Research and Thesis Projects

**Project overview** One of the biggest barriers for therapeutic development for central nervous system diseases is the blood-brain barrier (BBB). This highly selective and tightly regulated interface protects the brain from harmful substances while controlling the transport of essential molecules. However, its complexity poses significant challenges for both drug delivery and in vitro modeling. Organ-on-chip technology offers a promising approach to replicate the structural and functional intricacies of human organs, including the BBB, in a controlled laboratory setting. While recent advances have enabled the recreation of basic BBB components and physiological flow conditions, accurately capturing the full spectrum of multicellular interactions - particularly those involving the immune system - remain an ongoing challenge. In vivo, the BBB is not only a physical barrier but also a dynamic immunological interface, influenced by constant communication between endothelial cells, astrocytes, pericytes, and the resident immune cells, microglia. This 6-month internship project focuses on the characterization of these multicellular interactions within an immunocompetent BBB-on-chip platform. Using a microfluidic device engineered to mimic the brain microvasculature, the study will investigate how cellular crosstalk influence barrier integrity under physiological conditions. This work aims to advance our understanding of neuroimmune dynamics and contribute to the development of more predictive models for CNS drug testing and disease research. **Main objectives:** • Characterize morphological and functional properties of individual cell types and their interactions using immunostaining and gene expression analysis. • Quantify junctional integrity (e.g., tight junction proteins: ZO-1, claudin-5). • Study immune-cell behavior (microglia activation status, communication with endothelium) under steady-state conditions. Ideal candidate: We are looking for a highly motivated and curious student with a strong interest in neurobiology, immunology, tissue engineering, or organ-on-chip systems. Given the complexity of the project, the ideal candidate should be comfortable working in a multidisciplinary environment that bridges microfluidics, cell biology, and immunological techniques. A hands-on mindset, willingness to troubleshoot, and a proactive approach to experimental work are essential. **Educational Background (preferred but not exclusive):** • Biomedical Engineering, Bioengineering, Immunology, Cell Biology, or related fields. • Prior laboratory experience (e.g., internships, academic projects) in cell culture, immunostaining, or microfluidics is an asset. • Prior experience with human induced pluripotent stem cell (hiPSC) or 3D cell models handling is a plus. **Personal Qualities:** • Strong attention to detail and excellent organizational skills. • Ability to work independently while contributing to a collaborative research environment. • Enthusiastic, communicative, and eager to learn new methodologies. **Skills to Be Acquired:** • Co-culture of primary human cell types (astrocytes and pericytes). • Handling and operation of organ-on-chip microfluidic platforms. • Immunofluorescence microscopy for cellular interaction and barrier integrity analysis. • Quantitative image analysis and biological data interpretation. • Protocol development and optimization for imaging and quantification of cellular crosstalk. • Scientific communication, data presentation, and collaborative research practices. **Requirements** • Currently enrolled in a BSc/MSc program in biomedical engineering, bioengineering, biotechnology, immunology, cell biology, or related fields. • Availability for a full-time internship of 6 months (flexible starting date, ideally from September 1st). • Basic knowledge of cell biology and/or tissue engineering, with familiarity with 3D cell culture being a plus. • Comfortable working in a laboratory environment, including handling pipettes, microscopes, and sterile technique. • Fluent in English (working language of the lab); good communication skills are essential. • Motivated to work at the interface of engineering and biology, with a proactive attitude toward problem-solving. **Labels:** Semester Project , Internship , Master Thesis. **Location and Application:** This is a 6 month internship, with flexible options for combining dry and wet lab (in the BSSE department, Basel, Switzerland) based on the project requirements and preferences. Applicants should submit a CV highlighting relevant laboratory experience lab. 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. This project is also available as a Master thesis or semester project. **Relevant literature**: Wei W, Cardes F, Hierlemann A, Modena MM. 3D In Vitro Blood-Brain-Barrier Model for Investigating Barrier Insults. Adv Sci (Weinh). 2023 Apr;10(11):e2205752. doi: 10.1002/advs.202205752. Epub 2023 Feb 13. PMID: 36782313; PMCID: PMC10104638. Obermeier B, Daneman R, Ransohoff RM. Development, maintenance and disruption of the blood-brain barrier. Nat Med. 2013 Dec;19(12):1584-96. doi: 10.1038/nm.3407. Epub 2013 Dec 5. PMID: 24309662; PMCID: PMC4080800. Hajal C, Offeddu GS, Shin Y, Zhang S, Morozova O, Hickman D, Knutson CG, Kamm RD. Engineered human blood-brain barrier microfluidic model for vascular permeability analyses. Nat Protoc. 2022 Jan;17(1):95-128. doi: 10.1038/s41596-021-00635-w. Epub 2022 Jan 7. PMID: 34997242.

• Characterize morphological and functional properties of individual cell types and their interactions using immunostaining and gene expression analysis. • Quantify junctional integrity (e.g., tight junction proteins: ZO-1, claudin-5). • Study immune-cell behavior (microglia activation status, communication with endothelium) under steady-state conditions.

Contact details: Catarina M. Gomes: catarina.monteiro@bsse.ethz.ch Organization: Bio Engineering Laboratory Host: Catarina M. Gomes, Mario M. Modena

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

This internship aims to develop a microfluidic device with a micropatterned hydrogel channel that mimics tubular structures like the kidney’s proximal tubule. The goal is to recreate key microenvironmental cues—such as 3D architecture and ECM—to support cell growth and function. The student will be responsible for: 1. Designing, fabricating, and optimizing a microfluidic chip tailored for hydrogel patterning. 2. Establishing a reliable protocol to form curved hydrogel microchannels within the device. 3. Culturing human proximal tubule epithelial cells inside the channel and assessing cell behavior and biocompatibility. 4. Characterizing the chip and cellular outcomes using advanced microscopy techniques, including immunofluorescence. This project lies at the intersection of bioengineering, microfabrication and cell biology, and offers a unique opportunity to contribute to the next generation of organ-on-chip platforms. Ideal Candidate: We are looking for a highly motivated student with a strong interest in tissue engineering, biomaterials, or microfluidics. The ideal candidate is curious, hands-on, and eager to learn both experimental and design techniques. **Educational background (preferred but not exclusive**): - Biomedical engineering, bioengineering, biology, materials science, or related fields - Previous lab experience (academic or internship) is a plus **Personal qualities**: - Attention to detail and good organizational skills - Ability to work independently while being part of a collaborative team - Proactive and communicative **Skills to Be Acquired**: - Microfluidic device design using CAD software (e.g., Fusion 360 or AutoCAD) - Microfabrication techniques, including laser cutting - ECM-like hydrogel patterning - Mammalian cell culture techniques, particularly with epithelial primary cells - Fluorescence and immunofluorescence microscopy for biological characterization - Protocol development, experimental troubleshooting, and data analysis - Scientific communication and presentation of experimental findings **Requirements** - Currently enrolled in a BSc/MSc program in biomedical engineering, bioengineering, materials science, biophysics, biotechnology, or a related field. - Availability for a full-time internship of 6 months (starting date from July, 1st). - Basic knowledge of cell biology and/or tissue engineering, ideally with familiarity in 2D or 3D cell culture. - Comfortable working in a laboratory environment, including handling pipettes, microscopes, and aseptic laboratory techniques. - Basic computer-aided design (CAD) knowledge or willingness to quickly learn software for microfluidic chip design (e.g., Fusion 360, SolidWorks, or AutoCAD). - Fluent in English (working language of the lab **Location and Application** This is a 6-month internship, with flexible options for combining dry and wet lab (in the BSSE department, Basel, Switzerland) based on the project requirements and preferences. Applicants should submit a CV highlighting relevant laboratory experience lab. 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. This project is also available as Master thesis or semester project. **Relevant literature** - Herland A, van der Meer AD, FitzGerald EA, Park T-E, Sleeboom JJF, Ingber DE (2016) Distinct Contributions of Astrocytes and Pericytes to Neuroinflammation Identified in a 3D Human Blood- Brain Barrier on a Chip. PLoS ONE 11(3): e0150360. - G Valverde, M et al. (2024) Thermoforming for Small Feature Replication in Melt Electrowritten Membranes to Model Kidney Proximal Tubule. Advanced Healthcare Materials 14(1): 2401800

Host: Marta G Valverde (marta.g.valverde@bsse.ethz.ch), Mario M Modena Earliest start: 01-07-2025 Organization: Bio Engineering Laboratory (Hierlemann AG)

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

Neural interfaces are aimed at creating links between neurons and computers, enabling advanced electrophysiology studies and opening paths to restoring lost functions in the nervous system. CMOS technology allows for low-noise recording from thousands of electrodes in parallel, either in-vitro or in-vivo. We are developing CMOS neural interfaces integrating different functionalities, including the detection of action potentials, stimulation of neurons, or impedance imaging. In this context, we can offer Master theses and semester projects tailored to the experience and interests of the student. These project may be, for example: - Design of the analog front-end for a CMOS neural interface in 180nm. This may include the design of low-noise amplifiers, filters, analog to digital converters, sigma-delta modulators, etc. Potential tasks would be: system design, circuit design and simulation, noise/power/area optimization, layout, parasitics extraction, post-layout simulations. - Design of a LVDS buffer for high-speed (>1Gbps) communication between the neural interface and the PC. Potential tasks would be: circuit design and simulation, speed/power optimization, LVDS receiver selection, PCB design. - Design of the on-chip digital signal processing and control logic. Potential tasks would be: VHDL/Verilog coding, synthesis, place and route, area/power optimization, simulation. Students interested in PCB design, programming or signal processing are also encouraged to contact me for other possible projects. 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)

Neural interfaces are aimed at creating links between neurons and computers, enabling advanced electrophysiology studies and opening paths to restoring lost functions in the nervous system. CMOS technology allows for low-noise recording from thousands of electrodes in parallel, either in-vitro or in-vivo. We are developing CMOS-based neural interfaces integrating different functionalities, including the detection of action potentials, stimulation of neurons, and impedance imaging. This instruments require real-time communication with a host computer, which is achieved combining FPGAs and System on a Chip. The backbone of the system is already implemented and tested, but there are multiple functionalities that need to be implemented to fully exploit the capabilities of our CMOS neural interfaces. In this Master thesis or semester project, the student will learn about CMOS technology and embedded systems, understand the existing solution, and develop different software tools to enable new electrophysiological studies. This project requires some previous experience with **Python and C++**. Basic knowledge of VHDL is advantageous, but not required. 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)

This project involves the precise manufacturing of microelectrode arrays designed to interact with neural tissues at a microscale level. Different microfabrication techniques will be utilized to engineer highly sensitive electrodes with dimensions below 10 um. We seek to explore novel methods and materials to enhance the functionality and biocompatibility of these neural interfaces. Students engaged in this project will delve into the process of designing, fabricating, and characterizing microelectrodes. Additionally, the development of specialized techniques for neural stimulation and imaging using these interfaces can be integrated into the scope of the project, aligning with the interests and skills of the student. The research offers opportunities for Master's theses or semester projects tailored to the individual's background and expertise. We welcome enthusiastic students from various disciplines, including nanotechnology, mechanical engineering, biomedical engineering, materials science, electrical engineering and related fields. Prior experience or familiarity with cleanroom protocols and semiconductor processing techniques is considered advantageous for this project, but it is not a mandatory requirement. The minimum duration of the project is 6 months. The cleanroom is located in Basel.

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