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Machine Learning-Driven Capillary Microfluidic Design Automation for Programmable Gradient Generation and Antimicrobial Testing
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DOI：10.1002/smll.73821.png)
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Abstract
En 中文
Rapid, portable, and automated determination of minimum inhibitory concentration (MIC) is critical for antimicrobial susceptibility testing in decentralized settings. We present TCG-CMDA (Tree-Shaped Concentration Gradient generator enabled by Capillary Microfluidic Design Automation), a machine learning-guided platform for the automated design of capillary microfluidic chips that passively generate programmable concentration gradients. A key innovation of TCG-CMDA is its ability to achieve fully synchronized, capillary-driven flow of two preloaded agents, enabling precise and reproducible gradient formation without external pumps or valves. By integrating computational fluid dynamics (CFD) simulations, a neural network surrogate model, and quasi-Newton optimization, the platform customizes tree-shaped geometries to match target mixing profiles. We validate TCG-CMDA through dye flow visualization and MIC testing of Escherichia coli against gentamicin, showing high concordance with conventional antibiotic susceptibility testing. The resulting chip supports a streamlined workflow consisting of passive loading, autonomous gradient generation, and incubation (similar to 2 h), followed by direct endpoint assessment, making it well suited for decentralized point-of-care applications. TCG-CMDA establishes a closed-loop, simulation-guided design paradigm for capillary microfluidic systems. Although demonstrated here for MIC-oriented antimicrobial testing, the framework is generalizable and can be extended to other gradient-dependent microfluidic applications through geometry reconfiguration and fluid-specific optimization.
Keywords:
capillary microfluidic
design automation
machine learning
minimum inhibitory concentration testing
neural network
tree-shaped concentration gradient generator
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