A nanobiosensing method based on force measurement of antibody-antigen interaction for direct detection of enterovirus 71 by the chemically modified atomic force microscopic probe.

Hand, Foot and mouth disease (HFMD) is a common disease with high infectivity for children, and enterovirus 71 (EV71) is one of the main pathogens to cause the type of illness. Therefore, the aim of this study was to propose a rapid and effective technique for detecting EV71 directly based on the mechanism of biological intermolecular force by using atomic force microscopy (AFM). At first, we coated EV71 particles on the mica surface and made the EV71 antibodies (anti-EV71) fixed on the AFM tip by means of several chemical procedures. Then, AFM chemically modified tip was applied to measure the unbinding forces between EV71 and anti-EV71 by contact mode. Finally, by using AFM imaging calculating software, the EV71 particle size (mean±SD) was 31.36±3.87 nm (n = 200) and this result was concordance with previous literature. Besides, the force (mean±SD) between EV71 antigen and antibody complex was 336.9±64.7 pN. The force (mean±SD) between anti-EV71 and non-specific specimens was 47.1±15.1 pN and was significantly smaller (P < 0.05). Apparently, the results show that we can precisely identify EV71 infection among the samples by measuring the force magnitude and observing the occurrence of EV71/anti-EV71 unbinding events. Therefore, the combination of AFM system and the chemically modified tip has the potential to be a rapid and effective method for detecting EV71 directly.

Engineering light outcoupling in 2D materials.

When light is incident on 2D transition metal dichalcogenides (TMDCs), it engages in multiple reflections within underlying substrates, producing interferences that lead to enhancement or attenuation of the incoming and outgoing strength of light. Here, we report a simple method to engineer the light outcoupling in semiconducting TMDCs by modulating their dielectric surroundings. We show that by modulating the thicknesses of underlying substrates and capping layers, the interference caused by substrate can significantly enhance the light absorption and emission of WSe2, resulting in a ∼11 times increase in Raman signal and a ∼30 times increase in the photoluminescence (PL) intensity of WSe2. On the basis of the interference model, we also propose a strategy to control the photonic and optoelectronic properties of thin-layer WSe2. This work demonstrates the utilization of outcoupling engineering in 2D materials and offers a new route toward the realization of novel optoelectronic devices, such as 2D LEDs and solar cells.

The effects of narrow-band middle infrared radiation in enhancing the antitumor activity of paclitaxel.

Paclitaxel is used as an adjuvant to enhance the effectiveness of ionization radiation therapy; however, high-energy radiation often damages the healthy cells surrounding cancer cells. Low-energy, middle-infrared radiation (MIR) has been shown to prevent tissue damage, and recent studies have begun combining MIR with paclitaxel. However, the cytotoxic effects of this treatment combination remain unclear, and the mechanism underlying its effects on HeLa cells has yet to be elucidated. This study investigated the effectiveness of treating HeLa human cervical cancer cells with a combination of paclitaxel for 48 h in conjunction with narrow-band MIR from 3.0 to 5.0 µm. This combined treatment significantly inhibited the growth of HeLa cells. Specifically, results from Annexin V-FITC/PI apoptosis detection and cell mitochondrial membrane potential analyses revealed an increase in apoptotic cell death and a collapse of mitochondrial membrane potential. One possible mechanism underlying cellular apoptosis is an increase in oxidative stress. These preliminary findings provide evidence to support the combination of narrow-band MIR with paclitaxel as an alternative approach in the treatment of human cervical cancer.

Quantitative proteomics reveals middle infrared radiation-interfered networks in breast cancer cells.

Breast cancer is one of the leading cancer-related causes of death worldwide. Treatment of triple-negative breast cancer (TNBC) is complex and challenging, especially when metastasis has developed. In this study, we applied infrared radiation as an alternative approach for the treatment of TNBC. We used middle infrared (MIR) with a wavelength range of 3-5 µm to irradiate breast cancer cells. MIR significantly inhibited cell proliferation in several breast cancer cells but did not affect the growth of normal breast epithelial cells. We performed iTRAQ-coupled LC-MS/MS analysis to investigate the MIR-triggered molecular mechanisms in breast cancer cells. A total of 1749 proteins were identified, quantified, and subjected to functional enrichment analysis. From the constructed functionally enriched network, we confirmed that MIR caused G2/M cell cycle arrest, remodeled the microtubule network to an astral pole arrangement, altered the actin filament formation and focal adhesion molecule localization, and reduced cell migration activity and invasion ability. Our results reveal the coordinative effects of MIR-regulated physiological responses in concentrated networks, demonstrating the potential implementation of infrared radiation in breast cancer therapy.

Immobilization of Piromyces rhizinflata ß-glucanase on poly(dimethylsiloxane) and Si wafer and prediction of optimum reaction for enzyme activity.

EglA, a ß-1,4-glucanase isolated from the ruminal fungus Piromyces rhizinflata, shows promise in a wide range of industrial applications because of its broad substrate specificity. In this study, EglA was immobilized on different supporting materials including poly(dimethylsiloxane) (PDMS), Si wafer, textured Si wafer, and indium tin oxide-coated (ITO-coated) glass. The binding abilities of PDMS and Si wafer toward EglA were significantly higher than those of the other supporting materials. The optimized temperature and pH conditions for EglA immobilized on PDMS and on Si wafer were further determined by a response surface methodology (RSM) combined with a central composite design (CCD). The results indicated that the optimum pH and temperature values as well as the specific ß-glucanase activity of EglA on PDMS were higher than those of free-form EglA. In addition, EglA immobilized on PDMS could be reused up to six times with detectable enzyme activity, while the enzyme activity of Eg1A on Si wafer was undetectable after three cycles of enzyme reaction. The results demonstrate that PDMS is an attractive supporting material for EglA immobilization and could be developed into an enzyme chip or enzyme tube for potential industrial applications.

Periodic anti-ring back reflectors for hydrogenated amorphous silicon thin-film solar cells.

Large and periodic anti-ring arrays are fabricated by using a monolayer of polymer/nanosphere hybrid technique and applied as back reflectors in substrate-type hydrogenated amorphous silicon (a-Si:H) thin-film solar cells. The structure of each anti-ring comprises a nanodome centered inside a nanohole. The excitation of Bloch wave surface plasmon polaritons is observed in the Ag-coated anti-ring arrays. The nanodomes of the anti-ring arrays turn out to enhance large-angle light scattering and increase the effective optical path in the solar cell. The resulting efficiency of an ultrathin a-Si:H (thickness: 150 nm) solar cell is enhanced by 39% compared to that with a flat back reflector and by 13% compared to that with a nanohole back reflector.

Plasmonic ITO-free polymer solar cell.

The aluminum and sliver multilayered nano-grating structure is fabricated by laser interference lithography and the intervals between nanoslits is filled with modified PEDOT:PSS. The grating structured transparent electrode functions as the anti-reflection layer which not only decreases the reflected light but also increases the absorption of the active layer. The performances of P3HT:PC61BM solar cells are studied experimentally and theoretically in detail. The field intensities of the transverse magnetic (TM) and transverse electrical (TE) waves distributed in the active layer are simulated by rigorous coupled wave analysis (RCWA). The power conversion efficiency of the plasmonic ITO-free polymer solar cell can reach 3.64% which is higher than ITO based polymer solar cell with efficiency of 3.45%.

Design and fabrication of birefringent nano-grating structure for circularly polarized light emission.

Three different nano-grating structures are designed as phase retarders that can transform linearly polarized light to circularly polarized emission for the wavelengths of 488 nm, 532 nm and 632.8 nm, respectively. Gold based nano-grating structures with various periods are fabricated by utilizing laser interference lithography. The ellipticity of all circularly polarized emission can reach around 90% such that the structure has great potential in the applications of three-dimensional (3D) display. The effects of the slit width and metal thickness modulations are simulated by rigorous coupled wave analysis (RCWA) method. Besides, the field intensity and phase of the transmitted TM and TE waves are also simulated to understand their polarization characteristics.

Localized shape resonance on silver film perforated by H-shaped and more complex shaped hole arrays.

The experimental results of light transmission through periodic array of H-shaped hole and more complicated hole which is a combination of multiple U shape are demonstrated. The observations indicate that the localized shape resonance in the longest resonant length of unfolded U-shaped part of the hole always appears. However, localized modes resonant in smaller U-shaped length don't always appear. Localized mode with non-U-shaped resonant path cannot be seen in our sample. In addition, localized mode with different order and resonant path can be excited by different polarized light.

Detection of nighttime melatonin level in Chinese Original Quiet Sitting.

BACKGROUND/PURPOSE: Some research has shown that melatonin levels increase after meditation practices, but other research has shown that they do not. In our previous functional magnetic resonance imaging study, we found positive activation of the pineal body during Chinese Original Quiet Sitting (COQS). To find other supporting evidence for pineal activation, the aim of this study was to evaluate the effect of COQS on nighttime melatonin levels. METHODS: Twenty subjects (11 women and 9 men, aged 29-64 years) who had regularly practiced daily meditation for 5-24 years participated in this study. All subjects served alternately as participants in the mediation and control groups. COQS was adopted in this study. Tests were performed during two nighttime sessions. Saliva was sampled at 0, 10, 20, 30, 45, 60 and 90 minutes after COQS and tested for level of melatonin. Time period effect analysis and mixed effect model analysis were preceded by paired t test analysis. RESULTS: In the meditation group (n = 20), the mean level of melatonin was significantly higher than the baseline level at various times post-meditation (p < 0.001). Within the control group (n = 20), the mean level of melatonin at various times was not significantly different compared with baseline (p>0.05). These results suggested that the melatonin level was statistically elevated in the meditation group and almost unchanged in the control group after nighttime meditation. The urine serotonin levels detected by measuring 5-hydroxy-indole-3-acetic acid levels were also studied, but no detectable difference between the groups was found. CONCLUSION: Our results support the hypothesis that meditation might elevate the nighttime salivary melatonin levels. It suggests that COQS can be used as a psychophysiological stimulus to increase endogenous secretion of melatonin, which in turn, might contribute to an improved sense of well-being.

Characteristics of Harmonic Indexes of the Arterial Blood Pressure Waveform in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is an important public health issue worldwide. T2DM correlates with cardiovascular disease. Arterial stiffness is also a key factor that can be thought of as a surrogate marker. Nevertheless, it was unclear which harmonic indexes of blood pressure waveforms (BPWs) from subjects' radial artery pulses would be affected by T2DM. Therefore, the objective of this study was to investigate whether and how harmonic indexes can be used to discriminate hemodynamic differences between patients with T2DM and non-T2DM. This helps us to build objective results no matter who conducts the examination instead of pulse diagnosis in traditional way. We enrolled T2DM and non-T2DM patients as experimental and control groups, respectively, from the Department of Family Medicine in the National Taiwan University Hospital and the Department of Internal Medicine in Taipei's Veterans General Hospital from December 2017 to January 2019. ANSWatch® Model TS-0411 was used to capture the BPWs. Amplitude proportions (Cn values) were calculated from harmonics 1-10 of the BPW using fast Fourier transform. Thirty-two T2DM and 15 non-T2DM patients were enrolled. T2DM patients had significant differences in C1 (p = 0.031) and C5 (p = 0.041). The study suggests that analyzing the harmonic characteristics of non-invasively measured BPW of radial artery may be a potential and easy-to-perform approach to discriminate T2DM-induced hemodynamic changes.

Effect of Wood's anomalies on the profile of extraordinary transmission spectra through metal periodic arrays of rectangular subwavelength holes with different aspect ratio.

The extraordinary transmission through silver film perforated with rectangular hole array with different aspect ratio was investigated. It was found that when the aspect ratio exceeded 7, the propagating surface plasmon polaritons (SPPs) transformed to localized resonance mode. The role of the Wood's anomaly on the shape of the transmission spectrum is investigated. By designing the rectangular hole arrays in a rectangular lattice, the Wood's anomaly can be shifted far apart from the transmission peak, the real localized resonance peak wavelength was identified and fitted well with the theoretical calculation using a simplified transmission-line model.

Characteristics of a waveguide mode in a trilayer Ag/SiO(2)/Au plasmonic thermal emitter.

A suitably designed trilayer Ag/SiO(2)/Au thermal emitter can be used as the narrow bandwidth infrared light source. The thermal radiation generated in the SiO(2) layer resonates between the two metal films and results in not only the Ag/SiO(2) surface plasmon polaritons but also the waveguide mode (WM) in the Ag/SiO(2)/Au structure owing to the thick SiO(2) layer. This study investigated the influence of dielectric thickness on energy dispersion relations and derived the theoretical dispersion relation, which fit well with experimental results. This WM light source can be applied in the area of gas sensing and probing the response of the animal cells and plants to infrared radiation.

Enhanced early immune response of leptospiral outer membrane protein LipL32 stimulated by narrow band mid-infrared exposure.

Previous studies revealed significant impact on cancer cell by mid-infrared (MIR) radiation. However, the effects of narrow band MIR on immune reaction and infectious disease are still unknown. In this study, an enhanced innate immune response was observed through the interaction between Leptospiral outer membrane protein (LipL32) and toll-like receptor 2 (TLR2). Thereafter, human kidney proximal tubular cells (HK-2 cells) initiated a serial reaction of enhanced MCP-1 production. The 6 µm narrow bandwidth light source emitted by waveguide thermal emitter (WTE) was applied to induce carbonyl group (CO bond) stretching vibration during the stage of antigen-receptor complex formation. The amount of MCP-1 gene expression had 2.5 folds increase after narrow band MIR illumination comparing to non-MIR illumination at low dose LipL32 condition. Besides, both ELISA and confocal microscopy results also revealed that the chemokine concentration increased significantly after narrow band MIR illumination either at low or high concentration of LipL32. Furthermore, a specific phenomenon that narrow band MIR can amplify the signal of weak immune response by enhancing sensitivity of the interaction between antigen and receptor was observed. This study exhibits clear evidence that the narrow band MIR exposure can modulate the early immune response of infectious disease and play a potential role to develop host-directed therapy in the future.

Current Enhancement and Bipolar Current Modulation of Top-Gate Transistors Based on Monolayer MoS2 on Three-Layer W xMo1- xS2.

We demonstrated the top-gate transistors composed of monolayer MoS2 grown on three-layer alloys Mo xW1- xS2 prepared by sequential sulfurization of predeposited transition metal films. The elemental mapping of the alloy indicates a uniform distribution of both cations Mo and W in the grown samples. Surprisingly, we find that the drain current of transistors could be enhanced by 2 orders of magnitude as the composition of Mo increases, whereas the gate-controlled current modulation turns bipolar and ultimately vanishes. These features might originate from the formation of in-gap defect states, with modest activation energy for transport and moderate hopping probability for current conduction, or a reduced electronic band gap of the conducting channel because of strain.

Facilitating tumor spheroid-based bioassays and in vitro blood vessel modeling via bioinspired self-formation microstructure devices.

Non-planar microstructure-based tissue culture devices have emerged as powerful tools to mimic in vivo physiological microenvironments in a wide range of medical applications. Here we report a spontaneous aqueous molding approach - inspired by Stenocara gracilipes beetles - to rapidly fabricate non-planar microstructure devices for facilitating tissue-based bioassays. The device fabrication is determined from the self-assembled liquid morphology, which is induced by condensation or guided by surface tension. Through experiments and modeling, we reveal that the molding mainly comprises two typical circular and striped domains, highlighting versatile applications for bioengineering. In addition, the molding characteristic is dependent on the geometry of the patterned wetting surfaces, the working volume of the liquid, and the interaction between the liquid and the substrate. The theoretical model, based on the geometry of the patterned liquid, is highly consistent with experimental data. We also demonstrate that our approach can facilitate the culturing of tumor spheroids incorporated with biomimic nano-cilia, rapid high-throughput drug screening, tumor spheroid migration assay, and in vitro modeling of blood vessels. Remarkably, the delivery of multiple concentrations of drugs and their associate mixtures (a total of 25 test spots in one device) can be carried out simultaneously within seconds. Taken together, these insights may offer new opportunities to tailor non-planar microstructures, and our proposed methodology can be applicable for the emerging needs in tumor cell biology and tissue engineering.

Reflection and emission properties of an infrared emitter.

The reflection and emission properties of an infrared emitter, which is a plasmonic multilayer structure consisting of a relief metallic grating, a waveguide layer, and a metallic substrate are investigated both experimentally and theoretically. A localized surface plasmon polariton (SPP) mode which is angular-independent in almost the full range of incident angles is observed. The thermal emission of this structure is also measured. It is found that the emission peak coincides with the angular-independent localized SPP mode. In addition, the emission spectrum of the plasmonic emitter can be predicted by investigating the reflectance spectrum.

Graphene/h-BN Heterostructures for Vertical Architecture of RRAM Design.

The development of RRAM is one of the mainstreams for next generation non-volatile memories to replace the conventional charge-based flash memory. More importantly, the simpler structure of RRAM makes it feasible to be integrated into a passive crossbar array for high-density memory applications. By stacking up the crossbar arrays, the ultra-high density of 3D horizontal RRAM (3D-HRAM) can be realized. However, 3D-HRAM requires critical lithography and other process for every stacked layer, and this fabrication cost overhead increases linearly with the number of stacks. Here, it is demonstrated that the 2D material-based vertical RRAM structure composed of graphene plane electrode/multilayer h-BN insulating dielectric stacked layers, AlOx/TiOx resistive switching layer and ITO pillar electrode exhibits reliable device performance including forming-free, low power consumption (Pset = ~2 µW and Preset = ~0.2 µW), and large memory window (>300). The scanning transmission electron microscopy indicates that the thickness of multilayer h-BN is around 2 nm. Due to the ultrathin-insulating dielectric and naturally high thermal conductivity characteristics of h-BN, the vertical structure combining the graphene plane electrode with multilayer h-BN insulating dielectric can pave the way toward a new area of ultra high-density memory integration in the future.

Dual-functional Memory and Threshold Resistive Switching Based on the Push-Pull Mechanism of Oxygen Ions.

The combination of nonvolatile memory switching and volatile threshold switching functions of transition metal oxides in crossbar memory arrays is of great potential for replacing charge-based flash memory in very-large-scale integration. Here, we show that the resistive switching material structure, (amorphous TiOx)/(Ag nanoparticles)/(polycrystalline TiOx), fabricated on the textured-FTO substrate with ITO as the top electrode exhibits both the memory switching and threshold switching functions. When the device is used for resistive switching, it is forming-free for resistive memory applications with low operation voltage (<± 1 V) and self-compliance to current up to 50 µA. When it is used for threshold switching, the low threshold current is beneficial for improving the device selectivity. The variation of oxygen distribution measured by energy dispersive X-ray spectroscopy and scanning transmission electron microscopy indicates the formation or rupture of conducting filaments in the device at different resistance states. It is therefore suggested that the push and pull actions of oxygen ions in the amorphous TiOx and polycrystalline TiOx films during the voltage sweep account for the memory switching and threshold switching properties in the device.

Low-level light therapy potentiates NPe6-mediated photodynamic therapy in a human osteosarcoma cell line via increased ATP.

BACKGROUND: Low-level light therapy (LLLT) is used to stimulate healing, reduce pain and inflammation, and preserve tissue from dying. LLLT has been shown to protect cells in culture from dying after various cytotoxic insults, and LLLT is known to increase the cellular ATP content. Previous studies have demonstrated that maintaining a sufficiently high ATP level is necessary for the efficient induction and execution of apoptosis steps after photodynamic therapy (PDT). METHODS: We asked whether LLLT would protect cells from cytotoxicity due to PDT, or conversely whether LLLT would enhance the efficacy of PDT mediated by mono-l-aspartyl chlorin(e6) (NPe6). Increased ATP could lead to enhanced cell uptake of NPe6 by the energy dependent process of endocytosis, and also to more efficient apoptosis. In this study, human osteosarcoma cell line MG-63 was subjected to 1.5J/cm(2) of 810nm near infrared radiation (NIR) followed by addition of 10µM NPe6 and after 2h incubation by 1.5J/cm(2) of 652nm red light for PDT. RESULTS: PDT combined with LLLT led to higher cell death and increased intracellular reactive oxygen species compared to PDT alone. The uptake of NPe6 was moderately increased by LLLT, and cellular ATP was increased. The mitochondrial respiratory chain inhibitor antimycin A abrogated the LLLT-induced increase in cytotoxicity. CONCLUSIONS: Taken together, these results demonstrate that LLLT potentiates NPe6-mediated PDT via increased ATP synthesis and is a potentially promising strategy that could be applied in clinical PDT.