Photon counting Raman spectroscopy: a benchmarking study vs surface plasmon enhancement.

We demonstrate a single-photon counting Raman spectroscope and benchmark it against conventional and surface-enhanced Raman spectroscopy. For direct comparison without ambiguity, we use the same solutions of Rhodamine 6G and a common optical setup with either a spectrometer or an acousto-optic tunable filter, whereas the surface enhancement is realized with immobilized Ag nanoparticles. Our results find that the single photon counting significantly elevates the detection sensitivity by up to eight orders of magnitude, arriving at a comparable level of surface-enhanced Raman spectroscopy. Another significant advantage is with the time-resolving measurement, where we demonstrate time-gated and time-correlated single-photon counting with sub-nanosecond resolution. It offers insights into the samples' transient responses and enables the isolation of Raman scattering from fluorescence signals.

Untargeted urine metabolite profiling by mass spectrometry aided by multivariate statistical analysis to predict prostate cancer treatment outcome.

Deciphering metabolomic networks has been demonstrated to provide valuable information for diagnosing and monitoring diseases. Herein, we report a technique to monitor untargeted urine metabolites to evaluate prostate cancer aggressiveness and treatment outcome. Direct chemical profiling of urine was achieved by a combined procedure of hyphenating laser diode thermal desorption with atmospheric pressure chemical ionization mass spectrometry (LDTD-APCI-MS). We describe a conceptually new approach to monitoring preoperative urinary metabolic alterations associated with prostate cancer recurrence. By evaluating mass/charge (m/z) ratios and peak intensities of ions detected by mass spectroscopy of urine samples, we revealed that intensities at m/z 313.2740 (±0.0003) and 341.3054 (±0.0006) attributable to monoacylglycerol backbone fragments from glycerides can be statistically correlated to disease progression.

Au-on-Ag nanostructure forin-situSERS monitoring of catalytic reactions.

Dual-functionality Au-on-Ag nanostructures (AOA) were fabricated on a silicon substrate by first immobilizing citrate-reduced Ag nanoparticles (Ag NPs, ∼43 nm in diameter), followed by depositing ∼7 nm Au nanofilms (Au NFs) via thermal evaporation. Au NFs were introduced for their catalytic activity in concave-convex nano-configuration. Ag NPs underneath were used for their significant enhancement factor (EF) in surface-enhanced Raman scattering (SERS)-based measurements of analytes of interest. Rhodamine 6G (R6G) was utilized as the Raman-probe to evaluate the SERS sensitivity of AOA. The SERS EF of AOA is ∼37 times than that of Au NPs. Using reduction of 4-nitrothiophenol (4-NTP) by sodium borohydride (NaBH4) as a model reaction, we demonstrated the robust catalytic activity of AOA as well as its capacity to continuously monitor via SERS the disappearance of reactant 4-NTP, emergence and disappearance of intermediate 4,4'-DMAB, and the appearance of product 4-ATP throughout the reduction process in real-time andin situ.

Atomic, Molecular and Hybrid Oxygen Structures on Silver.

Interactions between oxygen and silver are important in many areas of science and technology, including materials science, medical, biomedical and environmental applications, spectroscopy, photonics, and physics. In the chemical industry, identification of oxygen structures on Ag catalysts is important in the development of environmentally friendly and sustainable technologies that utilize gas-phase oxygen as the oxidizing reagent without generating byproducts. Gas-phase oxygen adsorbs on Ag atomically by breaking the O-O bond and molecularly by preserving the O-O bond. Atomic O structures have Ag-O vibrations at 240-500 cm-1. Molecular O2 structures have O-O vibrations at significantly higher values of 870-1150 cm-1. In this work, we identify hybrid atomic-molecular oxygen structures, which form when one adsorbed O atom reacts with one lattice O atom on the surface or in the subsurface of Ag. Thus, these hybrid structures require dissociation of adsorbed molecular oxygen into O atoms but still possess the O-O bond. The hybrid structures have O-O vibrations at 600-810 cm-1, intermediate between the Ag-O vibrations of atomic oxygen and the O-O vibrations of molecular oxygen. The hybrid O-O structures do not form by a recombination of two adsorbed O atoms because one of the O atoms in the hybrid structure must be embedded into the Ag lattice. The hybrid oxygen structures are metastable and, therefore, serve as active species in selective oxidation reactions on Ag catalysts.

Fiber Coupled Near-Field Thermoplasmonic Emission from Gold Nanorods at 1100 K.

Nanostructured gold has attracted significant interest from materials science, chemistry, optics and photonics, and biology due to their extraordinary potential for manipulating visible and near-infrared light through the excitation of plasmon resonances. However, gold nanostructures are rarely measured experimentally in their plasmonic properties and hardly used for high-temperature applications because of the inherent instability in mass and shape due to the high surface energy at elevated temperatures. In this work, the first direct observation of thermally excited surface plasmons in gold nanorods at 1100 K is demonstrated. By coupling with an optical fiber in the near-field, the thermally excited surface plasmons from gold nanorods can be converted into the propagating modes in the optical fiber and experimentally characterized in a remote manner. This fiber-coupled technique can effectively characterize the near-field thermoplasmonic emission from gold nanorods. A direct simulation scheme is also developed to quantitively understand the thermal emission from the array of gold nanorods. The experimental work in conjunction with the direct simulation results paves the way of using gold nanostructures as high-temperature plasmonic nanomaterials, which has important implications in thermal energy conversion, thermal emission control, and chemical sensing.

Therapeutic prognosis of prostate cancer using surface-enhanced Raman scattering of patient urine and multivariate statistical analysis.

Surface-enhanced Raman scattering (SERS) is highly sensitive and label-free analytical technique based on Raman spectroscopy aided by field-multiplying plasmonic nanostructures. We report the use of SERS measurements of patient urine in conjunction with biostatistical algorithms to assess the treatment response of prostate cancer (PCa) in 12 recurrent (Re) and 63 nonrecurrent (NRe) patient cohorts. Multiple Raman spectra are collected from each urine sample using monodisperse silver nanoparticles (AgNPs) for Raman signal enhancement. Genetic algorithms-partial least squares-linear discriminant analysis (GA-PLS-LDA) was employed to analyze the Raman spectra. Comprehensive GA-PLS-LDA analyses of these Raman spectral features (p = 3.50 × 10-16 ) yield an accuracy of 86.6%, sensitivity of 86.0%, and specificity 87.1% in differentiating the Re and NRe cohorts. Our study suggests that SERS combined with multivariate GA-PLS-LDA algorithm can potentially be used to detect and monitor the risk of PCa relapse and to aid with decision-making for optimal intermediate secondary therapy to recurred patients.

Nanostructured sapphire optical fiber embedded with Au nanorods for high-temperature plasmonics in harsh environments.

Sensors for harsh environments must exhibit robust sensing response and considerable thermal and chemical stability. We report the exploration of a novel all-alumina nanostructured sapphire optical fiber (NSOF) embedded with Au nanorods (Au NRs) for plasmonics-based sensing at high temperatures. Temperature dependence of the localized surface plasmon resonance (LSPR) of Au NRs was studied in conjunction with numerical calculations using the Drude model. It was found that LSPR of Au NRs changes markedly with temperature, red shifting and increasing in transmission amplitude as the temperature increases. Furthermore, this variation is highly localized through tunneling by overlapping the near-field of thin cladding and sapphire optical fiber. The NSOF embedded with Au NRs has the potential for sensing in advanced energy generation systems.

Ocean Salinity Sensing Using Long-Period Fiber Gratings Functionalized with Layer-by-Layer Hydrogels.

Rapid, accurate, and real-time measurements of ocean salinity are of great importance for a host of scientific, commercial, and defense applications. We demonstrate a highly sensitive, fast-responding fiber-optic salinity sensor that integrates long-period fiber gratings (LPFGs) with ionic strength-responsive hydrogel. The submicron-thick hydrogel was synthesized via layer-by-layer electrostatic assembly of partially quaternized poly(4-vinylpyridine) (qP4VP) and poly(acrylic acid), followed by chemical cross-linking. Spectroscopic ellipsometry measurement of a hydrogel made of 37% quaternized qP4VP showed robust and reversible swelling/deswelling in solutions with salt concentrations ranging from 0.4 to 0.8 M (22.8-44.7 g/kg) around pH 8.1. The swelling/deswelling process induced large changes in the refractive index of the hydrogel, leading to resultant shift in the resonance wavelength (RW) of LPFGs. The salinity-dependent optical response of the hydrogel-coated LPFGs is in good agreement with ellipsometry measurement. LPFGs coated with the hydrogel exhibited a sensitivity of 7 nm RW shift/M (125.5 pm/‰) with a measurement time less than 5 s. The shift in the resonance wavelength correlated linearly with salt concentration, making quantification of measured salinity straightforward.

Plasmonic Au nanorods stabilized within anodic aluminum oxide pore channels against high-temperature treatment.

Au nanorods (Au NRs) are promising candidates for sensing applications due to their tunable localized surface plasmon resonance wavelength. At temperatures above 250 °C, however, these structures are morphologically unstable and tend to evaporate. We herein report a novel refractory plasmonic nanocomposite system comprising Au NRs entrapped in anodized aluminum oxide (AAO) scaffolds that are stable up to 800 °C. Au NRs were synthesized in the cylindrical pores of sapphire-supported AAO via in situ electroless deposition on catalytic Au nanoparticles (Au NPs) anchored on the pore walls. The morphological characteristics and surface-enhanced Raman scattering (SERS) functionality of Au NRs before and after heat treatment were evaluated using SEM, XRD and Raman spectroscopy. Compared to unconfined Au NRs that evolved into spherical particles at temperatures below 250 °C and subsequently evaporated from the substrate surface, the morphology of Au NRs in AAO was preserved upon heat treatment at temperatures up to 800 °C. Furthermore, by tuning the AAO scaffolds thickness and pore diameter, the aspect ratio (AR) of the entrapped Au NRs was varied from 2.4 to 7.8. The SERS sensitivity of Au NRs in AAO was found to increase with decreasing AR when the incident light was parallel to the rod longitudinal axis, in close agreement with the calculated fourth power of the local electromagnetic field using the finite-difference time domain method.

Label-free detection of Staphylococcus aureus bacteria using long-period fiber gratings with functional polyelectrolyte coatings.

Highly sensitive long-period fiber gratings (LPFG) was developed for label-free and rapid detection of Staphylococcus aureus (S. aureus). Specifically, the LPFG was functionalized with antibody and nanopitted polyelectrolyte coatings to facilitate bacterial adhesion and thus enhance the sensitivity of bacteria detection. The kinetics of S. aureus adhesion on functional coatings were tracked by surface morphology evolution and time-resolved resonance wavelength shift of the coated LPFG at a flow rate of 30 µl/ml and 37 °C in the concentration range of 104-108 colony forming unit (CFU)/ml. S. aureus detection at concentrations as low as 224 CFU/ml can be achieved within a short time span of 30 min. The LPFG-based biosensor can be readily adapted to a variety of biophotonic platforms, for applications such as food safety inspection, environmental monitoring, clinical diagnostics, and medical applications.

Colloidal plasmonic gold nanoparticles and gold nanorings: shape-dependent generation of singlet oxygen and their performance in enhanced photodynamic cancer therapy.

INTRODUCTION: In recognition of the potentials of gold nanoparticles (Au NPs) in enhanced photodynamic therapy (PDT) for cancer, it is desirable to further understand the shape-dependent surface plasmonic resonance (SPR) properties of various gold nanostructures and evaluate their performances in PDT. MATERIALS AND METHODS: Monodispersed colloidal spherical solid Au NPs were synthesized by UV-assisted reduction using chloroauric acid and sodium citrate, and hollow gold nanorings (Au NRs) with similar outer diameter were synthesized based on sacrificial galvanic replacement method. The enhanced electromagnetic (EM) field distribution and their corresponding efficiency in enhancing singlet oxygen (1O2) generation of both gold nanostructures were investigated based on theoretical simulation and experimental measurements. Their shape-dependent SPR response and resulted cell destruction during cellular PDT in combination with 5-aminolevulinic acid (5-ALA) were further studied under different irradiation conditions. RESULTS: With comparable cellular uptake, more elevated formation of 1O2 in 5-ALA-enabled PDT was detected with the presence of Au NRs than that with Au NPs under broadband light irradiation in both cell-free and intracellular conditions. As a result of the unique morphological attributes, exhibiting plasmonic effect of Au NRs was still achievable in the near infrared (NIR) region, which led to an enhanced therapeutic efficacy of PDT under NIR light irradiation. CONCLUSION: Shape-dependent SPR response of colloidal Au NPs and Au NRs and their respective effects in promoting PDT efficiency were demonstrated in present study. Our innovative colloidal Au NRs with interior region accessible to surrounding photosensitizers would serve as efficient enhancers of PDT potentially for deep tumor treatment.

Thin-core fiber structures with overlays for sensing applications.

We investigate thin-core fiber-optic structures with film overlays that can be used for sensing applications. The structures are formed by a section of thin-core fibers (SM630 or SM450) spliced between standard SMF-28 fibers. The fibers are coated with overlays using the layer-by-layer assembly technology based on sequential alternating adsorption of polymer monolayers via electrostatic attraction. Transmission spectrum of the structures exhibits resonance dips caused by interaction between cladding modes. We measure the shifts of spectra with increasing thickness of the overlay and with pH value of the external medium. We calculate the shift of resonance wavelengths, which we compare with the experiment.

Surface-enhanced Raman scattering analysis of urine from deceased donors as a prognostic tool for kidney transplant outcome.

We report the utility of surface-enhanced Raman scattering (SERS) analysis of urine from deceased donors for prognosis of kidney transplant outcomes. Iodide-modified silver nanoparticles were used as the enabler for sensitive measurements of urine proteins. Principal component analysis (PCA) and linear discriminant analysis (LDA) were employed for the statistical analysis of the SERS data. Thirty urine samples in three classes were analysed. The ATN class consists of donors whose kidneys had acute tubular necrosis (ATN), the most common type of acute kidney injury (AKI) with high risk of poor graft performance in recipients, yet yielded acceptable transplant outcome. The DGF class is comprised of donors whose kidney had delayed graft function (DGF) in recipients. The control class includes donors whose kidneys did not have donor ATN or recipient DGF. We show a sensitivity of more than 90 % in differentiating the ATN class from the DGF and control classes. Our methodology can thus help clinicians choose kidneys in the high-risk ATN category for transplant which would otherwise be discarded. Our research is impactful in that it could serve as a valuable guidance to expand the deceased donor pool to include those perceived as high-risk AKI type based on common urinary biomarkers. Picutre: Scheme of SERS analysis of urine samples from deceased donors for kidney transplant outcome indication.

Strategy and method for nanoporous cladding formation on silica optical fiber.

We demonstrate the proof of an innovative concept of fabricating nanostructured aluminum oxide cladding on silica optical fiber. Our fabrication strategy entails freeze-coating aluminum on silica fiber and its subsequent anodization, resulting in the formation of anodized aluminum oxide (AAO) cladding with highly organized nanopore channels vertically aligned to the fiber axis. We show that the structure (diameter of pore channels and the porosity) of AAO cladding can be controlled by varying anodization conditions such as the type and concentration of electrolyte solutions and applied voltage. The versatility of AAO as a cladding with tunable structural and optical characteristics and/or a host of other functional nanostructures within the pore channels has the potential to enable a new class of specialty optical fiber for new sensor architecture and applications.

Lab-on-fiber optofluidic platform for in situ monitoring of drug release from therapeutic eluting polyelectrolyte multilayers.

A lab-on-fiber (LOF) optofluidic platform that provides physiologically relevant microenvironment was developed by integrating a long period grating (LPG) coupled with high order cladding mode to achieve high index sensitivity and a liquid-tight capillary tube assembly as a microfluidic chamber for LPG to mimic physiologically relevant microenvironment. We demonstrate the utility of LOF for in situ monitoring the construction of the [chitosan (CHI)/poly (acrylic acid) (PAA)/gentamicin sulfate (GS)/PAA]n multilayers at monolayer resolution as well as evaluating the rate of GS release at a flow rate of 0.127 mL/min at 37 °C in real time. We reveal that GS is released at a faster rate under the dynamic flow condition than in a static medium. Our findings underscore the importance of conducting drug release studies in physiologically relevant conditions.

Long-period gratings inscribed in photonic crystal fiber by symmetric CO(2) laser irradiation: erratum.

This erratum amends the wrongly cited NSF grant number in acknowledgment section in our publication.

Synergistic Integration of Layer-by-Layer Assembly of Photosensitizer and Gold Nanorings for Enhanced Photodynamic Therapy in the Near Infrared.

A layer-by-layer (LbL) assembly strategy was used to incorporate high concentrations of Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) photosensitizer (PS) onto plasmonic Au nanorings (Au NRs) for increasing the cellular uptake of AlPcS4 and subsequently enhancing the efficacy of photodynamic therapy (PDT) of human breast cancer cells (MDA-MB-231) in the near-infrared (NIR) range. Au NRs with two layers of AlPcS4 (Au NR/(AlPcS4)2) markedly increased the cellular internalization of AlPcS4 and elevated the generation of reactive oxygen species (ROS). Quenching the photosensitivity of AlPcS4 on the Au NR surface during the uptake and then significant ROS formation only upon PS release inside the cellular compartment made it possible to achieve a high PDT specificity and efficacy. PDT of breast cancer cells following 4 h of incubation with various formula revealed the following cell destruction rate: ∼10% with free AlPcS4, ∼23% with singly layered Au NR/(AlPcS4)1 complex, and ∼50% with doubly layered Au NR/(AlPcS4)2. Incubation with Au NR/(AlPcS4)2 for an additional 2 h resulted in ∼85% cell killing, more than 8-fold increase compared to AlPcS4 alone. Together, integration of LbL of PS with Au NRs holds a significant promise for PDT therapeutic treatment of a variety of cancers.

Gold nanoparticle-enhanced photodynamic therapy: effects of surface charge and mitochondrial targeting.

AIM: The authors aimed to further improve the efficiency and selectivity of gold nanoparticle (Au NP)-assisted photodynamic therapy by modulating the surface charge of Au NPs and delivering Au NPs particularly to mitochondria of breast cancer cells. METHODS: Solid gold nanospheres (˜50 nm) with negative and positive surface charge were synthesized respectively, and mitochondria-targeting Au NPs were prepared by conjugating with triphenylphosphonium molecules. CONCLUSION: Positively charged Au NPs were preferably taken up by breast cancer cells. Combination of positive surface charge with mitochondria-targeting domain onto Au NPs allowed their accumulation in the mitochondria of breast cancer cells to significantly elevate reactive oxygen species formation in 5-aminolevulinic-acid-enabled photodynamic therapy and improve selective destruction of breast cancer cells.

Use of surface-enhanced Raman scattering as a prognostic indicator of acute kidney transplant rejection.

We report an early, noninvasive and rapid prognostic method of predicting potential acute kidney dysfunction using surface-enhanced Raman scattering (SERS). Our analysis was performed on urine samples collected prospectively from 58 kidney transplant patients using a He-Ne laser (632.8 nm) as the excitation source. All abnormal kidney function episodes (three acute rejections and two acute kidney failures that were eventually diagnosed independently by clinical biopsy) consistently exhibited unique SERS spectral features in just one day following the transplant surgery. These results suggested that SERS analysis provides an early and more specific indication to kidney function than the clinically used biomarker, serum creatinine (sCr).

Evaluation of photodynamic therapy efficiency using an in vitro three-dimensional microfluidic breast cancer tissue model.

In recognition of the limitations of monolayer cell cultures and resource-intensive animal studies, a microfluidic culture system was developed for creation of physiologically relevant three-dimensional (3D) tissues. In this study, an in vitro 3D breast cancer tissue model was established in a microfluidic system with human breast cancer cells (MCF-7) and primary adipose-derived stromal cells (ASCs). It was evaluated for utility in determining the efficiency of photodynamic therapy (PDT) with therapeutic agents (i.e. photosensitizer and gold nanoparticles) under various irradiation conditions. We demonstrated, for the first time, the potential use of a microfluidic-based in vitro 3D breast cancer model for effective evaluation of PDT, with the capability of controlling 3D microenvironments for breast cancer tissue formation, real-time monitoring of tissue progression, implementing a circulation-like dynamic medium flow and drug supplements, and investigating the relation between light penetration and tissue depth in PDT.