Nanosensor Platform Research Articles

Bifunctional silicon quantum dots sensing platform for selective and sensitive detection of p-dihydroxybenzene with double signals

Being awfully harmful to the environment and human health, the sensitive and selective determination of p-dihydroxybenzene (p-DHB) in environmental water is of great significance. However, the similar structures and properties of p-DHB with catechol (CC; one p-DHB isomer) make the selective and reliable determination of p-DHB from CC in environmental waters being still a formidable challenge. In this manuscript, by preparing CC stabilized silicon quantum dots (C-SiQDs) via a simple hydrothermal process and using C-SiQDs simultaneously as a catalyst and fluorescence indicator, a novel nanosensing platform was successfully developed to selectively and sensitively detect p-DHB with double signals: fluorescence and colorimetric. For detecting p-DHB, C-SiQDs could catalyze the oxidation of p-DHB to form benzoquinone (BQ), an intermediate, which lead to the color change from pale yellow to dark brown and the efficient quenching the fluorescence of C-SiQDs. While for CC in samples, it could not contact C-SiQDs surface due to the great steric hindrance effect from CC on quantum dots surface, thus restricting the oxidation of CC and production of BQ, and leading that the obtained C-SiQDs have no response towards CC. Meanwhile, the developed nanosensor could also avoid various other possible interferences. Under optimized conditions, wide linear ranges (from 0.01 μM to 50.0 μM) and low detection limits (4.0 nM) were obtained for p-DHB. The simple and reliable C-SiQDs-based double signals proposal demonstrated to be potentially applicable for the highly selective and sensitive detection of trace p-DHB in various environmental water samples.

Nano-electric field sensor based on Two Dimensional Photonic Crystal resonator

In this paper, hybrid Silicon-Barium Titanate (Si-BTO) based Two Dimensional Photonic Crystal (2DPC) platform is proposed for electric field sensing based on the effective refractive index modulation of electro-optic material. The nano-sensing platform is composed of the PC based resonator and inline quasi-waveguides in a 2D triangular lattice with circular rods that are arranged in the air medium. The BTO based nano-cavity resonator is playing a very important role in sensing the different electric field over a wide wavelength range. The operating wavelength range of the proposed sensor is investigated via Photonic Band Gap (PBG) which is obtained by the Plane Wave Expansion (PWE) method. The transmission efficiency, quality factor, electric field sensitivity and change in refractive index are analyzed by using Finite Difference Time Domain method (FDTD). The simulation results reveal that the resonant wavelength of the electric field sensor is linearly shifted to the higher wavelength region while increasing the electric field from 0 kV/mm to 25 kV/mm. The proposed sensing platform provides high transmission efficiency and very high refractive index sensitivity with an ultra-compact size. Hence, it is highly suitable for nano-chip based sensing applications.

Inverse surface‐enhanced spatially offset Raman spectroscopy (SESORS) through a monkey skull

AbstractThe use of nanoparticles in nanomedicine has received increasing interest. However, in vivo detection of nanoparticles using optical techniques is still a formidable challenge. Detecting surface‐enhanced Raman scattering (SERS)‐labeled nanoparticles through thick tissue is crucial due to its large number of potential applications in the field of disease diagnostics and monitoring. As gold nanoparticles are becoming an important nanoprobe and nanosensor platform for SERS in vivo applications, accurate detection and quantitation of these particles has become even more important. Conventional optical methods, however, are typically limited in obtaining SERS signals at the surface level, due to the attenuation caused by the highly scattering and absorbing tissue. Herein, we utilize spatially offset Raman spectroscopy to overcome this depth limitation and obtain specific spectrochemical signatures of SERS‐labeled nanoprobes, such as gold nanostars, beneath thick material and bone. The efficacy of this method, referred to as surface‐enhanced spatially offset Raman spectroscopy is demonstrated through the detection of layer‐specific and subsurface SERS signals beneath three different substrates: (a) 4‐mm tissue phantom, (b) 4‐mm paraffin film, and (c) 5 mm bone of a macaque skull. Additionally, we show the possibility of recovering the pure SERS signal that belongs to a specific layer within a two‐layer system using scaled subtraction.

Nano-Pressure and Temperature Sensor Based on Hexagonal Photonic Crystal Ring Resonator

In the present work, two-dimensional (2D) hexagonal photonic crystal ring resonator (PCRR) structure is designed for both pressure and temperature sensing based on effective refractive index modulation of silicon. The nanosensor is designed to monitor the pressure from 0.04 to 6 GPa and temperature from 5 to 540 °C. The proposed nanosensing platform is composed of hexagonal PCRR and two inline quasi-waveguides in a 2D hexagonal lattice with circular rods arranged in air host. The hexagonal PCRR is playing a very important role in sensing the different pressure and temperature levels over a wide dynamic range. The plane wave expansion method (PWE) is implemented to calculate photonic band gap (PBG), which is used to identify the operating wavelength range of the sensor. The functional parameters of the sensor are evaluated by finite-difference time-domain method (FDTD). The functional parameters are the dynamic range, resonant wavelength, sensitivity, transmission efficiency, and quality factor. The FDTD results show that the resonant wavelength of the PCRR is red shifted with increasing the pressure and temperature. The designed sensor offers high sensitivity, high transmission efficiency and good quality factor with ultra-compact size; hence, it is extremely suitable for nanotechnology-based sensing applications.

N-Doped Graphene Quantum Dots-Decorated V2O5 Nanosheet for Fluorescence Turn Off-On Detection of Cysteine.

The development of a fast-response sensing technique for detection of cysteine can provide an analytical platform for prescreening of disease. Herein, we have developed a fluorescence turn off-on fluorescence sensing platform by combining nitrogen-doped graphene quantum dots (N-GQDs) with V2O5 nanosheets for the sensitive and selective detection of cysteine in human serum samples. V2O5 nanosheets with 2-4 layers are successfully synthesized via a simple and scalable liquid exfoliation method and then deposited with 2-8 nm of N-GQDs as the fluorescence turn off-on nanoprobe for effective detection of cysteine in human serum samples. The V2O5 nanosheets serve as both fluorescence quencher and cysteine recognizer in the sensing platform. The fluorescence intensity of N-GQDs with quantum yield of 0.34 can be quenched after attachment onto V2O5 nanosheets. The addition of cysteine triggers the reduction of V2O5 to V4+ as well as the release of N-GQDs within 4 min, resulting in the recovery of fluorescence intensity for the turn off-on detection of cysteine. The sensing platform exhibits a two-stage linear response to cysteine in the concentration range of 0.1-15 and 15-125 μM at pH 6.5, and the limit of detection is 50 nM. The fluorescence response of N-GQD@V2O5 exhibits high selectivity toward cysteine over other 22 electrolytes and biomolecules. Moreover, this promising platform is successfully applied in detection of cysteine in human serum samples with excellent recovery of (95 ± 3.8) - (108 ± 2.4)%. These results clearly demonstrate a newly developed redox reaction-based nanosensing platform using N-GQD@V2O5 nanocomposites as the sensing probe for cysteine-associated disease monitoring and diagnosis in biomedical applications, which can open an avenue for the development of high performance and robust sensing probes to detect organic metabolites.

Flexible and Tunable 3D Gold Nanocups Platform as Plasmonic Biosensor for Specific Dual LSPR-SERS Immuno-Detection

Early medical diagnostic in nanomedicine requires the implementation of innovative nanosensors with highly sensitive, selective, and reliable biomarker detection abilities. In this paper, a dual Localized Surface Plasmon Resonance - Surface Enhanced Raman Scattering (LSPR- SERS) immunosensor based on a flexible three-dimensional (3D) gold (Au) nanocups platform has been implemented for the first time to operate as a relevant “proof-of-concept” for the specific detection of antigen-antibody binding events, using the human IgG - anti-human IgG recognition interaction as a model. Specifically, polydimethylsilane (PDMS) elastomer mold coated with a thin Au film employed for pattern replication of hexagonally close-packed monolayer of polystyrene nanospheres configuration has been employed as plasmonic nanoplatform to convey both SERS and LSPR readout signals, exhibiting both well-defined LSPR response and enhanced 3D electromagnetic field. Synergistic LSPR and SERS sensing use the same reproducible and large-area plasmonic nanoplatform providing complimentary information not only on the presence of anti-human IgG (by LSPR) but also to identify its specific molecular signature by SERS. The development of such smart flexible healthcare nanosensor platforms holds promise for mass production, opening thereby the doors for the next generation of portable point-of-care devices.

Multiple-targeted graphene-based nanocarrier for intracellular imaging of mRNAs

Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) mRNA and 2.45 nM for β-actin mRNA. Additionally, this nanosensing platform composed of fluorescent labelled single strand DNA probes and GO nanocarrier can identify Mn-SOD mRNA and endogenous mRNA of β-actin in living cancer cells, showing rapid response, high specificity, nuclease stability, and good biocompatibility during the cell imaging. Thirdly, changes of the expression levels of mRNA in living cells before or after the drug treatment can be monitored successfully. By using multiple ssDNA as probes and GO nanocarrier as the cellular delivery cargo, the proposed simultaneous multiple-targeted sensing platform will be of great potential as a powerful tool for intracellular trafficking process from basic research to clinical diagnosis.

Performance analysis of zinc oxide-implemented lossy mode resonance-based optical fiber refractive index sensor utilizing thin film/nanostructure.

A detailed primeval study on the lossy mode resonance (LMR) behavior of zinc oxide (ZnO)-coated optical fiber as a refractive index sensor is carried out. Theoretical evaluation predicts ZnO as a good choice for the LMR-based chemical and gas sensor operating in the visible region of the electromagnetic spectrum. To confirm, the optical fiber probe has been fabricated with an optimized film thickness of ZnO over an unclad core of fiber and characterized. Additionally, an LMR-based nanosensor platform utilizing ZnO has also been investigated to find the compatibility of a nanotechnological LMR sensor. The nanostructured LMR sensors have shown enhanced sensitivity in comparison to a bulk layered probe.

A Carbon-Dot-Based Fluorescent Nanosensor for Simple Visualization of Bacterial Nucleic Acids.

A simple and facile method for sensing of nucleic acids is in great need for disease biomarker detection and diagnosis. Herein, a fluorescent nanosensor utilizing carbon dot nanoparticles is introduced that form visible precipitates in the presence of target DNA. Carbon dot nanoparticles are fabricated by microwave pyrolysis of polyethylenimine, which emits strong photoluminescence and can form precipitates when added to target DNA oligonucleotides. The precipitates can be easily visualized by UV illumination, and data can be acquired as images using a smartphone, which are analyzed for quantification. This carbon-dot-based assay allowed fluorescent sensing of target oligonucleotides with various sizes and visualization even with minimal amount of DNA (≈100 pmol). Finally, the assay can be applied as a nanosensor platform for detecting bacterial DNA for the antibiotic-resistance gene KPC-2 from Klebsiella pneumoniae. This method provides a simple technique for detecting molecular targets, showing wide applicability for diagnostics on the bedside or point-of-care testing.

Nanosensor Technology Applied to Living Plant Systems.

An understanding of plant biology is essential to solving many long-standing global challenges, including sustainable and secure food production and the generation of renewable fuel sources. Nanosensor platforms, sensors with a characteristic dimension that is nanometer in scale, have emerged as important tools for monitoring plant signaling pathways and metabolism that are nondestructive, minimally invasive, and capable of real-time analysis. This review outlines the recent advances in nanotechnology that enable these platforms, including the measurement of chemical fluxes even at the single-molecule level. Applications of nanosensors to plant biology are discussed in the context of nutrient management, disease assessment, food production, detection of DNA proteins, and the regulation of plant hormones. Current trends and future needs are discussed with respect to the emerging trends of precision agriculture, urban farming, and plant nanobionics.

A shear-enhanced CNT-assembly nanosensor platform for ultra-sensitive and selective protein detection

Detection and quantification of low-concentration proteins in heterogeneous media are generally plagued by two distinct obstacles: lack of sensitivity due to high dissociation equilibrium constant KD and non-specificity due to an abundance of non-targets with similar KD. Herein, we report a nanoscale protein-sensing platform with a non-equilibrium on-off switch that employs dielectrophoretic and hydrodynamic shear forces to overcome these thermodynamic limitations with irreversible kinetics. The detection sensitivity is achieved with complete association of the antibody-antigen-antibody (Ab-Ag-Ab) complex by precisely and rapidly assembling carbon nanotubes (CNT) across two parallel electrodes via sequential DC electrophoresis and AC dielectrophoresis (DEP), and with single-CNT electron tunneling conductance. The high selectivity is achieved with a critical hydrodynamic shear rate between the activated dissociation shear rates of target and non-target linkers of the aligned CNTs. We are able to reach detection limits of 100 attomolar (aM) and 10 femtomolar (fM) in pure samples for two ELISA assays with low and high dissociation constant: biotin/streptavidin (10 fM) and HER2/HER2 antibody (0.44 ± 0.07nM), respectively. For both models, irreversible capture and shearing allow us to tune the dynamic range up to 5 decades by increasing the CNT numbers. We also demonstrate in spiked serum sample high selectivity towards target HER2 proteins against non-target HER2 isoform of a similar KD. The detection limit for HER2 in serum is lower than 100fM.

Design and fabrication of fluorescence resonance energy transfer-mediated fluorescent polymer nanoparticles for ratiometric sensing of lysosomal pH

The design of effective tools capable of sensing lysosome pH is highly desirable for better understanding its biological functions in cellular behaviors and various diseases. Herein, a lysosome-targetable ratiometric fluorescent polymer nanoparticle pH sensor (RFPNS) was synthesized via incorporation of miniemulsion polymerization and surface modification technique. In this system, the donor: 4-ethoxy-9-allyl-1,8-naphthalimide (EANI) and the acceptor: fluorescein isothiocyanate (FITC) were covalently linked to the polymer nanoparticle to construct pH-responsive fluorescence resonance energy transfer (FRET) system. The FITC moieties on the surface of RFPNS underwent structural and spectral transformation as the presence of pH changes, resulting in ratiometric fluorescent sensing of pH. The as-prepared RFPNS displayed favorable water dispersibility, good pH-induced spectral reversibility and so on. Following the living cell uptake, the as-prepared RFPNS with good cell-membrane permeability can mainly stain in the lysosomes; and it can facilitate visualization of the intracellular lysosomal pH changes. This nanosensor platform offers a novel method for future development of ratiometric fluorescent probes for targeting other analytes, like ions, metabolites,and other biomolecules in biosamples.

Label-free ratiometric electrochemical detection of the mutated apolipoprotein E gene associated with Alzheimer's disease.

A novel ratiometric electrochemical nanosensing platform was developed based on graphene and mesoporous hybrid nanomaterials for detection of the mutated apolipoprotein E gene associated with Alzheimer's disease. The introduction of ratiometric assay could cancel out some systematic errors and significantly improved the sensing performance, such as reproducibility, reliability and accuracy.

Enzyme-linked DNA dendrimer nanosensors for acetylcholine.

It is currently difficult to measure small dynamics of molecules in the brain with high spatial and temporal resolution while connecting them to the bigger picture of brain function. A step towards understanding the underlying neural networks of the brain is the ability to sense discrete changes of acetylcholine within a synapse. Here we show an efficient method for generating acetylcholine-detecting nanosensors based on DNA dendrimer scaffolds that incorporate butyrylcholinesterase and fluorescein in a nanoscale arrangement. These nanosensors are selective for acetylcholine and reversibly respond to levels of acetylcholine in the neurophysiological range. This DNA dendrimer architecture has the potential to overcome current obstacles to sensing in the synaptic environment, including the nanoscale size constraints of the synapse and the ability to quantify the spatio-temporal fluctuations of neurotransmitter release. By combining the control of nanosensor architecture with the strategic placement of fluorescent reporters and enzymes, this novel nanosensor platform can facilitate the development of new selective imaging tools for neuroscience.

A Nanoparticle-based Sensor Platform for Cell Tracking and Status/Function Assessment.

Nanoparticles are increasingly popular choices for labeling and tracking cells in biomedical applications such as cell therapy. However, all current types of nanoparticles fail to provide real-time, noninvasive monitoring of cell status and functions while often generating false positive signals. Herein, a nanosensor platform to track the real-time expression of specific biomarkers that correlate with cell status and functions is reported. Nanosensors are synthesized by encapsulating various sensor molecules within biodegradable polymeric nanoparticles. Upon intracellular entry, nanosensors reside within the cell cytoplasm, serving as a depot to continuously release sensor molecules for up to 30 days. In the absence of the target biomarkers, the released sensor molecules remain ‘Off’. When the biomarker(s) is expressed, a detectable signal is generated (On). As a proof-of-concept, three nanosensor formulations were synthesized to monitor cell viability, secretion of nitric oxide, and β-actin mRNA expression.

Quadruplex Integrated DNA (QuID) Nanosensors for Monitoring Dopamine.

Dopamine is widely innervated throughout the brain and critical for many cognitive and motor functions. Imbalances or loss in dopamine transmission underlie various psychiatric disorders and degenerative diseases. Research involving cellular studies and disease states would benefit from a tool for measuring dopamine transmission. Here we show a Quadruplex Integrated DNA (QuID) nanosensor platform for selective and dynamic detection of dopamine. This nanosensor exploits DNA technology and enzyme recognition systems to optically image dopamine levels. The DNA quadruplex architecture is designed to be compatible in physically constrained environments (110 nm) with high flexibility, homogeneity, and a lower detection limit of 110 µM.

Preparation of Graphene-Modified Acupuncture Needle and Its Application in Detecting Neurotransmitters.

We report a unique nanosensing platform by combining modern nanotechnology with traditional acupuncture needle to prepare graphene-modified acupuncture needle (G-AN), and using it for sensitive detection of neurotransmitters via electrochemistry. An electrochemical deposition method was employed to deposit Au nanoparticles (AuNPs) on the tip surface of the traditional acupuncture needle, while the other part of the needle was coated with insulation paste. Subsequently, the G-AN was obtained by cyclic voltammetry reduction of a graphene oxide solution on the surface of the AuNPs. To investigate the sensing property of the G-AN, pH dependence was measured by recording the open circuit potential in the various pH buffer solutions ranging from 2.0 to 10.0. What’s more, the G-AN was further used for detection of dopamine (DA) with a limit of detection of 0.24 μM. This novel G-AN exhibited a good sensitivity and selectivity, and could realize direct detection of DA in human serum.

A novel sensitive Cu(II) and Cd(II) nanosensor platform: Graphene oxide terminated p-aminophenyl modified glassy carbon surface

Graphene oxide (GO) based glassy carbon (GC) electrode has been prepared. Firstly, p-nitrophenyl (NP) modified GC (NP/GC) electrode was prepared via the electrochemical reduction of its tetraflouroborate diazonium salt. After the formation of NP/GC electrode, the negative potential was applied to NP/GC electrode to reduce the nitro groups to amine. p-Aminophenyl (AP) modified GC (AP/GC) electrode was immersed into a graphene oxide solution containing 1-ethyl-3(3-(dimethlyamino)propyl)-carbodiimide. Hence, we constructed GO terminated AP modified GC (GO/AP/GC) electrode. NP/GC, AP/GC and GO/AP/GC electrodes were characterized sequentially using cyclic voltammetry (CV) in the presence of 1.0mM of potassium ferricyanide in 0.1M KCl. In addition, GO and GO/AP/GC surfaces were characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The GO/AP/GC electrode was used for the analysis of Cd(II) and Cu(II) ions by adsorptive stripping voltammetry. The linearity range and the detection limit of Cd(II) and Cu(II) ions were 1.0×10−11–5.0×10−10M and 3.3×10−12M (S/N=3), respectively.

Supraparticles comprised of molecularly imprinted nanoparticles and modified gold nanoparticles as a nanosensor platform

A highly selective and sensitive nanosensing system for small molecules is proposed based on the supraparticles of molecularly imprinted polymer nanoparticles (MIP-NPs) and modified gold nanoparticles (Au-NPs). The MIP-NPs function as molecular recognition materials and the Au-NPs function as signal transduction materials, from molecular recognition-based binding events to spectral changes of localized surface plasmon resonance (LSPR) of Au-NPs in the visible region. This novel supraparticles-based nanosensing system enables specific sensing towards target molecules that can be achieved simply, rapidly and inexpensively, using only a UV-vis spectrophotometer. Moreover, an affinity constant is obtained with this sensing system that is 120 000 times larger than that previously reported. As a result, a sub-nanomolar concentration of target molecules was successfully detected, which is comparable to the corresponding enzyme-linked immunosorbent assays. The proposed supraparticles-based spectroscopic sensing system could open a new era for sensing tools in a broad range of important research/industrial fields, such as the environmental, life, medical and pharmaceutical sciences.

Localized surface plasmon-enhanced nanosensor platform using dual-responsive polymer nanocomposites

The fast and accurate identification of unknown liquids is important for the safety and security of human beings. Recently, sensors based on the localized surface plasmon resonance (LSPR) effect demonstrated an outstanding sensitivity in detecting chemical and biological species. In the present study, we suggest that a dual-responsive nanocomposite composed of two polymer brushes and two noble metal nanoparticles provides a significantly improved selectivity (improvement of a factor of 30 in figure-of-merit) for distinguishing diverse liquids compared to a single-responsive LSPR sensor. The dual-responsive LSPR sensor platform was realized by the synergic combinations of two hydrophobic and hydrophilic polymer brushes, which respond differently depending on the degree of interaction between the polymer brushes and the surrounding liquids. Moreover, the mixing ratio of two solvents can also be estimated with high accuracy using the dual-nanocomposite LSPR sensor, suggesting that this approach would be highly practical for in situ process monitoring systems that can instantly detect the change of solvent composition.