed finite element simulations for the diffusivity in the channel interior and found good agreement with the measurements. Our results reveal the distinctive influence of strong confinement on Brownian motion, which is of significance to microfluidics as well as quantitative models of facilitated membrane transport.

Voltage-dependent properties of DNA origami nanopores.

We show DNA origami nanopores that respond to high voltages by a change in conformation on glass nanocapillaries. Our DNA origami nanopores are voltage sensitive as two distinct states are found as a function of the applied voltage. We suggest that the origin of these states is a mechanical distortion of the DNA origami. A simple model predicts the voltage dependence of the structural change. We show that our responsive DNA origami nanopores can be used to lower the frequency of DNA translocation by 1 order of magnitude.

DNA origami nanopores for controlling DNA translocation.

We combine DNA origami structures with glass nanocapillaries to reversibly form hybrid DNA origami nanopores. Trapping of the DNA origami onto the nanocapillary is proven by imaging fluorescently labeled DNA origami structures and simultaneous ionic current measurements of the trapping events. We then show two applications highlighting the versatility of these DNA origami nanopores. First, by tuning the pore size we can control the folding of dsDNA molecules ("physical control"). Second, we show that the specific introduction of binding sites in the DNA origami nanopore allows selective detection of ssDNA as a function of the DNA sequence ("chemical control").

DNA interactions in crowded nanopores.

The motion of DNA in crowded environments is a common theme in physics and biology. Examples include gel electrophoresis and the self-interaction of DNA within cells and viral capsids. Here we study the interaction of multiple DNA molecules within a nanopore by tethering the DNA to a bead held in a laser optical trap to produce a "molecular tug-of-war". We measure this tether force as a function of the number of DNA molecules in the pore and show that the force per molecule decreases with the number of molecules. A simple scaling argument based on a mean field theory of the hydrodynamic interactions between multiple DNA strands explains our observations. At high salt concentrations, when the Debye length approaches the size of the counterions, the force per molecule becomes essentially independent of the number of molecules. We attribute this to a sharp decrease in electroosmotic flow which makes the hydrodynamic interactions ineffective.