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The study of photochemical reactions is of great importance in many fields including the pharmaceutical, food, and paint industry. Most of these photochemical processes are being studied to better understand how to apply them for a specific purpose or how unwanted effects can be prevented. Advances are still being made in photoreactor design, where in-situ detection of the involved reagents and products is an important development. Liquid-core waveguides (LCWs) allow simultaneous illumination and optical assessment of liquid samples and, therefore, constitute one way of combining photoreactor design with on-line or in-situ analytical detection methods. LCWs possess several interesting characteristics, such as low light loss, increased optical path length, and possibilities for coupling with spectroscopic techniques. The current review discusses the state-of-the-art of LCWs applied as photoreactors, for analytical detection, and their combinations. We discuss the differences between several total internal reflection (TIR)-based LCWs, including polymer and polymer-coated capillaries, and silica aerogels, and interference-based waveguides, including Bragg fibers, holey fibers, Kagomé fibers and anti-resonance reflecting optical waveguides (ARROWs). Assessed characteristics include the (freedom of) design, the degree of light attenuation, the range of transmittable wavelengths, gas permeability, compatibility with analytical techniques, current challenges, and applications.

High-resolution compressive imaging via a flexible multimode fiber is demonstrated using a swept-laser source and wavelength dependent speckle illumination. An in-house built swept-source allowing for independent control of bandwidth and scanning range is used to explore and demonstrate a mechanically scan-free approach for high-resolution imaging through an ultrathin and flexible fiber probe. The computational image reconstruction is shown by utilizing a narrow sweeping bandwidth of $$< 10$$ < 10 nm while acquisition time is decreased by 95% compared to conventional raster scanning endoscopy. Demonstrated narrow-band illumination in the visible spectrum is vital for the detection of fluorescence biomarkers in neuroimaging applications. The proposed approach yields device simplicity and flexibility for minimally invasive endoscopy.

Coherent multi-spectral extreme ultraviolet beams have great potential for providing high spatial and temporal resolution for microscopy and spectroscopy applications. But due to the limitations of short-wavelength optics and the broad bandwidth, it remains a challenge to perform quantitative, high-resolution beam characterization. Here we present a wavefront sensing solution based on multiplexed ptychography, with which we show spectrally resolved, high-resolution beam reconstructions. Furthermore, using these high-fidelity quantitative wavefront measurements, we investigate aberration transfer mechanisms in the high-harmonic-generation process, where we present and explain harmonic-order-dependent astigmatism inheritance from the fundamental wavefront. This ptychographic wavefront sensing concept thus enables detailed studies of the high-harmonic-generation process, such as spatiotemporal effects in attosecond pulse formation.

The detection of methane, a strong greenhouse gas, has increased in importance due to rising emissions, which partly originate from unreported and undetected leaks in oil and gas fields. The gas emitted by these leaks could be detected using an optical fiber-based photoacoustic sensor called PAS-WRAP. Here, we investigate the potential of silicon-based membranes as more sensitive microphones in the PAS-WRAP concept. Toward this goal, we built a setup with which the frequency response of the membranes was interrogated by an optical fiber. Multiple mounting mechanisms were tested by adapting commercial interferometry systems (OP1550, ZonaSens, Optics11 B.V.) to our case. Finally, methane detection was attempted using a silicon nitride membrane as a sensor. Our findings show a quality factor of 2.4 at 46 kHz and 33.6 at 168 kHz for a thin silicon nitride membrane. This membrane had a frequency response with a signal-to-background ratio of 1 ± 0.7 at 44 kHz when tested in a vacuum chamber with 4% methane at 0.94 bar. The signal-to-background ratio was not significant for methane detection; however, we believe that the methods and experimental procedures that we used in this work can provide a useful reference for future research into gas trace detection with optical fiber-based photoacoustic spectroscopy.

A multimode fiber represents the ultimate limit in miniaturization of imaging endoscopes. However, such a miniaturization usually comes as a cost of a low spatial resolution and a long acquisition time. Here we propose a fast superresolution-fiber-imaging technique employing compressive sensing through a multimode fiber with a data-driven machine-learning framework. We implement a generative adversarial network (GAN) to explore the sparsity inherent to the model and provide compressive reconstruction images that are not sparse in a representation basis. The proposed method outperforms other widespread compressive imaging algorithms in terms of both image quality and noise robustness. We experimentally demonstrate machine-learning ghost imaging below the diffraction limit at a sub-Nyquist speed through a thin multimode fiber probe. We believe that this work has great potential in applications in various fields ranging from biomedical imaging to remote sensing.

The laser ablation threshold is an important parameter that governs the response of materials to intense laser irradiation. Here we study the ablation threshold of liquid tin, by irradiating tin microdroplets with nanosecond laser pulses having finely controlled temporal shape and duration. We use the time-dependent reflection from the droplet as the main observable, which exhibits a sharp decrease in magnitude at a given time instance that depends on the laser intensity. This moment marks the generation of a plasma that strongly absorbs the following incident laser light, rapidly expands, and thereby sets in motion the remainder of the liquid droplet. We find an inverse-square dependence of this plasma-onset time on laser intensity and attribute this scaling to the presence of one-dimensional heat diffusion during irradiation. This scaling and its one-dimensional thermal origin is strongly established in literature and follows from a square-root scaling of the thermal diffusion depth with time. Our experiment unambiguously shows that this scaling law holds for our specific case of nanosecond laser impact on tin microdroplets. The results presented in this work are of particular interest to target preparation and metrology in extreme-ultraviolet sources utilizing tin microdroplet targets.

We present a new experimental setup for high-order harmonic generation in laser-produced plasmas, allowing the generation of coherent VUV and EUV light, as well as characterisation of the laser-produced plasmas by studying the emitted harmonics. We have successfully generated high-order harmonics in laser-produced Al, Ni, Ag, In, and Sn plasmas. Large differences in harmonic spectra and signal yields have been observed for these different targets. Harmonics up to order 25, corresponding to a wavelength of 62.4 nm and photon energy of 19.9 eV, have been measured with tin plasmas. Scanning laser parameters and delay between pump and fundamental laser pulses allows us to optimise the harmonic yield and observe the temporal dynamics of the laser-produced tin plasma.

Dielectric optical waveguides constitute the main building blocks of photonic integrated circuits (PICs). Channels with high refractive index contrast can provide very compact PIC components, whereas structures with lower index exhibit less propagation loss. A hybrid concept that can combine the best of high- and low-index materials is highly required. Here, we devise a new approach to realize compact and low-loss hybrid optical waveguides based on the interaction of weak optical modes. This is a rather universal approach that can be applied to a wide range of optical materials. To prove the principle, the hybrid waveguide structure is formed by combining a low-index polymer and a thin layer of silicon nitride. For this material combination, a minimum bending radius of 90 µm (for a bending loss of 0.005 dB/90°) and a propagation loss of 0.7 dB/cm are achieved. The viability of this platform is demonstrated through a series of high-performance novel PIC components. This hybrid waveguide platform enabled by a powerful and simple design concept holds great promise for high-density and low-loss PICs.

Visual inspection is a powerful tool that doctors have for medical assessment. Given the limit imposed by scattering and absorption of light into tissue, visual inspection can only provide information over the most superficial layers of the human body. The advent of medical imaging revolutionized the medical practice with imaging modalities such X-ray computed tomography (CT) and magnetic resonance imaging (MRI) and stimulated the development of new imaging technologies. Among the imaging technologies developed, optical imaging enables to reveal details with 10-100 times higher resolution than CT and MRI. However, optical imaging techniques suffers from limited penetration depth within biological tissues. To circumvent this shortcoming, endoscopes have been developed to enable imaging of internal organs. The focus of this thesis is optical coherence tomography (OCT), an interferometric optical imaging technique that allows to create cross-sectional images of tissue. After a brief introduction (Chapter 1), the fundamental principles of OCT and its extensions adopted in this thesis are discussed (Chapter 2). In this thesis, polarization-sensitive OCT (PS-OCT), an extension of conventional OCT, which makes use of polarization properties of light was adopted to highlight birefringent tissues. Form birefringence is exhibited by several tissue types with fiber-like structures (e.g. smooth muscle, collagen, fibrosis), therefore PS-OCT is particularly valuable to highlight the presence of specific tissue types which are birefringent. A PS-OCT system was developed and used for in-vivo imaging of the human lungs. Moreover, an endoscope suitable for lung airway imaging was developed and adopted to perform endobronchial PS-OCT imaging of human lungs. In chapter 3, endobronchial PS-OCT was used to visualize and quantify airway smooth muscle in severe asthma patients undergoing bronchial thermoplasty (BT) treatment. In chapter 4, the use of endobronchial PS-OCT was extended to interstitial lung disease (ILD) patients, in which the amount of pulmonary fibrosis was assessed. Results of the studies presented in chapter 3 and 4 suggest that PS-OCT holds the potential as imaging modality to study airway remodeling in asthma patients and to evaluate pulmonary fibrosis in ILD patients respectively. Although (PS-)OCT has potential for structural imaging it is not able to provide molecular imaging contrast and distinguish the presence of specific cell types within the tissue. Molecular imaging contrast can be achieved with fluorescence molecular imaging, which relies on the use of targeted fluorescent tracers: fluorophores conjugated to a tumor-specific target. Among targeted fluorescent tracers, monoclonal antibodies fluorescently labelled with near infrared (NIR) fluorophores can target specific tumor targets by targeting tumor cell receptors or signaling proteins (immuno- near infrared fluorescence, immuno-NIRF). A dual-modality system in which OCT was combined with immuno-NIRF imaging (immuno-OCT) was developed, as described in chapter 5. The dual modality system developed for immuno-OCT imaging was demonstrated to image ex-vivo esophageal specimens resected from patients with different stages of esophageal cancer. In the study presented in chapter 5, the immuno-OCT system proved to have the sensitivity needed to detect early stage of esophageal cancer with administration of an imaging dose of NIR fluorescently labeled monoclonal antibodies. Moreover, OCT provided morphological information over the esophageal tissue complementing immuno-NIRF, which provided tissue molecular information allowing to reveal the heterogeneity of the tumor microenvironment. Results of this ex-vivo study suggest that immuno-OCT could have potential to enhance early diagnosis of esophageal cancer. However, results should be further validated in-vivo. To this purpose, chapter 6 was dedicated to the design of a dual-modality capsule endoscope that in future will be demonstrated to perform in-vivo immuno-OCT imaging in patients diagnosed with esophageal cancer. Finally, chapter 7, discusses future research directions and a potential translation of the PS-OCT system into the medical-devices market.

Mechanical changes in tumors have long been linked to increased malignancy and therapy resistance and attributed to mechanical changes in the tumor extracellular matrix (ECM). However, to the best of our knowledge, there have been no mechanical studies on decellularized tumors. Here, we studied the biochemical and mechanical progression of the tumor ECM in two models of lung metastases: lung carcinoma (CAR) and melanoma (MEL). We decellularized the metastatic lung sections, measured the micromechanics of the tumor ECM, and stained the sections for ECM proteins, proliferation, and cell death markers. The same methodology was applied to MEL mice treated with the clinically approved anti-fibrotic drug nintedanib. When compared to healthy ECM (~0.40 kPa), CAR and MEL lung macrometastases produced a highly dense and stiff ECM (1.79 ± 1.32 kPa, CAR and 6.39 ± 3.37 kPa, MEL). Fibronectin was overexpressed from the early stages (~118%) to developed macrometastases (~260%) in both models. Surprisingly, nintedanib caused a 4-fold increase in ECM-occupied tumor area (5.1 ± 1.6% to 18.6 ± 8.9%) and a 2-fold in-crease in ECM stiffness (6.39 ± 3.37 kPa to 12.35 ± 5.74 kPa). This increase in stiffness strongly correlated with an increase in necrosis, which reveals a potential link between tumor hypoxia and ECM deposition and stiffness. Our findings highlight fibronectin and tumor ECM mechanics as attractive targets in cancer therapy and support the need to identify new anti-fibrotic drugs to abrogate aberrant ECM mechanics in metastases.

A spectroscopic study of atomic oxygen (O i) is performed using the Fourier-transform vacuum ultraviolet (VUV) spectrometer at the Dichroïsme Et Spectroscopie par Interaction avec le Rayonnement Synchrotron beamline of the SOLEIL synchrotron. Transition frequencies of O i lines in the range between 76,000 and 151,000 cm−1, corresponding to wavelengths between 665 and 1306 Å, are presented. In the wavelength window a data set of 208 lines is obtained for which line centers were determined at an accuracy of ≤0.035 cm−1, verified through a comparison with previous VUV-laser spectroscopy at an accuracy of 0.008 cm−1. Transitions to upper states belonging to several ns and nd Rydberg series that converge to the 4S3/2, 2D, and 2P ionization limits are presented. Besides studies on the main 16O isotope, measurements of the 18O isotope are also performed, for which an enriched sample of 18O2 gas is used. A least-squares optimization analysis is performed after merging the present new data set with some relevant accurate literature data to extract a list of level energies at high accuracy. When comparing with the database of the National Institute of Standards and Technology, good agreement is found for levels with low principal quantum numbers n ≤ 7 or below excitation energies of 108,000 cm−1; however, significant deviations were found for levels with n > 7. The main result of the present study is the realization of an improved data set of transition frequencies and level energies for O i, with its usefulness demonstrated in a comparison with high-resolution astronomical spectra showing absorption in the line of sight to distant quasars.

Mars is one of the prime candidates in the search for extraterrestrial life. At the most comparable terrestrial Martian analogue sites, life often occurs in endolithic form; i.e. hiding below the surface. To detect biomarkers of endolithic life, the two most promising options are drilling or measuring through the surface, the latter being less invasive and preferable. Raman spectroscopy is an established chemical identification method, and advanced Raman modes have been developed for sub-surface analysis. Time-resolved Raman spectroscopy (TRRS), based on picosecond pulsed excitation and a gated intensified charge-coupled device (ICCD) detector, adds the capability of fluorescence suppression and depth selection. This paper focuses on the separation of layers with time differences that are much smaller than the 200 ps full width at half-maximum gating time of the detector. As an analogue for endolithic life on Mars, Deinococcus radiodurans bacteria were measured through a 2.5 mm and 7.5 mm top layer of translucent calcite. TRRS spectra were recorded in a backscattering geometry, while stepwise increasing the detector delay in 25 ps steps. Through both of these layers, the Raman spectrum of the bacteria’s carotenoids could be detected. Global analysis was used to model a complete time-resolved spectrum of the sample. Using this analysis, the signals could be separated into three components: mineral Raman, bacterial Raman and bacterial fluorescence. The model also corrects for gating differences across the horizontal axis of the ICCD camera. With this approach well-separated Raman spectra were obtained even for the 2.5 mm calcite layer despite the temporal separation of approximately 20 ps , which is much shorter than the 200 ps detector gating time. TRRS could be a suitable approach for non-invasive detection of extraterrestrial subsurface biomarkers.

Upscaling motor protein activity to perform work in man-made devices has long been an ambitious goal in bionanotechnology. The use of hierarchical motor assemblies, as realized in sarcomeres, has so far been complicated by the challenges of arranging sufficiently high numbers of motor proteins with nanoscopic precision. Here, we describe an alternative approach based on actomyosin cortex-like force production, allowing low complexity motor arrangements in a contractile meshwork that can be coated onto soft objects and locally activated by ATP. The design is reminiscent of a motorized exoskeleton actuating protein-based robotic structures from the outside. It readily supports the connection and assembly of micro-three-dimensional printed modules into larger structures, thereby scaling up mechanical work. We provide an analytical model of force production in these systems and demonstrate the design flexibility by three-dimensional printed units performing complex mechanical tasks, such as microhands and microarms that can grasp and wave following light activation.

In many areas, studying photostability or the mechanism of photodegradation is of high importance. Conventional methods to do so can be rather time-consuming, laborious, and prone to experimental errors. In this paper we evaluate an integrated and fully automated system for the study of light-induced degradation, comprising a liquid handler, an irradiation source and exposure cell with dedicated optics and spectrograph, and a liquid chromatography (LC) system. A liquid core waveguide (LCW) was used as an exposure cell, allowing efficient illumination of the sample over a 12 cm path length. This cell was coupled to a spectrograph, allowing in situ absorbance monitoring of the exposed sample during irradiation. The LCW is gas-permeable, permitting diffusion of air into the cell during light exposure. This unit was coupled online to LC with diode array detection for immediate and automated analysis of the composition of the light-exposed samples. The analytical performance of the new system was established by assessing linearity, limit of detection, and repeatability of the in-cell detection, sample recovery and carryover, and overall repeatability of light-induced degradation monitoring, using riboflavin as the test compound. The applicability of the system was demonstrated by recording a photodegradation time profile of riboflavin.

A multimode fiber (MMF) is a minimally invasive imaging probe. The most popular approach of MMF-based microscopy is raster-scan imaging, where the sample is illuminated by foci optimized on the fiber output facet by wavefront shaping (WFS). Imaging quality can be quantified by characteristic parameters of the optimized spots. We investigate the influence of the input light position on WFS through a round-core MMF with partial mode control, a situation often encountered in real life. We further demonstrate a trade-off between the shape and contrast of the foci generated on the output facet: the center input position is beneficial for high-contrast imaging, while the edge input position helps to reduce focus aberrations. These results are important for high field-of-view raster-scan imaging via an MMF.

The light source that has revolutionized attosecond science over the last decades is based on the process of high-harmonic generation (HHG), which is a unique method to generate a broadband coherent spectrum extending into the extreme-ultraviolet (XUV) range. The temporal and spatial resolution of HHG enables investigation of strong-field light-matter interaction in the ultrafast and ultrasmall dimensions, and finds applications in attosecond science, lensless imaging, and industrial metrology. Unfortunately, the intrinsic low conversion efficiency of HHG and the limited methods to control the generated XUV wavefront, slow down present research and future development of applications that are based on HHG. Control over the HHG process is essential to improve the conversion efficiency and XUV wavefront characteristics, in order to facilitate next-generation attosecond science and metrology. This thesis presents experimental techniques and results that demonstrate control over both gas-based and solid-based HHG in the extreme-ultraviolet regime. Additionally, the underlying mechanism and working principles are explained through theoretical models and simulations. In Chapter 4, we demonstrate divergence and yield optimization in polarization controlled two-color gas-based HHG. Imaging, spectroscopy, and metrology applications using HHG sources require high XUV brightness, related to the conversion efficiency and the focusability of the generated XUV pulses. We systematically investigate, both experimentally and theoretically, the effect of the relative polarization between the fundamental and its second harmonic in two-color HHG, and compare the results to a one-color configuration. In a perpendicular two-color field, the relative phase between the two colors can be used to manipulate the long or the short trajectories, allowing control over the divergence of the harmonics. In a parallel two-color field, the relative phase can be used to modify the ionization rate to select trajectories and additionally allows to enhance the total yield. Next, we describe extreme-ultraviolet shaping and imaging by HHG from nanostructured silica in Chapter 5. Tailoring of any XUV wavefront after generation is challenged by the lack of efficient optical elements and limits HHG applications. We demonstrate how HHG from a structured generation medium enables control over the phase, amplitude, and polarization properties of extreme-ultraviolet pulses. Moreover, we use the emitted patterns to reconstruct height profiles, probe the near-field confinement in nanostructures below the diffraction limit of the fundamental, and image complex structures using the coherent diffractive emission from the structures. In another experiment, we establish efficient extreme-ultraviolet high-order wavemixing from laser-dressed silica, described in Chapter 6. Solid-based HHG allows to produce a coherent, broadband, extreme-ultraviolet light source with tailored emission profiles, but is put at disadvantage due to the low conversion efficiency from infrared to XUV photons. Here, we overcome the low conversion efficiency by driving the HHG simultaneously with the fundamental and its second harmonic, in a non-collinear geometry. The observed high-order wave mixing emission follows perturbative intensity scalings and enhances the XUV efficiency by at least one order of magnitude. The underlying generation mechanism is described by a quantum theory, that reveals that solid HHG is boosted through laser-dressed states. Finally, we demonstrate transient grating high-harmonic spectroscopy in MgO in Chapter 7, and investigate how an excited carrier population influences solid-state HHG. Two crossed 266-nm pulses induce a transient grating of excited carrier population due to two-photon absorption in the MgO. The modification of the relative amplitude and phase of the harmonics at the generation plane results in diffraction in the far field. Preliminary analysis demonstrates that both the macroscopic propagation effects onto the fundamental and the microscopic generation mechanism of the HHG process contribute to the amplitude and phase modulation.

An ultra-thin multimode fiber is an ideal platform for minimally invasive microscopy with the advantages of a high density of modes, high spatial resolution, and a compact size. In practical applications, the probe needs to be long and flexible, which unfortunately destroys the imaging capabilities of a multimode fiber. In this work, we propose and experimentally demonstrate sub-diffraction imaging through a flexible probe based on a unique multicore-multimode fiber. A multicore part consists of 120 Fermat’s spiral distributed single-mode cores. Each of the cores offers stable light delivery to the multimode part, which provides optimal structured light illumination for sub-diffraction imaging. As a result, perturbation-resilient fast sub-diffraction fiber imaging by computational compressive sensing is demonstrated.

Deliquescence is a first-order phase transition, happening when a salt absorbs water vapor. This has a major impact on the stability of crystalline powders that are important for example in pharmacology, food science and for our environment and climate. Here we show that during deliquescence, the abundant salt sodium sulfate decahydrate, mirabilite (Na2SO4·10H2O), behaves differently than anhydrous salts. Using various microscopy techniques combined with Raman spectroscopy, we show that mirabilite crystals not only lose their facets but also become soft and deformable. As a result, microcrystals of mirabilite simultaneously behave crystalline-like in the core bulk and liquid-like at the surface. Defects at the surface can heal at a speed much faster than the deliquescence rate by the mechanism of visco-capillary flow over the surface. While magnesium sulfate hexahydrate (MgSO4⋅6H2O) behaves similarly during deliquescence, a soft and deformable state is completely absent for the anhydrous salts sodium chloride (NaCl) and sodium sulfate thenardite (Na2SO4). The results highlight the effect of crystalline water, and its mobility in the crystalline structure on the observed softness during deliquescence. Controlled hydrated salts have potential applications such as thermal energy storage, where the key parameter is relative humidity rather than temperature., Nature Communications, 14 (1), ISSN:2041-1723

Tissue mechanics determines tissue homeostasis, disease development and progression. Bladder strongly relies on its mechanical properties to perform its physiological function, but these are poorly unveiled under normal and pathological conditions. Here we characterize the mechanical fingerprints at the micro-scale level of the three tissue layers which compose the healthy bladder wall, and identify modifications associated with the onset and progression of pathological conditions (i.e., actinic cystitis and bladder cancer). We use two indentation-based instruments (an Atomic Force Microscope and a nanoindenter) and compare the micromechanical maps with a comprehensive histological analysis. We find that the healthy bladder wall is a mechanically inhomogeneous tissue, with a gradient of increasing stiffness from the urothelium to the lamina propria, which gradually decreases when reaching the muscle outer layer. Stiffening in fibrotic tissues correlate with increased deposition of dense extracellular matrix in the lamina propria. An increase in tissue compliance is observed before the onset and invasion of the tumor. By providing high resolution micromechanical investigation of each tissue layer of the bladder, we depict the intrinsic mechanical heterogeneity of the layers of a healthy bladder as compared with the mechanical properties alterations associated with either actinic cystitis or bladder tumor.

Here we demonstrate a new, to the best of our knowledge, type of 3-dB coupler that has an ultra-broadband operational range from 1300 to 1600 nm with low fabrication sensitivity. The overall device size is 800 µm including in/out S-bend waveguides. The coupler is an asymmetric non-uniform directional coupler that consists of two tapered waveguides. One of the coupler arms is shifted by 100 µm in the propagation direction, which results in a more wavelength-insensitive 3-dB response compared to a standard (not shifted) coupler. Moreover, compared to a long adiabatic coupler, we achieved a similar wavelength response at a 16-times-smaller device length. The couplers were fabricated using the silicon nitride platform of Lionix International. We also experimentally demonstrated an optical switch that is made by using two of these couplers in a Mach–Zehnder interferometer configuration. According to experimental results, this optical switch exhibits –10 dB of extinction ratio over the 1500–1600 nm wavelength range. Our results indicate that this new type of coupler holds great promise for various applications, including optical imaging, telecommunications, and reconfigurable photonic processors where compact, fabrication-tolerant, and wavelength-insensitive couplers are essential.

We demonstrate a highly sensitive acoustic vibration sensor based on a tapered-tip optical fiber acting as a microcantilever. The tapered-tip fiber has a unique output profile that exhibits a circular fringe pattern, whose distribution is highly sensitive to the vibration of the fiber tip. A piezo transducer is used for the acoustic excitation of the fiber microcantilever, which results in a periodic bending of the tip and thereby a significant output power modulation. Using a multimode readout fiber connected to an electric spectrum analyzer, we measured the amplitude of these power modulations over the 10–50 kHz range and observed resonances over certain frequency ranges. Two types of tapered-tip fibers were fabricated with diameter values of 1.5 µm and 1.8 µm and their frequency responses were compared with a non-tapered fiber tip. Thanks to the resonance effect as well as the sensitive fringe pattern of the tapered-tip fibers, the limit of detection and the sensitivity of the fiber sensor were obtained as 0.1 nm and 15.7 V/nm, respectively, which were significantly better than the values obtained with the non-tapered fiber tip (i.e., 1.1 nm and 0.12 V/nm, respectively). The sensor is highly sensitive, easy to fabricate, low-cost, and can detect sub-nanometer displacements, which makes it a promising tool for vibration sensing, particularly in the photoacoustic sensing of greenhouse gases.

Measuring overlay between two layers of semiconductor devices is a crucial step during electronic chip fabrication. We present dark-field digital holographic microscopy that addresses various overlay metrology challenges that are encountered in the semiconductor industry. We present measurement results that show that the point-spread function of our microscope depends on the position in the field-of-view. We will show that this novel observation can be explained by a combination of the finite bandwidth of the light source and a wavelength-dependent focal length of the imaging lens. Moreover, we will also present additional experimental data that supports our theoretical understanding. Finally, we will propose solutions that reduce this effect to acceptable levels.

Full-field swept-source optical coherence tomography (FF-SS-OCT) and laser Doppler holography (LDH) are two holographic imaging techniques presenting unique capabilities for ophthalmology. We report on interlaced FF-SS-OCT and LDH imaging with a single instrument. Effectively, retinal blood flow and pulsation could be quasi-simultaneously monitored. This instrument holds potential for a wide scope of ophthalmic applications.

The parallel-plate compression test is one of the simplest ways to measure the mechanical properties of a material. In this test, the Young’s modulus ( E ) and the Poisson’s ratio ( ν ) of the material are determined directly without applying any additional modelling and parameter fitting in the post-processing. This is, however, limited when dealing soft biological materials due to their inherent properties such as being inhomogeneous, microscopic, and overly compliant. By combining an interferometry-assisted parallel-plate compression system and a confocal microscope, we were able to overcome these limitations and measure the E (315 ± 52 Pa) and ν (0.210 ± 0.043) of fixated and permeabilized bovine oocytes.

Purpose To evaluate the relationship between the occurrence of optic disc hemorrhages (DH) and glaucoma progression as determined by multiple glaucoma testing modalities. Design A prospective cohort study. Methods A longitudinal study of 124 open angle glaucoma patients who had yearly disc photography (DP), visual fields (VFs), spectral-domain optical coherence tomography (SD-OCT) retinal nerve fiber layer (RNFL) thickness scans, and optic nerve volume scans (Spectralis, Heidelberg Engineering, Heidelberg, Germany), all performed on the same day over a 5-year period. The minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter, was calculated from optic nerve volume scans. Patients were classified as glaucoma progressors or non-glaucoma progressors using event-based analysis. Results Out of 124 open angle glaucoma patients, 19 (15.3%) had one or more DHs on yearly DPs. Presence of a DH was associated with localized 3D neuroretinal rim thickness progression (superior MDB progression; OR 3.96, P = 0.04), but not with global or inferior MDB progression (P = 0.14 and 0.81 respectively), DP progression (P = 0.08), VF progression (P = 0.45), or RNFL global, inferior or superior progression (P = 0.17, 0.26 and 0.76 respectively). In the majority of patients with MDB progression (14/17, or 82%), the progression was noted before or concurrently with the first instance of DH. Conclusions Glaucoma progression detected by high-density 3D SD-OCT neuroretinal rim measurements preceded DH occurrence in the majority of patients. These findings support the hypothesis that DHs are indicators of ongoing glaucoma progression rather than discrete events that cause subsequent progression.

Light-induced degradation (LID) strongly depends on experimental conditions, among which the presence of oxygen is a major parameter. Elucidating LID processes is of high concern to many areas of interest, e.g., for the conservation of cultural heritage, safety and shelf life of food, and UV-disinfection methods for water purification. Recently, we presented a new, fully automated tool to study molecular photodegradation in solution. The tool employs a gas-permeable liquid-core waveguide (LCW) as a light-exposure cell with in-situ absorption spectroscopy for real-time monitoring, coupled on-line to liquid chromatography (LC) with diode-array (DAD) and mass spectrometry (MS) for characterization of the photodegradation products. The current work reports on the assessment of the potential of the LCW in a tube-in-tube geometry for studying the role of oxygen in photodegradation processes, using Riboflavin and Eosin Y as model compounds. The LID results obtained for Riboflavin and Eosin Y using the LCW set-up were in line with reported data obtained with conventional approaches. On-line LC-MS analysis allowed semi-quantitative monitoring of LID differences under oxic and anoxic circumstances. An increase in degradation by 9% and 30% for Riboflavin and Eosin Y, respectively, was observed after 10 min under anoxic conditions. Moreover, for the first time, the fully debrominated species of Eosin Y (i.e. fluorescein), was identified as a photodegradation product in solution. The presented set-up can be highly useful for the investigation of photodegradation mechanisms and kinetics in solution, including the role of oxygen while increasing analytical efficiency and reducing time spent in the lab.

We propose a new type of self-referencing and multiplexed refractive index (RI) sensor based on a compound optical microresonator structure consisting of Fabry-Pérot (FP) resonators coupled with microring resonators. The transmission spectra shows resonant features that are superimposed on a background defined by FP oscillations. The resonances have asymmetric Fano-like non-Lorentzian shapes, which are used as sensing peaks, while the FP oscillations are used as reference peaks for internal self-referencing. The sensing peaks shift linearly with the increased RI of the cladding in the microring resonator, while FP peaks stay constant. When the temperature is increased, both the FP peaks and the Fano resonances shift linearly at the same rate, which eliminates the temperature effect on RI measurements. We theoretically analyzed that the two-mirror FP resonator coupled with a single microring resonator and optimized its sensing performance through finite-difference time-domain simulations. A sensitivity value of 220 nm/RIU and a maximum figure of merit of 4400 RIU-1 were achieved. We also proposed two possible multiplexing schemes consisting of two-mirror and three-mirror FP resonators coupled with two microring resonators of different radii. The proposed sensor concept is simple, easy-to-fabricate, self-calibrating and can be used for simultaneous measurements of different samples.

Background The biomechanical properties of the brain have increasingly been shown to relate to brain pathology in neurological diseases, including multiple sclerosis (MS). Inflammation and demyelination in MS induce significant changes in brain stiffness which can be linked to the relative abundance of glial cells in lesions. We hypothesize that the biomechanical, in addition to biochemical, properties of white (WM) and gray matter (GM)-derived microglia may contribute to the differential microglial phenotypes as seen in MS WM and GM lesions. Methods Primary glial cultures from WM or GM of rat adult brains were treated with either lipopolysaccharide (LPS), myelin, or myelin+LPS for 24 h or left untreated as a control. After treatment, microglial cells were indented using dynamic indentation to determine the storage and loss moduli reflecting cell elasticity and cell viscosity, respectively, and subsequently fixed for immunocytochemical analysis. In parallel, gene expression of inflammatory-related genes were measured using semi-quantitative RT-PCR. Finally, phagocytosis of myelin was determined as well as F-actin visualized to study the cytoskeletal changes. Results WM-derived microglia were significantly more elastic and more viscous than microglia derived from GM. This heterogeneity in microglia biomechanical properties was also apparent when treated with LPS when WM-derived microglia decreased cell elasticity and viscosity, and GM-derived microglia increased elasticity and viscosity. The increase in elasticity and viscosity observed in GM-derived microglia was accompanied by an increase in Tnfα mRNA and reorganization of F-actin which was absent in WM-derived microglia. In contrast, when treated with myelin, both WM- and GM-derived microglia phagocytose myelin decrease their elasticity and viscosity. Conclusions In demyelinating conditions, when myelin debris is phagocytized, as in MS lesions, it is likely that the observed differences in WM- versus GM-derived microglia biomechanics are mainly due to a difference in response to inflammation, rather than to the event of demyelination itself. Thus, the differential biomechanical properties of WM and GM microglia may add to their differential biochemical properties which depend on inflammation present in WM and GM lesions of MS patients.

Micropipette aspiration (MPA) is an essential tool in mechanobiology; however, its potential is far from fully exploited. The traditional MPA technique has limited temporal and spatial resolution and requires extensive post processing to obtain the mechanical fingerprints of samples. Here, we develop a MPA system that measures pressure and displacement in real time with sub-nanometer resolution thanks to an interferometric readout. This highly sensitive MPA system enables studying the nanoscale behavior of soft biomaterials under tension and their frequency-dependent viscoelastic response., Beradi et al. establish a micropipette aspiration platform which enables sensitive real-time viscoelastic measurements of soft biomaterials. They use it to characterize the rheological behavior of cells and soft materials at very small deformations, yielding consistent and reproducible values.

Two simulation programs of a stimulated Raman scattering microscopy (SRS) imaging system with lock-in amplifier (LIA) detection were developed. SRS is an imaging technique based on the vibrational Raman cross-section as the contrast mechanism and enables fast, label-free imaging. Most SRS implementations are based on LIA detection of a modulated signal. However, building and operating such SRS set-ups still poses a challenge when selecting the LIA parameter settings for optimized acquisition speed or image quality. Moreover, the type of sample, e.g. a sparse sample vs. a densely packed sample, the required resolution as well as the Raman cross-section and the laser powers affect the parameter choice.A simulation program was used to find these optimal parameters. The focal spot diameters of the individual lasers (pump and Stokes) were used to estimate the effective SRS signal focal spot and the (optical) spatial resolution. By calibrating the signal and noise propagation through an SRS system for a known molecule, we estimated the signal and noise input to the LIA. We used a low pass filter model to simulate the LIA behavior in order to find the optimal parameters (i.e. filter order and time constant).Optimization was done for either image quality (expressed as contrast to noise ratio) or acquisition time. The targeted object size was first determined as a measure for the required resolution. The simulation output consisted of the LIA parameters, pixel dwell time and contrast to noise ratio.In a second simulation we evaluated SRS imaging based on the same principles as the optimal setting simulation, i.e. the signals were propagated through an imaging system and LIA detection. The simulated images were compared to experimental SRS images of polystyrene beads.Finally, the same software was used to simulate multiplexed SRS imaging. In this study we modeled a six-channel frequency-encoded multiplexed SRS system demodulated with six LIA channels. We evaluated the inter-channel crosstalk as a function of chosen LIA parameters, which in multiplex SRS imaging also needs to be considered.These programs to optimize the contrast to noise ratio, acquisition speed, resolution and crosstalk will be useful for operating stimulated Raman scattering imaging setup, as well as for designing novel setups.

In this investigation on the mechanical behaviour of paint films, we use a new ferrule-top nanoindentation protocol developed for cultural heritage studies to examine the impact of repeated relative humidity variations on the viscoelastic behaviour of paint films and their mechanical properties in different paint stratigraphies through the changes in their storage and loss moduli. We show that the moisture weathering impact on the micromechanics varies for each of these pigment-oil systems. Data from the nanoindentation protocol provide new insights into the evolution of the viscoelastic properties dsue to the impact of moisture weathering on paint films.

Leukocyte extravasation into inflamed tissue is a complex process that is difficult to capture as a whole in vitro. We employed a blood-vessel-on-a-chip model in which endothelial cells were cultured in a tube-like lumen in a collagen-1 matrix. The vessels are leak-tight, creating a barrier for molecules and leukocytes. Addition of inflammatory cytokine TNF-α caused vasoconstriction, actin remodelling and upregulation of ICAM-1. Introducing leukocytes into the vessels allowed real-time visualisation of all different steps of the leukocyte transmigration cascade including migration into the extracellular matrix. Individual cell tracking over time distinguished striking differences in migratory behaviour between T-cells and neutrophils. Neutrophils cross the endothelial layer more efficiently than T-cells, but upon entering the matrix, neutrophils display high speed but low persistence, whereas T-cells migrate with low speed and rather linear migration. In conclusion, 3D imaging in real-time of leukocyte extravasation in a vessel-on-a-chip enables detailed qualitative and quantitative analysis of different stages of the full leukocyte extravasation process in a single assay.SummaryA functional hydrogel-based blood-vessel-on-a-chip model is used to study the complete leukocyte transendothelial migration process in real time. T-lymphocytes and neutrophils exhibit distinct migration dynamics in the extravascular matrix after transendothelial migration, which can be altered using a chemotactic gradient.

A non-invasive diagnostic tool to assess remodeling of the lung airways caused by disease is currently missing in the clinic. Measuring key features such as airway smooth muscle (ASM) thickness would increase the ability to improve diagnosis and enable treatment evaluation. In this research, polarization-sensitive optical coherence tomography (PS-OCT) has been used to image a total of 24 airways from two healthy lungs and four end-stage diseased lungs ex vivo, including fibrotic sarcoidosis, chronic obstructive pulmonary disease (COPD), fibrotic hypersensitivity pneumonitis, and cystic fibrosis. In the diseased lungs, except COPD, the amount of measured airway smooth muscle was increased. In COPD, airway smooth muscle could not be distinguished from surrounding collagen. COPD lungs showed increased alveolar size. 3D pullbacks in the same lumen provided reproducible assessment of airway smooth muscle (ASM). Image features such as thickened ASM and size/presence of alveoli were recognized in histology. The results of this study are preliminary and must be confirmed with further ex vivo and in vivo studies. PS-OCT is applicable for in vivo assessment of peribronchial and peribronchiolar lung structures and may become a valuable tool for diagnosis in pulmonology.

Purpose: To compare onset times of glaucoma progression among different glaucoma tests: disc photography (DP), visual field (VF) testing, 2-dimensional (2D) retinal nerve fiber layer (RNFL) thickness, and 3-dimensional (3D) spectral-domain (SD) OCT neuroretinal rim measurements. Design: Prospective, longitudinal cohort study. Participants: One hundred twenty-four eyes of 124 patients with open-angle glaucoma. Methods: Over a 5-year period, 124 patients with open-angle glaucoma underwent yearly DP, VF testing, SD OCT RNFL thickness scans, and optic nerve volume scans (Spectralis; Heidelberg Engineering), all performed on the same day. From high-density optic nerve volume scans, custom-built software calculated the minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter. Patients were classified as glaucoma progressors or nonglaucoma progressors using event-based analysis. Progression by DP and VF testing occurred when 3 masked glaucoma specialists unanimously concurred. Progression by RNFL and MDB thickness occurred if change of more than test–retest variability was observed. Kaplan-Meier curves were constructed to analyze time-to-progression data. Kappa Coefficients were used to measure agreement of progressing eyes among methods. Main Outcome Measures: Time to glaucoma progression among all 4 methods. Results: Global MDB thickness detected glaucoma progression in the highest percentage of eyes (52.4%) compared with DP (16.1%; P < 0.001) and global RNFL thickness (15.3%; P < 0.001). Global MDB thickness detected glaucoma progression earlier than either DP (23 months vs. 44 months; P < 0.001) or global RNFL thickness (23 months vs. 33 months; P < 0.001). Among MDB progressing eyes, 46.2% were confirmed simultaneously or later by other conventional methods. Agreement of glaucoma-progressing eyes for all 4 methods in paired fashion were slight to fair (κ = 0.095–0.300). Conclusions: High-density 3D SD OCT neuroretinal rim measurements detected glaucoma progression approximately 1 to 2 years earlier compared with current clinically available structural tests (i.e., DP and 2D RNFL thickness measurements).

© 2022 the Alzheimer's Association.Background: The retina provides an opportunity for development of a screening tool to detect early stages of AD. Studies showing the presence of Aβ and p-tau in AD retina are contradictory, and their characterization in a large, neuropathologically confirmed cohort with different neurodegenerative diseases is scarce. In this study we assessed the presence of different tau isoforms and Aβ (4G8) in the retinas of AD cases, control cases, as well as other neurodegenerative diseases, and correlated these directly to cortical cerebral tau and amyloid pathology loads. Method: Post mortem eyes (N = 62) with both clinical history and post-mortem neuropathological reports available were collected through the Netherlands Brain Bank. Donors included AD, PSP, CBD, FTLD, PD(D), DLB, MSA, ALS, MS and controls, with and without cerebral cortical p-tau. Superior-temporal quadrants were cut in 10 µm sections. Sections were immunostained using antibodies directed against p-tau (AT270, AT100, AT8, pS422) and Aβ (4G8). Linear mixed models were used to analyze between-group differences and the relation between brain and retina. Result: Tau appeared as a diffuse neuritic staining, and in some cases as somatodendritic-like staining and was mainly present in the plexiform layers of the retina. AT8, AT100 and AT270 immunoreactivity showed a predilection in the far periphery. AT8 was generally found in tauopathy cases as opposed to non-tauopathy cases. A strong correlation was found between retinal AT8 and brain cortical tau pathology. 4G8 appeared sporadically as extracellular structures, mainly present in the retinal nerve fiber layer, ganglion cell layer and near blood vessels. 4G8 did not differ between control and disease cases, and no group differences or relation with cortical amyloid load was found. Conclusion: P-tau measured with AT8 in the retina correlates with the presence of tau pathology in cortical brain areas. In contrast, Aβ (4G8) immunoreactivity is sporadically present in the retina, is not specific for AD and does not correlate with cortical amyloid load in a large cross-disease cohort. Our study shows that p-tau detected in the retina by AT8 is a potential biomarker candidate for tauopathies.

© 2022 The AuthorsQuantitative MRI (qMRI) acquired at the ultra-high field of 7 Tesla has been used in visualizing and analyzing subcortical structures. qMRI relies on the acquisition of multiple images with different scan settings, leading to extended scanning times. Data redundancy and prior information from the relaxometry model can be exploited by deep learning to accelerate the imaging process. We propose the quantitative Recurrent Inference Machine (qRIM), with a unified forward model for joint reconstruction and R2*-mapping from sparse data, embedded in a Recurrent Inference Machine (RIM), an iterative inverse problem-solving network. To study the dependency of the proposed extension of the unified forward model to network architecture, we implemented and compared a quantitative End-to-End Variational Network (qE2EVN). Experiments were performed with high-resolution multi-echo gradient echo data of the brain at 7T of a cohort study covering the entire adult life span. The error in reconstructed R2* from undersampled data relative to reference data significantly decreased for the unified model compared to sequential image reconstruction and parameter fitting using the RIM. With increasing acceleration factor, an increasing reduction in the reconstruction error was observed, pointing to a larger benefit for sparser data. Qualitatively, this was following an observed reduction of image blurriness in R2*-maps. In contrast, when using the U-Net as network architecture, a negative bias in R2* in selected regions of interest was observed. Compressed Sensing rendered accurate, but less precise estimates of R2*. The qE2EVN showed slightly inferior reconstruction quality compared to the qRIM but better quality than the U-Net and Compressed Sensing. Subcortical maturation over age measured by a linearly increasing interquartile range of R2* in the striatum was preserved up to an acceleration factor of 9. With the integrated prior of the unified forward model, the proposed qRIM can exploit the redundancy among repeated measurements and shared information between tasks, facilitating relaxometry in accelerated MRI.

Management of gliomas requires an invasive treatment strategy, including extensive surgical resection. The objective of the neurosurgeon is to maximize tumor removal while preserving healthy brain tissue. However, the lack of a clear tumor boundary hampers the neurosurgeon’s ability to accurately detect and resect infiltrating tumor tissue. Nonlinear multiphoton microscopy, in particular higher harmonic generation, enables label-free imaging of excised brain tissue, revealing histological hallmarks within seconds. Here, we demonstrate a real-time deep learning-based pipeline for automated glioma image analysis, matching video-rate image acquisition. We used a custom noise detection scheme, and a fully-convolutional classification network, to achieve on average 79% binary accuracy, 0.77 AUC and 0.83 mean average precision compared to the consensus of three pathologists, on a preliminary dataset. We conclude that the combination of real-time imaging and image analysis shows great potential for intraoperative assessment of brain tissue during tumor surgery.

Cell migration in confining physiological environments relies on the concerted dynamics of several cellular components, including protrusions, adhesions with the environment, and the cell nucleus. However, it remains poorly understood how the dynamic interplay of these components and the cell polarity determine the emergent migration behavior at the cellular scale. Here, we combine data-driven inference with a mechanistic bottom-up approach to develop a model for protrusion and polarity dynamics in confined cell migration, revealing how the cellular dynamics adapt to confining geometries. Specifically, we use experimental data of joint protrusion-nucleus migration trajectories of cells on confining micropatterns to systematically determine a mechanistic model linking the stochastic dynamics of cell polarity, protrusions, and nucleus. This model indicates that the cellular dynamics adapt to confining constrictions through a switch in the polarity dynamics from a negative to a positive self-reinforcing feedback loop. Our model further reveals how this feedback loop leads to stereotypical cycles of protrusion-nucleus dynamics that drive the migration of the cell through constrictions. These cycles are disrupted upon perturbation of cytoskeletal components, indicating that the positive feedback is controlled by cellular migration mechanisms. Our data-driven theoretical approach therefore identifies polarity feedback adaptation as a key mechanism in confined cell migration.

Self-heating in organic electronics can lead to anomalous electrical performance and even accelerated degradation. However, in the case of disordered organic semiconductors, self-heating effects are difficult to quantify using electrical techniques alone due to complex transport properties. Therefore, more direct methods are needed to monitor the impact of self-heating on device performance. Here, self-heating in poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta [2,1-b;3,4-b′] dithiophene)-alt-4,7(2,1,3-benzothiadiazole)] (PCPDTBT) diodes is visualized using Raman spectroscopy, and thermal effects due to self-heating are quantified by exploiting temperature-dependent shifts in the polymer vibrational modes. The temperature increases due to self-heating are quantified by correlating the Raman shifts observed in electrically biased diodes with temperature-dependent Raman measurements. Temperature elevations up to 75 K are demonstrated in the PCPDTBT diodes at moderate power of about 2.6–3.3 W cm−2. Numerical modeling rationalizes the significant role of Joule and recombination heating on the diode current–voltage characteristics. This work demonstrates a facile approach for in situ monitoring of self-heating in organic semiconductors for a range of applications, from fundamental transport studies to thermal management in devices.

Visualization of the subcellular structures deep into the living brain is a major challenge in life science. Miniaturized microendoscopes allow for imaging of deep brain structures in vivo. Conventional approaches use gradient index (GRIN) microlenses, which unfortunately suffer from greater aberrations and restricted fields of view if they become smaller and less invasive. Multimode fiber based endoscopes offer minimal invasive access to deep tissue, and when combined with advanced wavefront engineering techniques, they provide high-resolution imaging. Here, we report auto-fluorescence human brain imaging through a single 50 μm-core multimode fiber probe with a numerical aperture of 0.22 via two approaches: raster-scan imaging by active wavefront shaping and speckle-based compressive imaging enabled by computational image recovery. The compressive imaging approach significantly decreases the acquisition time for an up to three times bigger area of interest while maintaining a high spatial resolution. Accumulation of age-related pigment lipofuscin in Alzheimer’s disease human brain has been visualized with sub-Nyquist–Shannon speed with an improvement of up to 18 times. The proposed technique offers fast, sensitive, and high-resolution endoscopic imaging through a single hair-thin fiber, which would be of broader interest in the fields of neuroimaging and (pre-)clinical research.

Many organic compounds undergo changes under the influence of light. This might be beneficial in, for example, water purification, but undesirable when cultural-heritage objects fade or when food ingredients (e.g., vitamins) degrade. It is often challenging to establish a strong link between photodegradation products and their parent molecules due to the complexity of the sample. To allow effective study of light-induced degradation (LID), a low-volume exposure cell was created in which solutes are efficiently illuminated (especially at low concentrations) while simultaneously analysed by absorbance spectroscopy. The new LID cell encompasses a gas-permeable liquid-core waveguide (LCW) connected to a spectrograph allowing collection of spectral data in real-time. The aim of the current study was to evaluate the overall performance of the LID cell by assessing its transmission characteristics, the absolute photon flux achieved in the LCW, and its capacity to study solute degradation in presence of oxygen. The potential of the LID set-up for light-exposure studies was successfully demonstrated by monitoring the degradation of the dyes eosin Y and crystal violet.

Purpose To assess the structure-function relationship in glaucoma using Humphrey visual field (HVF) perimetry and a three-dimensional neuroretinal rim parameter derived from spectral domain optical coherence tomography (SD-OCT) volume scans. Methods Structure-function correlation was analyzed globally and regionally (four quadrants and four sectors). Structural data included peripapillary retinal nerve fiber layer (RNFL) thickness and minimum distance band (MDB) neuroretinal rim thickness, defined as the shortest distance between the inner cup surface and the outer retinal pigment epithelium/Bruch's membrane complex. Logarithmic regression analyses were performed and Pearson correlation coefficients determined to assess relationship strength. Results The study consisted of 102 open-angle glaucoma patients and 58 healthy subjects. The Pearson correlation coefficient for global MDB thickness (R = 0.585) was higher than for global RNFL thickness (R = 0.492), but the difference was not statistically significant (P = 0.18). The correlation coefficients for regional MDB thicknesses and corresponding HVF sensitivities were higher than those for regional RNFL thicknesses and HVF in six out of eight regions (P = 0.08 to 0.47). In the remaining two out of eight regions, the correlation coefficients were higher for RNFL thickness than for MDB thickness (P = 0.15 to 0.20). Conclusions Three-dimensional MDB neuroretinal rim thickness relates to visual function as strongly as the most commonly used SD-OCT parameter for glaucoma, two-dimensional peripapillary RNFL thickness. Translational relevance This paper illustrates the potential for 3D OCT algorithms to improve in vivo imaging in glaucoma.

Flexible and fast control of the phase and amplitude of coherent light, enabled by digital micromirror devices (DMDs) and spatial light modulators, has been a driving force for recent advances in optical tweezers, nonlinear microscopy, and wavefront shaping. In contrast, engineering spatially partially coherent light remains widely elusive due to the lack of tools enabling a joint analysis and control sequence. Here, we report an approach to coherence engineering that combines a quasi-monochromatic, thermal source and a DMD together with a ptychographic scanning microscope. The reported method opens up new routes to low-cost coherence control, with applications in micromanipulation, nanophotonics, and quantitative phase contrast imaging.

Raman spectroscopy is a valuable tool for non-destructive vibrational analysis of chemical compounds in various samples. Through 2D scanning, it one can map the chemical surface distribution in a heterogeneous sample. These hyperspectral Raman images typically contain spectra of pure compounds that are hidden within thousands of sum spectra. Inspecting each spectrum to find the pure compounds in the dataset is impractical, and several algorithms have been described in the literature to help analyze such complex datasets. However, choosing the best approach(es) and optimizing the parameters is often difficult, and the necessary software was not yet combined in a single program. Therefore, we introduce RamanLIGHT, a fast and simple app to pre-process Raman mapping datasets and apply up to eight unsupervised unmixing algorithms to find endmember spectra of pure compounds. The user can select from six smoothing methods, four fluorescence baseline-removal methods, four normalization methods, and cosmic-ray and outlier removal to generate a uniform dataset prior to the unmixing. We included the most promising pre-processing methods, since there is no routine that perfectly fits all types of samples. Unmixed endmember spectra can be further used to visualize the distribution of compounds in a sample by creating abundance maps for each endmember separately, or a single labeled image containing all endmembers. It is also possible to create a mean spectrum for each endmember, which better describes the true compound spectrum. We tested RamanLIGHT on three samples: an aspirin-paracetamol-caffeine tablet, Alzheimer’s disease brain tissue and a phase-separated polymer coating. The datasets were pre-processed and unmixed within seconds to gain endmembers of known and unknown chemical compounds. The unmixing algorithms are sensitive to noisy spectra and strong fluorescence backgrounds, so it is important to apply pre-processing methods to a suitable degree. RamanLIGHT is freely available as an MATLAB and soon as standalone app.

Non-invasive spatially resolved functional imaging in the human retina has recently attracted considerable attention. Particularly functional imaging of bipolar and ganglion cells could aid in studying neuronal activity in humans, including an investigation of processes of the central nervous system. Recently, we imaged the activity of the inner neuronal layers by measuring nanometer-size changes of the cells within the inner plexiform layer (IPL) using phase-sensitive optical coherence tomography (OCT). In the IPL, there are connections between the neuronal cells that are dedicated to the processing of different aspects of the visual information, such as edges in the image or temporal changes. Still, so far, it was not possible to assign functional changes to single cells or cell classes in living humans, which is essential for studying the vision process. One characteristic of signal processing in the IPL is that different aspects of the visual impression are only processed in specific sub-layers (strata). Here, we present an investigation of these functional signals for three different sub-layers in the IPL with the aim to separate different properties of the visual signal processing. Whereas the inner depth-layer, closest to the ganglion cells, exhibits an increase in the optical path length, the outer depth-layer, closest to the bipolar cell layer, exhibits a decrease in the optical path length. Additionally, we found that the central depth is sensitive to temporal changes, showing a maximum response at a stimulation frequency of around 12.5 Hz. The results demonstrate that the signals from different cell types can be distinguished by phase-sensitive OCT.

We propose a coupled optical microresonator system that can be used as a new and flexible platform to form asymmetric Fano-like resonances and dynamically control their line shapes and frequencies. The coupled microresonator system was formed using two microring resonators coupled via a 3 × 3 coupler. The upper microring resonator is the add-drop type, whereas the lower one is the all-pass type, providing the (semi-) continuum and discrete states, respectively. We simulated the behavior of the coupled system using the finite-difference time-domain method and observed asymmetric Fano line shapes in the transmission spectra. We demonstrated that the line shapes and frequencies of Fano resonances can be controlled by dynamically varying the refractive index of a small region of the upper or lower microring resonators. We also introduced a small gap in the upper microring resonator to control the continuum state more efficiently. The proposed coupled microresonator concept is simple, easy to fabricate and sufficiently flexible to be engineered for different applications.

Alzheimer’s disease (AD) is a neurodegenerative disease, characterized by the presence of extracellular deposits (plaques) of amyloid-beta peptide and intracellular aggregates of phosphorylated tau. In general, these hallmarks are studied by techniques requiring chemical pre-treatment and indirect labeling. Imaging techniques that require no labeling and could be performed on tissue in its native form could contribute to a better understanding of the disease. In this article a combination of label-free and non-invasive techniques is presented to study the biomolecular composition of AD human brain tissue. We build on previous research that already revealed the autofluorescence property of plaque, and the presence of carotenoids in cored plaques. Here, we present further results on cored plaques: showing blue and green autofluorescence emission coming from the same plaque location. Raman microscopy was used to confirm the presence of carotenoids in the plaque areas, with clear peaks around 1150 and 1514 cm−1. Carotenoid reference spectra were recorded in hexane solution, but also adsorbed on aggregated Aβ42 peptides; the latter agreed better with the Raman spectra observed in plaques. From the six single carotenoids measured, lycopene matched closest with the peak positions observed in the cored plaques. Lastly, stimulated Raman scattering (SRS) microscopy measurements were performed, targeting the shift of the beta-sheet Amide I peak observed in plaques. Employing SRS in the C–H stretch region we also looked for the presence of a lipid halo around plaque, as reported in the literature for transgenic AD mice, but such a halo was not observed in these human AD brain samples.

Multimode fibers (MMFs) show great promise as miniature probes for sensing, imaging and spectroscopy applications. Different parameters of the fibers, such as numerical aperture, refractive index profile and length, have been already optimized for better performance. Here we investigate the role of the core shape, in particular for wavefront shaping applications where a focus is formed at the output of the MMF. We demonstrate that in contrast to a conventional round-core MMF, a square-core design doesn't suffer from focus aberrations. Moreover, we find that how the interference pattern behind a square-core fiber decorrelates with the input frequency is largely independent of the input light coupling. Finally, we demonstrate that a square core shape provides an on-average uniform distribution of the output intensity, free from the input-output correlations seen in round fibers, showing great promise for imaging and spectroscopy applications., Comment: 9 pages, 5 figures

We present a new optomechanical probe for mechanical testing of soft matter. The probe consists of a micromachined cantilever equipped with an indenting sphere, and an array of 16 single‐mode optical fibres, which are connected to an optical coherence tomography (OCT) system that allows subsurface analysis of the sample during the indentation stroke. To test our device and its capability, we performed indentation on a PDMS‐based phantom. Our findings demonstrate that Common Path (CP)‐OCT via lensed optical fibres can be successfully combined with a microindentation sensor to visualise the phantom's deformation profile at different indentation depths and locations in real time. Lay Description This work presents a new approach to simultaneously perform micro‐indentation experiments and OCT imaging. An optical fiber array‐based sensor is used to develop a new hybrid tool where micro‐indentation is combined with optical coherence tomography. The sensor is therefore capable of compressing a sample with a small force and simultaneously collecting OCT depth profiles underneath and around the indentation point. This method offers the opportunity to characterize the mechanical properties of soft materials and simultaneously visualize their deformation profile. The ability to integrate OCT imaging with indentation technology is promising for the non‐invasive and precise characterization of different soft materials.