Highly sensitive and selective detection of nitrite using a fiber optofluidic laser.

Nitrite ion (NO2-) is a common contaminant that can significantly threaten human health and the environment. In this study, we demonstrate a chemical sensing platform to monitor the nitrite concentration using a fiber optofluidic laser (FOFL). An optical fiber, integrated into a microchannel, is used both as an optical micro-cavity and the sensing element. Rhodamine 6 G (Rh6G) in an aqueous micellar solution is used as the laser gain medium. The light intensity change of the lasing spectra is employed as an indicator for the NO2- ion concentration sensing. The lasing properties under different NO2- ion concentrations are experimentally and theoretically investigated to examine the sensing performance of the FOFL. The results show that the limit detection of the FOFL sensor is 0.54 µM, which is 2-order-of-magnitude lower than fluorescence measurement. The sensing mechanism of Rh6G for NO2- detection is studied by using density functional theory (DFT). The calculation results indicate that nitrite influences the electronic distribution of Rh6G based on the heavy atom effect, which leads to the fluorescence quenching of Rh6G in the excited state. In addition, the detection system exhibits favorable selectivity for NO2- ions.

Large dynamic range dual-mode pH sensors via dye-doped ionic liquid fiber optofluidic lasers.

We report a fiber optofluidic laser (FOFL) using an RhB-doped ionic liquid (BmimPF6) as the gain medium and explore its application for large dynamic range highly sensitive pH sensing. Due to the high Q-factor of the FOFL and the unique merits of BmimPF6, lasing emission presents a threshold of only 0.61 µJ mm-1. Particularly, lasing emission behaviors are strongly dependent on the pH value of the gain medium, i.e., in the pH range 4.28-6.37, the lasing central wavelength blue-shifts monotonically with a sensitivity as high as 5.02 nm per pH unit, which we attribute to the conversion of the cationic form of RhB to the zwitterionic form caused by the deprotonation of the COOH group. Under alkaline conditions (pH 7.20-11.17), the lasing emission intensity exhibits a significant decrease and the corresponding lasing central wavelength is also blue-shifted due to the solvent effect. The sensitivity based on the wavelength shift is 3.03 nm per pH unit, which is 4-fold higher than that of fluorescence-based sensing, while the sensitivity based on the variation of the lasing emission intensity is almost three orders of magnitude higher than that of fluorescence-based sensing. Our work presents a novel dual sensing paradigm in response to different pH conditions, which can greatly improve the reliability and discrimination of pH sensing.

The Efficacy of REG Proteins as a Diagnostic Biomarker for Pancreatic Cancer: a Meta-Analysis.

BACKGROUND: Regenerating gene (REG) family proteins play a pivotal role in cell proliferation, tissue regeneration, and tumor metastasis. Recent studies have concentrated on the role of REG proteins in pancreatic cancer, but the results remain controversial. In this study, a meta-analysis was performed to evaluate the precise diagnostic value of REG proteins in pancreatic cancer. METHODS: A search was conducted in PubMed, Medline, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Biomedical Literature Database (CBM), and WANFANG Data up to May 5, 2021. The QUADAS-2 tool was used to evaluate the quality of the included studies. The statistical analysis of the diagnostic tests was conducted using RevMan5 and Meta-Disc 1.4. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (95% CIs) were calculated from each eligible study. RESULTS: The meta-analysis included 15 articles containing 796 patients and 584 controls. The pooled sensitivity was 0.71 (95% CI: 0.67 - 0.74), the pooled specificity was 0.73 (95% CI: 0.70 - 0.76), and the pooled DOR was 11.35 (95% CI: 5.92 - 21.77), respectively. The overall area under the receiver operating characteristic curve (AUC) was 0.84. Spearman's correlation coefficient was 0.34 (p = 0.221). For the subgroup analysis, the REG4 protein showed higher diagnostic accuracy compared with the other REG proteins. CONCLUSIONS: REG proteins have moderate diagnostic accuracy in pancreatic cancer. Further well-designed studies with larger sample sizes and clinical application are needed to validate the results of this meta-analysis.

Optical fiber optofluidic laser based on surfactant solubilization of rhodamine B gain in an aqueous solution.

We report a whispering gallery mode (WGM)-based fiber optofluidic laser (FOFL), in which rhodamine B (RhB) in an aqueous surfactant solution of sodium dodecylbenzene sulfonate (SDBS) is used as the laser gain medium. Here, the role of SDBS is to scatter the RhB dye molecules to effectively prevent its self-association in the aqueous solution. Therefore, the fluorescence quantum yield of the used RhB dye is improved due to the enhanced solubilization, which results in a low lasing threshold of ∼2.2 µJ/mm2 when the concentration of SDBS aqueous solution reaches up to 20 mM, on par with or even better than most of the optofluidic dye lasers using RhB as the gain medium in an organic solution. We then establish a model of solubilization capacity of SDBS micelles, which successfully addresses the mechanisms of dye-surfactant interactions in the proposed FOFL system. We further apply this FOFL platform to the case of concentration sensing of the used SDBS, which exhibits a 2-order-of-magnitude improvement in sensitivity compared to the fluorescence measurement due to the signal amplification inherent to the lasing process. The proposed FOFL platform in combination with surfactant solubilization gain medium in an aqueous solution promises to enable chip-scale coherent light sources for various environmental and bio-chemical sensing applications.

High sensitivity pH sensing by using a ring resonator laser integrated into a microfluidic chip.

We present a chip-scale integrated pH sensor with high sensitivity by using an optofluidic ring resonator (OFRR) laser. An optical fiber with a high refractive index (RI) is employed both as an optical cavity and the sensing reactor along a microchannel, while disodium fluorescein (DSF) aqueous solution with a low RI is served as the cladding gain medium and fluorescent probes. The pump light is introduced along the fiber axis and guided by the total internal reflection at the fiber/cladding interface. The evanescent field of the pump light extends out of the fiber surface and efficiently excites the dye molecules residing in the evanescent field region of the Whispering Gallery Modes (WGMs) of the OFRRs to produce lasing emission. This pumping scheme provides a uniform excitation to the gain medium and significantly increases the signal-to-noise ratio, ensuring a low lasing threshold and highly sensitive sensing. The lasing threshold property under different pH conditions is experimentally and theoretically conducted to evaluate the sensing performance, which shows that the lasing threshold highly depends on the pH value of the cladding solution due to the increasing deprotonation process. We further verify that the intensity of the lasing emission and the pH value shows good linearity in the pH range 6.51-8.13, with a 2-order-of-magnitude sensitivity enhancement compared to fluorescence measurement. The proposed OFRR lasing platform shows excellent robustness and low sample consumption, providing a powerful sensing strategy in medicine, and hazardous/toxic/volatile sensing, which require label-free, real-time, and in situ detection.

Detection of free DNA septin 9 gene methylation in plasma. / 血浆游离DNA Septin 9åŸºå› ç”²åŸºåŒ–æ£€æµ‹æ–¹æ³•.

OBJECTIVES: To explore the correlation between cytosine-phosphoric-guanylic (CpG) site of Septin 9 gene and colorectal cancer, and to develop a real-time PCR detection system in plasma in patients with colorectal cancer. METHODS: The methylation of training samples was detected by high-throughput sequencing technology, and the sites highly consistent with the clinical information of colorectal cancer were identified. Then the detection system of real-time PCR was designed to analyze the consistency of plasma and tissue based on methylationa sensitive enzyme digestion. Finally, 100 clinical trials were conducted to evaluate the performance of the detection system with the methylation sensitive enzyme digestion-real-time PCR. RESULTS: The highly consistent sites, which were selected by high-throughput sequencing from 71 training set samples, was the 38th CpG. Based on the detection region, the screened methylation sensitive enzymes were BstU1, HhaI and HinP1I. The limit for the detection of methylation sensitive enzyme digestion-real-time PCR was 0.5%, and the Ct value was 38.5. The sensitivity was 87.27%, the specificity was 91.49%, the positive predictive value was 92.31%, and the negative predictive value was 86.00%. CONCLUSIONS: The 38th CpG site of Septin 9 detected by the detection system of methylation sensitive enzyme digestion-real-time PCR can highly predict the occurrence of colorectal cancer with great clinical application value.

Versatile Optofluidic Solid-Core/Liquid-Cladding Waveguide Based on Evanescent Wave Excitation.

In this paper, we present the design and operation of a solid-core/liquid-cladding (SL) waveguide excited by an evanescent wave. To do this, an optical fiber is integrated into a microfluidic channel and pumped along the fiber axis, ensuring the cladding solution is excited by the evanescent field of the guided mode at the core/cladding interface. The pump beam is guided by the total internal reflection in the fiber, providing a uniform excitation along the microfluidic channel. The evanescent wave provides precise excitation to the dye molecules in close proximity to the core/cladding interface, which significantly reduces the background fluorescence and increases the signal-to-noise ratio. Fluorescence intensity measurements of different dye concentrations and refractive indices of the cladding solution are conducted to evaluate their influences on the propagation loss, which shows that the peak intensity propagation loss can be as low as about 0.1 dB/cm. We further exemplify that the intensity of the fluorescence emission and the dye concentration show good linearity when the dye is in the low concentration region (<250 µM). A broad-band and simultaneous light source with a single pump light is also demonstrated by employing cascade SL waveguide segments through fluorescence resonance energy transfer. The proposed SL waveguide demonstrates excellent robustness and is easy to fabricate and use, providing a versatile platform for a variety of applications, such as high-sensitivity detection of low-concentration samples, multiband on-chip light sources, and simultaneous measurement of multiplexed parameters.

Design of spherical aberration free liquid-filled cylindrical zoom lenses over a wide focal length range based on ZEMAX.

A systematic design idea for liquid-filled cylindrical zoom lenses with ideal imaging quality over a wide focal length range is introduced in detail. The PWC method is used to calculate the initial structure parameters of the zoom lenses, and the optical design software ZEMAX is used to eliminate the spherical aberration at different focal lengths. Lenses named SLCL-Doublet are finally designed, which are formed by a symmetric liquid-core cylindrical lens (SLCL) filled with variable refractive index (RI) liquid and a doublet cylindrical lens capable of significantly weakening the spherical aberration. The focal length of the SLCL-Doublet continuously decreases from 101.406 mm to 54.162 mm as the liquid RI changes from 1.3300 to 1.5000. Calculated over 75% of the full aperture, the root mean square (RMS) spot radius of the SLCL-Doublet is always less than 7 µm over the whole focal length range, and the peak-to-valley wavefront error remains below the λ/4 limit when the focal length ranges from 62.373 mm to 65.814 mm, within which the lenses approach the diffraction limit, demonstrating improvement in the optical performance over that of previously designed liquid-core cylindrical lenses. The sources of potential fabrication and installation errors in the practical implementation of the SLCL-Doublet are also analyzed in detail. The SLCL-Doublet is demonstrated to be characterized by high imaging quality and easy installation, which enriches the types of core optical element for measuring the liquid RI and liquid diffusion coefficient and provides guarantee for improving the measurement accuracy.

Rapid and sensitive detection of interleukin-6 in serum via time-resolved lateral flow immunoassay.

Interleukin 6 (IL-6) is an interleukin that acts as both a proinflammatory and anti-inflammatory cytokine. It can be used as a potential diagnostic biomarker for sepsis. The aim of this study was to establish an easy-to-use detection kit for rapid, quantitative and on-site detection of IL-6. To develop the new IL-6 quantitative detecting kit, a double-antibody sandwich immunofluorescent assay was employed based on europium nanoparticles (Eu-np) combined with lateral flow immunoassay (LFIA). The performance of the new developed kit was evaluated in the aspects of parallel analysis, linearity, sensitivity, precision, accuracy, specificity and clinical sample analysis. Two-hundred and fourteen serum samples were used to carry out the clinical sample analysis. The new IL-6 quantitative detecting kit exhibited a wide linear range (2-500 pg/mL) and a good sensitivity (0.37 pg/mL). The intra-assay coefficient of variation (CV) and the inter-assay CV were 5.92%-8.87% and 7.59%-9.04%, respectively. The recovery rates ranged from 102% to 106%. Furthermore, a high correlation (n = 214, r = 0.9756, p < 0.01) was obtained when compared with SIEMENS CLIA IL-6 kit. Thus, the new quantitative method for detecting IL-6 has been successfully established. The results indicated that the newly-developed strip based on Eu-np combined with LFIA was a facile, fast, highly sensitive, low-cost, reliable biosensor and suitable for rapid and point-of-care test (POCT) for IL-6 in serum.

α-Glucosidase Inhibitory and Anti-Inflammatory Coumestans from the Roots of Dolichos trilobus.

Four new coumestans dolichosins A - D (1: -4: ) were isolated from the roots of Dolichos trilobus, together with four known compounds: isosojagol (5: ), phaseol (6: ), psoralidin (7: ), and 4″,5″-dehydroisopsoralidin (8: ). Their structures were elucidated on the basis of spectroscopic data interpretation, mass spectrometric analyses, and the comparison with literature data of related compounds. The anti-inflammatory activity of these compounds (1: -8: ) was evaluated through the inhibition of nitric oxide production in lipopolysaccharide-activated murine macrophage RAW 264.7 cells, in which compounds 1: and 6: displayed moderate inhibitory activity and no cytotoxic effects. In a α-glucosidase inhibitory assay, compounds 1: and 5: -8: exhibited appreciable inhibition on α-glucosidase. Especially compounds 1, 7: , and 8: showed IC50 values lower than 20.0 µM.

Chemical constituents from the whole herb of Hemiphragma heterophyllum.

Phytochemical investigation on Hemiphragma heterophyllum led to the isolation of two new compounds, heterophyllumin A (1) and heterophylliol (3), along with nine known compounds, (‒)-sibiricumin A (2), iridolactone (4), jatamanin A (5), dihydrocatalpolgenin (6), 25-hydroperoxycycloart-23-en-3ß-ol (7), 24-methylenecycloartanol (8), (+)-pinoresinol (9), hexadec-(4Z)-enoic acid (10), and 9,12, 15-octadecatrienoic acid (11). Their structures were elucidated on the basis of detailed spectroscopic analyses and by comparison with literature data. Further, the structure of compound 3 was unambiguously confirmed by single-crystal X-ray analysis. Some of those compounds showed moderate activity in the α-glucosidase inhibition assay.

Double liquid-core cylindrical lens utilized to measure liquid diffusion coefficient.

We design and fabricate an aplanatic double liquid-core cylindrical lens (DLCL), which is used to measure the binary liquid diffusion coefficient (D). The front lens of the DLCL is used as both a diffusion cell and a key imaging element; the refractive index (RI) of liquid filled in its core can be measured in the way of spatial resolution. The rear lens of the DLCL is used as an aplanatic component, and either the RI position of spherical aberration (SA) or the SA in a range of RI caused by the front lens can be regulated by selecting the liquid, of which RI is pre-prepared and filled in the rear liquid core. Equipped with the aplanatic DLCL, two methods have been applied to measure the D value of 0.33mol/L KCL aqueous solution at temperature 298.15K. The first method derives D value precisely from the drift rate of diffusion image and the measured D is 1.8508 × 10-5 cm2/s. Meanwhile, the second method obtains the D value rapidly by analyzing an instantaneous diffusion image and the measured D is 1.8619 × 10-5 cm2/s. The measured values are in good agreement with the literature value, demonstrating that the designed DLCL works well in measuring liquid diffusion coefficients.

Radial phased-locked partially coherent flat-topped vortex beam array in non-Kolmogorov medium.

The analytical expressions for the cross-spectral density, the average intensity and the complex degree of spatial coherence of a radial phased-locked partially coherent flat-topped vortex beam array propagating through non-Kolmogorov medium are obtained by using the extended Huygens-Fresnel principle. The evolution behaviors of a radial phased-locked partially coherent flat-topped vortex beam array propagating through non-Kolmogorov medium are studied in detail. It is shown that the evolution behaviors of average intensity depend on beam parameters including the spatial correlation length, the radius of the beam array, as well as the propagation distance. A radial phased-locked partially coherent flat-topped vortex beam array with high coherence evolves more rapidly than that with low coherence.

Asymmetric liquid-core cylindrical lens used to measure liquid diffusion coefficient.

We design and fabricate an asymmetric liquid-core cylindrical lens (ALCL), which is used to measure the binary liquid diffusion coefficient (D). Acting as both diffusion cell and key imaging element, ALCL is of the function to measure the refractive index (RI) of liquid filled in its core in the way of spatial resolution. Comparing the ALCL with a symmetric liquid-core cylindrical lens (SLCL), the spherical aberration is reduced from about 300 µm (SLCL) to less than 5 µm (ALCL) when the RI of filled liquid is near 1.333, while the measurement accuracy of the RI of the ALCL is superior to 0.0002, which is much better than that of the SLCL. Equipped with the ALCL, the D value of triethylene glycol diffusing in water is measured at 25°C. The result is D=0.7515×10⁻5 cm²/s, a value very close to the literature value. The rational design of ALCL gives the optical method for measuring the D value good measurement precision and direct observation of the diffusive process as well as a simple experimental instrument.

New method to measure liquid diffusivity by analyzing an instantaneous diffusion image.

A novel optical method was applied to measure the binary liquid diffusion coefficient (D) quickly. Equipped with an asymmetric liquid-core cylindrical lens (ALCL), the spatially resolving ability of the ALCL in measuring refractive index of liquid was utilized to obtain the gradient distribution of the liquid concentration along diffusive direction. Based on Fick's second law, the D value was then calculated by analyzing diffusion images. It was worth mentioning that only one instantaneous diffusive image was required to measure D value by the method, reducing the measurement time greatly from several hours in traditional methods to a few seconds. The diffusion coefficients of ethylene glycol diffusing in pure water, at temperatures from 288.15 to 308.15 K, were measured by analyzing instantaneous diffusion images, the results were consistent well with the values measured by using holographic interferometry and Taylor dispersion methods. The method is characterized by faster measurement, direct observation of diffusive process, and easy operation, which provides a new method in measuring diffusion coefficient of liquids rapidly.

Demonstration of polarization mode selection and coupling efficiency of optofluidic ring resonator lasers.

We demonstrate the polarization mode selection and the dependence of coupling efficiency on polarization state of pump light for an optofluidic ring resonator (OFRR) laser. An optical fiber is chosen to serve as the ring resonator and surrounded by rhodamine 6G dye solution of lower refractive index as the fluidic gain medium. When the ring resonator is pumped by a linearly s-polarized laser, the emitted whispering gallery mode (WGM) lasing is of parallel polarization (TM mode), while p-polarized laser excitation generates a vertically polarized lasing emission (TE mode), both TM and TE mode lasing emission coexist simultaneously if the ring resonator is pumped by the s- and p-mixed polarized light. Further investigation reveals that the lasing intensity of the TM mode is approximately twice that of the TE mode for the same pump energy density, meaning an obvious difference of coupling efficiency on the polarization state of pump light; the experimental results of coupling efficiency are well explained by an induced dipole model.

An electrochemical aptasensor for detection of IFN-γ using graphene and a dual signal amplification strategy based on the exonuclease-mediated surface-initiated enzymatic polymerization.

Tuberculosis is one of the major health problems in the world. The cytokine interferon γ (IFN-γ) is associated with the disease-specific immune responses and is used as a tuberculosis diagnosis marker. In this study, a novel electrochemical aptasensor was developed for IFN-γ detection based on the exonuclease-catalyzed target recycling and the TdT-mediated cascade signal amplification. To construct the aptasensor, a previously hybridized double-stranded DNA (capture probe hybridization with a complementary IFN-γ binding aptamer) was immobilized on a gold nanoparticle-graphene (Au-Gra) nanohybrid film-modified electrode. In the presence of IFN-γ, the formation of an aptamer-IFN-γ complex leads to the liberation of the aptamer from the double-stranded DNA (dsDNA). Using exonuclease, the aptamer was selectively digested, and IFN-γ was released for the target recycling. A large amount of single-stranded capture probes formed and led to the hybridization with signal probe-labelled Au@Fe3O4. Then, the labelled signal probe sequences were catalyzed at the 3'-OH group by terminal deoxynucleotidyl transferase (TdT) to form a long single-stranded DNA structure. As a result, the electron mediator hexaammineruthenium(III) chloride ([Ru(NH3)6](3+)) electrostatically adsorbed onto DNA producing a strong electrochemical signal which can be used to quantitatively measure the IFN-γ levels. With the conducting nanomaterial Au-Gra as a substrate and the target recycling-based surface-initiated enzymatic polymerization-mediated signal amplification strategy, the proposed aptasensor displayed a broad linearity with a low detection limit of 0.003 ng mL(-1). Moreover, the resulting aptasensor exhibited good specificity, acceptable reproducibility and stability, which makes this method versatile and suitable for detecting IFN-γ and other biomolecules.

A novel ultrasensitive ECL sensor for DNA detection based on nicking endonuclease-assisted target recycling amplification, rolling circle amplification and hemin/G-quadruplex.

In this study, we describe a novel universal and highly sensitive strategy for the electrochemiluminescent (ECL) detection of sequence specific DNA at the aM level based on Nt.BbvCI (a nicking endonuclease)-assisted target recycling amplification (TRA), rolling circle amplification (RCA) and hemin/G-quadruplex. The target DNAs can hybridize with self-assembled capture probes and assistant probes to form "Y" junction structures on the electrode surface, thus triggering the execution of a TRA reaction with the aid of Nt.BbvCI. Then, the RCA reaction and the addition of hemin result in the production of numerous hemin/G-quadruplex, which consume the dissolved oxygen in the detection buffer and result in a significant ECL quenching effect toward the O2/S2O8(2-) system. The proposed strategy combines the amplification ability of TRA, RCA and the inherent high sensitivity of the ECL technique, thus enabling low aM (3.8 aM) detection for sequence-specific DNA and a wide linear range from 10.0 aM to 1.0 pM. At the same time, this novel strategy shows high selectivity against single-base mismatch sequences, which makes our novel universal and highly sensitive method a powerful addition to specific DNA sequence detection.

An electrochemical DNA biosensor for the detection of Mycobacterium tuberculosis, based on signal amplification of graphene and a gold nanoparticle-polyaniline nanocomposite.

Due to its low growth rate and its fastidious nature, Mycobacterium tuberculosis is difficult to identify. Its rapid and sensitive detection is, however, critical for the control of tuberculosis. Molecular biology, and more recently electrochemical technology, have been exploited for the detection of this pathogen. In the present study, a novel DNA biosensor was developed for the highly sensitive detection of the specific DNA insertion sequence IS6110 of M. tuberculosis, using reduced graphene oxide-gold nanoparticles (rGO-AuNPs) as a sensing platform and gold nanoparticles-polyaniline (Au-PANI) as a tracer label for amplification. Reduced graphene oxide, which has a large surface area, provided a biocompatible matrix. Gold nanoparticles were electrodeposited on the surface of the rGO modified electrode, which not only increased immobilisation of the capture probe but also promoted electronic transfer. The Au-PANI nanocomposite exhibited good biocompatibility and excellent electrochemical activity. It was therefore used as a tracer label for electrochemical detection, which provided a simple preparation process for a signal-on DNA biosensor. With the excellent electroactivity of the Au-PANI nanocomposite, the resulting DNA biosensor exhibited high sensitivity for the detection of M. tuberculosis over a broad linear range, between 1.0 × 10(-15) and 1.0 × 10(-9) M. The DNA biosensor showed good stability and high specificity and provides a new strategy for clinical M. tuberculosis diagnostics and probably also for pathogenic bacteria in general.

Polarization characteristics of Whispering-Gallery-Mode fiber lasers based on evanescent-wave-coupled gain.

The polarization characteristics of Whispering-Gallery-Mode (WGM) fiber lasers based on evanescent-wave-coupled gain are investigated. For the laser gain is excited by side-pumping scheme, it is found that the polarization property of lasing emission is simply dependent on the polarized states of the pump beams. The polarization property of lasing emission depends on the propagating situation of the pump beams in an optical fiber if the laser gain is excited by evanescent-wave pumping scheme, that is, if the pump beams within the fiber are meridional beams, the lasing emission is a transverse electric (TE) wave that forms a special radial polarization emission. However, if the pump beams within the fiber are skew beams, both transverse magnetic (TM) and TE waves exist simultaneously in lasing emission that forms a special axially and radially mixed polarization emission. Pumped by skew beams, the wave-number differences between TE and TM waves are also investigated quantitatively, the results demonstrate that the wave-number difference decreases with the increase of the fiber diameter and the refractive index (RI) of the cladding solution. The observed polarization characteristics have been well explained based on lasing radiation mechanism of WGM fiber laser of gain coupled by evanescent wave.