Pulse Oximetry Imaging System Using Spatially Uniform Dual Wavelength Illumination.

Pulse oximetry is a non-invasive method for measuring blood oxygen saturation. However, its detection scheme heavily relies on single-point measurements. If the oxygen saturation is measured at a single location, the measurements are influenced by the profile of illumination, spatial variations in blood flow, and skin pigment. To overcome these issues, imaging systems that measure the distribution of oxygen saturation have been demonstrated. However, previous imaging systems have relied on red and near-infrared illuminations with different profiles, resulting in inconsistent ratios between transmitted red and near-infrared light over space. Such inconsistent ratios can introduce fundamental errors when calculating the spatial distribution of oxygen saturation. In this study, we developed a novel illumination system specifically designed for a pulse oximetry imaging system. For the illumination system, we customized the integrating sphere by coating a mixture of barium sulfate and white paint inside it and by coupling eight red and eight near-infrared LEDs. The illumination system created identical patterns of red and near-infrared illuminations that were spatially uniform. This allowed the ratio between transmitted red and near-infrared light to be consistent over space, enabling the calculation of the spatial distribution of oxygen saturation. We believe our developed pulse oximetry imaging system can be used to obtain spatial information on blood oxygen saturation that provides insight into the oxygenation of the blood contained within the peripheral region of the tissue.

Biological SERS-active sensor platform based on flexible silk fibroin film and gold nanoislands.

In contrast to conventional surface-enhanced Raman scattering (SERS) platforms implemented on non-biological substrates, silk fibroin has the unique advantages of long-term biosafety and controllable biodegradability for in vitro and in vivo biomedical applications, as well as flexibility and process-compatibility. In this study, a silk fibroin film was developed to fabricate a flexible SERS sensor template with nanogap-rich gold nanoislands. The proposed biological SERS platform presents fairly good enhancements in detection performance such as detection limit, sensitivity, and signal-to-noise ratio. In particular, the sensitivity improvement was by more than 10 times compared to that of the counterpart sample, and an excellent spatial reproducibility of 2.8% was achieved. In addition, the near-field calculation results were consistent with the experimental results, and the effect of surface roughness of the silk substrate was investigated in a quantitative way. It is believed that biological SERS-active sensors could provide the potential for highly sensitive, cost-effective, and easily customizable nanophotonic platforms that include new capabilities for future healthcare devices.

Fabrication and Characterization of Novel Silk Fiber-Optic SERS Sensor with Uniform Assembly of Gold Nanoparticles.

Biocompatible optical fibers and waveguides are gaining attention as promising platforms for implantable biophotonic devices. Recently, the distinct properties of silk fibroin were extensively explored because of its unique advantages, including flexibility, process compatibility, long-term biosafety, and controllable biodegradability for in vitro and in vivo biomedical applications. In this study, we developed a novel silk fiber for a sensitive optical sensor based on surface-enhanced Raman spectroscopy (SERS). In contrast to conventional plasmonic nanostructures, which employ expensive and time-consuming fabrication processes, gold nanoparticles were uniformly patterned on the top surface of the fiber employing a simple and cost-effective convective self-assembly technique. The fabricated silk fiber-optic SERS probe presented a good performance in terms of detection limit, sensitivity, and linearity. In particular, the uniform pattern of gold nanoparticles contributed to a highly linear sensing feature compared to the commercial multi-mode fiber sample with an irregular and aggregated distribution of gold nanoparticles. Through further optimization, silk-based fiber-optic probes can function as useful tools for highly sensitive, cost-effective, and easily tailored biophotonic platforms, thereby offering new capabilities for future implantable SERS devices.

Dual modal plasmonic substrates based on a convective self-assembly technique for enhancement in SERS and LSPR detection.

In this study, surface-enhanced Raman scattering (SERS) scheme is combined with localized surface plasmon resonance (LSPR) detection on a thin gold film with stripe patterns of gold nanoparticles (GNPs) via convective self-assembly (CSA) method. The potential of dual modal plasmonic substrates was evaluated by binding 4-ABT and IgG analytes, respectively. SERS experiments presented not only a high sensitivity with a detection limit of 4.7 nM and an enhancement factor of 1.34 × 105, but an excellent reproducibility with relative standard deviation of 5.5%. It was found from plasmonic sensing experiments by immobilizing IgG onto GNP-mediated gold film that detection sensitivity was improved by more than 211%, compared with a conventional bare gold film. Our synergistic SERS-LSPR approach based on a simple and cost-effective CSA method could open a route for sensitive, reliable and reproducible dual modal detection to expand the application areas.

Highly reliable SERS substrate based on plasmonic hybrid coupling between gold nanoislands and periodic nanopillar arrays.

To improve both sensitivity and reliability, a hybrid SERS substrate of combining gold nanoislands (GNI) with periodic MgF2 nanopillar arrays was successfully developed. SERS detection performance of the proposed substrates was evaluated in terms of enhancement effect, signal-to-noise ratio (SNR), linearity, reproducibility and repeatability, and compared with the performance of a conventional SERS substrate based on GNI. Experimental and simulation results presented that significant improvement of SERS intensity and SNR by more than 3 times and a notable reduction in relative standard deviation were obtained. We hope that the suggested SERS platform with unique advantages in sensitivity and reliability could be extended to point-of-care detection of a variety of biomolecular reactions.

Sensitivity and Stability Enhancement of Surface Plasmon Resonance Biosensors based on a Large-Area Ag/MoS2 Substrate.

Surface plasmon resonance (SPR) sensors based on a silver film suffer from signal degradation due to silver oxidation in aqueous sensing environments. To overcome this limitation, we fabricated the planar plasmonic substrate employing an atomic MoS2 layer on a silver surface. Successful production of a large-area MoS2 monolayer blocks the penetration of oxygen and water molecules. In addition, we theoretically and experimentally found that MoS2 layer on the silver film can improve the SPR sensitivity and stability significantly. In this study, the proposed SPR substrate has the potential to provide highly enhanced sensor platforms for surface-limited molecular detections.

Theoretical Study on Gold-Nanorod-Enhanced Near-Infrared Neural Stimulation.

Over the past decade, optical methods have emerged for modulating brain functions as an alternative to electrical stimulation. Among various optical techniques, infrared neural stimulation has been effective via a thermal mechanism enabling focused and noninvasive stimulation without any genetic manipulation, but it results in bulk heating of neural tissue. Recently, it has been shown that neural cells can be activated more efficiently by pulsed near-infrared (NIR) light delivered to gold nanorods (GNRs) near the neural cells. Despite its potential, however, the biophysical mechanism underlying this GNR-enhanced NIR stimulation has not been clearly explained yet. Here, we propose an integrative and quantitative model to elucidate the mechanism by modeling heat generated from interaction between NIR light and GNRs, the temperature-dependent ion channels (transient receptor potential vanilloid 1; TRPV1) in the neuronal membrane, and a heat-induced capacitive current through the membrane. Our results show that NIR pulses induce abrupt temperature elevation near the neuronal membrane and lead to both the TRPV1-channel and capacitive currents. Both current sources synergistically increase the membrane potential and elicit an action potential, and which mechanism is dominant depends on conditions such as the laser pulse duration and TRPV1 channel density. Although the TRPV1 mechanism dominates in most cases we tested, the capacitive current makes a larger contribution when a very short laser pulse is illuminated on neural cells with relatively low TRPV1 channel densities.

Strong enhancement of emission efficiency in GaN light-emitting diodes by plasmon-coupled light amplification of graphene.

Recently, we have demonstrated that excitation of plasmon-polaritons in a mechanically-derived graphene sheet on the top of a ZnO semiconductor considerably enhances its light emission efficiency. If this scheme is also applied to device structures, it is then expected that the energy efficiency of light-emitting diodes (LEDs) increases substantially and the commercial potential will be enormous. Here, we report that the plasmon-induced light coupling amplifies emitted light by ∼1.6 times in doped large-area chemical-vapor-deposition-grown graphene, which is useful for practical applications. This coupling behavior also appears in GaN-based LEDs. With AuCl3-doped graphene on Ga-doped ZnO films that is used as transparent conducting electrodes for the LEDs, the average electroluminescence intensity is 1.2-1.7 times enhanced depending on the injection current. The chemical doping of graphene may produce the inhomogeneity in charge densities (i.e., electron/hole puddles) or roughness, which can play a role as grating couplers, resulting in such strong plasmon-enhanced light amplification. Based on theoretical calculations, the plasmon-coupled behavior is rigorously explained and a method of controlling its resonance condition is proposed.

Dispersion Curve Engineering of TiO2/Silver Hybrid Substrates for Enhanced Surface Plasmon Resonance Detection.

As surface plasmon resonance (SPR)-based biosensors are well translated into biological, chemical, environmental, and clinical fields, it is critical to further realize stable and sustainable systems, avoiding oxidation susceptibility of metal films-in particular, silver substrates. We report an enhanced SPR detection performance by incorporating a TiO2 layer on top of a thin silver film. A uniform TiO2 film fabricated by electron beam evaporation at room temperature is an effective alternative in bypassing oxidation of a silver film. Based on our finding that the sensor sensitivity is strongly correlated with the slope of dispersion curves, SPR sensing results obtained by parylene film deposition shows that TiO2/silver hybrid substrates provide notable sensitivity improvement compared to a conventional bare silver film, which confirms the possibility of engineering the dispersion characteristic according to the incidence wavelength. The reported SPR structures with TiO2 films enhance the sensitivity significantly in water and air environments and its overall qualitative trend in sensitivity improvement is consistent with numerical simulations. Thus, we expect that our approach can extend the applicability of TiO2-mediated SPR biosensors to highly sensitive detection for biomolecular binding events of low concentrations, while serving a practical and reliable biosensing platform.

Enhanced NIR radiation-triggered hyperthermia by mitochondrial targeting.

Mitochondria are organelles that are readily susceptible to temperature elevation. We selectively delivered a coumarin-based fluorescent iron oxide nanoparticle, Mito-CIO, to the mitochondria. Upon 740 nm laser irradiation, the intracellular temperature of HeLa cells was elevated by 2.1 °C within 5 min when using Mito-CIO, and the treatment resulted in better hyperthermia and a more elevated cytotoxicity than HeLa cells treated with coumarin iron oxide (CIO), which was missing the mitochondrial targeting unit. We further confirmed these results in a tumor xenograft mouse model. To our knowledge, this is the first report of a near-infrared laser irradiation-induced hyperthermic particle targeted to mitochondria, enhancing the cytotoxicity in cancer cells. Our present work therefore may open a new direction in the development of photothermal therapeutics.

Improved biomolecular detection based on a plasmonic nanoporous gold film fabricated by oblique angle deposition.

We demonstrated an enhanced surface plasmon resonance (SPR) detection by incorporating a nanoporous gold film on a thin gold substrate. Nanoscale control of thickness and roughness of the nanoporous layer was successfully accomplished by oblique angle deposition. In biosensing experiments, the results obtained by biotin-streptavidin interaction showed that SPR samples with a nanoporous gold layer provided a notable sensitivity improvement compared to a conventional bare gold film, which is attributed to an excitation of local plasmon field and an increased surface reaction area. Imaging sensitivity enhancement factor was employed to estimate an overall sensor performance of the fabricated samples and an optimal SPR structure was determined. Our approach is intended to show the feasibility and extend the applicability of the nanoporous gold film-mediated SPR biosensor to diverse biomolecular binding events.

Excitation of multiple resonances in 1D Anderson localized systems for efficient light amplification.

Excitation of hybridized multiple resonances can be an effective route for coherent light generation in irregular 1D systems larger than the localization length of light. Necklace states are often considered to have nonlocalized states. However, we propose that some hybridized/coupled states can have high-resonant tunneling with spatially extended fields. If strong localization properties are preserved in hybridized resonances, the excitation of such states allows for deposition of the excitation energy deep into the structure and spatial overlap with local gain regions. This result could allow for better utilizing hybridized resonances in biological or natural photonic systems.

Enhanced infrared neural stimulation using localized surface plasmon resonance of gold nanorods.

An advanced optical activation of neural tissues is demonstrated using pulsed infrared light and plasmonic gold nanorods. Photothermal effect localized in plasma membrane triggers action potentials of in vivo neural tissues. Compared with conventional infrared stimulation, the suggested method can increase a neural responsivity and lower a threshold stimulation level significantly, thereby reducing a requisite radiant exposure and the concern of tissue damage.

How to avoid a negative shift in reflection-type surface plasmon resonance biosensors with metallic nanostructures.

We experimentally demonstrate that introduction of a dielectric film can prevent the surface plasmon resonance (SPR) curve from being shifted to a smaller angle, called negative shift, which occurs unpredictably when metallic nanostructures deposited on a metal film are exposed to an adsorption of binding analytes. From parylene coating experiments, we find that the proposed reflection-type SPR system with a low refractive index MgF2 film and gold nanorods can provide an enhanced sensitivity by more than 6 times as well as a reliable positive shift. It is due to the fact that use of a dielectric film can contribute to the compensation of an anomalous dispersion relation and the prevention of a destructive interaction of propagating surface plasmons with multiple localized plasmon modes. Our approach is intended to show the feasibility and extend the applicability of the proposed SPR system to diverse biomolecular reactions.

Multi-color fluorescence imaging based on plasmonic wavelength selection and double illumination by white light.

We demonstrate the proof-of-concept for developing a multi-color fluorescence imaging system based on plasmonic wavelength selection and double illumination by white light source. This technique is associated with fluorescence excitation by transmitted light via a diffraction of propagating surface plasmons. Since double illumination through both sides of isosceles triangle prism in the Kretschmann configuration enables multiple transmission beams of different wavelengths to interact with the specimen, our approach can be an alternative to conventional fluorescence detection owing to alignment stability and functional expandability. After fabricating a plasmonic wavelength splitter and integrating it with microscopic imaging system, we successfully confirm the performance by visualizing in vitro neuron cells labeled with green and red fluorescence dyes. The suggested method has a potential that it could be combined with plasmonic biosensor scheme to realize a multi-functional platform which allows imaging and sensing of biological samples at the same time.

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.

Development of nanogap-rich hybrid gold nanostructures by use of two non-lithographic deposition techniques for a sensitive and reliable SERS biosensor.

Practical application of surface-enhanced Raman spectroscopy (SERS) has suffered from several limitations by heterogeneous distribution of hot-spots, such as high signal fluctuation and the resulting low reliability in detection. Herein, we develop a strategy of more sensitive and reliable SERS platform through designing spatially homogeneous gold nanoparticles (GNPs) on a uniform gold nanoisland (GNI) pattern. The proposed SERS substrate is successfully fabricated by combining two non-lithographic techniques of electron beam evaporation and convective self-assembly. These bottom-up methods allow a simple, cost-effective, and large-area fabrication. Compared to the SERS substrates obtained from two separate nanofabrication methods, Raman spectra measured by the samples with both GNPs and GNIs present a significant increase in the signal intensity as well as a notable improvement in signal fluctuation. The simulated near-field analyses demonstrate the formation of highly amplified plasmon modes within and at the gaps of the GNP-GNI interfaces. Moreover, the suggested SERS sensor is evaluated to detect the glucose concentration, exhibiting that the detection sensitivity is improved by more than 10 times compared to the sample with only GNI patterns and a fairly good spatial reproducibility of 7% is accomplished. It is believed that our suggestion could provide a potential for highly sensitive, low-cost, and reliable SERS biosensing platforms that include many advantages for healthcare devices. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00381-4.

Development of a 3D Printing-Enabled Cost-Effective Multimodal Raman Probe with High Signal-to-noise Ratio Raman Spectrum Measurements.

Raman spectroscopy has emerged as a pivotal analytical instrument, valued for its nondestructive capabilities and its capacity to provide essential material-specific insights. However, the excessive costs associated with commercially available Raman instruments present a barrier to their accessibility for many academic institutions and broader usage. Herein, we introduce an affordable and accessible approach to constructing a versatile Raman instrument capable of accommodating both spectroscopic and microscopic analyses. Through this multimodal approach that concurrently captures Raman signal and image data, we demonstrate color-based alcohol detection, showcase a high signal-to-noise ratio achieved through meticulous hardware design and signal processing, and present a cost-effective, modular design utilizing 3D printing technology. This system offers adaptability to address diverse research needs and requirements. We systematically detail the fabrication process, including the utilization of a 3D printer to produce necessary components, ultimately resulting in the assembly of a functional Raman probe system. Our experiments and subsequent analyses substantiate the accuracy and reliability of the constructed system. Specifically, we conducted experiments involving three distinct samples: water, ethanol, and methanol using the Raman probe, successfully confirming their unique Raman spectra. Furthermore, our Raman probe accurately identified ethanol concentration by assessing mixed samples with varying water-to-ethanol ratios and demonstrated a coefficient of determination value of 0.9993. This underscores the performance of the constructed Raman probe and positions it as a viable option for characterization, particularly in regions where access to conventional Raman probe may be limited.

Plasmonic wavelength splitter based on a large-area dielectric grating and white light illumination.

An optical process by which transmission wavelengths can be divided selectively by changing a resonance condition of surface plasmons (SPs) is demonstrated. When white light is incident to an SP resonance substrate with a dielectric grating, SP waves are excited at resonance and transmitted into the air via diffraction by a large-area grating pattern fabricated by nanoimprint lithography. While only a limited range of certain wavelengths is allowed to transmit, the peak transmission wavelength can be tuned continuously in the visible band. We also show that multiple wavelengths are transmitted into different directions simultaneously by using a wedge-shaped white light.

Numerical study on an application of subwavelength dielectric gratings for high-sensitivity plasmonic detection.

Although subwavelength dielectric gratings can be employed to achieve a high sensitivity of the surface plasmon resonance (SPR) biosensor, the plasmonic interpretation verifying the resulting sensitivity improvement remains unclear. The aim of this study is to elucidate the effects of the grating's geometric parameters on the amplification of SPR responses and to understand the physical mechanisms associated with the enhancement. Our numerical results show that the proposed SPR substrate with a dielectric grating can provide a better sensitivity due to the combined effects of surface reaction area and field distribution at the binding region. An influence of adhesion layer on the sensor performance is also discussed. The obtained results will be promising in high-sensitivity plasmonic biosensing applications.