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We present TCG\u2010CMDA (Tree\u2010Shaped Concentration Gradient generator enabled by Capillary Microfluidic Design Automation), a machine learning\u2013guided platform for the automated design of capillary microfluidic chips that passively generate programmable concentration gradients. A key innovation of TCG\u2010CMDA is its ability to achieve fully synchronized, capillary\u2010driven 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\u2010Newton optimization, the platform customizes tree\u2010shaped geometries to match target mixing profiles. We validate TCG\u2010CMDA 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 (\u223c2\u00a0h), followed by direct endpoint assessment, making it well suited for decentralized point\u2010of\u2010care applications. TCG\u2010CMDA establishes a closed\u2010loop, simulation\u2010guided design paradigm for capillary microfluidic systems. Although demonstrated here for MIC\u2010oriented antimicrobial testing, the framework is generalizable and can be extended to other gradient\u2010dependent microfluidic applications through geometry reconfiguration and fluid\u2010specific optimization.<\/jats:p>","DOI":"10.1002\/smll.73821","type":"journal-article","created":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T16:09:26Z","timestamp":1779034166000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Machine Learning\u2010Driven Capillary Microfluidic Design Automation for Programmable Gradient Generation and Antimicrobial Testing"],"prefix":"10.1002","volume":"22","author":[{"given":"Mahmood","family":"Khalghollah","sequence":"first","affiliation":[{"name":"Department of Electrical and Software Engineering University of Calgary  Calgary Alberta Canada"},{"name":"BioMEMS and Bioinspired Microfluidic Laboratory Department of Mechanical and Manufacturing 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