PROJECT SUMMARY After decades of using implantable neural probes with implantable multielectrode arrays for medical studies, the exact failure mechanisms of these implants still remain to be fully understood. However, more and more studies have shown that minimizing the mismatches between the soft biological tissue and bioelectronic devices would be a key to achieving long-term, accurate, real-time, and large-scale neural recordings and stimulations without inflammatory immune responses. To mitigate the mechanical mismatch found in hard metal or silicon probes, soft neural probes that are both flexible and stretchable have been developed in recent years. However, bioelectronics on current soft probes has fundamental limits in the stability of their electrochemical impedance under physiological conditions, resulting in a compromise between electronic performance and mechanical matching. The long-term goal is to create a next-generation brain-computer interface (BCI) for advancement in biology, neuroscience, biomedical engineering, and regenerative medicine. The overall objective of this application is to elucidate the design rules to enable electronic-tissue interfaces with reliable electrochemical impedance, tunable mechanical stiffness, using an approach that combines two unique material types – nontoxic liquid metals and biocompatible elastomers. The central hypothesis is that a combination of low-melting-point nontoxic gallium-based liquid metals and intrinsically stretchable polymers will synergistically enhance the electrical, and mechanical interfacial properties in the biological environment and provide unified interfaces for multifunctional integrated systems with embodied intelligence. The successful completion of this research will result in significant advances in the methodology of liquid-metal-embedded soft neural probes. The rationale underlying the proposed research is that the successful development of a truly stretchable and reliable probe-tissue interface offers neuroscientists an unprecedented platform technology to design specific neural probes to investigate fundamental life science questions that were unexplorable before, such as “how neuronal circuits are formed during brain development” where high-density high-resolution stretchable neural probes are needed as a mammalian brain may grow more than 100% in size and add vast amounts of new tissue and resulting new functions. The proposed research is innovative, because it departs from both the conventional and existing neuroscientific instrumentations and introduces a new framework for next-generation neural probe systems using low-melting-point metals and soft polymers. The proposed research is transformative because it will enable “invisible” brain-computer interfaces (BCI) to provide fundamental insights into the underlying physics of brain circuitry formation and functionality. Ultimately, such knowledge paves the way for us to understand the brain and ourselves better, o...