Cortisol Monitoring Devices toward Implementation for Clinically Relevant Biosensing In Vivo.

Cortisol is a steroid hormone that regulates energy metabolism, stress reactions, and immune response. Cortisol is produced in the kidneys' adrenal cortex. Its levels in the circulatory system are regulated by the neuroendocrine system with a negative feedback loop of the hypothalamic-pituitary-adrenal axis (HPA-axis) following circadian rhythm. Conditions associated with HPA-axis disruption cause deteriorative effects on human life quality in numerous ways. Psychiatric, cardiovascular, and metabolic disorders as well as a variety of inflammatory processes accompanying age-related, orphan, and many other conditions are associated with altered cortisol secretion rates and inadequate responses. Laboratory measurements of cortisol are well-developed and based mainly on the enzyme linked immunosorbent assay (ELISA). There is a great demand for a continuous real-time cortisol sensor that is yet to be developed. Recent advances in approaches that will eventually culminate in such sensors have been summarized in several reviews. This review compares different platforms for direct cortisol measurements in biological fluids. The ways to achieve continuous cortisol measurements are discussed. A cortisol monitoring device will be essential for personified pharmacological correction of the HPA-axis toward normal cortisol levels through a 24-h cycle.

Broadband silicon grating couplers with high efficiency and a robust design.

A record-high efficiency and bandwidth for a fiber-to-chip grating coupler have been achieved with a robust design and cost-effective fabrication on a silicon-on-insulator platform. The design optimization involves the usual geometrical parameters, period, and fill factor, and a mode matching for the fiber output and grating. The measured coupling efficiency for TE polarization and 1 dB bandwidth are -2.64 dB (54 %) per grating and 67 nm, respectively. The 3 dB bandwidth exceeds 100 nm, fully covering the C + L band. The results fill the gap between theory and experimental realization in the existing literature.

Mechanical Enhancement and Kinetics Regulation of Fmoc-Diphenylalanine Hydrogels by Thioflavin†T.

The self-assembly of peptides is a key direction for fabrication of advanced materials. Novel approaches for fine tuning of macroscopic and microscopic properties of peptide self-assemblies are of a high demand for constructing biomaterials with desired properties. In this work, while studying the kinetics of the Fmoc-Diphenylalanine (Fmoc-FF) dipeptide self-assembly using the Thioflavin T (ThT) dye, we observed that the presence of ThT strongly modifies structural and mechanical properties of the Fmoc-FF hydrogel. Notably, the presence of ThT resulted in a tenfold increase of the gelation time and in the formation of short and dense fibers in the hydrogel. As a result of these morphological alteration higher thermal stability, and most important, tenfold increase of the hydrogel rigidity was achieved. Hence, ThT not only slowed the kinetics of the Fmoc-FF hydrogel formation, but also strongly enhanced its mechanical properties. In this study, we provide a detailed description of the ThT effect on the hydrogel properties and suggest the mechanisms for this phenomenon, paving the way for the novel approach to the control of the peptide hydrogels' micro- and macroscale properties.

The Oxidation-Induced Autofluorescence Hypothesis: Red Edge Excitation and Implications for Metabolic Imaging.

Endogenous autofluorescence of biological tissues is an important source of information for biomedical diagnostics. Despite the molecular complexity of biological tissues, the list of commonly known fluorophores is strictly limited. Still, the question of molecular sources of the red and near-infrared excited autofluorescence remains open. In this work we demonstrated that the oxidation products of organic components (lipids, proteins, amino acids, etc.) can serve as the molecular source of such red and near-infrared excited autofluorescence. Using model solutions and cell systems (human keratinocytes) under oxidative stress induced by UV irradiation we demonstrated that oxidation products can contribute significantly to the autofluorescence signal of biological systems in the entire visible range of the spectrum, even at the emission and excitation wavelengths higher than 650 nm. The obtained results suggest the principal possibility to explain the red fluorescence excitation in a large class of biosystems-aggregates of proteins and peptides, cells and tissues-by the impact of oxidation products, since oxidation products are inevitably presented in the tissue. The observed fluorescence signal with broad excitation originated from oxidation products may also lead to the alteration of metabolic imaging results and has to be taken into account.

Loss-free and active optical negative-index metamaterials.

The recently emerged fields of metamaterials and transformation optics promise a family of exciting applications such as invisibility, optical imaging with deeply subwavelength resolution and nanophotonics with the potential for much faster information processing. The possibility of creating optical negative-index metamaterials (NIMs) using nanostructured metal-dielectric composites has triggered intense basic and applied research over the past several years. However, the performance of all NIM applications is significantly limited by the inherent and strong energy dissipation in metals, especially in the near-infrared and visible wavelength ranges. Generally the losses are orders of magnitude too large for the proposed applications, and the reduction of losses with optimized designs seems to be out of reach. One way of addressing this issue is to incorporate gain media into NIM designs. However, whether NIMs with low loss can be achieved has been the subject of theoretical debate. Here we experimentally demonstrate that the incorporation of gain material in the high-local-field areas of a metamaterial makes it possible to fabricate an extremely low-loss and active optical NIM. The original loss-limited negative refractive index and the figure of merit (FOM) of the device have been drastically improved with loss compensation in the visible wavelength range between 722 and 738 nm. In this range, the NIM becomes active such that the sum of the light intensities in transmission and reflection exceeds the intensity of the incident beam. At a wavelength of 737 nm, the negative refractive index improves from -0.66 to -1.017 and the FOM increases from 1 to 26. At 738 nm, the FOM is expected to become macroscopically large, of the order of 10(6). This study demonstrates the possibility of fabricating an optical negative-index metamaterial that is not limited by the inherent loss in its metal constituent.

Hyperbolic metamaterials: new physics behind a classical problem.

Hyperbolic materials enable numerous surprising applications that include far-field subwavelength imaging, nanolithography, and emission engineering. The wavevector of a plane wave in these media follows the surface of a hyperboloid in contrast to an ellipsoid for conventional anisotropic dielectric. The consequences of hyperbolic dispersion were first studied in the 50's pertaining to the problems of electromagnetic wave propagation in the Earth's ionosphere and in the stratified artificial materials of transmission lines. Recent years have brought explosive growth in optics and photonics of hyperbolic media based on metamaterials across the optical spectrum. Here we summarize earlier theories in the Clemmow's prescription for transformation of the electromagnetic field in hyperbolic media and provide a review of recent developments in this active research area.

Nanoimprinted plasmonic nanocavity arrays.

We demonstrate high resonant absorption of visible light with a plasmonic nanocavity chain structure fabricated through resistless nanoimprinting in metal (RNIM). The RNIM approach provides a simple, reproducible, and accurate means to fabricate metallic nanopatterns with high fidelity. The nanocavities are shown to be efficiently excited using normally incident light, and the resonant wavelength can be controlled by either the width or the depth of the cavity. Numerical simulations confirm the experimental observations, and illustrate the behavior of the nanocavity chain waveguide and insensitivity to incident angle. The resonant absorption is due to the excitation of a localized metal-insulator-metal cavity mode. The interacting surface waves allow cavity lengths on the order of ten nanometers for light having a free space wavelength of about four hundred nanometers. Coupling of the cavities with an intervening surface plasmon wave results in a collective excitation and a chain waveguide mode that should prove valuable for more sensitive detection based on surface enhanced Raman scattering.

Direct measurement of group delay dispersion in metamagnetics for ultrafast pulse shaping.

In this paper, we explore the use of magnetic resonant metamaterials, so called metamagnetics, as dispersive elements for optical pulse shaping. We measure both positive and negative group delay dispersion (GDD) values in a metamagnetic material using the multiphoton interference phase scan (MIIPS) technique and show pulse temporal profiles numerically. The results are compared with finite element models. These GDD properties of metamagnetics, along with previously shown tunability and loss control with gain media, enable their use in ultrashort pulse optical applications.

Experimental retrieval of the kinetic parameters of a dye in a solid film.

Effects of a solid matrix on the dye kinetic parameters for Rh800 were experimentally studied. Saturation intensity dependencies were measured with a seeding pulse amplification method using a picosecond and a femtosecond white light supercontinuum source. The kinetic parameters were obtained by fitting experimental dependencies with Yee's finite-difference time-domain model coupled to the rate equations of the 4-level Rh800-system. The comparison of these parameters (Rh800-solid host) with liquid host parameters revealed a slight change of the radiative lifetime and a strong change of the non-radiative decay rate. This experimentally determined model enables predictive simulations of time-domain responses of active metamaterials.

Metal nanoslit lenses with polarization-selective design.

We present comprehensive studies on thin diffraction lenses made of arrays of subwavelength, parallel nanoslits in a gold film. Such a nanoslit lens can operate either as a conventional convex or concave lens. The lenses can be designed to focus linearly polarized light with polarization either perpendicular (TM-lens) or parallel to the slits (TE-lens), while the orthogonal polarization diverges when passing through the lens. The designs of each lens are initially built on the dispersion relations for wave propagation through a parallel-plate waveguide. Both TM- and TE-lenses were realized experimentally, and full-wave numerical simulations fully support the experimental results.

Numerical modeling of plasmonic nanoantennas with realistic 3D roughness and distortion.

Nanostructured plasmonic metamaterials, including optical nanoantenna arrays, are important for advanced optical sensing and imaging applications including surface-enhanced fluorescence, chemiluminescence, and Raman scattering. Although designs typically use ideally smooth geometries, realistic nanoantennas have nonzero roughness, which typically results in a modified enhancement factor that should be involved in their design. Herein we aim to treat roughness by introducing a realistic roughened geometry into the finite element (FE) model. Even if the roughness does not result in significant loss, it does result in a spectral shift and inhomogeneous broadening of the resonance, which could be critical when fitting the FE simulations of plasmonic nanoantennas to experiments. Moreover, the proposed approach could be applied to any model, whether mechanical, acoustic, electromagnetic, thermal, etc, in order to simulate a given roughness-generated physical phenomenon.

Drude relaxation rate in grained gold nanoantennas.

The effect of grain boundaries on the electron relaxation rate is significant even for large area noble metal films and more so for plasmonic nanostructures. Optical spectroscopy and X-ray diffraction show a substantial improvement in plasmon resonance quality for square-particle nanoantennas after annealing due to an enlarged grain size from 22 to 40 nm and improved grain boundaries described by the electron reflection coefficient. The electron relaxation rate due to the grains is shown to decrease by a factor of 3.2.

Surface-specific washing-free immunosensor for time-resolved cortisol monitoring.

Cortisol is a steroid hormone that regulates a wide range of vital processes. Its level changes with diurnal rhythm and reacts to stress. Measurement of cortisol levels is still a complex multi-step process. A reversible washing-free registration method is required. Here we describe metal-enhanced fluorescence assay based on a displacement of a dye labeled BSA-cortisol conjugate from the immune complex immobilized on the golden islands by free cortisol. This competitive approach allows time-resolved monitoring of the fluorescent signal, surface-enhanced by the gold film, and provides the possibility of continuous real-time cortisol monitoring based on the implantable surface-enhanced immunosensor, which was not demonstrated so far even in vitro.

Yellow-light negative-index metamaterials.

A well-established, silver fishnet design has been further miniaturized to function as a negative-index material at the shortest wavelength to date (to our knowledge). By studying the transmittance, reflectance, and corresponding numerical simulations of the sample, we report in this Letter a negative refractive index of -0.25 at the yellow-light wavelength of 580 nm.

New mechanism of plasmons specific for spin-polarized nanoparticles.

Here it is experimentally shown that Co nanoparticles with a single-domain crystal structure support a plasmon resonance at approximately 280 nm with better quality than gold nanoparticle resonance in the visible. Magnetic nature of the nanoparticles suggests a new type of these plasmons. The exchange interaction of electrons splits the energy bands between spin-up electrons and spin-down electrons. It makes it possible for coexistence of two independent channels of conductivity as well as two independent plasmons in the same nanoparticle with very different electron relaxation. Indeed, the density of empty states in a partially populated d-band is high, resulting in a large relaxation rate of the spin-down conduction electrons and consequently in low quality of the plasmon resonance. In contrast, the majority electrons with a completely filled d-band do not provide final states for the scattering processes of the conduction spin-up electrons, therefore supporting a high quality plasmon resonance. The scattering without spin flip is required to keep these two plasmons independent.

Label-free characterization of white blood cells using fluorescence lifetime imaging and flow-cytometry: molecular heterogeneity and erythrophagocytosis [Invited].

Blood cell analysis is one of the standard clinical tests. Despite the widespread use of exogenous markers for blood cell quantification, label-free optical methods are still of high demand due to their possibility for in vivo application and signal specific to the biochemical state of the cell provided by native fluorophores. Here we report the results of blood cell characterization using label-free fluorescence imaging techniques and flow-cytometry. Autofluorescence parameters of different cell types - white blood cells, red blood cells, erythrophagocytic cells - are assessed and analyzed in terms of molecular heterogeneity and possibilities of differentiation between different cell types in vitro and in vivo.

Amplification of photoacoustic effect in bimodal polymer particles by self-quenching of indocyanine green.

A new type of bimodal contrast agent was made that is based on the self-quenching of indocyanine green (ICG) encapsulated in a biocompatible and biodegradable polymer shell. The increasing of a local ICG concentration that is necessary for the obtaining of self-quenching effect was achieved by freezing-induced loading and layer-by-layer assembly. As a result, an efficient photoacoustic(optoacoustic)/fluorescent contrast agent based on composite indocyanine green/polymer particles was successfully prepared and was characterized by fluorescence and photoacoustic(optoacoustic) tomography in vitro. This type of contrast agent holds good promise for clinical application owing to its high efficiency and biosafety.

The Ag dielectric function in plasmonic metamaterials.

Ag permittivity (dielectric function) in coupled strips is different from bulk and has been studied for strips of various dimensions and surface roughness. Arrays of such paired strips exhibit the properties of metamagnetics. The surface roughness does not affect the Ag dielectric function, although it does increase the loss at the plasmon resonances of the coupled strips. The size effect in the imaginary part of the dielectric function is significant for both polarizations of light, parallel and perpendicular to the strips with relatively large A-parameter.

Cooperative bi-exponential decay of dye emission coupled via plasmons.

Bi-exponential decay of dye fluorescence near the surface of plasmonic metamaterials and core-shell nanoparticles is shown to be an intrinsic property of the coupled system. Indeed, the Dicke, cooperative states involve two groups of transitions: super-radiant, from the most excited to the ground states and sub-radiant, which cannot reach the ground state. The relaxation in the sub-radiant system occurs mainly due to the interaction with the plasmon modes. Our theory shows that the relaxation leads to the population of the sub-radiant states by dephasing the super-radiant Dicke states giving rise to the bi-exponential decay in agreement with the experiments. We use a set of metamaterial samples consisting of gratings of paired silver nanostrips coated with Rh800 dye molecules, having resonances in the same spectral range. The bi-exponential decay is demonstrated for Au\SiO2\ATTO655 core-shell nanoparticles as well, which persists even when averaging over a broad range of the coupling parameter.

Waveguide coupling via magnetic gratings with effective strips.

Gratings with complex multilayer strips are studied under inclined incident light. Great interest in these gratings is due to applications as input/output tools for waveguides and as subwavelength metafilms. The structured strips introduce anisotropy in the effective parameters, providing additional flexibility in polarization and angular dependences of optical responses. Their characterization is challenging in the intermediate regime between subwavelength and diffractive modes. The transition between modes occurs at the Wood's anomaly wavelength, which is different at different angle of incidence. The usual characterization with an effective film using permittivity ε and permeability µ has limited effectiveness at normal incidence but does not apply at inclined illumination, due to the effect of periodicity. The optical properties are better characterized with effective medium strips instead of an effective medium layer to account for the multilayer strips and the underlying periodic nature of the grating. This approach is convenient for describing such intermediate gratings for two types of applications: both metafilms and the coupling of incident waves to waveguide modes or diffraction orders. The parameters of the effective strips are retrieved by matching the spectral-angular map at different incident angles.