Microfluidic system for on-chip high-throughput whole-animal sorting and screening at subcellular resolution

Area of Science:

• Biotechnology
• Genetics
• Pharmacology

Background:

• High-throughput screening (HTS) is crucial for genetic and drug discovery.
• Analyzing whole animals at subcellular resolution presents significant technical challenges.

Purpose of the Study:

• To develop and present a suite of microfluidic devices for complex, high-throughput whole-animal genetic and drug screens.
• To enable subcellular resolution phenotypic analysis in physiologically active animals without anesthesia.

Main Methods:

• High-speed microfluidic sorter for isolating and immobilizing Caenorhabditis elegans.
• Integrated chip with individually addressable screening chambers for compound exposure and time-lapse imaging.
• Novel designs for compound library delivery and animal dispensing.

Main Results:

• Demonstrated a microfluidic sorter capable of isolating and immobilizing C. elegans for subcellular phenotypic screening.
• Developed an integrated chip for anesthesia-free, high-resolution imaging and compound exposure of multiple animals.
• Showcased compatibility with standard multiwell plates for compound delivery and animal collection.

Conclusions:

• The developed microfluidic devices facilitate high-throughput assays, including genetic, RNAi, and drug screens at subcellular resolution.
• These tools support advanced in vivo manipulations like femtosecond laser microsurgery for neural studies.
• The system enhances the efficiency and precision of whole-animal screening and manipulation studies.