Characterizing the Conformational Free-Energy Landscape of RNA Stem-Loops Using Single-Molecule Field-Effect Transistors.

We have developed and used single-molecule field-effect transistors (smFETs) to characterize the conformational free-energy landscape of RNA stem-loops. Stem-loops are one of the most common RNA structural motifs and serve as building blocks for the formation of complex RNA structures. Given their prevalence and integral role in RNA folding, the kinetics of stem-loop (un)folding has been extensively characterized using both experimental and computational approaches. Interestingly, these studies have reported vastly disparate timescales of (un)folding, which has been interpreted as evidence that (un)folding of even simple stem-loops occurs on a highly rugged conformational energy landscape. Because smFETs do not rely on fluorophore reporters of conformation or mechanical (un)folding forces, they provide a unique approach that has allowed us to directly monitor tens of thousands of (un)folding events of individual stem-loops at a 200 µs time resolution. Our results show that under our experimental conditions, stem-loops (un)fold over a 1-200 ms timescale during which they transition between ensembles of unfolded and folded conformations, the latter of which is composed of at least two sub-populations. The 1-200 ms timescale of (un)folding we observe here indicates that smFETs report on complete (un)folding trajectories in which unfolded conformations of the RNA spend long periods of time wandering the free-energy landscape before sampling one of several misfolded conformations or the natively folded conformation. Our findings highlight the extremely rugged landscape on which even the simplest RNA structural elements fold and demonstrate that smFETs are a unique and powerful approach for characterizing the conformational free-energy of RNA.

Surface State Dynamics Dictating Transport in InAs Nanowires.

Because of their high aspect ratio, nanostructures are particularly susceptible to effects from surfaces such as slow electron trapping by surface states. However, nonequilibrium trapping dynamics have been largely overlooked when considering transport in nanoelectronic devices. In this study, we demonstrate the profound influence of dynamic trapping processes on transport in InAs nanowires through an investigation of the hysteretic and time-dependent behavior of the transconductance. We observe large densities (∼1013 cm-2) of slow surface traps and demonstrate the ability to control and permanently fix their occupation and charge through electrostatic manipulation by the gate potential followed by thermal deactivation by cryogenic cooling. Furthermore, we observe a transition from enhancement- to depletion-mode and a 400% change in field-effect mobility within the same device when the initial gate voltage and sweep rate are varied, revealing the severe impact of electrostatic history and dynamics on InAs nanowire field-effect transistors. A time-dependent model for nanowire transconductance based on nonequilibrium carrier population dynamics with thermally activated capture and emission was constructed and showed excellent agreement with experiments, confirming the effects to be a direct result of the dynamics of slow surface traps characterized by large thermal activation barriers (∼ 700 meV). This work reveals a clear and direct link between the electrical conductivity and the microscopic interactions of charged species with nanowire surfaces and highlights the necessity for considering dynamic properties of surface states in nanoelectronic devices.

Sensing Responses Based on Transfer Characteristics of InAs Nanowire Field-Effect Transistors.

Nanowire-based field-effect transistors (FETs) have demonstrated considerable promise for a new generation of chemical and biological sensors. Indium arsenide (InAs), by virtue of its high electron mobility and intrinsic surface accumulation layer of electrons, holds properties beneficial for creating high performance sensors that can be used in applications such as point-of-care testing for patients diagnosed with chronic diseases. Here, we propose devices based on a parallel configuration of InAs nanowires and investigate sensor responses from measurements of conductance over time and FET characteristics. The devices were tested in controlled concentrations of vapour containing acetic acid, 2-butanone and methanol. After adsorption of analyte molecules, trends in the transient current and transfer curves are correlated with the nature of the surface interaction. Specifically, we observed proportionality between acetic acid concentration and relative conductance change, off current and surface charge density extracted from subthreshold behaviour. We suggest the origin of the sensing response to acetic acid as a two-part, reversible acid-base and redox reaction between acetic acid, InAs and its native oxide that forms slow, donor-like states at the nanowire surface. We further describe a simple model that is able to distinguish the occurrence of physical versus chemical adsorption by comparing the values of the extracted surface charge density. These studies demonstrate that InAs nanowires can produce a multitude of sensor responses for the purpose of developing next generation, multi-dimensional sensor applications.

Surface Properties from Transconductance in Nanoscale Systems.

Because of the continued scaling of transistor dimensions and incorporation of nanostructured materials into modern electronic and optoelectronic devices, surfaces and interfaces have become a dominant factor dictating material properties and device performance. In this study, we investigate the temperature-dependent electronic transport properties of InAs nanowire field-effect transistors. A point where the nanowire conductance becomes independent of temperature is observed, known as the zero-temperature-coefficient. The distribution of surface states is determined by a spectral analysis of the conductance activation energy and used to develop a carrier transport model that explains the existence and gate voltage dependence of this point. We determine that the position of this point in gate voltage is directly related to the fixed oxide charge on the nanowire surface and demonstrate the utility of this method for studying surface passivations in nanoscale systems by characterizing (NH4)2Sx and H2 plasma surface treatments on InAs nanowires.

RNA adapts its flexibility to efficiently fold and resist unfolding.

Recent studies have demonstrated that the mechanisms through which biopolymers like RNA interconvert between multiple folded structures are critical for their cellular functions. A major obstacle to elucidating these mechanisms is the lack of experimental approaches that can resolve these interconversions between functionally relevant biomolecular structures. Here, using a nano-electronic device with microsecond time resolution, we dissect the complete set of structural rearrangements executed by an ultra-stable RNA, the UUCG stem-loop, at the single-molecule level. We show that the stem-loop samples at least four conformations along two folding pathways leading to two distinct folded structures, only one of which has been previously observed. By modulating its flexibility, the stem-loop can adaptively select between these pathways, enabling it to both fold rapidly and resist unfolding. This paradigm of stabilization through compensatory changes in flexibility broadens our understanding of stable RNA structures and is expected to serve as a general strategy employed by all biopolymers.

Carbon-nanotube field-effect transistors for resolving single-molecule aptamer-ligand binding kinetics.

Small molecules such as neurotransmitters are critical for biochemical functions in living systems. While conventional ultraviolet-visible spectroscopy and mass spectrometry lack portability and are unsuitable for time-resolved measurements in situ, techniques such as amperometry and traditional field-effect detection require a large ensemble of molecules to reach detectable signal levels. Here we demonstrate the potential of carbon-nanotube-based single-molecule field-effect transistors (smFETs), which can detect the charge on a single molecule, as a new platform for recognizing and assaying small molecules. smFETs are formed by the covalent attachment of a probe molecule, in our case a DNA aptamer, to a carbon nanotube. Conformation changes on binding are manifest as discrete changes in the nanotube electrical conductance. By monitoring the kinetics of conformational changes in a binding aptamer, we show that smFETs can detect and quantify serotonin at the single-molecule level, providing unique insights into the dynamics of the aptamer-ligand system. In particular, we show the involvement of G-quadruplex formation and the disruption of the native hairpin structure in the conformational changes of the serotonin-aptamer complex. The smFET is a label-free approach to analysing molecular interactions at the single-molecule level with high temporal resolution, providing additional insights into complex biological processes.

Mixed-Dimensional 1D/2D van der Waals Heterojunction Diodes and Transistors in the Atomic Limit.

Inverting a semiconducting channel is the basis of all field-effect transistors. In silicon-based metal-oxide-semiconductor field-effect transistors (MOSFETs), a gate dielectric mediates this inversion. Access to inversion layers may be granted by interfacing ultrathin low-dimensional semiconductors in heterojunctions to advance device downscaling. Here we demonstrate that monolayer molybdenum disulfide (MoS2) can directly invert a single-walled semiconducting carbon nanotube (SWCNT) transistor channel without the need for a gate dielectric. We fabricate and study this atomically thin one-dimensional/two-dimensional (1D/2D) van der Waals heterojunction and employ it as the gate of a 1D heterojunction field-effect transistor (1D-HFET) channel. Gate control is based on modulating the conductance through the channel by forming a lateral p-n junction within the CNT itself. In addition, we observe a region of operation exhibiting a negative static resistance after significant gate tunneling current passes through the junction. Technology computer-aided design (TCAD) simulations confirm the role of minority carrier drift-diffusion in enabling this behavior. The resulting van der Waals transistor architecture thus has the dual characteristics of both field-effect and tunneling transistors, and it advances the downscaling of heterostructures beyond the limits of dangling bonds and epitaxial constraints faced by III-V semiconductors.

Nonlinear Chemical Sensitivity Enhancement of Nanowires in the Ultralow Concentration Regime.

Much recent attention has been focused on the development of field-effect transistors based on low-dimensional nanostructures for the detection and manipulation of molecules. Because of their extraordinarily high charge sensitivity, InAs nanowires present an excellent material system in which to probe and study the behavior of molecules on their surfaces and elucidate the underlying mechanisms dictating the sensor response. So far, chemical sensors have relied on slow, activated processes restricting their applicability to high temperatures and macroscopic adsorbate coverages. Here, we identify the transition into a highly sensitive regime of chemical sensing at ultralow concentrations (<1 ppm) via physisorption at room temperature using field-effect transistors with channels composed of several thousand InAs nanowires and ethanol as a simple analyte molecule. In this regime, the nanowire conductivity is dictated by a local gating effect from individual dipoles, leading to a nonlinear enhancement of the sensitivity. At higher concentrations (>1 ppm), the nanowire channel is globally gated by a uniform dipole layer at the nanowire surface. The former leads to a dramatic increase in sensitivity due to weakened screening and the one-dimensional geometry of the nanowire. In this regime, we detect concentrations of ethanol vapor as low as 10 ppb, 100 times below the lowest concentrations previously reported. Furthermore, we demonstrate electrostatic control of the sensitivity and dynamic range of the InAs nanowire-based sensor and construct a unified model that accurately describes and predicts the sensor response over the tested concentration range (10 ppb to 10 ppm).