The ability to generate combinatorial libraries of chemical compounds is important for a variety of problems, particularly sensory neurobiology, and for drug screens and development of potential therapeutics for diseases. Currently combinatorial screens using small model organisms such as C. elegans and zebrafish is virtually cost inhibitive and complex to carry out, because of these animals are cultured and screened usually in multi-well plates. Additionally, handling small animals with complex maneuvers fluidically is challenging. Our main interest in the long-term is to develop technological platforms and study sensory biology in C. elegans as a model for human neurological diseases. In this project, we will design a droplet-microfluidic chip that can be automated for generating combinatorial libraries of chemicals, and then to demonstrate the utility of this system in studying the combinatorial effects of a few pheromone compounds on C. elegans. This project is significant because it addresses two current major bottlenecks for combinatorial screens with small model organisms. Both the hardware design and the software (automation and quantitative behavioral analysis) will be translatable to other problems and systems. We envision the technology will enable a variety of combinatorial screens using small model organisms that will lead to new biological discoveries.
Combinatorial screens can potentially lead to better understanding of sensory biology, which is relevant to many human sensory diseases. Combinatorial screens can also yield better combination drugs to treat diseases. This project addresses a current technical bottleneck in combinatorial screens, which in the long run will lead to better designs for therapeutics in a variety of human diseases.
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