Localized Surface Plasmon Resonance Substrate Research Articles

An Odor Trace Visualization System Using a Two-Dimensional Backside Scattering Localized Surface Plasmon Resonance Gas Sensor

Odor information fills every corner of our lives yet obtaining its spatiotemporal distribution is a difficult challenge. Localized surface plasmon resonance has shown good sensitivity and a high response/recovery speed in odor sensing and converts chemical information such as odor information into optical information, which can be captured by charge-coupled device cameras. This suggests that the utilization of localized surface plasmon resonance has great potential in two-dimensional odor trace visualization. In this study, we developed a two-dimensional imaging system based on backside scattering from a localized surface plasmon resonance substrate to visualize odor traces, providing an intuitive representation of the spatiotemporal distribution of odor, and evaluated the performance of the system. In comparative experiments, we observed distinct differences between odor traces and disturbances caused by environmental factors in differential images. In addition, we noted changes in intensity at positions corresponding to the odor traces. Furthermore, for indoor experiments, we developed a method of finding the optimal capture time by comparing changes in differential images relative to the shape of the original odor trace. This method is expected to assist in the collection of spatial information of unknown odor traces in future research.

Wearable Localized Surface Plasmon Resonance-Based Biosensor with Highly Sensitive and Direct Detection of Cortisol in Human Sweat

Wearable biosensors have the potential for developing individualized health evaluation and detection systems owing to their ability to provide continuous real-time physiological data. Among various wearable biosensors, localized surface plasmon resonance (LSPR)-based wearable sensors can be versatile in various practical applications owing to their sensitive interactions with specific analytes. Understanding and analyzing endocrine responses to stress is particularly crucial for evaluating human performance, diagnosing stress-related diseases, and monitoring mental health, as stress takes a serious toll on physiological health and psychological well-being. Cortisol is an essential biomarker of stress because of the close relationship between cortisol concentration in the human body and stress level. In this study, a flexible LSPR biosensor was manufactured to detect cortisol levels in the human body by depositing gold nanoparticle (AuNP) layers on a 3-aminopropyltriethoxysilane (APTES)-functionalized poly (dimethylsiloxane) (PDMS) substrate. Subsequently, an aptamer was immobilized on the surface of the LSPR substrate, enabling highly sensitive and selective cortisol capture owing to its specific cortisol recognition. The biosensor exhibited excellent detection ability in cortisol solutions of various concentrations ranging from 0.1 to 1000 nM with a detection limit of 0.1 nM. The flexible LSPR biosensor also demonstrated good stability under various mechanical deformations. Furthermore, the cortisol levels of the flexible LSPR biosensor were also measured in the human epidermis before and after exercise as well as in the morning and afternoon. Our biosensors, which combine easily manufactured flexible sensors with sensitive cortisol-detecting molecules to measure human stress levels, could be versatile candidates for human-friendly products.

Gold Nanoparticle Enabled Localized Surface Plasmon Resonance on Unique Gold Nanomushroom Structures for On-Chip CRISPR-Cas13a Sensing.

A novel localized surface plasmon resonance (LSPR) system based on the coupling of gold nanomushrooms (AuNMs) and gold nanoparticles (AuNPs) is developed to enable a significant plasmonic resonant shift. The AuNP size, surface chemistry, and concentration are characterized to maximize the LSPR effect. A 31 nm redshift is achieved when the AuNMs are saturated by the AuNPs. This giant redshift also increases the full width of the spectrum and is explained by the 3D finite-difference time-domain (FDTD) calculation. In addition, this LSPR substrate is packaged in a microfluidic cell and integrated with a CRISPR-Cas13a RNA detection assay for the detection of the SARS-CoV-2 RNA targets. Once activated by the target, the AuNPs are cleaved from linker probes and randomly deposited on the AuNM substrate, demonstrating a large redshift. The novel LSPR chip using AuNP as an indicator is simple, specific, isothermal, and label-free; and thus, provides a new opportunity to achieve the next generation multiplexing and sensitive molecular diagnostic system.

Comparison of Hydrogen Peroxide Secretion From Living Cells Cultured in Different Formats Using Hydrogel-Based LSPR Substrates.

Reactive oxygen species (ROS), a number of reactive molecules and free radicals derived from molecular oxygen, are generated as by-products during mitochondrial electron transport within cells. Physiologically, cells are capable of metabolizing the ROS exploiting specific mechanisms. However, if excessive ROS accumulate inside the cells, it will cause the cells apoptosis or necrosis. Hydrogen peroxide (H2O2) is one of the essential ROS often participating in chemical reactions in organisms and regulating homeostasis in the body. Therefore, rapid and sensitive detection of H2O2 is a significant task in cell biology research. Furthermore, it has been found that cells cultured in different formats can result in different cellular responses and biological activities. In order to investigate the H2O2 secretion from the cells cultured in different formats, a hydrogel-based substrate is exploited to separate relatively large molecular (e.g., proteins) for direct measurement of H2O2 secreted from living cells in complete cell culture medium containing serum. The substrate takes advantage of the localized surface plasmon resonance (LSPR) method based on enzyme immunoprecipitation. In addition, the H2O2 secreted from the cells cultured in different dimensions (suspension of single cells and three-dimensional cell spheroids) treated with identical drugs is measured and compared. The spheroid samples can be prepared with ample amount using a designed microfluidic device with precise control of size. The results show that the H2O2 secretion from the cells are great affected by their culture formats.

Wafer-Scale LSPR Substrate: Oblique Deposition of Gold on a Patterned Sapphire Substrate.

Label-free detection of biomolecules using localized surface plasmon resonance (LSPR) substrates is a highly attractive method for point-of-care (POC) testing. One of the remaining challenges to developing LSPR-based POC devices is to fabricate the LSPR substrates with large-scale, reproducible, and high-throughput. Herein, a fabrication strategy for wafer-scale LSPR substrates is demonstrated using reproducible, high-throughput techniques, such as nanoimprint lithography, wet-etching, and thin film deposition. A transparent sapphire wafer, on which SiO2-nanodot hard masks were formed via nanoimprint lithography, was anisotropically etched by a mixed solution of H2SO4 and H3PO4, resulting in a patterned sapphire substrate (PSS). An LSPR substrate was finally fabricated by oblique deposition of Au onto the PSS, which was then applied to label-free detection of the binding events of biomolecules. To the best of our knowledge, this paper is the first report on the application of the PSS used as an LSPR template by obliquely depositing a metal.

Plasmonic gel films for time-lapse LSPR detection of hydrogen peroxide secreted from living cells

In this paper, we developed a low-cost and easy-to-fabricate hydrogel-based localized surface plasmon resonance (LSPR) substrate for sensitive, consistent, specific, and time-lapse detection of hydrogen peroxide (H2O2) secreted from living cells in cell culture medium. The uniform and reproducible LSPR substrate was made from agarose, gold nanorods (AuNRs), horseradish peroxidase (HRP), and 3-amino-9-ethylcarbazole (AEC). In H2O2 sensing, insoluble precipitates were generated in the gel film by an HRP-catalyzed reaction in the presence H2O2, and the precipitates near the AuNRs caused a LSPR shift of the substrate, which could be used for H2O2 quantification. Using the developed substrate, we showed that a H2O2 concentration as low as 0.5 μM could be detected in complete cell culture medium within 30 min with good reproducibility. In addition, we demonstrated time-lapse detection of H2O2 secreted from living cells after the cells were stimulated by ascorbic acid. The results indicated that the agarose gel of the substrate provided the filtration capability and the improved stability of the AuNRs allowing detection of H2O2 in cell culture medium without tedious sample preparation procedures. Moreover, the HRP-catalyzed reaction-based LSPR biosensing offered good selectivity for H2O2 detection and possessed great potential for various in vitro cell studies.

Labeling-free detection of ECD-HER2 protein using aptamer-based nano-plasmonic sensor

A gold nanoparticle-based localized surface plasmon resonance substrate has been developed as nano-sensors for various bio-applications. However, reproducible and robust sensing substrates anchored gold nanoparticles has not yet been explored. In this study, dopamine-coated gold nanorods (DGNRs) were prepared and immobilized onto the micro-grooving PDMS substrates (mgPDMS). Subsequently, HER2-specific aptamers were conjugated with DGNR/mgPDMS for ECD-HER2 detection. By screening of the optimal concentration of DGNR and aptamers, the effective HER2-specific aptasensor was built up. In particular, the real-time binding assay for the evaluation of limit-of-detection (<5 ng ml−1) was conducted. Furthermore, the binding kinetics for ECD-HER2 was investigated under the biological fluid using a rat serum. Our HER2-specific aptasensor demonstrated the effective sensitivity and selectivity for ECD-HER2.

Localized surface plasmon resonance aptasensor for the highly sensitive direct detection of cortisol in human saliva

Cortisol, which is a stress biomarker that causes various mental disorders, is found in sweat, saliva, blood, and urine. Because mental disorders resulting from stress are a silent contributor to various diseases, the detection of cortisol level is an important step in their prevention. Here, we developed a highly sensitive, localized surface plasmon resonance (LSPR) aptasensor for the direct detection of cortisol in saliva. The LSPR aptasensor was constructed using gold nanoparticles of different sizes. Subsequently, the surface of the LSPR substrate was immobilized using an aptamer for capturing cortisol. The detection capability of the LSPR aptasensor was compared with that of the antibody- immobilized sensor. The LSPR aptasensor displayed excellent detection capability for a wide range of cortisol concentrations extending from 0.1–1000 nM with a detection limit of 0.1 nM. In addition, the LSPR aptasensor was able to selectively detect cortisol among other substances with similar chemical structures (e.g., cortisone, corticosterone, progesterone, and triamcinolone). These results indicate that the LSPR aptasensor may be used for the highly sensitive and selective detection of cortisol in salivary samples.

Reproducible Plasmonic Nanopyramid Array of Various Metals for Highly Sensitive Refractometric and Surface-Enhanced Raman Biosensing.

Localized surface plasmon resonance (LSPR) biosensors show great potential for practical/commercial use in clinical diagnosis, home healthcare, environmental analysis, and public healthcare. However, two main issues, that is, low refractometric sensitivity and low reproducibility (large-area uniformity and batch-to-batch consistency), hinder the extensive applications of LSPR biosensors. Therefore, plasmonic nanostructures with high sensitivity and excellent reproducibility are desirable for preparing reliable LSPR sensors. Herein, we have fabricated plasmonic nanopyramid arrays (NPAs) for several batches with reproducible morphology and optical properties by elastic soft lithography and metal thermal evaporation. NPAs of various metals (i.e., Al, Au, and Ag) were also prepared by thermal evaporation with the according metals. The transmission spectra of these NPAs showed several narrow LSPR peaks in the visible-infrared wavelength region. The refractometric sensitivities of the LSPR peaks were systematically studied, and high refractometric sensitivities of 774.0, 472.8, and 421.0 nm/RIU were achieved on Al, Au, and Ag NPAs, respectively. To demonstrate the potential of the NPAs for multiplex applications, we first applied this highly sensitive Al NPA biosensor to monitoring the process of proliferation of HeLa cancer cells, in situ and in real time. Then, we demonstrated that the Au NPA was able to identify the absorbed analytes on its surface through the surface-enhanced Raman scattering spectrum. In addition, the finite difference time domain simulations were performed to reveal the electromagnetic field enhancement on NPAs. Because of the properties of high sensitivity and excellent reproducibility of the metal NPA LSPR substrates, as well as the simplicity and cost efficiency of the fabrication method, our proposed work will accelerate the practical use of LSPR sensors.

Homologous Gold Nanoparticles and Nanoclusters Composites with Enhanced Surface Raman Scattering and Metal Fluorescence for Cancer Imaging.

A large number of deaths from cancer can be attributed to the lack of effective early-stage diagnostic techniques. Thus, accurate and effective early diagnosis is a major research goal worldwide. With the unique phenomenon of localized surface plasmon resonance (LSPR), plasmonic nanomaterials have attracted considerable attention for applications in surface-enhanced Raman scattering (SERS) and metal-enhanced fluorescence (MEF). Both SERS and MEF are ultra-sensitive methods for the detection and identification of early tumor at molecular level. To combine the merits of the fast and accurate imaging of MEF and the stable and clear imaging of SERS, we propose a novel dual functional imaging nanoprobe based on gold nanoparticles and gold nanocluster composites (denoted AuNPC-RGD). The gold nanoparticles are used as LSPR substrates to realized enhancement of Raman or fluorescence signal, while the gold nanoclusters serve as a fluorophore for MEF imaging, and exhibit better biocompatibility and stability. Furthermore, target molecule of cyclic Arg-Gly-Asp (cRGD) is incorporated into the composite to improve delivery efficiency, selectivity and imaging accuracy. These integrated properties endow AuNPC-RGD composites with outstanding biocompatibility and excellent imaging abilities, which could be used to achieve accurate and effective diagnosis for early cancer.

High sensitive detection of copper II ions using D-penicillamine-coated gold nanorods based on localized surface plasmon resonance

In this paper, we describe the development of a nanoplasmonic biosensor based on the localized surface plasmon resonance (LSPR) effect that enables a sensitive and selective recognition of copper II ions. First, we fabricated the nanoplasmonics as LSPR substrates using gold nanorods (GNR) and the nano-adsorption method. The LSPR sensitivity of the nanoplasmonics was evaluated using various solvents with different refractive indexes. Subsequently, D-penicillamine (DPA)—a chelating agent of copper II ions—was conjugated to the surface of the GNR. The limit of detection (LOD) for the DPA-conjugated nanoplasmonics was 100 pM. Furthermore, selectivity tests were conducted using various divalent cations, and sensitivity tests were conducted on the nanoplasmonics under blood-like environments. Finally, the developed nanoplasmonic biosensor based on GNR shows great potential for the effective recognition of copper II ions, even in human blood conditions.

A new technique to detect antibody-antigen reaction (biological interactions) on a localized surface plasmon resonance (LSPR) based nano ripple gold chip

We demonstrate that the gold nano-ripple localized surface plasmon resonance (LSPR) chip is a low cost and a label-free method for detecting the presence of an antigen. A uniform stable layer of an antibody was coated on the surface of a nano-ripple gold pattern chip followed by the addition of different concentrations of the antigen. A red shift was observed in the LSPR spectral peak caused by the change in the local refractive index in the vicinity of the nanostructure. The LSPR chip was fabricated using oblique gas cluster ion beam (GCIB) irradiation. The plasmon-resonance intensity of the scattered light was measured by a simple optical spectroscope. The gold nano ripple chip shows monolayer scale sensitivity and high selectivity. The LSPR substrate was used to detect antibody-antigen reaction of rabbit X-DENTT antibody and DENTT blocking peptide (antigen).

Superior LSPR substrates based on electromagnetic decoupling for on-a-chip high-throughput label-free biosensing

Localized surface plasmon resonance (LSPR) biosensing based on supported metal nanoparticles offers unparalleled possibilities for high-end miniaturization, multiplexing and high-throughput label-free molecular interaction analysis in real time when integrated within an opto-fluidic environment. However, such LSPR-sensing devices typically contain extremely large regions of dielectric materials that are open to molecular adsorption, which must be carefully blocked to avoid compromising the device readings. To address this issue, we made the support essentially invisible to the LSPR by carefully removing the dielectric material overlapping with the localized plasmonic fields through optimized wet-etching. The resulting LSPR substrate, which consists of gold nanodisks centered on narrow SiO2 pillars, exhibits markedly reduced vulnerability to nonspecific substrate adsorption, thus allowing, in an ideal case, the implementation of thicker and more efficient passivation layers. We demonstrate that this approach is effective and fully compatible with state-of-the-art multiplexed real-time biosensing technology and thus represents the ideal substrate design for high-throughput label-free biosensing systems with minimal sample consumption.

Antibody modified gold nano-mushroom arrays for rapid detection of alpha-fetoprotein

Localized surface plasmon resonance (LSPR) combined with immunoassay shows greatly potential in fast detection of tumor markers. In this paper, a highly sensitive LSPR substrate has been fabricated and modified for direct detection of alpha-fetoprotein (AFP). The biosensor was prepared by interference lithography, and modified by covalently immobilizing anti-AFP on the surface of gold nano-mushroom arrays (GNMA). The modification process was investigated by Vis–NIR reflectance spectra and cyclic voltammogram measurements. We revealed the optical properties of the modified GNMA by measuring the Vis–NIR reflectance spectra and simulating its electric intensity field distribution under light illumination. The GNMA substrate was highly sensitive, with a refractive index sensitivity of ~465nm/RIU. The substrate can be applied to label-free detection of AFP, with the linear range and the limit of detection determined to be 20–200ng/mL and 24ng/mL (S/N=3), respectively. We also demonstrated its clinical application by directly detecting AFP in human serum samples. It is expected that our biosensor could be integrated on microfluidic chips for high-throughput detection in portable early diagnosis, post-operative and point-of-care (POC) in clinical applications.

Blue-Shifted Narrow Localized Surface Plasmon Resonance from Dipole Coupling in Gold Nanoparticle Random Arrays

In this work, we develop a simple method to produce highly uniform localized surface plasmon resonance (LSPR) substrates based on self-assembly of colloidal gold nanoparticles onto pretreated glass substrates. The LSPR wavelength of the gold nanoparticle arrays is blue-shifted from that of the gold nanoparticles in solution and the single gold nanoparticles on glass substrate. The LSPR width is narrower than that of the single gold nanoparticles. The blue-shifted LSPR is due to the long-range dipole coupling in the gold nanoparticle random arrays indicated from simulations using the T-matrix method. In addition to the popularly used LSPR wavelength dependence on the dielectric environment, we have found that the LSPR width of the gold nanoparticle random arrays is also sensitive to the change in the dielectric environment. The LSPR substrates are reproducible, uniform, and robust with potential applications in LSPR sensing and imaging.

LSPR Sensor Combining Sharp Resonance and Differential Optical Measurements

A new optical sensor based on the localized surface plasmon resonance (LSPR) in 2D arrays of silver nanoparticles (AgNPs) combined with a differential optical measurement method is developed. LSPR substrates comprised of self-assembled, 2D arrays of AgNPs exhibit coherent plasmon coupling manifested as a sharp peak in the blue spectral region. A bottom-up approach was used to fabricate reproducible and cost-effective substrates with a figure of merit (FOM) of ~24. The LSPR shift was determined by measuring the difference between light extinction at two wavelengths selected on each side of the sharp peak. The sharpness of the coherent plasmon resonance together with the differential measurement method enabled a record sensing resolution in bulk for a LSPR sensor of ~4.8E-6 RIU.

Localized surface plasmon resonance-based label-free biosensor for highly sensitive detection of dopamine.

Localized surface plasmon resonance (LSPR) is the phenomenon that is observed on specific metal nanoparticles (NPs) like Au, Ag which can be used for sensitive detection for many kinds of biomaterials. Dopamine (DA) is a typical neurotransmitter considered as indicator of some neural diseases. Due to its small size, it is very difficult to detect DA at low concentrations directly and sensitively with conventional sensing techniques. In this research, we propose a DA detection sensor based on LSPR phenomenon. Electrochemical deposition technique was used to make LSPR substrates, where Au NPs were electrochemically deposited on ITO glasses and these substrates showed optical characteristic of LSPR phenomenon. Different concentrations of DA solution were deposited on antibody immobilized LSPR substrates. With additions of increasing concentrations of DA, LSPR peak intensity was increased linearly. These results could be applied to many fields of clinical trials for diseases caused by small molecules.

A compact differential refractive index sensor based on localized surface plasmons

Here we present a small-scale differential refractive index sensor configuration based on localized surface plasmon resonance (LSPR) sensing on top of a photodiode array. A thin gold film containing short-range ordered holes with localized SPR properties is placed onto two photodiode elements. The LSPR substrate is covered by two immersion media having one known (reference) on the first photodetector element and one unknown refractive index on the second. Transmitted light is detected and a lateral position of maximum light transmission (PosMLT) between the two photodetector elements is calculated. Multiple incident wavelengths are chosen to compute the lateral PosMLT in the wavelength regime of 620–640nm, which coincides with a region of linear LSPR extinction. The sensor layout is tested with media of varying refractive indices. A linear dependency between the change of PosMLT per wavelength shift on the change of the refractive index is obtained and determined to be of 203.2μm/nm per refractive index unit (RIU) for our LSPR substrate. The obtained results are explained by the extinction properties of the LSPR substrate. The resolution limit is governed by the statistical noise if the difference in refractive index decreases, which is discussed here in detail. With this small-scale sensor configuration, the determination of refractive index changes can be carried out with light incident normal to the plane of the sensor. Furthermore, the evaluation of the transmitted light can be conducted without the use of spectrometers and bulky optics. The sensor principle outlined here can be adapted to other LSPR substrates and can be employed for various sensing tasks, e.g. in water monitoring, chemical industries or medical/biological lab on a chip applications.

Plasmonic metal-dielectric-metal stack structure with subwavelength metallic gratings for improving sensor sensitivity and signal quality.

In this study, we investigated the performance improvement of a localized surface plasmon resonance (LSPR) biosensor by incorporating a metal-dielectric-metal (MDM) stack structure and subwavelength metallic nanograting. The numerical results showed that the LSPR substrate with a MDM stack can provide not only a better sensitivity by more than five times but also a notably improved signal quality. While the gold nanogratings on a gold film inevitably lead to a broad and shallow reflectance curve, the presence of a MDM stack can prevent propagating surface plasmons from interference by locally enhanced fields excited at the gold nanogratings, finally resulting in a strong and deep absorption band at resonance. Therefore, the proposed LSPR structure could potentially open a new possibility of enhanced detection for monitoring biomolecular interactions of very low molecular weights.

Fabrication of Gold Nanodot Array for the Localized Surface Plasmon Resonance

Localized surface plasmon resonance (LSPR) is a promising method for detecting antigen‐antibody binding in label‐free biosensors. In this study, the fabrication of a LSPR substrate with a gold nanodot array through the lift‐off process of an alumina mask is reported. The substrate showed an extinction peak in its extinction spectrum, and the peak position was dependent on the height of the gold nanodot array, and the change of extinction peak with the height could be predicted by the numerical simulation. In addition, the peak position was observed to be red‐shifted with the increasing RIU value of the medium surrounding the gold nanodot array. In particular, the peak position in the 10 nm thick gold nanodot array was approximately 710 nm in air, and the sensitivity, defined as the ratio of the shift of peak position to the RIU of the medium, was 323.6 nm/RIU. The fabrication procedure could be applied to fabricate the LSPR substrates with a large area.