All-electrical monitoring of bacterial antibiotic susceptibility in a microfluidic device

Abstract

The lack of rapid antibiotic susceptibility tests adversely affects the treatment of bacterial infections and contributes to increased prevalence of multidrug resistant bacteria. Here, we describe an all-electrical approach that allows for ultra-sensitive measurement of growth signals from only tens of bacteria in a microfluidic device. Our device is essentially a set of microfluidic channels, each with a nano-constriction at one end and cross-sectional dimensions close to that of a single bacterium. Flowing a liquid bacteria sample (e.g., urine) through the microchannels rapidly traps the bacteria in the device, allowing for subsequent incubation in drugs. We measure the electrical resistance of the microchannels, which increases (or decreases) in proportion to the number of bacteria in the microchannels. The method and device allow for rapid antibiotic susceptibility tests in about two hours. Further, the short-time fluctuations in the electrical resistance during an antibiotic susceptibility test are correlated with the morphological changes of bacteria caused by the antibiotic. In contrast to other electrical approaches, the underlying geometric blockage effect provides a robust and sensitive signal, which is straightforward to interpret without electrical models. The approach also obviates the need for a high-resolution microscope and other complex equipment, making it potentially usable in resource-limited settings.