Publications by authors named "Raman Sankar"

199 Publications

Engineering an Indium Selenide van der Waals Interface for Multilevel Charge Storage.

ACS Appl Mater Interfaces 2021 Jan 14;13(3):4618-4625. Epub 2021 Jan 14.

Center for Condensed Matter Sciences, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.

As the continuous miniaturization of floating-gate transistors approaches a physical limit, new innovations in device architectures, working principles, and device materials are in high demand. This study demonstrated a nonvolatile memory structure with multilevel data storage that features a van der Waals gate architecture made up of a partially oxidized surface layer/indium selenide (InSe) van der Waals interface. The key functionality of this proof-of-concept device is provided through the generation of charge-trapping sites via an indirect oxygen plasma treatment on the InSe surface layer. In contrast to floating-gate nonvolatile memory, these sites have the ability to retain charge without the help of a gate dielectric. Together with the layered structure, the surface layer with charge-trapping sites facilitates continual electrostatic doping in the underlying InSe layers. The van der Waals gating effect is further supported by trapped charge-induced core-level energy shifts and relative work function variations obtained from operando scanning X-ray photoelectron spectroscopy and Kelvin probe microscopy, respectively. On modulating the amount of electric field-induced trapped electrons by the electrostatic gate potential, eight distinct storage states remained over 3000 s. Moreover, the device exhibits a high current switching ratio of 10 within 11 cycles. The demonstrated characteristics suggest that the engineering of an InSe interface has potential applications for nonvolatile memory.
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http://dx.doi.org/10.1021/acsami.0c16336DOI Listing
January 2021

Magnetotransport in hybrid InSe/monolayer graphene on SiC.

Nanotechnology 2021 Apr;32(15):155704

Graduate Institute of Applied Physics, National Taiwan University, Taipei 106, Taiwan.

The magnetotransport properties of a hybrid InSe/monolayer graphene in a SiC system are systematically studied. Compared to those of its bare graphene counterpart, in InSe/graphene, we can effectively modify the carrier density, mobility, effective mass, and electron-electron (e-e) interactions enhanced by weak disorder. We show that in bare graphene and hybrid InSe/graphene systems, the logarithmic temperature (lnT) dependence of the Hall slope R  = δR /δB = δρ /δB can be used to probe e-e interaction effects at various temperatures even when the measured resistivity does not show a lnT dependence due to strong electron-phonon scattering. Nevertheless, one needs to be certain that the change of R is not caused by an increase of the carrier density by checking the magnetic field position of the longitudinal resistivity minimum at different temperatures. Given the current challenges in gating graphene on SiC with a suitable dielectric layer, our results suggest that capping a van der Waals material on graphene is an effective way to modify the electronic properties of monolayer graphene on SiC.
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http://dx.doi.org/10.1088/1361-6528/abd726DOI Listing
April 2021

Potential induction of epileptic spasms by nonselective voltage-gated sodium channel blockade: Interaction with etiology.

Epilepsy Behav 2021 Feb 16;115:107624. Epub 2020 Dec 16.

Division of Pediatric Neurology, David Geffen School of Medicine and UCLA Mattel Children's Hospital, Los Angeles, CA, United States.

Purpose: Epileptic spasms are often preceded by focal (or multifocal) seizures. Based on a series of case reports suggesting that carbamazepine and oxcarbazepine may induce epileptic spasms, we set out to rigorously evaluate the potential association between exposure to voltage-gated sodium channel blockade and latency to epileptic spasms.

Methods: We identified 50 cases (children with focal seizures and evolution to epileptic spasms) and 50 controls (children with focal seizures without evolution to epileptic spasms). For each patient, we reviewed all sequential neurology encounters between onset of epilepsy and emergence of epileptic spasms. For each encounter we recorded seizure-frequency and all anti-seizure therapy exposures. Using multivariable Cox proportional hazards regression, we evaluated the association between voltage-gated sodium channel exposure (carbamazepine, oxcarbazepine, lacosamide, or phenytoin) and latency to epileptic spasms onset, with adjustment for etiology and seizure-frequency.

Results: Latency to epileptic spasms onset was independently associated with exposure to sodium channel blockade (hazard ratio = 2.4; 95% CI 1.1-5.2; P = 0.03) and high-risk etiology (hazard ratio = 2.8; 95% CI 1.5-5.1; P = 0.001). With assessment for interaction between sodium channel blockade and etiology, we identified an estimated 7-fold increased risk of epileptic spasms with the combination of sodium channel blockade and high-risk etiology (hazard ratio = 7.0, 95% CI 2.5-19.8; P < 0.001).

Conclusion: This study suggests that voltage-gated sodium channel blockade may induce epileptic spasms among children at risk on the basis of etiology. Further study is warranted to replicate these findings, ascertain possible drug- and dose-specific risks, and identify potential mechanisms of harm.
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http://dx.doi.org/10.1016/j.yebeh.2020.107624DOI Listing
February 2021

Repurposing INCI-registered compounds as skin prebiotics for probiotic Staphylococcus epidermidis against UV-B.

Sci Rep 2020 12 9;10(1):21585. Epub 2020 Dec 9.

Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan.

Repurposing existing compounds for new indications may facilitate the discovery of skin prebiotics which have not been well defined. Four compounds that have been registered by the International Nomenclature of Cosmetic Ingredients (INCI) were included to study their abilities to induce the fermentation of Staphylococcus epidermidis (S. epidermidis), a bacterial species abundant in the human skin. Liquid coco-caprylate/caprate (LCC), originally used as an emollient, effectively initiated the fermentation of S. epidermidis ATCC 12228, produced short-chain fatty acids (SCFAs), and provoked robust electricity. Application of LCC plus electrogenic S. epidermidis ATCC 12228 on mouse skin significantly reduced ultraviolet B (UV-B)-induced injuries which were evaluated by the formation of 4-hydroxynonenal (4-HNE), cyclobutane pyrimidine dimers (CPD), and skin lesions. A S. epidermidis S2 isolate with low expressions of genes encoding pyruvate dehydrogenase (pdh), and phosphate acetyltransferase (pta) was found to be poorly electrogenic. The protective action of electrogenic S. epidermidis against UV-B-induced skin injuries was considerably suppressed when mouse skin was applied with LCC in combination with a poorly electrogenic S. epidermidis S2 isolate. Exploring new indication of LCC for promoting S. epidermidis against UV-B provided an example of repurposing INCI-registered compounds as skin prebiotics.
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http://dx.doi.org/10.1038/s41598-020-78132-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725810PMC
December 2020

Long-term safety and tolerability of adjunctive eslicarbazepine acetate in children with focal seizures.

Epilepsy Behav 2020 11 24;112:107458. Epub 2020 Sep 24.

Sunovion Pharmaceuticals Inc., Marlborough, MA, USA. Electronic address:

Objective: The objective of this study was to evaluate long-term safety and tolerability outcomes in two open-label extension (OLE) studies of adjunctive eslicarbazepine acetate (ESL) in children with focal seizures.

Methods: Safety data from patients aged 4-17 years in OLEs of Studies 2093-208 and -305 were pooled and analyzed. Studies 208 and 305 were randomized, double-blind, placebo-controlled studies of adjunctive treatment with ESL in children with focal seizures refractory to treatment with 1-2 antiseizure drugs; patients could continue into uncontrolled OLEs (up to 5 years total duration). The OLEs evaluated the safety and tolerability of ESL (10-30 mg/kg/day; maximum 1200 mg/day).

Results: The 1-year OLE and post-1-year OLE safety populations comprised 337 and 177 ESL-treated patients, respectively. The overall incidence of treatment-emergent adverse events (TEAEs) with ESL was 64.1% during the 1-year OLE and 52.5% during the post-1-year OLE. Nasopharyngitis, partial seizures, vomiting, pyrexia, headache, somnolence, and respiratory tract infection were the most frequently reported TEAEs during the 1-year OLE. The overall incidence of serious adverse events (AEs) was 8.9% during the 1-year OLE and 10.2% during the post-1-year OLE. Partial seizures (1.2%) and pneumonia (1.2%) were the most frequently reported serious AEs during the 1-year OLE. The overall incidence of TEAEs leading to discontinuation was 4.2% during the 1-year OLE and 0.6% during the post-1-year OLE. Partial seizures (1.5%) was the most frequently reported TEAE leading to discontinuation during the 1-year OLE.

Conclusions: Overall, long-term treatment with ESL was generally well tolerated in pediatric patients aged 4-17 years with focal seizures. TEAEs were comparable to those observed in adults with no new events of concern.
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http://dx.doi.org/10.1016/j.yebeh.2020.107458DOI Listing
November 2020

Scalp EEG interictal high frequency oscillations as an objective biomarker of infantile spasms.

Clin Neurophysiol 2020 Nov 3;131(11):2527-2536. Epub 2020 Sep 3.

Division of Pediatric Neurology, Department of Pediatrics, UCLA Mattel Children's Hospital, David Geffen School of Medicine, Los Angeles, California, USA.

Objective: To investigate the diagnostic utility of high frequency oscillations (HFOs) via scalp electroencephalogram (EEG) in infantile spasms.

Methods: We retrospectively analyzed interictal slow-wave sleep EEGs sampled at 2,000 Hz recorded from 30 consecutive patients who were suspected of having infantile spasms. We measured the rate of HFOs (80-500 Hz) and the strength of the cross-frequency coupling between HFOs and slow-wave activity (SWA) at 3-4 Hz and 0.5-1 Hz as quantified with modulation indices (MIs).

Results: Twenty-three patients (77%) exhibited active spasms during the overnight EEG recording. Although the HFOs were detected in all children, increased HFO rate and MIs correlated with the presence of active spasms (p < 0.001 by HFO rate; p < 0.01 by MIs at 3-4 Hz; p = 0.02 by MIs at 0.5-1 Hz). The presence of active spasms was predicted by the logistic regression models incorporating HFO-related metrics (AUC: 0.80-0.98) better than that incorporating hypsarrhythmia (AUC: 0.61). The predictive performance of the best model remained favorable (87.5% accuracy) after a cross-validation procedure.

Conclusions: Increased rate of HFOs and coupling between HFOs and SWA are associated with active epileptic spasms.

Significance: Scalp-recorded HFOs may serve as an objective EEG biomarker for active epileptic spasms.
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http://dx.doi.org/10.1016/j.clinph.2020.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606823PMC
November 2020

Unprecedented random lasing in 2D organolead halide single-crystalline perovskite microrods.

Nanoscale 2020 Sep 28;12(35):18269-18277. Epub 2020 Aug 28.

Department of Physics, National Taiwan University, Taipei 10617, Taiwan.

Three-dimensional organic-inorganic hybrid halide perovskites have been demonstrated as great materials for applications in optoelectronics and photonics. However, their inherent instabilities in the presence of moisture, light, and heat may hinder their commercialization. Alternatively, emerging two-dimensional (2D) organic-inorganic hybrid perovskites have recently attracted increasing attention owing to their great environmental stability and inherent natural quantum-well structure. In this work, we have synthesized a high-quality long-chain organic diammonium spacer assisted 2D hybrid perovskite FA-(N-MPDA)PbBr (FA = formamidinium and N-MPDA = N-methylpropane-1,3-diammonium) by the slow evaporation at constant temperature method. The millimeter-sized single-crystalline microrods demonstrate low threshold random lasing behavior at room temperature. The single-crystalline 2D hybrid perovskite random laser achieved a very narrow linewidth (∼0.1 nm) with a low threshold (∼0.5 μJ cm) and a high quality factor (∼5350). Furthermore, the 2D hybrid microrod laser shows stable lasing emission with no measurable degradation after at least 2 h under continuous illumination, which substantially proves the stability of 2D perovskites. Our results demonstrate the promise of 2D organic-inorganic microrod-shaped perovskites and provide an important step toward the realization of high-performance optoelectronic devices.
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http://dx.doi.org/10.1039/d0nr01171aDOI Listing
September 2020

Anisotropic Transport and Quantum Oscillations in the Quasi-One-Dimensional TaNiTe: Evidence for the Nontrivial Band Topology.

J Phys Chem Lett 2020 Sep 2;11(18):7782-7789. Epub 2020 Sep 2.

Department of Applied Physics, Zhejiang University of Technology, Hangzhou 310023, China.

The past decade has witnessed the burgeoning discovery of a variety of topological states of matter with distinct nontrivial band topologies. Thus far, most materials that have been studied possess two-dimensional or three-dimensional electronic structures, with only a few exceptions that host quasi-one-dimensional (quasi-1D) topological electronic properties. Here we present clear-cut evidence for Dirac Fermions in the quasi-1D telluride TaNiTe. We show that its transport behaviors are highly anisotropic, and we observe nontrivial Berry phases via quantum oscillation measurements. The nontrivial band topology is further corroborated by first-principles calculations. Our results may help to guide the future quest for topological states in this new family of quasi-1D ternary chalcogenides.
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http://dx.doi.org/10.1021/acs.jpclett.0c02382DOI Listing
September 2020

Femtosecond time-evolution of mid-infrared spectral line shapes of Dirac fermions in topological insulators.

Sci Rep 2020 Jun 17;10(1):9803. Epub 2020 Jun 17.

Department of Electrophysics, National Chiao Tung University, Hsinchu, Taiwan.

Mid-infrared (MIR) light sources have much potential in the study of Dirac-fermions (DFs) in graphene and topological insulators (TIs) because they have a low photon energy. However, the topological surface state transitions (SSTs) in Dirac cones are veiled by the free carrier absorption (FCA) with same spectral line shape that is always seen in static MIR spectra. Therefore, it is difficult to distinguish the SST from the FCA, especially in TIs. Here, we disclose the abnormal MIR spectrum feature of transient reflectivity changes (ΔR/R) for the non-equilibrium states in TIs, and further distinguish FCA and spin-momentum locked SST using time-resolved and linearly polarized ultra-broadband MIR spectroscopy with no environmental perturbation. Although both effects produce similar features in the reflection spectra, they produce completely different variations in the ΔR/R to show their intrinsic ultrafast dynamics.
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http://dx.doi.org/10.1038/s41598-020-66720-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299937PMC
June 2020

Synergistic optimization of thermoelectric performance in earth-abundant CuZnSnS by inclusion of graphene nanosheets.

Nanotechnology 2020 Sep 15;31(36):365402. Epub 2020 May 15.

University School of Basic and Applied Sciences, Guru Gobind Singh Indraprastha University, Dwarka, Delhi 110078, India.

Earth-abundant quaternary chalcogenide semiconductors with complex structures, such as copper zinc tin sulphide (CuZnSnS; CZTS), have the potential to become economic and non-toxic thermoelectric materials. However, the inferior power factor of CZTS, due to its insignificant electrical conductivity, negates the advantage of inherent small thermal conductivity. In the present report, the thermoelectric properties of CZTS composites integrated with graphene nanosheets (GNs) CZTS/x (x = 0.25, 0.5, 0.75 or 1 wt% GNs) were synergistically optimized. The inclusion of GNs (⩽0.75 wt%) simultaneously enhanced the carrier transport (electrical conductivity σ) by providing conductive pathways as well as suppressed lattice thermal conductivity (κ ) due to the enhanced grain barriers in addition to interface scattering. This synergistic optimization enhanced the figure of merit, ZT, of CZTS/GN nanocomposites to its highest value (∼0.5) at 623 K for the addition of 0.75 wt% GNs, which is nearly a seven-fold enhancement over the pristine sample. The novel strategy of fabricating CZTS/GN nanocomposites by utilizing GNs is an alternative way to obtain the highest thermoelectric performance (ZT ∼ 0.5) in CZTS, and can be extended to other environmentally friendly quaternary chalcogenides.
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http://dx.doi.org/10.1088/1361-6528/ab9393DOI Listing
September 2020

Modulating Charge Separation with Hexagonal Boron Nitride Mediation in Vertical Van der Waals Heterostructures.

ACS Appl Mater Interfaces 2020 Jun 28;12(23):26213-26221. Epub 2020 May 28.

Department of Physics, National Taiwan University, Taipei 10617, Taiwan.

Tuning the optical and electrical properties by stacking different layers of two-dimensional (2D) materials enables us to create unusual physical phenomena. Here, we demonstrate an alternative approach to enhance charge separation and alter physical properties in van der Waals heterojunctions with type-II band alignment by using thin dielectric spacers. To illustrate our working principle, we implement a hexagonal boron nitride (h-BN) sieve layer in between an InSe/GeS heterojunction. The optical transitions at the junctions studied by photoluminescence and the ultrafast pump-probe technique show quenching of emission without h-BN layers exhibiting an indirect recombination process. This quenching effect due to strong interlayer coupling was confirmed with Raman spectroscopic studies. In contrast, h-BN layers in between InSe and GeS show strong enhancement in emission, giving another degree of freedom to tune the heterojunction property. The two-terminal photoresponse study supports the argument by showing a large photocurrent density for an InSe/h-BN/GeS device by avoiding interlayer charge recombination. The enhanced charge separation with h-BN mediation manifests a photoresponsivity and detectivity of 9 × 10 A W and 3.4 × 10 Jones, respectively. Moreover, a photogain of 1.7 × 10 shows a high detection of electrons for the incident photons. Interestingly, the photovoltaic short-circuit current is switched from positive to negative, whereas the open-circuit voltage changes from negative to positive. Our proposed enhancement of charge separation with 2D-insulator mediation, therefore, provides a useful route to manipulate the physical properties of heterostructures and for the future development of high-performance optoelectronic devices.
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http://dx.doi.org/10.1021/acsami.0c06077DOI Listing
June 2020

Interictal scalp fast ripple occurrence and high frequency oscillation slow wave coupling in epileptic spasms.

Clin Neurophysiol 2020 Jul 10;131(7):1433-1443. Epub 2020 Apr 10.

Division of Pediatric Neurology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Objective: Intracranial high frequency oscillation (HFO) occurrence rate (OR) and slow wave activity (SWA) coupling are potential markers of epileptogenicity in epileptic spasms (ES). Scalp ripple (R) detection and SWA coupling have been described in ES; however, the feasibility of scalp fast ripple (FR) detection and measurement of scalp FR coupling to SWA is not known. We evaluated interictal scalp R and FR OR and SWA coupling in pre-treatment EEG in children with short-term treatment-refractory ES compared to short-term treatment non-refractory ES.

Methods: We retrospectively identified children with ES and identified HFOs using a semi-automated HFO detector on pre-treatment scalp EEG during sleep. We evaluated HFO OR and event-triggered modulation index (MI) to quantify R (100-250 Hz) and FR (250-600 Hz) coupling strength with different SWA passbands (0.5-1, 1-2, 2-3, 3-4, and 4-8 Hz). We used HFO phasor transform and circular statistics to evaluate phase coupling angle distributions.

Results: We identified 15 children with ES with pre-treatment EEG recorded at 2000 Hz. Thirteen out of 15 patients had HFOs and were included for analysis. There were six treatment responders and seven nonresponders three months after treatment initiation. Responders and nonresponders were similar in age (6.1 vs 7.2 mo), ES diagnosis duration (0.7 vs 2.6 mo), and HFO OR (R: 1.07 vs 2.30/min, FR: 0.43 vs 1.96/min). No differences between responders and nonresponders were seen in HFO MI at different SWA. Coupling of R and FR to 2-3 Hz SWA demonstrated increased incidence rate ratio in nonresponders relative to responders at distinct phase coupling angle distributions.

Conclusions: This study demonstrates the feasibility of interictal scalp R and FR detection and quantification of scalp R and FR coupling to SWA in ES.

Significance: HFO phase coupling with SWA may be useful as a marker of potential treatment refractoriness in patients with ES.
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http://dx.doi.org/10.1016/j.clinph.2020.03.025DOI Listing
July 2020

Ultralow Schottky Barriers in Hexagonal Boron Nitride-Encapsulated Monolayer WSe Tunnel Field-Effect Transistors.

ACS Appl Mater Interfaces 2020 Apr 13;12(16):18667-18673. Epub 2020 Apr 13.

Department of Physics, National Taiwan University, Taipei 10617, Taiwan.

To explore the potential of field-effect transistors (FETs) based on monolayers (MLs) of the two-dimensional semiconducting channel (SC) for spintronics, the two most important issues are to ensure the formation of variable low-resistive tunnel ferromagnetic contacts (FCs) and to preserve intrinsic properties of the SC during fabrication. Large Schottky barriers lead to the formation of high resistive contacts, and methods adopted to control the barriers often alter the intrinsic properties of the SC. This work aims at addressing both issues in fully encapsulated ML WSe FETs using bilayer hexagonal boron nitride (h-BN) as a tunnel barrier at the FC/SC interface. We investigate the electrical transport in ML WSe FETs with the current-in-plane geometry that yields hole mobilities of ∼38.3 cm V s at 240 K and on/off ratios of the order of 10, limited by the contact regions. We have achieved an ultralow effective Schottky barrier (∼5.34 meV) with an encapsulated tunneling device as opposed to a nonencapsulated device in which the barrier heights are considerably higher. These observations provide an insight into the electrical behavior of the FC/h-BN/SC/h-BN heterostructures, and such control over the barrier heights opens up the possibilities for WSe-based spintronic devices.
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http://dx.doi.org/10.1021/acsami.0c01025DOI Listing
April 2020

Limited efficacy of zonisamide in the treatment of refractory infantile spasms.

Epilepsia Open 2020 Mar 24;5(1):121-126. Epub 2020 Jan 24.

Department of Pediatrics (Division of Pediatric Neurology) David Geffen School of Medicine and UCLA Mattel Children's Hospital Los Angeles California.

A series of relatively small studies collectively suggest that zonisamide may be effective in the treatment of infantile spasms. Using a large single-center cohort of children with infantile spasms, we set out to evaluate the efficacy and safety of zonisamide. We retrospectively identified all patients with infantile spasms who were treated with zonisamide at our center. For each patient, we recorded dates of birth, infantile spasms onset, response (if any), and most recent follow-up. To quantify zonisamide exposure, we recorded daily dosage and patient weight at each sequential encounter so as to allow calculation of peak and weighted-average weight-based dosage. We identified 87 children who were treated with zonisamide, of whom 78 had previously been treated with hormonal therapy or vigabatrin. Peak and weighted-average zonisamide dosage were 7.1 (interquartile range 3.6, 10.2) and 5.4 (interquartile range 3.0, 8.9) mg/kg/day, respectively. Whereas five (6%) patients exhibited resolution of epileptic spasms, only two (2%) patients exhibited video-EEG confirmed resolution of both epileptic spasms and hypsarrhythmia (electroclinical response). Importantly, both electroclinical responders had not previously been treated with hormonal therapy or vigabatrin; in contrast, none of the 78 children with prior failure of hormonal therapy or vigabatrin subsequently responded to zonisamide. Zonisamide was well tolerated, and there were no deaths. This study suggests that zonisamide exhibits favorable tolerability but very limited efficacy among patients who do not respond to first-line therapy.
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http://dx.doi.org/10.1002/epi4.12381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049796PMC
March 2020

Selenium nanoparticle prepared by femtosecond laser-induced plasma shock wave.

Opt Express 2020 Jan;28(1):685-694

A novel approach for the production of both amorphous and crystalline selenium nanoparticles (SeNPs) using femtosecond laser-induced plasma shock wave on the surface of BiSe topological insulators at room temperature and ambient pressure is demonstrated. The shape and size of SeNPs can be reliably controlled via the kinetic energy obtained from laser pulses, so these are applicable as active components in nanoscale applications. Importantly, the rapid, low-cost and eco-friendly synthesis strategy developed in this study could also be extendable to other systems.
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http://dx.doi.org/10.1364/OE.381898DOI Listing
January 2020

Felbamate in the treatment of refractory epileptic spasms.

Epilepsy Res 2020 03 3;161:106284. Epub 2020 Feb 3.

David Geffen School of Medicine and UCLA Mattel Children's Hospital, Los Angeles, CA, United States; Department of Neurology, David Geffen School of Medicine, Los Angeles, CA, United States.

Several small case series provide conflicting impressions of the efficacy of felbamate for treatment of epileptic spasms. Using a large single-center cohort of children with epileptic spasms, we retrospectively evaluated the efficacy and safety of felbamate. We identified all patients with video-EEG confirmed epileptic spasms who were treated with felbamate at our center. We quantified felbamate exposure by calculating peak and weighted-average weight-based dose. Clinical response was defined as resolution of epileptic spasms for at least 28 days, beginning not more than 3 months after felbamate initiation. Electroclinical response was defined as clinical response accompanied by overnight video-EEG demonstrating freedom from epileptic spasms and hypsarrhythmia. Among a cohort of 476 infants, we identified 62 children who were treated with felbamate, of whom 58 had previously failed treatment with hormonal therapy or vigabatrin. Median peak and weighted-average felbamate dosages were 47 and 40 mg/kg/day, respectively. Five (8%) children were classified as clinical responders and two (3%) children were classified as electroclinical responders. Among 17 patients with latency from epileptic spasms onset to felbamate initiation of less than 12 months, we observed 4 (24%) clinical responders. This study suggests that felbamate may be efficacious for treatment of epileptic spasms and that further rigorous study is warranted.
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http://dx.doi.org/10.1016/j.eplepsyres.2020.106284DOI Listing
March 2020

Synthetic pharmaceutical grade cannabidiol for treatment of refractory infantile spasms: A multicenter phase-2 study.

Epilepsy Behav 2020 01 6;102:106826. Epub 2019 Dec 6.

Department of Pediatrics (Division of Neurology), David Geffen School of Medicine and UCLA Mattel Children's Hospital, Los Angeles, CA, United States; Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.

Purpose: Limited data suggest that cannabidiol (CBD) may be effective for treatment of refractory infantile spasms (IS). This study was designed to more rigorously evaluate the efficacy and safety of synthetic CBD in the treatment of IS.

Methods: Children six to 36 months of age with IS that failed treatment with both adrenocorticotropic hormone (ACTH) and vigabatrin (VGB) were eligible for enrollment. Children receiving clobazam were excluded. After baseline overnight video-electroencephalography (vEEG) to confirm diagnosis and ascertain hypsarrhythmia, patients were treated with synthetic CBD oral solution (20 mg/kg/day). Overnight video-EEG was repeated after 14 days, and both baseline and repeat video-EEGs were completely de-identified and reviewed in a pairwise fashion by an independent, blinded pediatric electroencephalographer. The primary efficacy endpoint was freedom from spasms and hypsarrhythmia on day 14.

Results: Nine patients were enrolled, comprising an older (median age = 23 months) cohort with long-standing IS (median duration = 13 months) and numerous prior treatment failures (median = 6). One patient responded to therapy and eight patients exhibited neither clinical nor electrographic response.

Conclusions: The immediate but temporary response in a single patient suggests that CBD oral solution is not particularly effective in highly refractory cases, but may, nevertheless, be effective in younger patients with shorter durations of IS. Further study, examining both short- and long-term outcomes, is warranted to further evaluate the efficacy and safety of CBD oral solution in the treatment of IS.
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http://dx.doi.org/10.1016/j.yebeh.2019.106826DOI Listing
January 2020

Prospective observational study: Fast ripple localization delineates the epileptogenic zone.

Clin Neurophysiol 2019 11 17;130(11):2144-2152. Epub 2019 Sep 17.

Division of Pediatric Neurology, Department of Pediatrics, UCLA Mattel Children's Hospital, David Geffen School of Medicine, Los Angeles, CA, USA.

Objective: To investigate spatial correlation between interictal HFOs and neuroimaging abnormalities, and to determine if complete removal of prospectively identified interictal HFOs correlates with post-surgical seizure-freedom.

Methods: Interictal fast ripples (FRs: 250-500 Hz) in 19 consecutive children with pharmacoresistant focal epilepsy who underwent extra-operative electrocorticography (ECoG) recording were prospectively analyzed. The interictal FRs were sampled at 2000 Hz and were visually identified during 10 min of slow wave sleep. Interictal FRs, MRI and FDG-PET were delineated on patient-specific reconstructed three-dimensional brain MRI.

Results: Interictal FRs were observed in all patients except one. Thirteen out of 18 patients (72%) exhibited FRs beyond the extent of neuroimaging abnormalities. Fifteen of 19 children underwent resective surgery, and survival analysis with log-rank test demonstrated that complete resection of cortical sites showing interictal FRs correlated with longer post-operative seizure-freedom (p < 0.01). Complete resection of seizure onset zones (SOZ) also correlated with longer post-operative seizure-freedom (p = 0.01), yet complete resection of neuroimaging abnormalities did not (p = 0.43).

Conclusions: Prospective visual analysis of interictal FRs was feasible, and it seemed to accurately localize epileptogenic zones.

Significance: Topological extent of epileptogenic region may exceed what is discernible by multimodal neuroimaging.
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http://dx.doi.org/10.1016/j.clinph.2019.08.026DOI Listing
November 2019

Possible precision medicine implications from genetic testing using combined detection of sequence and intragenic copy number variants in a large cohort with childhood epilepsy.

Epilepsia Open 2019 Sep 1;4(3):397-408. Epub 2019 Jul 1.

Invitae San Francisco California.

Objective: Molecular genetic etiologies in epilepsy have become better understood in recent years, creating important opportunities for precision medicine. Building on these advances, detailed studies of the complexities and outcomes of genetic testing for epilepsy can provide useful insights that inform and refine diagnostic approaches and illuminate the potential for precision medicine in epilepsy.

Methods: We used a multi-gene next-generation sequencing (NGS) panel with simultaneous sequence and exonic copy number variant detection to investigate up to 183 epilepsy-related genes in 9769 individuals. Clinical variant interpretation was performed using a semi-quantitative scoring system based on existing professional practice guidelines.

Results: Molecular genetic testing provided a diagnosis in 14.9%-24.4% of individuals with epilepsy, depending on the NGS panel used. More than half of these diagnoses were in children younger than 5 years. Notably, the testing had possible precision medicine implications in 33% of individuals who received definitive diagnostic results. Only 30 genes provided 80% of molecular diagnoses. While most clinically significant findings were single-nucleotide variants, ~15% were other types that are often challenging to detect with traditional methods. In addition to clinically significant variants, there were many others that initially had uncertain significance; reclassification of 1612 such variants with parental testing or other evidence contributed to 18.5% of diagnostic results overall and 6.1% of results with precision medicine implications.

Significance: Using an NGS gene panel with key high-yield genes and robust analytic sensitivity as a first-tier test early in the diagnostic process, especially for children younger than 5 years, can possibly enable precision medicine approaches in a significant number of individuals with epilepsy.
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http://dx.doi.org/10.1002/epi4.12348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698688PMC
September 2019

Crystal Growth and Magnetic Properties of Topological Nodal-Line Semimetal GdSbTe with Antiferromagnetic Spin Ordering.

Inorg Chem 2019 Sep 15;58(17):11730-11737. Epub 2019 Aug 15.

Center for Condensed Matter Sciences , National Taiwan University , Taipei 10617 , Taiwan.

We report crystal growth, AC and DC magnetic susceptibilities [(, )], magnetization [(, )], and heat capacity [(, )] measurement results of GdSbTe single crystal. GdSbTe is isostructural to the confirmed nonmagnetic nodal-line semimetal ZrSiS of noncentrosymmetric tetragonal crystal structure in space group 4/ (No. 129), but it shows additional long-range antiferromagnetic spin ordering for the Gd spins of = / below T. Both χ(, ) and (, ) measurements confirm the existence of a long-range antiferromagnetic (AFM) spin ordering of Gd spins below ∼ 12 K, and an additional spin reorientation/recovery (sr) behavior is identified from the change of on-site spin anisotropy between ∼ 7 and ∼ 4 K. The anisotropic magnetic susceptibilities of χ(, ) below clearly demonstrate that the AFM long-range spin ordering of GdSbTe has an easy axis parallel to the ab-plane direction. The field- and orientation-dependent magnetization of (, ) at 2 K shows two plateaus to indicate the spin-flop transition for || near ∼2.1 T and a metamagnetic state near ∼5.9 T having ∼/ of the fully polarized magnetization by the applied field. The heat capacity measurement results yield Sommerfeld coefficient of γ ∼ 7.6(4) mJ/mol K and θ ∼ 195(2) K being less than half of that for the nonmagnetic ZrSiS. A three-dimensional (3D) AFM spin structure is supported by the calculations for Gd having magnetic moment of 7.1 μ and the calculated AFM band structure indicates that GdSbTe is a semimetal with bare density of states (0.36 states/eV fu) at the Fermi level, which is 10 times smaller than the measured one to suggest strong spin-fluctuation.
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http://dx.doi.org/10.1021/acs.inorgchem.9b01698DOI Listing
September 2019

Very-High-Dose Prednisolone Before ACTH for Treatment of Infantile Spasms: Evaluation of a Standardized Protocol.

Pediatr Neurol 2019 10 28;99:16-22. Epub 2019 Jun 28.

Division of Pediatric Neurology, David Geffen School of Medicine and UCLA Mattel Children's Hospital, Los Angeles, California. Electronic address:

Background: There is ongoing debate regarding the comparative effectiveness of adrenocorticotropic hormone and prednisolone in the treatment of infantile spasms. With a large cohort and extended follow-up, we set out to evaluate a protocol in which adrenocorticotropic hormone is reserved for prednisolone nonresponders.

Methods: The following standardized hormonal therapy protocol was adopted. Patients initially receive prednisolone (8 mg/kg/day [maximum 60 mg/day], divided in three daily doses for 14 days). Prednisolone responders taper it over 14 days, whereas prednisolone nonresponders immediately transition to natural adrenocorticotropic hormone (150 U/m/day, divided in two daily doses for 14 days). We evaluated short-term response, defined as video-electroenecphaloagraphy-confirmed resolution of both epileptic spasms and hypsarrhythmia on day 14, without relapse for 28 additional days. We then evaluated long-term relapse and calculated the rates of sustained response at six, 12, and 18 months.

Results: We identified 102 children with infantile spasms who were treated with prednisolone. Prior exposure to hormonal therapy and vigabatrin was observed among 12% and 35% of patients, respectively. Sixty (59%) patients responded to prednisolone, and 13 (33%) prednisolone nonresponders then responded to adrenocorticotropic hormone. Cumulative response to prednisolone and adrenocorticotropic hormone (if needed) was higher among treatment-naive patients (84%) than among patients with prior exposure to first-line treatment (51%), with P < 0.001. Relapse was relatively common among all subgroups.

Conclusion: Short-term response to prednisolone was favorable and higher among treatment-naive patients. These data suggest that prednisolone is a reasonable approach to initial therapy and that adrenocorticotropic hormone exhibits substantial efficacy after prednisolone failure.
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http://dx.doi.org/10.1016/j.pediatrneurol.2019.06.012DOI Listing
October 2019

Heavy Mediator at Quantum Dot/Graphene Heterojunction for Efficient Charge Carrier Transfer: Alternative Approach for High-Performance Optoelectronic Devices.

ACS Appl Mater Interfaces 2019 Jul 12;11(29):26518-26527. Epub 2019 Jul 12.

Advanced Research Centre for Green Materials Science and Technology , National Taiwan University , Taipei , Taiwan.

Two-dimensional (2D) material nanocomposites have emerged as a material system for discovering new physical phenomena and developing novel devices. However, because of the low density of states of most two-dimensional materials such as graphene, the heterostructure of nanocomposites suffers from an enhanced depletion region, which can greatly reduce the efficiency of the charge carrier transfer and deteriorate the device performance. To circumvent this difficulty, here we propose an alternative approach by inserting a second 2D mediator with a heavy effective mass having a large density of states in-between the heterojunction of 2D nanocomposites. The mediator can effectively reduce the depletion region and form a type-II band alignment, which can speed up the dissociation of electron-hole pairs and enhance charge carrier transfer. To illustrate the principle, we demonstrate a novel stretchable photodetector based on the combination of graphene/ReS/perovskite quantum dots. Two-dimensional ReS acts as a mediator in-between highly absorbing perovskite quantum dots and a high-mobility graphene channel and a thiol-based linker between the ReS and the perovskite. It is found that the optical sensitivity can be enhanced by 22 times. This enhancement was ascribed to the improvement of the charge transfer efficiency as evidenced by optical spectroscopy measurements. The produced photosensors are capable of reaching the highest reported value of photoresponsivity (>10 A W) and detectivity compared to previously studied stretchable devices. Mechanical robustness with tolerable strain up to 100% and excellent stability make our device ideal for future wearable electronics.
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http://dx.doi.org/10.1021/acsami.9b08294DOI Listing
July 2019

Sn-Doping Enhanced Ultrahigh Mobility InSnSe Phototransistor.

ACS Appl Mater Interfaces 2019 Jul 28;11(27):24269-24278. Epub 2019 Jun 28.

Physics Division , National Center for Theoretical Sciences , Hsinchu 30013 , Taiwan.

Two-dimensional ternary materials are attracting widespread interest because of the additional degree of freedom available to tailor the material property for a specific application. An InSnSe phototransistor possessing tunable ultrahigh mobility by Sn-doping engineering is demonstrated in this study. A striking feature of InSnSe flakes is the reduction in the oxide phase compared to undoped InSe, which is validated by spectroscopic analyses. Moreover, first-principles density functional calculations performed for the InSnSe crystal system reveal the same effective mass when doped with Sn atoms. Hence, because of an increased lifetime owing to the enhanced crystal quality, the carriers in InSnSe have higher mobility than in InSe. The internally boosted electrical properties of InSnSe exhibit ultrahigh mobility of 2560 ± 240 cm V s by suppressing the interfacial traps with substrate modification and channel encapsulation. As a phototransistor, the ultrathin InSnSe flakes are highly sensitive with a detectivity of 10 Jones. It possesses a large photoresponsivity and photogain ( = 40 V) as high as 3 × 10 A W and 0.5 × 10, respectively. The obtained results outperform all previously reported performances of InSe-based devices. Thus, the doping-engineered InSnSe-layered semiconductor finds a potential application in optoelectronics and meets the demand for faster electronic technology.
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http://dx.doi.org/10.1021/acsami.9b06433DOI Listing
July 2019

A chitosan grafted mesoporous carbon aerogel for ultra-sensitive voltammetric determination of isoniazid.

Mikrochim Acta 2019 06 11;186(7):419. Epub 2019 Jun 11.

Institute of Physics, Academia Sinica, Taipei, 10617, Taiwan.

A screen-printed carbon electrode (SPCE) was modified with chitosan (Chit) supported on carbon aerogel (CA) to obtain an electrochemical sensor for the tuberculosis drug isoniazid (INZ). The interconnected mesoporous structure of Chit/CA provides a large surface area (S = 461 m g) and good porosity (V = 0.69 cm g). Besides, the modified SPCE displayed enhanced electrocatalytic activity due to the presence of numerous active sites (such as >C=O, -NH-, -NH, -OH). Figures of merit include (a) a typical working voltage of 0.28 V (vs. Ag/AgCl), (b) high sensitivity (8.09 μA μM cm), (c) a wide linear response to INZ (0.01-115 μM) and (d) a low detection limit (8 nM). The modified electrode has successfully been applied to the determination of INZ in spiked serum and urine, and recoveries ranged from 97.8 to 99.8%. Graphical abstract Schematic illustration of preparation and applications of a nanocomposite consisting of chitosan (Chit; CS) supported on carbon aerogel (CA) for electrochemical detection of isoniazid.
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http://dx.doi.org/10.1007/s00604-019-3533-3DOI Listing
June 2019

Photodriven Dipole Reordering: Key to Carrier Separation in Metalorganic Halide Perovskites.

ACS Nano 2019 Apr 27;13(4):4402-4409. Epub 2019 Mar 27.

Peter Grünberg Institut, Forschungszentrum Jülich GmbH , 52425 Jülich , Germany.

Photodriven dipole reordering of the intercalated organic molecules in halide perovskites has been suggested to be a critical degree of freedom, potentially affecting physical properties, device performance, and stability of hybrid perovskite-based optoelectronic devices. However, thus far a direct atomically resolved dipole mapping under device operation condition, that is, illumination, is lacking. Here, we map simultaneously the molecule dipole orientation pattern and the electrostatic potential with atomic resolution using photoexcited cross-sectional scanning tunneling microscopy and spectroscopy. Our experimental observations demonstrate that a photodriven molecule dipole reordering, initiated by a photoexcited separation of electron-hole pairs in spatially displaced orbitals, leads to a fundamental reshaping of the potential landscape in halide perovskites, creating separate one-dimensional transport channels for holes and electrons. We anticipate that analogous light-induced polarization order transitions occur in bulk and are at the origin of the extraordinary efficiencies of organometal halide perovskite-based solar cells as well as could reconcile apparently contradictory materials' properties.
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http://dx.doi.org/10.1021/acsnano.8b09645DOI Listing
April 2019

Melanotan-II reverses autistic features in a maternal immune activation mouse model of autism.

PLoS One 2019 10;14(1):e0210389. Epub 2019 Jan 10.

Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impaired social interactions, difficulty with communication, and repetitive behavior patterns. In humans affected by ASD, there is a male pre-disposition towards the condition with a male to female ratio of 4:1. In part due to the complex etiology of ASD including genetic and environmental interplay, there are currently no available medical therapies to improve the social deficits of ASD. Studies in rodent models and humans have shown promising therapeutic effects of oxytocin in modulating social adaptation. One pharmacological approach to stimulating oxytocinergic activity is the melanocortin receptor 4 agonist Melanotan-II (MT-II). Notably the effects of oxytocin on environmental rodent autism models has not been investigated to date. We used a maternal immune activation (MIA) mouse model of autism to assess the therapeutic potential of MT-II on autism-like features in adult male mice. The male MIA mice exhibited autism-like features including impaired social behavioral metrics, diminished vocal communication, and increased repetitive behaviors. Continuous administration of MT-II to male MIA mice over a seven-day course resulted in rescue of social behavioral metrics. Normal background C57 male mice treated with MT-II showed no significant alteration in social behavioral metrics. Additionally, there was no change in anxiety-like or repetitive behaviors following MT-II treatment of normal C57 mice, though there was significant weight loss following subacute treatment. These data demonstrate MT-II as an effective agent for improving autism-like behavioral deficits in the adult male MIA mouse model of autism.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210389PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328175PMC
October 2019

Successful use of pure cannabidiol for the treatment of super-refractory status epilepticus.

Epilepsy Behav Case Rep 2018 17;10:141-144. Epub 2018 Jul 17.

Department of Pediatrics (Division of Neurology), David Geffen School of Medicine and UCLA Mattel Children's Hospital, Los Angeles, CA, USA.

We present the case of a child with long-standing, super-refractory status epilepticus (SRSE) who manifested prompt and complete resolution of SRSE upon exposure to pure cannabidiol. SRSE emerged in the context of remote suspected encephalitis with previously well-controlled epilepsy. We discuss the extent to which response may be specifically attributed to cannabidiol, with consideration and discussion of multiple potential drug-drug interactions. Based on this case, we propose that adjunctive cannabidiol be considered in the treatment of SRSE.
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http://dx.doi.org/10.1016/j.ebcr.2018.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306515PMC
July 2018

Interrater reliability in visual identification of interictal high-frequency oscillations on electrocorticography and scalp EEG.

Epilepsia Open 2018 Dec 2;3(Suppl Suppl 2):127-132. Epub 2018 Nov 2.

Division of Pediatric Neurology UCLA Mattel Children's Hospital David Geffen School of Medicine Los Angeles California U.S.A.

High-frequency oscillations (HFOs), including ripples (Rs) and fast ripples (FRs), are promising biomarkers of epileptogenesis, but their clinical utility is limited by the lack of a standardized approach to identification. We set out to determine whether electroencephalographers experienced in HFO analysis can reliably identify and quantify interictal HFOs. Two blinded raters independently reviewed 10 intraoperative electrocorticography (ECoG) samples from epilepsy surgery cases, and 10 scalp EEG samples from epilepsy monitoring unit evaluations. HFOs were visually marked using bandpass filters (R, 80-250 Hz; FR, 250-500 Hz) with a sampling frequency of 2,000 Hz. There was agreement as to the presence or absence of epileptiform discharges (EDs), Rs, and FRs, in 17, 18, and 18 cases, respectively. Interrater reliability (IRR) was favorable with κ = 0.70, 0.80, and 0.80, respectively, and similar for ECoG and scalp electroencephalography (EEG). Furthermore, interclass correlation for rates of Rs (0.99, 95% confidence interval [CI] 0.96-0.99) and FRs (0.77, 95% CI 0.41-0.91) were superior in comparison to EDs (0.37, 95% CI -0.60 to 0.75). Our data suggest that HFO identification and quantification are reliable among experienced electroencephalographers. Our findings support the reliability of utilizing HFO data in both research and clinical arenas.
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http://dx.doi.org/10.1002/epi4.12266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293061PMC
December 2018

Optical signatures of Dirac nodal lines in NbAs.

Proc Natl Acad Sci U S A 2019 01 17;116(4):1168-1173. Epub 2018 Dec 17.

Department of Physics, Columbia University, New York, NY 10027.

Using polarized optical and magneto-optical spectroscopy, we have demonstrated universal aspects of electrodynamics associated with Dirac nodal lines that are found in several classes of unconventional intermetallic compounds. We investigated anisotropic electrodynamics of [Formula: see text] where the spin-orbit coupling (SOC) triggers energy gaps along the nodal lines. These gaps manifest as sharp steps in the optical conductivity spectra [Formula: see text] This behavior is followed by the linear power-law scaling of [Formula: see text] at higher frequencies, consistent with our theoretical analysis for dispersive Dirac nodal lines. Magneto-optics data affirm the dominant role of nodal lines in the electrodynamics of [Formula: see text].
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http://dx.doi.org/10.1073/pnas.1809631115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347680PMC
January 2019

Intrinsic Carrier Transport of Phase-Pure Homologous 2D Organolead Halide Hybrid Perovskite Single Crystals.

Small 2018 Dec 14;14(52):e1803763. Epub 2018 Nov 14.

Department of Materials Science and Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, 10617, Taiwan.

This work reveals the intrinsic carrier transport behavior of 2D organolead halide perovskites based on phase-pure homologous (n = 1, 2, and 3) Ruddelsden-Popper perovskite (RPP) (BA) (MA) Pb I single crystals. The 2D perovskite field effect transistors with high-quality exfoliated 2D perovskite bulk crystals are fabricated, and characteristic output and transfer curves are measured from individual single-crystal flakes with various n values under different temperatures. Unipolar n-type transport dominated the electrical properties of all these 2D RPP single crystals. The transport behavior of the 2D organolead halide hybrid perovskites exhibits a strong dependence on the n value and the mobility substantially increases as the ratio of the number of inorganic perovskite slabs per organic spacer increases. By extracting the effect of contact resistances, the corrected mobility values for n = 1, 2, and 3 are 2 × 10 , 8.3 × 10 , and 1.25 cm V s at 77 K, respectively. Furthermore, by combining temperature-dependent electrical transport and optical measurements, it is found that the origin of the carrier mobility dependence on the phase transition for 2D organolead halide perovskites is very different from that of their 3D counterparts. Our findings offer insight into fundamental carrier transport behavior of 2D organic-inorganic hybrid perovskites based on phase-pure homologous single crystals.
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http://dx.doi.org/10.1002/smll.201803763DOI Listing
December 2018