Soft and Flexible Bioelectronics for Brain-Machine Interfaces

Large-scale brain mapping through brain-machine interfaces is important for deciphering neuron dynamics, addressing neurological disorders, and developing advanced neuroprosthetics. Ultimately, brain mapping aims to simultaneously record activities from millions, if not billions, of neurons with single-cell resolution, millisecond temporal resolution and cell-type specificity, across three-dimensional (3D) brain tissues over the course of brain development, learning, and aging. In this talk, I will first introduce flexible and soft bioelectronics with tissue-like properties that can track electrical activity from the same neurons in the brain of behaving animals over their entire adult life. Specifically, I will discuss the fundamental limitations of the electrochemical stability of soft electronic materials in bioelectronics and present our strategies to overcome these limitations, enabling a scalable platform for large-scale, long-term, stable brain mapping. Then, I will discuss the creation of “cyborg organisms”, achieved by embedding stretchable mesh-like electrode arrays in 2D sheets of stem/progenitor cells and reconfiguring them through 2D-to-3D organogenesis, which enables continuous 3D electrophysiology during the development of human stem cell-derived brain organoids and animal embryonic brains. Next, I will highlight our current efforts that merge 3D single-cell spatial transcriptomics, machine learning, and electrical recording, enabling cell-type-specific brain activity mapping. In conclusion, I will envision the fusion of soft and flexible electronics, spatial transcriptomics, and AI for a comprehensive brain cell functional atlas to enhance future brain-machine interface applications.