Abstract
This study presented an integrated microfluidic device which can perform rapid antimicrobial susceptibility tests (AST) of antibiotics combination against clinical bacteria. A new approach to measure either drug interactions of three antibiotics or minimum inhibitory concentration (MIC) of antibiotics by performing bacteria dispensation and antibiotics dilution automatically was proposed and it substantially reduced detection time (from 24 hr to 4 hr) and bacteria consumption (from 100 μL to 3 μL) when compared to the broth microdilution method. A new membrane-type micromixer composed of two circular micropumps was integrated in order to achieve on-chip pumping/mixing with high accuracy and efficiency. Experimental results revealed that the proposed device can produce accurate liquid transportation and chaotic mixing and visually interpret AST results including individual MIC determination and drug interactions. Synergistic and antagonistic effects of pairwise and triple interactions among three common antibiotics (vancomycin, gentamicin and ceftazidime) with ten different combinations were demonstrated on one clinical isolate of vancomycin-intermediate staphylococcus aureus. It is the first time that a microfluidic device was demonstrated for drug screening to inhibit bacteria growth with three antibiotics by performing AST automatically. The developed device could be utilized as a robust tool to rapidly explore drug screening for drug cocktail therapy.