Pseudomonas aeruginosa infected nematode-on-a-chip model array for antibacterials screening

Abstract

In this work, we have developed a novel pneumatic microfluidic chip (pChip) for in-vivo antibacterials screening at single-organism resolution using a P. aeruginosa-C. elegans infection model. To improve the accuracy and efficiency of nematode infection-based drug screening, we designed a pneumatic-controlled micro-sampler that enables simultaneous dispensing of a large number of individual free-moving worms into each culture chamber under physiological conditions without any mechanical squeezing, and the average probability of a single worm in a chamber is 88.5%, with RSD of 2.8%. Furthermore, we proposed an effective liquid P. aeruginosa-C. elegans infection model based on microfluidic chip, and the performance of the platform was verified with multiple clinical antibiotics. By applying this developed worm pChip to evaluate the antimicrobial activity of some natural medicinal compounds (coptisine, baicalin and gypenoside), we found that gypenoside can increase the P. aeruginosa infected worm survival by 2.3-fold at 30.0 μg/mL, whereas it does not suppress pathogen growth in vitro. It indicates that the well-established pneumatic chip will be an efficient platform for evaluation of antibacterial potential of medicinal natural compounds.