Highly stable integration of graphene Hall sensors on a microfluidic platform for magnetic sensing in whole blood.

The detection and analysis of rare cells in complex media such as blood is increasingly important in biomedical research and clinical diagnostics. Micro-Hall detectors (µHD) for magnetic detection in blood have previously demonstrated ultrahigh sensitivity to rare cells. This sensitivity originates from the minimal magnetic background in blood, obviating cumbersome and detrimental sample preparation. However, the translation of this technology to clinical applications has been limited by inherently low throughput (<1 mL/h), susceptibility to clogging, and incompatibility with commercial CMOS foundry processing. To help overcome these challenges, we have developed CMOS-compatible graphene Hall sensors for integration with PDMS microfluidics for magnetic sensing in blood. We demonstrate that these graphene µHDs can match the performance of the best published µHDs, can be passivated for robust use with whole blood, and can be integrated with microfluidics and sensing electronics for in-flow detection of magnetic beads. We show a proof-of-concept validation of our system on a silicon substrate and detect magnetic agarose beads, as a model for cells, demonstrating promise for future integration in clinical applications with a custom CMOS chip.

Label-free detection of synthetic, full genomic length HIV-1 RNA at the few-copy level.

Oligonucleotide-functionalized graphene biosensors show immense promise for use as label-free point of care devices for detection of nucleic acid biomarkers at clinically relevant levels. Graphene-based nucleic acid sensors can be fabricated at low cost and have been shown to reach limits of detection in the attomolar range. Here we demonstrate devices functionalized with 22mer or 8omer DNA probes are capable of detecting full length genomic HIV-1 subtype B RNA, with a limit of detection below 1 aM in nuclease free water. We also show that these sensors are suitable for detection directly in Qiazol lysis reagent, again with a limit of detection below 1 aM for both 22mer and 8omer probes.

Metal-insulator crossover in monolayer MoS2.

We report on transport measurements in monolayer MoS2devices, close to the bottom of the conduction band edge. These devices were annealedin situbefore electrical measurements. This allows us to obtain good ohmic contacts at low temperatures, and to measure precisely the conductivity and mobility via four-probe measurements. The measured effective mobility up toµeff= 180 cm2V-1s-1is among the largest obtained in CVD-grown MoS2monolayer devices. These measurements show that electronic transport is of the insulating type forσ≤ 1.4e2/handn≤ 1.7 × 1012cm-2, and a crossover to a metallic regime is observed above those values. In the insulating regime, thermally activated transport dominates at high temperature (T> 120 K). At lower temperatures, conductivity is driven by Efros-Schklovkii variable range hopping in all measured devices, with a universal and constant hopping prefactor, that is a clear indication that hopping is not phonon-mediated. At higher carrier density, and high temperature, the conductivity is well modeled by the Boltzmann equation for a non-interacting Fermi gas, taking into account both phonon and impurity scatterings. Finally, even if this apparent metal-insulator transition can be explained by phonon-related phenomena at high temperature, the possibility of a genuine 2D MIT cannot be ruled out, as we can observe a clear power-law diverging localization length close to the transition, and a one-parameter scaling can be realized.

General duality and magnet-free passive phononic Chern insulators.

Integrated phononics plays an important role in both fundamental physics and technology. Despite great efforts, it remains a challenge to break time-reversal symmetry to achieve topological phases and non-reciprocal devices. Piezomagnetic materials offer an intriguing opportunity as they break time-reversal symmetry intrinsically, without the need for an external magnetic field or an active driving field. Moreover, they are antiferromagnetic, and possibly compatible with superconducting components. Here, we develop a theoretical framework that combines linear elasticity with Maxwell's equations via piezoelectricity and/or piezomagnetism beyond the commonly adopted quasi-static approximation. Our theory predicts and numerically demonstrates phononic Chern insulators based on piezomagnetism. We further show that the topological phase and chiral edge states in this system can be controlled by the charge doping. Our results exploit a general duality relation between piezoelectric and piezomagnetic systems, which can potentially be generalized to other composite metamaterial systems.

Quantifying the Size and Duration of a Microburst-Producing Chorus Region on 5 December 2017.

Microbursts are impulsive (<1 s) injections of electrons into the atmosphere, thought to be caused by nonlinear scattering by chorus waves. Although attempts have been made to quantify their contribution to outer belt electron loss, the uncertainty in the overall size and duration of the microburst region is typically large, so that their contribution to outer belt loss is uncertain. We combine datasets that measure chorus waves (Van Allen Probes [RBSP], Arase, ground-based VLF stations) and microburst (>30 keV) precipitation (FIREBIRD II and AC6 CubeSats, POES) to determine the size of the microburst-producing chorus source region beginning on 5 December 2017. We estimate that the long-lasting (∼30 hr) microburst-producing chorus region extends from 4 to 8 Δ MLT and 2-5 Δ L. We conclude that microbursts likely represent a major loss source of outer radiation belt electrons for this event.

Multimodal, Multiscale Insights into Hippocampal Seizures Enabled by Transparent, Graphene-Based Microelectrode Arrays.

Hippocampal seizures are a defining feature of mesial temporal lobe epilepsy (MTLE). Area CA1 of the hippocampus is commonly implicated in the generation of seizures, which may occur because of the activity of endogenous cell populations or of inputs from other regions within the hippocampal formation. Simultaneously observing activity at the cellular and network scales in vivo remains challenging. Here, we present a novel technology for simultaneous electrophysiology and multicellular calcium imaging of CA1 pyramidal cells (PCs) in mice enabled by a transparent graphene-based microelectrode array (Gr MEA). We examine PC firing at seizure onset, oscillatory coupling, and the dynamics of the seizure traveling wave as seizures evolve. Finally, we couple features derived from both modalities to predict the speed of the traveling wave using bootstrap aggregated regression trees. Analysis of the most important features in the regression trees suggests a transition among states in the evolution of hippocampal seizures.

Quantum-Well Bound States in Graphene Heterostructure Interfaces.

We present experimental evidence of electronic and optical interlayer resonances in graphene van der Waals heterostructure interfaces. Using the spectroscopic mode of a low-energy electron microscope (LEEM), we characterized these interlayer resonant states up to 10 eV above the vacuum level. Compared with nontwisted, AB-stacked bilayer graphene (AB BLG), an ≈0.2 Å increase was found in the interlayer spacing of 30° twisted bilayer graphene (30°-tBLG). In addition, we used Raman spectroscopy to probe the inelastic light-matter interactions. A unique type of Fano resonance was found around the D and G modes of the graphene lattice vibrations. This anomalous, robust Fano resonance is a direct result of quantum confinement and the interplay between discrete phonon states and the excitonic continuum.

The C-terminus of the mu opioid receptor is critical in G-protein interaction as demonstrated by a novel graphene biosensor.

Several water-soluble variants of the human mu opioid receptor (wsMORs) have been designed and expressed, which enables the detection of opioids in the nM to pM range using biosensing platforms. The tools previously developed allowed us to investigate MOR and G-protein interactions in a lipid free system to demonstrate that the lipid bilayer might not be essential for the G-protein recognition and binding. In this study, we are able to investigate G-protein interactions with MOR by using graphene enabled technology, in a lipid free system, with a high sensitivity in a real time manner. A new wsMOR with the native C-terminus was designed, expressed and then immobilized on the surfaces of scalable graphene field effect transistor (GFET)-based biosensors, enabling the recording of wsMOR/G-protein interaction with an electronic readout. G-protein only interacts with the wsMOR in the presence of the native MOR C-terminus with a KA of 32.3±11.1 pM. The electronic readout of such interaction is highly reproducible with little variance across 50 devices in one biosensor array. For devices with receptors that do not have the native C-terminus, no significant electronic response was observed in the presence of G-protein, indicating an absence of interaction. These findings reveal that lipid environment is not essential for the G-protein interaction with MOR, however, the C-terminus of MOR is essential for G-protein recognition and high affinity binding. A system to detect MOR-G protein interaction is developed. wsMOR-G2_Cter provides a novel tool to investigate the role of C terminus in the signaling pathway.

Multimodal in vivo recording using transparent graphene microelectrodes illuminates spatiotemporal seizure dynamics at the microscale.

Neurological disorders such as epilepsy arise from disrupted brain networks. Our capacity to treat these disorders is limited by our inability to map these networks at sufficient temporal and spatial scales to target interventions. Current best techniques either sample broad areas at low temporal resolution (e.g. calcium imaging) or record from discrete regions at high temporal resolution (e.g. electrophysiology). This limitation hampers our ability to understand and intervene in aberrations of network dynamics. Here we present a technique to map the onset and spatiotemporal spread of acute epileptic seizures in vivo by simultaneously recording high bandwidth microelectrocorticography and calcium fluorescence using transparent graphene microelectrode arrays. We integrate dynamic data features from both modalities using non-negative matrix factorization to identify sequential spatiotemporal patterns of seizure onset and evolution, revealing how the temporal progression of ictal electrophysiology is linked to the spatial evolution of the recruited seizure core. This integrated analysis of multimodal data reveals otherwise hidden state transitions in the spatial and temporal progression of acute seizures. The techniques demonstrated here may enable future targeted therapeutic interventions and novel spatially embedded models of local circuit dynamics during seizure onset and evolution.

Nanoscale Friction Behavior of Transition-Metal Dichalcogenides: Role of the Chalcogenide.

Despite extensive research on the tribological properties of MoS2, the frictional characteristics of other members of the transition-metal dichalcogenide (TMD) family have remained relatively unexplored. To understand the effect of the chalcogen on the tribological behavior of these materials and gain broader general insights into the factors controlling friction at the nanoscale, we compared the friction force behavior for a nanoscale single asperity sliding on MoS2, MoSe2, and MoTe2 in both bulk and monolayer forms through a combination of atomic force microscopy experiments and molecular dynamics simulations. Experiments and simulations showed that, under otherwise identical conditions, MoS2 has the highest friction among these materials and MoTe2 has the lowest. Simulations complemented by theoretical analysis based on the Prandtl-Tomlinson model revealed that the observed friction contrast between the TMDs was attributable to their lattice constants, which differed depending on the chalcogen. While the corrugation amplitudes of the energy landscapes are similar for all three materials, larger lattice constants permit the tip to slide more easily across correspondingly wider saddle points in the potential energy landscape. These results emphasize the critical role of the lattice constant, which can be the determining factor for frictional behavior at the nanoscale.

Phase Transition in a Memristive Suspended MoS2 Monolayer Probed by Opto- and Electro-Mechanics.

Semiconducting monolayers of a 2D material are able to concatenate multiple interesting properties into a single component. Here, by combining opto-mechanical and electronic measurements, we demonstrate the presence of a partial 2H-1T' phase transition in a suspended 2D monolayer membrane of MoS2. Electronic transport shows unexpected memristive properties in the MoS2 membrane, in the absence of any external dopants. A strong mechanical softening of the membrane is measured concurrently and may only be related to the 2H-1T' phase transition, which imposes a 3% directional elongation of the topological 1T' phase with respect to the semiconducting 2H. We note that only a few percent 2H-1T' phase switching is sufficient to observe measurable memristive effects. Our experimental results combined with first-principles total energy calculations indicate that sulfur vacancy diffusion plays a key role in the initial nucleation of the phase transition. Our study clearly shows that nanomechanics represents an ultrasensitive technique to probe the crystal phase transition in 2D materials or thin membranes. Finally, a better control of the microscopic mechanisms responsible for the observed memristive effect in MoS2 is important for the implementation of future devices.

Electron Microburst Size Distribution Derived With AeroCube-6.

Microbursts are an impulsive increase of electrons from the radiation belts into the atmosphere and have been directly observed in low Earth orbit and the upper atmosphere. Prior work has estimated that microbursts are capable of rapidly depleting the radiation belt electrons on the order of a day; hence, their role to radiation belt electron losses must be considered. Losses due to microbursts are not well constrained, and more work is necessary to accurately quantify their contribution as a loss process. To address this question, we present a statistical study of > 35 keV microburst sizes using the pair of AeroCube-6 CubeSats. The microburst size distribution in low Earth orbit and the magnetic equator was derived using both spacecraft. In low Earth orbit, the majority of microbursts were observed, while the AeroCube-6 separation was less than a few tens of kilometers, mostly in latitude. To account for the statistical effects of random microburst locations and sizes, Monte Carlo and analytic models were developed to test hypothesized microburst size distributions. A family of microburst size distributions were tested, and a Markov chain Monte Carlo sampler was used to estimate the optimal distribution of model parameters. Finally, a majority of observed microbursts map to sizes less than 200 km at the magnetic equator. Since microbursts are widely believed to be generated by scattering of radiation belt electrons by whistler mode waves, the observed microburst size distribution was compared to whistler mode chorus size distributions derived in prior literature.

MoS2-enabled dual-mode optoelectronic biosensor using a water soluble variant of µ-opioid receptor for opioid peptide detection.

Owing to their unique electrical and optical properties, two-dimensional transition metal dichalcogenides have been extensively studied for their potential applications in biosensing. However, simultaneous utilization of both optical and electrical properties has been overlooked, yet it can offer enhanced accuracy and detection versitility. Here, we demonstrate a dual-mode optoelectronic biosensor based on monolayer molybdenum disulfide (MoS2) capable of producing simultaneous electrical and optical readouts of biomolecular signals. On a single platform, the biosensor exhibits a tunable photonic Fano-type optical resonance while also functioning as a field-effect transistor (FET) based on a optically transparent gate electrode. Furthermore, chemical vapor deposition grown MoS2 provides a clean surface for direct immobilization of a water-soluble variant of the µ-opioid receptor (wsMOR), via a nickel ion-mediated linker chemistry. We utilize a synthetic opioid peptide to show the operation of the electronic and optical sensing modes. The responses of both modes exhibit a similar trend with dynamic ranges of four orders of magnitude and detection limits of <1 nM. Our work explores the potential of a versatile multimodal sensing platform enabled by monolayer MoS2, since the integration of electrical and optical sensors on the same chip can offer flexibility in read-out and improve the accuracy in detection of low concentration targets.

The FIREBIRD-II CubeSat mission: Focused investigations of relativistic electron burst intensity, range, and dynamics.

FIREBIRD-II is a National Science Foundation funded CubeSat mission designed to study the scale size and energy spectrum of relativistic electron microbursts. The mission consists of two identical 1.5 U CubeSats in a low earth polar orbit, each with two solid state detectors that differ only in the size of their geometric factors and fields of view. Having two spacecraft in close orbit allows the scale size of microbursts to be investigated through the intra-spacecraft separation when microbursts are observed simultaneously on each unit. Each detector returns high cadence (10 s of ms) measurements of the electron population from 200 keV to >1 MeV across six energy channels. The energy channels were selected to fill a gap in the observations of the Heavy Ion Large Telescope instrument on the Solar, Anomalous, and Magnetospheric Particle Explorer. FIREBIRD-II has been in orbit for 5 years and continues to return high quality data. After the first month in orbit, the spacecraft had separated beyond the expected scale size of microbursts, so the focus has shifted toward conjunctions with other magnetospheric missions. FIREBIRD-II has addressed all of its primary science objectives, and its long lifetime and focus on conjunctions has enabled additional science beyond the scope of the original mission. This paper presents a brief history of the FIREBIRD mission's science goals, followed by a description of the instrument and spacecraft. The data products are then discussed along with some caveats necessary for proper use of the data.

Large-area epitaxial growth of curvature-stabilized ABC trilayer graphene.

The properties of van der Waals (vdW) materials often vary dramatically with the atomic stacking order between layers, but this order can be difficult to control. Trilayer graphene (TLG) stacks in either a semimetallic ABA or a semiconducting ABC configuration with a gate-tunable band gap, but the latter has only been produced by exfoliation. Here we present a chemical vapor deposition approach to TLG growth that yields greatly enhanced fraction and size of ABC domains. The key insight is that substrate curvature can stabilize ABC domains. Controllable ABC yields ~59% were achieved by tailoring substrate curvature levels. ABC fractions remained high after transfer to device substrates, as confirmed by transport measurements revealing the expected tunable ABC band gap. Substrate topography engineering provides a path to large-scale synthesis of epitaxial ABC-TLG and other vdW materials.

Statistical Properties of Electron Curtain Precipitation Estimated With AeroCube-6.

Curtain precipitation is a recently discovered stationary, persistent, and latitudinally narrow electron precipitation phenomenon in low Earth orbit. Curtains are observed over consecutive passes of the dual AeroCube-6 CubeSats while their in-track lag varied from a fraction of a second to 65 s, with dosimeters that are sensitive to >35-keV electrons. This study uses the AeroCube-6 mission to quantify the statistical properties of 1,634 curtains observed over 3 years. We found that many curtains are narrower than 10 km in the latitudinal direction with 90% narrower than 20 km. We examined the geographic, magnetic local time, and geomagnetic dependence of curtains. We found that curtains are observed in the late-morning and premidnight magnetic local times, with a higher occurrence rate at premidnight, and curtains are observed more often during times of enhanced Auroral Electrojet. We found a few curtains in the bounce loss cone region above the North Atlantic, whose electrons were continuously scattered for at least 6 s. Such observations suggest that continuous curtain precipitation may be a significant loss of >35-keV electrons from the magnetosphere into the atmosphere. We hypothesize that the curtains observed in the bounce loss cone were accelerated by parallel electric fields, and we show that this mechanism is consistent with the observations.

Characterization of an engineered water-soluble variant of the full-length human mu opioid receptor.

A water-soluble variant of the transmembrane domain of the human mu opioid receptor (wsMOR-TM) was previously characterized. This study explored whether the full-length version of the engineered water-soluble receptor, (wsMOR-FL), could be overexpressed in Escherichia coli and if it would retain water solubility, binding capability and thermostability. wsMOR was over-expressed and purified in E. coli BL21(DE3) cells (EMD/Novagen) as we reported previously for the wsMOR-TM. Both native N and C termini were added back to the highly engineered wsMOR-TM. Six His-tag was added in the N terminus for purification purposes. The wsMOR-FL was characterized using atomic force microscope for its monomeric state, circular dichroism for its secondary structure and thermostability. Its binding with naltrexone is also determined. Compared to the native human MOR, wsMOR-FL displays similar helical secondary structure content and comparable affinity (nM) for the antagonist naltrexone. The secondary structure of the receptor remains stable within a wide range of pH (6-9). In contrast to the transmembrane portion, the secondary structure of full-length receptor tolerated a wide range of temperature (10-90 °C). The receptor remains predominantly as a monomer in solution, as directly imaged using atomic force microscopy. This study demonstrated that functional full-length water-soluble variant of human mu receptor can be over-expressed and purified using an E. coli over-expression system. This provides a novel tool for the investigation of structural and functional properties of the human MOR. N- and C-termini strengthened the thermostability of the protein in this specific water soluble variant. Communicated by Ramaswamy H. Sarma.

Water Soluble G-protein Coupled Receptor Enabled Biosensors.

This article will briefly overview our efforts in the engineering of water soluble variants of a G-protein coupled receptor (GPCR) and its novel applications to develop biosensors using such water soluble variants of GPCR. While the technologies using water soluble GPCR are still under development, they offer new tools and strategies to study the function of GPCR, explore potential new compounds for potential clinical usage, and monitor endogenous peptides in various physiological and pathological conditions.

Atomic-scale patterning in two-dimensional van der Waals superlattices.

Two-dimensional (2D) van der Waals superlattices comprised of two stacked monolayer materials have attracted significant interest as platforms for novel optoelectronic and structural behavior. Although studies are focused on superlattice fabrication, less effort has been given to the nanoscale patterning and structural modification of these systems. In this report, we demonstrate the localized layer-by-layer thinning and formation of nanopores/defects in 2D superlattices, such as stacked MoS2-WS2 van der Waals heterostructures and chemical vapor deposited bilayer WSe2, using aberration-corrected scanning transmission electron microscopy (STEM). Controlled electron beam irradiation is used to locally thin superlattices by removing the bottom layer of atoms, followed by defect formation through ablation of the second layer of atoms. The resulting defects exhibit atomically-sharp pore edges with tunable diameters down to 0.6 nm. Structural periodicities and focused STEM irradiation are also utilized to form close-packed nanopore arrays in superlattices with varying twist angles and commensurability. Applying these methods and mechanisms provides a forward approach in the atomic-scale patterning of stacked 2D nanodevices.

Scalable Arrays of Chemical Vapor Sensors Based on DNA-Decorated Graphene.

Arrays of DNA-functionalized graphene field-effect transistors (gFETs) hold great promise for high-performance vapor sensing. In this chapter, we describe methods for the scalable production of gFET-based vapor sensors with high sensitivity and efficiency in size, cost, and time. Large-area graphene sheets were prepared via chemical vapor deposition (CVD); a standard photolithographic processing for large-area graphene was used to fabricate gFETs with high mobility and low doping level under ambient conditions. The gFETs were functionalized by single-stranded DNA (ssDNA), which binds to the graphene channels through π-π stacking interaction and provides affinity to a wide range of chemical vapors. The resulting sensing arrays demonstrate detection of target vapor molecules down to parts-per-million concentrations with high selectivity among analytes with high chemical similarity including a series of carboxylic acids and structural isomers of carboxylic acids and pinene.