Abstract
High-throughput biological and chemical experiments typically use either multiwell plates or microfluidic devices to analyze numerous independent samples in a compact format. Multiwell plates are convenient for screening chemical libraries in static fluid environments, whereas microfluidic devices offer immense flexibility in flow control and dynamics. Interfacing these platforms in a simple and automated way would introduce new high-throughput experimental capabilities, such as compound screens with precise exposure timing. Whereas current approaches to integrate microfluidic devices with multiwell plates remain expensive or technically complicated, we present here a simple open-source robotic system that delivers liquids sequentially through a single connected inlet. We first characterized reliability and performance by automatically delivering 96 dye solutions to a microfluidic device. Next, we measured odor dose-response curves of in vivo neural activity from two sensory neuron types in dozens of living C. elegans in a single experiment. We then identified chemicals that suppressed optogenetically-evoked neural activity, demonstrating a functional screening platform for neural modulation in whole organisms. Lastly, we automated an 85-minute, ten-step cell staining protocol. Together, these examples show that our system can automate various protocols and accelerate experiments by economically bridging two common elements of high-throughput systems: multiwell plates and microfluidics.
Highlights
Microfluidic devices offer several advantages for biomedical research, for presenting precise physical and chemical environments to cells and organisms[1,2,3,4], multiplexing experimental conditions[4,5,6], and reducing reagent volumes for screening applications[7,8,9]
The modular system mounts to a microscope for visualization and monitoring of samples contained within an integrated microfluidic device
The robotic system described in this paper automates sequential delivery of different fluids from multiwell plates to microfluidic devices
Summary
Microfluidic devices offer several advantages for biomedical research, for presenting precise physical and chemical environments to cells and organisms[1,2,3,4], multiplexing experimental conditions[4,5,6], and reducing reagent volumes for screening applications[7,8,9]. Current approaches include complex setups with separate inlet tubes for each well (i.e., 96 inlet tubes for a 96-well plate)[5], the use of conventional liquid-handling robots to inject liquids to device inlets[10,11], and microfluidic designs that are integrated into plastic multiwell dishes[12,13,14,15,16] These approaches are generally expensive, either due to laborious fabrication processes or to single-use cartridges operated by specialized flow control equipment. We present a robotic system that reliably and automatically transfers a single microfluidic inlet tube from one fluid reservoir to another, without introducing a bubble In this manner, numerous liquids can be delivered sequentially into any microfluidic device. We demonstrate that this system, based on inexpensive open-source hardware and software, can completely automate: (1) the measurement of neural dose responses and optimization of chemical concentrations for robust and non-saturating responses, (2) a complex chemical screen www.nature.com/scientificreports/
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