Silver nanoparticle (AgNP)/poly(N-isopropylacrylamide) (PNIPAAm) composite solution was electrospun followed by crosslinking to fabricate AgNP/PNIPAAm composite nanofiber mats. Embedded AgNPs were found to align along the PNIPAAm nanofibers, which generate more hotspots upon laser-induced plasmonic heating. This kind of AgNP/PNIPAAm mats show enhanced surface-enhanced Raman scattering (SERS) effect upon continuous pulsed laser irradiation, showing a laser heating sensitive' SERS effect. Laser-induced plasmonic heating can also tune the temperature-responsive interaction between PNIPAAm and analytes and has been applied in the on-site laser heating sensitive' separation and SERS detection of analytes. The composite nanofiber mats also showed good reproducibility and stability. What is more, this laser heating sensitivity' has also been applied in the direct SERS detection of adenosine in urea solution without urea interference. Together with the advantages of ease of large-scale fabrication, stable and laser heating sensitivity', AgNP/PNIPAAm mats might find application in sensitive multicomponent biosensing. Copyright (c) 2016 John Wiley & Sons, Ltd.

An intelligent PNIPAAm/AgNP composite film with dynamic SERS effect was fabricated by the simple assembly of silver nanoparticles on the surface of photo-polymerized PNIPAAm filmviaelectrostatic interaction.

This article is a review on the design, fabrication, and applications of fiberoptic nanosensors for in vivo monitoring of individual living cells. The nanosensors were fabricated with tapered optical fibers with distal ends having nanometer-sized diameters. Bioreceptors, such as antibody, peptides, and nucleic acids, are immobilized on the fiber tips and designed to be selective to target analyte molecules of interest. A laser beam is transmitted into the fiber, producing an evanescent field at the tip of the nanofiber that is used to excite target molecules bound to the bioreceptor molecules. The fluorescence originated from the analyte molecules is detected by a photo-detection system. The advantages and limitations of nanosensors in providing minimally invasive tools to probe subcellular compartments inside individual living cells for health effect studies and medical applications are discussed in detail.

We report the development of a compact point-detection fluorescence spectroscopy system and two data analysis methods to quantify the intrinsic fluorescence redox ratio and diagnose brain cancer in an orthotopic brain tumor rat model. Our system employs one compact cw diode laser (407 nm) to excite two primary endogenous fluorophores, reduced nicotinamide adenine dinucleotide, and flavin adenine dinucleotide. The spectra were first analyzed using a spectral filtering modulation method developed previously to derive the intrinsic fluorescence redox ratio, which has the advantages of insensitivity to optical coupling and rapid data acquisition and analysis. This method represents a convenient and rapid alternative for achieving intrinsic fluorescence-based redox measurements as compared to those complicated model-based methods. It is worth noting that the method can also extract total hemoglobin concentration at the same time but only if the emission path length of fluorescence light, which depends on the illumination and collection geometry of the optical probe, is long enough so that the effect of absorption on fluorescence intensity due to hemoglobin is significant. Then a multivariate method was used to statistically classify normal tissues and tumors. Although the first method offers quantitative tissue metabolism information, the second method provides high overall classification accuracy. The two methods provide complementary capabilities for understanding cancer development and noninvasively diagnosing brain cancer. The results of our study suggest that this portable system can be potentially used to demarcate the elusive boundary between a brain tumor and the surrounding normal tissue during surgical resection.

This paper describes the design and fabrication of fiber-optic nanoprobes developed for optical detection in single living cells. It is critical to fabricate probes with well-controlled nanoapertures for optimized spatial resolution and optical transmission. The detection sensitivity of fiber-optic nanoprobe depends mainly on the extremely small excitation volume that is determined by the aperture sizes and penetration depths. We investigate the angle dependence of the aperture in shadow evaporation of the metal coating onto the tip wall. It was found that nanoaperture diameters of approximately 50 nm can be achieved using a 25° tilt angle. On the other hand, the aperture size is sensitive to the subtle change of the metal evaporation angle and could be blocked by irregular metal grains. Through focused ion beam (FIB) milling, optical nanoprobes with well-defined aperture size as small as 200 nm can be obtained. Finally, we illustrate the use of the nanoprobes by detecting a fluorescent species, benzo[a]pyrene tetrol (BPT), in single living cells. A quantitative estimation of the numbers of BPT molecules detected using fiber-optic nanoprobes for BPT solutions shows that the limit of detection was approximately 100 molecules.

A strong interaction between cyanide anion and copper(I) cation in combination with non-resonant Raman fingerprinting allows the selective sensing of aqueous free cynanide with high sensitivity to parts per billion (ppb)-level.

This paper describes a direct optical approach based on Raman scattering for selective and sensitive detection of cyanide ions in aqueous environment without requiring time-consuming sample pretreatment and the formation of hydrogen cyanide. Due to the strong affinity between copper (I) and cyanide ion, evaporated copper (I) iodide (CuI) thin films are shown to be excellent substrates for selective recognition of free cyanide ions in aqueous matrices. The amount of cyanide ion retained by the copper (I) in the CuI thin films reflects its actual concentration in tested samples, and the subsequent Raman measurements of the substrate are shown to be capable of detecting toxic cyanide content at levels under international drinking water standard and environmental regulatory concentrations. Measurements obtained from the same batch of evaporated CuI thin films (∼100-nm thickness) show excellent linearity over a variety of cyanide concentrations ranging from 1.5μM to 0.15mM. This detection method offers the advantage of selectively detecting cyanides causing a health hazard while avoiding detection of other common interfering anions such as Cl−, Br−, PO43−, SO42−, NO2−, S2− and SCN−. Coupled with portable Raman systems that are commercially available, our detection approach will provide on-site monitoring capability with little sample preparation or instrument supervision, which will greatly expedite the assessment of potential environmental cyanide risks.

BACKGROUND:Fiber-optic nanosensors are fabricated by heating and pulling optical fibers to yield sub-micron diameter tips and have been used for in vitro analysis of individual living mammalian cells. Immobilization of bioreceptors (e.g., antibodies, peptides, DNA) selective to targeting analyte molecules of interest provides molecular specificity. Excitation light can be launched into the fiber, and the resulting evanescent field at the tip of the nanofiber can be used to excite target molecules bound to the bioreceptor molecules. The fluorescence or surface-enhanced Raman scattering produced by the analyte molecules is detected using an ultra-sensitive photodetector.OBJECTIVE:This article provides an overview of the development and application of fiber-optic nanosensors for drug discovery.CONCLUSIONS:The nanosensors provide minimally invasive tools to probe subcellular compartments inside single living cells for health effect studies (e.g., detection of benzopyrene adducts) and medical applications (e.g., monitoring of apoptosis in cells treated with anticancer drugs).

This paper describes the development of fiber optic sensor probes and planar substrates containing patterned nanostructures such as nanoholes in gold films, as well as gold nanoparticles, nano-pillars, nanorods, and nano-islands. Several methods of producing gold nanofeatures on fiber tips and planar substrates were investigated such as annealing of thin gold films and focused ion beam (FIB) milling. A Hitachi FB-2100 FIB milling machine with a gallium ion source was employed to form the nanoparticles from 20-100 nm gold films deposited on the fiber tip. Nano-engineered gold features were also formed by coating planar substrates and fiber tips with thin gold films (4-10 nm) and annealing these thin films. Excitation of surface plasmons in gold nanostructures leads to substantial enhancement in the Raman scattering signal obtained from molecules attached to the nanostructure surface. In this work, a comparison was made between the SERS signals obtained from the gold substrates developed by employing the different procedures mentioned above. Fiber samples and planar substrates with these nanostructures were coated with SERS, active dyes such as p-mercaptobenzoic acid (pMBA) and cresyl fast violet (CFV). It was observed that the SERS signal obtained from these gold nanofeatures was much higher than that obtained from a continuous gold film and that the SERS enhancement was shape and size dependent.

This paper describes the use of plasmonics-based nanoprobes for detection of multidrug-resistant tuberculosis gene. The plasmonics nanoprobe is composed of a silver nanoparticle pre-coated with a stem-loop DNA probe that is tagged with a Raman label at one end of the stem region, while the other end of the probe is covalently conjugated to the nanoparticle via a thiol-silver bond. The loop region is designed to detect a specific target gene sequence. In the absence of target, the Raman label is in close proximity to the metal surface, resulting in an intense SERS signal upon laser excitation. In the presence of the target DNA sequence, hybridization between the target and probe disrupts the stem-loop configuration, separating the Raman label from the metal surface and quenching the SERS signal. In this study, we successfully demonstrated for the first time the feasibility of using plasmonics nanoprobes for the detection of multidrug-resistant tuberculosis gene.

A critical aspect of the use of nanoprobes for intracellular studies in chemical and biological sensing involves a fundamental understanding of their uptake and trajectory in cells. In this study, we describe experiments using surface-enhanced Raman scattering (SERS) spectroscopy and mapping to track cellular uptake of plasmonics-active labeled nanoparticles. Three different Raman-active labels with positive, negative, and neutral charges were conjugated to silver colloidal nanoparticles with the aim of spatially and temporally profiling intracellular delivery and tracking of nanoprobes during uptake in single mammalian cells. 1-D Raman spectra and 2-D Raman mapping are used to identify and locate the probes via their SERS signal intensities. Because Raman spectroscopy is very specific for identification of chemical and molecular signatures, the development of functionalized plasmonics-active nanoprobes capable of exploring intracellular spaces and processes has the ability to provide specific information on the effects of biological and chemical pollutants in the intracellular environment. The results indicate that this technique will allow study of when, where, and how these substances affect cells and living organisms.

The authors present a label-free method for direct detection of deoxyribonucleic acid (DNA) sequences. The capture DNA is immobilized onto the surface of a silica optical fiber tip by means of the layer-by-layer electrostatic self-assembly technique. Hybridization of target DNA with complementary capture DNA increases the optical thickness of the fiber tip. This phenomenon can be detected by demodulation of the spectrum of a Fabry-Pérot cavity fabricated in the optical fiber. Experimental results demonstrate sequence specificity and sensitivity to nanogram quantities of target DNA sequences with short (∼5min) hybridization time.

The effect of layer-by-layer electrostatic self-assembly processing parameters on resulting thin-film characteristics was determined in order to optimize the thin-film structure for optical biosensing. The use of long-period fiber gratings (LPFGs) requires careful control of the refractive index of the surrounding medium, which can be achieved by tuning the refractive index and thickness of an optical thin film deposited directly on the optical fiber surface. The high-sensitivity LPFG refractometry range falls in a window just below the effective index of the relevant cladding mode. We investigated five factors at two levels using variable-angle spectroscopic ellipsometry and analysis of variance. Salt concentration and pH were found to be critical parameters for refractive index control.

A fiber-optic multicavity Fabry-Pe/spl acute/rot interferometric thin-film sensor with built-in temperature compensation has been constructed and demonstrated. Temperature information can be extracted from the multicavity structure to correct the temperature dependence of the optical thickness measurement of self-assembled thin-films. Experimental results demonstrate that the sensor is able to automatically compensate the temperature-induced optical-thickness error over the range from 0/spl deg/C to 100/spl deg/C.

A fiber-optic sensor is designed based on multicavity Fabry-Perot interferometry for the study of optical thickness in self-assembled thin-film layers. This miniature sensor is applicable not only to the measurement of self-assembled polyelectrolyte layers but also to the immobilization of proteins such as immunoglobulin G (IgG). The binding of IgG and the corresponding antigen is observed, and the nonspecific binding characteristics are investigated. The optical thickness changes are used to evaluate the immobilization of the IgG and the immunological activities of the immobilized layers.

We present two novel schemes for refractometry based on a long-period fiber grating- (LPG-) based Michelson interferometer. These schemes are designed to overcome the measurement dependence of previously demonstrated LPG-based refractometry on the immersion depth. The first utilizes an unshielded LPG and the second, a shielded one. Both schemes were tested over a certain refractive-index range, and the measurement of glucose concentration in water was experimentally demonstrated. In addition, the temperature sensitivity of the two schemes is discussed.