High-throughput injection with microfluidics using picoinjectors

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A. R. Abate, T. Hung, P. Mary, J. J. Agresti, and D. A. Weitz

"High-throughput injection with microfluidics using picoinjectors"

PNAS 107, 19163-19166 (2010).


Entry by Meredith Duffy, AP 225, Fall 2011


Keywords: droplet microfluidics, Laplace pressure, high throughput, thin film, emulsion

Summary

Microfluidics-based research requires manipulation of fluid volumes on a sub-microliter scale. Although this can prove advantageous for maximizing efficiency and throughput of assays, measuring and especially combining such small quantities with accuracy can prove difficult. The authors present a technique for adding multiple reagents to droplets in microchannels with sub-picoliter accuracy by taking advantage of a two-phase system with electrically induced thin-film instabilities.


This "picoinjector" technique provides advantages over current standards such as T-junctions and electro-coalescence. T-junction devices fail for stable emulsions, whose surfactant surface denies the reagent entry into the drop. Electro-coalescence, in which an electric field is used to merge the droplet with the reagent droplet in flow, is effective for one reagent but fails when trying to add multiple reagents in sequence, due to the difficulties of synchronizing multiple droplet streams. The picoinjector, conversely, can inject controlled quantities of reagent into surfactant-lined drops and can be placed in series with more picoinjectors to allow the independent addition of as many reagents as needed.

Methods and Results

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The picoinjector device (Figure 1) is designed to take advantage of the properties of the interface between the two phases of an emulsion. Water droplets stabilized by a surfactant (perfluorinated PEG) enter the microfluidic devide at high volume fraction. They are immediately passed single-file into a narrow channel and mixed with a stream of oil to spread them apart. An injector sits perpendicular to one side of the channel, with electrodes lined up across from it.


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As a drop passes by, a laser detects its presence and the electrodes are turned on, destabilizing the thin film interface and allowing the injection of reagent. Additionally, the channel narrows suddenly at the injector creating a pressure differential, the Laplace pressure, between reagent and oil, due to the high curvature of the interface. Reagent enters the drop until the higher convex curvature of the drop that its addition causes balances the higher concave curvature caused by the narrowed channel. As the drop moves away from the injector, its connection to the injector breaks and the drop, now containing reagent, restabilizes (Figure 2).


Thus, for a controlled original drop size and all other conditions equal, the same amount of reagent will be injected into each drop. Additionally, increasing the injection pressure linearly increases injection volume by increasing velocity of injection, while increasing flow rate in the channel decreases injection volume through an inverse dependence of injection time on drop velocity (Figure 3). This dual-control system allows for injection volumes between 0.1 and 3 pL. It is also notable that the electrode voltage applied is independent of both injection volume and injection volume error as long as it exceeds 30V (below which nothing is injected).


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The switching rate of the injector is limited not by the electrodes but by the detection of droplets to 10 kHz. Similarly, the accuracy of the system is limited by optical resolution to 0.1 pL, due to their system of quantifying reagent added by calculating the change in drop volume (modeling the drops as cylinders with hemispherical ends).


The authors also demonstrate that several picoinjectors, each on the scale of a few hundred microns, can be placed side-by-side along the same channel and activated independently, allowing the injection of different combinations of reagents for different drops.


Conclusions

Overall, due to its high accuracy, fast switch rate and small footprint, this picoinjector system has a good potential for use in two-phase microfluidic systems requiring high throughput, such as screening and sequencing assays. Moreover, it serves as an example of emulsions and the dynamic properties of the liquid interface in a useful application.