Organ-on-e-Chip: 3D Self-Rolled Biosensor Array for Electrical Interrogations of Electrogenic Spheroids

Abstract

Cell-cell communication plays a pivotal role in the coordination and function of biological systems. Three-dimensional (3D) cellular constructs provide venues to explore cellular communication for tissue development and drug discovery, as their 3D architecture mimics native in vivo microenvironments. Cellular electrophysiology (EP) is a prevalent signaling paradigm for studying electroactive cells. Currently, electrophysiological studies do not provide direct, multisite, simultaneous investigation of tissues in 3D. In this thesis, a controlled 3D assembly of biosensors was achieved via self-rolling. The 3D self-rolled biosensor arrays (3D-SR-BAs) were fabricated with customized geometries, designed to tightly interface 3D cellular constructs of varied sizes. The geometric arrangement of the sensors on the array provided a high spatial resolution in such a way that the electrical signal from individual cells can be recorded. 3D-SR-BA platform was shown to accommodate different sensor types: active field-effect transistors and passive microelectrodes. 3D-SR-BAs were interfaced with a few models of 3D-cultured constructs: human cardiac spheroids, human cardiac tissues, and rat cortical spheroids. The arrays provided continuous and stable multiplexed recordings of extracellular potentials with high sensitivity and spatiotemporal resolution, supported with simultaneous calcium imaging. The approach established in this work enabled EP investigation and monitoring of the complex signal transduction in 3D cardiac constructs. Additionally, the platform was sensitive enough to detect single-neuron and network activity in cortical spheroids. 3D-SR-BAs developed in this thesis provide a novel and versatile technology toward an organ-on-an-electronic-chip (organ-on-e-chip) platform for studying EP of 3D constructs in both healthy and diseased states. This platform can be further used in long-term EP studies to investigate and advance engineered tissue maturation, as well as develop and test therapeutics for personalized medicine.