3D Multifunctional Bioelectronics for Multimodal Charting of the Human Induced Pluripotent Stem Cell Derived Organoids

Induced pluripotent stem cells (iPSCs) technology has created great opportunity for modelling human diseases and offers potential for application of personalized regenerative cell therapies. To fully understand and assess the function and maturation of stem cells-derived tissues and organoids, we need multimodal methods capable of long-term stably recording individual cell electrical activity with high spatiotemporal resolution across three-dimensional (3D) tissues, multiplexed profiling of a large number of genes in electrically recorded cells, and cross-modal computational analysis. However, none of existing technologies can fulfill these requirements. In this talk, I will first introduce the development of soft “tissue-like” stretchable mesh nanoelectronics, which match the physical and mechanical properties of soft tissue. I will also present how to integrate multifunctional sensors into the soft “tissue-like” nanoelectronics to map the multimodal tissue functions. Then I will discuss how to distribute the stretchable tissue-like bioelectronics across the entire 3D organoids by their organogenetic processes. I will discuss the seamless and noninvasive coupling of electrodes to cells, capable of providing long-term stable electrical contacts with progenitor or stem cell, captures the emergence of single-cell action potentials and enables long-term stable, continuous recording from 3D organoids during their development process. Third, I will introduce our efforts to combine the <i>in situ</i> single-cell RNA sequencing with soft bioelectronics as a method termed “<i>in situ</i> electro-seq”. <i>In situ</i> electro-seq enables large-scale single-cell electrical recording and high-throughput single-cell sequencing to systematically and simultaneously investigate single-cell electrophysiology and gene expression across the intact iPSC-CMs organoids. Finally, the future perspective to apply these technologies to both <i>in vitro</i> and <i>in vivo</i> biosystems for stem cell therapies will be discussed.