Gold Nanohole Arrays Research Articles

Angle-Resolved Fluorescence of a Dye Coupled to a Plasmonic Nanohole Array

Gold nanohole arrays are periodic metasurfaces that are gathering huge interest in biosensing applications. The bi-dimensional grating-like structure defines their plasmonic response, together with the corresponding mode of angular dispersion. These properties can be used to investigate the interaction processes with the fluorescence features of a properly chosen emitting molecule. By employing a custom gold nanohole array alongside a commercial organic dye, we conducted an accurate angle-resolved optical characterization resorting to fluorescence, reflectance, and transmittance spectra. The coupling between the plasmonic modes and the fluorescence features was then identified as a modification of the dye fluorescence signal in terms of both spectral redistribution and enhancement. By carefully analyzing the results, different measurement efficiencies can be identified, depending on the set-up configuration, to be properly engineered for sensitivity maximization in plasmon-enhanced fluorescence-based applications.

Nanofabrication Process Scale-Up via Displacement Talbot Lithography of a Plasmonic Metasurface for Sensing Applications

The selection of an affordable method to fabricate plasmonic metasurfaces needs to guarantee complex control over both tunability and reproducibility of their spectral and morphological properties, making plasmonic metasurfaces suitable for integration into different sensing devices. Displacement Talbot lithography could be a valid solution thanks to the limited fabrication steps required, also providing the highly desired industrial scalability. Fabricated plasmonic metasurfaces are represented by a gold nanohole array on a glass substrate based on a triangular pattern. Scanning electron microscopy measurements have been recorded, showing the consistency of the surface features with the optimized design parameters. Reflectance and transmittance measurements have also been carried out to test the reliability and standardization of the metasurface’s optical response. Furthermore, these plasmonic metasurfaces have also been successfully tested for probing refractive index variations in a microfluidic system, paving the way for their use in sensitive, real-time, label-free, and multiplexing detection of bio-molecular events.

Convergence and Performance Analysis of a Particle Swarm Optimization Algorithm for Optical Tuning of Gold Nanohole Arrays.

Gold nanohole arrays, hybrid metal/dielectric metasurfaces composed of periodically arranged air holes in a thick gold film, exhibit versatile support for both localized and propagating surface plasmons. Leveraging their capabilities, particularly in surface plasmon resonance-oriented applications, demands precise optical tuning. In this study, a customized particle swarm optimization algorithm, implemented in Ansys Lumerical FDTD, was employed to optically tune gold nanohole arrays treated as bidimensional gratings following the Bragg condition. Both square and triangular array dispositions were considered. Convergence and evolution of the particle swarm optimization algorithm were studied, and a mathematical model was developed to interpret its outcomes.

Tip-based Lithography with a Sacrificial Layer.

The fabrication of a highly controlled gold (Au) nanohole (NH) array via tip-based lithography is improved by incorporating a sacrificial layer-a tip-crash buffer layer. This inclusion mitigates scratches during the nano-indentation process by employing a 300nm thick poly(methyl methacrylate) layer as a sacrificial layer on top of the Au film. Such a precaution ensures minimal scratches on the Au film, facilitating the creation of sub-50nm Au NHs with a 15nm gap between the Au NHs. The precision of this method exceeds that of fabricating Au NHs without a sacrificial layer. Demonstrating its versatility, this Au NH array is utilized in two distinct applications: as a dry etching mask to form a molybdenum disulfide hole array and as a catalyst in metal-assisted chemical etching, resulting in conical-shaped silicon nanostructures. Additionally, a significant electric field is generated when Au nanoparticles (NPs) are placed within the Au NHs. This effect arises from coupling electromagnetic waves, concentrated by the Au NHs and amplified by the Au NPs. A notable result of this configuration is the enhancement factor of surface-enhanced Raman scattering, which is an order of magnitude greater than that observed with just Au NHs and Au NPs alone.

Deep learning-driven forward and inverse design of nanophotonic nanohole arrays: streamlining design for tailored optical functionalities and enhancing accessibility.

In nanophotonics, nanohole arrays (NHAs) are periodic arrangements of nanoscale apertures in thin films that provide diverse optical functionalities essential for various applications. Fully studying NHAs' optical properties and optimizing performance demands understanding both materials and geometric parameters, which presents a computational challenge due to numerous potential combinations. Efficient computational modeling is critical for overcoming this challenge and optimizing NHA-based device performance. Traditional approaches rely on time-consuming numerical simulation processes for device design and optimization. However, using a deep learning approach offers an efficient solution for NHAs design. In this work, a deep neural network within the forward modeling framework accurately predicts the optical properties of NHAs by using device structure data such as periodicity and hole radius as model inputs. We also compare three deep learning-based inverse modeling approaches-fully connected neural network, convolutional neural network, and tandem neural network-to provide approximate solutions for NHA structures based on their optical responses. Once trained, the DNN accurately predicts the desired result in milliseconds, enabling repeated use without wasting computational resources. The models are trained using over 6000 samples from a dataset obtained by finite-difference time-domain (FDTD) simulations. The forward model accurately predicts transmission spectra, while the inverse model reliably infers material attributes, lattice geometries, and structural parameters from the spectra. The forward model accurately predicts transmission spectra, with an average Mean Squared Error (MSE) of 2.44 × 10-4. In most cases, the inverse design demonstrates high accuracy with deviations of less than 1.5 nm for critical geometrical parameters. For experimental verification, gold nanohole arrays are fabricated using deep UV lithography. Validation against experimental data demonstrates the models' robustness and precision. These findings show that the trained DNN models offer accurate predictions about the optical behavior of NHAs.

Surface-enhanced Raman spectroscopy with single cell manipulation by microfluidic dielectrophoresis.

When exposed to an alternating current (AC) electric field, a polarized microparticle is moved by the interaction between the voltage-induced dipoles and the AC electric field under dielectrophoresis (DEP). The DEP force is widely used for manipulation of microparticles in diverse practical applications such as 3D manipulation, sorting, transfer, and separation of various particles such as living cells. In this study, we propose the integration of surface-enhanced Raman spectroscopy (SERS), an extremely sensitive and versatile technique based on the Raman scattering of molecules supported by nanostructured materials, with DEP using a microfluidic device. The microfluidic device combines microelectrodes with gold nanohole arrays to characterize the electrophysiological and biochemical properties of biological cells. The movement of particles, which varies depending on the electrical properties such as conductivity and permittivity of particles, can be manipulated by the cross-frequency change. For proof of concept, Raman spectroscopy using the DEP-SERS integration was performed for polystyrene beads and biological cells and resulted in an improved signal-to-noise ratio by determining the direction of the DEP force applied to the cells with respect to the applied AC power and collecting them on the nanohole arrays. The result illustrates the potential of the concept for simultaneously examining the electrical and biochemical properties of diverse chemical and biological microparticles in the microfluidic environment.

Impact of Optical Cavity on Refractive Index Sensitivity of Gold Nanohole Arrays.

Refractive index sensing based on surface plasmon resonance (SPR) is a highly efficient label-free technique for biomolecular detection. The performance of this method is defined by the dielectric properties of a sensing layer and its structure. Nanohole arrays in thin metal films provide good refractive index sensitivity but often suffer from a large resonance linewidth, which limits their broad practical application in biosensorics. Coupling the broad plasmon modes to sharp resonances can reduce the peak widths, but at the same time it can also degrade the sensitivity. Here, we use Finite-Difference Time Domain simulations to study the factors affecting the sensing performance of gold-silica-gold optical cavities with nanohole arrays in the dielectric and top metal layers. We demonstrate that by tuning resonator size and inter-hole spacing, the performance of the biosensor can be optimized and the figure of merit of the order of 5-7 is reached.

Gold nanohole arrays with ring-shaped silver nanoparticles for highly efficient plasmon-enhanced fluorescence

To enhance the interaction between electromagnetic fields and reduce photoluminescence (PL) lifetime in plasmon-enhanced fluorescence, this study presents a novel approach involving the fabrication of gold (Au) nanohole arrays (ANA) decorated with ring-shaped silver nanoparticles (AgNPs) on a silicon-dioxide (SiO2)/silver (Ag) substrate. The surface plasmon resonance coupling in terms of the PL reactions of ANA substrates with and without ring-shaped AgNPs is investigated via experiments and numerical simulations. The remarkable enhancement of PL intensity of the proposed substrate is attributed to increased absorption, which enables the tuning of surface-enhanced electromagnetic fields. Specifically, the Raman signal of rhodamine 6G (R6G) dye and the PL intensity of 4-(dicyanomethylene)-2-t-butyl-6-(1,1,7,7-tetramethyljulolidyl-9-enyl)-4H-pyran (DCJTB) molecules are significantly enhanced 3.7 and 2.2 times, respectively, compared to those of the bare ANA substrate. Meanwhile, the PL lifetime is reduced by 46.15%. These results confirm that ANAs decorated with ring-shaped AgNPs can significantly improve plasmon-enhanced fluorescence. The findings presented herein demonstrate the potential to revolutionize biosensing, imaging, and photonics.

Multiple Features-Based Improved Nanohole Array Plasmonic Biosensor

In recent years, gold nanohole array-based biosensors have gained tremendous attention due to their high sensitivity, label-free biosensing, and real-time simultaneous multiple analyte detection capabilities. However, nanohole array-based biosensors using conventional sensing methods lack the resolution of traditional surface plasmon resonance (SPR) sensors. In this work, we present numerical methods utilizing multiple peaks of these biosensors’ transmission spectra to achieve higher sensitivity and lower detection limits. Using finite-difference time-domain (FDTD) simulations, we compared the sensing performance of the proposed numerical methods to traditional peak-shift and spectral integration methods. We added noise to the transmission spectra to simulate a realistic system and determined the change in the performance. We also optimized the geometrical parameters of the gold nanohole array for optimal sensing performance. Finally, we applied the proposed method to two critical real-life biosensing applications and reported the sensitivity and limit of detection (LOD). The proposed numerical methods show much higher sensitivity and lower detection limits than the traditional techniques. The observed detection limits are as low as <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\sim {2} \times {10}^{-{6}}$ </tex-math></inline-formula> refractive index unit changes near the surface. The proposed methods can be utilized for any sensing systems that employ transmission spectra and will outperform traditional methods if there are multiple peaks present in the transmission spectra.

Dielectrophoretic trapping of nanosized biomolecules on plasmonic nanohole arrays for biosensor applications: simple fabrication and visible-region detection.

Surface plasmon resonance is an optical phenomenon that can be applied for label-free, real-time sensing to directly measure biomolecular interactions and detect biomarkers in solutions. Previous studies using plasmonic nanohole arrays have monitored and detected various biomolecules owing to the propagating surface plasmon polaritons (SPPs). Extraordinary optical transmission (EOT) that occurs in the near-infrared (NIR) and infrared (IR) regions is usually used for detection. Although these plasmonic nanohole arrays improve the sensitivity and throughput for biomolecular detection, these arrays have the following disadvantages: (1) molecular diffusion in the solution (making the detection of biomolecules difficult), (2) the device fabrication's complexities, and (3) expensive equipments for detection in the NIR or IR regions. Therefore, there is a need to fabricate plasmonic nanohole arrays as biomolecular detection platforms using a simple and highly reproducible procedure based on other SPP modes in the visible region instead of the EOT in the NIR or IR regions while suppressing molecular diffusion in the solution. In this paper, we propose the combination of a polymer-based gold nanohole array (Au NHA) obtained through an easy process as a simple platform and dielectrophoresis (DEP) as a biomolecule manipulation method. This approach was experimentally demonstrated using SPP and LSPR modes (not EOT) in the visible region and simple, label-free, rapid, cost-effective trapping and enrichment of nanoparticles (trapping time: <50 s) and bovine serum albumin (trapping time: <1000 s) was realized. These results prove that the Au NHA-based DEP devices have great potential for real-time digital and Raman bioimaging, in addition to biomarker detection.

Voltage-modulated surface plasmon resonance biosensors integrated with gold nanohole arrays.

Surface plasmon resonance (SPR) has emerged as one of the most efficient and attractive techniques for optical sensors in biological applications. The traditional approach of an EC (electrochemical)-SPR biosensor to generate SPR is by adopting a prism underneath the sensing substrate, and an angular scan is performed to characterize the reflectivity of target analytes. In this paper, we designed and investigated a novel optical biosensor based on a hybrid plasmonic and electrochemical phenomenon. The SPR was generated from a thin layer of gold nanohole array on a glass substrate. Using C-Reactive Protein (CRP) as the target analyte, we tested our device for different concentrations and observed the optical response under various voltage bias conditions. We observed that SPR response is concentration-dependent and can be modulated by varying DC voltages or AC bias frequencies. For CRP concentrations ranging from 1 to 1000 µg/mL, at the applied voltage of -600 mV, we obtained a limit of detection for this device of 16.5 ng/mL at the resonance peak wavelength of 690 nm. The phenomenon is due to spatial re-distribution of electron concentration at the metal-solution interface. The results suggest that CRP concentration can be determined from the SPR peak wavelength shift by scanning the voltages. The proposed new sensor structure is permissible for various future optoelectronic integration for plasmonic and electrochemical sensing.

Plasmonic Biosensing for Label-Free Detection of Two Hallmarks of Cancer Cells: Cell-Matrix Interaction and Cell Division.

Two key features of cancer cells are sustained proliferation and invasion, which is preceded by a modification of the adhesion properties to the extracellular matrix. Currently, fluorescence-based techniques are mainly used to detect these processes, including flow cytometry and fluorescence resonance energy transfer (FRET) microscopy. We have previously described a simple, fast and label-free method based on a gold nanohole array biosensor to detect the spectral response of single cells, which is highly dependent on the actin cortex. Here we used this biosensor to study two cellular processes where configuration of the actin cortex plays an essential role: cell cycle and cell–matrix adhesion. Colorectal cancer cells were maintained in culture under different conditions to obtain cells stopped either in G0/G1 (resting cells/cells at the initial steps of cell growth) or G2 (cells undergoing division) phases of the cell cycle. Data from the nanohole array biosensor showed an ability to discriminate between both cell populations. Additionally, cancer cells were monitored with the biosensor during the first 60 min after cells were deposited onto a biosensor coated with fibronectin, an extracellular matrix protein. Spectral changes were detected in the first 20 min and increased over time as the cell–biosensor contact surface increased. Our data show that the nanohole array biosensor provides a label-free and real-time procedure to detect cells undergoing division or changes in cell–matrix interaction in both clinical and research settings.

FDTD Analysis of Hotspot-Enabling Hybrid Nanohole-Nanoparticle Structures for SERS Detection.

Metallic nanoparticles (MNPs) and metallic nanostructures are both commonly used, independently, as SERS substrates due to their enhanced plasmonic activity. In this work, we introduce and investigate a hybrid nanostructure with strong SERS activity that benefits from the collective plasmonic response of the combination of MNPs and flow-through nanohole arrays (NHAs). The electric field distribution and electromagnetic enhancement factor of hybrid structures composed of silver NPs on both silver and gold NHAs are investigated via finite-difference time-domain (FDTD) analyses. This computational approach is used to find optimal spatial configurations of the nanoparticle positions relative to the nanoapertures and investigate the difference between Ag-NP-on-Ag-NHAs and Ag-NP-on-Au-NHAs hybrid structures. A maximum GSERS value of 6.8 × 109 is achieved with the all-silver structure when the NP is located 0.5 nm away from the rim of the NHA, while the maximum of 4.7 × 1010 is obtained when the nanoparticle is in full contact with the NHA for the gold-silver hybrid structure. These results demonstrate that the hybrid nanostructures enable hotspot formation with strong SERS activity and plasmonic enhancement compatible with SERS-based sensing applications.

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.

Label-free plasmonic-based biosensing using a gold nanohole array chip coated with a wafer-scale deposited WS2 monolayer.

This paper reports the fabrication, testing and obtained performance of a plasmonic sensor employing a gold (Au) nanohole array chip coated with tungsten disulphide (WS2), which is then functionalized for the detection of protein-protein interactions. A key novelty is that the WS2 was deposited as a monoatomic layer using a wafer-scale synthesis method that successfully provided a film of both high quality and uniform thickness. The deposited WS2 film was transferred onto a Au nanohole array chip using a novel method and was subsequently functionalized with biotin. The final sensor was tested and it demonstrated efficient real-time and label-free plasmonic detection of biotin-streptavidin coupling. Specifically, compared to a standard (i.e. uncoated) Au nanohole-based sensor, our WS2-coated Au nanohole array boosted the spectral shift of the resonance wavelength by ∼190%, resulting in a 7.64-fold improvement of the limit of detection (LOD).

Engineering the Optical Response of the Novel Plasmonic Binary Nanohole Array

The phenomenon of extraordinary optical transmission (EOT) due to its advantages has been considered by researchers in various applications, and in recent years, many efforts have been made to engineer these structures to get the best possible response for desired applications. In this work, the optical properties of novel binary gold nanohole arrays are investigated theoretically. We engineered the optical response of the system by adjusting the ratio of contribution of surface plasmon polariton (SPP) to localized surface plasmon resonance (LSPR) through the manipulation of the geometrical properties. The changes in the topology of this nanohole array affected the intensity and the wavelength of transmission peaks. The sensitivity of the optical response to the refractive index was also investigated. The designed structure is a good candidate for use as a polarization-independent optical label-free sensor.

A label-free optical system with a nanohole array biosensor for discriminating live single cancer cells from normal cells

Abstract Developing a simple, fast, and label-free method for discrimination between live cancer cells and normal cells in biological samples still remains a challenge. Here, a system is described that fulfills these features to analyze individual living cells. The system consists of a gold nanohole array biosensor plus a microscope optical design to isolate the spectral response of a single cell. It is demonstrated that differences in the spectral behavior between tumor (colorectal cancer cell lines and primary cells from colorectal cancer tissue) and non-tumor cells (peripheral blood mononuclear cells, skin fibroblasts and colon epithelial cells) are influenced by the actin cortex, which lies within the short penetration depth of the surface plasmon electromagnetic field. The efficacy of this system was assessed by the analysis of about one thousand single cells showing the highest discrimination capacity between normal colon epithelial cells and colorectal cancer cells from surgical specimens, with values of sensitivity and specificity ranging 80–100% and 87–100%, respectively. It is also demonstrated that cell discrimination capacity of the system is highly reduced by disrupting the formation of actin cortex. This plasmonic system may find wide applications in biomedicine and to study key cellular processes that involve the actin cortex, including proliferation, differentiation, and migration.

Differential Interference Contrast-Based Interrogation of Plasmonic Gold Nanohole Arrays for Label-Free Imaging Sensing

Differential Interference Contrast-Based Interrogation of Plasmonic Gold Nanohole Arrays for Label-Free Imaging Sensing

Direct fabrication and characterization of gold nanohole arrays.

We demonstrate a one-step fabrication method to realize desired gold (Au) nanoholes arrays by using a one-photon absorption based direct laser writing technique. Thanks to the optically induced thermal effect of Au material at 532 nm excitation wavelength, the local temperature at the laser focus area can reach as high as 600°C, which induces an evaporation of the Au thin film resulting in a metallic nanohole. By controlling the laser spot movement and exposure time, different two-dimensional Au nanoholes structures with periodicity as small as 500 nm have been demonstrated. This allows obtaining plasmonic nanostructures in a single step without needing the preparation of polymeric template and lift-off process. By this direct fabrication technique, the nanoholes do not have circular shape as the laser focusing spot, due to the non-uniform heat transfer in a no-perfect flat Au film. However, the FDTD simulation results and the experimental measurement of the transmission spectra show that the properties of fabricated plasmonic nanoholes arrays are very close to those of ideal plasmonic nanostructures. Actually, the plasmonic resonance depends strongly on the periodicity of the metallic structures while the heterogeneous form of the holes simply enlarges the resonant peak. Furthermore, it is theoretically demonstrated that the non-perfect circular shape of the Au hole allows amplifying the electromagnetic field of the resonant peak by several times as compared to the case of perfect circular shape. This could be an advantage for application of this fabricated structure in laser and nonlinear optics domains.

Characterization of extracellular vesicles derived from mesenchymal stromal cells by surface-enhanced Raman spectroscopy.

Extracellular vesicles (EVs) are secreted by all cells into bodily fluids and play an important role in intercellular communication through the transfer of proteins and RNA. There is evidence that EVs specifically released from mesenchymal stromal cells (MSCs) are potent cell-free regenerative agents. However, for MSC EVs to be used in therapeutic practices, there must be a standardized and reproducible method for their characterization. The detection and characterization of EVs are a challenge due to their nanoscale size as well as their molecular heterogeneity. To address this challenge, we have fabricated gold nanohole arrays of varying sizes and shapes by electron beam lithography. These platforms have the dual purpose of trapping single EVs and enhancing their vibrational signature in surface-enhanced Raman spectroscopy (SERS). In this paper, we report SERS spectra for MSC EVs derived from pancreatic tissue (Panc-MSC) and bone marrow (BM-MSC). Using principal component analysis (PCA), we determined that the main compositional differences between these two groups are found at 1236, 761, and 1528 cm-1, corresponding to amide III, tryptophan, and an in-plane -C=C- vibration, respectively. We additionally explored several machine learning approaches to distinguish between BM- and Panc-MSC EVs and achieved 89 % accuracy, 89 % sensitivity, and 88 % specificity using logistic regression.