Ion Gating Research Articles

Simulating the performance of a distance-3 surface code in a linear ion trap

We explore the feasibility of implementing a small surface code with 9 data qubits and 8 ancilla qubits, commonly referred to as surface-17, using a linear chain of 171Yb+ ions. Two-qubit gates can be performed between any two ions in the chain with gate time increasing linearly with ion distance. Measurement of the ion state by fluorescence requires that the ancilla qubits be physically separated from the data qubits to avoid errors on the data due to scattered photons. We minimize the time required to measure one round of stabilizers by optimizing the mapping of the two-dimensional surface code to the linear chain of ions. We develop a physically motivated Pauli error model that allows for fast simulation and captures the key sources of noise in an ion trap quantum computer including gate imperfections and ion heating. Our simulations showed a consistent requirement of a two-qubit gate fidelity of ≥99.9% for the logical memory to have a better fidelity than physical two-qubit operations. Finally, we perform an analysis of the error subsets from the importance sampling method used to bound the logical error rates to gain insight into which error sources are particularly detrimental to error correction.

Structural basis for the ethanol action on G-protein–activated inwardly rectifying potassium channel 1 revealed by NMR spectroscopy

Ethanol consumption leads to a wide range of pharmacological effects by acting on the signaling proteins in the human nervous system, such as ion channels. Despite its familiarity and biological importance, very little is known about the molecular mechanisms underlying the ethanol action, due to extremely weak binding affinity and the dynamic nature of the ethanol interaction. In this research, we focused on the primary in vivo target of ethanol, G-protein-activated inwardly rectifying potassium channel (GIRK), which is responsible for the ethanol-induced analgesia. By utilizing solution NMR spectroscopy, we characterized the changes in the structure and dynamics of GIRK induced by ethanol binding. We demonstrated here that ethanol binds to GIRK with an apparent dissociation constant of 1.0 M and that the actual physiological binding site of ethanol is located on the cavity formed between the neighboring cytoplasmic regions of the GIRK tetramer. From the methyl-based NMR relaxation analyses, we revealed that ethanol activates GIRK by shifting the conformational equilibrium processes, which are responsible for the gating of GIRK, to stabilize an open conformation of the cytoplasmic ion gate. We suggest that the dynamic molecular mechanism of the ethanol-induced activation of GIRK represents a general model of the ethanol action on signaling proteins in the human nervous system.

Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms.

The transient receptor potential (TRP) channel TRPV4 participates in multiple biological processes, and numerous TRPV4 mutations underlie several distinct and devastating diseases. Here we present the cryo-EM structure of Xenopus tropicalis TRPV4 at 3.8-Å resolution. The ion-conduction pore contains an intracellular gate formed by the inner helices, but lacks any extracellular gate in the selectivity filter, as observed in other TRPV channels. Anomalous X-ray diffraction analyses identify a single ion-binding site in the selectivity filter, thus explaining TRPV4 nonselectivity. Structural comparisons with other TRP channels and distantly related voltage-gated cation channels reveal an unprecedented, unique packing interface between the voltage-sensor-like domain and the pore domain, suggesting distinct gating mechanisms. Moreover, our structure begins to provide mechanistic insights to the large set of pathogenic mutations, offering potential opportunities for drug development.

Role of outer surface probes for regulating ion gating of nanochannels

Nanochannels with functional elements have shown promise for DNA sequencing, single-molecule sensing, and ion gating. Ionic current measurement is currently a benchmark, but is focused solely on the contribution from nanochannels’ inner-wall functional elements (NIWFE); the attributes of functional elements at nanochannels’ outer surface (NOSFE) are nearly ignored, and remain elusive. Here we show that the role of NOSFE and NIWFE for ion gating can be distinguished by constructing DNA architectures using dual-current readout. The established molecular switches have continuously tunable and reversible ion-gating ability. We find that NOSFE exhibits negligible ion-gating behavior, but it can produce a synergistic effect in alliance with NIWFE. Moreover, the high-efficiency gating systems display more noticeable synergistic effect than the low-efficiency ones. We also reveal that the probe amount of NOSFE and NIWFE is almost equally distributed in our biomimetic nanochannels, which is potentially a premise for the synergistic ion-gating phenomena.

Bioinspired Heterogeneous Ion Pump Membranes: Unidirectional Selective Pumping and Controllable Gating Properties Stemming from Asymmetric Ionic Group Distribution.

The creation of an artificial solid-state ion pump that mimics the delicate ion transport behaviors of a biological protein-based ion pump is drawing more and more research attention due to its potential applications in energy conversion, biosensor, and desalination. However, the reported bioinspired double-gated ion pump systems are generally very primary and can only realize nonselective ion pumping functions with no directionality and uncontrollable ion gating functions, which are far from their biological counterparts. To make the bioinspired device "smart" in a real sense, the implementation of high-level selectivity and directionality in the ion pumping process, while achieving great controllability in the ion gating process, is a necessity. Here, we developed a bioinspired heterogeneous ion pump membrane by combining block copolymer membrane sacrificial coating and plasma grafting technique. The system has unidirectional selective ion pumping and controllable ion gating properties. The introduction of asymmetric ionic group distribution is the key reason for its novel transport behaviors. Such a heterogeneous ion pump could not only provide a basic platform that potentially sparks further efforts to simulate the smart ion transport processes in living bodies but also promote the application of artificial nanofluidic devices in energy conversion, water treatment, and biosensing.

Recent Progress in the Discovery and Development of Small-Molecule Modulators of CFTR.

Cystic fibrosis (CF) is a genetic disorder driven by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. While different mutations lead to varying levels of disease severity, the most common CFTR F508del mutation leads to defects in protein stability, trafficking to the cell membrane and gating of chloride ions. Recently, advances in medicinal chemistry have led to the identification small-molecule drugs that result in significant clinical efficacy in improving lung function in CF patients. Multiple CFTR modulators are required to fix the various defects in the CFTR protein. Small-molecule potentiators increase the open-channel probability and improve the gating of ions through CFTR. Small-molecule correctors stabilize the protein fold of the mutant channel, facilitating protein maturation and translocation to the cellular membrane. Recent data suggest that triple-combination therapy consisting of a potentiator and two correctors that operate through distinct mechanisms will be required to deliver highly significant clinical efficacy for most CF patients. The progress in medicinal chemistry that has led to the identification of novel CFTR potentiators and correctors is presented in this chapter.

In-depth study of in-trap high-resolution mass separation by transversal ion ejection from a multi-reflection time-of-flight device.

The recently introduced method of ion separation by transversal ejection of unwanted species in electrostatic ion-beam traps and multi-reflection time-of-flight devices has been further studied in detail. As this separation is performed during the ion storage itself, there is no need for additional external devices such as ion gates or traps for either pre- or postselection of the ions of interest. The ejection of unwanted contaminant ions is performed by appropriate pulses of the potentials of deflector electrodes. These segmented ring electrodes are located off-center in the trap, i.e., between one of the two ion mirrors and the central drift tube, which also serves as a potential lift for capturing incoming ions and axially ejecting ions of interest after their selection. The various parameters affecting the selection effectivity and resolving power are illustrated with tin-cluster measurements, where isotopologue ion species provide mass differences down to a single atomic mass unit at ion masses of several hundred. Symmetric deflection voltages of only 10 V were found sufficient for the transversal ejection of ion species with as few as three deflection pulses. The duty cycle, i.e., the pulse duration with respect to the period of ion revolution, has been varied, resulting in resolving powers of up to several tens of thousands for this selection technique.

Physical properties of voltage gated pores

Experiments on single ionic channels have contributed to a large extent to our current view on the function of cell membrane. In these experiments the main observables are the physical quantities: ionic concentration, membrane electrostatic potential and ionic fluxes, all of them presenting large fluctuations. The classical theory of Goldman--Hodking--Katz assumes that an open channel can be well described by a physical pore where ions follow statistical physics. Nevertheless real molecular channels are active pores with open and close dynamical states. By skipping the molecular complexity of real channels, here we present the internal structure and calibration of two active pore models. These models present a minimum set of degrees of freedom, specifically ion positions and gate states, which follow Langevin equations constructed from an unique potential energy functional and by using standard rules of statistical physics. Numerical simulations of both models are implemented and the results show that they have dynamical properties very close to those observed in experiments of Na and K molecular channels. In particular a significant effect of the external ion concentration on gating dynamics is predicted, which is consistent with previous experimental observations. This approach can be extended to other channel types with more specific phenomenology.

Electric-field control of ferromagnetism through oxygen ion gating

Electric-field-driven oxygen ion evolution in the metal/oxide heterostructures emerges as an effective approach to achieve the electric-field control of ferromagnetism. However, the involved redox reaction of the metal layer typically requires extended operation time and elevated temperature condition, which greatly hinders its practical applications. Here, we achieve reversible sub-millisecond and room-temperature electric-field control of ferromagnetism in the Co layer of a Co/SrCoO2.5 system accompanied by bipolar resistance switching. In contrast to the previously reported redox reaction scenario, the oxygen ion evolution occurs only within the SrCoO2.5 layer, which serves as an oxygen ion gating layer, leading to modulation of the interfacial oxygen stoichiometry and magnetic state. This work identifies a simple and effective pathway to realize the electric-field control of ferromagnetism at room temperature, and may lead to applications that take advantage of both the resistance switching and magnetoelectric coupling.

Pushing the Resolving Power of Tyndall-Powell Gate Ion Mobility Spectrometry over 100 with No Sensitivity Loss for Multiple Ion Species.

Ion gate is a key buildup for drift tube ion mobility spectrometry (IMS) and its combination with mass spectrometry. Bradbury-Nielsen gate, as the most commonly used ion gate in IMS, possesses a distinct ion mobility discrimination effect due to its depletion features. This impedes the scaling of the ion gate opening time to improve the separation capability of IMS while keeping its sensitivity for multiple ion species. In this work, a Tyndall-Powell gate (TPG) simply composed of two identical wire grids was used to develop an ion gate with nearly no ion mobility discrimination for IMS. Experimental results showed that the TPG features a gate region where the electric field for opening the gate could be enhanced to effectively solve the ion mobility discrimination problem related to it. Meanwhile, enhancing that electric field enabled the TPG-IMS to keep a resolving power over 106 at 100 °C for ion peak with a signal-to-noise ratio up to 800. With that TPG-IMS, baseline separation of two ion peaks, the hydronium and the acetone monomer peaks with a reduced mobility difference of only 0.04 cm2 V-1 s-1, was achieved with no sensitivity loss for the least mobile acetone dimer ions.

Leveraging spectral sparsity to realize enhanced separation of gas-phase ion populations

When coupled with mass spectrometry, gas-phase ion mobility can enable the separation of isomers provided sufficient resolution. However, traditional limits on drift tube ion mobility resolution have been imposed by thermal diffusion and the duration of the initial ion gate pulse width. We demonstrate the first application of a post processing technique, specifically basis pursuit denoising (BPDN), for multiplexed IMS–MS experiments that not only minimizes data acquisition times, but realizes resolutions that exceed traditional predicted values. The multiplexing waveform used was based upon linear frequency modulation of the ion gate producing an ion gate pulsing sequence with a 50% duty cycle. This pulsing sequence further maximizes ion transmission and improved ion statistics in the m/z domain. Traditional, single pulse (signal averaged) and multiplexing IMS acquisitions demonstrate lowered resolution at extended ion gate pulse widths and minimizing this parameter results in decreased sensitivity from gate depletion effects and lowered ion gate duty cycle. Signal processing techniques involving BPDN was demonstrated on experimentally acquired IMS–MS data using the diastereoisomer ractopamine which exhibits two distinct gas-phase conformations with K0 values differing by 0.022cm2V−1s−1. Systematically adjusting the experimental parameters related to effective ion gate pulse width, we illustrate the capacity of this method to yield peak resolutions >1.0 for ion gate pulse widths that routinely yield unresolved arrival time distributions utilizing standard deconvolution procedures or equivalent gate pulse widths that utilize traditional signal averaged IMS datasets. When viewed from the perspective of a single peak, BPDN can increase the observed resolving power by more than a factor of 2. Because resolution and ion throughput are simultaneously maximized, the application of this optimization method represents a fundamentally different approach to multiplexed IMS signal processing.

An innovative ion sensitive device based on side‐contacted field effect diode

In this paper, side‐contacted field effect diode as an ion sensitive device is proposed to take advantages of field effect diodes family in sensing ionic species in solutions. To analyze the behavior of ion sensitive side‐contacted field effect diode, an accurate model has been developed in a simulation environment tool to mimic the characteristics of the solution and the results compared with the literature. While dual gate ion sensitive FETs have been introduced to beat the Nernst limit, results show that dual gate ion sensitive side‐contacted field effect diodes can provide better performance. Effects of various parameters such as silicon body thickness and doping concentration have been studied. In contrast of ISFETs, the proposed device offers more sensitivity at the thicker silicon body. Results indicate that dual gate ion sensitive side‐contacted field effect diodes can be regarded as an interesting candidate for bio‐sensing applications.

Atmospheric Pressure Drift Tube Ion Mobility–Orbitrap Mass Spectrometry: Initial Performance Characterization

Atmospheric pressure drift tube ion mobility spectrometry (AP-DTIMS) was coupled with Fourier transform Orbitrap mass spectrometry. The performance capabilities of this versatile new arrangement were demonstrated for different DTIMS ion gating operation modes and Orbitrap mass spectrometer parameters with regard to sensitivity and resolving power. Showcasing the optimized AP-DTIMS-Orbitrap MS system, isobaric peptide and sugar isomers were successfully resolved and the identities of separated species validated by high-energy collision dissociation experiments.

An open source ion gate pulser for ion mobility spectrometry

Excluding the ion source, an ion mobility spectrometer is fundamentally comprised of drift chamber, ion gate, pulsing electronics, and a mechanism for amplifying and recording ion signals. Historically, the solutions to each of these challenges have been custom and rarely replicated exactly. For the IMS research community few detailed resources exist that explicitly detail the construction and operation of ion mobility systems. In an effort to address this knowledge gap we outline a solution to one of the key aspects of a drift tube ion mobility system, the ion gate pulser. Bradbury-Nielsen or Tyndall ion gates are found in nearly every research-grade and commercial IMS system. While conceptually simple, these gate structures often require custom, high-voltage, floating electronics. In this report we detail the operation and performance characteristics of a wifi-enabled, MOSFET-based pulser design that uses a lithium-polymer battery and does not require high voltage isolation transformers. Currently, each output of this circuit follows a TTL signal with ~20 ns rise and fall times, pulses up to +/− 200 V, and is entirely isolated using fiber optics. Detailed schematics and source code are provided to enable continued use of robust pulsing electronics that ease experimental efforts for future comparison.

A binding-block ion selective mechanism revealed by a Na/K selective channel

Mechanosensitive (MS) channels are extensively studied membrane protein for maintaining intracellular homeostasis through translocating solutes and ions across the membrane, but its mechanisms of channel gating and ion selectivity are largely unknown. Here, we identified the YnaI channel as the Na+/K+ cation-selective MS channel and solved its structure at 3.8 Å by cryo-EM single-particle method. YnaI exhibits low conductance among the family of MS channels in E. coli, and shares a similar overall heptamer structure fold with previously studied MscS channels. By combining structural based mutagenesis, quantum mechanical and electrophysiological characterizations, we revealed that ion selective filter formed by seven hydrophobic methionine (YnaIMet158) in the transmembrane pore determined ion selectivity, and both ion selectivity and gating of YnaI channel were affected by accompanying anions in solution. Further quantum simulation and functional validation support that the distinct binding energies with various anions to YnaIMet158 facilitate Na+/K+ pass through, which was defined as binding-block mechanism. Our structural and functional studies provided a new perspective for understanding the mechanism of how MS channels select ions driven by mechanical force.

An alternative field switching ion gate for ESI-ion mobility spectrometry

In electrospray ionization (ESI)-ion mobility spectrometry, continuously generated ions must be desolvated in a first tube before short ion pulses are introduced into a second (drift) tube. Both tubes are separated by an ion-gate. The resolving power of the resulting drift time spectrum is strongly influenced by the design of the ion gate. In the case of the Bradbury-Nielsen gates typically used, an orthogonal field between oppositely charged, parallel wires blocks ions from entering the drift tube. However, the blocking field also distorts the entering ion cloud. One alternative, which eliminates these effects and therefore enables a potentially higher resolving power, is already known for spectrometers with small ionization volumes, where ions are formed between two electrodes and subsequently transferred into the drift tube by a high voltage pulse. Based on this setup, we introduce an alternative ion gate design for liquid samples, named field switching ion gate (FSIG). The continuous flow of ions generated by ESI is desolvated in the first tube and introduced into the space between two electrodes (repeller and transfer electrodes). A third (blocking) electrode prevents the movement of ions into the drift tube in the closed state. Ions are transferred during the open state by pulsing the voltages of the repeller and blocking electrodes. First results demonstrate an increase of the resolving power by 100% without intensity losses and further changes in the spectrometer setup. The parameters of the FSIG, such as electrode voltages and pulse width, are characterized allowing the optimization of the spectrometer’s resolving power.

Time-of-flight ion mobility spectrometry in combination with laser-induced fluorescence detection system.

A laser-induced fluorescence (LIF) was used as a complimentary detection system for time-of-flight ion mobility spectrometry (TOF-IMS). A LIF detection system is potentially faster than a conventional electrometer detector and can provide additional (to usual for IMS drift time) analytical information, namely wavelength of fluorescence maxima and fluorescence lifetime. Therefore, better discrimination ability can be expected. Additionally, the combination of IMS and LIF operates at atmospheric pressure. This allows fluorescence measurements of specified ions and ion clusters, which would not survive in a mass spectrometer. An IMS drift cell of open design with both the electrometer and LIF detectors was designed. The feasibility of IMS-LIF was demonstrated on the example of the Xanthene dye Rhodamine 6G (R6G). Electrospray was used as an ionization source. The release and desolvation of R6G ions from the electrospray with following IMS-LIF analysis were demonstrated. The effects of experimental parameters (e.g., ion gate and drift voltages, distance to ESI emitter) are demonstrated and discussed. The obtained results are promising enough to ensure the potential of LIF as a complimentary/alternative detection system for time-of-flight ion mobility spectrometry.

Simultaneous Improvement of Resolving Power and Signal-to-Noise Ratio Using a Modified Hadamard Transform-Inverse Ion Mobility Spectrometry Technique.

In order to improve the resolving power (RP) and signal-to-noise ratio (SNR) of ion mobility spectrometry (IMS) simultaneously, a modified Hadamard transform-inverse ion mobility spectrometry (MHT-IIMS) technique was developed. In this novel technique, a series of isolating codes were appended to each element of the pseudo random binary sequence (PRBS), and then the modified modulation sequence was formed and used to control the ion gate of the inverse IMS (IIMS). Experimental results demonstrate that the MHT-IIMS technique can significantly enhance the resolving power and SNR simultaneously by measuring the spectra of reaction ions. Furthermore, the gas sample CCl4 and CHCl3 were measured for evaluating the capability of detecting those samples which have single and multiple product ions. The results show that this novel technique is able to simultaneously improve the resolving power and SNR notablely for the real sample detection without any significant instrumental changes. Graphical Abstract ᅟ.

SMITten for KCNQ Channels

Over the last two decades, members of the KCNQ channel family of potassium channels (KCNQ1–5) have emerged as critical regulators of cardiac and neuronal excitability (1,2). KCNQ1 channels are the molecular determinants of the cardiac slow potassium current, IKS (1), which is partly responsible for the repolarization of the cardiac action potential. Loss-of-function variants of KCNQ1 channels lead to a rare heart condition, long QT syndrome, and gain-of-function variants lead to atrial fibrillation.

SMIT1 Modifies KCNQ Channel Function and Pharmacology by Physical Interaction with the Pore

Voltage-gated potassium channels of the KCNQ (Kv7) subfamily are essential for control of cellular excitability and repolarization in a wide range of cell types. Recently, we and others found that some KCNQ channels functionally and physically interact with sodium-dependent solute transporters, including myo-inositol transporters SMIT1 and SMIT2, potentially facilitating various modes of channel-transporter signal integration. In contrast to indirect effects such as channel regulation by SMIT-transported, myo-inositol-derived phosphatidylinositol 4,5-bisphosphate (PIP2), the mechanisms and functional consequences of the physical interaction of channels with transporters have been little studied. Here, using co-immunoprecipitation with different channel domains, we found that SMIT1 binds to the KCNQ2 pore module. We next tested the effects of SMIT1 co-expression, in the absence of extracellular myo-inositol or other SMIT1 substrates, on fundamental functional attributes of KCNQ2, KCNQ2/3, KCNQ1, and KCNQ1-KCNE1 channels. Without exception, SMIT1 altered KCNQ ion selectivity, sensitivity to extracellular K+, and pharmacology, consistent with an impact on conformation of the KCNQ pore. SMIT1 also altered the gating kinetics and/or voltage dependence of KCNQ2, KCNQ2/3, and KCNQ1-KCNE1. In contrast, SMIT1 had no effect on Kv1.1 (KCNA1) gating, ion selectivity, or pharmacology. We conclude that, independent of its transport activity and indirect regulatory mechanisms involving inositol-derived increases in PIP2, SMIT1, and likely other related sodium-dependent solute transporters, regulates KCNQ channel ion selectivity, gating, and pharmacology by direct physical interaction with the pore module.