3D printed three-flow microfluidic concentration gradient generator for clinical E. Coli-antibiotic drug screening

This paper presents a symmetric three-flow microfluidic concentration gradient generator, made possible by a 3D microchannel network fabricated via ultra-high resolution Multijet 3D printing. The prototype fluidic device is utilized as an effective tool for the expedited screening of multi-drug combinations. It rapidly generates 15 discrete combinations of three input drugs which are used to determine the minimum inhibitory concentration (MIC) value of the three individual antibiotics, as well as to perform simultaneous clinical three-way antibiotic interaction studies on ampicillin-resistant Escherichia coli (E. coli) bacteria. The results from individual antibiotic experiments are used to determine the discrete MIC values, and the multi-drug study reveals clinically relevant antagonistic, synergistic and suppressive interactions between the three different families of antibiotics commonly used to combat antibiotic resistant infections. Furthermore, a simple and effective method of visual interpretation of the experimental results is employed, demonstrating this device's use as an effective multi-drug screening platform for applications in point-of-care biomedical research and clinical medicine.