Research and Thesis Projects

Measurement of transepithelial electrical resistance (TEER) is a widely used method to assess tight junction integrity in in vitro barrier models without compromising tissue viability. While several commercial systems exist, they are primarily designed for static culture formats such as Transwell inserts and are not suited for continuous, real-time monitoring of barrier responses under dynamic conditions. As part of the **NCCR AntiResist** consortium, we have developed a novel microfluidic platform (https://doi.org/10.1002/admt.202400326) that enables the transition of transwell-grown epithelial tissues from static to perfused environments. This allows for more physiologically relevant modeling of human tissues. The device is currently used to study stem cell-derived bladder models in the context of urinary tract infections (UTIs), where pathogen invasion can lead to varying degrees of barrier disruption, modulated by therapeutic intervention. Current methods for assessing barrier function rely on: - **High-resolution confocal microscopy** - **Permeability assays using fluorescent tracers** While informative, these approaches provide only discrete, time-point-specific data. To overcome this limitation and enhance temporal resolution, we have integrated a prototype impedance-based TEER sensor into the microfluidic chip for continuous, non-invasive monitoring of barrier integrity: https://doi.org/10.1109/SENSORS60989.2024.10785013 The focus of this project is the **further development and validation** of this integrated TEER system, including: - **Electrode design optimization**: Refine electrode geometry, spacing, and materials to maximize signal sensitivity, stability, and compatibility with fluidic environments. - **System characterization under biological conditions**: Evaluate sensor performance using tissue models with both intact and compromised barrier function under varying flow rates, media conditions, and treatment regimens. - **Validation against standard assays**: Benchmark impedance-based readouts against traditional techniques (e.g., confocal imaging, permeability assays) to ensure biological relevance. - **Implementation in infection models**: Replicate infection protocols with uropathogenic *E. coli* under perfusion, and quantify real-time changes in barrier integrity during infection and recovery with therapeutics. - **Development of a robust data analysis pipeline** This is an **interdisciplinary project**, offering hands-on experience in: - Mammalian cell and tissue culture (including stem-cell-derived epithelial models) - Microfabrication and cleanroom techniques - Electrical measurements and sensor integration - Bacterial infection assays under dynamic flow - Advanced microscopy - Data analysis and visualization **Preferred background** (at least two of the following): - Solid understanding of electronics or signal processing - Programming experience (Python, MATLAB) - Experience in microfabrication or cleanroom work

- Design and fabricate TEER sensors compatible with integration into microfluidic chips - Characterize the electrical performance and sensitivity of the integrated sensors - Use the system to monitor cellular barrier formation and disruption in real-time - Develop and implement a method for analyzing multi-frequency TEER data to extract biologically meaningful parameters

akurmashev@ethz.ch odysseas.chaliotis@bsse.ethz.ch

We offer a master thesis project centered on the use of in vitro neuronal cultures to study neuronal communication through advanced imaging techniques, including electrical and optical imaging. The aim is to develop and apply imaging-based methods to visualize and quantify neuronal activity, with a focus on understanding network dynamics and synaptic interactions. The project includes: - Culturing and maintaining neuronal cells under controlled conditions - Implementing and optimizing imaging protocols (e.g., live-staining, confocal microscopy, microelectrode arrays) - Developing analytical pipelines for quantifying neuronal activity and connectivity - Potential integration with computational tools for image and signal analysis This project is well-suited for students in biology, biotechnology, biomedical engineering, or related fields. Prior experience in cell culture, microscopy, or image analysis is advantageous but not mandatory. The scope and focus of the project will be tailored to the candidate’s background and interests. You will work in a collaborative research environment with access to state-of-the-art imaging facilities and mentorship from experienced scientists. The project is based in **Basel** and is available for master’s thesis and semester projects throughout the year.

Dr. Fernando Cardes | fernando.cardes@bsse.ethz.ch

We are offering several projects centered around the in vitro culture of neurons on CMOS microelectrode arrays (MEAs). These high-density MEAs allow for detailed, non-invasive recordings of neuronal activity, enabling the study of network dynamics, development, and responses to stimuli or pharmacological agents. The projects are ideal for students with a background in biology, biotechnology, biomedical engineering, or related fields. Prior experience in sterile techniques and cell culture is highly desirable. Depending on your interests and skills, your project may involve: - Optimizing neuronal culture protocols on CMOS MEAs - Long-term monitoring of neuronal development and activity - Pharmacological modulation of network behavior - Data analysis of electrophysiological recordings - Integration with imaging or stimulation techniques You will work in a collaborative and supportive environment with access to state-of-the-art facilities and mentorship from experienced researchers. The specific research question and methods will be defined together with you, allowing for a personalized and meaningful research experience. The position is located in **Basel** and is available for master's thesis and semester projects throughout the year.

Dr. Fernando Cardes | fernando.cardes@bsse.ethz.ch

CMOS microelectrode arrays allow studying the electrical activity of neurons. In-vitro neural networks can be cultured on top of thousands of very small electrodes (<10um), which can detect action potentials from hundreds of neurons simultaneously. The student will develop an FPGA-based platform to expand the capabilities of our CMOS microelectrode arrays, allowing real-time spike detection and massive stimulation of neurons. Since most of the hardware required for the platform is already available, the student will focus on developing different algorithms in VHDL. Minor wet-lab tasks with neurons would be ideally included in the project, in order to test the developed algorithms. Depending on the experience and interests of the student, the development of other algorithms in C++/Python can be included as part of the project. The position is located in Basel and is available for master's thesis and semester projects throughout the year. Part-time remote work arrangements can be discussed.

Dr. Fernando Cardes | fernando.cardes@bsse.ethz.ch

In vitro studies using high-density CMOS microelectrode arrays (MEAs) enable groundbreaking insights into the functioning of neural networks outside the living body. These advanced tools provide unparalleled spatial and temporal resolution, allowing researchers to: - Study Neural Dynamics: Precisely observe neuronal behavior, connectivity, and activity in controlled environments. - Advance Drug Discovery: Test drug efficacy and safety in vitro before progressing to in vivo studies. - Understand Neurological Disorders: Explore the mechanisms underlying conditions such as epilepsy, neurodegeneration, and psychiatric disorders. High-density CMOS MEAs play a vital role in capturing complex neural signals with high fidelity. Advanced software solutions are essential for enabling key functionalities, such as allowing experimenters to select specific areas of neural tissue for study, or visualizing neuronal signals in real time. **Key Responsibilities** - Develop, optimize, and maintain software for in vitro neural studies using CMOS MEAs. - Implement algorithms for real-time neural data acquisition, processing, and visualization. - Enhance usability and functionality of software for researchers conducting experiments. - Collaborate with neuroscientists and engineers to align software with research needs. - Create clear, user-friendly documentation for software tools and workflows. **Requirements** - Proficiency in Python; C++ and conda knowledge is a plus. - Strong documentation skills for clear, user-friendly guides. - Effective communication and teamwork for interdisciplinary collaboration. **Location & Application** This internship is for a 6-month duration, with flexible options for remote or on-site work (in Basel, Switzerland) based on project requirements and candidate preferences. Applicants should submit a CV highlighting relevant experience in software development, including any portfolio or repository links (e.g., GitHub) if available. Additionally, please include information about availability, specifying when you would be ready to start. While the position is open immediately, the actual start date will depend on administrative processes. Incomplete applications will not be considered. This project is also available as Master thesis or semester project.

Dr. Fernando Cardes fernando.cardes@bsse.ethz.ch