Microfluidics Platforms for High Throughput In Vivo Screening

Preclinical research and development are the cornerstone of modern drug discovery. A variety of biological systems including in vitro, 3D cultures, and organoids are essential tools, with ultimately lead candidates being tested in animal models. Microfluidics has played a significant role in advancing research and providing high content data in in vitro biological systems. In this talk, I will discuss our laboratory’s effort to apply microfluidic approaches to perform high throughput phenotypic screening in C. elegans – a nematode that offers human-relevant biology and is suitable to microfluidic automation.  This in vivo model addresses the limitations of in vitro models, where tissue-level and multi-organ interactions are difficult to capture. Likewise, it alleviates the need for expensive and unsustainable testing in rodent models. Thus, C. elegans based phenotypic screening offers an attractive paradigm to re-think modern drug discovery. Moreover, with recent advances in transgenics, a variety of disease models have been engineered in C. elegans capturing relevant biology for neurodegeneration, muscle disorders and rare genetic diseases. I will also discuss, the use of microfluidics to conduct C. elegans based studies on the International Space Station with a focus on muscle health. The results from our studies show that whole-life in vivo data can be obtained using C. elegans and microfluidic automation. Our technology platform could be used to screen compound libraries for in vivo efficacy at a fraction of cost and time compared to rodent models.  

Learning Objectives:

1. Discuss the challenges of preclinical drug discovery.

2. List the advantages of C. elegans and microfluidics for in vivo screening.

3. Discuss the phenotypes that can be quantified in microfluidic in vivo screening.