@article{CibaPetzoldAlvesetal.2025, author = {Ciba, Manuel and Petzold, Marc and Alves, Caroline L. and Rodrigues, Francisco A. and Jimbo, Yasuhiko and Thielemann, Christiane}, title = {Machine learning and complex network analysis of drug effects on neuronal microelectrode biosensor data}, series = {Scientific Reports}, volume = {15}, journal = {Scientific Reports}, number = {1}, publisher = {Springer Science and Business Media LLC}, issn = {2045-2322}, doi = {https://doi.org/10.1038/s41598-025-99479-7}, year = {2025}, abstract = {Biosensors, such as microelectrode arrays that record in vitro neuronal activity, provide powerful platforms for studying neuroactive substances. This study presents a machine learning workflow to analyze drug-induced changes in neuronal biosensor data using complex network measures from graph theory. Microelectrode array recordings of neuronal networks exposed to bicuculline, a GABA \$\$_A\$\$ receptor antagonist known to induce hypersynchrony, demonstrated the workflow's ability to detect and characterize pharmacological effects. The workflow integrates network-based features with synchrony, optimizing preprocessing parameters, including spike train bin sizes, segmentation window sizes, and correlation methods. It achieved high classification accuracy (AUC up to 90\%) and used Shapley Additive Explanations to interpret feature importance rankings. Significant reductions in network complexity and segregation, hallmarks of epileptiform activity induced by bicuculline, were revealed. While bicuculline's effects are well established, this framework is designed to be broadly applicable for detecting both strong and subtle network alterations induced by neuroactive compounds. The results demonstrate the potential of this methodology for advancing biosensor applications in neuropharmacology and drug discovery.}, subject = {Maschinelles Lernen}, language = {en} } @article{KrstićJuettnerGiegerichetal.2023, author = {Krstić, Nenad and J{\"u}ttner, Jens and Giegerich, Lars and Mayer, Margot and Knuth, Monika and M{\"u}ller, Achim and Thielemann, Christiane}, title = {3D printed biosensor for continuous glucose measurement in cell cultures}, series = {Annals of 3D Printed Medicine}, volume = {10}, journal = {Annals of 3D Printed Medicine}, publisher = {Elsevier BV}, issn = {2666-9641}, doi = {doi.org/10.1016/j.stlm.2023.100111}, year = {2023}, subject = {Biosensor}, language = {en} } @article{ThielemannKrstićJuettneretal.2023, author = {Thielemann, Christiane and Krstić, Nenad and J{\"u}ttner, Jens and Giegerich, Lars and Mayer, Margot and Knuth, Monika and M{\"u}ller, Achim}, title = {3D printed biosensor for continuous glucose measurement in cell cultures}, series = {Annals of 3D Printed Medicine}, volume = {2023}, journal = {Annals of 3D Printed Medicine}, number = {-}, doi = {https://doi.org/10.1016/j.stlm.2023.100111}, pages = {- -- -}, year = {2023}, abstract = {A novel 3D-printed glucose sensor is presented for cell culture application. Glucose sensing was performed using a fluorescence resonance energy transfer (FRET)-based assay principle based on ConA and dextran. Both molecules are encapsulated in alginate microspheres and embedded in the UV-curable, stable hydrogel polyvinyl alcohol (PVA). The rheology of the formulation was adapted to obtain good properties for an extrusion-based printing process. The printed sensor structures were tested for their ability to detect glucose in vitro. A proportional increase in fluorescence intensity was observed in a concentration range of 0 - 2 g/L glucose. Tests with HEK cell cultures also showed good cell compatibility and excellent adhesion properties on plasma-treated Petri dishes. The printed sensors were able to detect the glucose decay associated with the metabolic activities of the fast-growing HEK cells in the cell culture medium over ten days. The proof-of-principle study shows that metabolic processes in cell cultures can be monitored with the new printed sensor using a standard fluorescence wide-field microscope.}, subject = {Biosensor}, language = {en} } @article{FlachsEtzelMayeretal.2022, author = {Flachs, Dennis and Etzel, Johannes and Mayer, Margot and Harbecke, Frederic and Belle, Stefan and Rickmeyer, Tim and Thielemann, Christiane}, title = {Characterization of electrically conductive, printable ink based on alginate hydrogel and graphene nanoplatelets}, series = {Biomedical Engineering Advances}, volume = {2022}, journal = {Biomedical Engineering Advances}, number = {4}, doi = {https://doi.org/10.1016/j.bea.2022.100045}, pages = {1 -- 2}, year = {2022}, abstract = {In recent years, there has been an increasing interest in electrically conductive hydrogels for a wide range of biomedical applications, like tissue engineering or biosensors. In this study, we present a cost-effective conductive hydrogel based on alginate and graphene nanoplatelets for extrusion-based bioprinters. The hydrogel is prepared under ambient conditions avoiding high temperatures detrimental for cell culture environments. Investigation of the hydrogel revealed a conductivity of up to 7.5 S/cm, depending on the ratio of platelets. Furthermore, in vitro tests with human embyronic kidney cells - as an example cell type - showed good adhesion of the cells to the surface of the conductive hydrogel. Electrochemical measurements revealed a low electrode impedance which is desirable for the extracellular recording, but also low electrode capacitance, which is unfavorable for electrical stimulation purposes. Therefore, future experiments with the graphene nanoplatelets-based hydrogels will focus on electrodes for biosensors and extracellular recordings of neurons or cardiac myocytes.}, subject = {Hydrogel}, 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} } @article{FlachsCiba2016, author = {Flachs, Dennis and Ciba, Manuel}, title = {Cell-based sensor chip for neurotoxicity measurements in drinking water}, series = {L{\´e}kař a technika - Clinician and Technology}, volume = {46}, journal = {L{\´e}kař a technika - Clinician and Technology}, number = {2}, pages = {46 -- 50}, year = {2016}, abstract = {Our drinking water contains residues of pharmaceuticals. A sub-group of these contaminants are neuro-active substances, the antiepileptic carbamazepine being one of the most relevant. For assessment of the neurotoxicity of this drug at a sub-therapeutic level, a cell-based sensor chip platform has been realized and characterized. For this purpose, a microelectrode array chip was designed and processed in a clean room and optimized in terms of low processing costs and good recording properties. For characterization of the system neuronal cells were plated on microelectrode array chips and electrical activity was measured as a function of applied carbamazepine concentration. We found that the relative spike rate decreased with increasing drug concentration resulted in IC50 values of around 36 μM. This value is five orders of magnitude higher than the maximal dose found in drinking water. IC50 values for burst rate, burst duration and synchrony were slightly higher, suggesting spike rate being a more sensitive parameter to carbamazepine.}, subject = {Mikroelektrode}, language = {en} } @phdthesis{Daus2013, author = {Daus, Andreas}, title = {Zellbasierte Biosensoren - Hybride Systeme aus dreidimensionalen in vitro Netzwerken und Mikroelektroden Arrays}, school = {Technische Hochschule Aschaffenburg}, year = {2013}, abstract = {Mit der Entwicklung hybrider Strukturen aus Mikroelektroden Arrays und dreidimensionalen Sph{\"a}roiden wurde in dieser Arbeit ein funktionaler, deskriptiver Ansatz der Biosensorik adressiert. W{\"a}hrend biochemische Sensoren ausschließlich analytische Informationen {\"u}ber die Wechselwirkung von Liganden und Rezeptoren liefern, erlauben zellbasierte Biosensoren eine physiologische Beschreibung biologischer Systeme in nativen bzw. chemisch oder physikalisch provozierten Zust{\"a}nden. Dies impliziert f{\"u}r Anwendungen der Pharmakologie, Toxikologie und Grundlagenforschung hohes Potenzial, evoziert jedoch eine multidisziplin{\"a}re Aufgabe. Es werden zum einen in vitro Systeme ben{\"o}tigt, die den Anspr{\"u}chen eines physiologisch repr{\"a}sentativen Abbilds eines Organismus gen{\"u}gen. Zum anderen sind technische Systeme erforderlich, die Zellreaktionen qualitativ und quantitativ verwertbar machen.}, subject = {Array}, language = {de} } @inproceedings{DausBestelThielemann2014, author = {Daus, Andreas and Bestel, Robert and Thielemann, Christiane}, title = {A multivariate spike-detection algorithm to assess activity patterns of three-dimensional in vitro models}, series = {MEA Meeting 2014, Reutlingen, Germany}, volume = {2014}, booktitle = {MEA Meeting 2014, Reutlingen, Germany}, issn = {2199-1596}, pages = {194 -- 195}, year = {2014}, subject = {Mikroelektrode}, language = {en} } @article{DausThielemann2010, author = {Daus, Andreas and Thielemann, Christiane}, title = {Spheroids on microelectrode arrays: A highly sensitive system for biosensing applications}, series = {European Journal of cell biology}, journal = {European Journal of cell biology}, number = {89 Sonderheft 1}, pages = {67 -- 68}, year = {2010}, subject = {Array}, language = {en} } @inproceedings{DausGoldhammerThielemann2010, author = {Daus, Andreas and Goldhammer, Michael and Thielemann, Christiane}, title = {Using three-dimensional cell culture systems on Microelectrode arrays for biosensing applications}, series = {7th international Meeting on subtrate-intergrated microelectrode arrays, Reutlingen}, booktitle = {7th international Meeting on subtrate-intergrated microelectrode arrays, Reutlingen}, isbn = {978-3-938345-08-5}, pages = {314 -- 315}, year = {2010}, subject = {Array}, language = {en} } @article{PaxRiegerThielemannetal.2005, author = {Pax, Markus and Rieger, Janosch and Thielemann, Christiane and Johannsmann, Diethelm}, title = {Cell-Based Biosensors for Drug Screening: Detection of the Beating Rate of Cardiac Myocytes with a Quartz crystal Resonator}, series = {Analyst}, volume = {130}, journal = {Analyst}, pages = {1451 -- 1458}, year = {2005}, subject = {Biosensor}, language = {en} } @article{DausLayerThielemann2012, author = {Daus, Andreas and Layer, Paul and Thielemann, Christiane}, title = {A spheroid-based biosensor for the label-free detection of drug-induced field potential alterations}, series = {Sensors and actuators B: Chemical}, volume = {165}, journal = {Sensors and actuators B: Chemical}, number = {1}, doi = {10.1016/j.snb.2012.02.011}, pages = {53 -- 58}, year = {2012}, subject = {Biosensor}, language = {en} } @article{Daus2012, author = {Daus, Andreas}, title = {Leben auf dem Mikrochip - Biosensoren auf der Basis von Mikroelektroden-Arrays}, series = {Labor \& More}, volume = {2012}, journal = {Labor \& More}, number = {8}, pages = {20 -- 24}, year = {2012}, subject = {Biosensor}, language = {de} } @inproceedings{ObmannPoltLooseetal.2013, author = {Obmann, Julia and Polt, Christopher and Loose, Thomas and Asmus, Tim and Wienand, Karlheinz and Thielemann, Christiane}, title = {Novel Resistive Bioaffinity Sensor based on Ultra-Thin Gold Films}, series = {3rd International Conference on Bio-Sensing Technology 2013, Sitges, Spain}, booktitle = {3rd International Conference on Bio-Sensing Technology 2013, Sitges, Spain}, year = {2013}, subject = {Biosensor}, language = {en} }