High-Content and High-Throughput In Vivo Drug Screening Platforms Using Microfluidics

The drug-discovery process is expensive and lengthy, and has been causing a rapid increase in the global health care cost. Despite extensive efforts, many human diseases still lack a cure. To improve the outcomes, there is a growing need to implement novel approaches into the early stages of the drug-discovery pipeline. A specific such effort has focused on the development of novel disease models such as cellular models (genetically modified cell lines, spheroids, and organoids) and whole-animal models (small animal models and genetically modified large animal models). The whole-animal screens are advantageous as they can provide system-level information, off-target effects, complete absorption, distribution, metabolism, excretion, and toxicity architectures, and early in vivo toxicity, which help to prioritize compounds before using them for human trials. Such multivariate analysis helps to improve the translational potential of drug compounds. Drug testing in large animals is expensive and time consuming. A solution is small animal models that have simplified biological system with intact physiology and sufficient homology with human genes. In recent times, many such models have constantly been developed and tested to identify new disease mechanisms. Caenorhabditis elegans is one such small animal model that has been considered for large-scale drug testing. In this review, we will discuss the current state-of-the-art technologies, including two platforms developed in my group that have enabled high-throughput and high-content screening using C. elegans disease models.