MP04: A droplet microfluidic device for high-throughput screening of reaction conditions

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Krzysztof Churski, Tomasz Kaminski, Slawomir Jakiela, Piotr Garstecki

Institute of Physical Chemistry of the Polish Academy of Sciences, Warsaw, Poland

Current standard in high throughput screening is set by the microtiter technology that provides a minimum reaction volume of ~ 2 µL and a minimum filling time of few seconds per well. From the very advent of droplet microfluidics the vision has been put forward for the droplets to serve as reaction beakers. This technology offers several attractive features: i) lack of dispersion of time of residence, ii) fast mixing, iii) control over kinetics of reactions, iv) improved statistics through repeated experiments, v) minute consumption of reagents. These characteristics (fast mixing, temporal resolution and ability to integrate detection in-situ) have the potential of forming a basis for technology competitive with the microtiter platform.

To date, the true potential of droplet microfluidics is largely unexplored, as it requires flexibility to perform arbitrary protocols of compositions of the reaction mixtures. For example, such integrated systems must allow for samples of reagents to be drawn from multiple sources, mixed, reacted and analyzed in a high-throughput combinatorial manner.

We demonstrate a new droplet on demand (DOD) technique and an integrated system for scanning of arbitrary combinations of N solutions in ~ 1 µL droplets at 3 Hz. The system generates synchronized packets of droplets and merges them into reaction mixtures. The DOD system that we developed i) uses standard electromagnetic valves that are external to the chip, ii) is compatible with virtually any microfluidic chip, iii) can generate arbitrarily large range of volumes of droplets, iv) has a maximum operational frequency of ~ 30 Hz, and v) has an on-chip footprint of less than 1 mm2. The integrated system that we demonstrate can be used to scan up to 104 conditions of chemical and biochemical reactions per hour using ~ 10 mL of solutions in total.

The system we developed can be useful in microbiology in screening of epistatic interactions among genes and biologically active compounds. We have applied this technology to screening interactions between antibiotics acting on bacteria E. coli and demonstrated a scan revealing an antagonistic interaction between chloramphenicol and tetracycline within 3 hours, with the preparation time of the sequence of incubation mixtures spanning only 40 seconds.

The system offers slightly higher rates and slightly smaller volumes of reaction mixtures than those offered by the microtiter technology. Development of a similar technology using piezoelectric valves provides a tenfold increase in the rate and greater than a tenfold decrease in the volumes of the samples extending the capabilities of automated droplet microfluidic chips well above the standard set by the well plate technology.

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