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Programming Microbe-Computer Interaction for Customized Life-Nonlife and Cross-Life Communication

Feng, Z.; Zhang, C.; Huang, X.; Zhang, Y.; Liu, H.; Cui, M.; Zhang, H.; Song, Z.; Li, M.; Li, H.; Ma, B.; Lu, S.; Li, M.; Bai, G.; Sun, D.; Zhang, X.; Zou, Z.; Zhou, Y.; Ye, B.; Gao, M.; Yin, H.; Tao, M.; Liu, P.; Liu, D.; Luo, H.; Wang, H.

2025-09-28 synthetic biology
10.1101/2025.09.27.679003 bioRxiv
Show abstract

This extension of human-computer interaction (HCI) paradigm to the non-intelligent microbe-computer interaction (MCI) is attractive for building generalized life-nonlife communication. Main challenges lie in how to construct biohybrid interface within individual MCI unit and thereafter program cross-life communication based on these MCI units. Here, we propose the design and construction of opto-interfaced MCI unit composed of engineered microbes and computer terminals, for enabling quantifiable transduction between microbial signals and digital signals. These units were able to serve as biohybrid sensors, actuators and transceivers, supporting biomonitoring, bio-actuation and microbe-centric bidirectional operations. Based on these functional units, we established programmable cross-life communication architectures capable of unicast, multicast, and logic-gate-driven communication with temporal dynamic control. The architectures were validated in biomedical scenarios including tumor hypoxia biomarking, epidermal heavy metal detoxification, and colitis intervention, demonstrating robust performance in closed-loop diagnostic-therapeutic applications. Additionally, we integrated MCI with an unmanned surface vessel for environmental monitoring, highlighting its cross-domain potential. Collectively, we provide a scalable strategy for building customized life-nonlife and cross-life communication, which is expected as an important complement to internet of things (IoT).

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