Theses 2023

Bisacylphosphane Oxides (BAPOs) as Potential Photolatent Therapeutic Compounds

Abstract: This work presented a novel approach for the induction of oxidative stress in target sys-tems via a light-activated compound called bisacylphosphane oxides (BAPOs). BAPOs are non-toxic and cost-effective initiators of photolatent polymerization reactions. Once sub-jected to light up to 450 nm wavelength, BAPOs undergo homolytic cleavage and produce cytotoxic radical species. Having an interesting therapeutic potential, in this work, the biochemical and optical characterization and optimization of BAPOs were realized. Functionalized BAPO analogs for targeted therapy and higher bio-compatibility were engineered by attaching functional groups to the core structure, which were administered to several model systems. The systems included cancerous and noncancerous cell lines, Escherichia coli, and zebrafish larvae (Danio rerio). It was shown that the efficacy of BAPOs is only arising from their activation by light and that neither the light nor BAPO treatment alone cause a notable effect on any of the target systems. Moreover, attributing the putative cause of cell death to oxidative stress warranted its verification by introducing a radical scavenger, which resulted in cellular rescue. Additionally, a fiber-based irradiation scheme was constructed to introduce the possibility of irradiation with a higher spatial resolution to support the targeted therapy and reduce side effects. This scheme was also utilized to irradiate a cancerous cell line in the presence of a tissue phantom layer which attenuates incident light, showing that a lower intensity entails a longer irradiation duration to obtain the same effect. Analysis of cellular morphology and formation of stress granules indicated the apoptotic manner in which the cytotoxicity occurs upon BAPO+light treatment. Therefore, this work suggests BAPOs as novel photoactivatable cytotoxic agents, with promising use in cancer therapy, and antimicrobial potential.

Improving the Evaluation of Wide-Angle Light Scattering (WALS) Data using Machine Learning Algorithms

Conclusions:  This research investigates the emergence of exceptional points (EPs) in non-Hermitian systems, a phenomenon where eigenvectors of the Hamiltonian matrix coalesce. By representing a non-Hermitian system as a directed graph, we identify new symmetries which both simplify the distribution of complex energy eigenvalues and allow for the emergence of exceptional points.
We study properties of these exceptional points in a 2D nearest-neighbor toy model. Even when the coupling strength and system geometry are varied, exceptional points persist in this model. As this makes the exceptional points robust to noise, these insights may be relevant to realizing them in a laboratory setting.
Finally, the paper considers analytical methods for path integrals around EPs. By representing an EP of order n as an n-farb graph, we identify a basis that simplifies the time-dependent Schrödinger equation, providing an analytical expression for the non-adiabatic time evolution around an EP.

Improving the Evaluation of Wide-Angle Light Scattering (WALS) Data using Machine Learning Algorithms

Conclusions:  Spray play a vital role in many industires and scientific applications such as fuel injection in combustion processes, pharmaceutical distribution and soon. Inorder to monitor, optimize and control such processes, estimating droplet size distribution accurately is crucial.
Existing droplet size distributions algorithms were developed and applied to estimate droplet size distributions. However such algorithms used parameterized functions, for example, to detect local maxima of Mie scattering signals. This can lead to biased and inaccurate results.
In this study, we explored the potential of different neural network models for estimating droplet size distribution. The results show that it is possible to apply deep neural network for accurate estimation of droplet size distribution. In addition to significant improvement of droplet size distribution estimation, such an approach does not rely on input parameters that humans have to choose. Therefore, a pre-trained neural network can play a significant role in spray characterization which is crucial to monitor, optimize and control of numerous industrial and scientific processes.
To train the deep neural network, two different training dataset were extracted from WALS acquired original images. Training dataset A consists of scattering 1D signals (data) from left and right mirror section of WALS image data. Training dataset B contains cropped images of the WALS images. These two datasets were applied to train three deep neural network models. The results showed that training dataset B (cropped images) contains richer information compared to training dataset A (1D scattering data) to train the deep neural network models better. Even though the result was only shown for U-Net model, dataset B provided an improved performance of the Res-Net and also custom CNN models.
To address the challenge of estimating droplet size, three different CNN models, Res-Net, U-Net and custom CNN, were trained and compared in estimating droplet size distribution with the WALS data. The learning curves of the Res-Net model show an improved performance where the training and validations curves decrease to the point of stability with minimal gap between the curves. In contrary, the custom CNN could not learn the training dataset very well which showed it has low capacity to train all the trends of the WALS data. The U-Net model did a great job in learning the training dataset but ends up with a large generalization error when tested by the validation dataset. It achieved a minimum MSE loss which is more than 8 times higher compared to the validation curve of Res-Net. This indicates overfitting where the model performs well in learning the training dataset but failed to predict when tested with new dataset. The improved performance of the Res-Net is because it uses a bottleneck design of residual blocks that increases network performance. It also protects the network from vanishing gradient problems by using identity/short-cut connection.

Optical Characterization of a Novel Fluorescent Protein Staygold

Conclusions:  The discovery of fluorescent proteins boosted the application of fluorescence microscopy within cell science. In parallel, the evolution of fluorescence microscopy resulted in various new imaging techniques. Today cell biological research is unthinkable without the possibilities of fluorescence microscopy. Still, it is a challenge to find the appropriate fluorophore for a specific fluorescence microscopic technique. There is no available fluorophore that can be used for each microscopic application.
While chemical dyes are stable, they can alter cellular behavior and are unsuitable for long-term live-cell microscopy. For long-term live cell microscopy, fluorescent proteins have a lag-up. Constitutive expression enables imaging for days, and proteins are less noxious than chemical dyes. Unfortunately, all of the available fluorescent proteins also have their pros and cons. Therefore, this study was performed with the aim of defining the optimal fluorescent protein for the respective microscopic technique. Three available GFPs and the newly discovered StayGold were compared. All GFPs were tested for their application in living cells and also upon fixation. In addition to fluorescence intensity, the fluorescence lifetime was defined for these GFPs. In summary, this thesis facilitates the directed use of GFPs, recommending Venus for Methanol fixation. Regardless of the fixation method, GFP fluorescence lifetime stays stable (1.5 – 2.3ns). StayGold exhibits the highest fluorescence in living and formalin-fixed cells. Finally, the two-photon excitability of StayGold was determined at 930nm.

Experimental Characterisation of Spatially and Temporally Focused Femtosecond Laser Pulses

Conclusions and recommendations:  SSTF offers a wide variety of potential applications where light with a high energy density is required and needs to be controlled in all three dimension. Differently to SF of ultrashort pulses, this technique enables its users to manipulate the duration, shape and propagation of light pulses in unique ways and it is not surprising that variations of the concept are ariseing, specially for medical, industrial and reserch applications. The current setup can certainly be improved by embracing one or more of the approaches mentioned in the discussion. It could also be helpful to characterise the beam prior to the focusing with a FROG, TERMITES or STRIPED FISH technique, to better understand and model experiments using SSTF. One final thought is that even if an unexpected result, the steady exclusion of a part of the optical axis with two strongly focused ultrafast beams on either side could find their own application in scenarion wher something has to be illuminiated which confines another part which should remain unaffected, or the concept could be expanded similarly to what is being research for so-called optical bottle which could be employed for inducing flat-top temperature distributions.

Summary and outlook: This thesis has shown, that an end-side pumped solar laser gives a stable output with a novel secondary concentrator as a light guide to transfer the radiation from the primary concentrator to the laser medium. The cooling cavity is designed as a coil pipe to ensure that the high calcium oxide concentration in the cooling water has no contact with the laser medium. Due to the properties of a coil, the pipe inside screws through the cavity which implies at the beginning of the coil there is an incomplete round-trip.
This incomplete round-trip of the pipe affects the laser crystal with a low cooling rate at a specific side. This missing piece induces thermal effects such as thermal lensing and further effects, which explains the low output power of the laser. Nevertheless, the secondary concentrator in combination with a large-diameter laser medium shows a stable and highly reproducible output. Due to the low laser output power of 3mW the cooling cavity needs to be improved to achieve higher power.
Today’s greatest challenge is to stop climate change and reduce greenhouse emissions. In history, the usage of fossil fuels has been sufficient to form modern society and accelerate technological progress. One insurmountable challenge is that sooner or later the resources of fossil fuels are depleted. Therefore, reliable and available energy sources from renewable energy sources, such as the sun, must be used more efficiently. The total intensity provided by the sun in space is higher compared to the sea level due to the attenuation of the atmosphere [1]. Above the atmospheric layers the intensity is well known as the solar constant and is given = 1367W/m2 [2]. This value is given for the whole spectrum of the sun and includes all wavelengths. Due to the higher solar intensity in space, it is efficient to generate energy directly in space and transmit it through the atmosphere.
Furthermore, in space, the spatial dimensions permit a larger structure design compared to Photovoltaic (PV) parks on Earth nowadays. This concept of a space-based solar power (SBSP) and came up first by Peter Glaser in 1968 [1, 3]. The basic concept is that solar light is collected in space and converted into a laser beam which radiates at the transmission wavelength of Earth’s atmosphere. On Earth’s surface PV arrays are placed, they act as receivers and convert the energy into electricity. An illustration is depicted in figure 1 [3–7]. To invent such a mega project, some challenges need to be solved such as the efficiency, thermal effects, and safe radiation transmission of the solar laser in space [8,9], which will be addressed in the next steps of this project.

Towards Two-Dimensional Sources of Quantum Light

Conclusions:  This thesis is dedicated to the generation of correlated photon pairs via SPDC in a 2D flake of GaSe. In the following, I will describe the conclusions of this work.

• I demonstrated for the rst time the generation of entangled photons from a flake of GaSe with 130 nm thickness. To my knowledge, so far, this is the first time that photon pairs have been generated via SPDC in a subwavelength GaSe flake. I built a setup for generation and detection of photon pairs and using 10 mW of CW pumping, I achieved a pair generation rate of 3.6 Hz from the sample.
• I measured the dependence of the rate of photon pair generation on the power of the pump and veried its linear dependence. I also used a long dispersive fiber to measure the spectrum of photon pairs using single-photon spectroscopy technique and veried that the spectrum is broad and extends over the entire range allowed by the transmission window of the single-mode bers used in the setup.

The results of this work will pave the way for future investigations.