Nano-Diamond-Enhanced Integrated Response of a Surface Plasmon Resonance Biosensor.

Surface plasmon resonance (SPR) sensing is a real-time detection technique for measuring biomolecular interactions on gold surfaces. This study presents a novel approach using nano-diamonds (NDs) on a gold nano-slit array to obtain an extraordinary transmission (EOT) spectrum for SPR biosensing. We used anti-bovine serum albumin (anti-BSA) to bind NDs for chemical attachment to a gold nano-slit array. The covalently bound NDs shifted the EOT response depending on their concentration. The number of ND-labeled molecules attached to the gold nano-slit array was quantified from the change in the EOT spectrum. The concentration of anti-BSA in the 35 nm ND solution sample was much lower than that in the anti-BSA-only sample (approximately 1/100). With the help of 35 nm NDs, we were able to use a lower concentration of analyte in this system and obtained better signal responses. The responses of anti-BSA-linked NDs had approximately a 10-fold signal enhancement compared to anti-BSA alone. This approach has the advantage of a simple setup and microscale detection area, which makes it suitable for applications in biochip technology.

Broadband Metallic Fiber-to-Chip Couplers and a Low-Complexity Integrated Plasmonic Platform.

We present a plasmonic platform featuring efficient, broadband metallic fiber-to-chip couplers that directly interface plasmonic slot waveguides, such as compact and high-speed electro-optic modulators. The metallic gratings exhibit an experimental fiber-to-slot coupling efficiency of -2.7 dB with -1.4 dB in simulations with the same coupling principle. Further, they offer a huge spectral window with a 3 dB passband of 350 nm. The technology relies on a vertically arranged layer stack, metal-insulator-metal waveguides, and fiber-to-slot couplers and is formed in only one lithography step with a minimum feature size of 250 nm. As an application example, we fabricate new modulator devices with an electro-optic organic material in the slot waveguide and reach 50 and 100 Gbit/s data modulation in the O- and C-bands within the same device. The devices' broad spectral bandwidth and their relaxed fabrication may render them suitable for experiments and applications in the scope of sensing, nonlinear optics, or telecommunications.

High-Contrast Infrared Absorption Spectroscopy via Mass-Produced Coaxial Zero-Mode Resonators with Sub-10 nm Gaps.

We present a wafer-scale array of resonant coaxial nanoapertures as a practical platform for surface-enhanced infrared absorption spectroscopy (SEIRA). Coaxial nanoapertures with sub-10 nm gaps are fabricated via photolithography, atomic layer deposition of a sacrificial Al2O3 layer to define the nanogaps, and planarization via glancing-angle ion milling. At the zeroth-order Fabry-Pérot resonance condition, our coaxial apertures act as a "zero-mode resonator (ZMR)", efficiently funneling as much as 34% of incident infrared (IR) light along 10 nm annular gaps. After removing Al2O3 in the gaps and inserting silk protein, we can couple the intense optical fields of the annular nanogap into the vibrational modes of protein molecules. From 7 nm gap ZMR devices coated with a 5 nm thick silk protein film, we observe high-contrast IR absorbance signals drastically suppressing 58% of the transmitted light and infer a strong IR absorption enhancement factor of 104∼105. These single nanometer gap ZMR devices can be mass-produced via batch processing and offer promising routes for broad applications of SEIRA.

Three-Dimensional Integration of Black Phosphorus Photodetector with Silicon Photonics and Nanoplasmonics.

We demonstrate the integration of a black phosphorus photodetector in a hybrid, three-dimensional architecture of silicon photonics and metallic nanoplasmonics structures. This integration approach combines the advantages of the low propagation loss of silicon waveguides, high-field confinement of a plasmonic nanogap, and the narrow bandgap of black phosphorus to achieve high responsivity for detection of telecom-band, near-infrared light. Benefiting from an ultrashort channel (∼60 nm) and near-field enhancement enabled by the nanogap structure, the photodetector shows an intrinsic responsivity as high as 10 A/W afforded by internal gain mechanisms, and a 3 dB roll-off frequency of 150 MHz. This device demonstrates a promising approach for on-chip integration of three distinctive photonic systems, which, as a generic platform, may lead to future nanophotonic applications for biosensing, nonlinear optics, and optical signal processing.

High-Throughput Fabrication of Resonant Metamaterials with Ultrasmall Coaxial Apertures via Atomic Layer Lithography.

We combine atomic layer lithography and glancing-angle ion polishing to create wafer-scale metamaterials composed of dense arrays of ultrasmall coaxial nanocavities in gold films. This new fabrication scheme makes it possible to shrink the diameter and increase the packing density of 2 nm-gap coaxial resonators, an extreme subwavelength structure first manufactured via atomic layer lithography, both by a factor of 100 with respect to previous studies. We demonstrate that the nonpropagating zeroth-order Fabry-Pérot mode, which possesses slow light-like properties at the cutoff resonance, traps infrared light inside 2 nm gaps (gap volume ∼ λ(3)/10(6)). Notably, the annular gaps cover only 3% or less of the metal surface, while open-area normalized transmission is as high as 1700% at the epsilon-near-zero (ENZ) condition. The resulting energy accumulation alongside extraordinary optical transmission can benefit applications in nonlinear optics, optical trapping, and surface-enhanced spectroscopies. Furthermore, because the resonance wavelength is independent of the cavity length and dramatically red shifts as the gap size is reduced, large-area arrays can be constructed with λresonance ≫ period, making this fabrication method ideal for manufacturing resonant metamaterials.

Surface plasmon resonance spectroscopy for characterisation of membrane protein-ligand interactions and its potential for drug discovery.

Surface plasmon resonance (SPR) spectroscopy is a rapidly developing technique for the study of ligand binding interactions with membrane proteins, which are the major molecular targets for validated drugs and for current and foreseeable drug discovery. SPR is label-free and capable of measuring real-time quantitative binding affinities and kinetics for membrane proteins interacting with ligand molecules using relatively small quantities of materials and has potential to be medium-throughput. The conventional SPR technique requires one binding component to be immobilised on a sensor chip whilst the other binding component in solution is flowed over the sensor surface; a binding interaction is detected using an optical method that measures small changes in refractive index at the sensor surface. This review first describes the basic SPR experiment and the challenges that have to be considered for performing SPR experiments that measure membrane protein-ligand binding interactions, most importantly having the membrane protein in a lipid or detergent environment that retains its native structure and activity. It then describes a wide-range of membrane protein systems for which ligand binding interactions have been characterised using SPR, including the major drug targets G protein-coupled receptors, and how challenges have been overcome for achieving this. Finally it describes some recent advances in SPR-based technology and future potential of the technique to screen ligand binding in the discovery of drugs. This article is part of a Special Issue entitled: Structural and biophysical characterisation of membrane protein-ligand binding.

Reflection based Extraordinary Optical Transmission Fiber Optic Probe for Refractive Index Sensing.

Fiber optic probes for chemical sensing based on the extraordinary optical transmission (EOT) phenomenon are designed and fabricated by perforating subwavelength hole arrays on the gold film coated optical fiber endface. The device exhibits a red shift in response to the surrounding refractive index increases with high sensitivity, enabling a reflection-based refractive index sensor with a compact and simple configuration. By choosing the period of hole arrays, the sensor can be designed to operate in the near infrared telecommunication wavelength range, where the abundant source and detectors are available for easy instrumentation. The new sensor probe is demonstrated for refractive index measurement using refractive index matching fluids. The sensitivity reaches 573 nm/RIU in the 1.333~1.430 refractive index range.

Resistless nanoimprinting in metal for plasmonic nanostructures.

Metal nanostructures are the main building blocks of metamaterials and plasmonics which show many extraordinary properties not existing in nature. A simple and widely applicable method that can directly pattern metals with silicon molds without the need of resists, using pressures of <4 MPa and temperatures of 25-150 °C is reported. Three-dimensional structures with smooth and vertical sidewalls, down to sub-10 nm resolution, are generated in silver and gold films in a single patterning step. Using this nanopatterning scheme, large-scale vivid images through extraordinary optical transmission and strong surface-enhanced Raman scattering substrates are realized. Resistless nanoimprinting in metal (RNIM) is a new class of metal patterning that allows plasmonic nanostructures to be fabricated quickly, repeatedly, and at a low-cost.

Discriminating Glioblastoma from Peritumoral Tissue by a Nanohole Array-Based Optical and Label-Free Biosensor.

In glioblastoma (GBM) patients, maximal safe resection remains a challenge today due to its invasiveness and diffuse parenchymal infiltration. In this context, plasmonic biosensors could potentially help to discriminate tumor tissue from peritumoral parenchyma based on differences in their optical properties. A nanostructured gold biosensor was used ex vivo to identify tumor tissue in a prospective series of 35 GBM patients who underwent surgical treatment. For each patient, two paired samples, tumor and peritumoral tissue, were extracted. Then, the imprint left by each sample on the surface of the biosensor was individually analyzed, obtaining the difference between their refractive indices. The tumor and non-tumor origins of each tissue were assessed by histopathological analysis. The refractive index (RI) values obtained by analyzing the imprint of the tissue were significantly lower (p = 0.0047) in the peritumoral samples (1.341, Interquartile Range (IQR) 1.339-1.349) compared with the tumor samples (1.350, IQR 1.344-1.363). The ROC (receiver operating characteristic) curve showed the capacity of the biosensor to discriminate between both tissues (area under the curve, 0.8779, p < 0.0001). The Youden index provided an optimal RI cut-off point of 0.003. The sensitivity and specificity of the biosensor were 81% and 80%, respectively. Overall, the plasmonic-based nanostructured biosensor is a label-free system with the potential to be used for real-time intraoperative discrimination between tumor and peritumoral tissue in patients with GBM.

Ultrafast Dynamics of Extraordinary Optical Transmission through Two-Slit Plasmonic Antenna.

We have theoretically investigated the spatial-temporal dynamics of extraordinary optical transmission (EOT) through a two-slit plasmonic antenna under femtosecond laser dual-beam irradiation. The dynamic interference of the crossed femtosecond laser dual-beam with the transiently excited surface plasmon polariton waves are proposed to characterize the particular spatial-temporal evolutions of EOT. It is revealed that the dynamic EOT can be flexibly switched with tunable symmetry through the respective slit of a two-slit plasmonic antenna by manipulating the phase correlation of the crossed femtosecond laser dual-beam. This is explained as tunable interference dynamics by phase control of surface plasmon polariton waves, allowing the dynamic modulation of EOT at optimized oblique incidences of dual-beams. Furthermore, we have obtained the unobserved traits of symmetry-broken transient spectra of EOT from the respective up- and down-slit of the antenna under crossed femtosecond laser dual-beam irradiation. This study can provide fundamental insights into the ultrafast dynamics of EOT in two-slit plasmonic antennas, which can be helpful to advance a wide range of applications, such as ultrafast plasmonic switch, ultrahigh resolution imaging, the transient amplification of non-linear effects, etc.

Enhanced Optical Transmission through a Hybrid Bull's Eye Structure Integrated with a Silicon Hemisphere.

In this work, we demonstrate a novel structure that can generate extraordinary optical transmission with a silicon hemisphere placed on a conventional bull's eye structure. There is a single subwavelength aperture surrounded by concentric periodic grooves on a substrate. The extraordinary optical transmission in this work is realized by the coupling of the surface plasmon polaritons in the periodic grooves and the localized electromagnetic field generated by the Mie resonance in the silicon hemisphere. The maximum normalized-to-area transmission peak can reach up to 662 with a decreasing device area and size. The electromagnetic field distribution at different geometry parameters is analyzed to clarify the mechanisms of the work in this paper. Additionally, the use of dielectric material in the aperture can avoid ohmic losses of metal material compared with the conventional one, which may suggest that a wider range of bull's-eye-structure applications is possible.

Plasmonic Split-Trench Resonator for Trapping and Sensing.

On-chip integration of plasmonics and electronics can benefit a broad range of applications in biosensing, signal processing, and optoelectronics. A key requirement is a chip-scale manufacturing method. Here, we demonstrate a split-trench resonator platform that combines a high-quality-factor resonant plasmonic biosensor with radio frequency (RF) nanogap tweezers. The split-trench resonator can simultaneously serve as a dielectrophoretic trap and a nanoplasmonic sensor. Trapping is accomplished by applying an RF electrical bias across a 10 nm gap, thereby either attracting or repelling analytes. Trapped analytes are detected in a label-free manner using refractive-index sensing, enabled by interference between surface-plasmon standing waves in the trench and light transmitted through the gap. This active sample concentration mechanism enables detection of nanoparticles and proteins at a concentration as low as 10 pM. We can manufacture centimeter-long split-trench cavity resonators with high throughput via photolithography and atomic layer deposition, toward practical applications in biosensing, spectroscopy, and optoelectronics.

Extraordinary Optical Transmission by Hybrid Phonon-Plasmon Polaritons Using hBN Embedded in Plasmonic Nanoslits.

Hexagonal boron nitride (hBN) exhibits natural hyperbolic dispersion in the infrared (IR) wavelength spectrum. In particular, the hybridization of its hyperbolic phonon polaritons (HPPs) and surface plasmon resonances (SPRs) induced by metallic nanostructures is expected to serve as a new platform for novel light manipulation. In this study, the transmission properties of embedded hBN in metallic one-dimensional (1D) nanoslits were theoretically investigated using a rigorous coupled wave analysis method. Extraordinary optical transmission (EOT) was observed in the type-II Reststrahlen band, which was attributed to the hybridization of HPPs in hBN and SPRs in 1D nanoslits. The calculated electric field distributions indicated that the unique Fabry-Pérot-like resonance was induced by the hybridization of HPPs and SPRs in an embedded hBN cavity. The trajectory of the confined light was a zigzag owing to the hyperbolicity of hBN, and its resonance number depended primarily on the aspect ratio of the 1D nanoslit. Such an EOT is also independent of the slit width and incident angle of light. These findings can not only assist in the development of improved strategies for the extreme confinement of IR light but may also be applied to ultrathin optical filters, advanced photodetectors, and optical devices.

Nanoplasmonic biosensors: Theory, structure, design, and review of recent applications.

Nanoplasmonic biosensing shows an immense potential to satisfy the needs of the global health industry - low-cost, fast, and portable automated systems; highly sensitive and real-time detection; multiplexing and miniaturization. In this review, we presented the theory of nanoplasmonic biosensing for popular detection schemes - SPR, LSPR, and EOT - and underline the consideration for nanostructure design, material selection, and their effects on refractometric sensing performance. Later, we covered the bottom-up and top-down nanofabrication methods for nanoplasmonic biosensors. Subsequently, we reviewed the recent examples of nanoplasmonic biosensors over a wide range of clinically relevant analytes in the diagnosis and prognosis of a wide range of diseases and conditions such as biomarker proteins, infectious bacteria, viral agents. Finally, we discussed the challenges of nanoplasmonic biosensing toward clinical translation and proposed strategic avenues to be competitive against current clinical detection methods. Hopefully, nanoplasmonic biosensing can realize its potential through successful demonstrations of clinical translation in the upcoming years.

Large-Area Fabrication of Complex Nanohole Arrays with Highly Tunable Plasmonic Properties.

By combining nanosphere lithography with oblique angle deposition, large-area asymmetric compound Ag nanohole arrays with nanorods inside the hole were patterned on substrates. The technique enabled the production of complex nanohole arrays with controlled hole diameter, thickness, and rod structure inside the hole. The compound asymmetric Ag nanohole structures showed strong polarization-dependent optical properties, and a new extraordinary optical transmission (EOT) mode with tunable resonance wavelength at the near-IR region was observed. The transmission at the new EOT wavelength region can increase from 27% of nanohole to 69% of the compound structure, and these structures can achieve a refractive index sensitivity as high as 847 nm RIU-1. The tunable EOT wavelength and strong polarization-dependent optical properties make the structure ideal for ultrathin optical filters, polarizers, surface-enhanced spectroscopies, etc.

A novel micromachined Fabry-Perot interferometer integrating nano-holes and dielectrophoresis for enhanced biochemical sensing.

Single-layered gold nano-hole arrays lead to extraordinary optical transmission (EOT)-modulated surface plasmonic resonance (SPR) and have seen much progress in biochemical sensing. To further improve the sensing performance, the single-layered structure need to be changed. In this paper, a micromachined Fabry-Perot interferometer (µFPI), featuring two parallel and flat gold-coated mirrors, one of which has sub-wavelength nano-hole arrays, was designed, fabricated, and tested experimentally. Its transmission spectrum was confirmed to have EOT-modulated SPR patterns, and its characteristic peak wavelength was found to have a refractive index sensitivity of 593 nm / RIU and a Q factor up to 128.4, which is 10.2 times its EOT counterparts. By applying AC electric signals across the two gold layers, dielectrophoresis (DEP) induced near the nano-holes was proven to enrich particles significantly. To remove the thermal effects on the transmission spectrum, heat was dissipated by flowing sample during measurement. Biochemical sensing experiments were conducted using BSA protein medium of different low concentrations, demonstrating the detection sensitivity enhancement of ~ 6-fold for 1 pM compared to 100 pM. This novel µFPI presents a new paradigm in EOT-based SPR sensing technology by combining the benefits of µFPI interference, EOT near-field measurement and DEP enrichment of molecules.

Spectrometer-Free Plasmonic Biosensing with Metal-Insulator-Metal Nanocup Arrays.

The development of high performing and accessible sensors is crucial to future point-of-care diagnostic sensing systems. Here, we report on a gold-titanium dioxide-gold metal-insulator-metal plasmonic nanocup array device for spectrometer-free refractometric sensing with a performance exceeding conventional surface plasmon resonance sensors. This device shows distinct spectral properties such that a superstrate refractive index increase causes a transmission intensity increase at the peak resonance wavelength. There is no spectral shift at this peak and there are spectral regions with no transmission intensity change, which can be used as internal device references. The sensing mechanism, plasmon-cavity coupling optimization, and material properties are studied using electromagnetic simulations. The optimal device structure is determined using simulation and experimental parameter sweeps to tune the cavity confinement and the resonance coupling. An experimental sensitivity of 800 ΔT%/RIU is demonstrated. Spectrometer-free, imaged-based detection is also carried out for the cancer biomarker carcinoembryonic antigen with a 10 ng/mL limit of detection. The high performance and distinct spectral features of this metal-insulator-metal plasmonic nanocup array make this device promising for future portable optical sensing systems with minimal instrumentation requirements.

Three-Dimensional Superlocalization Imaging of Gliding Mycoplasma mobile by Extraordinary Light Transmission through Arrayed Nanoholes.

In this paper, we describe super-resolved sampling of live bacteria based on extraordinary optical transmission (EOT) of light. EOT is produced by surface plasmon confinement and coupling with nanostructures. Bacterial fluorescence is excited by the localized fields for subdiffraction-limited sampling. The concept was applied to elucidating bacterial dynamics of gliding Mycoplasma mobile (M. mobile). The results analyzed with multiple M. mobile bacteria show individual characters and reveal that M. mobile undergoes a significant axial variation at 94 nm. The sampling error of the method is estimated to be much smaller than 1/10 of the diffraction limit both in the lateral and depth axis. The method provides a powerful tool for investigation of biomolecular dynamics at subwavelength precision.