Syringe-injectable mesh electronics: Seamless integration with the central nervous system and biomedical applications

Abstract

The ability to carry out stable chronic mapping and manipulation of single neurons at the action potential level with high temporal resolution could significantly benefit both fundamental neuroscience research and biomedical applications, including cognitive studies, memory encoding and retrieval, and neural prostheses. Over the past century various technologies have been developed to study neurons and neural activity. Of these technologies, implantable electrical probes provide higher spatiotemporal-resolution neural recordings independent of probing depth compared with other techniques. However, conventional implanted electrical probes, such as silicon probes and microwire probes, generally trigger immune responses that lead to glial scar formation and neuronal cell depletion at the interface between tissue and probe. The Lieber group has previously reported ultra-flexible mesh electronics that can be delivered into nonliving and living systems by syringe injection. In this thesis, I present systematic studies of the interface between ultra-flexible mesh electronics and in vivo neural tissue, including the mouse brain and spinal cord, as well as functional applications of ultra-flexible mesh electronics implanted in the central nervous sysem (CNS). First, I introduce design, fabrication and in vitro injection of ultra-flexible mesh electronics. Second, I present systematic histology studies of the interface between ultra-flexible mesh electronics and brain tissue and compare them with conventional flexible thin-film probes at multiple time points post-implantation, illustrating the seamless integration of mesh electronics with minimal chronic immune response in the brain. Third, I present studies of mesh electronics implanted in mouse brains for stable long-term chronic brain mapping and manipulation at the single-neuron level. Fourth, I demonstrate a unique method to implant ultra-flexible mesh electronics into the spinal cord of mice through minimally invasive syringe injection, as evidenced by post-implantation behavior studies and histology of the tissue-probe interface. Finally, I present chronic electrophysiological recordings of spinal cord neurons by implanted mesh electronics, as well as biomedical applications of mesh electronics implanted in the mouse spinal cord.