arXiv subjects

Ulrich F. Keyser

Publications and source records attributed to Ulrich F. Keyser.

At least 19 recordsLinked to original sources

arXiv2024

Resolution dependence of most probable pathways with state-dependent diffusivity

Recent experiments have probed the relative likelihoods of trajectories in stochastic systems by observing survival probabilities within a tube of radius $R$ in spacetime. We measure such probabilities here for a colloidal particle in a corrugated channel, corresponding to a bistable potential with state-dependent diffusivity. In contrast to previous findings for state-independent noise, we find that the most probable pathway changes qualitatively as the tube radius $R$ is altered. We explain this by computing the survival probabilities predicted by overdamped Langevin dynamics. At high enough resolution (small enough $R$), survival probabilities depend solely on diffusivity variations, independent of deterministic forces; finite $R$ corrections yield a generalization of the Onsager-Machlup action. As corollary, ratios of survival probabilities are singular as $R \to 0$, but become regular, and described by the classical Onsager-Machlup action, only in the special case of state-independent noise.

cond-mat.stat-mech↗

arXiv2021

3D Flow Field Measurements Outside Nanopores

We demonstrate a non-stereoscopic, video-based particle tracking system with optical tweezers to study fluid flow in 3D in the vicinity of glass nanopores. In particular, we used the Quadrant Interpolation algorithm to extend our video-based particle tracking to displacements out of the trapping plane of the tweezers. This permitted the study of flow from nanopores oriented at an angle to the trapping plane, enabling the mounting of nanopores on a micromanipulator with which it was then possible to automate the mapping procedure. Mapping of voltage driven flow in 3D volumes outside nanopores revealed polarity dependent flow fields. This is in agreement with the model of voltage driven flow in conical nanopores depending on the interaction of distinct flows within the nanopore and along the outer walls.

physics.flu-dyn↗

arXiv2021

Experimental measurement of relative path probabilities and stochastic actions

For diffusive stochastic dynamics, the probability to observe any individual trajectory is vanishingly small, making it unclear how to experimentally validate theoretical results for ratios of path probabilities. We provide the missing link between theory and experiment, by establishing a protocol to extract ratios of path probabilities from measured time series. For experiments on a single colloidal particle in a microchannel, we extract both ratios of path probabilities, and the most probable path for a barrier crossing, and find excellent agreement with independently calculated predictions based on the Onsager-Machlup stochastic action. Our experimental results at room temperature are found to be inconsistent with the low-noise Freidlin-Wentzell stochastic action, and we discuss under which circumstances the latter is expected to describe the most probable path. Furthermore, while the experimentally accessible ratio of path probabilities is uniquely determined, the formal path-integral action is known to depend on the time-discretization scheme used for deriving it; we reconcile these two seemingly contradictory facts by careful analysis of the time-slicing derivation of the path integral. Our experimental protocol enables us to probe probability distributions on path space, and allows us to relate theoretical single-trajectory results to measurement.

cond-mat.stat-mech↗

arXiv2020

Experimental evidence of symmetry breaking of transition-path times

While Kramers' rates have been studied for almost a century, the transition path time between states has only recently received attention. Transition paths between different energy levels are expected to be indistinguishable in shape and have equal uphill and downhill lengths. This fundamental symmetry often prevents directional sensing in experiments. Here, we report experimental evidence for transition path time symmetry and its breakdown on the single-molecule and mesoscale. In automated Brownian dynamics experiments, we establish first-passage time symmetries of colloids driven by femtoNewton-range forces in holographically-created optical landscapes confined in microchannels. Conversely, we show that transitions which couple in a path-dependent manner to fluctuating forces exhibit asymmetry. We reproduce this asymmetry in folding transitions of DNA-hairpins driven out of equilibrium and suggest a topological mechanism for the symmetry breakdown. Our results can reveal directionality in molecular transitions or translocations through membrane channels and nanopores.

cond-mat.stat-mech↗

arXiv2019

Optimizing Brownian escape rates by potential shaping

Brownian escape is key to a wealth of physico-chemical processes, including polymer folding, and information storage. The frequency of thermally activated energy barrier crossings is assumed to generally decrease exponentially with increasing barrier height. Here, we show experimentally that higher, fine-tuned barrier profiles result in significantly enhanced escape rates in breach of the intuition relying on the above scaling law, and address in theory the corresponding conditions for maximum speed-up. Importantly, our barriers end on the same energy on which they start. For overdamped dynamics, the achievable boost of escape rates is, in principle, unbounded so that the barrier optimization has to be regularized. We derive optimal profiles under two different regularizations, and uncover the efficiency of N-shaped barriers. We then demonstrate the viability of such a potential in automated microfluidic Brownian dynamics experiments using holographic optical tweezers and achieve a doubling of escape rates compared to unhindered Brownian motion. Finally, we show that this escape rate boost extends into the low-friction inertial regime.

cond-mat.soft↗

arXiv2019

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 work, 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.

cond-mat.soft↗

arXiv2019

Cation dependent electroosmotic flow in glass nanopores

We present our findings on the changes to electroosmotic flow outside glass nanopores with respect to the choice of Group 1 cation species. In contrast with standard electrokinetic theory, flow reversal was observed for all salts under a negative driving voltage. Moving down Group 1 resulted in weaker flow when the driving voltage was negative, in line with the reduction in the zeta potential on the glass surface going down the periodic table. No trend emerged with a positive driving voltage, however for Cs, flow was uniquely found to be in reverse. These results are explained by the interplay between the flow inside the nanopore and flow along the outer walls in the vicinity of the nanopore.

physics.bio-ph↗

arXiv2019

Current enhancement in solid-state nanopores depends on three-dimensional DNA structure

The translocation of double-stranded DNA through a solid-state nanopore may either decrease or increase the ionic current depending on the ionic concentration of the surrounding solution. Below a certain crossover ionic concentration, the current change inverts from a current blockade to current enhancement. In this paper, we show that the crossover concentration for bundled DNA nanostructures composed of multiple connected DNA double-helices is lower than that of double-stranded DNA. Our measurements suggest that counterion mobility in the vicinity of DNA is reduced depending on the three-dimensional structure of the molecule. We further demonstrate that introducing neutral polymers such as polyethylene glycol into the measurement solution reduces electroosmotic outflow from the nanopore, allowing translocation of large DNA structures at low salt concentrations. Our experiments contribute to an improved understanding of ion transport in confined DNA environments, which is critical for the development of nanopore sensing techniques as well as synthetic membrane channels. Our salt-dependent measurements of model DNA nanostructures will guide the development of computational models of DNA translocation through nanopores.

physics.bio-ph↗

arXiv2019

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 sub-diffusive 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 piston-like effect. Our discovery is fundamentally important for understanding protein channels and transport through porous materials and for designing novel sensors and filters.

cond-mat.soft↗

arXiv2019

Bayesian inference for nanopore data analysis

Nanopore sensors detect the substructure of individual molecules from modulations in an ion current as molecules pass through them. In this work, we present the classification of features in the substructure as a case study to illustrate the power of Bayesian inference when analysing nanopore data. A brief introductory section provides an overview of the core concepts, followed by a detailed description of the analysis procedure to facilitate other researchers to add Bayesian inference to their toolbox. Our hybrid approach of a classical peak-finding algorithm and Bayesian model comparison allows the probabilistic classification of features as "0" or "1" bits by calculating relative evidences for two competing models. We correctly classify on average ~ 70% of bits for individual events and use the probabilistic nature of the approach to calculate a cumulative estimate with an accuracy of > 94%. The technique presented here is readily extensible to models of the translocation process which can take into account arbitrary molecular designs, our approach may therefore be used to analyse a wide range of features observed in nanopore experiments.

physics.bio-ph↗

arXiv2018

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 dataset 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 analysable events by a factor of five. Our results demonstrate that deep learning can achieve significant improvements in single molecule nanopore detection with potential applications in rapid diagnostics.

q-bio.QM↗

arXiv2018

Promoting single-file DNA translocations through nanopores using electroosmotic flow

Double-stranded DNA translocates through sufficiently large nanopores either in a linear, single-file fashion or in a folded hairpin conformation when captured somewhere along its length. We show that the folding state of DNA can be controlled by changing the electrolyte concentration, pH and PEG content of the measurement buffer. At 1 M LiCl or 0.35 M KCl in neutral pH, single-file translocations make up more than 90% of the total. We attribute the effect to the onset of electroosmotic flow from the pore at low ionic strength. Our hypothesis on the critical role of flows is supported by the preferred orientation of entry of a strand that has been folded into a multi-helix structure at one end. Control over DNA folding is critical for nanopore sensing approaches that use modifications along a DNA strand and the associated secondary current drops to encode information.

physics.bio-ph↗

arXiv2017

Mapping nanoscale hotspots with single-molecule emitters assembled into plasmonic nanocavities using DNA origami

Fabricating nanocavities in which optically-active single quantum emitters are precisely positioned, is crucial for building nanophotonic devices. Here we show that self-assembly based on robust DNA-origami constructs can precisely position single molecules laterally within sub-5nm gaps between plasmonic substrates that support intense optical confinement. By placing single-molecules at the center of a nanocavity, we show modification of the plasmon cavity resonance before and after bleaching the chromophore, and obtain enhancements of $\geq4\times10^3$ with high quantum yield ($\geq50$%). By varying the lateral position of the molecule in the gap, we directly map the spatial profile of the local density of optical states with a resolution of $\pm1.5$ nm. Our approach introduces a straightforward non-invasive way to measure and quantify confined optical modes on the nanoscale.

physics.optics↗

arXiv2017

Particle transport across a channel via an oscillating potential

Membrane protein transporters alternate their substrate-binding sites between the extracellular and cytosolic side of the membrane according to the alternating access mechanism. Inspired by this intriguing mechanism devised by nature, we study particle transport through a channel coupled with an energy well that oscillates its position between the two entrances of the channel. We optimize particle transport across the channel by adjusting the oscillation frequency. At the optimal oscillation frequency, the translocation rate through the channel is a hundred times higher with respect to free diffusion across the channel. Our findings reveal the effect of time dependent potentials on particle transport across a channel and will be relevant for membrane transport and microfluidics application.

physics.bio-ph↗

arXiv2017

Suppressed Quenching and Strong Coupling of Purcell-Enhanced Single-Molecule Emission in Plasmonic Nanocavities

An emitter in the vicinity of a metal nanostructure is quenched by its decay through non-radiative channels, leading to the belief in a zone of inactivity for emitters placed within $<$10nm of a plasmonic nanostructure. Here we demonstrate that in tightly-coupled plasmonic resonators forming nanocavities "quenching is quenched" due to plasmon mixing. Unlike isolated nanoparticles, plasmonic nanocavities show mode hybridization which massively enhances emitter excitation and decay via radiative channels. This creates ideal conditions for realizing single-molecule strong-coupling with plasmons, evident in dynamic Rabi-oscillations and experimentally confirmed by laterally dependent emitter placement through DNA-origami.

physics.optics↗

arXiv2017

Direction- and Salt-Dependent Ionic Current Signatures for DNA Sensing with Asymmetric Nanopores

Solid-state nanopores are promising tools for single molecule detection of both DNA and proteins. In this study, we investigate the patterns of ionic current blockades as DNA translocates into or out of the geometric confinement of such conically shaped pores. We studied how the geometry of a nanopore affects the detected ionic current signal of a translocating DNA molecule over a wide range of salt concentration. The blockade level in the ionic current depends on the translocation direction at a high salt concentration, and at lower salt concentrations we find a non-intuitive ionic current decrease and increase within each single event for the DNA translocations exiting from confinement. We use recently developed DNA rulers with markers and finite element calculations to explain our observations. Our calculations explain the shapes of the signals observed at all salt concentrations and show that the unexpected current decrease and increase are due to the competing effects of ion concentration polarization and geometric exclusion of ions. Our analysis shows that over a wide range of geometry, voltage and salt concentrations we are able to understand the ionic current signals of DNA in asymmetric nanopores enabling signal optimization in molecular sensing applications.

physics.bio-ph↗

arXiv2016

Direct measurements reveal non-Markovian fluctuations of DNA threading through a solid-state nanopore

The threading of a polymer chain through a small pore is a classic problem in polymer dynamics and underlies nanopore sensing technology. However important experimental aspects of the polymer motion in a solid-state nanopore, such as an accurate measurement of the velocity variation during translocation, have remained elusive. In this work we analysed the translocation through conical quartz nanopores of a 7 kbp DNA double-strand labelled with six markers equally spaced along its contour. These markers, constructed from DNA hairpins, give direct experimental access to the translocation dynamics. On average we measure a 5% reduction in velocity during the translocation. We also find a striking correlation in velocity fluctuations with a decay constant of 100s of μs. These results shed light on hitherto unresolved problems in the dynamics of DNA translocation and provide guidance for experiments seeking to determine positional information along a DNA strand.

physics.bio-ph↗

arXiv2016

Selective Trapping of DNA using Glass Microcapillaries

We show experimentally that a cheap glass microcapillary can accumulate λ-phage DNA at its tip and deliver the DNA into the capillary using a combination of electro-osmotic flow, pressure-driven flow, and electrophoresis. We develop an efficient simulation model for this phenomenon based on the electrokinetic equations and the finite-element method. Using our model, we explore the large parameter space of the trapping mechanism by varying the salt concentration, the capillary surface charge, the applied voltage, the pressure difference, and the mobility of the analyte molecules. Our simulation results show that this system can be tuned to capture a wide range of analyte molecules, such as DNA or proteins, based on their electrophoretic mobility. Our method for separation and pre-concentration of analytes has implications for the development of low-cost lab-on-a-chip devices.

cond-mat.soft↗