TY - JOUR A1 - Bruun, Kristina A1 - Löhmannsröben, Hans-Gerd A1 - Hille, Carsten T1 - Benefits of Combined Fluorescence Lifetime Imaging Microscopy and Fluorescence Correlation Spectroscopy for Biomedical Studies Demonstrated by Using a Liposome Model System JF - Biophysica N2 - Drug delivery systems play a pivotal role in targeted pharmaceutical transport and controlled release at specific sites. Liposomes, commonly used as drug carriers, constitute a fundamental part of these systems. Moreover, the drug–liposome model serves as a robust platform for investigating interaction processes at both cellular and molecular levels. To advance our understanding of drug carrier uptake mechanisms, we employed fluorescence lifetime imaging microscopy (FLIM) and fluorescence correlation spectroscopy (FCS), leveraging the unique benefits of two-photon (2P) excitation. Our approach utilized giant unilamellar vesicles (GUVs) as a simplified model system for cell membranes, labelled with the amphiphilic fluorescent dye 3,3′-dioctadecyloxa-carbocyanine (DiOC18(3)). Additionally, large unilamellar vesicles (LUVs) functioned as a drug carrier system, incorporating the spectrally distinct fluorescent sulforhodamine 101 (SRh101) as a surrogate drug. The investigation emphasized the diverse interactions between GUVs and LUVs based on the charged lipids employed. We examined the exchange kinetics and structural alterations of liposome carriers during the uptake process. Our study underscores the significance of employing 2P excitation in conjunction with FLIM and FCS. This powerful combination offers a valuable methodological approach for studying liposome interactions, positioning them as an exceptionally versatile model system with a distinct technical advantage. KW - drug delivery KW - fluorescence correlation spectroscopy KW - fluorescence lifetime imaging microscopy KW - liposome KW - membrane interaction Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19189 VL - 4 IS - 2 SP - 207 EP - 227 PB - MDPI ER - TY - JOUR A1 - Prylutska, Svitlana A1 - Grebinyk, Anna A1 - Ponomarenko, Stanislav A1 - Gövem, Defne A1 - Chumachenko, Vasyl A1 - Kutsevol, Nataliya A1 - Petrovsky, Mykola A1 - Ritter, Uwe A1 - Frohme, Marcus A1 - Piosik, Jacek A1 - Prylutskyy, Yuriy T1 - Toxicity of Water-Soluble D-g-PNIPAM Polymers in a Complex with Chemotherapy Drugs and Mechanism of Their Action In Vitro JF - International Journal of Molecular Sciences N2 - The application of a biocompatible polymer nanocarrier can provide target delivery to tumor tissues, improved pharmacokinetics, controlled drug release, etc. Therefore, the proposed strategy was to use the water-soluble star-like copolymers with a Dextran core and Poly(N-isopropylacrylamide) grafts (D-g-PNIPAM) for conjugation with the widely used chemotherapy drugs in oncology–Cisplatin (Cis-Pt) and Doxorubicin (Dox). The molecular characteristics of the copolymer were received using size-exclusion chromatography. The physicochemical characterization of the D-g-PNIPAM-Cis-Pt (or Dox) nanosystem was conducted using dynamic light scattering and FTIR spectroscopy. Using traditional biochemical methods, a comparative analysis of the enhancement of the cytotoxic effect of free Cis-Pt and Dox in combination with D-g-PNIPAM copolymers was performed in cancer cells of the Lewis lung carcinoma line, which are both sensitive and resistant to Dox; in addition, the mechanism of their action in vitro was evaluated. KW - star-like copolymer KW - drug KW - Lewis lung carcinoma KW - cytotoxicity Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-18790 SN - 1422-0067 VL - 25 IS - 5 PB - MDPI ER - TY - THES A1 - Marehn, David Thomas T1 - Reliability of Data Acquisition and Processing Approaches for Chromatography Detection Systems in Pharmacy N2 - Nowadays pharmaceutical analysis and industry could not be imagined without using chromatographic methods like the High Performance Liquid Chromatography (HPLC) and Gas Chromatography (GC). Therefore, the field of chromatography is already firmly anchored in the three important, regional pharmacopeias: EP, USP and JP. Deficits of specifications within these pharmacopoeias relating to the detector parameters sampling rate and signal filtration are the major motivation of this thesis. Furthermore investigations on the data acquisition and processing within the detectors and software products dealing with collected data were done. Several concepts like double entry method, smoothing optimization and signal filtration based on persistence have been developed and are used as tools to examine the data integrity of commercial Chromatography Data System (CDS), improve the signal-to-noise ratio of small peaks to lower the LOD and LOQ by efficient denoising, and determine the suitable filter parameters and sampling rates an user can apply on his system to accelerate the method development and validation. All developments have been tested on simulated and real chromatograms and have shown that they are suitable for their specific purposes. In the end optimizations in the concepts still exist but some new aspects in the long-term investigated field of chromatography have been discovered. KW - sampling rate KW - chromatography KW - signal filtration Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-15438 ER - TY - JOUR A1 - Li, Xiangkun A1 - Amirkhanyan, Zohrab A1 - Grebinyk, Anna A1 - Gross, Matthias A1 - Komar, Yuliia A1 - Riemer, Felix A1 - Asoyan, Aida A1 - Boonpornprasert, Prach A1 - Borchert, Paul A1 - Davtyan, Hakob A1 - Dmytriiev, Dmytro A1 - Frohme, Marcus A1 - Hoffmann, Andreas A1 - Krasilnikov, Mikhail A1 - Loisch, Gregor A1 - Lotfi, Zahra A1 - Müller, Frieder A1 - Schmitz, Michael A1 - Obier, Frank A1 - Oppelt, Anne A1 - Philipp, Sebastian A1 - Richard, Christopher A1 - Vashchenko, Grygorii A1 - Villani, Daniel A1 - Worm, Steven A1 - Stephan, Frank T1 - Demonstration of ultra-high dose rate electron irradiation at FLASHlab@PITZ JF - Physics in Medicine & Biology N2 - Objective. The photo injector test facility at DESY in Zeuthen (PITZ) is building up an R&D platform, known as FLASHlab@PITZ, for systematically studying the FLASH effect in cancer treatment with its high-brightness electron beams, which can provide a uniquely large dose parameter range for radiation experiments. In this paper, we demonstrate the capabilities by experiments with a reduced parameter range on a startup beamline and study the potential performance of the full beamline by simulations. Approach. To measure the dose, Gafchromic films are installed both in front of and after the samples; Monte Carlo simulations are conducted to predict the dose distribution during beam preparation and help understand the dose distribution inside the sample. Plasmid DNA is irradiated under various doses at conventional and ultra-high dose rate (UHDR) to study the DNA damage by radiations. Start-to-end simulations are performed to verify the performance of the full beamline. Main results. On the startup beamline, reproducible irradiation has been established with optimized electron beams and the delivered dose distributions have been measured with Gafchromic films and compared to FLUKA simulations. The functionality of this setup has been further demonstrated in biochemical experiments at conventional dose rate of 0.05 Gy s−1 and UHDR of several 105 Gy s−1 and a varying dose up to 60 Gy, with the UHDR experiments finished within a single RF pulse (less than 1 millisecond); the observed conformation yields of the irradiated plasmid DNA revealed its dose-dependent radiation damage. The upgrade to the full FLASHlab@PITZ beamline is justified by simulations with homogeneous radiation fields generated by both pencil beam scanning and scattering beams. Significance. With the demonstration of UHDR irradiation and the simulated performance of the new beamline, FLASHlab@PITZ will serve as a powerful platform for studying the FLASH effects in cancer treatment. KW - ultra-high dose rate KW - FLASH effect KW - electron beams KW - FLASHlab@PITZ Y1 - 2025 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-20092 VL - 70 IS - 5 PB - Institute of Physics Publishing (IOP) ER - TY - CHAP A1 - Gross, Matthias A1 - Kuhl, Thorsten A1 - Stephan, Frank A1 - Li, Xiangkun A1 - Philipp, Sebastian A1 - Grebinyk, Anna A1 - Khachatryan, Vitali A1 - Qian, Houjun A1 - Aboulbanine, Zakaria A1 - Amirkhanyan, Zohrab A1 - Riemer, Felix A1 - Oppelt, Anne A1 - Krasilnikov, Mikhail ED - Istituto Nazionale Di Fisca Nucleare, T1 - A beam line setup for flash radiation therapy with focused electron beams at the Pitz facility at DESY in Zeuthen: basic concept and dosimetry simulations T2 - IPAC'23 : 14th International Particle Accelerator Conference, 7-12 May 2023, Venice, Italy : proceedings N2 - The aim of this work is to demonstrate the principal possibility to enhance the electron beam dose deposition in the depth of the sample for radiation therapy purposes. Trains of electron bunches of 22 MeV generated at PITZ are focused inside the sample using a dedicated fast deflector and a solenoid magnet. To explore the capabilities of the proposed setup, dose distributions are calculated for multiple electron bunches focused in a single point inside a water phantom. Electron beam focusing produces dose peaks with a tunable maximal dose depth which is interesting for healthy tissue sparing at the surface and enhancing treatment quality. The duration of the full bunch train is 1 ms. During this time interval, the FLASH effect could be efficiently triggered inside the irradiated target volume. Monte Carlo simulations based on the FLUKA code were performed to evaluate the depth dose curves distributions in a water phantom. Using the PITZ electron beam parameters, simulations have shown the possibility to produce a peak dose in water seven times higher than compared to the dose at the surface. Moreover, the RMS size homogeneous area around the maximal dose is approximately 25 mm. Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-21132 SP - 5000 EP - 5003 PB - JACoW Publishing ER - TY - CHAP A1 - Gross, Matthias A1 - Hoffmann, Andreas A1 - Georgiev, Georgi A1 - Kuhl, Thorsten A1 - Li, Xiangkun A1 - Oppelt, Anne A1 - Boonpornprasert, Prach A1 - Philipp, Sebastian A1 - Grebinyk, Anna A1 - Vashchenko, Grygorii A1 - Aftab, Namra A1 - Adhikari, Gowri A1 - Richard, Christopher A1 - Stephan, Frank A1 - Khachatryan, Vitali A1 - Riemer, Felix A1 - Krasilnikov, Mikhail A1 - Amirkhanyan, Zohrab ED - Istituto Nazionale Di Fisca Nucleare, T1 - Comparison of measurements and simulation results of dose for the FLASH radiation therapy beamline at PITZ T2 - IPAC'23 : 14th International Particle Accelerator Conference, 7-12 May 2023, Venice, Italy : proceedings N2 - The high-brightness electron beam at the Photo Injector Test facility at DESY in Zeuthen (PITZ) is now also used for FLASHlab@PITZ: an R&D platform for studying radiation biology and the FLASH effect in radiation therapy. The available parameter space of the electron beam with a momentum of 22 MeV/c allows bunch charges from 10 pC up to 5nC, bunch durations of 0.1–60ps, and bunch train lengths up to 1 ms. The number of bunches in the single train can currently be varied between 1 and 1000 bunches, with an upgrade to 4500 foreseen in 2023. Radiation biology studies require accurate dose prediction, therefore Monte Carlo simulations based on the FLUKA code were performed. According to estimations, dose delivery of 0.002 Gy (low charge case 0.1pC) and 10Gy (high charge case 5nC) is possible, if the beam is confined to a circular area with a radius of 5 mm with a lead collimator. For the Monte Carlo simulations, the experimental setup was accurately modeled, including the exit window, lead collimator, etc. Dose measurements were used to compare simulations with experiments. Dose profiles were experimentally measured with Gafchromic films and then compared with Monte Carlo simulations. The first experiments at FLASHlab@PITZ in 2023 have demonstrated flexible dose options for studying the FLASH effect and radiation biology studies. Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-21126 SP - 4996 EP - 4999 PB - JACoW Publishing ER - TY - CHAP A1 - Breithecker, Janine A1 - Szymanski, Mateusz A1 - Stolpmann, Alexander ED - Reiff-Stephan, Jörg ED - Jäkel, Jens ED - Reichelt, Dirk T1 - Entwicklung eines robotergestützten Systems zur standardisierten Applikation von Hautpflegeprodukten T2 - Tagungsband AALE 2025 : menschenzentrierte Automation im digitalen Zeitalter N2 - In diesem Beitrag wird ein System zur automatisierten Applikation von Hautpflegeprodukten vorgestellt, das speziell für dermatologische Studien entwickelt wird. Ziel ist es, die Variabilitäten bei der manuellen Cremeapplikation zu reduzieren und die Reproduzierbarkeit von Studienergebnissen zu verbessern. Die Grundlage des Systems bildet ein kollaborativer Roboter (Cobot), der mit einer präzisen Kraftregelung und Echtzeit-Bildverarbeitung ausgestattet ist. Diese Kombination ermöglicht die dynamische Anpassung an unterschiedliche Hautareale und eine gleichmäßige Verteilung von Cremes und Lotionen. Der Entwicklungsprozess umfasste die Konstruktion eines spezialisierten Endeffektors für das Verteilen der Creme, der mit Kraftsensorik und austauschbaren Elementen für hygienische Anwendungen ausgestattet ist, sowie die Integration einer Eppendorf Multipette M4 zur präzisen Dosierung als wechselbarer Endeffektor am Cobot. Ergänzt wird das System durch eine Intel RealSense Kamera, die mithilfe von Farb- und Tiefenbildern eine zuverlässige Erkennung von Hand- und Armpositionen gewährleistet. Erste Tests zeigen, dass das System eine exakte und reproduzierbare Applikation ermöglicht, wobei die Sicherheit und Benutzerfreundlichkeit im Fokus stehen. Die vorgestellten Validierungsstrategien und geplanten Nutzerstudien sollen die Funktionalität weiter optimieren und das Potenzial für den Einsatz in dermatologischen Studien unterstreichen. Dieses Projekt stellt einen bedeutenden Schritt in Richtung Automatisierung und Standardisierung in der dermatologischen Forschung dar. KW - Automatisierung KW - Bildverarbeitung KW - Cobot KW - Konstruktion KW - Mensch-Roboter-Kollaboration KW - Regelung Y1 - 2025 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-20150 SP - 387 EP - 394 PB - Hochschule für Technik, Wirtschaft und Kultur CY - Leipzig ER -