An integrated system of micromixers and microfluidic concentration gradient chips assisted drug screening over large...

There is an unmet need for a versatile platform that enables flexible multi-drug combination screening with a wide concentration range and automated operation. Accordingly, an automated multi-drug combination screening platform (ISMMCGs) integrating elliptical baffle micromixers (EBMixers) and three types of microfluidic concentration gradient (MCG) chips was developed. The EBMixer achieves > 90% mixing efficiency within a 40 mm channel (Re = 0-70), ensuring rapid uniform mixing. The MCG chips (linear, two-fold, ten-fold dilution), designed via the equivalent circuit method, spanning a four-order-of-magnitude concentration gradient (10⁻⁴-1). Automated switching via a micro-solenoid valve array enables "rough/fine/precise" screening. Validation with sodium fluorescein confirms gradient reliability; Screening experiments of vancomycin against MRSA demonstrate that this system can narrow the OD600-determined apparent MIC range down to 0.78-1.01 µg/mL, verifying the application potential of this platform in rapid screening of antimicrobial concentration ranges; and tigecycline-colistin sulfate combination screening for MDR-AB verifies the platform's flexibility for concentration-dependent combinatorial testing. This integrated platform addresses the limitations of traditional methods by balancing wide concentration coverage, multi-drug flexibility, and automation. It provides a refined, cost-effective tool for drug screening, facilitating the development of personalized treatment regimens and accelerating drug discovery processes, with broad applications in antimicrobial resistance research and pharmaceutical development.