We present a numerical analysis of the average intercore crosstalk (IC-XT) of wavelength-division multiplexed (WDM) optical channels in a homogeneous two-core fiber system. This analysis is performed considering cores with zero-dispersion wavelengths at 1550 nm. In the analysis, we consider 11 WDM channels spaced 100 GHz apart transmitted in three different schemes, one centered at 1510 nm with negative dispersion D = − 3.5 ps / nm · km, one centered at 1550 nm with D = 0, and one centered at 1590 nm with D = + 3.5 ps / nm · km. This selection allows for the observation of how the IC-XT of WDM channels is modified using positive, zero, and negative dispersion parameters. To analyze more realistic scenarios of IC-XT in multicore fibers, we considered random bending and twisting perturbations along the fiber. In addition, we considered fiber nonlinearities such as four-wave mixing (FWM) among WDM channels. The results show that FWM produces a power transfer among the transmitted WDM channels that depends on the dispersion parameter D at core 1, and this effect is transferred to the average crosstalk of the WDM channels at core 2. Therefore, the average IC-XT of WDM channels can be modified in a controlled way by selecting an adequate dispersion parameter D in combination with FWM nonlinearity. These results provide valuable information for understanding the wavelength dependence of the average IC-XT of homogeneous multichannel MCF systems working around a zero-dispersion wavelength.
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.
Aim: Our aim is for a fast microscopic analysis that can be done directly on the excised tissue in or near the operating theatre.
Approach: We demonstrate the combination of three nonlinear imaging techniques at selected wavelengths to delineate tumor boundaries. We use hyperspectral coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG), and two-photon excited fluorescence (TPF) on excised patient tissue.
Results: We show the discriminatory power of each of the signals and demonstrate a sensitivity of 0.87 and a specificity of 0.95 using four CARS wavelengths in combination with SHG and TPF. We verify that the information is independent of sample treatment.
Conclusions: Nonlinear multispectral imaging can be used to accurately determine tumor boundaries. This demonstration using microscopy in the epi-direction directly on thick tissue slices brings this technology one step closer to clinical implementation.
The temperature response of a tapered holmium-doped fiber amplifier and its impact in the performance of fiber lasers and temperature fiber sensors has numerically been analyzed. Different pump schemes and different longitudinal shapes of the tapered-doped fiber were investigated, and it was found that a parabolic shape of the tapered fiber amplifier in a co-propagating pump scheme shows the highest sensitivity to temperature changes. In particular, the temperature sensitivity of the amplified signal was 2.5 × 10 − 4 ° C for 1 W of pump power and 1 m of doped fiber length. In addition, this sensitivity can be increased up to 10 times for fiber lengths shorter than 1 m and pump powers lower than 300 mW. Our results can be used to describe the temperature response of tapered fiber amplifiers in the mid-infrared spectral region and contribute with new information for the development of fiber lasers and fiber temperature sensors.
Gratings in optical fibers have been increasingly used in a variety of applications such as sensors and Telecomm. Depending on perturbation separation, they are classified as: fiber Bragg gratings (FBG), and long period gratings (LPG), whose each spectral output offer advantages for certain applications. Nowadays there is a great interest in the study of arrays formed by the combination of long period gratings and Bragg gratings in cascade (CLBG), where the propagation modes of the core and the cladding propagate in the Bragg grating after they propagate in the LPG. In this work, analysis and modeling of Cascaded Long Bragg Gratings using the Transfer Matrix method was performed for the case of two gratings in series along one fiber. We analyzed the variation of the FWHM of the reflectance and transmittance spectra for different values of the difference of the refractive indexes of the core and the perturbation of the grating, using the typical core refractive index of an SMF-28 as reference value. For smaller index difference a narrow intensity peak was observed. After the number of perturbations was varied, when there is a greater number of perturbations in the grating, there is greater intensity in reflectance. However, as our results show, this dependence is not a linear function. The results were obtained under the maximum-reflectivity condition (tuned) for each single grating. The development of the mathematical model, the results of the simulation and the analysis of results are part of the development of the present work.
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.
A centimeter-scale micromixer was fabricated by two-photon polymerization inside a closed microchannel using direct laser writing. The structure consists of a repeating pattern of 20 μm×20 μm×155 μm acrylate pillars and extends over 1.2 cm. Using external ultrasonic actuation, the micropillars locally induce streaming with flow speeds of 30 μm s−1. The fabrication method allows for large flexibility and more complex designs.
We report on a novel type of laser in which a semiconductor optical amplifier (SOA) receives frequency-selective feedback from a glass-waveguide circuit. The laser we present here is based on InP for operation in the 1.55 μm wavelength range. The Si3N4/SiO2 glass waveguide circuit comprises two sequential high-Q ring resonators. Adiabatic tapering is used for maximizing the feedback. The laser shows single-frequency oscillation with a record-narrow spectral linewidth of 24 kHz at an output power of 5.7 mW. The hybrid laser can be tuned over a broad range of 46.8 nm (1531 nm to 1577.8 nm). Such InP-glass hybrid lasers can be of great interest in dense wavelength division multiplexing (DWDM) and as phase reference in optical beam-forming networks (OBFN). The type of laser demonstrated here is also of general importance because it may be applied over a huge wavelength range including the visible, limited only by the transparency of glass (400 nm to 2.35 μm).
A custom-built intrinsic flow-through dissolution setup was developed and incorporated into a home-built CARS microscope consisting of a synchronously pumped optical parametric oscillator (OPO) and an inverted microscope with a 20X/0.5NA objective. CARS dissolution images (512×512 pixels) were collected every 1.12s for the duration of the dissolution experiment. Hyperspectral CARS images were obtained pre- and postdissolution by rapidly imaging while sweeping the wavelength of the OPO in discrete steps so that each frame in the data stack corresponds to a vibrational frequency. An image-processing routine projects this hyperspectral data into a single image wherein each compound appears with a unique color. Dissolution was conducted using theophylline and cimetidine-naproxen co-amorphous mixture. After 15 minutes of theophylline dissolution, hyperspectral imaging showed a conversion of theophylline anhydrate to the monohydrate, confirmed by a peak shift in the CARS spectra. CARS dissolution images showed that monohydrate crystal growth began immediately and reached a maximum with complete surface coverage at about 300s. This result correlated with the UV dissolution data where surface crystal growth on theophylline compacts resulted in a rapidly reducing dissolution rate during the first 300s. Co-amorphous cimetidinenaproxen didn’t appear to crystallize during dissolution. We observed solid-state conversions on the compact’s surface in situ during dissolution. Hyperspectral CARS imaging allowed visual discrimination between the solid-state forms on the compact’s surface. In the case of theophylline we were able to correlate the solid-state change with a change in dissolution rate.
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 Δ 9 -tetrahydrocannabinolic acid (THCa) in Cannabis sativa L. using coherent anti-Stokes Raman scattering microscopy. In line with previous observations we find high concentrations of THCa in pistillate flowering bodies and relatively low amounts within flowering bracts. Surprisingly, we find differences in the local morphologies of the THCa-containing bodies: organelles within bracts are large, diffuse, and spheroidal, whereas in pistillate flowers they are generally compact, dense, and have heterogeneous structures. We have also identified two distinct vibrational signatures associated with THCa, both in pure crystalline form and within Cannabis plants; at present the exact natures of these spectra remain an open question.
Hyperspectral coherent anti-Stokes Raman scattering (CARS) microscopy is quickly becoming a prominent imaging
modality because of its many advantages over the traditional paradigm of multispectral CARS. In particular, recording a
significant portion of the vibrational spectrum at each spatial pixel allows image-wide spectral analysis at much higher
rates than can be achieved with spontaneous Raman. We recently developed a hyperspectral CARS method, the driving
principle behind which is the fast acquisition and display of a hyperspectral datacube as a set of intuitive images wherein each material in a sample appears with a unique trio of colors. Here we use this system to image and analyze two types of polymorphic samples: the pseudopolymorphic hydration of theophylline, and the packing polymorphs of the sugar alcohol mannitol. In addition to these solid-state form modifications we have observed spectral variations of crystalline mannitol and diprophylline as functions of their orientations relative to the optical fields. We use that information to visualize the distributions of these compounds in a pharmaceutical solid oral dosage form.
A detailed description of a common path interferometer is given for CARS and SRS applications. In this
interferometer, both probe and reference arms are separated in time and polarization by a birefringent crystal.
In order to generate the pump pulse a Ti:Sa laser centered at 808 nm is used, as for the Stokes pulses a
Nd:YVO centered at 1064 nm is used, both lasers are synchronized in phase and frequency at a repetition rate
of 80MHz. Acetone is employed for analysis and detection in this experiment, with a extinction ratio of
1/250, a temperature heating control system is developed for the calcite birefringent crystals with a precision
of de ±0.01°C as well as an analysis of the contributions of both processes CARS and SRS by using a lock-in
amplifier.
We explore strategies for optimizing selectivity, specificity, and sensitivity in broadband CARS by precalculating
pulse shapes using an evolutionary algorithm. We show the possibility of selective excitation of a single constituent
in a test case of a mixture of five resonant compounds. The obtainable contrast ratio for a test case
of PMMA in a mixture of five resonant compounds is predicted to be 2000:1, and is related the uniqueness of
the complex vibrational response of the compound of interest compared to that of the surrounding molecules.
Furthermore we investigate how the effects of homodyne mixing in the focal volume affect the obtainable contrast
ratio and how noise affects the optimization. We also show preliminary results of experimental optimization of
the CARS signal from PMMA microspheres, resulting in high contrast imaging, free of non-resonant background
signal.
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 (VMI) technique allows imaging at high speed free of non-resonant background, and is able to
distinguish between electronic and vibrational contributions to the total signal.
In biological samples the resonant CARS signal of less abundant constituents can be overwhelmed by the nonresonant
background, preventing detection of those molecules. We demonstrate a method to obtain the phase of
the oscillators in the focal volume that allows discrimination of those hidden molecules. The phase is measured
with respect to the local excitation fields using a cascaded
phase-preserving chain. It is measured point-bypoint
and takes into account refractive index changes in the sample, phase curvature over the field-of-view and
interferometric instabilities. The detection of the phase of the vibrational motion can be regarded as a vibrational
extension of the linear (refractive index) phase contrast microscopy introduced by Zernike around 1933.
In this article we show that heterodyne CARS, based on a controlled and stable phase-preserving chain, can be
used to measure amplitude and phase information of molecular vibration modes. The technique is validated by
a comparison of the imaginary part of the heterodyne CARS spectrum to the spontaneous Raman spectrum of
polyethylene. The detection of the phase allows for rejection of the non-resonant background from the data. The
resulting improvement of the signal to noise ratio is shown by measurements on a sample containing lipid.
By spectral phase shaping of both the pump and probe pulses in coherent anti-Stokes Raman scattering (CARS)
spectroscopy we demonstrate the extraction of the frequencies of vibrational lines using an unamplified oscillator.
Furthermore we demonstrate chemically selective broadband CARS microscopy on a mixed sample of 4 μm
diameter polystyrene (PS) and poly(methyl methacrylate) (PMMA) beads. The CARS signal from either the
PS or the PMMA beads is shown to be enhanced or suppressed, depending on the phase profile applied to the
broadband spectrum. Using a combination of negative and positive (sloped) π-phase steps in the pump and
probe spectrum the purely non-resonant background signal is removed.
We demonstrate heterodyne detection of CARS signals using a cascaded phase-preserving chain to generate the CARS input wavelengths and a coherent local oscillator. The heterodyne amplification by the local oscillator reveals a window for shot noise limited detection before the signal-to-noise is limited by amplitude fluctuations. We demonstrate an improvement in sensitivity by more than 3 orders of magnitude for detection using a photodiode. This will enable CARS microscopy to reveal concentrations below the current mMolar range.
We report on the concept, generation and first observations of focused surface plasmons on shaped gratings. The gratings patterns are engineered to perform functions such as focusing or directing through noncolinear grating-assisted phasematching. We present local probing of the plasmon propagation by phase sensitive PSTM of the field distribution on engineered gratings showing the focusing of plasmons.
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