Research and Thesis Projects

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 MATLAB 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. 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 available as Master thesis or semester project.

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

High-density CMOS MEAs are versatile tools used in neuroscience that high-resolution recordings of neural activity. To fully leverage these capabilities, custom PCBs are required to manage high-speed data transfer, power delivery, and signal routing. This project focuses on: - Designing PCBs to interface with CMOS MEAs for neural signal acquisition. - Ensuring signal integrity and minimizing noise in high-speed circuits. - Validating and testing boards in lab environments. Requirements - Experience with PCB design tools (Altium preferred). - Understanding of high-speed electronics and signal integrity. - Strong documentation and communication skills. - Ability to work independently and in teams.

Dr. Fernando Cardes

Digital signature circuits are used to verify authenticity, ensure data integrity, and prevent tampering in applications ranging from secure boot to hardware-based identity verification. This project offers the opportunity to design and evaluate such a circuit with the goal of integrating it into a chip. The student will begin by exploring various interpretations of what a signature circuit can be, considering both functional and architectural perspectives. While the final implementation may include standard cryptographic components such as SHA-256 for hashing and RSA for public-key encryption, the exact structure is open to exploration. The student is expected to propose and justify a design that balances performance, area, power consumption, and security. A key part of the project will be the evaluation of security, including resistance to side-channel attacks and fault injection. The student will also consider how the circuit fits into a broader chip architecture, including synthesis, layout constraints, and key management. This is a hands-on project that combines digital design, cryptographic engineering, and hardware security. It is ideal for students with an interest in secure systems, embedded hardware, and low-level cryptographic implementation.

Dr. Fernando Cardes

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

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)

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

Advances in human iPSC technology have revolutionised our ability to interrogate mechanisms underlying neurodevelopmental disorders (NDDs) in human cellular models that retain individual genetic signatures. To fully harness this potential, we need robust, reliable high-throughput screening methods and unbiased, biologically meaningful phenotypic readouts. Building on recently published work (DOI: 10.1126/science.adn612), we will combine TF–based forward programming of human iPSCs into neurons with functional screening on HD-MEAs. TF-based programming to obtain induced glutamatergic neurons (iGluta; via NGN2) or GABAergic neurons (iGABA; via ASCL1/DLX2) is highly reproducible, yields defined neuronal subtypes, and requires only a relatively short differentiation period to achieve functional maturity. These features offer major advantages for disease modelling over traditional differentiation protocols and allow systematic genotype–phenotype mapping in functionally intact human neurons. In this project, we will integrate TF-based protocols with CRISPR/Cas9 genome editing to introduce a panel of ASD-related mutations into iGluta/iGABA co-cultures and quantify their functional consequences.

Develop an inducible CRISPR/Cas9 knock-out system We will establish dual-inducible iPSC lines that harbour inducible TFs (NGN2 for iGluta; ASCL1-DLX2 for iGABA), and an inducible Cas9 nuclease, each driven by distinct promoters. We will begin with iGluta/NGN2 lines to enable temporally controlled perturbations in induced neurons. Perform functional phenotypic screening We will plate patterned iGluta/iGABA co-cultures at defined ratios on HD-MEAs and introduce gRNAs via lentiviral transduction. As an initial proof-of-principle, we will conduct an array-format screen targeting ~10 selected ASD-risk genes. We will then carry out longitudinal, high-content electrophysiology on multi-well HD-MEAs to characterise emerging phenotypes at the single-cell level (e.g., firing rate, waveform features) and the network level (e.g., connectivity metrics). Post-hoc immunohistochemistry and single-cell gene expression analysis will link functional readouts to molecular identity. The resulting methodology will deliver advanced in vitro models for high-throughput, deep phenotyping. This work will support a more generalisable understanding of ASD pathophysiology, including deficits in synaptic transmission and excitability. The ideal candidate has a background in neuroscience, biology, physics, or a related field, and is motivated to learn new experimental techniques as well as computational analysis. Minimum project duration: 6 months.

Applicants should submit a brief letter of motivation and an up-to-date CV to Dr. Manuel Schröter (manuel.schroeter@bsse.ethz.ch), Aayush Marishi (aayush.marishi@bsse.ethz.ch), and Benedikt Eisinger (benedikt.eisinger@bsse.ethz.ch). Please do not hesitate to get in contact, if you have any queries.

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