@article{SamhaberSchottdorfElHadyetal.2016, author = {Samhaber, Robert and Schottdorf, Manuel and El Hady, Ahmed and Br{\"o}king, Kai and Daus, Andreas and Thielemann, Christiane and St{\"u}hmer, Walter and Wolf, Fred}, title = {Growing neuronal islands on multi-electrode arrays using an accurate positioning-μCP device}, series = {Journal of Neuroscience Methods}, volume = {2016}, journal = {Journal of Neuroscience Methods}, number = {257}, doi = {10.1016/j.jneumeth.2015.09.022}, pages = {194 -- 203}, year = {2016}, abstract = {Background: Multi-electrode arrays (MEAs) allow non-invasive multi-unit recording in-vitro from cultured neuronal networks. For sufficient neuronal growth and adhesion on such MEAs, substrate preparation is required. Plating of dissociated neurons on a uniformly prepared MEA's surface results in the formation of spatially extended random networks with substantial inter-sample variability. Such cultures are not optimally suited to study the relationship between defined structure and dynamics in neuronal networks. To overcome these shortcomings, neurons can be cultured with pre-defined topology by spatially structured surface modification. Spatially structuring a MEA surface accurately and reproducibly with the equipment of a typical cell-culture laboratory is challenging. New method: In this paper, we present a novel approach utilizing micro-contact printing (μCP) combined with a custom-made device to accurately position patterns on MEAs with high precision. We call this technique AP-μCP (accurate positioning micro-contact printing). Comparison with existing methods: Other approaches presented in the literature using μCP for patterning either relied on facilities or techniques not readily available in a standard cell culture laboratory, or they did not specify means of precise pattern positioning. Conclusion: Here we present a relatively simple device for reproducible and precise patterning in a standard cell-culture laboratory setting. The patterned neuronal islands on MEAs provide a basis for high throughput electrophysiology to study the dynamics of single neurons and neuronal networks.}, subject = {Mehrfachelektrode}, language = {en} } @article{LiebStarkThielemann2017, author = {Lieb, Florian and Stark, Hans-Georg and Thielemann, Christiane}, title = {A stationary wavelet transform and a time-frequency based spike detection algorithm for extracellular recorded data}, series = {Journal of Neural Engineering}, volume = {2017}, journal = {Journal of Neural Engineering}, number = {14}, doi = {10.1088/1741-2552/aa654b}, pages = {1 -- 13}, year = {2017}, abstract = {Objective. Spike detection from extracellular recordings is a crucial preprocessing step when analyzing neuronal activity. The decision whether a specific part of the signal is a spike or not is important for any kind of other subsequent preprocessing steps, like spike sorting or burst detection in order to reduce the classification of erroneously identified spikes. Many spike detection algorithms have already been suggested, all working reasonably well whenever the signal-to-noise ratio is large enough. When the noise level is high, however, these algorithms have a poor performance. Approach. In this paper we present two new spike detection algorithms. The first is based on a stationary wavelet energy operator and the second is based on the time-frequency representation of spikes. Both algorithms are more reliable than all of the most commonly used methods. Main results. The performance of the algorithms is confirmed by using simulated data, resembling original data recorded from cortical neurons with multielectrode arrays. In order to demonstrate that the performance of the algorithms is not restricted to only one specific set of data, we also verify the performance using a simulated publicly available data set. We show that both proposed algorithms have the best performance under all tested methods, regardless of the signal-to-noise ratio in both data sets. Significance. This contribution will redound to the benefit of electrophysiological investigations of human cells. Especially the spatial and temporal analysis of neural network communications is improved by using the proposed spike detection algorithms.}, subject = {Neuronales Netz}, language = {en} } @article{SzewczykMoniciThielemann2024, author = {Szewczyk, Nathaniel J. and Monici, Monica and Thielemann, Christiane}, title = {How to obtain an integrated picture of the molecular networks involved in adaptation to microgravity in different biological systems?}, series = {npj Microgravity}, volume = {2024}, journal = {npj Microgravity}, number = {10}, doi = {DOI: 10.1038/s41526-024-00395-3}, pages = {1 -- 5}, year = {2024}, abstract = {Periodically, the European Space Agency (ESA) updates scientific roadmaps in consultation with the scientific community. The ESA SciSpacE Science Community White Paper (SSCWP) 9, "Biology in Space and Analogue Environments", focusses in 5 main topic areas, aiming to address key community-identified knowledge gaps in Space Biology. Here we present one of the identified topic areas, which is also an unanswered question of life science research in Space: "How to Obtain an Integrated Picture of the Molecular Networks Involved in Adaptation to Microgravity in Different Biological Systems?" The manuscript reports the main gaps of knowledge which have been identified by the community in the above topic area as well as the approach the community indicates to address the gaps not yet bridged. Moreover, the relevance that these research activities might have for the space exploration programs and also for application in industrial and technological fields on Earth is briefly discussed.}, subject = {Weltraumforschung}, language = {en} } @article{NickYadavJoshietal.2015, author = {Nick, Christoph and Yadav, Sandeep and Joshi, Ravi and Schneider, J{\"o}rg and Thielemann, Christiane}, title = {A three-dimensional microelectrode array composed of vertically aligned ultra-dense carbon nanotube networks}, series = {Applied Physics Letters}, volume = {2015}, journal = {Applied Physics Letters}, number = {107}, doi = {10.1063/1.4926330}, pages = {1 -- 1}, year = {2015}, abstract = {Electrodes based on carbon nanotubes are a promising approach to manufacture highly sensitive sensors with a low limit of signal detection and a high signal-to-noise ratio. This is achieved by dramatically increasing the electrochemical active surface area without increasing the overall geometrical dimensions. Typically, carbon nanotube electrodes are nearly planar and composed of randomly distributed carbon nanotube networks having a limited surface gain for a specific geometrical surface area. To overcome this limitation, we have introduced vertically aligned carbon nanotube (VACNT) networks as electrodes, which are arranged in a microelectrode pattern of 60 single electrodes. Each microelectrode features a very high aspect ratio of more than 300 and thus a dramatically increased surface area. These microelectrodes composed of VACNT networks display dramatically decreased impedance over the entire frequency range compared to planar microelectrodes caused by the enormous capacity increase. This is experimentally verified by electrochemical impedance spectroscopy and cyclic voltammetry.}, subject = {Mikroelektrode}, language = {en} } @article{KupnikThielemann2017, author = {Kupnik, Mario and Thielemann, Christiane}, title = {In vitro platform for acoustic and electrophysiological investigations of ultrasound stimulation}, series = {Brain Stimulation}, volume = {10}, journal = {Brain Stimulation}, number = {2}, doi = {10.1016/j.brs.2017.01.465}, pages = {501}, year = {2017}, abstract = {Since the first time discovered that ultrasound can influence neuronal activity - more than half a century ago - a lot of progress has been made in this field. The possibilities of ultrasound for neuromodulation have been demonstrated in many experiments such as in vivo stimulation of rodent brain or of human cochlear, Further, in vitro experiments with hippocampal slices and other cell types have been performed as well.}, subject = {Neuronales Netz}, language = {en} } @misc{CibaMayerThielemann2019, author = {Ciba, Manuel and Mayer, Margot and Thielemann, Christiane}, title = {Experimental setup to investigate the effect of psychedelics on in vitro neuronal networks}, doi = {10.6084/m9.figshare.11980434.v1}, year = {2019}, abstract = {Experimental setup to investigate the effect of psychedelics on in vitro neuronal networks: A demonstration of the application of in vitro neuronal networks on high-density-microelectrode arrays (HDMEA) to study electrophysiological properties of neuronal networks in response to psychedelics.}, subject = {Neuronales Netz}, language = {en} } @article{NickDausBesteletal.2013, author = {Nick, Christoph and Daus, Andreas and Bestel, Robert and Goldhammer, Michael and Steger, Frederik and Thielemann, Christiane}, title = {DrCell - a software tool for the analysis of cell signals recorded with extracellular microelectrodes}, series = {Signal processing: an international journal (SPIJ)}, volume = {7}, journal = {Signal processing: an international journal (SPIJ)}, number = {2}, pages = {96 -- 109}, year = {2013}, subject = {Mikroelektrode}, language = {de} } @article{AlvesToutainAguiaretal.2023, author = {Alves, Caroline L. and Toutain, Thaise and Aguiar, Patricia and Pineda, Aruane M. and Roster, Kirstin and Thielemann, Christiane and Porto, Joel and Rodrigues, Francisco A.}, title = {Diagnosis of autism spectrum disorder based on functional brain networks and machine learning}, series = {Scientific Reports}, volume = {2023}, journal = {Scientific Reports}, number = {13/8072}, doi = {https://doi.org/10.1038/s41598-023-34650-6}, pages = {1 -- 20}, year = {2023}, abstract = {Autism is a multifaceted neurodevelopmental condition whose accurate diagnosis may be challenging because the associated symptoms and severity vary considerably. The wrong diagnosis can affect families and the educational system, raising the risk of depression, eating disorders, and self-harm. Recently, many works have proposed new methods for the diagnosis of autism based on machine learning and brain data. However, these works focus on only one pairwise statistical metric, ignoring the brain network organization. In this paper, we propose a method for the automatic diagnosis of autism based on functional brain imaging data recorded from 500 subjects, where 242 present autism spectrum disorder considering the regions of interest throughout Bootstrap Analysis of Stable Cluster map. Our method can distinguish the control group from autism spectrum disorder patients with high accuracy. Indeed the best performance provides an AUC near 1.0, which is higher than that found in the literature. We verify that the left ventral posterior cingulate cortex region is less connected to an area in the cerebellum of patients with this neurodevelopment disorder, which agrees with previous studies. The functional brain networks of autism spectrum disorder patients show more segregation, less distribution of information across the network, and less connectivity compared to the control cases. Our workflow provides medical interpretability and can be used on other fMRI and EEG data, including small data sets.}, subject = {Maschinelles Lernen}, language = {en} } @inproceedings{NickHockEmmerichetal.2015, author = {Nick, Christoph and Hock, Christina and Emmerich, Florian and Belle, Stefan and Thielemann, Christiane and Asmus, Tim and Loose, Thomas and Wienand, Karlheinz}, title = {Ultrathin gold as sensor platform for biomolecules}, series = {2015 International Conference on Manipulation, Manufacturing and Measurement on the Nanoscale (3M-NANO), Changchun, China}, booktitle = {2015 International Conference on Manipulation, Manufacturing and Measurement on the Nanoscale (3M-NANO), Changchun, China}, doi = {10.1109/3M-NANO.2015.7425462}, year = {2015}, abstract = {Due to the increasing number of diabetes patients worldwide there is an enormous need for accurate, fast and someday also continuous or even closed loop monitoring of blood glucose level. More than 50 years after Clark and Lyons proposed the first glucose enzyme electrodes this concept is still widely in use today. Most concepts use the enzyme glucose oxidase (GOx) that reacts with glucose. These reactions cause a current that is proportional to the amount of glucose present at the sensor. Thus, if the sample volume is known, the blood sugar level can be measured. Although these electrodes have been in use for so long they have the disadvantage of a limited shelf time. In this work we present an enzyme free approach for glucose detection applying ultrathin gold films. According to the basic Fuchs-Sondheimer-theory and other more sophisticated models the resistivity of ultrathin metal films is dominated by scattering effects at their surface. Chemical reactions at the metallic surface are expected to change the conductivity properties and thus these changes can be used to detect molecules. This can be done by creating a self-assembled monolayer at the gold surface. When molecules such as glucose bind to the end groups of this layer the electron scattering and thus the conductivity of the film is expected to change. Ultrathin gold films with a thickness of 6 nm show the largest relative change in resistivity and are thus the preferred film thickness for this application. These gold films show a significant change in resistance when model molecules sodium sulfide and dextran are present, whereas the resistance of a platinum reference electrode does not change significantly.}, subject = {Biosensor}, language = {en} } @inproceedings{EmmerichThielemann2015, author = {Emmerich, Florian and Thielemann, Christiane}, title = {Patterning of PMMA by gold-nanoparticle initiated localized decomposition}, series = {2015 International Conference on Manipulation, Manufacturing and Measurement on the Nanoscale (3M-NANO), Changchun, China}, booktitle = {2015 International Conference on Manipulation, Manufacturing and Measurement on the Nanoscale (3M-NANO), Changchun, China}, doi = {10.1109/3M-NANO.2015.7425480}, year = {2015}, abstract = {The need for manipulating matter at its smallest scale has been a hot topic in research for the last decades. As the final goal of arranging single atoms has been achieved, research focuses on two targets: firstly, improving the capabilities of existing technologies towards nanometer resolution and secondly, finding new methods for producing nanostructures in a fast and easy way. Here, we present a new maskless method for sub-micro-patterning of poly(methyl methacrylate) (PMMA) thin films. By applying atomic-force-microscope (AFM) assisted nano-xerography, electric charges were locally injected with an AFM-tip into PMMA. The resulting electrostatic patterns attracted charged gold-nanoparticles, which were selectively deposited onto the PMMA layers with lateral dimensions below 200 nm. In a second step, heat treatment at 275 °C initiated a selective decomposition of the PMMA layer, only observed in PMMA-areas covered with nanoparticles, whereas uncovered areas were not modified by the heat treatment. Analyzing the grooves with the AFM, we found that lines with a width in the sub-micrometer range to several micrometers have successfully been realized. We propose this new and promising method to manufacture nano-grooves used as masking for lift-off processes, for functionalization of underlying areas, or for micro-contact-printing.}, subject = {Polymethylmethacrylate}, language = {en} } @article{TrentThielemannMonici2024, author = {Trent, Davis and Thielemann, Christiane and Monici, Monica}, title = {How are cell and tissue structure and function influenced by gravity and what are the gravity perception mechanisms?}, series = {npj Microgravity}, volume = {2014}, journal = {npj Microgravity}, number = {10 / 16}, doi = {10.1038/s41526-024-00357-9}, pages = {1 -- 7}, year = {2024}, abstract = {Progress in mechanobiology allowed us to better understand the important role of mechanical forces in the regulation of biological processes. Space research in the field of life sciences clearly showed that gravity plays a crucial role in biological processes. The space environment offers the unique opportunity to carry out experiments without gravity, helping us not only to understand the effects of gravitational alterations on biological systems but also the mechanisms underlying mechanoperception and cell/tissue response to mechanical and gravitational stresses. Despite the progress made so far, for future space exploration programs it is necessary to increase our knowledge on the mechanotransduction processes as well as on the molecular mechanisms underlying microgravity-induced cell and tissue alterations. This white paper reports the suggestions and recommendations of the SciSpacE Science Community for the elaboration of the section of the European Space Agency roadmap "Biology in Space and Analogue Environments" focusing on "How are cells and tissues influenced by gravity and what are the gravity perception mechanisms?" The knowledge gaps that prevent the Science Community from fully answering this question and the activities proposed to fill them are discussed.}, subject = {Zellkultur}, language = {en} } @inproceedings{NickThielemannJoshietal.2011, author = {Nick, Christoph and Thielemann, Christiane and Joshi, Ravi and Schneider, J{\"o}rg}, title = {Niedrigtemperatur-Transfer von vertikal ausgerichteten Kohlenstoff Nanor{\"o}hren auf Mikrostrukturen}, series = {Mikro-Nano-Integration - 3. GMM-Workshop, Stuttgart, Deutschland, 2011}, booktitle = {Mikro-Nano-Integration - 3. GMM-Workshop, Stuttgart, Deutschland, 2011}, pages = {5}, year = {2011}, abstract = {Vertikal angeordnete Kohlenstoff Nanor{\"o}hren (engl. vertically aligned carbon nanotubes; VA-CNT) k{\"o}nnen seit einigen Jahren mit hoher Reproduzierbarkeit durch CVD-Verfahren bei 600 °C - 800 °C auf Katalysatorschichten aus Aluminium und Eisen hergestellt werden. Sie zeigen sehr gute Eigenschaften im Bereich der Feldemission, aber auch in sub-µm Vias. Allerdings sind die relativ hohen Temperaturen oft nicht prozesskompatibel und m{\"u}ssen vermieden werden um keine Degradation darunterliegender Strukturen in Kauf zu nehmen. Da die Reduzierung der CVD-Temperaturen beim Wachstum der VA-CNTs unter 600 °C zu hohen Defektraten f{\"u}hrt, schlagen wir ein neues Verfahren zum Transfer der VA-CNTs bei niedrigen Temperaturen vor. In einer Kombination aus Flip-Chip- und Stempel-Technik werden hoch geordnete, mikrostrukturierte VA-CNTs auf temperaturempfindliche Substrate aus Kalk-Natron-Glas, Gold oder Kupfer bei Temperaturen von 100 °C transferiert. Die vertikale Struktur der Nanor{\"o}hren bleibt dabei erhalten. Eine leitende Verbindung kann durch ein leitf{\"a}higes, bio-kompatibles Polymer gew{\"a}hrleistet werden, was eine Erweiterung des Einsatzbereichs auf Life-Science Applikationen erlauben w{\"u}rde.}, subject = {Kohlenstoff-Nanor{\"o}hre}, language = {de} }