Understanding the conditions for the optimum nonlinear refraction of epsilon-near-zero films based on transparent conducting oxides.

Transparent Conducting Oxides (TCOs) exhibit a large and ultrafast intensity-dependent refractive index in their Epsilon-Near-Zero (ENZ) spectral region, which depends dramatically on the material properties and measurement arrangement conditions. Therefore, attempts to optimize the nonlinear response of ENZ TCOs usually involve extensive nonlinear optical measurements. In this work, we show that significant experimental work can be avoided by carrying out an analysis of the material's linear optical response.

Tethering Cells via Enzymatic Oxidative Crosslinking Enables Mechanotransduction in Non-Cell-Adhesive Materials.

Cell-matrix interactions govern cell behavior and tissue function by facilitating transduction of biomechanical cues. Engineered tissues often incorporate these interactions by employing cell-adhesive materials. However, using constitutively active cell-adhesive materials impedes control over cell fate and elicits inflammatory responses upon implantation.

Axon-Myelin Unit Blistering as Early Event in MS Normal Appearing White Matter.

Objective: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease of unknown etiology. Although the prevalent view regards a CD4 -lymphocyte autoimmune reaction against myelin at the root of the disease, recent studies propose autoimmunity as a secondary reaction to idiopathic brain damage. To gain knowledge about this possibility we investigated the presence of axonal and myelinic morphological alterations, which could implicate imbalance of axon-myelin units as primary event in MS pathogenesis.

Nonlinear multispectral imaging for tumor delineation.

Significance: In breast-preserving tumor surgery, the inspection of the excised tissue boundaries for tumor residue is too slow to provide feedback during the surgery. The discovery of positive margins requires a new surgery which is difficult and associated with low success. If the re-excision could be done immediately this is believed to improve the success rate considerably.

Dynamic Consolidation Measurements in a Well Field Using Fiber Bragg Grating Sensors.

Currently available groundwater flow prediction tools and methods are limited by insufficient spatial resolution of subsurface data and the unknown local heterogeneity. In this field study, fiber Bragg grating (FBG) sensors were installed in an extraction well field to investigate its potential to measure groundwater flow velocity. Reference in-situ pore pressure and temperature measurements were used to identify possible sources of FBG responses.

Possibilities for Groundwater Flow Sensing with Fiber Bragg Grating Sensors.

An understanding of groundwater flow near drinking water extraction wells is crucial when it comes to avoiding well clogging and pollution. A promising new approach to groundwater flow monitoring is the deployment of a network of optical fibers with fiber Bragg grating (FBG) sensors. In preparation for a field experiment, a laboratory scale aquifer was constructed to investigate the feasibility of FBG sensors for this application.

Label-Free Prostate Cancer Detection by Characterization of Extracellular Vesicles Using Raman Spectroscopy.

Mammalian cells release extracellular vesicles (EVs) into their microenvironment that travel the entire body along the stream of bodily fluids. EVs contain a wide range of biomolecules. The transported cargo varies depending on the EV origin.

Intracellular Delivery of Poorly Soluble Polyphenols: Elucidating the Interplay of Self-Assembling Nanocarriers and Human Chondrocytes.

Increased molecular understanding of multifactorial diseases paves the way for novel therapeutic approaches requiring sophisticated carriers for intracellular delivery of actives. We designed and characterized self-assembling lipid-core nanocapsules for coencapsulation of two poorly soluble natural polyphenols curcumin and resveratrol. The polyphenols were identified as high-potential therapeutic candidates intervening in the intracellular inflammation cascade of chondrocytes during the progress of osteoarthritis.

Imaging local acoustic pressure in microchannels.

A method for determining the spatially resolved acoustic field inside a water-filled microchannel is presented. The acoustic field, both amplitude and phase, is determined by measuring the change of the index of refraction of the water due to local pressure using stroboscopic illumination. Pressure distributions are measured for the fundamental pressure resonance in the water and two higher harmonic modes.

Hybrid imaging of fluorescently labeled cancer drugs and label-free four-wave mixing microscopy of cancer cells and tissues.

Fluorescent labels are well suited as tracers for cancer drug monitoring. Identifying cellular target regions of these drugs with a high resolution is important to assess the working principle of a drug. We investigate the applications of label-free nonresonant four-wave mixing (NR-FWM) microscopy in biological imaging in combination with fluorescence imaging of fluorescently labeled cancer drugs.

Skin penetration behavior of lipid-core nanocapsules for simultaneous delivery of resveratrol and curcumin.

Polyphenols, which are secondary plant metabolites, gain increasing research interest due to their therapeutic potential. Among them, resveratrol and curcumin are two agents showing antioxidant, anti-inflammatory, antimicrobial as well as anticarcinogenic effects. In addition to their individual therapeutic effect, increased activity was reported upon co-delivery of the two compounds.

Identification and quantification of 16 inorganic ions in water by Gaussian curve fitting of near-infrared difference absorbance spectra.

This study shows two novel fitting strategies applied to differential absorbance spectra for identification and quantification of electrolytes. The effects of 16 dissolved salts were investigated in the wavelength range from 14000 to 9091 wavenumbers (714-1100 nm) by linear fits of the differential absorbance values (Y(υ,c)=offset(υ)+b(υ)×c) recorded for each wavenumber (υ) and concentration (c) ranges from 500 to 30 mM. The slopes (b) of these fits resulted in clear fingerprints of the electrolytes.

Raman microscopy for cellular investigations--From single cell imaging to drug carrier uptake visualization.

Progress in advanced therapeutic concepts requires the development of appropriate carrier systems for intracellular drug delivery. Consequently, analysis of interaction between carriers, drugs and cells as well as their uptake and intracellular fate is a current focus of research interest. In this context, Raman spectroscopy recently became an emerging analytical technique, due to its non-destructive, chemically selective and label-free working principle.

Epi-detection of vibrational phase contrast coherent anti-Stokes Raman scattering.

We demonstrate a system for the phase-resolved epi-detection of coherent anti-Stokes Raman scattering (CARS) signals in highly scattering and/or thick samples. With this setup, we measure the complex vibrational responses of multiple components in a thick, highly-scattering pharmaceutical tablet in real time and verify that the epi- and forward-detected information are in very good agreement.

Coherent anti-Stokes Raman scattering microscopy driving the future of loaded mesoporous silica imaging.

This study reports the use of variants of coherent anti-Stokes Raman scattering (CARS) microscopy as a novel method for improved physicochemical characterization of drug-loaded silica particles. Ordered mesoporous silica is a biomaterial that can be loaded to carry a number of biochemicals, including poorly water-soluble drugs, by allowing the incorporation of drug into nanometer-sized pores. In this work, the loading of two poorly water-soluble model drugs, itraconazole and griseofulvin, in MCM-41 silica microparticles is characterized qualitatively, using the novel approach of CARS microscopy, which has advantages over other analytical approaches used to date and is non-destructive, rapid, label free, confocal and has chemical and physical specificity.

Coherent anti-Stokes Raman scattering (CARS) microscopy visualizes pharmaceutical tablets during dissolution.

Traditional pharmaceutical dissolution tests determine the amount of drug dissolved over time by measuring drug content in the dissolution medium. This method provides little direct information about what is happening on the surface of the dissolving tablet. As the tablet surface composition and structure can change during dissolution, it is essential to monitor it during dissolution testing.

In situ dissolution analysis using coherent anti-Stokes Raman scattering (CARS) and hyperspectral CARS microscopy.

The solid-state form of an active pharmaceutical ingredient (API) in an oral dosage form plays an important role in determining the dissolution rate of the API. As the solid-state form can change during dissolution, there is a need to monitor the oral dosage form during dissolution testing. Coherent anti-Stokes Raman scattering (CARS) microscopy provides rapid, spectrally selective imaging to monitor the oral dosage form during dissolution.

In planta imaging of Δ⁹-tetrahydrocannabinolic acid in Cannabis sativa L. with hyperspectral coherent anti-Stokes Raman scattering microscopy.

Nature has developed many pathways to produce medicinal products of extraordinary potency and specificity with significantly higher efficiencies than current synthetic methods can achieve. Identification of these mechanisms and their precise locations within plants could substantially increase the yield of a number of natural pharmaceutics. We report label-free imaging of Δ⁹-tetrahydrocannabinolic acid (THCa) in Cannabis sativa L.

Polyglutamine aggregate structure in vitro and in vivo; new avenues for coherent anti-Stokes Raman scattering microscopy.

Coherent anti-Stokes Raman scattering (CARS) microscopy is applied for the first time for the evaluation of the protein secondary structure of polyglutamine (polyQ) aggregates in vivo. Our approach demonstrates the potential for translating information about protein structure that has been obtained in vitro by X-ray diffraction into a microscopy technique that allows the same protein structure to be detected in vivo. For these studies, fibres of polyQ containing peptides (D(2)Q(15)K(2)) were assembled in vitro and examined by electron microscopy and X-ray diffraction methods; the fibril structure was shown to be cross β-sheet.

Background-free nonlinear microspectroscopy with vibrational molecular interferometry.

We demonstrate a method for performing nonlinear microspectroscopy that provides an intuitive and unified description of the various signal contributions, and allows the direct extraction of the vibrational response. Three optical fields create a pair of Stokes Raman pathways that interfere in the same vibrational state. Frequency modulating one of the fields leads to amplitude modulations on all of the fields.

Implementation of vibrational phase contrast coherent anti-Stokes Raman scattering microscopy.

Detection of molecules using vibrational resonances in the fingerprint region for narrowband coherent anti-Stokes Raman scattering (CARS) is challenging. The spectrum is highly congested resulting in a large background and a reduced specificity. Recently we introduced vibrational phase contrast CARS (VPC-CARS) microscopy as a technique capable of detecting both the amplitude and phase of the CARS signal, providing background-free images and high specificity.

Pharmaceutical applications of non-linear imaging.

Non-linear optics encompasses a range of optical phenomena, including two- and three-photon fluorescence, second harmonic generation (SHG), sum frequency generation (SFG), difference frequency generation (DFG), third harmonic generation (THG), coherent anti-Stokes Raman scattering (CARS), and stimulated Raman scattering (SRS). The combined advantages of using these phenomena for imaging complex pharmaceutical systems include chemical and structural specificities, high optical spatial and temporal resolutions, no requirement for labels, and the ability to image in an aqueous environment. These features make such imaging well suited for a wide range of pharmaceutical and biopharmaceutical investigations, including material and dosage form characterisation, dosage form digestion and drug release, and drug and nanoparticle distribution in tissues and within live cells.

Visualizing resonances in the complex plane with vibrational phase contrast coherent anti-Stokes Raman scattering.

In coherent anti-Stokes Raman scattering (CARS), the emitted signal carries both amplitude and phase information of the molecules in the focal volume. Most CARS experiments ignore the phase component, but its detection allows for two advantages over intensity-only CARS. First, the pure resonant response can be determined, and the nonresonant background rejected, by extracting the imaginary component of the complex response, enhancing the sensitivity of CARS measurements.

Exploring, tailoring, and traversing the solution landscape of a phase-shaped CARS process.

Pulse shaping techniques are used to improve the selectivity of broadband CARS experiments, and to reject the overwhelming background. Knowledge about the fitness landscape and the capability of tailoring it is crucial for both fundamental insight and performing an efficient optimization of phase shapes. We use an evolutionary algorithm to find the optimal spectral phase of the broadband pump and probe beams in a background-suppressed shaped CARS process.

Tailoring a coherent control solution landscape by linear transforms of spectral phase basis.

Finding an optimal phase pattern in a multidimensional solution landscape becomes easier and faster if local optima are suppressed and contour lines are tailored towards closed convex patterns. Using wideband second harmonic generation as a coherent control test case, we show that a linear combination of spectral phase basis functions can result in such improvements and also in separable phase terms, each of which can be found independently. The improved shapes are attributed to a suppressed nonlinear shear, changing the relative orientation of contour lines.