Wide-field single metal nanoparticle spectroscopy for high throughput localized surface plasmon resonance sensing

Noble metal nanoparticles (mNPs) have a distinct extinction spectrum arising from their ability to support Localized Surface Plasmon Resonance (LSPR). Single-particle biosensing with LSPR is label free and offers a number of advantages, including single molecular sensitivity, multiplex detection, and in vivo quantification of chemical species etc. In this article, we introduce Single-particle LSPR Imaging (SLI), a wide-field spectral imaging method for high throughput LSPR biosensing. The SLI utilizes a transmission grating to generate the diffraction spectra from multiple mNPs, which are captured using a Charge Coupled Device (CCD). With the SLI, we are able to simultaneously image and track the spectral changes of up to 50 mNPs in a single (～1 s) exposure and yet still retain a reasonable spectral resolution for biosensing. Using the SLI, we could observe spectral shift under different local refractive index environments and demonstrate biosensing using biotin-streptavidin as a model system. To the best of our knowledge, this is the first time a transmission grating based spectral imaging approach has been used for mNPs LSPR sensing. The higher throughput LSPR sensing, offered by SLI, opens up a new possibility of performing label-free, single-molecule experiments in a high-throughput manner.     

Plasmonic biosensing based on non-noble-metal materials

This review focuses on the research progress of non-noble-metal materials with nanostructures for plasmonic biosensing. Firstly, the physical and sensing principles of localized surface plasmon resonance (LSPR) sensors are briefly introduced; then non-noble-metal materials, such as copper, aluminum, semiconductor, graphene and other materials, for plasmonic sensing are categorized and presented. Finally, a rational discussion about the future prospective of novel materials for plasmonic sensing is given.     

Engineering electrochemical interface for biomolecular sensing

Sensing interfaces where molecular recognition processes occur plays a central role in biosensors, which directly affect the biosensing sensitivity, specificity, stability, and response dynamics. However, the target accessibility of conventional sensing interfaces is limited, resulting in low molecular recognition efficiency. Engineering the sensing interfaces of biosensors provides an effective strategy to improve the performance of the biosensors. In this review, we summarize recent advances during the past two years in the development of biosensing interface engineering for enhanced electrochemical sensing. Three types of emerging engineering approaches, including constructing nanostructured sensing interfaces, molecule-mediated interfacial regulation, and functionalizing the interfaces with self-assembled DNA nanostructures, especially framework nucleic acid, are discussed. Also, the remaining challenges and opportunities are outlined for the important research area.     

Analysis of immunoreaction with localized surface plasmon resonance biosensor

The localized surface plasmon resonance (LSPR)-based optical biosensor was used as a potential tool for label-free detection of immunoreaction. The glass substrate covered with the self-assembled monolayer (SAM) of gold colloids was used widely in the sensors. Here, the glass substrate was modified by chemical hydroxylation first, and then gold colloids were immobilized on the substrate by electrostatic adsorption. The LSPR spectra were obtained on UV–vis absorption spectrometer. The specificity was examined by extensive nonspecific binding tests. The resonance condition on the local dielectric environment enables a simple form of molecular sensing. The binding of analyte to the biosensor surface causes a change in the absorbance which was responsive to the concentration of human IgG. So, the LSPR sensing yields similar results to the SPR technique, yet with much simpler instrument.     

Present and future of surface plasmon resonance biosensors

Surface plasmon resonance (SPR) biosensors are optical sensors exploiting special electromagnetic waves—surface plasmon-polaritons—to probe interactions between an analyte in solution and a biomolecular recognition element immobilized on the SPR sensor surface. Major application areas include detection of biological analytes and analysis of biomolecular interactions where SPR biosensors provide benefits of label-free real-time analytical technology. This paper reviews fundamentals of SPR affinity biosensors and discusses recent advances in development and applications of SPR biosensors.     

Sensing using localised surface plasmon resonance sensors

The bright colours of noble metal particles have attracted considerable interest since historical times, where they were used as decorative pigments in stained glass windows. More recently, the tuneable optical properties of metal nanoparticles and their addressability via spectroscopic techniques have brought them back into the forefront of fundamental and applied research fields. Much of the recent attention concerning metal nanoparticles such as gold and silver has been their use as small-volume, ultra-sensitive label-free optical sensors. Plasmonic nanoparticles act in this case as transducers that convert changes in the local refractive index into spectral shifts of the localized surface plasmon resonance (LSPR) band. This LSPR-shift assay is a general technique for measuring binding affinities and rates from any molecule that induces a change in the local refractive index around the metallic nanostructures. By attaching molecular recognition elements (chemical or biological ligands) on the nanostructures, specificity and selectivity to the analyte of interest are introduced into the nanosensor. In this review, we will discuss the different methods used to fabricate plasmonic nanosensors. A special emphasis will be given to techniques used to link plasmonic nanostructures to surfaces. While the difference between colorimetric and refractive index sensing approaches will be briefly described, the importance to distinguish between bulk refractive index (RI) sensing and molecular near-field refractive index sensing will be discussed. The recent progress made in the development of novel surface functionalization strategies together with the formation of optically and mechanically stable LSPR sensors will be highlighted.     

A comparative analysis of localized and propagating surface plasmon resonance sensors: the binding of concanavalin a to a monosaccharide functionalized self-assembled monolayer

A comparative analysis of the properties of two optical biosensor platforms: (1) the propagating surface plasmon resonance (SPR) sensor based on a planar, thin film gold surface and (2) the localized surface plasmon resonance (LSPR) sensor based on surface confined Ag nanoparticles fabricated by nanosphere lithography (NSL) are presented. The binding of Concanavalin A (ConA) to mannose-functionalized self-assembled monolayers (SAMs) was chosen to highlight the similarities and differences between the responses of the real-time angle shift SPR and wavelength shift LSPR biosensors. During the association phase in the real-time binding studies, both SPR and LSPR sensors exhibited qualitatively similar signal vs time curves. However, in the dissociation phase, the SPR sensor showed an approximately 5 times greater loss of signal than the LSPR sensor. A comprehensive set of nonspecific binding studies demonstrated that this signal difference was not the consequence of greater nonspecific binding to the LSPR sensor but rather a systematic function of the Ag nanoparticle's nanoscale structure. Ag nanoparticles with larger aspect ratios showed larger dissociation phase responses than those with smaller aspect ratios. A theoretical analysis based on finite element electrodynamics demonstrates that this results from the characteristic decay length of the electromagnetic fields surrounding Ag nanoparticles being of comparable dimensions to the ConA molecules. Finally, an elementary (2 x 1) multiplexed version of an LSPR carbohydrate sensing chip to probe the simultaneous binding of ConA to mannose and galactose-functionalized SAMs has been demonstrated.     

Thermal‐Induced Formation of a Three‐Dimensional Nanoplasmonic Sensor from Ag Nanocubes with High Stability and Reusability

Nanoplasmonic sensors based on the localized surface plasmon resonance (LSPR) of noble metal nanoparticles have many advantages, such as real‐time detection, no need for reagent labelling, and no use of complicated equipment. However, the nanoplasmonic sensors with two dimensional structures usually suffer from a low LSPR signal and thus low sensitivity due to the low density of the nanoparticles. In addition, complicated surface functionalization is always required to suppress the non‐specific binding of the analyst to the substrate of the sensor, because the two types of surface, that is, metal and substrate surfaces, are simultaneously exposed to the reaction medium. To overcome these problems, an innovative thermal‐induced method has been proposed in the present work, to construct three dimensional (3D) nanostructure of Ag nanocubes on both surfaces of the substrate by using the unique amphiphilic property of 2‐diethylaminoethanethiol. The prepared nanoplasmonic sensor is highly sensitive due to the high density of 3D structure of the nanoparticles and the low non‐specific binding since only one type of surface is exposed. To enhance the stability of the sensor, a thin SiO₂ overlayer was formed on the surface without using an additional coupling agent. Furthermore, the Ni^II‐nitriloacetic acid (Ni^II‐NTA) complex was covalently bound on the surface, so that the regeneration and reuse of the sensor becomes easy. Therefore, the easy fabrication, high stability, and good reusability of this 3D LSPR sensor makes our method competitive for the development of nanoplasmonic sensors.     

Detecting Alzheimer's disease biomarkers: From antibodies to new bio-mimetic receptors and their application to established and emerging bioanalytical platforms – A critical review

The failure of therapeutic treatment of Alzheimer's disease (AD) patients can be related to the late onset of symptoms and, consequently, to a delayed pharmacological aid to counteract neurodegenerative progression. This is coupled to the fact that the diagnosis based on clinical criteria alone introduces high misdiagnosis rate. The availability of assessed biomarkers is therefore of crucial importance not only to counteract late diagnosis, but also to manage patients at high risk of AD development eligible for novel therapies. At the present time, amyloid-β peptides (Aβ_1-40 and Aβ_1-42 isoforms), alone or in combination with Tau protein (total and phosphorylated forms (p-tau)) constitute reliable AD biomarkers and result highly predictive of progression to AD dementia in patients with mild cognitive impairment (MCI), the earliest clinical presentation of AD. Improvement of existing diagnostic tools must take advantage of innovative bioanalytical approaches. In this review, starting from commercially available diagnostic platforms based on antibodies as recognition elements, we intended to provide a double point of view on the issue: 1) progresses achieved on innovative bioanalytical platforms (mainly sensors and biosensors) by using antibodies as consolidated receptors; 2) advance on promising bio-mimetic receptors alternative to antibodies in AD research, and their applications on conventional or innovative analytical platforms. In particular, we first focused on optical- (Propagating and Localized Surface Plasmon Resonance, named here SPR and LSPR) and electrochemical (voltammetric and impedimetric) transduction principles. Together with bioanalytical assays for AD biomarkers quantification, works aimed to investigate and understand their behavior, characteristics, and roles will also be considered in the discussion.     

Characterization of thin polymer and biopolymer layers by ellipsometry and evanescent field technology

The characterization of sensitive layers is the prerequisite for the optimization of chemical and biochemical sensors. The application of SE (Spectral Ellipsometry) and SPR (Surface Plasmon Resonance) as methods of characterization of such sensitive layers is discussed. In combination with infrared spectroscopy, the properties of polymer networks, micro-porous polymers, liquid crystals, and biomimetic polymers can be examined regarding their applicability for optical sensing. Apart from the basic principles regarding the characterization approaches, applications in the area of environmental sensing, optimization of hydrogel layers for antigen/antibody interaction, and discrimination of analytes in homologous series of alcohols are discussed. The effects of analytes on the phase transition in combination with disordering of liquid crystals are given.     

基于局域表面等离子体共振效应的光学生物传感器*

贵金属纳米粒子表现出许多常规块体材料所不具备的优异性能,其中局域表面等离子体共振 (LSPR) 特性是研究热点之一。LSPR 的形状和位置与纳米粒子的组成、大小、形状、介电性质以及局域介质环境密切相关。基于这一特性,贵金属纳米粒子已广泛应用于光学生物传感器、光过滤器和表面增强光谱等领域。本文对各种结构的贵金属纳米粒子的制备方法及其在光学生物传感器中的应用进行了综述,并对 LSPR 纳米传感器的未来发展前景做了展望。     

Chemical surface modifications for the development of silicon-based label-free integrated optical (IO) biosensors: A review

Increasing interest has been paid to label-free biosensors in recent years. Among them, refractive index (RI) optical biosensors enable high density and the chip-scale integration of optical components. This makes them more appealing to help develop lab-on-a-chip devices. Today, many RI integrated optical (IO) devices are made using silicon-based materials. A key issue in their development is the biofunctionalization of sensing surfaces because they provide a specific, sensitive response to the analyte of interest. This review critically discusses the biofunctionalization procedures, assay formats and characterization techniques employed in setting up IO biosensors. In addition, it provides the most relevant results obtained from using these devices for real sample biosensing. Finally, an overview of the most promising future developments in the fields of chemical surface modification and capture agent attachment for IO biosensors follows.     

Enhancement of Nonlinear Optical Scattering by Gold Nanoparticles through Aggregation-Induced Plasmon Coupling in the Near-Infrared

Gold nanoparticles (AuNPs) are regarded as promising building blocks in functional nanomaterials for sensing, drug delivery and catalysis. One remarkable property of these particles is the localized surface plasmon resonance (LSPR), which gives rise to augmented optical properties through local field enhancement. LSPR also influences the nonlinear optical properties of metal NPs (MNPs) making them potentially interesting candidates for fast, high resolution nonlinear optical imaging. In this work we characterize and discuss the wavelength dependence of the hyper-Rayleigh scattering (HRS) behavior of spherical gold nanoparticles (GNP) and gold nanorods (GNR) in solution, from 850 nm up to 1300 nm, covering the near-infrared (NIR) window relevant for deep tissue imaging. The high-resolution spectral data allows discriminating between HRS and two photon photoluminescence contributions. Upon particle aggregation, we measured very large enhancements (ca. 10⁴) of the HRS intensity in the NIR, which is explained by considering aggregation-induced plasmon coupling effects and local field enhancement. These results indicate that purposely designed coupled nanostructures could prove advantageous for nonlinear optical imaging and biosensing applications.     

Recent advancements in optical DNA biosensors: exploiting the plasmonic effects of metal nanoparticles

The emerging field of plasmonics, the study of electromagnetic responses of metal nanostructures, has revealed many novel signal enhancing phenomena. As applied to the development of label-free optical DNA biosensors, it is now well established that plasmon-based surface enhanced spectroscopies on nanostructured metal surfaces or metal nanoparticles can markedly improve the sensitivity of optical biosensors, with some showing great promise for single molecule detection. In this review, we first summarize the basic concepts of plasmonics in metal nanostructures, as well as the characteristic optical phenomena to which plasmons give rise. We will then describe recent advances in optical DNA biosensing systems enabled by metal nanoparticle-derived plasmonic effects, including the use of surface enhanced Raman scattering (SERS), colorimetric methods, "scanometric" processes, and metal-enhanced fluorescence (MEF).     

Surface-enhanced Raman scattering: realization of localized surface plasmon resonance using unique substrates and methods

Surface-enhanced Raman scattering (SERS) enhancement and the reproducibility of the SERS signal strongly reflect the quality and nature of the SERS substrates because of diverse localized surface plasmon resonance (LSPR) excitations excited at interstitials or sharp edges. LSPR excitations are the most important ingredients for achieving huge enhancements in the SERS process. In this report, we introduce several gold and silver nanoparticle-based SERS-active substrates developed solely by us and use these substrates to investigate the influence of LSPR excitations on SERS. SERS-active gold substrates were fabricated by immobilizing colloidal gold nanoparticles on glass slides without using any surfactants or electrolytes, whereas most of the SERS-active substrates that use colloidal gold/silver nanoparticles are not free of surfactant. Isolated aggregates, chain-like elongated aggregates and two-dimensional (2D) nanostructures were found to consist mostly of monolayers rather than agglomerations. With reference to correlated LSPR and SERS, combined experiments were carried out on a single platform at the same spatial position. The isolated aggregates mostly show a broadened and shifted SPR peak, whereas a weak blue-shifted peak is observed near 430 nm in addition to broadened peaks centered at 635 and 720 nm in the red spectral region in the chain-like elongated aggregates. In the case of 2D nanostructures, several SPR peaks are observed in diverse frequency regions. The characteristics of LSPR and SERS for the same gold nanoaggregates lead to a good correlation between SPR and SERS images. The elongated gold nanostructures show a higher enhancement of the Raman signal than the the isolated and 2D samples. In the case of SERS-active silver substrates for protein detection, a new approach has been adopted, in contrast to the conventional fabrication method. Colloidal silver nanoparticles are immobilized on the protein functionalized glass slides, and further SERS measurements are carried out based on LSPR excitations. A new strategy for the detection of biomolecules, particularly glutathione, under aqueous conditions is proposed. Finally, supramolecular J-aggregates of ionic dyes incorporated with silver colloidal aggregates are characterized by SERS measurements and correlated to finite-difference time-domain analysis with reference to LSPR excitations. Figure SPR and SERS images for isolated, elongated and two-dimensional gold nanostructures     

The pillar[5]arene-based spun thin films: preparation,characterization, development of optical and mass sensitive sensors for swelling dynamics and gas sensing abilities

Pillar[5]arene (P5)-based materials can be preferable one of the most sensing elements in chemical sensor applications due to their high cavity and their special chiral structure. While the P5-based macrocycle molecules have been utilized as thin-film materials, the reports of chemical sensor application by performing P5 as sensor molecules have been very limited in the available literature. In this report, quinoline P5 (P5-Q) molecules were used to produce thin films via spin coating technique. P5-Q spun films were characterized with Atomic Force Microscopy (AFM) and Ultraviolet–Visible (UV–Vis) spectrophotometer. The gas sensing abilities of these P5-Q spun films were investigated by Quartz Crystal Microbalance (QCM) and Surface Plasmon Resonance (SPR) techniques. In order to illuminate the gas sensing properties of P5-Q spun films, they were prepared as mass-sensitive and optical sensors. These sensors were utilized for its sensing abilities against organic vapours (acetone, methyl alcohol, and ethyl alcohol) by the mechanism of host–guest interaction. The current study also describes the diffusion coefficients of these organic vapors to illuminate the swelling dynamics of P5-Q spun films by performing Fick’s diffusion equation. The responses of P5-based optical (SPR) or mass sensitive (QCM) sensor in terms of the change in reflective intensity or the change in frequency and the values of diffusion coefficients showed that P5-Q molecules can be developed as potential chemical sensor element for acetone vapor compared to alcohol vapors.

     

Electrochemical biosensors based on Ti3C2Tx MXene: future perspectives for on-site analysis

MXenes are recently developed two-dimensional layered materials composed of early transition metal carbides and/or nitrides that provide unique characteristics for biosensor applications. This review presents the recent progress made on the usage and applications of MXenes in the field of electrochemical biosensors, including microfluidic biosensors and wearable microfluidic biosensors, and highlights the challenges with possible solutions and future needs. The multilayered configuration and high conductivity make these materials as an immobilization matrix for the biomolecule immobilization with activity retention and to be explored in the fabrication of electrochemical sensors, respectively. First, how the MXene nanocomposite as an electrode modifier affects the sensing performance of the electrochemical biosensors based on enzymes, aptamer/DNA, and immunoassays is well described. Second, recent developments in MXene nanocomposites as wearable biosensing platforms for the biomolecule detection are highlighted. This review pointed out the future concerns and directions for the use of MXene nanocomposites to fabricate advanced electrochemical biosensors with high sensitivity and selectivity. Specifically, possibilities for developing microfluidic electrochemical sensors and wearable electrochemical microfluidic sensors with integrated biomolecule detection are emphasized.     

EOT or Kretschmann configuration? Comparative study of the plasmonic modes in gold nanohole arrays

The debate is still ongoing on the optimal mode of interrogation for surface plasmon resonance (SPR) sensors. Comparative studies previously demonstrated that nanoparticles exhibiting a localized SPR (LSPR) have superior sensitivity to molecular adsorption processes while thin Au film-based propagating SPR is more sensitive to bulk refractive index. In this paper, it is demonstrated that nanohole arrays (1000 nm periodicity, 600 nm diameter and 125 nm depth), which support both LSPR and propagating SPR modes, exhibited superior sensitivity to bulk refractive index and improved detection limits for IgG sensing by using the Kretschmann configuration. The greater sensitivity to IgG detection in the Kretschmann configuration was obtained despite the shorter penetration depth of nanohole arrays excited in the enhanced optical transmission (EOT) configuration. The decay length of the electromagnetic field in EOT mode was estimated to be approximately 140 nm using a layer-by-layer deposition technique of polyelectrolytes (PAH and PSS) and was confirmed with 3D FDTD simulations, which was lengthen by almost a factor of two in the Kretschmann configuration. Spectroscopic data and field depth were correlated with RCWA and FDTD simulations, which were in good agreement with the experimental results. Considering these analytical parameters, it is advantageous to develop sensors based on nanohole arrays in the Kretschmann configuration of SPR.     

Performance improvement of plasmonic sensors using a combination of AC electrokinetic effects for (bio)target capture

Analytes concentration techniques are being developed with the appealing expectation to boost the performance of biosensors. One promising method lies in the use of electrokinetic forces. We present hereafter a new design for a microstructured plasmonic sensor which is obtained by conventional microfabrication techniques, and which can easily be adapted on a classical surface plasmon resonance imaging (SPRI) system without further significant modification. Dielectrophoretic trapping and electro‐osmotic displacement of the targets in the scanned fluid are performed through interdigitated 200 μm wide gold electrodes that also act as the SPR‐sensing substrate. We demonstrate the efficiency of our device's collection capabilities for objects of different sizes (200 nm and 1 μm PS beads, as well as 5–10 μm yeast cells). SPRI is relevant for the spatial analysis of the mass accumulation at the electrode surface. We demonstrate that our device overcomes the diffusion limit encountered in classical SPR sensors thanks to rapid collection capabilities (<1 min) and we show a consequent improvement of the detection limit, by a factor >300. This study of an original device combining SPRI and electrokinetic forces paves the way to the development of fully integrated active plasmonic sensors with direct applications in life sciences, electrochemistry, environmental monitoring and agri‐food industry.