Exalos (Switzerland)

Introduction and Objective: In type 1 diabetes (T1D), β-cells co-orchestrate their own demise by increasing their visibility to the immune system. The balance between HLA Class I and PDL1 expression is particularly critical: β-cells in T1D overexpress HLA Class I, increasing antigen presentation and immune targeting, but also upregulate PDL1, which promotes immune self-tolerance. Strategies to dissociate these mechanisms may aid development of novel T1D therapies. Methods: To study the misguided immune and β-cell dialogue in a relevant and scalable manner, we established three in vitro islet-immune injury models by culturing spheroids from primary human islets with proinflammatory cytokines, activated peripheral blood mononuclear cells or HLA-A2-restricted preproinsulin-specific cytotoxic T lymphocytes. We then modulated activity or expression of putative targets to investigate their effects on PDL1 and HLA Class I expression, β-cell function, survival and T cell infiltration. Results: In the established models, declining β-cell health manifested as increased basal and decreased glucose-stimulated insulin release, reduced intracellular insulin, loss of the first-phase insulin response and elevated proinsulin-to-insulin ratios. 3D microscopy revealed increased HLA Class I and PDL1 expression, and β-cell death. Extensive T cell infiltration and proinflammatory cytokine secretion confirmed immune activation in co-culture models. Liraglutide and HLA Class I blocking antibodies demonstrated anti-inflammatory and immune-protective effects, serving as controls for future studies. We are currently investigating TYK2-inhibitors and STAT2 knockdown as strategies for decoupling HLA Class I and PDL1 expression and immune protection. Our preliminary results shows TYK2 inhibition can protect islets from proinflammatory cytokine damage. Conclusion: The described biomimetic islet-immune assays provide scalable in vitro tools for studying interventions that can protect the β-cells from the immune-mediated attack that leads to T1D. Disclosure S. Jawurek: None. A.C. Title: None. C. Rufer: None. F. Forschler: Employee; InSphero AG. D.L. Eizirik: Advisory Panel; InSphero. B. Yesildag: Other Relationship; Novo Nordisk, Boehringer-Ingelheim, Eli Lilly and Company, Biomea Fusion, Biosplice Therapeutics, Abata Therapeutics, AstraZeneca, Amgen Inc.

High-resolution optical coherence tomography (OCT) requires broadband, spatially coherent light sources. Today, the source of choice for visible light OCT, the supercontinuum (SC), is bulky, expensive, and prone to excess noise. Here we demonstrate high-resolution visible light OCT of the human retina with a combined superluminescent diode (SLD) source. The source is longer in wavelength than the high blue light hazard range but shorter in wavelength than the high photopic efficiency range, ensuring subject safety and comfort. We report an axial resolution of 3.2 µm in the retina. We find that Bruch's membrane is well-delineated in subjects without ocular pathology, even though the axial resolution is ∼3× coarser than SC visible light OCT.Imaging of intermediate age-related macular degeneration is also shown. Within the cyan-green wavelength range of the SLD, optical density spectra resemble those of macular pigments. While the combined SLD approach does not achieve the micrometer-scale resolution of the SC, it potentially reduces the cost and complexity of visible light OCT while providing novel disease-relevant biomarkers, to the best of our knowledge, in human retina.

An optical transceiver module, based on a broadband Superluminescent Light-Emitting Diode (SLED) at 1550 nm and an integrated receiver photodiode, has been developed. The compact 14-pin butterfly (BTF) module integrates micro-optical lenses, a flatpack optical isolator, a 50:50 beam splitter and other components on a temperature-controlled, free-space optical bench platform and is delivering, at an SLED current of 250 mA, around 5 mW of output power at a polarization-maintaining (PM) output fiber with a polarization extinction ratio (PER) larger than 20 dB over a temperature operating range from $- 40 ^{\circ}\mathrm{C}$ to $+ 85 ^{\circ}\mathrm{C}$.

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We are demonstrating a high-power, broadband 840-nm light source, where amplified spontaneous emission (ASE) from a superluminescent light emitting diode (SLED) is amplified by a semiconductor optical amplifier (SOA) in order to generate power levels of 100-300 mW in free-space. The optical architecture of this light source resembles a master oscillator power amplifier (MOPA) configuration.

We present the first light source module that is realized with RGB superluminescent LEDs in a compact 14-pin butterfly housing for speckle-free display applications. The module provides a free-space output with collimated RGB beams that are colinearly aligned having 10 mW output power per color.

We present a quasi-static model for the accurate simulation of swept source external cavity lasers. The model is based on steady-state solutions of multi-mode rate equations. The wavelength sweep is incorporated in the model by a spectral slicing technique. A comparison with experimental results demonstrates the usefulness of our approach. Limitations for the simulation of high-speed swept sources arising from the quasi-static approach presented here are discussed. Our model is a first step towards a time-dependent model that contains a full dynamic description of all relevant nonlinear effects.

We developed an FPGA-based engine for Fourier-domain OCT that performs real-time signal processing based on Non- Uniform Fast Fourier Transform (NUFFT). The basic NUFFT algorithm is discussed and compared with cubic-spline interpolation regarding efficient re-sampling in k-space with different phase nonlinearities of sinusoidal swept sources. The NUFFT algorithm was adapted for an implementation in an FPGA and its accuracy is analyzed and assessed using simulated numerical data. When implemented, the NUFFT algorithm allows a processing performance at a sampling rate of 100 MS/s. The real-time processing capability was tested with sinusoidal bi-directional swept sources with A-scan rates of 50 kHz.

We report on the achievement of III-nitride blue superluminescent light-emitting diodes on GaN substrates. The epitaxial structure includes an active region made of In0.12Ga0.88N quantum wells in a GaN/AlGaN waveguide. Superluminescence under cw operation is observed at room temperature for a current of 130 mA and a current density of 8 kA/cm2. The central emission wavelength is 420 nm and the emission bandwidth is ∼5 nm in the superluminescence regime. A peak optical output power of 100 mW is obtained at 630 mA under pulsed operation and an average power of 10 mW is achieved at a duty cycle of 20%.

Using a pump-probe differential transmission experiment in heterodyne detection, we measured the refractive index dynamics at the ground-state excitonic transition in electrically pumped InAs/GaAs quantum-dot amplifiers emitting near 1.3 mum at room temperature. We compare three samples differing only in the level of <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</i> -doping, and interpret the measured index changes taking into account the gain dynamics in these devices. We find that in absorption, the excess hole density due to <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</i> -doping accelerates the recovery and reduces the refractive index change, since filling of the hole states by <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</i> -doping shifts the induced changes in the hole population toward high energy states. Conversely, in gain, the reduced electron reservoir in the excited states in <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</i> -doped devices results in slower gain recovery dynamics and in larger refractive index changes compared to undoped devices operating at the same modal gain. The linewidth enhancement factor inferred from these measurements shows that <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</i> -doping is effective in reducing this parameter mainly due to the larger differential gain in <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</i> -doped devices in the gain regime.