Autonomous Liquid-handling Robotics Scripting for Accessible and Responsible Protein Engineering
Yuan, G.; Luo, L.; Li, W.; Lan, Y.; Jiang, H.; Chen, Y.; Yi, X.; Li, B.; Alinejad-Rokny, H.; Wang, T.; Fu, L.; Yang, M.; Si, T.
10.1101/2025.09.30.679666 bioRxivShow abstract
Laboratory automation enhances experimental throughput and reproducibility, yet widespread adoption is constrained by the expertise required for robotic programming. Here, we introduce LabscriptAI, a multi-agent framework that enables large language models to autonomously generate and validate executable Python scripts for protein engineering automation. Across a 55-task benchmark spanning four difficulty levels and multiple liquid-handling platforms, LabscriptAI achieved high success rates and outperformed both direct large language model baselines and a commercial solution. LabscriptAI automated cell-free protein synthesis and characterization of 298 green fluorescent protein (GFP) variants designed by 53 teams from five countries in a student challenge; the top variant achieved functional performance comparable to an extensively optimized benchmark while exploring distinct sequence space. Furthermore, LabscriptAI orchestrated distributed automation across a biofoundry and fume hood-enclosed systems to engineer enzyme variants utilizing formaldehyde, a sustainable but hazardous substrate, and identified a double mutant with sevenfold increase in catalytic efficiency. The platform implements rigorous safety measures, including biosecurity screening, physical containment, and human-in-the-loop oversight, to safeguard autonomous protein engineering. LabscriptAI democratizes laboratory automation by eliminating programming barriers while promoting responsible research practices.
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