Ion Current Measurements Research Articles

Activation energy for pore opening in lipid membranes under an electric field

The standard model of pore formation was introduced more than fifty years ago, and it has been since, despite some refinements, the cornerstone for interpreting experiments related to pores in membranes. A central prediction of the model concerning pore opening under an electric field is that the activation barrier for pore formation is lowered proportionally to the square of the electric potential. However, this has only been scarcely and inconclusively confronted to experiments. In this paper, we study the electropermeability of model lipid membranes composed of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) containing different fractions of POPC-OOH, the hydroperoxidized form of POPC, in the range 0 to 100 mol %. By measuring ion currents across a 50-μm-diameter black lipid membrane (BLM) with picoampere and millisecond resolution, we detect hydroperoxidation-induced changes to the intrinsic bilayer electropermeability and to the probability of opening angstrom-size or larger pores. Our results over the full range of lipid compositions show that the energy barrier to pore formation is lowered linearly by the absolute value of the electric field, in contradiction with the predictions of the standard model.

PITX2 Knockout Induces Key Findings of Electrical Remodeling as Seen in Persistent Atrial Fibrillation.

Electrical remodeling in human persistent atrial fibrillation is believed to result from rapid electrical activation of the atria, but underlying genetic causes may contribute. Indeed, common gene variants in an enhancer region close to PITX2 (paired-like homeodomain transcription factor 2) are strongly associated with atrial fibrillation, but the mechanism behind this association remains unknown. This study evaluated the consequences of PITX2 deletion (PITX2-/-) in human induced pluripotent stem cell-derived atrial cardiomyocytes. CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) was used to delete PITX2 in a healthy human iPSC line that served as isogenic control. Human induced pluripotent stem cell-derived atrial cardiomyocytes were differentiated with unfiltered retinoic acid and cultured in atrial engineered heart tissue. Force and action potential were measured in atrial engineered heart tissues. Single human induced pluripotent stem cell-derived atrial cardiomyocytes were isolated from atrial engineered heart tissue for ion current measurements. PITX2-/- atrial engineered heart tissue beats slightly slower than isogenic control without irregularity. Force was lower in PITX2-/- than in isogenic control (0.053±0.015 versus 0.131±0.017 mN, n=28/3 versus n=28/4, PITX2-/- versus isogenic control; P<0.0001), accompanied by lower expression of CACNA1C and lower L-type Ca2+ current density. Early repolarization was weaker (action potential duration at 20% repolarization; 45.5±13.2 versus 8.6±5.3 ms, n=18/3 versus n=12/4, PITX2-/- versus isogenic control; P<0.0001), and maximum diastolic potential was more negative (-78.3±3.1 versus -69.7±0.6 mV, n=18/3 versus n=12/4, PITX2-/- versus isogenic control; P=0.001), despite normal inward rectifier currents (both IK1 and IK,ACh) and carbachol-induced shortening of action potential duration. Complete PITX2 deficiency in human induced pluripotent stem cell-derived atrial cardiomyocytes recapitulates some findings of electrical remodeling of atrial fibrillation in the absence of fast beating, indicating that these abnormalities could be primary consequences of lower PITX2 levels.

High-Figure-of-Merit Biosensing and Enhanced Excitonic Absorption in an MoS2-Integrated Dielectric Metasurface.

Among the transitional metal dichalcogenides (TMDCs), molybdenum disulfide (MoS2) is considered an outstanding candidate for biosensing applications due to its high absorptivity and amenability to ionic current measurements. Dielectric metasurfaces have also emerged as a powerful platform for novel optical biosensing due to their low optical losses and strong near-field enhancements. Once functionalized with TMDCs, dielectric metasurfaces can also provide strong photon-exciton interactions. Here, we theoretically integrated a single layer of MoS2 into a CMOS-compatible asymmetric dielectric metasurface composed of TiO2 meta-atoms with a broken in-plane inversion symmetry on an SiO2 substrate. We numerically show that the designed MoS2-integrated metasurface can function as a high-figure-of-merit (FoM=137.5 RIU-1) van der Waals-based biosensor due to the support of quasi-bound states in the continuum. Moreover, owing to the critical coupling of the magnetic dipole resonances of the metasurface and the A exciton of the single layer of MoS2, one can achieve a 55% enhanced excitonic absorption by this two-port system. Therefore, the proposed design can function as an effective biosensor and is also practical for enhanced excitonic absorption and emission applications.

Flame detection via active plasma probing

Combustion diagnostics of highly diluted air fuel mixtures are of great importance for reducing the carbon footprint of various types of combustion systems. Flame detection techniques, such as ion sensing and optical diagnostics, have been reported for diagnosing combustion status. In this paper, a flame front detection technique based on active plasma probing is introduced and analyzed. Unlike the conventional ion sensing used in internal combustion engines, a separate electrode gap is used to detect the flame front arrival. Further, the voltage potential across the electrodes of the spark plug probe is modulated actively to be slightly below the breakdown threshold prior to flame arrival. At the arrival of the flame front, the ions in the flame tend to decrease the breakdown voltage threshold and trigger a breakdown event. An optically accessible constant volume combustion vessel is employed to investigate the efficacy of such active plasma probing for the detection of the flame front under quiescent and flow conditions. Three types of fuels are used in the tests, including methane, propane, and DME, with an air fuel ratio sweep (from stoichiometric to extremely lean) for each fuel. Efforts are made to characterize the probing criteria of minimum, yet adequate voltage to succeed in the detection of the arrival and departure of the flame front most sensitively and reliably, for all three types of fuels under various mixture strengths. For comparison, conventional ion current measurements are conducted under identical background conditions to benchmark the efficacy of flame detection. Results show that the active plasma probing can promptly detect the arrival and departure of the flame front, robustly regardless of the fuel type and excess air ratios. The precise control of the detecting voltage is key for reliable flame detection with high sensitivity.

Ion-induced electron emission by keV-range energy indium ions: Influence of material and geometry

This work provides measurements of the ion-induced electron emission yield caused by keV-range energy indium ions (3–8 keV). In our experiment, the ion sources, fueled with indium, are based on the working principle of field-emission electric propulsion (FEEP) technologies. The measured yields are given for different material properties (plain structure vs foam) and geometries (flat surface vs conical). Study outcomes show that electrons induced by keV-range indium ions can lead to overestimating the measured ion current by 30%–200% depending on the collector materials and geometry. We spotlighted that molybdenum, tungsten, and stainless steel 316L have relatively low yields compared to aluminum 2017A. Moreover, it is possible to lower down a specific material yield by two-thirds when using a foam structure. Finally, it is shown that off-axis ion influence on a collector increases the resulting electron emission yield. In the case of an indium-FEEP thruster, ion-induced electron emissions are a major perturbation when measuring ion current. Mainly, due to the energy range of ions studied, yields retrieved are orders of magnitudes larger than what is usually measured when studying the plume of an electrostatic electric propulsion system. It is, therefore, strongly recommended to use a so-called Faraday cup to study the ion beam from an indium-FEEP thruster as the probe’s close architecture allows us to greatly mitigate these perturbations.

Air ionization in self-neutralizing air-breathing plasma thruster

The paper describes an arc electron source for air ionization applications in a self-neutralizing air-breathing plasma thruster. The arc electron source is an electron source with a prominent level of electron energy control that is required for the air-breathing plasma thruster. The mean energy of the electrons in the arc electron source is controlled by changing the grid voltage in the range of 0 V–300 V. The Langmuir/Faraday probes were used to obtain ion/electron current, electron temperature, and electron density as a function of pressure and electron energy. Ion current measurements concerning distance from the source were obtained as a function of pressure and grid voltage. Optical emission spectroscopy was used to obtain electron temperature, spectral intensities, and ion formation rate. Additionally, a drift tube based on radial magnetic field electron confinement was designed to detect the presence of negative ions. It has been shown that both positive and negative ions can be produced thus providing conditions for a self-neutralizing air-breathing plasma thruster.

Ionic Signal Amplification of DNA in a Nanopore.

Ionic signal amplification is a key challenge for single-molecule analyses by solid-state nanopore sensing. Here, a permittivity gradient approach for amplifying ionic blockade characteristics of DNA in a nanofluidic channel is reported. The transmembrane ionic current response is found to change substantially through modifying the liquid permittivity at one side of a pore with an organic solvent. Imposing positive liquid permittivity gradients with respect to the direction of DNA electrophoresis, this study observes the resistive ionic signals to become larger due to the varying contributions of molecular counterions. On the contrary, negative gradients render adverse effects causing conductive ionic current pulses upon polynucleotide translocations. Most importantly, both the positive and negative gradients are demonstrated to be capable of amplifying the ionic signals by an order of magnitude with a 1.3-fold difference in the transmembrane liquid dielectric constants. This phenomenon allows a novel way to enhance the single-molecule sensitivity of nanopore sensing that may be useful in analyzing secondary structures and genome sequence of DNA by ionic current measurements.

Focusing ions at atmospheric pressure using nonlinear DC voltage sequences applied to a stacked ring ion guide

Many modern ion mobility (IM) and mass spectrometers (MS) operate under low pressure (≤10 Torr) and employ high voltage radiofrequencies (RF) to provide ion confinement. Unfortunately, RF effectiveness drastically decreases as pressure increases, and few techniques for focusing ions at elevated pressures exist. Here we demonstrate a new approach for focusing ions at atmospheric pressure (AP) by applying nonlinear DC voltage sequences following quadratic and power (exponential) functions to a stacked ring ion guide. We used ion trajectory simulations to rigorously explore how ions react to nonlinear electric fields and validate the simulations with a set of ion current measurements performed at AP. Ion trajectory simulations show that ions initially defocus near the entrance of the device but then become intensely focused as they travel through the device. Contour plots for both nonlinear voltage sequences show electric field lines that increasingly curve inwards as a function of distance, resulting in spatial ion focusing. Experimental ion current and spot size measurements were performed at AP using a 10-cm stacked ring ion guide and a segmented Faraday cup detector. Quadratic sequences produced ∼5% smaller spot sizes (∼22.8 mm) and ∼25% higher ion current compared to a linear voltage sequence (∼24.0 mm). Alternatively, power sequences produced ∼64% smaller spot sizes (∼8.7 mm), albeit with ∼10x lower ion current. However, both nonlinear voltage sequences produced similar ion currents at the center of the Faraday cup detector, indicating that higher ion densities are achieved when using nonlinear voltage gradients. These results demonstrate a new way to focus ions at AP, and the capabilities demonstrated here provide fundamental insights on how to keep ions inside analytical devices at elevated pressures without RF.

Interference of electrochemical ion diffusion in nanopore sensing

SummaryStable and fast-responding ionic current is a prerequisite for reliable measurements of small objects with a nanopore. Here, we report on the interference of ion diffusion kinetics at liquid-electrode interfaces in nanopore sensing. Using platinum as electrodes, we observed a slow and large decrease in the ionic current through a nanopore in a salt solution suggestive of the considerable influence of the growing impedance at the liquid-metal interfaces via Cottrell diffusion. When detecting nanoparticles, the resistive pulses became weaker following the steady increase in the resistance at the partially polarizable electrodes. The interfacial impedance was also demonstrated to couple with the nanopore chip capacitance thereby degraded the temporal resolution of the ionic current measurements in a time-varying manner. These findings can be useful for choosing the suitable size and material of electrodes for the single-particle and -molecule analyses by ionic current.

Oleic and nitro-oleic acid behavior at an electrified water-1,2-dichloroethane interface

In this work, oleic and 9/10-nitro oleic acid were studied at a polarized water-1,2-dichloroethane interface. We found that both fatty acids can undergo a simple interfacial ion transfer reaction that is mainly limited by diffusion. The possibility of spontaneous partitioning of the fatty acid into the organic phase and acting as a ligand for the facilitated sodium ion transfer was excluded. The ionic currents originating from the chemical species interfacial transfer were recorded starting from a pH of around 8.5, which agreed with their poor acidity. The acid-base properties of fatty acids were studied with pKa 9.7 (for oleic acid) and 8.5 for the 9/10-nitro derivative. The formal Galvani potential difference of the fatty acids ion transfer reaction was used to calculate the water-1,2-dichloroethane partition coefficients. The results indicated similar water solubility for 9/10-nitro oleic acid (logP' −3.47) and oleic acid (logP' −3.42), where 9/10-nitro oleic acid is slightly more hydrophilic. The partial water solubility of the fatty acids was confirmed by the measurement of ionic currents, which did not increase linearly with their increasing aqueous phase concentration. The obtained results were correlated with the dynamic light scattering of the fatty acids, indicating the formation of supramolecular structures. 9/10-Nitro oleic acid is an endogenously produced signaling molecule involved in cell redox homeostasis. The results obtained here could contribute to further (bio)chemical studies on fatty acid nitroalkenes.

Transport receptor occupancy in nuclear pore complex mimics

Nuclear pore complexes (NPCs) regulate all molecular transport between the nucleus and the cytoplasm in eukaryotic cells. Intrinsically disordered Phe-Gly nucleoporins (FG-Nups) line the central conduit of NPCs to impart a selective barrier where large proteins are excluded unless bound to a transport receptor (karyopherin; Kap). Here, we assess “Kap-centric” NPC models, which postulate that Kaps participate in establishing the selective barrier. We combine biomimetic nanopores, formed by tethering Nsp1 to the inner wall of a solid-state nanopore, with coarse-grained modeling to show that yeast Kap95 exhibits two populations in Nsp1-coated pores: one population that is transported across the pore in milliseconds, and a second population that is stably assembled within the FG mesh of the pore. Ionic current measurements show a conductance decrease for increasing Kap concentrations and noise data indicate an increase in rigidity of the FG-mesh. Modeling reveals an accumulation of Kap95 near the pore wall, yielding a conductance decrease. We find that Kaps only mildly affect the conformation of the Nsp1 mesh and that, even at high concentrations, Kaps only bind at most 8% of the FG-motifs in the nanopore, indicating that Kap95 occupancy is limited by steric constraints rather than by depletion of available FG-motifs. Our data provide an alternative explanation of the origin of bimodal NPC binding of Kaps, where a stable population of Kaps binds avidly to the NPC periphery, while fast transport proceeds via a central FG-rich channel through lower affinity interactions between Kaps and the cohesive domains of Nsp1.

Measurement of viscoelastic particle deformation using pipette ion currents

Ion pipette aspiration (IPA) is a technique for measuring the mechanical properties of soft microparticles. This method combines the principles of micropipette aspiration (MA), which uses optical images to observe particle deformation, and resistive pulse sensing (RPS), which uses the ion current passing through a pipette tip. It is important to better understand the relationship between these two data streams for advanced applications such as nanoscale or high throughput measurements, which would remove reliance on optical microscopy. Here, IPA has been used to investigate polydimethylsiloxane (PDMS) microparticles in a comparative study with atomic force microscopy (AFM), an established material characterisation technique. The IPA apparatus provides data resolution that is unprecedented for this type of experiment. A correlation between the mechanical properties derived using conventional MA and the corresponding ion current measurement was established. Subsequently, the mechanical properties of particles deforming through micropipettes could be predicted with good agreement using a regression model built upon the observed relationship. IPA can be used to study bioparticles and should find applications in the field of mechanobiology.

Docking and Activity of DNA Polymerase on Solid-State Nanopores.

Integration of motor enzymes with biological nanopores has enabled commercial DNA sequencing technology; yet studies of the similar principle applying to solid-state nanopores are limited. Here, we demonstrate the real-life monitoring of phi29 DNA polymerase (DNAP) docking onto truncated-pyramidal nanopore (TPP) arrays through both electrical and optical readout. To achieve effective docking, atomic layer deposition of hafnium oxide is employed to reduce the narrowest pore opening size of original silicon (Si) TPPs to sub-10 nm. On a single TPP with pore opening size comparable to DNAP, ionic current measurements show that a polymerase–DNA complex can temporally dock onto the TPP with a certain docking orientation, while the majority become translocation events. On 5-by-5 TPP arrays, a label-free optical detection method using Ca2+ sensitive dye, are employed to detect the docking dynamics of DNAP. The results show that this label-free detection strategy is capable of accessing the docking events of DNAP on TPP arrays. Finally, we examine the activity of docked DNAP by performing on-site rolling circle amplification to synthesize single-stranded DNA (ssDNA), which serves as a proof-of-concept demonstration of utilizing this docking scheme for emerging nanopore sensing applications.

Ionic heat dissipation in solid-state pores.

Energy dissipation in solid-state nanopores is an important issue for their use as a sensor for detecting and analyzing individual objects in electrolyte solution by ionic current measurements. Here, we report on evaluations of heating via diffusive ion transport in the nanoscale conduits using thermocouple-embedded SiNx pores. We found a linear rise in the nanopore temperature with the input electrical power suggestive of steady-state ionic heat dissipation in the confined nanospace. Meanwhile, the heating efficiency was elucidated to become higher in a smaller pore due to a rapid decrease in the through-water thermal conduction for cooling the fluidic channel. The scaling law suggested nonnegligible influence of the heating to raise the temperature of single-nanometer two-dimensional nanopores by a few kelvins under the standard cross-membrane voltage and ionic strength conditions. The present findings may be useful in advancing our understanding of ion and mass transport phenomena in nanopores.

Designing Angstrom-Scale Asymmetric MOF-on-MOF Cavities for High Monovalent Ion Selectivity.

Biological ion channels feature angstrom-scale asymmetrical cavity structures, which are the key to achieving highly efficient separation and sensing of alkali metal ions from aqueous resources. The clean energy future and lithium-based energy storage systems heavily rely on highly efficient ionic separations. However, artificial recreation of such a sophisticated biostructure has been technically challenging. Here, a highly tunable design concept is introduced to fabricate monovalent ion-selective membranes with asymmetric sub-nanometer pores in which energy barriers are implanted. The energy barriers act against ionic movements, which hold the target ion while facilitating the transport of competing ions. The membrane consists of bilayer metal-organic frameworks (MOF-on-MOF), possessing a 6 to 3.4-angstrom passable cavity structure. The ionic current measurements exhibit an unprecedented ionic current rectification ratio of above 100 with exceptionally high selectivity ratios of 84 and 80 for K+ /Li+ and Na+ / Li+ , respectively (1.14 Li+ mol m-2 h-1 ). Furthermore, using quantum mechanics/molecular mechanics, it is shown that the combined effect of spatial hindrance and nucleophilic entrapment to induce energy surge baffles is responsible for the membrane's ultrahigh selectivity and ion rectification. This work demonstrates a striking advance in developing monovalent ion-selective channels and has implications in sensing, energy storage, and separation technologies.

Study on the correlation between ion current integral signal and combustion pressure

Based on the self-designed and developed gas mixture combustion and flame ion current measurement and control system, this paper studies correlation research between the ion current integral signal and combustion pressure under different initial pressures, equivalent ratios and hydrogen and carbon dioxide volume fractions. The experiments obtained the change rules under the different initial parameters of the ion current waveform and combustion pressure waveform along with the combustion time, the change rules of the characteristic parameters of ion current integral signal (Iθ80, t80) and combustion pressure (Pmax, tPmax) are analysed, revealing a high correlation between the t80 and the tPmax; a method for timely and effective determining the pressure peak moment using ion current integral signals is presented. The conclusions of this study provide new technological approaches for effectively and accurately acquiring the combustion pressure information of gas mixture in cylinders using ion current integral signals, thereby realising accurate combustion control.

Single nucleobase identification for transversally-confined ssDNA using longitudinal ionic currents.

High-fidelity DNA sequencing using solid-state nanopores remains a big challenge, partly due to difficulties related to efficient molecular capture and subsequent control of the dwell time. To help address these issues, here we propose a sequencing platform consisting of stacked two-dimensional materials with tailored structures containing a funnel-shaped step defect and a nanopore drilled inside the nanochannel. Our all-atom molecular dynamics (MD) simulations showed that, assisted by the step defect, single-stranded DNA (ssDNA) can be transported to the nanopore in a deterministic way by pulsed transversal electric fields. Furthermore, different types of DNA bases can reside in the pore for a sufficiently long time which can be successfully differentiated by longitudinal ionic currents. By using the decoupled driving forces for ssDNA transport and ionic current measurements, this approach holds potential for high-fidelity DNA sequencing.

Salt Gradient Control of Translocation Dynamics in a Solid-State Nanopore.

Tuning capture rates and translocation time of analytes in solid-state nanopores are one of the major challenges for their use in detecting and analyzing individual nanoscale objects via ionic current measurements. Here, we report on the use of salt gradient for the fine control of capture-to-translocation dynamics in 300 nm sized SiNx nanopores. We demonstrated a decrease up to a factor of 3 in the electrophoretic speed of nanoparticles at the pore exit along with an over 3-fold increase in particle detection efficiency by subjecting a 5-fold ion concentration difference across the dielectric membrane. The improvement in the sensor performance was elucidated to be a result of the salt-gradient-mediated electric field and electroosmotic flow asymmetry at nanochannel orifices. The present findings can be used to enhance nanopore sensing capability for detecting biomolecules such as amyloids and proteins.

Nanopores in Graphene and Other 2D Materials: A Decade's Journey toward Sequencing.

Nanopore techniques offer a low-cost, label-free, and high-throughput platform that could be used in single-molecule biosensing and in particular DNA sequencing. Since 2010, graphene and other two-dimensional (2D) materials have attracted considerable attention as membranes for producing nanopore devices, owing to their subnanometer thickness that can in theory provide the highest possible spatial resolution of detection. Moreover, 2D materials can be electrically conductive, which potentially enables alternative measurement schemes relying on the transverse current across the membrane material itself and thereby extends the technical capability of traditional ionic current-based nanopore devices. In this review, we discuss key advances in experimental and computational research into DNA sensing with nanopores built from 2D materials, focusing on both the ionic current and transverse current measurement schemes. Challenges associated with the development of 2D material nanopores toward DNA sequencing are further analyzed, concentrating on lowering the noise levels, slowing down DNA translocation, and inhibiting DNA fluctuations inside the pores. Finally, we overview future directions of research that may expedite the emergence of proof-of-concept DNA sequencing with 2D material nanopores.

Ion Current Sensor for Gas Turbine Condition Dynamical Monitoring: Modeling and Characterization.

This paper aims to thoroughly investigate the potential of ion current measurements in the context of combustion process monitoring in gas turbines. The study is targeted at characterizing the dynamic behavior of a typical ion-current measurement system based on a spark-plug. Starting from the preliminary study published in a previous work, the authors propose a refined model of the electrode (spark plug), based on the Langmuir probe theory, that incorporates the physical surface effects and proposes an optimized design of the conditioning electronics, which exploits a low frequency AC square wave biasing of the electrodes and allows for compensating some relevant parasitic effects. The authors present experimental results obtained in the laboratory, which allow for the evaluation of the validity of the model and the interpreting of the characteristics of the measurement signal. Finally, measurements carried out in the field on an industrial combustor are presented. The results confirm that the charged chemical species density sensed by the proposed measurement system and related to the mean value of the output signal is an indicator of the ‘average’ combustion process conditions in terms e.g., of air/fuel ratio, whereas the high frequency spectral component of the measured signal can give information related to the turbulent regime and to the presence of pressure pulsations. Results obtained with a prototype system demonstrated an achievable resolution of about 5 Pa on the estimated amplitude, even under small biasing voltage (22.5 V) and an estimated bandwidth of 10 kHz.