Plasmonic Chips Research Articles

A plasmonic biosensor pre-diagnostic tool for Familial Mediterranean Fever

Familial Mediterranean Fever (FMF) is an autosomal recessive genetic disorder, primarily observed in populations around the Mediterranean Sea, linked to MEFV gene mutations. These mutations disrupt inflammatory responses, increasing pyrin-protein production. Traditional diagnosis relies on clinical symptoms, family history, acute phase reactants, and excluding similar syndromes with MEFV testing, which is expensive and often inconclusive due to heterozygous mutations. Here, we present a biosensor platform that detects differences in pyrin-protein levels between healthy and affected individuals, offering a cost-effective alternative to genetic testing. Our platform uses gold nanoparticle-based plasmonic chips enhanced with anti-pyrin antibodies, achieving a detection limit of 0.24 ng/mL with high specificity. The system integrates an optofluidic system and visible light spectroscopy for real-time analysis, with signal stability maintained for up to six months. Our technology will enhance FMF diagnosis accuracy, enabling early treatment initiation and providing a cost-effective alternative to genetic testing, thus improving patient care.

Features of the modern development of metal‐insulator‐metal waveguide based plasmonic sensors

AbstractPlasmonic sensors based on metal‐insulator‐metal (MIM) waveguides are renowned for their miniaturization and high sensitivity in various sensing applications. A broad spectrum of researchers is numerically investigating the characteristics of MIM waveguide‐based plasmonic sensors with diverse cavity shapes. However, practical demonstrations of these sensors have not yet been realized, primarily due to the overlooked aspect of the light coupling mechanism into these waveguides. In this context, two distinct methods for coupling light into and out of plasmonic chips based on MIM waveguides are presented.

Heterogeneous Analysis of Extracellular Vesicles for Osteosarcoma Diagnosis.

Osteosarcoma (OS) is the most prevalent primary tumor of bones, often diagnosed late with a poor prognosis. Currently, few effective biomarkers or diagnostic methods have been developed for early OS detection with high confidence, especially for metastatic OS. Tumor-derived extracellular vesicles (EVs) are emerging as promising biomarkers for early cancer diagnosis through liquid biopsy. Here, we report a plasmonic imaging-based biosensing technique, termed subpopulation protein analysis by single EV counting (SPASEC), for size-dependent EV subpopulation analysis. In our SPASEC platform, EVs are accurately sized and counted on plasmonic sensor chips coated with OS-specific antibodies. Subsequently, EVs are categorized into distinct subpopulations based on their sizes, and the membrane proteins of each size-dependent subpopulation are profiled. We measured the heterogeneous expression levels of the EV markers (CD63, BMP2, GD2, and N-cadherin) in each of the EV subsets from both OS cell lines and clinical plasma samples. Using the linear discriminant analysis (LDA) model, the combination of four markers is applied to classify the healthy donors (n = 37), nonmetastatic OS patients (n = 13), and metastatic patients (n = 12) with an area under the curve of 0.95, 0.92, and 0.99, respectively. SPASEC provides accurate EV sensing technology for early OS diagnosis.

Development of one-step roll-to-roll system with incorporated vacuum sputtering for large-scale production of plasmonic sensing chips

The trade-off relationship between cost and performance is a major challenge in the development of surface-enhanced Raman spectroscopy (SERS) sensors for practical applications. We propose a roll-to-roll system with incorporated vacuum sputtering to manufacture Ag-coated nanodimples (Ag/NDs) on A4-scale films in a single step. The Ag/ND SERS platforms were prepared via O2 ion beam sputtering and Ag sputtering deposition. The concave three-dimensional spaces in the Ag/NDs functioned as hotspots, and their optimal fabrication conditions were investigated with two variables: moving speed and Ag thickness. The entire process was automated, which resulted in highly consistent optical responses (i.e., relative standard deviation of ∼10%). The activation of plasmonic hotspots was demonstrated by electric-field profiles calculated via the finite-difference time-domain method. The wavelength dependency of the Ag/ND platforms was also examined by dark-field microscopy. The results indicate that the developed engineering technique for the large-scale production of Ag/ND plasmonic chips would likely be competitive in the commercial market.

Orthogonal mode couplers for plasmonic chip based on metal–insulator–metal waveguide for temperature sensing application

In this work, a plasmonic sensor based on metal–insulator–metal (MIM) waveguide for temperature sensing application is numerically investigated via finite element method (FEM). The resonant cavity filled with PDMS polymer is side-coupled to the MIM bus waveguide. The sensitivity of the proposed device is ~ − 0.44 nm/°C which can be further enhanced to − 0.63 nm/°C by embedding a period array of metallic nanoblocks in the center of the cavity. We comprehend the existence of numerous highly attractive and sensitive plasmonic sensor designs, yet a notable gap exists in the exploration of light coupling mechanisms to these nanoscale waveguides. Consequently, we introduced an attractive approach: orthogonal mode couplers designed for plasmonic chips, which leverage MIM waveguide-based sensors. The optimized transmission of the hybrid system including silicon couplers and MIM waveguide is in the range of − 1.73 dB to − 2.93 dB for a broad wavelength range of 1450–1650 nm. The skillful integration of these couplers not only distinguishes our plasmonic sensor but also positions it as a highly promising solution for an extensive array of sensing applications.

Towards a point-of-care test to cover atto-femto and pico-nano molar concentration ranges in interleukin 6 detection exploiting PMMA-based plasmonic biosensor chips

Point-of-Care tests based on biomarkers, useful to monitor acute and chronic inflammations, are required for advances in medicine. In this scope, a key role is played by pro-inflammatory cytokines, of which interleukin 6 (IL-6) is generally thought as one of the most relevant. To use IL-6 in real scenarios, detection in ultra-low concentration ranges is required. In this work, two IL-6 biosensors are obtained by exploiting the combination of the same antibody self-assembled monolayer with two different plasmonic probes. This approach has demonstrated, via experimental results, that two different IL-6 concentration ranges can be explored. More specifically, IL-6 in an atto-femto molar range can be detected via polymer-based nanoplasmonic chips. On the other hand, a pico-nano molar range is obtained by a surface plasmon resonance platform in plastic optical fibers. As a proof of concept, the detection of IL-6 at the femto molar range has been obtained in Saliva and Serum. The results show that the proposed sensing approach could be useful in developing Point-of-Care devices based on a general setup with the capability to exploit both the plasmonic biosensor chips to monitor the IL-6 in the concentration range of interest, to provide an important support for the diagnosis and monitoring of oral and systemic diseases.

Investigation of the Plasmon-Activated C-C Coupling Reactions by Liquid-State SERS Measurement.

The implementation of plasmonic materials in heterogeneous catalysis was limited due to the lack of experimental access in managing the plasmonic hot carriers. Herein, we propose a liquid-state surface-enhanced Raman scattering (SERS) technique to manipulate and visualize heterogeneous photocatalysis with transparent plasmonic chips. The liquid-state measurement conquers the difficulties that arise from the plasmon-induced thermal effects, and thus the plasmon based strategies can be extended to investigate a wider range of catalytic reactions. We demonstrated the selection of reaction products by modulating the plasmonic hot carriers and explored the mechanisms in several typical C-C coupling reactions with 4-bromothiophenol (4-BTP) as reactants. The real-time experimental results suggest brand new mechanisms of the formation of C-C bonds on plasmonic metal nanoparticles (NPs): the residue of 4-BTP, but not thiophenol (TP), is responsible for the C-C coupling. Furthermore, this technique was extended to study the evolution of the Suzuki-Miyaura reaction on nonplasmonic palladium metals by establishing the charge transfer channels between palladium and Au NPs. The cleavage and formation of chemical bonds in each individual reaction step were discerned, and the corresponding working mechanisms were clarified.

Nanoantenna effect dependent on the center structure of Bull's eye-type plasmonic chip.

A bright spot is observable in the center of Bull's eye plasmonic pattern with a fluorescence microscope due to the plasmonic nanoantenna effect. In this effect, a propagating wave of surface plasmon resonance concentrates in the center. This study focused on the relationship between the center structure of Bull's eye pattern and the nanoantenna effect in four fabricated Bull's eye-type plasmonic chips with centers of different sizes (full- or half-pitch diameter) and shapes (convex or concave). The fluorescence intensity of the fluorescent nanoparticles adsorbed to these plasmonic chips was measured with an upright-inverted microscope to evaluate the plasmonic chip enhancement factor composed of the product of the excitation and emission enhancement and individual factors. When the emission enhancement factor was investigated under nonresonance excitation conditions, by the disappearance of a bright spot, excitation enhancement was found to contribute to the plasmonic nanoantenna effect. The concave Bull's eye structure with a half-pitch diameter demonstrates the highest nanoantenna effect due to the formation of a larger constructive wave in the superposition of the diffraction wave of incident light under resonance conditions. In addition, the electromagnetic field intensity simulated by discrete dipole approximation agrees with the microscopy results. Overall, the results indicate that the plasmonic nanoantenna effect could be controlled depending on the resonance condition and center structure.

Rayleigh anomaly-enabled mode hybridization in gold nanohole arrays by scalable colloidal lithography for highly-sensitive biosensing

Abstract Plasmonic sensors exhibit tremendous potential to accomplish real-time, label-free, and high-sensitivity biosensing. Gold nanohole array (GNA) is one of the classic plasmonic nanostructures that can be readily fabricated and integrated into microfluidic platforms for a variety of applications. Even though GNA has been widely studied, new phenomena and applications are still emerging continuously expanding its capabilities. In this article, we demonstrated narrow-band high-order resonances enabled by Rayleigh anomaly in the nanohole arrays that are fabricated by scalable colloidal lithography. We fabricated large-area GNAs with different hole diameters, and investigated their transmission characteristics both numerically and experimentally. We showed that mode hybridization between the plasmon mode of the nanoholes and Rayleigh anomaly of the array could give rise to high-quality decapole resonance with a unique nearfield profile. We experimentally achieved a refractive index sensitivity, i.e., RIS up to 407 nm/RIU. More importantly, we introduced a spectrometer-free refractive index sensing based on lens-free smartphone imaging of GNAs with (intensity) sensitivity up to 137%/RIU. Using this platform, we realized the label-free detection of BSA molecules with concentration as low as 10−8 M. We believe our work could pave the way for highly sensitive and compact point-of-care devices with cost-effective and high-throughput plasmonic chips.

Nanostructured plasmonic chips employing nanopillar and nanoring hole arrays for enhanced sensitivity of SPR-based biosensing.

We present a theoretical analysis of the different nanostructured plasmonic sensor chips—consisting of plasmonic nanostructures present on the surface of plasmonic thin films—interrogated using the Kretschmann configuration for highly sensitive localized sensing, with high tunability from the visible to the infrared regions. Rigorous coupled-wave analysis is performed to analyze all the proposed nanostructured sensor chips and compare their sensing performance. The sensitivity parameters are defined to focus on the detection of a thin layer of biomolecules on the surface of nanostructures. The dimensions of the nanostructures and the incident angle shift the plasmon resonance wavelengths and can be used to tune the operating wavelength. The nanostructured films create local regions of high electric fields, which results in enhanced sensitivity of the proposed structures. The proposed sensors can be used in surface plasmon resonance imaging to detect multiple biomolecules in a single measurement. An extremely high surface sensitivity and figure of merit (FOMS) of 91 nm nm−1 and 0.59 nm−1 has been found, respectively, for one of the proposed nanostructured sensing platforms. Moreover, we demonstrate a very high differential reflectance of 55% per nm thickness of the biolayer.

Surface engineering of plasmonic gold nanoisland platforms for high-sensitivity refractometric biosensing applications

Plasmonic chips comprising gold nanoisland structures that are fabricated by solution-phase seeding, have demonstrated excellent promise as high-sensitivity substrates for molecular detection and medical diagnostic applications. Even so, there still remains an outstanding need to examine the potential utility of these plasmonic chips for label-free refractometric biosensing and to understand how nanostructure design principles affect measurement sensitivity. Herein, we developed a thiol-based surface functionalization strategy to fabricate gold nanoislands on a functionalized glass surface with improved fractional surface coverages and inter-island gap distances of 80–85% and 5–10 nm, respectively, as compared to values of 50–65% and 15–20 nm for gold nanoislands on bare glass substrates. By tuning the gap distance, it was possible to adjust the bulk refractive index sensitivity of the measurement signal from ∼99 nm per refractive index unit (nm/RIU) for gold nanoislands on a non-functionalized glass surface to ∼180 nm/RIU for gold nanoislands on a functionalized glass surface. The nanoplasmonic biosensing capabilities of the latter plasmonic chip were further investigated and demonstrated larger measurement responses for detecting bovine serum albumin (BSA) protein adsorption compared to other types of plasmonic gold nanostructures. It was also possible to detect antigen-antibody interactions related to coronavirus disease-2019 (COVID-19), especially binding events that occurred near the sensor surface. These findings demonstrate the broad application possibilities of gold nanoisland platforms for refractometric biosensing and emphasize the importance of finetuning nanostructure dimensions to optimize sensing performance.

Effect of Methadone and Tramadol Opioids on Stem Cells Based on Integrated Plasmonic-Ellipsometry Technique.

Introduction: Plasmonic biosensors provide high sensitivity in detecting the low amount of biomarkers and pharmaceutical drugs. We studied the mesenchyme cell activity under the treatment of common sedative drugs of methadone and tramadol using the integrated plasmonic-ellipsometry technique. Methods: Mesenchymal stem cells were cultured on patterned plasmonic chips under the treatment of methadone and tramadol drugs. Three cultured chips were kept non-treated as the control ones. The plasmonic-ellipsometry technique was applied to study the signaling characteristic of the cells affected by these two drugs. In this technique, optical information regarding the amplitude ratio and phase change between p- and s-polarized light was recorded. Results: This drug treatment could affect the spectral plasmonic resonance and subsequently the phase shift (Δ) and the amplitude ratio (Ψ) values under p- and s-polarized impinging light. A more significant Δ value for tramadol treatment meant that the phase split was larger between p- and s-polarized light. Tramadol also had more prominent absolute Δ eff and Ψ eff values in comparison with methadone. Conclusion: We showed that tramadol caused more contrast in phase shift (Δ) and amplitude ratio (Ψ) between p- and s-polarized impinging light for cultured stem cells in comparison with methadone. It means that tramadol differentiated more the optical responses for p- and s-polarized lights compared to methadone. Our proposed technique possesses the potential of quantitative and qualitative analysis of drugs on humans even on a cell scale.

Annealed plasmonic Ag nanoparticle films for surface enhanced fluorescence substrate

In this work, the silver nanoparticle (Ag NP) films were deposited on glass slide by dc magnetron sputtering. The effect of annealing temperature on morphology and optical property were characterized by field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM) and UV–Vis-NIR spectroscopy, respectively. From the results, the size and inter-particle distance of Ag NPs depend on annealing temperature. The localized surface plasmon resonance (LSPR) band position shift to the blue with the annealing temperature increased. The surface enhanced fluorescence (SEF) effect of the Ag NPs films was investigated by emission spectra of Rhodamine 6G (Rh6G) fluorescent molecules. It was found that the florescent intensity of R6G, corresponding to the diameter and surface roughness of Au NP films. Finally, the Ag NPs film substrate offer a cost-effective with non-lithography fabrication potentially applied in plasmonic sensor chips for biomedical and food safety applications.

Large-Scale Inhomogeneous Fluorescence Plasmonic Silver Chips: Origin and Mechanism

Summary Large-scale inhomogeneous plasmonic metal chips have been demonstrated as a promising platform for biochemical sensing, but the origin of their strong fluorescence enhancements and average gap dependence is a challenging issue due to the complexity of modeling tremendous molecules within inhomogeneous gaps. To address this issue, we bridged microscopic mechanisms and macroscopic observations, developed a kinetic model, and experimentally investigated the fluorescence enhancement factors of IR800-streptavidin immobilized on metal nanoisland films (NIFs). Inspired by the kinetic model, we controlled the distribution of IR800-streptavidin within the valleys of NIFs by regioselective modification and achieved the fluorescence intensity enhancement up to 488-fold. The kinetic model allows us to qualitatively explain the mechanism of fluorescence intensity enhancements and quantitatively predict the trend of experimental enhancement factors, thereby determining the design principles of the plasmonic metal chips. Our study provides one key step further toward the sensing applications of large-scale plasmonic metal chips.

Microscopic Study on Excitation and Emission Enhancement by the Plasmon Mode on a Plasmonic Chip.

Excitation and emission enhancement by using the plasmon mode formed on a plasmonic chip was studied with a microscope and micro-spectroscope. Surface plasmon resonance wavelengths were observed on one-dimensional (1D) and two-dimensional (2D) plasmonic chips by measuring reflection and transmission spectra, and they were assigned to the plasmon modes predicted by the theoretical resonance wavelengths. The excitation and emission enhancements were evaluated using the fluorescence intensity of yellow–green fluorescence particles. The 2D grating had plasmon modes of (diagonal direction with m = 2) in addition to the fundamental mode of (direction of a square one side) in the visible range. In epifluorescence detection, the excitation enhancement factors of on the 1D and 2D chips were found to be 1.3–1.4, and the emission enhancement factor of on the 2D chip was 1.5–1.8, although the emission enhancement was not found on the 1D chip. Moreover, enhancement factors for the other fluorophores were also studied. The emission enhancement factor of was shown to depend on the fluorescence quantum yield. The emission enhancement of 2D was 1.3-fold larger than that of 1D considering all azimuth components, and the 2D pattern was shown to be advantageous for bright fluorescence microscopic observation.

Multifunctional shape-dependent plasmonic nanoprobe by enzymatic etching of single gold triangular nanoplate

Hydrogen peroxide (H2O2), as a signaling molecule, plays a vital role in a wide variety of signaling transduction processes, aging, and diseases. However, the excessive production of H2O2 causes various diseases. Herein, we develop a novel method for H2O2 detection in live cells via dark-field scattering spectroscopy with gold triangular nanoprisms (AuTNPs) as probes. The corners of AuTNPs would be gradually oxidatively etched by the strong coordination of Br• which is generated by enzymatic reactions in the presence of horseradish peroxidase (HRP), bromide ion and trace hydrogen peroxide. Benefitting from the morphological change, the single AuTNP based plasmonic nanoprobe shows notable blueshifts and scattering color changes which could be real-time monitored under the dark-field microscopy. The peak position in the scattering spectra of individual AuTNP blueshifts linearly with the increase of H2O2 concentration, and exhibits high sensitivity to H2O2 in a large range from 2.5 to 100 µM with a low detection limit (LOD) of 0.74 µM. Moreover, the experimental results were supported by the simulated results via the finite-difference time-domain (FDTD) method. The nanoprobes have been further used for intracellular H2O2 detection in live cells. Besides, the etching of AuTNP also provides an alternative method to design novel plasmonic logic chips and write-once plasmonic memories.

Two-Photon-Excited Emission of Quantum Dots with a Plasmonic Chip

Plasmonic chips have wavelength-size periodic structures coated with thin metal films and can provide enhanced electric fields near the chip surfaces. Herein, a plasmonic chip was developed to carr...

Integrated graphene/ferroelectric based plasmonic random access memory

Using ferroelectric domains in lead zirconate titanate (PZT: PbZr0.3Ti0.7O3), we propose and simulate a graphene/ferroelectric-based integrated plasmonic random access memory (P-RAM). The proposed P-RAM poses bistable behavior between two transmission levels when the polarization of the ferroelectric film is switched via tuning an applied bias. Simulation results show that when a voltage applied to a 500-nm long P-RAM is swept from −1.5 V to +6 V and vice versa, the possible extinction ratio is about 18 dB. This integrated P-RAM, operating at a wavelength of 7 µm, can be used as a memory by measuring two distinct levels of transmission. The proposed integrated memory device, also functioning as a latching plasmonic switch, does not require any external unit for generating the required plasmonic wave. In the ON state, the wavelength of the plasmonic mode prorating across the memory unit is ∼156 nm. Its corresponding propagation length (∼5.57 μm) is longer than two-and-a-half times the entire P-RAM length. This proposed integrated P-RAM of footprint 2 μm2 that does not suffer from coupling loss is a promising device for applications in the storage of information and the development of future plasmonic chips. To obtain the presented numerical results, we solve the full Maxwell equations, by the 3D finite element method using the COMSOL multiphysics.

Optical nanogap antennas as plasmonic biosensors for the detection of miRNA biomarkers.

Nanoplasmonic biosensors based on nanogap antenna structures usually demand complex and expensive fabrication processes in order to achieve a good performance and sensitive detection. We here report the fabrication of large-area nanoplasmonic sensor chips based on nanogap antennas by employing a customized, simple and low-cost colloidal lithography process. By precisely controlling the angle for tilted e-beam metal evaporation, an elliptical mask is produced, which defines the total length of the dipole antenna nanostructures while assuring that the plasmonic response is oriented in the same direction along the sensor chip. Large-area sensor chips of nanogap antennas formed by pairs of gold nanodisks separated by gaps with an average size of 11.6 ± 4.7 nm are obtained. The optical characterization of the nanogap antenna structures in an attenuated total reflection (ATR) configuration shows a bulk refractive index sensitivity of 422 nm per RIU, which is in agreement with FDTD numerical simulations. The biosensing potential of the cm2-sized nanostructured plasmonic sensor chips has been evaluated for the detection of miRNA-210, a relevant biomarker for lung cancer diagnosis, through a DNA/miRNA hybridization assay. A limit of detection (LOD) of 0.78 nM (5.1 ng mL-1) was achieved with no need of further amplification steps, demonstrating the high sensitivity of these plasmonic nanogap antennas for the direct and label-free detection of low molecular weight biomolecules such as miRNAs.

Plasmonic metal carbide SERS chips

Plasmonic tungsten carbide, niobium carbide, titanium carbide and molybdenum carbide chips possess remarkable SERS activity.