ORCID

0000-0002-6833-9110

Date of Award

Fall 2025

Language

English

Embargo Period

11-28-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Nanoscale Science and Engineering

Program

Nanoscale Engineering

First Advisor

Susan Sharfstein

Committee Members

Yubing Xie, Nathaniel Cady, Thomas Kiehl

Keywords

Microelectrode Arrays, Electrophysiology, Flexible Devices, Brain Organoids, Self-folding, Biocompatibility

Subject Categories

Bioelectrical and Neuroengineering | Biomedical Devices and Instrumentation | Biophysics | Systems and Integrative Engineering

Abstract

Neurodegenerative diseases pose a formidable challenge in modern medicine, necessitating the development of advanced research tools that can elucidate their complex pathophysiology. Recent advancements in neurodegenerative disease research have led to the development of three-dimensional (3D) neurodegenerative organoids using human induced pluripotent stem cells (hiPSCs). These organoids closely mimic human brain architecture and functionality, providing a valuable tool for understanding complex diseases. Additionally, the ability to generate and study brain organoids consistently and in large quantities holds potential for a controlled in vitro setting and high-throughput drug screening. However, these models are complex systems requiring specialized maintenance, analysis, and manipulation techniques. Electrophysiology is a key method for studying neural activity. Microelectrode arrays (MEAs) are essential tools for recording and stimulating electrical signals from multiple neurons at once. Typically, traditional two-dimensional (2D) MEAs are well-established for in vitro studies; however, they are not suitable for modern 3D cell cultures, such as organoids. Applying 2D MEAs to 3D samples often requires compressing or slicing the tissue, which results in the 3D culture flattening and losing its original structure. Therefore, the development of new technologies, such as conformal MEAs, plays a pivotal role in advancing in-vitro brain organoid research. This work initially investigates the interface between neuronal cells and typical electronic materials. We evaluate the biocompatibility of materials that are potential candidates for use in devices that interface with neuronal cells. Biocompatibility refers to the ability of these materials to interact with living cells and tissues without causing an adverse response. Therefore, the biocompatibility of these materials used in electronic devices is crucial for the development of implantable devices, as well as in vitro biodevices, such as pacemakers, neuroprosthetics, microelectrode arrays, and future biomanufacturing applications. Here, we assessed the biocompatibility of a collection of diced silicon chips coated with a variety of metal thin films, interfacing them with different cell types, including murine mastocytoma cells in suspension culture, adherent NIH 3T3 fibroblasts, and hiPSC-derived neural progenitor cells (NPCs). All materials tested were biocompatible and showed potential to support the neural differentiation of hiPSC-NPCs, creating an opportunity to utilize these materials in the scalable production of a range of biohybrid devices, such as electronic devices, for studying neural behaviors and neuropathies. Moreover, we developed a 3D Flexible, Self-folding Microelectrode Array (FSMEA) device, comprised of a bilayer of polyimide and SU-8 photoresist, or an SU-8/SU-8 bilayer, which utilizes the strain differences between two layers to drive self-assembly. Our studies have demonstrated that FSMEA devices can effectively record spontaneous action potentials and local field potentials in two types of 3D tissues, cortical organoids ranging from 800 to 1,500 µm in diameter, and human elongating multi-lineage organized cardiac (EMLOC) gastruloids. These FSMEAs represent a new class of strain-based 3D MEA devices, leading to a versatile platform for minimally invasive interrogation of complex 3D tissue dynamics. By leveraging their intrinsic ability to self-assemble, these devices enable intimate, conformal contact with heterogeneous organoid surfaces, thereby improving spatial coverage without compromising tissue integrity.

License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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