Coherently parallel fiber-optic distributed acoustic sensing using dual Kerr soliton microcombs.

Fiber-optic distributed acoustic sensing (DAS) has proven to be a revolutionary technology for the detection of seismic and acoustic waves with ultralarge scale and ultrahigh sensitivity, and is widely used in oil/gas industry and intrusion monitoring. Nowadays, the single-frequency laser source in DAS becomes one of the bottlenecks limiting its advance. Here, we report a dual-comb-based coherently parallel DAS concept, enabling linear superposition of sensing signals scaling with the comb-line number to result in unprecedented sensitivity enhancement, straightforward fading suppression, and high-power Brillouin-free transmission that can extend the detection distance considerably. Leveraging 10-line comb pairs, a world-class detection limit of 560 fε/√Hz@1 kHz with 5 m spatial resolution is achieved. Such a combination of dual-comb metrology and DAS technology may open an era of extremely sensitive DAS at the fε/√Hz level, leading to the creation of next-generation distributed geophones and sonars.

Submonolayer biolasers for ultrasensitive biomarker detection.

Biomarker detection is key to identifying health risks. However, designing sensitive and single-use biosensors for early diagnosis remains a major challenge. Here, we report submonolayer lasers on optical fibers as ultrasensitive and disposable biosensors. Telecom optical fibers serve as distributed optical microcavities with high Q-factor, great repeatability, and ultralow cost, which enables whispering-gallery laser emission to detect biomarkers. It is found that the sensing performance strongly depends on the number of gain molecules. The submonolayer lasers obtained a six-order-of-magnitude improvement in the lower limit of detection (LOD) when compared to saturated monolayer lasers. We further achieve an ultrasensitive immunoassay for a Parkinson's disease biomarker, alpha-synuclein (α-syn), with a lower LOD of 0.32 pM in serum, which is three orders of magnitude lower than the α-syn concentration in the serum of Parkinson's disease patients. Our demonstration of submonolayer biolaser offers great potentials in high-throughput clinical diagnosis with ultimate sensitivity.

A novel intelligent displacement prediction model of karst tunnels.

Karst is a common engineering environment in the process of tunnel construction, which poses a serious threat to the construction and operation, and the theory on calculating the settlement without the assumption of semi-infinite half-space is lack. Meanwhile, due to the limitation of test conditions or field measurement, the settlement of high-speed railway tunnel in Karst region is difficult to control and predict effectively. In this study, a novel intelligent displacement prediction model, following the machine learning (ML) incorporated with the finite difference method, is developed to evaluate the settlement of the tunnel floor. A back propagation neural network (BPNN) algorithm and a random forest (RF) algorithm are used herein, while the Bayesian regularization is applied to improve the BPNN and the Bayesian optimization is adopted for tuning the hyperparameters of RF. The newly proposed model is employed to predict the settlement of Changqingpo tunnel floor, located in the southeast of Yunnan Guizhou Plateau, China. Numerical simulations have been performed on the Changqingpo tunnel in terms of variety of karst size, and locations. Validations of the numerical simulations have been validated by the field data. A data set of 456 samples based on the numerical results is constructed to evaluate the accuracy of models' predictions. The correlation coefficients of the optimum BPNN and BR model in testing set are 0.987 and 0.925, respectively, indicating that the proposed BPNN model has more great potential to predict the settlement of tunnels located in karst areas. The case study of Changqingpo tunnel in karst region has demonstrated capability of the intelligent displacement prediction model to well predict the settlement of tunnel floor in Karst region.

A sequentially bioconjugated optofluidic laser for wash-out-free and rapid biomolecular detection.

Microstructures can improve both sensitivity and assay time in heterogeneous assays (such as ELISA) for biochemical analysis; however, it remains a challenge to perform the essential wash process in those microstructure-based heterogeneous assays. Here, we propose a sequential bioconjugation protocol to solve this problem and demonstrate a new type of fiber optofluidic laser for biosensing. Except for acting as an optical microresonator and a microstructured substrate, the miniaturized hollow optical fiber (HOF) is used as a microfluidic channel for storing and transferring reagents thanks to its capability in length extension. Through the capillary action, different reagents were sequentially withdrawn into the fiber for specific binding and washing purposes. By using the sequentially bioconjugated FOFL, avidin molecules are detected based on competitive binding with a limit of detection of 9.5 pM, ranging from 10 pM to 100 nM. It is demonstrated that a short incubation time of 10 min is good enough to allow the biomolecules to conjugate on the inner surface of the HOF. Owing to its miniaturized size, only 589 nL of liquid is required for incubation, which reduces the sample consumption and cost for each test. This work provides a tool to exploit the potential of microstructured optical fibers in high-performance biosensing.

Temporal changes in laboratory markers of survivors and non-survivors of adult inpatients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2, and outbreaks have occurred worldwide. Laboratory test results are an important basis for clinicians to determine patient condition and formulate treatment plans. METHODS: Fifty-two thousand six hundred forty-four laboratory test results with continuous values of adult inpatients who were diagnosed with COVID-19 and hospitalized in the Fifth Hospital in Wuhan between 16 January 2020 and 18 March 2020 were compiled. The first and last test results were compared between survivors and non-survivors with variance test or Welch test. Laboratory test variables with significant differences were then included in the temporal change analysis. RESULTS: Among 94 laboratory test variables in 82 survivors and 25 non-survivors with COVID-19, white blood cell count, neutrophil count/percentage, mean platelet volume, platelet distribution width, platelet-large cell percentage, hypersensitive C-reactive protein, procalcitonin, D-dimer, fibrin (ogen) degradation product, middle fluorescent reticulocyte percentage, immature reticulocyte fraction, lactate dehydrogenase were significantly increased (P < 0.05), and lymphocyte count/percentage, monocyte percentage, eosinophil percentage, prothrombin activity, low fluorescent reticulocyte percentage, plasma carbon dioxide, total calcium, prealbumin, total protein, albumin, albumin-globulin ratio, cholinesterase, total cholesterol, nonhigh-density/low-density/small-dense-low-density lipoprotein cholesterol were significantly decreased in non-survivors compared with survivors (P < 0.05), in both first and last tests. Prothrombin time, prothrombin international normalized ratio, nucleated red blood cell count/percentage, high fluorescent reticulocyte percentage, plasma uric acid, plasma urea nitrogen, cystatin C, sodium, phosphorus, magnesium, myoglobin, creatine kinase (isoenzymes), aspartate aminotransferase, alkaline phosphatase, glucose, triglyceride were significantly increased (P < 0.05), and eosinophil count, basophil percentage, platelet count, thrombocytocrit, antithrombin III, red blood cell count, haemoglobin, haematocrit, total carbon dioxide, acidity-basicity, actual bicarbonate radical, base excess in the extracellular fluid compartment, estimated glomerular filtration rate, high-density lipoprotein cholesterol, apolipoprotein A1/ B were significantly decreased in non-survivors compared with survivors (P < 0.05), only in the last tests. Temporal changes in 26 variables, such as lymphocyte count/percentage, neutrophil count/percentage, and platelet count, were obviously different between survivors and non-survivors. CONCLUSIONS: By the comprehensive usage of the laboratory markers with different temporal changes, patients with a high risk of COVID-19-associated death or progression from mild to severe disease might be identified, allowing for timely targeted treatment.

Imaging through opacity using a near-infrared low-spatial-coherence fiber light source: publisher's note.

This publisher's note contains corrections to Opt. Lett.45, 3816 (2020)OPLEDP0146-959210.1364/OL.397152.

Tailoring of spatial coherence in a multimode fiber by selectively exciting groups of eigenmodes.

Control of the properties of speckle patterns produced by mutual interference of light waves is important for various applications of multimode optical fibers. It has been shown previously that a high signal-to-noise ratio in a multimode fiber can be achieved by preferential excitation of lower order spatial eigenmodes in optical fiber communication. Here we demonstrate that signal spatial coherence can be tailored by changing relative contributions of the lower and higher order multimode fiber eigenmodes for the research of speckle formation and spatial coherence. It is found that higher order spatial eigenmodes are more conducive to the final speckle formation. The minimum speckle contrast occurs in the lower order spatial eigenmodes dominated regime. This work paves the way for control and manipulation of the spatial coherence of light in a multimode fiber varying from partially coherent or totally incoherent light.

Imaging through opacity using a near-infrared low-spatial-coherence fiber light source.

Memory-effect-based speckle correlation is one of the most practical techniques for imaging through scattering opaque media, where a light source with low spatial coherence and moderate bandwidth plays a pivotal role. Usually, a rapidly rotating diffuser is applied to make the light source spatially decoherent. Here, an all-fiber-based low-spatial-coherence light source is proposed and demonstrated for such speckle-correlated imaging. The illumination structure is greatly simplified, the lightening efficiency is enhanced, and the wavelength is extended to the near-infrared band, which is favorable for a larger memory effect range and deeper penetrating depth through opacity. Moreover, the proposed local illumination method can identify the orientation of the object, which has not been revealed by former methods. This work would facilitate the research in optical biomedical imaging and broaden the applications of multimode random fiber lasers.

Mass production of thin-walled hollow optical fibers enables disposable optofluidic laser immunosensors.

Disposable biosensors are of great importance in disease diagnosis due to their inherent merits of no cross-contamination and ease of use. Optofluidic laser (OFL) sensors are a new category of sensitive biosensors; however, it is challenging to cost-effectively mass-produce them to achieve disposability. Here, we report a disposable optofluidic laser immunosensor based on thin-walled hollow optical fibers (HOFs). Using a fiber draw tower, the fabrication parameters, including drawing speed and gas flow rate, are explored, and the HOF geometry is precisely controlled, which allows identical laser microring resonators to be distributed along the fibers. The disposable OFL immunosensor detects the protein concentration in the HOF through a wash-free immunoassay. Enabled by the disposable sensors, the statistical characteristics of 80 tests for each concentration greatly reduces the bioassay uncertainty. A low coefficient of variation (CV) of 3.3% confirms the high reproducibility of the disposable HOF-OFL sensors, and the mean of the normal distribution of the logarithmic OFL intensity serves as the sensing output. A limit of detection of 11 nM within a short assay time of 15 min is achieved. These disposable immunosensors possess the advantages of low cost, high reproducibility, fast assay, and low-volume consumption of sample and reagents. We believe that this work will inspire disposable optofluidics through the mass production of multifunctional microstructured optical fibers.

High-power low spatial coherence random fiber laser.

A high-power multi-transverse modes random fiber laser (RFL) is investigated by combining a master oscillator power-amplifier (MOPA) configuration with a segment of extra-large mode area step-index multimode fiber (MMF). Spatial coherence of the high-power multi-transverse modes RFL has been analyzed, which shows that speckle contrast is reduced dramatically with the output power increasing. In this way, considerably low speckle contrast of ~0.01 is achieved under high laser power of ~56 W, which are the records for multi-transverse modes RFLs in both spatial coherence and output power. This work paves a way to develop high-power RFLs with very low spatial coherence for wide-range speckle-free imaging and free-space communication applications.

Turbidimetric inhibition immunoassay revisited to enhance its sensitivity via an optofluidic laser.

Turbidimetric inhibition immunoassay (TIIA) is a classic immunodiagnostic method that has been extensively used for biomarker detection. However, the low sensitivity of this technique hinders its applications in the early diagnosis of diseases. Here, a new concept, optofluidic laser TIIA (OFL-TIIA), is proposed and demonstrated for sensitive protein detection. In contrast to the immunoreaction in traditional TIIA, in which the single-pass laser loss is detected, the immunoreaction in the OFL-TIIA method takes place in a laser cavity, which considerably increases the loss induced by antigen-antibody complexes (AACs) via the amplification effect of the laser. A commercial IgG TIIA kit was selected as a demonstrative model to characterize the performance of OFL-TIIA. A wide dynamic range of five orders of magnitude with an exceptional limit of detection (LOD) (1.8 × 10-10 g/L) was achieved. OFL-TIIA is a fast, sensitive, and low-cost immunoassay with a simple homogeneous and wash-free process and low-volume sample consumption, thus providing a new detection platform for disease diagnostics.

Polaritonic manipulation based on the spin-selective optical Stark effect in the WS2 and Tamm plasmon hybrid structure.

Exciton-polaritons have shown great potential as a low-energy consumption and robust solid-state platform for photoelectronics integration and quantum information applications. Here, an all-optical method that uses the spin-sensitive optical Stark effect is proposed to manipulate exciton-polaritons for functional polaritonic operations. We use a Tamm plasmon and WS2 hybrid structure with a patterned transverse potential to form the channeled bright state of polaritons. An optical Stark pulse causes perturbation of the polaritonic potential, so as to control the tunneling of polaritons between isolated channels. Polaritonic operations such as switching, splitting and routing were proposed through properly setting of the optical Stark pulse (e.g., pulse width). In addition, spin-sensitive manipulation of the polaritons was proposed taking advantage of the valley-selective excitonic energy shifting induced by the polarized optical Stark pulse. These basic operations together with time-space programming of the optical Stark pulses would pave a way of routing and addressing of polaritons for future optoelectronic integration and networking.

Decoherence of fiber supercontinuum light source for speckle-free imaging.

Speckle-free imaging is attractive in laser-illuminated imaging systems. The evolutionary process of supercontinuum decoherence in extra-large mode area step-index multimode fiber is analyzed to provide high-quality broadband light source for speckle-free imaging. It is found that spectral bandwidth, number of spatial transverse modes, and decoherence among different modes all greatly contribute to speckle reduction. The combination of supercontinuum and extra-large mode area step-index multimode fiber can considerably increase the efficiency of decoherence process for speckle-free imaging. This work may enrich the research of speckle-free imaging and also provide guidance on speckle-free imaging using fiber-optics based light source.

Distributed fibre optofluidic laser for chip-scale arrayed biochemical sensing.

Optofluidic lasers (OFLs) are an emerging technological platform for biochemical sensing, and their good performance especially high sensitivity has been demonstrated. However, high-throughput detection with an OFL remains a major challenge due to the lack of reproducible optical microcavities. Here, we introduce the concept of a distributed fibre optofluidic laser (DFOFL) and demonstrate its potential for high-throughput sensing applications. Due to the precise fibre geometry control via fibre drawing, a series of identical optical microcavities uniformly distributed along a hollow optical fibre (HOF) can be achieved to obtain a one-dimensional (1D) DFOFL. An enzymatic reaction catalysed by horseradish peroxidase (HRP) can be monitored over time, and the HRP concentration is detected by DFOFL-based arrayed colorimetric detection. Experimentally, five-channel detection in parallel with imaging has been demonstrated. Theoretically, spatial multiplexing of hundreds of channels is achievable with DFOFL-based detection. The DFOFL wavelength is tuned over hundreds of nanometers by optimizing the dye concentration or reconfiguring the liquid gain materials. Extending this concept to a two-dimensional (2D) chip through wavelength multiplexing can further enhance its multi-functionality, including multi-sample detection and spectral analysis. This work opens the door to high-throughput biochemical sensing.

Biofilm Formation Plays a Role in the Formation of Multidrug-Resistant Escherichia coli Toward Nutrients in Microcosm Experiments.

In this study, microcosms were established to determine the effect of nitrogen (N) and phosphorus (P) on the multidrug resistance and biofilm-forming abilities of Escherichia coli. The expression of biofilm-formation-related genes was detected to establish correlations between genotype and phenotype. Different concentrations of N and P were added to make one control group and four treatment groups. The glass tube method was used to determine biofilm-forming capabilities. Real-time PCR was used to detect the mRNA abundance of six biofilm-formation-related genes in E. coli. No resistant strains were isolated from the control group; meanwhile, multidrug resistance rates were high in the treatment groups. Expression of the biofilm-associated genes luxS, flhD, fliA, motA, and fimH was detected in all treatment groups; however, there was no expression of mqsR. The expression of luxS, flhD, fliA, motA, and fimH significantly correlated with the concentration of N and P, as well as with the appearance and duration of multidrug resistance in different groups. Overall, the results of this study suggest that biofilm-forming ability plays a key role in the formation of multidrug resistance in E. coli after the addition of N and P to a microcosm.

Reproducible fiber optofluidic laser for disposable and array applications.

Disposable sensors are widely used in biomedical detection due to their inherent safety, ease of use and low cost. An optofluidic laser is a sensitive bioassay platform; however, demonstrating its fabrication cheaply and reproducibly enough for disposable use has been challenging. Here, we report a low-cost, reproducible fiber optofluidic laser (FOFL) using a microstructured optical fiber (MOF). The MOF not only supports the whispering gallery modes for lasing but also serves as a microfluidic channel for sampling the liquid gain medium via capillary force. Because of the precise control of its geometry (δ < 0.4%) during the fiber-drawing process, good reproducibility in laser intensity (δ = 6.5%) was demonstrated by changing 10 sections of the MOF. The strong coupling between the in-fiber resonator and gain medium enables a low threshold of 3.2 µJ mm-2. The angular dependence of the laser emission was observed experimentally and analyzed with numerical simulations. An array of the FOFLs was also demonstrated. This technology has great potential for low-cost bioassay applications.

Targeting neuronal nitric oxide synthase by a cell penetrating peptide Tat-LK15/siRNA bioconjugate.

We developed a cell penetrating peptide (CPP) Tat-LK15, as a siRNA carrier to target nNOS. The feasibility, stability, efficiency and selectivity of this peptide-siRNA complex were evaluated in rat neuronal cells. We also compared the new method with conventional siRNA carrier Lipofectamine™. It was found that the CPP Tat-LK15 effectively and specifically delivered nNOS-siRNA into Rat retinal ganglia (RGC-5) cells and silenced the expression of nNOS. The CPP Tat-LK15 can conjugate with siRNA to form stable complex at a ratio of 2:1 (peptide/siRNA, w/w), which maintained stable in serum for as long as 4h. The CPP Tat-LK15 was low-toxicity to cells, as the apoptosis rate of treat cells was not increased significantly when the used peptide lower than 10µg/mL. Moreover, the cellular uptake of nNOS siRNA by Rat Neurons-dorsal spinal cord (RNdsc) cells was also significantly more than naked siRNA by RNdsc cells. The CPP Tat-LK15 was an efficient and stable, and non-cytotoxic siRNA delivery to neurons and effectively silenced the nNOS expression. The CPP Tat-LK15 mediated siRNA delivery was a potential tool to treat neuropathic diseases involving NO or nNOS neurotoxic cascades.

Fiber-Type Random Laser Based on a Cylindrical Waveguide with a Disordered Cladding Layer.

This letter reports a fiber-type random laser (RL) which is made from a capillary coated with a disordered layer at its internal surface and filled with a gain (laser dye) solution in the core region. This fiber-type optical structure, with the disordered layer providing randomly scattered light into the gain region and the cylindrical waveguide providing confinement of light, assists the formation of random lasing modes and enables a flexible and efficient way of making random lasers. We found that the RL is sensitive to laser dye concentration in the core region and there exists a fine exponential relationship between the lasing intensity and particle concentration in the gain solution. The proposed structure could be a fine platform of realizing random lasing and random lasing based sensing.

[Effect and mechanism of miR-206/miR-613 on expression of OATP1B1].

This study was designed to explore the effect and mechanism of miR-206/miR-613 on the expression of OATP1B1 gene. Bioinformatic analysis was used to predict the potential miRNAs target sites in 3'-untranslated region (3'-UTR) of OATP1B1 mRNA. The expression level of miR-206/miR-613 and OATP1B1 mRNA and protein was determined with RT-qPCR and Western blot, respectively. Luciferase assay was used to explore the exact mechanism of the effect of miR-206/miR-613 on the expression of OATP1B1 mRNA and protein. The results showed that the seed sequences of miR-206/miR-613 has perfect complementary with 3'-UTR of OATP1B1 mRNA in terms of sequence specificity. The secondary structure between miR-206/ miR-613 and 3'-UTR of OATP1B1 mRNA was rather stable. The OATP1B1 protein level was down-regulated by 24.7%, 38.8% by overexpression of miR-206/miR-613. The expression was up-regulated by 25%, 38.2% by inhibition of miR-206/miR-613. However, overexpression or inhibition of miR-206/miR-613 had no effect on the expression of OATP1B1 mRNA. The luciferase activity of p MIR/OATP1B1-WT luciferase reporter gene was decreased by 35% and 30% through overexpression of miR-206/miR-613. The expression was increased by 33.1% and 32.5% through inhibition of miR-206/miR-613. When the binding sites in the 3'-UTR of OATP1B1 mRNA complementary with miR-206/miR-613 was mutated, overexpression or inhibition of miR-206/miR-613 had no effect on the luciferase activity. Collectively, miR-206/miR-613 post-transcriptionally regulates the expression of OATP1B1 protein by directly targeting the 3'-UTR of OATP1B1 mRNA.

Novel sensing concept based on optical Tamm plasmon.

This paper proposes a novel concept of refractive index sensing taking advantage of a high-refractive-index-contrast optical Tamm plasmon (OTP) structure, i.e., an air/dielectric alternate-layered distributed Bragg reflector (DBR) coated with metal. In the reflection spectrum of the structure, a dip related to the formation of OTP appears. The wavelength and reflectivity of this dip are sensitive to variation of ambient refractive index, which provides a potential way to realize refractive index sensing with a large measuring range and high sensitivity.