Abstract
Automated biosorter platforms, including recently developed microfluidic devices, enable and accelerate high-throughput and/or high-resolution bioassays on small animal models. However, time-consuming delivery of different organism populations to these systems introduces a major bottleneck to executing large-scale screens. Current population delivery strategies rely on suction from conventional well plates through tubing periodically exposed to air, leading to certain disadvantages: 1) bubble introduction to the sample, interfering with analysis in the downstream system, 2) substantial time drain from added bubble-cleaning steps, and 3) the need for complex mechanical systems to manipulate well plate position. To address these concerns, we developed a multiwell-format microfluidic platform that can deliver multiple distinct animal populations from on-chip wells using multiplexed valve control. This Population Delivery Chip could operate autonomously as part of a relatively simple setup that did not require any of the major mechanical moving parts typical of plate-handling systems to address a given well. We demonstrated automatic serial delivery of 16 distinct C. elegans worm populations to a single outlet without introducing any bubbles to the samples, causing cross-contamination, or damaging the animals. The device achieved delivery of more than 90% of the population preloaded into a given well in 4.7 seconds; an order of magnitude faster than delivery modalities in current use. This platform could potentially handle other similarly sized model organisms, such as zebrafish and drosophila larvae or cellular micro-colonies. The device’s architecture and microchannel dimensions allow simple expansion for processing larger numbers of populations.
Highlights
Caenorhabditis elegans (C. elegans) is a powerful model organism in molecular biology due to its simple anatomy, highly conserved and fully sequenced genome, amenability to various molecular and genetic manipulations, and fully characterized cellular anatomy
Geometry, and habituation to liquid environments, these organisms are cultivated in well plates using robotic liquid-handling systems
The design considerations culminated in a computercontrolled multiplexed microfluidic device with built-in conical wells for high-speed population loading
Summary
Caenorhabditis elegans (C. elegans) is a powerful model organism in molecular biology due to its simple anatomy, highly conserved and fully sequenced genome, amenability to various molecular and genetic manipulations, and fully characterized cellular anatomy These attributes facilitated research to the point that the yearly publication rate of C. elegans papers doubled during the previous decade [1]. Thanks to their size, geometry, and habituation to liquid environments, these organisms are cultivated in well plates using robotic liquid-handling systems. Geometry, and habituation to liquid environments, these organisms are cultivated in well plates using robotic liquid-handling systems These worms can be subsequently characterized in high-throughput optical sorting systems, such as flow-cell imagers and microfluidic devices. We present a microfluidic system for ultra-rapid transportation of worm populations treated with different compounds from well plates to the given optical interrogation platform
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