Large Language Model Agents Enable Autonomous Design and Image Analysis of Microwell Microfluidics

Microwell microfluidics has been utilized for single-cell analysis to reveal heterogeneity in gene expression, signaling pathways, and phenotypic responses for identifying rare cell types, understanding disease progression, and developing more precise therapeutic strategies. However, designing microwell microfluidics is a considerably complex task, requiring knowledge, experience, and CAD software, as well as manual intervention, which often fails initial designs, demanding multiple costly and time-consuming iterations. In this study, we establish an autonomous large language model (LLM)-driven microwell design framework to generate code-based computer-aided design (CAD) scripts, that enables the rapid and reproducible creation of microwells with diverse geometries and imaging-based analysis. We propose a multimodal large language model (MLLM)-logistic regression framework based on integrating high-level semantic descriptions generated by MLLMs with image embeddings for image classification tasks, aiming to identify microwell occupancy and microwell shape. The fused multimodal representation is input to a logistic regression model, which is both interpretable and computationally efficient. We achieved significant improvements, exceeding 0.92 for occupancy classification and 0.99 for shape classification, across all evaluated MLLMs, compared with 0.50 and 0.55, respectively, when relying solely on direct classification. The MLLM-logistic regression framework is a scalable, efficient solution for high-throughput microwell image analysis. Our study demonstrates an autonomous design microwell platform by translating natural language prompts into optimized device geometries, CAD scripts and image analysis, facilitating the development of next-generation digital discovery by integration of literature mining, autonomous design and experimental data analysis.