Multi-node wearable optical sensor based on microfiber Bragg gratings.

Flexibly wearable sensors are widely applied in health monitoring and personalized therapy. Multiple-node sensing is essential for mastering the health condition holistically. In this work, we report a multi-node wearable optical sensor (MNWOS) based on the cascade of microfiber Bragg gratings (µFBG), which features the reflective operation mode and ultra-compact size, facilitating the functional integration in a flexible substrate pad. The MNWOS can realize multipoint monitoring on physical variables, such as temperature and pressure, in both static and dynamic modes. Furthermore, the eccentric package configuration endows the MNWOS with the discernibility of bending direction in addition to the bending angle sensing. The multi-parameter sensing is realized by solving the sensing matrix that represents different sensitivity regarding the bending and temperature between FBGs. The MNWOS offers great prospect for the development of human-machine interfaces and medical and health detection.

Near-infrared microfiber Bragg grating for sensitive measurement of tension and bending.

Fiber-optic devices working in the visible and near-infrared windows are attracting attention due to the rapid development of biomedicine that involves optics. In this work, we have successfully realized the fabrication of near-infrared microfiber Bragg grating (NIR-µFBG), which was operated at the wavelength of 785 nm, by harnessing the fourth harmonic order of Bragg resonance. The NIR-µFBG provided the maximum sensitivity of axial tension and bending to 211 nm/N and 0.18 nm/deg, respectively. By conferring the considerably lower cross-sensitivity, such as response to temperature or ambient refractive index, the NIR-µFBG can be potentially implemented as the highly sensitive tensile force and curve sensor.

Threshold switching strategy for unambiguous state discrimination of quadrature phase-shift-keying coherent states under thermal noise.

Quantum-enhanced measurement technologies can unambiguously discriminate coherent states with accuracy beyond the classical heterodyne measurement. However, typical quantum-enhanced measurement scheme is vulnerable to the thermal noise, which will change the photon counting statistics of the coherent state. This paper presents a threshold-switching strategy that can discriminate quadrature phase-shift-keying coherent states with performance surpassing the typical quantum-enhanced scheme. In our scheme, photon number resolving detectors are used to switch the value of the threshold, which can mitigate the influence of thermal noise and other imperfections. Simulation results show that our scheme unambiguously discriminates the signal states with higher correct probability and the same error ratio compared with the typical scheme. Besides, this scheme can reduce the error ratio simultaneously for thermal noise N ≤ 0.2. The paper demonstrations that quantum-enhanced measurement with the threshold-switching strategy can adapt to different thermal noises by switching the value of the threshold under situations of different thermal noises and signal states.

Surface-wettable nonenzymatic fiber-optic sensor for selective detection of hydrogen peroxide.

A micro-nanostructure-based surface-modified fiber-optic sensor has been developed herein to selectively detect hydrogen peroxide (H2O2). In our design, phenylboronic ester-modified polymers were used as a modified cladding medium that allows chemo-optic transduction. Sensing is mechanistically based on oxidation and subsequent hydrolysis of the phenylboronic ester-modified polymer, which modulates hydrophobic properties of fiber-optic devices, which was confirmed during characterization of the chemical functional group and hydrophobicity of the active sensing material. This work illustrates a useful strategy of exploiting principles of chemical modifications to design surface-wettable fiber-optic sensing devices for detecting reactive species of broad relevance to biological and environmental analyses.

Third harmonic phase-shifted Bragg grating sensor.

Improving sensitivity is critical for the higher-order harmonic fiber Bragg grating sensors. To this aim, in this work, we have successfully introduced the phase-shift into the third harmonic fiber Bragg grating for tailoring a double-dip spectrum with a high finesse notch. The dual dips showed reversed responses for the intensity regarding the change of the temperature or axial strain, enabling a highly sensitive measuring regime using the intensity contrast between the two dips. Deduced from the sinusoidal responding curves, the highest temperature and the axial strain sensitivity could reach 0.964 dB/°C, and 0.0257 dB/µ ε, three-fold times the other intensity-based fiber sensors. This work may promote the higher-order harmonic gratings into applications for enriching wavelength utilization.

Visualizing nitroreductase activity in living cells and tissues under hypoxia and hepatic inflammation.

Detecting nitroreductase (NTR) activity in hypoxic cells and tissues in situ represents an important step toward accurate delineation of hypoxic disease loci. However, it remains challenging to develop fluorescent probes with the necessary attributes of selectivity, sensitivity, precise targeting and aqueous solubility. Herein, two kinds of fluorescent probes (NNP and cRGD-NNP) built on a 2-nitroimidazole sensing platform were synthesized for the detection of NTR activity in cell and in vivo models of hypoxia. In the presence of NADH, NNP displayed high selectivity for NTR, a strong fluorescence enhancement (108 fold), and a low detection limit (3.6 ng mL-1). Benefiting from the hydrophilic structure and tumor-targeting properties of the cRGD cyclopeptide group, the probe cRGD-NNP efficiently detected NTR activity in MCF cancer cells under hypoxia. In addition, the liposome-encapsulated probe was successfully applied to visualize NTR during liver inflammation in mice.

Compact polarimetric heterodyning DBR fiber laser sensor with high temperature resistance.

We report on a short-cavity polarization beat-frequency distributed Bragg reflector (DBR) fiber laser that can operate in an unprecedentedly wide range of temperatures from -200∘ C to 500°C. The beat-frequency signal inherited by the intrinsic fiber birefringence enables implementation of the laser as an eligible temperature or hydrostatic pressure sensor. Furthermore, type-IIa Bragg reflectors allow the annealing of high temperature on the laser cavity to suppress the phase noise of the lasing signal effectively. This research will guide future attempts to achieve high-precision sensing and high-performance signal generation using polarized beat-frequency DBR fiber lasers in harsh environments.

Sensitivity enhancement of a fiber-based interferometric optofluidic sensor.

Optofluidic sensors, which tightly bridge photonics and micro/nanofluidics, are superior candidates in point-of-care testing. A fiber-based interferometric optofluidic (FIO) sensor can detect molecular biomarkers by fusing an optical microfiber and a microfluidic tube in parallel. Light from the microfiber side coupled to the microtube leads to lateral localized light-fluid evanescent interaction with analytes, facilitating sensitive detection of biomolecules with good stability and excellent portability. The determination of the sensitivity with respect to the interplay between light and fluidics, however, still needs to be understood quantitatively. Here, we theoretically and experimentally investigate the relationship between refractive index (RI) sensitivity and individual geometrical parameters to determine the lateral localized light-fluid evanescent interaction. Theoretical analysis predicted a sensitive maximum, which could be realized by synergically tuning the fiber diameter d and the tube wall thickness t at an abrupt dispersion transition region. As a result, an extremely high RI sensitivity of 1.6×104 nm/RIU (σ=4074 nm/RIU), an order of magnitude higher than our previous results, with detection limit of 3.0×10-6 RIU, is recorded by precisely governing the transverse geometry of the setup. The scientific findings will guide future exploration of both new light-fluid interaction devices and biomedical sensors.

Development of an optical microfiber immunosensor for prostate specific antigen analysis using a high-order-diffraction long period grating.

Fiber-optic biosensors are of great interest to many bio/chemical sensing applications. In this study, we demonstrate a high-order-diffraction long period grating (HOD-LPG) for the detection of prostate specific antigen (PSA). A HOD-LPG with a period number of less than ten and an elongated grating pitch could realize a temperature-insensitive and bending-independent biosensor. The bio-functionalized HOD-LPG was capable of detecting PSA in phosphate buffered saline with concentrations ranging from 5 to 500 ng/ml and exhibited excellent specificity. A limit of detection of 9.9 ng/ml was achieved, which is promising for analysis of the prostate specific antigen.

Label-Free and Reproducible Chemical Sensor Using the Vertical-Fluid-Array Induced Optical Fiber Long Period Grating (VIOLIN).

Fiber optical refractometers have gained a substantial reputation in biological and chemical sensing domain regarding their label-free and remote-operation working mode. However, the practical breakthrough of the fiber optical bio/chemosensor is impeded by a lack of reconfigurability as well as the explicitness of the determination between bulk and surface refractive indices. In this letter, we further implement the highly flexible and reproducible long period grating called "VIOLIN" in chemical sensing area for the demonstration of moving those obstacles. In this configuration, the liquid is not only leveraged as the chemical carrier but also the periodic modulation of the optical fiber to facilitate the resonant signal. The thiol compound that is adsorbed by the fluidic substrate can be transduced to the pure alteration of the bulk refractive index of the liquid, which can be sensitively perceived by the resonant drift. Taking advantage of its freely dismantled feature, the VIOLIN sensor enables flexible reproduction and high throughput detection, yielding a new vision to the fiber optic biochemical sensing field.

[Effect of Xiaoyao San on OVX combined with CUS anxiety and depression model rats based on hippocampal microglia M1 polarization].

To investigate the anti-anxiety and anti-depression effect and mechanism of Xiaoyao San on rats with ovariectomy(OVX) combined with chronic unpredictable stress(CUS) model. The model of perimenopausal depression was established by OVX and CUS; the level of anxiety and depression was evaluated by open field test; the levels of interleukin-1ß(IL-1ß) and interleukin-6(IL-6) mRNA in rat hippocampus were detected by Real-time qPCR; double staining immunofluorescence was used to detect the expression of ionized calcium binding adaptor molecule-1(Iba-1) and inducible nitric oxide synthase(iNOS) in microglia of rat dentate gyrus(DG); Western blot was used to detect the protein expression of Iba-1 and iNOS of microglia in DG region of rat hippocampus. The results showed that in the model group, the number of horizontal movement, the number of vertical movement and central residence time were significantly reduced, and the grooming time was significantly prolonged(P<0.05 or P<0.01); the levels of IL-1ß and IL-6 in hippocampus increased significantly(P<0.05); the number of positive cells with co-expression of Iba-1/iNOS of microglia cells in DG region of hippocampus increased; the expression levels of Iba-1 and iNOS protein in hippocampus were significantly increased(P<0.01), suggesting that microglia in DG region of hippocampus was activated and polarized toward M1 type in rats with stress. The high dose group of Xiaoyao San significantly increased the number of horizontal movement, vertical movement and central residence time of model rats(P<0.05 or P<0.01), and significantly down-regulated the levels of inflammatory factors IL-1ß and IL-6(P<0.05). Meanwhile, it reversed the activation and quantity change of microglia in hippocampus. Although the Xiaoyao San low dose group had no significant effect on the behavioral indicators in the open field test and the levels of IL-1ß and IL-6, they all showed a trend of improvement. Low dose Xiaoyao San significantly decreased iNOS protein level(P<0.05), and high dose Xiaoyao San significantly down-regulated the protein expression of Iba-1 and iNOS in hippocampus microglia(P<0.05 or P<0.01). In conclusion, Xiaoyao San can improve anxiety and depression-like behavior in OVX combined with CUS model rats, and its mechanism is related to its anti-inflammatory effect by inhibiting M1 polarization of hippocampal microglia.

Inverse Molecular Sentinel-Integrated Fiberoptic Sensor for Direct and in Situ Detection of miRNA Targets.

Molecular advances have been made in analysis systems for a wide variety of applications ranging from biodiagnostics, biosafety, bioengineering, and biofuel research applications. There are, however, limited practical tools necessary for in situ and accurate detection of nucleic acid targets during field work. New technology is needed to translate these molecular advances from laboratory settings into the real-life practical monitoring realm. The exquisite characteristics (e.g., sensitivity and adaptability) of plasmonic nanosensors have made them attractive candidates for field-ready sensing applications. Herein, we have developed a fiber-based plasmonic sensor capable of direct detection (i.e., no washing steps required) of nucleic acid targets, which can be detected simply by immerging the sensor in the sample solution. This sensor is composed of an optical fiber that is decorated with plasmonic nanoprobes based on silver-coated gold nanostars (AuNS@Ag) to detect target nucleic acids using the surface-enhanced Raman scattering (SERS) sensing mechanism of nanoprobes referred to as inverse molecular sentinels (iMS). These fiber-optrodes can be reused for several detection-regeneration cycles (>6). The usefulness and applicability of the iMS fiber-sensors was tested by detecting target miRNA in extracts from leaves of plants that were induced to have different expression levels of miRNA targets. These fiber-optrodes enable direct detection of miRNA in plant tissue extract without the need for complex assays by simply immersing the fiber in the sample solution. The results indicate the fiber-based sensors developed herein have the potential to be a powerful tool for field and in situ analysis of nucleic acid samples.

Phase-shifted type-IIa fiber Bragg gratings for high-temperature laser applications.

Phase-shifted Bragg gratings have been extensively implemented in superior in-fiber bandpass filters or wavelength selectors, although high-temperature operation remains a challenge. We propose a phase-shifted type-IIa fiber Bragg grating (PSBG-IIa), which can conduct a notch signal as narrow as 4.8 pm within the stopband. The notch's spectrum and wavelength can be adjusted according to the flexible design of the phase-mask translation. Using the thermal resistance as well as the narrow band notch, the PSBG-IIa is implemented in a distributed Bragg reflector laser structure to demonstrate a single longitudinal mode and single polarization laser output that can stabilize robustly at 500 °C. The results demonstrate that the proposed device qualifies as a high-quality optical regulator, without compromise, in the high-temperature region.

High-speed refractive index sensing system based on Fourier domain mode locked laser.

A high-speed refractive index sensing system based on the Fourier domain mode locked laser (FDML) and a microfiber Bragg grating (mFBG) is theoretically studied and experimentally demonstrated. Unlike traditional physical parameter sensing systems, which directly use the FDML as the wavelength scanning source and the optical sensor as the spectra shaping component, we inserted an mFBG into the FDML cavity in order to generate time domain pulse signals used for sensing. The wavelength shift in optical frequency domain is converted into time domain pulse drift. The sensitivity of the proposed refractive index (RI) sensing system is improved by two orders of magnitude, compared with the wavelength monitoring method. The scanning speed is as high as 43 kHz. Moreover, the sensitivity curve can be adjusted by tuning the direct current voltage. The nonlinear sensitivity and linear sensitivity with RI can be achieved.

Ultra-high sensitivity of dual dispersion turning point taper-based Mach-Zehnder interferometer.

We present here a detailed investigation into the sensitivity of the taper-based Mach-Zehnder interferometer as a function of external refractive index, with particular attention to the dispersion turning point (DTP) and possibilities for ultra-sensitive sensors. Our numerical simulation revealed that two DTPs exist with a decrease in the microfiber waist diameter; given this relationship, it is possible to obtain an ultra-sensitive operation. We then conducted experiments with fabricated devices with different waist diameters to achieve both positive and negative sensitivities at two DTPs. In particular, we achieved an ultrahigh refractive index sensitivity of approximately 95,832 nm/RIU at the second DTP when working with a diameter of 1.87 µm around the RI of air. These results show its potential for use in acoustic sensing and biochemical detection.

Temperature monitorable refractometer of microfiber Bragg grating using a duet of harmonic resonances.

To overcome the temperature cross-sensitivity of the microfiber Bragg grating (m-FBG) refractometer, we propose a novel refractive-index-temperature dual-sensing paradigm involving the third harmonic Bragg resonance that presents distinctive sensing characteristics. Strong resonances are obtained in both 1060 nm and 1550 nm wavebands under the modulation of the UV Talbot pattern. Moreover, higher-order transverse mode coupled resonance is also observed at the third harmonic waveband, supplementing an independent signal for enabling a sensing trio potentially. It is believed that the proposed dual-sensing paradigm would contribute to the m-FBT-based chemoprobes/bioprobes.

Fiber Light-Coupled Optofluidic Waveguide (FLOW) Immunosensor for Highly Sensitive Detection of p53 Protein.

Highly sensitive detection of molecular tumor markers is essential for biomarker-based cancer diagnostics. In this work, we showcase the implementation of fiber light-coupled optofluidic waveguide (FLOW) immunosensor for the detection of p53 protein, a typical tumor marker. The FLOW consists of a liquid-core capillary and an accompanying optical fiber, which allows evanescent interaction between light and microfluidic sample. Molecular binding at internal surface of the capillary induces a response in wavelength shift of the transmission spectrum in the optical fiber. To enable highly sensitive molecular detection, the evanescent-wave interaction has been strengthened by enlarging shape factor R via fine geometry control. The proposed FLOW immunosensor works with flowing microfluid, which increases the surface molecular coverage and improves the detection limit. As a result, the FLOW immunosensor presents a log-linear response to the tumor protein at concentrations ranging from 10 fg/mL up to 10 ng/mL. In addition, the nonspecifically adsorbed molecules can be effectively removed by the fluid at an optimal flow rate, which benefits the accuracy of the measurement. Tested in serum samples, the FLOW successfully maintains its sensitivity and specificity on p53 protein, making it suitable for diagnostics applications.

Dual-color distributed Bragg reflector fiber laser with simultaneous emission at 1.06 µm and 1.55 µm wavebands.

A dual-wavelength fiber laser is proposed by the use of Er/Yb co-doped active fiber and a pair of novel Bragg-grating reflectors. The Bragg grating presents strong reflections of both third and second harmonics in accordance with the gain of ytterbium and erbium ion, respectively, enabling the laser emitted at 1.06 µm and 1.55 µm wavebands simultaneously with a short linear cavity structure. Adjusting reflectivity of the harmonics in the grating can influence the intensity contrast of the two lasing signals. Optimization on the compactness and brightness of the laser is achieved by adapting the harmonic wavelengths with the optimal gain windows of the ytterbium and erbium ions.

High-sensitivity DNA biosensor based on microfiber Sagnac interferometer.

Nucleic acid detection with label-free biosensors circumvents the need for costly fluorophore functionalization steps associated with conventional assays by utilizing optical fiber transducers. In spite of their technological prowess, however, these biosensors' sensitivity is limited by the design/configuration of their transducers. Therefore, it is imperative to integrate novel optical fiber transducers with existing label-free approaches to overcome those limitations. Herein, we present a high sensitivity label-free fiber optic biosensor that employs polarimetric interference of a high-birefringence (Hi-Bi) microfiber to specifically detect DNA molecules. A slight target DNA concentration change is converted into an optical wavelength shift of polarimetric interference generated by the microfiber Sagnac interferometer. The sensor provides a log-linear response to target ssDNA concentrations range from 100 pM to 1 µM and a minimum detectable concentration of 75 pM.

Radical Difluororomethylation of Thiols with Difluoromethylphosphonium Triflate under Photoredox Catalysis.

A convenient, visible light-induced radical difluoromethylation of aryl-, heteroaryl-, and alkylthiols with difluoromethyltriphenylphosphonium triflate was developed to afford various difluoromethyl thioethers in moderate to excellent yields. The key reaction features include the use of a readily available CF2H radical source, mild reaction conditions, and excellent chemoselective thiol-difluoromethylation.