A Small Highly Sensitive Glucose Sensor Based on a Glucose Oxidase-Modified U-Shaped Microfiber.

Diabetes patients need to monitor blood glucose all year round. In this article, a novel scheme is proposed for blood glucose detection. The proposed sensor is based on a U-shaped microfiber prepared using hydrogen-oxygen flame-heating technology, and then 3-aminopropyltriethoxysilane (APTES) and glucose oxidase (GOD) are successively coated on the surface of the U-shaped microfiber via a coating technique. The glucose reacts with the GOD of the sensor surface to produce gluconic acid, which changes the effective refractive index and then shifts the interference wavelength. The structure and morphology of the sensor were characterized via scanning electron microscope (SEM) and confocal laser microscopy (CLM). The experimental results show that the sensitivity of the sensor is as high as 5.73 nm/(mg/mL). Compared with the glucose sensor composed of the same material, the sensitivity of the sensor increased by 329%. The proposed sensor has a broad application prospect in blood glucose detection of diabetic patients due to the advantages of miniaturization, high sensitivity, and good stability.

Direct Measurement of Dissolved Gas Using a Tapered Single-Mode Silica Fiber.

Dissolved gases in the aquatic environment are critical to understanding the population of aquatic organisms and the ocean. Currently, laser absorption techniques based on membrane separation technology have made great strides in dissolved gas detection. However, the prolonged water-gas separation time of permeable membranes remains a key obstacle to the efficiency of dissolved gas analysis. To mitigate these limitations, we demonstrated direct measurement of dissolved gas using the evanescent-wave absorption spectroscopy of a tapered silica micro-fiber. It enhanced the analysis efficiency of dissolved gases without water-gas separation or sample preparation. The feasibility of this sensor for direct measurement of dissolved gases was verified by taking the detection of dissolved ammonia as an example. With a sensing length of 5 mm and a consumption of ~50 µL, this sensor achieves a system response time of ~11 min and a minimum detection limit (MDL) of 0.015%. Possible strategies are discussed for further performance improvement in in-situ applications requiring fast and highly sensitive dissolved gas sensing.

Infrared Evanescent Wave Sensing Based on a Ge10As30Se40Te20 Fiber for Alcohol Detection.

Infrared evanescent wave sensing based on chalcogenide fiber is an emerging technology for qualitative and quantitative analysis of most organic compounds. Here, a tapered fiber sensor made from Ge10As30Se40Te20 glass fiber was reported. The fundamental modes and intensity of evanescent waves in fibers with different diameters were simulated with COMSOL. The 30 mm length tapered fiber sensors with different waist diameters, 110, 63, and 31 µm, were fabricated for ethanol detection. The sensor with a waist diameter of 31 µm has the highest sensitivity of 0.73 a.u./% and a limit of detection (LoD) of 0.195 vol.% for ethanol. Finally, this sensor has been used to analyze alcohols, including Chinese baijiu (Chinese distilled spirits), red wine, Shaoxing wine (Chinese rice wine), Rio cocktail, and Tsingtao beer. It is shown that the ethanol concentration is consistent with the nominal alcoholicity. Moreover, other components such as CO2 and maltose can be detected in Tsingtao beer, demonstrating the feasibility of its application in detecting food additives.

Enhancing Evanescent Wave Coupling of Near-Surface Waveguides with Plasmonic Nanoparticles.

Evanescent field excitation is a powerful means to achieve a high surface-to-bulk signal ratio for bioimaging and sensing applications. However, standard evanescent wave techniques such as TIRF and SNOM require complex microscopy setups. Additionally, the precise positioning of the source relative to the analytes of interest is required, as the evanescent wave is critically distance-dependent. In this work, we present a detailed investigation of evanescent field excitation of near-surface waveguides written using femtosecond laser in glass. We studied the waveguide-to-surface distance and refractive index change to attain a high coupling efficiency between evanescent waves and organic fluorophores. First, our study demonstrated a reduction in sensing efficiency for waveguides written at their minimum distance to the surface without ablation as the refractive index contrast of the waveguide increased. While this result was anticipated, it had not been previously demonstrated in the literature. Moreover, we found that fluorescence excitation by waveguides can be enhanced using plasmonic silver nanoparticles. The nanoparticles were also organized in linear assemblies, perpendicular to the waveguide, with a wrinkled PDMS stamp technique, which resulted in an excitation enhancement of over 20 times compared to the setup without nanoparticles.

Screening of Endocrine Disrupting Potential of Surface Waters via an Affinity-Based Biosensor in a Rural Community in the Yellow River Basin, China.

Overcoming the limitations of traditional analytical methods and developing technologies to continuously monitor environments and produce a comprehensive picture of potential endocrine-disrupting chemicals (EDCs) has been an ongoing challenge. Herein, we developed a portable nuclear receptor (NR)-based biosensor within 90 min to perform highly sensitive analyses of a broad range of EDCs in environmental water samples. Based on the specific binding of the fluorescence-labeled NRs with their ligands, the receptors were attached to the EDC-functionalized fiber surface by competing with EDCs in the samples. The biosensor emitted fluorescence due to the evanescent wave excitation, thereby resulting in a turn-off sensing mode. The biosensor showed a detection limit of 5 ng/L E2-binding activity equivalent (E2-BAE) and 93 ng/L T3-BAE. As a case study, the biosensor was used to map the estrogenic binding activities of surface waters obtained from a rural community in the Yellow River basin in China. When the results obtained were compared with those from the traditional yeast two-hybrid bioassay, a high correlation was observed. It is anticipated that the good universality and versatility exhibited by this biosensor for various EDCs, which is achieved by using different NRs, will significantly promote the continuous assessment of global EDCs.

Fluorescence enhancement of CdSe/ZnS quantum dots induced by mercury ions and its applications to the on-site sensitive detection of mercury ions.

The significant fluorescence enhancement of CdSe/ZnS quantum dots (QDs) induced by Hg2+ was observed for the first time based on a CdSe/ZnS QD-modified fiber nanoprobe. The fluorescence enhancement mechanism contributed to the Zn-to-Hg cation exchange in the ZnS shell, which allowed to form a HgxZn1-xS/CdSe heterojunction and increase the separation of electrons and holes and reduce the recombination rate. High concentrations of Hg2+ accelerated the generation of the fluorescence signal and lead to higher fluorescence intensity. The maximum fluorescence intensity increased more than eight times when Hg2+ concentration was 1 µM. The characteristic time (θc), i.e., the rising time to achieve the maximum fluorescence intensity, was linearly dependent on  initial concentration of Hg2+ solution in accordance with our proposed theory. When the evanescent wave optofluidic fluorescence platform was used, the linear detection range and detection limit of Hg2+ were 5.0-1000 nM and 0.80 nM, respectively. The fiber nanoprobe can be applied to the rapid, sensitive, and accurate on-site detection of Hg2+ in real water samples without significant matrix effect. Our work paves a novel way to develop a simple and reliable nanoprobe for mercuric pollution control, and achieve the high quantum efficiency of QDs by limiting the diffusion of Hg2+ in the ZnS shell.

Reusable optofluidic point-of-care testing platform with lyophilized specific antibody for fluorescence detection of cholylglycine in serum.

A reusable optofluidic point-of-care testing platform (OPOCT) was successfully constructed through integrating evanescent wave fluorescence technology into an all-fiber-based optofluidic system. The compact design of the OPOCT allows it to be portable and suitable for on-site sensitive determination of biomarkers in serum without complicated and costly procedures. The sensitivity of 90.9 pM for antibody determination is observed thanks to the high transmission efficiency of excitation light and fluorescence in the OPOCT. The affinity constant between cholylglycine (CG) and anti-CG antibody was quantified using this platform based on the proposed theory. Using the lyophilized fluorescence-labeled specific antibody and reusable fiber optic biosensor, the OPOCT is applied to the one-step sensitive determination of CG in serum, which eliminates the dearth associated with liquid reagent handling, disposable biosensors, and user intervention. A limit of detection of 0.025 µg/mL for CG is obtained, which is far more than adequate for meeting diagnostic requirements. The matrix effect of serum samples on the evanescent wave-based optofluidic biosensor can be effectively reduced by simple dilution of serum samples. The performance of the OPOCT also compared favorably with that of a commercial turbidimetric inhibition immunoassay through analyzing multiple serum samples. This platform is ready to expand to measure any other biomarker by using its specific antibody. The simplicity, sensitivity, cost-effectiveness, and robustness of the OPOCT enable the early diagnosis of disease and making a timely clinical decision. Graphical abstract .

Evanescent-Wave Fiber Optic Sensing of the Anionic Dye Uranine Based on Ion Association Extraction.

Herein, we propose an evanescent-wave fiber optic sensing technique for the anionic dye uranine based on ion association extraction. The sensor was prepared by removing a section of the cladding from a multimode fiber and hydrophobization of the exposed core surface. Uranine was extracted in association along with hexadecyltrimethylammonium (CTA) ion onto the fiber surface and detected via absorption of the evanescent wave generated on the surface of the exposed fiber core. The effect of CTA+ concentration added for ion association was investigated, revealing that the absorbance of uranine increased with increasing CTA+ concentration. A change in the sensor response as a function of the added uranine concentration was clearly observed. The extraction data were analyzed using a distribution equilibrium model and a Freundlich isotherm. The uranine concentration in the evanescent field of the fiber optic was up to 54 times higher than that in the bulk solution, and the limit of detection (3σ) for uranine was found to be 1.3 nM.

Air-Coupled Reception of a Slow Ultrasonic A0 Mode Wave Propagating in Thin Plastic Film.

At low frequencies, in thin plates the phase velocity of the guided A0 mode can become slower than that of the ultrasound velocity in air. Such waves do not excite leaky waves in the surrounding air, and therefore, it is impossible to excite and receive them by conventional air-coupled methods. The objective of this research was the development of an air-coupled technique for the reception of slow A0 mode in thin plastic films. This study demonstrates the feasibility of picking up a subsonic A0 mode in plastic films by air-coupled ultrasonic arrays. The air-coupled reception was based on an evanescent wave in air accompanying the propagating A0 mode in a film. The efficiency of the reception was enhanced by using a virtual array which was arranged from the data collected by a single air-coupled receiver. The signals measured at the points corresponding to the positions of the phase-matched array were recorded and processed. The transmitting array excited not only the A0 mode in the film, but also a direct wave in air. This wave propagated at ultrasound velocity in air and was faster than the evanescent wave. For efficient reception of the A0 mode, the additional signal-processing procedure based on the application of the 2D Fourier transform in a spatial-temporal domain. The obtained results can be useful for the development of novel air-coupled ultrasonic non-destructive testing techniques.

Tapered Optical Fibre Sensors: Current Trends and Future Perspectives.

The development of reliable, affordable and efficient sensors is a key step in providing tools for efficient monitoring of critical environmental parameters. This review focuses on the use of tapered optical fibres as an environmental sensing platform. Tapered fibres allow access to the evanescent wave of the propagating mode, which can be exploited to facilitate chemical sensing by spectroscopic evaluation of the medium surrounding the optical fibre, by measurement of the refractive index of the medium, or by coupling to other waveguides formed of chemically sensitive materials. In addition, the reduced diameter of the tapered section of the optical fibre can offer benefits when measuring physical parameters such as strain and temperature. A review of the basic sensing platforms implemented using tapered optical fibres and their application for development of fibre-optic physical, chemical and bio-sensors is presented.

Optical Biosensors for Label-Free Detection of Small Molecules.

Label-free optical biosensors are an intriguing option for the analyses of many analytes, as they offer several advantages such as high sensitivity, direct and real-time measurement in addition to multiplexing capabilities. However, development of label-free optical biosensors for small molecules can be challenging as most of them are not naturally chromogenic or fluorescent, and in some cases, the sensor response is related to the size of the analyte. To overcome some of the limitations associated with the analysis of biologically, pharmacologically, or environmentally relevant compounds of low molecular weight, recent advances in the field have improved the detection of these analytes using outstanding methodology, instrumentation, recognition elements, or immobilization strategies. In this review, we aim to introduce some of the latest developments in the field of label-free optical biosensors with the focus on applications with novel innovations to overcome the challenges related to small molecule detection. Optical label-free methods with different transduction schemes, including evanescent wave and optical fiber sensors, surface plasmon resonance, surface-enhanced Raman spectroscopy, and interferometry, using various biorecognition elements, such as antibodies, aptamers, enzymes, and bioinspired molecularly imprinted polymers, are reviewed.

Refractive Index Imaging of Cells with Variable-Angle Near-Total Internal Reflection (TIR) Microscopy.

The refractive index in the interior of single cells affects the evanescent field depth in quantitative studies using total internal reflection (TIR) fluorescence, but often that index is not well known. We here present method to measure and spatially map the absolute index of refraction in a microscopic sample, by imaging a collimated light beam reflected from the substrate/buffer/cell interference at variable angles of incidence. Above the TIR critical angle (which is a strong function of refractive index), the reflection is 100%, but in the immediate sub-critical angle zone, the reflection intensity is a very strong ascending function of incidence angle. By analyzing the angular position of that edge at each location in the field of view, the local refractive index can be estimated. In addition, by analyzing the steepness of the edge, the distance-to-substrate can be determined. We apply the technique to liquid calibration samples, silica beads, cultured Chinese hamster ovary cells, and primary culture chromaffin cells. The optical technique suffers from decremented lateral resolution, scattering, and interference artifacts. However, it still provides reasonable results for both refractive index (~1.38) and for distance-to-substrate (~150 nm) for the cells, as well as a lateral resolution to about 1 µm.

PDMAA Hydrogel Coated U-Bend Humidity Sensor Suited for Mass-Production.

We present a full-polymer respiratory monitoring device suited for application in environments with strong magnetic fields (e.g., during an MRI measurement). The sensor is based on the well-known evanescent field method and consists of a 1 mm plastic optical fiber with a bent region where the cladding is removed and the fiber is coated with poly-dimethylacrylamide (PDMAA). The combination of materials allows for a mass-production of the device by spray-coating and enables integration in disposable medical devices like oxygen masks, which we demonstrate here. We also present results of the application of an autocorrelation-based algorithm for respiratory frequency determination that is relevant for real applications of the device.

Repetitive Immunosensor with a Fiber-Optic Device and Antibody-Coated Magnetic Beads for Semi-Continuous Monitoring of Escherichia coli O157:H7.

A rapid and reproducible fiber-optic immunosensor for Escherichia coli O157:H7 (E. coli O157:H7) was described. The biosensor consisted of a flow cell, an optical fiber with a thin Ni layer, and a PC linked fluorometer. First, the samples with E. coli O157:H7 were incubated with magnetic beads coated with anti-E. coli O157:H7 antibodies and anti-E. coli O157:H7 antibodies labeled cyanine 5 (Cy5) to make sandwich complexes. Then the Cy5-(E. coli O157:H7)-beads were injected into a flow cell and pulled to the magnetized Ni layer on the optical fiber set in the flow cell. An excitation light (λ = 635 nm) was used to illuminate the optical fiber, and the Cy5 florescent molecules facing the optical fiber were exposed to an evanescent wave from the optical fiber. The 670 nm fluorescent light was measured using a photodiode. Finally, the magnetic intensity of the Ni layer was removed and the Cy5-E. coli O157:H7-beads were washed out for the next immunoassay. E. coli O157:H7, diluted with phosphate buffer (PB), was measured from 1 × 105 to 1 × 107 cells/mL. The total time required for an assay was less than 15 min (except for the pretreatment process) and repeating immunoassay on one optical fiber was made possible.

U-Shaped and Surface Functionalized Polymer Optical Fiber Probe for Glucose Detection.

In this work we show an optical fiber evanescent wave absorption probe for glucose detection in different physiological media. High selectivity is achieved by functionalizing the surface of an only-core poly(methyl methacrylate) (PMMA) polymer optical fiber with phenilboronic groups, and enhanced sensitivity by using a U-shaped geometry. Employing a supercontinuum light source and a high-resolution spectrometer, absorption measurements are performed in the broadband visible light spectrum. Experimental results suggest the feasibility of such a fiber probe as a low-cost and selective glucose detector.

Whispering-Gallery Mode Resonators for Detecting Cancer.

Optical resonators are sensors well known for their high sensitivity and fast response time. These sensors have a wide range of applications, including in the biomedical fields, and cancer detection is one such promising application. Sensor diagnosis currently has many limitations, such as being expensive, highly invasive, and time-consuming. New developments are welcomed to overcome these limitations. Optical resonators have high sensitivity, which enable medical testing to detect disease in the early stage. Herein, we describe the principle of whispering-gallery mode and ring optical resonators. We also add to the knowledge of cancer biomarker diagnosis, where we discuss the application of optical resonators for specific biomarkers. Lastly, we discuss advancements in optical resonators for detecting cancer in terms of their ability to detect small amounts of cancer biomarkers.

Emerging Cytokine Biosensors with Optical Detection Modalities and Nanomaterial-Enabled Signal Enhancement.

Protein biomarkers, especially cytokines, play a pivotal role in the diagnosis and treatment of a wide spectrum of diseases. Therefore, a critical need for advanced cytokine sensors has been rapidly growing and will continue to expand to promote clinical testing, new biomarker development, and disease studies. In particular, sensors employing transduction principles of various optical modalities have emerged as the most common means of detection. In typical cytokine assays which are based on the binding affinities between the analytes of cytokines and their specific antibodies, optical schemes represent the most widely used mechanisms, with some serving as the gold standard against which all existing and new sensors are benchmarked. With recent advancements in nanoscience and nanotechnology, many of the recently emerging technologies for cytokine detection exploit various forms of nanomaterials for improved sensing capabilities. Nanomaterials have been demonstrated to exhibit exceptional optical properties unique to their reduced dimensionality. Novel sensing approaches based on the newly identified properties of nanomaterials have shown drastically improved performances in both the qualitative and quantitative analyses of cytokines. This article brings together the fundamentals in the literature that are central to different optical modalities developed for cytokine detection. Recent advancements in the applications of novel technologies are also discussed in terms of those that enable highly sensitive and multiplexed cytokine quantification spanning a wide dynamic range. For each highlighted optical technique, its current detection capabilities as well as associated challenges are discussed. Lastly, an outlook for nanomaterial-based cytokine sensors is provided from the perspective of optimizing the technologies for sensitivity and multiplexity as well as promoting widespread adaptations of the emerging optical techniques by lowering high thresholds currently present in the new approaches.

Establishment of evanescent wave fiber-optic immunosensor method for detection bluetongue virus.

The evanescent wave fiber immunosensors (EWFI) technique was developed for the real-time rapidly sensitive and specific detection of the monoclonal antibody 3E2 of BTV. The outer-core protein VP7 of BTV was labled on the surface of the exposed fiber-optic core. The monoclonal antibody 3E2 of BTV VP7 were added and then the goat ant-rat IgG conjugated with Cy3 was captured. After the 532nm pulse (excitation source) reached the fiber probe, evanescent wave was generated, which excited the Cy3 bound to the immuno-complex and produced the fluorescent signal, which was changed into electrical signals read through computer. The preliminary results suggested that a detection limit of 10ng/ml was measured for the monoclonal antibody 3E2, which is equal to the sensitivity of ELISA. The 3E2 sample was specifically detected through the EWFI assay in 15min, and the fiber can be recycled at least ten times through TEA solution condition. This developed EWFI was a real-time rapidly sensitive and specific way for the detection of BTV antibodies.

Live Imaging of Cellular Internalization of Single Colloidal Particle by Combined Label-Free and Fluorescence Total Internal Reflection Microscopy.

In this work we utilize the combination of label-free total internal reflection microscopy and total internal reflectance fluorescence (TIRM/TIRF) microscopy to achieve a simultaneous, live imaging of single, label-free colloidal particle endocytosis by individual cells. The TIRM arm of the microscope enables label free imaging of the colloid and cell membrane features, while the TIRF arm images the dynamics of fluorescent-labeled clathrin (protein involved in endocytosis via clathrin pathway), expressed in transfected 3T3 fibroblasts cells. Using a model polymeric colloid and cells with a fluorescently tagged clathrin endocytosis pathway, we demonstrate that wide field TIRM/TIRF coimaging enables live visualization of the process of colloidal particle interaction with the labeled cell structure, which is valuable for discerning the membrane events and route of colloid internalization by the cell. We further show that 500 nm in diameter model polystyrene colloid associates with clathrin, prior to and during its cellular internalization. This association is not apparent with larger, 1 µm in diameter colloids, indicating an upper particle size limit for clathrin-mediated endocytosis.

Highly sensitive fiber-optic chemical pH sensor based on surface modification of optical fiber with ZnCdSe/ZnS quantum dots.

The pH value plays a vital role in many biological and chemical reactions. In this work, the fiber-optic chemical pH sensors were fabricated based on carboxyl ZnCdSe/ZnS quantum dots (QDs) and tapered optical fiber. The photoluminescence (PL) intensity of QDs is pH-dependence because protonation and deprotonation can affect the process of electron-hole recombination. The evanescent wave of tapered optical fiber was used as excitation source in the process of PL. To obtain higher sensitivity, the end faces of fiber were optimized for cone region. By lengthening the cone region and shrinking the end diameter of optical fiber, evanescent wave was enhanced and the excitation times of QDs were increased, which improved the PL intensity and the sensitivity of the sensor. The sensitivity of sensor can reach as high as 0.139/pH in the range of pH 6.00-9.01. The surface functional modification was adopted to prepare sensing films. The carboxyl groups on the QDs ligands are chemically bonded to the fiber surface, which is good for response time (40 s) and stability (decreased 0.9 % for 5 min). These results demonstrated that ZnCdSe/ZnS QDs-based fiber-optic chemical pH sensors are promising approach in rapid and precise pH detection.