High optical gain in erbium-doped potassium double tungstate channel waveguide amplifiers.

We report on the optical-gain properties of channel waveguides patterned into lattice-matched KGdxLuyEr1-x-y(WO4)2 layers grown onto undoped KY(WO4)2 substrates by liquid phase epitaxy. A systematic investigation of gain is performed for five different Er3+ concentrations in the range of 0.75 to 10at.% and different pump powers and signal wavelengths. In pump-probe-beam experiments, relative internal gain, i.e., signal enhancement minus absorption loss of light propagating in the channel waveguide, is experimentally demonstrated, with a maximum value of 12 ± 5 dB/cm for signals at the peak-emission wavelength of 1534.7 nm.

Temperature-dependent absorption and emission of potassium double tungstates with high ytterbium content.

We study the spectroscopic properties of thin films of potassium ytterbium gadolinium double tungstates, KYb0.57Gd0.43(WO4)2, and potassium ytterbium lutetium double tungstates, KYb0.76Lu0.24(WO4)2, specifically at the central absorption line near 981 nm wavelength, which is important for amplifiers and lasers. The absorption cross-section of both thin films is found to be similar to those of bulk potassium rare-earth double tungstates, suggesting that the crystalline layers retain their spectroscopic properties albeit having >50 at.% Yb3+ concentration. The influence of sample temperature is investigated and found to substantially affect the measured absorption cross-section. Since amplifiers and lasers typically operate above room temperature due to pump-induced heating, the temperature dependence of the peak-absorption cross-section of the KYb0.57Gd0.43(WO4)2 is evaluated for the sample being heated from 20 °C to 170 °C, resulting in a measured reduction of peak-absorption cross-section at the transitions near 933 nm and 981 nm by ~40% and ~52%, respectively. It is shown that two effects, the change of Stark-level population and linewidth broadening due to intra-manifold relaxation induced by temperature-dependent electron-phonon interaction, contribute to the observed behavior. The effective emission cross-sections versus temperature have been calculated. Luminescence-decay measurements show no significant dependence of the luminescence lifetime on temperature.

Optical antennas with sinusoidal modulation in width.

Small metal structures sustaining plasmon resonances in the optical regime are of great interest due to their large scattering cross sections and ability to concentrate light to subwavelength volumes. In this paper, we study the dipolar plasmon resonances of optical antennas with a constant volume and a sinusoidal modulation in width. We experimentally show that by changing the phase of the width-modulation, with a small 10 nm modulation amplitude, the resonance shifts over 160 nm. Using simulations we show how this simple design can create resonance shifts greater than 600 nm. The versatility of this design is further shown by creating asymmetric structures with two different modulation amplitudes, which we experimentally and numerically show to give rise to two resonances. Our results on both the symmetric and asymmetric antennas show the capability to control the localization of the fields outside the antenna, while still maintaining the freedom to change the antenna resonance wavelength. The antenna design we tested combines a large spectral tunability with a small footprint: all the antenna dimensions are factor 7 to 13 smaller than the wavelength, and hold potential as a design element in meta-surfaces for beam shaping.

A phased antenna array for surface plasmons.

Surface plasmon polaritons are electromagnetic waves that propagate tightly bound to metal surfaces. The concentration of the electromagnetic field at the surface as well as the short wavelength of surface plasmons enable sensitive detection methods and miniaturization of optics. We present an optical frequency plasmonic analog to the phased antenna array as it is well known in radar technology and radio astronomy. Individual holes in a thick gold film act as dipolar emitters of surface plasmon polaritons whose phase is controlled individually using a digital spatial light modulator. We show experimentally, using a phase sensitive near-field microscope, that this optical system allows accurate directional emission of surface waves. This compact and flexible method allows for dynamically shaping the propagation of plasmons and holds promise for nanophotonic applications employing propagating surface plasmons.

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. By combining measurement at a range of excitation frequencies, a frequency map of modes is made, from which the spectral line width and Q-factor of individual resonances can be obtained.

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. Results from human A431 tumor cells with stained nuclei and incubated with IRdye 800CW labeled cancer drug cetuximab targeting epidermal growth factor receptor at the cell membrane show that NR-FWM is well suited for cellular imaging. A comparison of vibrationally nonresonant FWM imaging with vibrational resonant coherent anti-Stokes Raman scattering signals revealed nearly identical qualitative information in cellular imaging. NR-FWM is also suitable for tumor tissue imaging in combination with fluorescence imaging of IRdye 800CW labeled, human epidermal growth factor 2 targeting cancer drug pertuzumab and provides additional information over transmission microscopy.

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.

Erbium-doped spiral amplifiers with 20 dB of net gain on silicon.

Spiral-waveguide amplifiers in erbium-doped aluminum oxide on a silicon wafer are fabricated and characterized. Spirals of several lengths and four different erbium concentrations are studied experimentally and theoretically. A maximum internal net gain of 20 dB in the small-signal-gain regime is measured at the peak emission wavelength of 1532 nm for two sample configurations with waveguide lengths of 12.9 cm and 24.4 cm and concentrations of 1.92 × 10(20) cm(-3) and 0.95 × 10(20) cm(-3), respectively. The noise figures of these samples are reported. Gain saturation as a result of increasing signal power and the temperature dependence of gain are studied.

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 this work coherent anti-Stokes Raman scattering microscopy is used to image the surface of tablets during dissolution while UV absorption spectroscopy is simultaneously providing inline analysis of dissolved drug concentration for tablets containing a 50% mixture of theophylline anhydrate and ethyl cellulose. The measurements showed that in situ CARS microscopy is capable of imaging selectively theophylline in the presence of ethyl cellulose. Additionally, the theophylline anhydrate converted to theophylline monohydrate during dissolution, with needle-shaped crystals growing on the tablet surface during dissolution. The conversion of theophylline anhydrate to monohydrate, combined with reduced exposure of the drug to the flowing dissolution medium resulted in decreased dissolution rates. Our results show that in situ CARS microscopy combined with inline UV absorption spectroscopy is capable of monitoring pharmaceutical tablet dissolution and correlating surface changes with changes in dissolution rate.

Active and passive control of zinc phthalocyanine photodynamics.

In this work we report on the ultrafast photodynamics of the photosensitizer zinc phthalocyanine (ZnPc) and manipulation thereof. Two approaches are followed: active control via pulse shaping and passive control via strategic manipulation in the periphery of the molecular structure. The objective of both of these control experiments is the same: to enhance the yield of the functional pathway and to minimize loss channels. The aim of the active control experiments is to increase the intersystem crossing yield in ZnPc, which is important for application in photodynamic therapy (PDT). Pulse shaping allowed an improvement in triplet to singlet ratio of 15% as compared to a transform-limited pulse. This effect is ascribed to a control mechanism that utilizes multiphoton pathways to higher-lying states from where intersystem crossing is more likely to occur. The passive control experiments are performed on ZnPc derivatives deposited onto TiO2, serving as a model system of a dye-sensitized solar cell (DSSC). Modification of the anchoring ligand of the molecular structure resulted in an increased rate for electron injection into TiO2 and slower back electron transfer, improving the DSSC efficiency.

Intraoperative near-infrared fluorescence tumor imaging with vascular endothelial growth factor and human epidermal growth factor receptor 2 targeting antibodies.

UNLABELLED: Fluorescence imaging is currently attracting much interest as a method for intraoperative tumor detection, but most current tracers lack tumor specificity. Therefore, this technique can be further improved by tumor-specific detection. With tumor-targeted antibodies bound to a radioactive label, tumor-specific SPECT or PET is feasible in the clinical setting. The aim of the present study was to apply antibody-based tumor detection to intraoperative optical imaging, using preclinical in vivo mouse models. METHODS: Anti-vascular endothelial growth factor (VEGF) antibody bevacizumab and anti-human epidermal growth factor receptor (HER) 2 antibody trastuzumab were labeled with the near-infrared (NIR) fluorescence dye IRDye 800CW. Tumor uptake of the fluorescent tracers and their (89)Zr-labeled radioactive counterparts for PET was determined in human xenograft-bearing athymic mice during 1 wk after tracer injection, followed by ex vivo biodistribution and pathologic examination. Intraoperative imaging of fluorescent VEGF- or HER2-positive tumor lesions was performed in subcutaneous tumors and in intraperitoneal dissemination tumor models. RESULTS: Tumor-to-background ratios, with fluorescent imaging, were 1.93 ± 0.40 for bevacizumab and 2.92 ± 0.29 for trastuzumab on day 6 after tracer injection. Real-time intraoperative imaging detected tumor lesions at even the submillimeter level in intraperitoneal dissemination tumor models. These results were supported by standard histology, immunohistochemistry, and fluorescence microscopy analyses. CONCLUSION: NIR fluorescence-labeled antibodies targeting VEGF or HER2 can be used for highly specific and sensitive detection of tumor lesions in vivo. These preclinical findings encourage future clinical studies with NIR fluorescence-labeled tumor-specific antibodies for intraoperative-guided surgery in cancer patients.

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. In this paper we present a new implementation of VPC-CARS based on a third-order cascaded phase-preserving chain, where the CARS signal is generated at a single (constant) wavelength independent of the vibrational frequency that is addressed. This implementation will simplify the detection side considerably.

Influence of the length and grafting density of PNIPAM chains on the colloidal and optical properties of quantum dot/PNIPAM assemblies.

Structural and optical characterization of water soluble, thermo-responsive quantum dot/poly(N-isopropyl acrylamide) (QD/PNIPAM) hybrid particles using fluorescence correlation spectroscopy (FCS) and time-correlated single photon counting (TCSPC) measurements performed at temperatures below and above the lower critical solution temperature (LCST) of PNIPAM is reported. By increasing the temperature above the LCST, the signature of the PNIPAM chain collapse covering the QDs is revealed by FCS measurements. Despite the significant structural change, the TCSPC measurements show that the fluorescence lifetimes remain of the same order of magnitude at T > LCST. Such QD/PNIPAM hybrid particles with water solubility and robust thermo-responsive behavior at physiologically relevant temperatures are potentially useful for (bio)molecular sensing and separation applications.

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. This vibrational molecular interferometry technique allows imaging at high speed free of nonresonant background, and is able to distinguish between electronic and vibrational contributions to the total signal.

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. Second, selectivity is increased via determination of the phase and amplitude, allowing separation of individual molecular components of a sample even when their vibrational bands overlap. Here, using vibrational phase contrast CARS (VPC-CARS), we demonstrate enhanced sensitivity in quantitative measurements of ethanol/methanol mixtures and increased selectivity in a heterogeneous mixture of plastics and water. This powerful technique opens a wide range of possibilities for studies of complicated systems where overlapping resonances limit standard methodologies.

Revisiting the optical properties of the FMO protein.

We review the optical properties of the FMO complex as found by spectroscopic studies of the Q ( y ) band over the last two decades. This article emphasizes the different methods used, both experimental and theoretical, to elucidate the excitonic structure and dynamics of this pigment-protein complex.

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. We then investigate the shapes, symmetries, and topologies of the landscape contour lines around the optimal solution and also around the point corresponding to zero phase. We demonstrate the significance of the employed phase bases in achieving convex contour lines, suppressed local optima, and high optimization fitness with a few (and even a single) optimization parameter.

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. The first order approximation of the process shows a simple relation between input and output phase profiles, useful for pulse shaping at ultraviolet wavelengths.

Robust orthogonal parameterization of evolution strategy for adaptive laser pulse shaping.

Many spectroscopic applications of femtosecond laser pulses require properly-shaped spectral phase profiles. The optimal phase profile can be programmed on the pulse by adaptive pulse shaping. A promising optimization algorithm for such adaptive experiments is evolution strategy (ES). Here, we report a four fold increase in the rate of convergence and ten percent increase in the final yield of the optimization, compared to the direct parameterization approach, by using a new version of ES in combination with Legendre polynomials and frequency-resolved detection. Such a fast learning rate is of paramount importance in spectroscopy for reducing the artifacts of laser drift, optical degradation, and precipitation.

Tunable aggregation and luminescence of bis(diarylethene)sexithiophenes.

Diarylethenes with two different side groups (phenyl and chloro) were appended to both alpha-ends of a sexithiophene unit. The temperature dependent aggregation properties for both compounds were characterized by steady state and transient absorption spectroscopy. The peripheral side groups show an unexpectedly significant influence on the electronic properties of the sexithiophene core. Furthermore, the relative influence of the phenyl and chloro substituents on the aggregation behavior observed is remarkable. The phenyl compound exhibits formation of H-aggregates over a narrow temperature range, between 240 and 200 K, typical of strong intermolecular interactions. In contrast, the chloro compound shows gradual aggregation over a wide temperature range, forming H-aggregates albeit with weaker intermolecular interactions. The results demonstrate that minor changes in the structure lead to tunability of the aggregation and corresponding luminescence properties of sexithiophenes in solution and hold particular relevance to supramolecular and polymer systems based on sexithiophene units.