In this ongoing project we have previously developed a new class of three-dimensional modular fluidic operators (i.e. fluidic diodes, capacitors and transistors); passive 3D internally- rifled mixers; and have previously demonstrated low- cost one-way pumping and mixing systems powered solely by the operator’s finger. In this semesters presentation we feature a 3D printed micromixer-integrated microfluidic gradient generator for antibiotic screening. Every year, more than twenty thousand people in the United States die from antibiotic- resistant bacterial infections. Despite increasing rates of antibiotic resistance, little clinical research is being performed into the discovery of new drugs; instead, a commonly used method to combat antibiotic resistance is combination therapy, where various antibiotics are combined into a “drug cocktail” to be simultaneously administered to the patient. However, biomedical research into the interactions of three or more antibiotics is fairly limited, a result of the critical functional-limitation of standard BioMEMS analytical devices (e.g., two- dimensional PDMS microfluidic chips fabricated via soft lithography) that such monolithic structures can only produce gradients of two fluidic inputs at a time. Furthermore, the biomedical community lacks a simple and accessible method of determining the minimum inhibitory concentration (MIC) of a single antibiotic where the gold standard is still manual labor- intensive pipetting, dilutions, and agar plates. For this project, we present a novel micro- scale 3D printed microfluidic concentration gradient generator (CGG) that produces a symmetric concentration gradient between three fluidic inputs, which we used to determine the interactions of various combinations of three commonly clinically administered antibiotics, as well as the MIC value for each individual antibiotic on ampicillin-resistant E. Coli. Bacteria. Our singular device could be used in a clinical setting, when attempting to treat a known or unknown antibiotic-resistant strain, to decrease the analysis time and required volume of antibiotics to perform a determination of the interactions of multiple antibiotics simultaneously, as well as to analyze the MIC value of each antibiotic, which could set a significant clinical precedent resulting in faster and more effective treatment of new infections and potentially a greater number of patient lives saved. Furthermore, our three-flow CGG could increase the efficacy and speed of experiments in other areas in biomedical research where concentration gradients of reagents are relevant, such as stem cell research.
Project end date: 07/18/19