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BACKGROUND: Artificial intelligence (AI) algorithms for the independent assessment of screening mammograms have not been well established in a large screening cohort of Asian women. We compared the performance of screening digital mammography considering breast density, between radiologists and AI standalone detection among Korean women. METHODS: We retrospectively included 89,855 Korean women who underwent their initial screening digital mammography from 2009 to 2020. Breast cancer within 12 months of the screening mammography was the reference standard, according to the National Cancer Registry. Lunit software was used to determine the probability of malignancy scores, with a cutoff of 10% for breast cancer detection. The AI's performance was compared with that of the final Breast Imaging Reporting and Data System category, as recorded by breast radiologists. Breast density was classified into four categories (A-D) based on the radiologist and AI-based assessments. The performance metrics (cancer detection rate [CDR], sensitivity, specificity, positive predictive value [PPV], recall rate, and area under the receiver operating characteristic curve [AUC]) were compared across breast density categories. RESULTS: Mean participant age was 43.5 ± 8.7 years; 143 breast cancer cases were identified within 12 months. The CDRs (1.1/1000 examination) and sensitivity values showed no significant differences between radiologist and AI-based results (69.9% [95% confidence interval [CI], 61.7-77.3] vs. 67.1% [95% CI, 58.8-74.8]). However, the AI algorithm showed better specificity (93.0% [95% CI, 92.9-93.2] vs. 77.6% [95% CI, 61.7-77.9]), PPV (1.5% [95% CI, 1.2-1.9] vs. 0.5% [95% CI, 0.4-0.6]), recall rate (7.1% [95% CI, 6.9-7.2] vs. 22.5% [95% CI, 22.2-22.7]), and AUC values (0.8 [95% CI, 0.76-0.84] vs. 0.74 [95% CI, 0.7-0.78]) (all P < 0.05). Radiologist and AI-based results showed the best performance in the non-dense category; the CDR and sensitivity were higher for radiologists in the heterogeneously dense category (P = 0.059). However, the specificity, PPV, and recall rate consistently favored AI-based results across all categories, including the extremely dense category. CONCLUSIONS: AI-based software showed slightly lower sensitivity, although the difference was not statistically significant. However, it outperformed radiologists in recall rate, specificity, PPV, and AUC, with disparities most prominent in extremely dense breast tissue.
Subject(s)
Artificial Intelligence , Breast Density , Breast Neoplasms , Early Detection of Cancer , Mammography , Radiologists , Humans , Female , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Breast Neoplasms/epidemiology , Mammography/methods , Adult , Middle Aged , Early Detection of Cancer/methods , Retrospective Studies , Republic of Korea/epidemiology , ROC Curve , Breast/diagnostic imaging , Breast/pathology , Algorithms , Mass Screening/methods , Sensitivity and SpecificityABSTRACT
A gate stack that facilitates a high-quality interface and tight electrostatic control is crucial for realizing high-performance and low-power field-effect transistors (FETs). However, when constructing conventional metal-oxide-semiconductor structures with two-dimensional (2D) transition metal dichalcogenide channels, achieving these requirements becomes challenging due to inherent difficulties in obtaining high-quality gate dielectrics through native oxidation or film deposition. Here, a gate-dielectric-less device architecture of van der Waals Schottky gated metal-semiconductor FETs (vdW-SG MESFETs) using a molybdenum disulfide (MoS2) channel and surface-oxidized metal gates such as nickel and copper is reported. Benefiting from the strong SG coupling, these MESFETs operate at remarkably low gate voltages, <0.5 V. Notably, they also exhibit Boltzmann-limited switching behavior featured by a subthreshold swing of ≈60 mV dec-1 and negligible hysteresis. These ideal FET characteristics are attributed to the formation of a Fermi-level (EF) pinning-free gate stack at the Schottky-Mott limit. Furthermore, authors experimentally and theoretically confirm that EF depinning can be achieved by suppressing both metal-induced and disorder-induced gap states at the interface between the monolithic-oxide-gapped metal gate and the MoS2 channel. This work paves a new route for designing high-performance and energy-efficient 2D electronics.
ABSTRACT
Adhesion has attracted great interest in science and engineering especially in the field pertaining to nano-science because every form of physical contact is fundamentally a macroscopic observation of interactions between nano-asperities under the adhesion phenomenon. Despite its importance, no practical adhesion prediction model has been developed due to the complexity of examining contact between nano-asperities. Here, we scrutinized the contact phenomenon and developed a contact model, reflecting the physical sequence in which adhesion develops. For the first time ever, our model analyzes the adhesion force and contact properties, such as separation distance, contact location, actual contact area, and the physical deformation of the asperities, between rough surfaces. Through experiments using atomic force microscopy, we demonstrated a low absolute percentage error of 2.8% and 6.55% between the experimental and derived data for Si-Si and Mo-Mo contacts, respectively, and proved the accuracy and practicality of our model in the analysis of the adhesion phenomenon.
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Bioresorbable neural implants based on emerging classes of biodegradable materials offer a promising solution to the challenges of secondary surgeries for removal of implanted devices required for existing neural implants. In this study, we introduce a fully bioresorbable flexible hybrid opto-electronic system for simultaneous electrophysiological recording and optogenetic stimulation. The flexible and soft device, composed of biodegradable materials, has a direct optical and electrical interface with the curved cerebral cortex surface while exhibiting excellent biocompatibility. Optimized to minimize light transmission losses and photoelectric artifact interference, the device was chronically implanted in the brain of transgenic mice and performed to photo-stimulate the somatosensory area while recording local field potentials. Thus, the presented hybrid neural implant system, comprising biodegradable materials, promises to provide monitoring and therapy modalities for versatile applications in biomedicine.
Subject(s)
Absorbable Implants , Central Nervous System Depressants , Animals , Mice , Optogenetics , Artifacts , Brain , Electronics , Mice, TransgenicABSTRACT
The advanced patterning process is the basis of integration technology to realize the development of next-generation high-speed, low-power consumption devices. Recently, area-selective atomic layer deposition (AS-ALD), which allows the direct deposition of target materials on the desired area using a deposition barrier, has emerged as an alternative patterning process. However, the AS-ALD process remains challenging to use for the improvement of patterning resolution and selectivity. In this study, we report a superlattice-based AS-ALD (SAS-ALD) process using a two-dimensional (2D) MoS2-MoSe2 lateral superlattice as a pre-defining template. We achieved a minimum half pitch size of a sub-10 nm scale for the resulting AS-ALD on the 2D superlattice template by controlling the duration time of chemical vapor deposition (CVD) precursors. SAS-ALD introduces a mechanism that enables selectivity through the adsorption and diffusion processes of ALD precursors, distinctly different from conventional AS-ALD method. This technique facilitates selective deposition even on small pattern sizes and is compatible with the use of highly reactive precursors like trimethyl aluminum. Moreover, it allows for the selective deposition of a variety of materials, including Al2O3, HfO2, Ru, Te, and Sb2Se3.
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Toxic gases have surreptitiously influenced the health and environment of contemporary society with their odorless/colorless characteristics. As a result, a pressing need for reliable and portable gas-sensing devices has continuously increased. However, with their negligence to efficiently microstructure their bulky supportive layer on which the sensing and heating materials are located, previous semiconductor metal-oxide gas sensors have been unable to fully enhance their power efficiency, a critical factor in power-stringent portable devices. Herein, an ultrathin insulation layer with a unique serpentine architecture is proposed for the development of a power-efficient gas sensor, consuming only 2.3 mW with an operating temperature of 300 °C (≈6% of the leading commercial product). Utilizing a mechanically robust serpentine design, this work presents a fully suspended standalone device with a supportive layer thickness of only ≈50 nm. The developed gas sensor shows excellent mechanical durability, operating over 10â¯000 on/off cycles and ≈2 years of life expectancy under continuous operation. The gas sensor detected carbon monoxide concentrations from 30 to 1 ppm with an average response time of ≈15 s and distinguishable sensitivity to 1 ppm (ΔR/R0 = 5%). The mass-producible fabrication and heating efficiency presented here provide an exemplary platform for diverse power-efficient-related devices.
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As semiconductor scaling continues to reach sub-nanometer levels, two-dimensional (2D) semiconductors are emerging as a promising candidate for the post-silicon material. Among these alternatives, Bi2O2Se has risen as an exceptionally promising 2D semiconductor thanks to its excellent electrical properties, attributed to its appropriate bandgap and small effective mass. However, unlike other 2D materials, growth of large-scale Bi2O2Se films with precise layer control is still challenging due to its large surface energy caused by relatively strong interlayer electrostatic interactions. Here, we present the successful growth of a wafer-scale (â¼3 cm) Bi2O2Se film with precise thickness control down to the monolayer level on TiO2-terminated SrTiO3 using metal-organic chemical vapor deposition (MOCVD). Scanning transmission electron microscopy (STEM) analysis confirmed the formation of a [BiTiO4]1- interfacial structure, and density functional theory (DFT) calculations revealed that the formation of [BiTiO4]1- significantly reduced the interfacial energy between Bi2O2Se and SrTiO3, thereby promoting 2D growth. Additionally, spectral responsivity measurements of two-terminal devices confirmed a bandgap increase of up to 1.9 eV in monolayer Bi2O2Se, which is consistent with our DFT calculations. Finally, we demonstrated high-performance Bi2O2Se field-effect transistor (FET) arrays, exhibiting an excellent average electron mobility of 56.29 cm2/(V·s). This process is anticipated to enable wafer-scale applications of 2D Bi2O2Se and facilitate exploration of intriguing physical phenomena in confined 2D systems.
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Trastuzumab is used to treat HER2-amplified metastatic gastric cancer; however, most patients become trastuzumab-resistant within a year. Knowledge of the mechanisms underlying trastuzumab resistance is required to overcome this limitation. Here, we aimed to elucidate this resistance mechanism using four trastuzumab-resistant (TR) cell lines and investigate the efficacy of HER2-targeted therapies to overcome treatment resistance. Each TR cell line had different phenotypic characteristics. Interestingly, HER2 expression remained as high as the parental cell lines in TR cell lines, suggesting that HER2-targeted agents were still useful. As expected, three tyrosine kinase inhibitors (lapatinib, neratinib, and tucatinib) and one antibody-drug conjugate (trastuzumab deruxtecan: T-DXd) exhibited good antitumor effects against TR cell lines. We further investigated the potential biological mechanism of T-DXd. When treated with trastuzumab or T-DXd, HER2 or its downstream signals were disrupted in parental cell lines, but not in TR cell lines. Moreover, T-DXd induced the expression of pH2A.X and cPARP and caused cell cycle arrest in the S or G2-M phase in TR cell lines. T-DXd showed promising antitumor activity in both parental and TR cell lines, suggesting that it is a potential candidate for overcoming trastuzumab resistance.
Subject(s)
Immunoconjugates , Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Receptor, ErbB-2/metabolism , Antibodies, Monoclonal, Humanized/therapeutic use , Drug Resistance, Neoplasm/genetics , Cell Line, Tumor , Cell Proliferation , Trastuzumab/pharmacology , Trastuzumab/therapeutic use , Immunoconjugates/pharmacologyABSTRACT
Numerous wireless optogenetic systems have been reported for practical tether-free optogenetics in freely moving animals. However, most devices rely on battery-powered or coil-powered systems requiring periodic battery replacement or bulky, high-cost charging equipment with delicate antenna design. This leads to spatiotemporal constraints, such as limited experimental duration due to battery life or animals' restricted movement within specific areas to maintain wireless power transmission. In this study, we present a wireless, solar-powered, flexible optoelectronic device for neuromodulation of the complete freely behaving subject. This device provides chronic operation without battery replacement or other external settings including impedance matching technique and radio frequency generators. Our device uses high-efficiency, thin InGaP/GaAs tandem flexible photovoltaics to harvest energy from various light sources, which powers Bluetooth system to facilitate long-term, on-demand use. Observation of sustained locomotion behaviors for a month in mice via secondary motor cortex area stimulation demonstrates the notable capabilities of our device, highlighting its potential for space-free neuromodulating applications.
Subject(s)
Optogenetics , Wireless Technology , Mice , Animals , Optogenetics/methods , Movement , Electric Power SuppliesABSTRACT
PURPOSE: Trastuzumab-containing chemotherapy is the recommended first-line regimen for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer. We evaluated the safety and efficacy of trastuzumab combined with ramucirumab and paclitaxel as second-line treatment for HER2-positive G/GEJ cancer. PATIENTS AND METHODS: Patients with HER2-positive advanced G/GEJ cancer who progressed after first-line treatment with trastuzumab-containing chemotherapy were enrolled from five centers in the Republic of Korea. Patients were administered a 28-day cycle of trastuzumab (once on days 1, 8, 15, and 22: 2 mg/kg followed by 4 mg/kg loading dose), ramucirumab (once on days 1 and 15: 8 mg/kg), and paclitaxel (once on days 1, 8, and 15: dose level 1, 80 mg/m2; or dose level -1, 70 mg/m2). Phase II was conducted with the recommended phase II dose (RP2D). Primary end points were determination of RP2D during phase Ib and investigator-assessed progression-free survival (PFS) in patients treated with RP2D. RESULTS: Dose-limiting toxicity at dose level 1 was not documented during phase Ib, and a full dose combination was selected as the RP2D. Among 50 patients with a median follow-up duration of 27.5 months (95% CI, 17.4 to 37.6), median PFS and overall survival were 7.1 months (95% CI, 4.8 to 9.4) and 13.6 months (95% CI, 9.4 to 17.7), respectively. Objective response rate was 54% (27 of 50, including one complete response), and disease control rate was 96% (48 of 50). Loss of HER2 expression was observed in 34.8% (8 of 23) patients after first-line treatment, and no definite association between HER2 expression and the outcome was revealed. Safety profiles were consistent with previous reports. CONCLUSION: Trastuzumab combined with ramucirumab and paclitaxel showed appreciable efficacy with manageable safety profiles in patients with previously treated HER2-positive G/GEJ cancer.
Subject(s)
Esophageal Neoplasms , Stomach Neoplasms , Humans , Trastuzumab , Paclitaxel , Disease-Free Survival , Receptor, ErbB-2/metabolism , Stomach Neoplasms/drug therapy , Esophagogastric Junction/metabolism , Esophageal Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , RamucirumabABSTRACT
Ultrathin crystalline silicon is widely used as an active material for high-performance, flexible, and stretchable electronics, from simple passive and active components to complex integrated circuits, due to its excellent electrical and mechanical properties. However, in contrast to conventional silicon wafer-based devices, ultrathin crystalline silicon-based electronics require an expensive and rather complicated fabrication process. Although silicon-on-insulator (SOI) wafers are commonly used to obtain a single layer of crystalline silicon, they are costly and difficult to process. Therefore, as an alternative to SOI wafers-based thin layers, here, a simple transfer method is proposed for printing ultrathin multiple crystalline silicon sheets with thicknesses between 300 nm to 13 µm and high areal density (>90%) from a single mother wafer. Theoretically, the silicon nano/micro membrane can be generated until the mother wafer is completely consumed. In addition, the electronic applications of silicon membranes are successfully demonstrated through the fabrication of a flexible solar cell and flexible NMOS transistor arrays.
ABSTRACT
The skin aging process is governed by intrinsic and extrinsic factors causing skin wrinkles, sagging, and loosening. The 1-monoeicosapentaenoin (1-MEST) is a component isolated from Micractinium, a genus of microalgae (Chlorophyta, Trebouxiophyceae). However, the anti-wrinkle effects of 1-MEST are not yet known. This study aimed to evaluate the anti-wrinkle effects of 1-MEST in vitro and in clinical trials. The cytotoxicity of 1-MEST was investigated in vitro using the MTS assay in human epidermal keratinocytes (HEKs). Expression of matrix metalloproteinase (MMP)-1 and MMP-9 was determined by ELISA in HEKs irradiated with UVB after treatment with 1-MEST. A split-face randomized, double-blind, placebo-controlled study was conducted to evaluate the safety and efficacy of 1-MEST. The study evaluated wrinkle parameters and visual assessment, self-efficacy and usability questionnaires, and adverse events. The study showed that the 1-MEST was not cytotoxic in HEKs, suppressed MMP-1 secretion and MMP-9 protein expression in HEKs irradiated with UVB. The wrinkle parameters and mean visual assessment score were significantly decreased in the test group after 12 weeks and differed from the control group. There were no significant differences in efficacy and usability. Adverse effects were also not observed. The 1-MEST showed anti-wrinkle properties to slow down or prevent skin aging.
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With the exponential growth of the semiconductor industry, radiation-hardness has become an indispensable property of memory devices. However, implementation of radiation-hardened semiconductor memory devices inevitably requires various radiation-hardening technologies from the layout level to the system level, and such technologies incur a significant energy overhead. Thus, there is a growing demand for emerging memory devices that are energy-efficient and intrinsically radiation-hard. Here, we report a nanoelectromechanical non-volatile memory (NEM-NVM) with an ultra-low energy consumption and radiation-hardness. To achieve an ultra-low operating energy of less than 10 [Formula: see text], we introduce an out-of-plane electrode configuration and electrothermal erase operation. These approaches enable the NEM-NVM to be programmed with an ultra-low energy of 2.83 [Formula: see text]. Furthermore, due to its mechanically operating mechanisms and radiation-robust structural material, the NEM-NVM retains its superb characteristics without radiation-induced degradation such as increased leakage current, threshold voltage shift, and unintended bit-flip even after 1 Mrad irradiation.
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The trap states and defects near the active region in deep-ultraviolet (DUV) light-emitting diodes (LED) were investigated through wavelength-dependent photocurrent spectroscopy. We observed anomalous photocurrent reversal and its temporal recovery in AlGaN-based DUV LEDs as the wavelength of illuminating light varied from DUV to visible. The wavelength-dependent photocurrent measurements were performed on 265 nm-emitting DUV LEDs under zero-bias conditions. Sharp near-band-edge (~265 nm) absorption was observed in addition to broad (300-800 nm) visible-range absorption peaks in the photocurrent spectrum, while the current direction of these two peaks were opposite to each other. In addition, the current direction of the photocurrent in the visible wavelength range was reversed when a certain forward bias was applied. This bias-induced current reversal displayed a slow recovery time (~6 h) when the applied forward voltage was removed. Furthermore, the recovery time showed strong temperature dependency and was faster as the sample temperature increased. This result can be consistently explained by the presence of hole traps at the electron-blocking layer and the band bending caused by piezoelectric polarization fields. The activation energy of the defect state was calculated to be 279 meV using the temperature dependency of the recovery time.
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Van der Waals (vdW) heterostructures have drawn much interest over the last decade owing to their absence of dangling bonds and their intriguing low-dimensional properties. The emergence of 2D materials has enabled the achievement of significant progress in both the discovery of physical phenomena and the realization of superior devices. In this work, the group IV metal chalcogenide 2D-layered Ge4 Se9 is introduced as a new selection of insulating vdW material. 2D-layered Ge4 Se9 is synthesized with a rectangular shape using the metalcorganic chemical vapor deposition system using a liquid germanium precursor at 240 °C. By stacking the Ge4 Se9 and MoS2 , vdW heterostructure devices are fabricated with a giant memory window of 129 V by sweeping back gate range of ±80 V. The gate-independent decay time reveals that the large hysteresis is induced by the interfacial charge transfer, which originates from the low band offset. Moreover, repeatable conductance changes are observed over the 2250 pulses with low non-linearity values of 0.26 and 0.95 for potentiation and depression curves, respectively. The energy consumption of the MoS2 /Ge4 Se9 device is about 15 fJ for operating energy and the learning accuracy of image classification reaches 88.3%, which further proves the great potential of artificial synapses.
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PURPOSE: Surgeons' skill in the operating room is a major determinant of patient outcomes. Assessment of surgeons' skill is necessary to improve patient outcomes and quality of care through surgical training and coaching. Methods for video-based assessment of surgical skill can provide objective and efficient tools for surgeons. Our work introduces a new method based on attention mechanisms and provides a comprehensive comparative analysis of state-of-the-art methods for video-based assessment of surgical skill in the operating room. METHODS: Using a dataset of 99 videos of capsulorhexis, a critical step in cataract surgery, we evaluated image feature-based methods and two deep learning methods to assess skill using RGB videos. In the first method, we predict instrument tips as keypoints and predict surgical skill using temporal convolutional neural networks. In the second method, we propose a frame-wise encoder (2D convolutional neural network) followed by a temporal model (recurrent neural network), both of which are augmented by visual attention mechanisms. We computed the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and predictive values through fivefold cross-validation. RESULTS: To classify a binary skill label (expert vs. novice), the range of AUC estimates was 0.49 (95% confidence interval; CI = 0.37 to 0.60) to 0.76 (95% CI = 0.66 to 0.85) for image feature-based methods. The sensitivity and specificity were consistently high for none of the methods. For the deep learning methods, the AUC was 0.79 (95% CI = 0.70 to 0.88) using keypoints alone, 0.78 (95% CI = 0.69 to 0.88) and 0.75 (95% CI = 0.65 to 0.85) with and without attention mechanisms, respectively. CONCLUSION: Deep learning methods are necessary for video-based assessment of surgical skill in the operating room. Attention mechanisms improved discrimination ability of the network. Our findings should be evaluated for external validity in other datasets.
Subject(s)
Cataract Extraction , Ophthalmology , Surgeons , Capsulorhexis , Humans , Neural Networks, ComputerABSTRACT
Advances in large-area and high-quality 2D transition metal dichalcogenides (TMDCs) growth are essential for semiconductor applications. Here, the gas-phase alkali metal-assisted metal-organic chemical vapor deposition (GAA-MOCVD) of 2D TMDCs is reported. It is determined that sodium propionate (SP) is an ideal gas-phase alkali-metal additive for nucleation control in the MOCVD of 2D TMDCs. The grain size of MoS2 in the GAA-MOCVD process is larger than that in the conventional MOCVD process. This method can be applied to the growth of various TMDCs (MoS2 , MoSe2 , WSe2 , and WSe2 ) and the generation of large-scale continuous films. Furthermore, the growth behaviors of MoS2 under different SP and oxygen injection time conditions are systematically investigated to determine the effects of SP and oxygen on nucleation control in the GAA-MOCVD process. It is found that the combination of SP and oxygen increases the grain size and nucleation suppression of MoS2 . Thus, the GAA-MOCVD with a precise and controllable supply of a gas-phase alkali metal and oxygen allows achievement of optimum growth conditions that maximizes the grain size of MoS2 . It is expected that GAA-MOCVD can provide a way for batch fabrication of large-scale atomically thin electronic devices based on 2D semiconductors.
ABSTRACT
The capability to finely tailor material thickness with simultaneous atomic precision and non-invasivity would be useful for constructing quantum platforms and post-Moore microelectronics. However, it remains challenging to attain synchronized controls over tailoring selectivity and precision. Here we report a protocol that allows for non-invasive and atomically digital etching of van der Waals transition-metal dichalcogenides through selective alloying via low-temperature thermal diffusion and subsequent wet etching. The mechanism of selective alloying between sacrifice metal atoms and defective or pristine dichalcogenides is analyzed with high-resolution scanning transmission electron microscopy. Also, the non-invasive nature and atomic level precision of our etching technique are corroborated by consistent spectral, crystallographic, and electrical characterization measurements. The low-temperature charge mobility of as-etched MoS2 reaches up to 1200 cm2 V-1s-1, comparable to that of exfoliated pristine counterparts. The entire protocol represents a highly precise and non-invasive tailoring route for material manipulation.
Subject(s)
Nasal Polyps , Rhinitis , Sinusitis , Chronic Disease , Cytokines , Humans , Immunity, Innate , LymphocytesABSTRACT
Two-dimensional (2D) organic-inorganic halide perovskites (OIHPs) with an alternating stacked structure of an organic layer and an inorganic layer draw significant attention for photovoltaics, multiple quantum-well, and passivation of three-dimensional perovskites. Although the low-cost and simple spin-coating process of these materials offers a vast platform to study fundamental properties and help them achieve rapid progress in electronics and optoelectronics, chemical vapor deposition (CVD) growth is also necessary for large-area, epitaxial, selective, and conformal growth. Here, one-step CVD strategies for 2D OIHP growth are proposed, and the growth trends depending on the precursor and substrate conditions are discussed. We report a CVD-grown nontoxic, lead-free 2D tin-OIHP flake to show the system offering a universal route to synthesize perovskite crystals based on arbitrary organic and inorganic components.