Identifying potential breath biomarkers for early diagnosis of papillary thyroid cancer based on solid-phase microextraction gas chromatography-high resolution mass spectrometry with metabolomics.

INTRODUCTION: Thyroid cancer incidence rate has increased substantially worldwide in recent years. Fine needle aspiration biopsy (FNAB) is currently the golden standard of thyroid cancer diagnosis, which however, is invasive and costly. In contrast, breath analysis is a non-invasive, safe and simple sampling method combined with a promising metabolomics approach, which is suitable for early cancer diagnosis in high volume population. OBJECTIVES: This study aims to achieve a more comprehensive and definitive exhaled breath metabolism profile in papillary thyroid cancer patients (PTCs). METHODS: We studied both end-tidal and mixed expiratory breath, solid-phase microextraction gas chromatography coupled with high resolution mass spectrometry (SPME-GC-HRMS) was used to analyze the breath samples. Multivariate combined univariate analysis was applied to identify potential breath biomarkers. RESULTS: The biomarkers identified in end-tidal and mixed expiratory breath mainly included alkanes, olefins, enols, enones, esters, aromatic compounds, and fluorine and chlorine containing organic compounds. The area under the curve (AUC) values of combined biomarkers were 0.974 (sensitivity: 96.1%, specificity: 90.2%) and 0.909 (sensitivity: 98.0%, specificity: 74.5%), respectively, for the end-tidal and mixed expiratory breath, indicating of reliability of the sampling and analysis method CONCLUSION: This work not only successfully established a standard metabolomic approach for early diagnosis of PTC, but also revealed the necessity of using both the two breath types for comprehensive analysis of the biomarkers.

Ultra-broadband TM-pass polarizer based on anisotropic metamaterials in lithium niobate on an insulator.

An ultra-broadband TM-pass polarizer is designed, fabricated, and experimentally demonstrated based on subwavelength grating (SWG) metamaterials in a lithium niobate on an insulator (LNOI) platform. According to our simulation, the designed device is predicted to work at a 220 nm wavelength range from 1460 to 1680 nm, covering the S-, C-, L-, U-bands of optical fiber communication. By depositing and subsequently etching a silicon nitride thin film atop the LNOI chip, the SWG structures are formed successfully by using complementary metal-oxide semiconductor (CMOS)-compatible fabrication processes. The measured results show a high polarization extinction ratio larger than 20 dB and a relatively low insertion loss below 2.5 dB over a 130 nm wavelength range from 1500 to 1630 nm, mainly limited by the operation bandwidth of our laser source.

Observing C-N bond formation in plasma: a case study of benzene and dinitrogen coupling via an arylnitrenium ion intermediate.

Directly fixing dinitrogen into value-added organics is one of the core issues, and yet a long-standing challenge, in chemical synthesis. In earlier discrete studies, direct amination of benzene with N2 has been achieved via non-thermal plasma-liquid reaction. Nonetheless, the reaction mechanism thereof remains elusive and the amination product was non-selective primarily including aniline and diphenylamine. Herein, non-thermal plasma reaction in combination with on-line mass spectrometry was employed to probe the reaction pathway by on-line detection of the transient intermediate and the stable amination product. The long-lived atomic nitrogen ions N+(3P) as well as the arylnitrenium ions' intermediacy were shown to play a pivotal role in the amination process, and the product distribution was affected by an external hydrogen source and likely dependent on the competing hydrogen abstraction reaction and intersystem crossing of the initially generated triplet state arylnitrenium ions. The mechanistic investigation in this work has implications for plasma-based nitrogen conversion into organics, but also has broader relevance for understanding the C-N coupling by other means directly with N2.

T-Shaped Aptamer-Based LSPR Biosensor Using Ω-Shaped Fiber Optic for Rapid Detection of SARS-CoV-2.

SARS-CoV-2, especially the variant strains, is rapidly spreading around the world. Rapid detection methods for the virus are crucial for controlling the COVID-19 epidemic. Herein, a localized surface plasmonic resonance (LSPR) biosensor based on Ω-shaped fiber optic (Ω-FO) was developed for dual assays of SARS-CoV-2 monitoring. Due to its strong ability to control the orientation and density, a new T-shaped aptamer exhibits enhanced binding affinity toward N proteins. After being combined on the fiber optic surface, the T-shaped aptamer sensitively captured N proteins of SARS-CoV-2 for a direct assay. Further, core-shell structured gold/silver nanoparticles functionalized with a T-shaped aptamer (apt-Ag@AuNPs) can amplify the signal of N protein detection for a sandwich assay. The real-time analytical feature of the dual assays endows time-dependent sensitivity enhancement behavior, which provides a guideline to save analytical time. With those characteristics, the LSPR biosensor has been successfully used to rapidly identify 39 healthy volunteers and 39 COVID-19 patients infected with the ancestral or variant SARS-CoV-2. With the help of simple pretreatment, we obtain a true negative rate of 100% and a true positive rate of 92.3% with a short analysis time of 45 min using the direct assay. Further, the LSPR biosensor could also broaden the detection application range to the surface of cold-chain foods using a sandwich assay. Thus, the LSPR biosensor based on Ω-FO was demonstrated to have broad application potential to detect SARS-CoV-2 rapidly.

Ridge resonators with compact guided mode coupling.

Ridge resonators are a recently introduced integrated photonic circuit element based on bound states in the continuum (BICs) which can produce a single, sharp resonance over a broad wavelength range with high extinction ratio. However, to excite these resonators, a broad beam of laterally unbound slab mode is required, resulting in a large device footprint, which is not attractive for integrated photonic circuits. In this contribution, we propose and numerically validate a guided-mode waveguide structure that can be analogue to the BIC-based ridge resonators. Our simulations show that the proposed guided-mode waveguide structure can produce resonances with similar characteristics, yet with a significantly reduced footprint. Furthermore, we investigate the influence of the resonator's dimensions on the bandwidth of the resonance, demonstrating that resonances with Q-factors from low to very high (> 10000) are feasible. We believe that the reduced footprint and ability to design filters systematically make the guided-mode waveguide resonators an attractive photonic circuit component with particular value for foundry fabricated silicon photonic circuits.

Integrated lithium niobate optical mode (de)interleaver based on an asymmetric Y-junction.

Lithium niobate on insulator (LNOI) platforms promise unique advantages in realizing high-speed, large-capacity, and large-scale photonic integrated circuits (PICs) by leveraging lithium niobate's attractive material properties, which include electro-optic and nonlinear optic properties, low material loss, and a wide transparency window. Optical mode interleavers can increase the functionality of future PICs in LNOI by enabling optical mode division multiplexing (MDM) systems, allowing variable mode assignment while maintaining high channel utilization and capacity. In this Letter, we experimentally demonstrate an optical mode interleaver based on an asymmetric Y-junction on the LNOI platform, which exhibits an insertion loss of below 0.46 dB and modal cross talk of below -13.0 dB over a wavelength range of 1500-1600 nm. The demonstrated mode interleaver will be an attractive circuit component in future high-speed and large-capacity PICs due to its simple structure, scalability, and capacity for efficient and flexible mode manipulation on the LNOI platform.

Integrated lithium niobate polarization beam splitter based on a photonic-crystal-assisted multimode interference coupler.

Lithium niobate on insulator (LNOI) is a promising platform for high-speed photonic integrated circuits (PICs) that are used for communication systems due to the excellent electro-optic properties of lithium niobate (LN). In such circuits, the high-speed electro-optical modulators and switches need to be integrated with passive circuit components that are used for routing the optical signals. Polarization beam splitters (PBSs) are one of the fundamental passive circuit components for high-speed PICs that can be used to (de)multiplex two orthogonal polarization optical modes, enabling on-chip polarization division multiplexing (PDM) systems, which are suitable for enhancing the data capacity of PICs. In this Letter, we design and experimentally demonstrate a high-performance PBS constructed by a photonic crystal (PC)-assisted multimode interference (MMI) coupler. The measured polarization extinction ratio (ER) of the fabricated device is 15 dB in the wavelength range from 1525 to 1565 nm, which makes them suitable for the high-speed and large data capacity PICs required for future communication systems.

Arbitrary access to optical carriers in silicon photonic mode/wavelength hybrid division multiplexing circuits.

The manipulation of optical modes directly in a multimode waveguide without affecting the transmission of undesired signal carriers is of significance to realize a flexible and simple structured optical network-on-chip. In this Letter, an arbitrary optical mode and wavelength carrier access scheme is proposed based on a series of multimode microring resonators and one multimode bus waveguide with constant width. As a proof-of-concept, a three-mode (de)multiplexing device is designed, fabricated, and experimentally demonstrated. A new, to the best of our knowledge, phase-matching idea is employed to keep the bus waveguide width constant. The mode coupling regions and transmission regions of the microring resonators are designed carefully to selectively couple and transmit different optical modes. The extinction ratio of the microring resonators is larger than 21.0 dB. The mode and wavelength cross-talk for directly (de)multiplexing are less than -12.8 dB and -19.0 dB, respectively. It would be a good candidate for future large-scale multidimensional optical networks.

Wnt/ß-Catenin Signaling Pathway Is Strongly Implicated in Cadmium-Induced Developmental Neurotoxicity and Neuroinflammation: Clues from Zebrafish Neurobehavior and In Vivo Neuroimaging.

Cadmium (Cd) is a toxic heavy metal and worldwide environmental pollutant which seriously threatens human health and ecosystems. It is easy to be adsorbed and deposited in organisms, exerting adverse effects on various organs including the brain. In a very recent study, making full use of a zebrafish model in both high-throughput behavioral tracking and live neuroimaging, we explored the potential developmental neurotoxicity of Cd2+ at environmentally relevant levels and identified multiple connections between Cd2+ exposure and neurodevelopmental disorders as well as microglia-mediated neuroinflammation, whereas the underlying neurotoxic mechanisms remained unclear. The canonical Wnt/ß-catenin signaling pathway plays crucial roles in many biological processes including neurodevelopment, cell survival, and cell cycle regulation, as well as microglial activation, thereby potentially presenting one of the key targets of Cd2+ neurotoxicity. Therefore, in this follow-up study, we investigated the implication of the Wnt/ß-catenin signaling pathway in Cd2+-induced developmental disorders and neuroinflammation and revealed that environmental Cd2+ exposure significantly affected the expression of key factors in the zebrafish Wnt/ß-catenin signaling pathway. In addition, pharmacological intervention of this pathway via TWS119, which can increase the protein level of ß-catenin and act as a classical activator of the Wnt signaling pathway, could significantly repress the Cd2+-induced cell cycle arrest and apoptosis, thereby attenuating the inhibitory effects of Cd2+ on the early development, behavior, and activity, as well as neurodevelopment of zebrafish larvae to a certain degree. Furthermore, activation and proliferation of microglia, as well as the altered expression profiles of genes associated with neuroimmune homeostasis triggered by Cd2+ exposure could also be significantly alleviated by the activation of the Wnt/ß-catenin signaling pathway. Thus, this study provided novel insights into the cellular and molecular mechanisms of Cd2+ toxicity on the vertebrate central nervous system (CNS), which might be helpful in developing pharmacotherapies to mitigate the neurological disorders resulting from exposure to Cd2+ and many other environmental heavy metals.

Direct Amination of Benzene with Molecular Nitrogen Enabled by Plasma-Liquid Interactions.

Nitrogen fixation is industrially realized by mass production of ammonia, the principal intermediate nitrogen source for N-containing organic molecules. Instead, direct C-N bond formation from dinitrogen (N2 ) is of great interest but remains a challenge. Here, by virtue of unique plasma-liquid interactions, we developed an environmentally benign one-pot approach to directly couple benzene and N2 , two naturally abundant yet chemically inert molecules, into value-added arylamines. Under the optimal conditions, an amination yield of 45 % was rapidly achieved, far better than the reported benzene amination efficiency using ammonia. A tentative reaction mechanism was proposed involving the long-lived N2 (A3 Σ u + ) and N2 + species, as evidenced by the key intermediates detected. With a deeper mechanistic understanding and by further optimizing the plasma reactor, the realization of cost-effective electrical amination of benzene with N2 could become reality.

Self-extending DNA-Mediated Isothermal Amplification System and Its Biosensing Applications.

Signal amplification is critical to achieving sensitive biosensing, but complex strategies often bring problems like system instability, false positive, or narrow target spectrum. Here, a self-extending DNA-mediated isothermal amplification (SEIA) system with simple reaction components is introduced to achieve rapid, robust, and significant signal amplification. In SEIA, based on spontaneous refolding of specific DNA domains and using the previous generation product as a template, a DNA strand can extend continuously in an approximate exponential growth pattern, which was accurately predicted by our formula and well supported by AFM results. Based on a set of proof-of-concept experiments, it was proved that the SEIA system can output different signals and flexibly integrate various functional nucleic acids, which makes it suitable for different scenarios and realizes broad-spectrum target detection. Taking into account the advantages of simplicity, flexibility, and efficiency, the SEIA system as an independent signal amplification module will enrich the toolbox of biosensing design.

Integrated non-blocking optical router harnessing wavelength- and mode-selective property for photonic networks-on-chip.

In this paper, we propose and demonstrate a 4×4 non-blocking optical router utilizing 8 mode (de)multiplexers and a 4×4 microring-based grid network, which can passively assign signals carried by optical wavelength and mode channels from an arbitrary input port to corresponding output ports without additional switch time, realizing the non-blocking property. The proposed device is fabricated on a silicon-on-insulator platform using the standard Complementary Metal-Oxide-Semiconductor (CMOS) fabrication processes. The insertion loss is lower than 5.7 dB including the loss of the auxiliary mode (de)multiplexers (AMUXs), while the crosstalk is lower than -15.6 dB for all routing states. Moreover, the transmission spectra from the input ports to the next cascading device are also measured to demonstrate the feasibility of further expanding via cascading multiple blocks, with the insertion loss and crosstalk lower than 7.1 dB (including the mode coupling loss of AMUXs) and -16.4 dB, respectively. The 12 Gbps dynamic transmission experiment is demonstrated with clear and open eye diagrams, illustrating the utility of the device. The device has high geometrical symmetry and good scalability, we exhibit all solutions to expand the 4×4 optical router to 8×8 and 16×16 optical routers with the advantages and deficiencies of each solution discussed.

Demonstration of various optical directed logic operations by using an integrated photonic circuit.

Optical directed logic is a novel logic operation scheme that employs electrical signals as operands to control the working states of optical switches to perform the logic operations. In this Letter, we propose and demonstrate an integrated photonic circuit which can implement five different optical logic operations by utilizing two optical modes. The proposed device is fabricated on a silicon-on-insulator substrate by using electron beam lithography and inductively coupled plasma etching processes. The static experimental results show that the fabricated device can implement five different operations correctly-XOR, XNOR, NOR, NOT, and AND-from which we can see that the signal-to-noise ratios are larger than 17.6 dB over the entire C band for all five logic functions. At last, all five logic operations with the speed of 10 Kbps are demonstrated. The proposed device with simple structure, large bandwidth, and versatility would be a promising candidate for information processing in optical mode division multiplexing networks.

High-speed electro-optic modulator based on silicon nitride loaded lithium niobate on an insulator platform.

Electro-optic (EO) modulators, which convert signals from the electrical to optical domain plays a key role in modern optical communication systems. Lithium niobate on insulator (LNOI) technology has emerged as a competitive solution to realize high-performance integrated EO modulators. In this Letter, we design and experimentally demonstrate a Mach-Zehnder interferometer-based modulator on a silicon nitride loaded LNOI platform, which not only takes full advantage of the excellent EO effect of LiNbO3, but also avoids the direct etching of LiNbO3 thin film. The measured half-wave voltage length product of the fabricated modulator is 2.24 V·cm, and the extinction ratio is ∼20dB. Moreover, the 3 dB EO bandwidth is ∼30GHz, while the modulated data rate for on-off key signals can reach up to 80 Gbps.

Trace detection of organophosphorus pesticides in vegetables via enrichment by magnetic zirconia and temperature-assisted ambient micro-fabricated glow discharge plasma desorption ionization mass spectrometry.

In this study, an innovative rapid detection technology for quickly screening and quantifying organophosphorus pesticides (OPPs) in vegetables was developed based on ambient micro-fabricated glow discharge plasma desorption/ionization mass spectrometry (MFGDP-MS), where Fe3O4/ZrO2 synthesized by a one-step coprecipitation was used for enrichment. It can not only effectively enrich OPPs, but can be separated by an external magnetic field, thereby simplifying the traditional steps of centrifugation and cleanup in sample preparation. The introduction of a temperature control system (TCS) can tackle the problem of the low ionization efficiency in MFGDP and expand its application range. Under optimized experimental conditions, the limits of detection (LODs) of the standard solution as low as 0.0068-0.7500 µg L-1 mm-2 were achieved, with relative standard deviations (RSDs) being less than 17.8%. Moreover, vegetable extracts were spiked to evaluate the accuracy of the method, and good recoveries (76.9-123.5%) were obtained. Remarkably, it took no more than 7 minutes from sample preparation to testing, resulting in significantly improved ability of the quantitative detection of plentiful samples.

The development of a wash-free homogeneous immunoassay method for the detection of tetracycline in environmental samples.

Antibiotic residues have become the major source of environmental pollutants. In order to monitor tetracycline (TC) in the environment, we have established a highly sensitive and wash-free homogeneous time-resolved immunoassay. This analytical method was based on a rare earth chelate with excellent fluorescence properties. The cryptate organic ligand had good stability and acted as an antenna for Eu3+ excitation. In a homogeneous system, the Eu3+ cryptate complex was used as a label to bind to antibodies. Under the action of immunoaffinity, fluorescent donors and acceptors were close to each other, which induced the FRET effect to produce proportional fluorescence. Under the optimal parameters, the half-inhibitory concentration (IC50) and limit of detection (LOD, IC10) of TC were 0.4188 ng mL-1 and 0.0106 ng mL-1, respectively. The linear range (IC20-IC80) was 0.0273-9.2645 ng mL-1. With the environmental samples, the recovery rate of TC was 84.3-107.2%, and the standard deviation (RSD) was 4.6-12.9%. The results showed the good sensitivity and reliability of the method. Compared with the traditional ELISA, our method has less background interference, only one step was required without the washing procedure, and the detection result can be obtained by 30 min incubation, which improves the detection efficiency. Because of the characteristics of immunoassays, different pollutants can be monitored by changing the antibodies. This method provides an alternative path for detecting environmental pollutants and has the potential to develop into an on-site detection kit.

An efficient localized catalytic hairpin assembly-based DNA nanomachine for miRNA-21 imaging in living cells.

As an enzyme-free isothermal amplification strategy, catalytic hairpin assembly (CHA) is a very promising method for cell imaging. However, the practical application of CHA on intracellular miRNA imaging is limited by slow kinetics, insufficient amplification efficiency and strong interference in living cells. Herein, a localized catalytic hairpin assembly-based DNA nanomachine (LCHA nanomachine) was developed for the rapid, efficient and reliable fluorescence resonance energy transformation (FRET) imaging of miRNA-21 in living cells. The nanomachine was simply constructed by a one-step self-assembly process of a stator strand, a pair of hairpin probes from CHA and an AS1411 aptamer. Benefiting from the spatial-confinement effect, a pair of hairpin probes with high collision frequency was rapidly and efficiently assembled using miRNA-21 as the catalyst on a stator strand in every nanomachine. Compared with the free-CHA nanomachine, the LCHA nanomachine shortened the reaction time by 4.5-fold for reaching a plateau and significant improved the sensitivity by 7.6-fold for miRNA-21 detection in vitro. Importantly, the nanomachine was successfully applied for miRNA-21 imaging in living cells. With the assistance of an AS1411 aptamer and stator strand, the pair of hairpin probes with the ratio of 1 : 1 synchronously transported into a co-site of the cytoplasm, which ensures efficient imaging of trace miRNA-21. The signal output of the ratio of 6-carboxy-fluorescein (FAM) to tetramethyl rhodamine (TAMRA) intensities guaranteed reliability through avoiding the interference from different amounts of the nanomachine that enters into cells. Notably, the nanomachine can distinguish the miRNA-21 expression level in different kinds of cancer cells. By virtue of the advantages of simplicity, efficiency and reliability, the proposed strategy provides a powerful method for exploring the functions of miRNA and diagnosis of disease.

Effective N2 capture by aryl cations at ambient temperature and pressure.

Here, we show that molecular N2 was efficiently captured by organic arylium cations in a well-defined manner at ambient pressure and temperature, which was monitored by on-line mass spectrometry analysis. A kinetic picture was proposed to disclose the principle of the ion-molecule reaction behavior for exclusive aryldiazonium production. The observation has an implication for direct nitrogen fixation into an organic framework via the intermediacy of such cationic species.

On-chip switchable and reconfigurable optical mode exchange device using cascaded three-waveguide-coupling switches.

Data exchange between different data channels can offer more flexible and advanced functions for many optical networks. In this paper, we propose a switchable and reconfigurable data exchange device for arbitrary two optical mode channels based on three-waveguide-coupling (TWC) switches in mode-division multiplexing (MDM) networks. The working principle of the TWC switches is numerically analyzed using the coupled supermode theory. As a proof of concept, switchable data exchange between arbitrary two mode channels among the first three-order quasi-transverse electric modes is experimentally demonstrated successfully. The insertion losses of the device are less than 5.6 dB, including the coupling loss of the multiplexer and demultiplexer, while the mode crosstalk is less than -13.0 dB for all functions. The proposed device is expected to offer more flexibility to on-chip MDM networks due to its low loss, low crosstalk and good scalability.

On-chip biochemical sensor using wide Gaussian beams in silicon waveguide-integrated plasmonic crystal.

An on-chip biochemical sensor based on two-dimensional waveguide-integrated plasmonic crystal formed by a nanogap tile (NGT) array is realized. By using on-chip optical lenses, an ultra-wide collimated Gaussian beam is launched, coupled with surface plasmonic crystals and collected with relatively low additional insertion loss, allowing a large sensing area. The optical field enhancement and stop-band shift of the NGT device for biochemical sensing are numerically and experimentally demonstrated with sensitivity reaching up to ${\sim}{260}\;{\rm nm/RIU}$∼260nm/RIU. Our sensor is demonstrated with monolayer thiol molecules illustrating that it can be functionalized with this class of molecule which is commonly used with bulk surface plasmon resonance sensors.