Complex droplet networks using pressure-driven microfluidics

Tayler Schimel; Mary-Anne Nguyen; Stephen Sarles; Scott Lenaghan

Microfluidic research summary

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Published on 09 September 2021

Complex droplet networks using pressure-driven microfluidics – a short review

The demonstrated pressure-driven microfluidic system utilized the precise control of pressure inputs and a microfluidic device with five inlets, for four independent aqueous channels and one continuous oil phase. This setup allows for the formation of complex droplet networks, and more specifically, droplet interface bilayer (DIB) networks. On the first hand, by applying sinusoidal pressure waves to the aqueous inlets, oscillating droplet production rates alter the generated droplet pattern. On the second hand, by increasing the potential for greater droplet combinations in a network, a greater complexity required for performing concurrent multiplexed biological assays can be achieved.

This short review article is based on the research article entitled “Pressure-driven generation of complex microfluidic droplet networks” written by Tayler Schimel, Mary-Anne Nguyen, Stephen Sarles, Scott Lenaghan and published in the journal “Microfluidics and Nanofluidics.”

ABSTRACT

This study focuses on producing complex droplet networks of droplet interface bilayers (DIBs) which mimic the cell membrane and provide a compartmentalized model-membrane platform for analyzing complex biosystems, such as cell-free bioreactors and compound screening [1-3]. To enable high-throughput screening and membrane-mediated processes, there is a need for automated and precise formation of higher-order combinatorial multicomponent biosystems. Our work addresses this demand by utilizing pressure-driven droplet production, complex DIB networks are formed from multiple independent inputs and droplet ordering is influenced by input pressure, providing an infinitely customizable biomolecular environment for studying many aspects of cellular functions and processes.

INTRODUCTION TO COMPLEX DROPLET NETWORKS

DIB networks provide a simplified and compartmentalized platform for investigating complex biosystems such as cell-free bioreactors, transmembrane proteins, integral membrane ion channels, and compound screening. Manual pipetting is commonly used to form DIB networks. This method lacks placement control and is limited by large droplet sizes. Microfluidics enables the generation of a large numbers of picoliter sized droplets and the rapid formation of DIB networks.

In order to form complex DIB networks, containing 4 droplets of 4 discrete aqueous types with controllable ordering, a microfluidic devices utilizing T-junction channel geometry and hydrodynamic trapping was coupled with Elveflow’s OB1 pressure-driven flow controller. A sinusoidal pressure wave was applied to each aqueous input pressure and a phase shift was added between opposing T-junctions to create varying droplet productions rates.

By manipulating individual droplet production rates, the order and combinations of droplets captured in the hydrodynamic trapping array is influenced. Each 4-droplet network within the trap array contains three serially connected DIBs, providing a platform for communication between droplets and the simultaneous study of multiplexed biological assays.

Principle of hydrodynamic trapping of droplets to form 4-droplet complex networks. Courtesy of Tayler Schimel.

AIM & OBJECTIVES

To apply sinusoidal pressure waves to four distinct aqueous inputs in order to influence droplet production rates and create complex droplet ordering.
To capture droplets in a hydrodynamic trapping array and form complex 4-droplet DIB networks with up to 35 possible droplet combinations.
To characterize pressure-driven flow for application in hydrodynamic trapping of droplets within a microfluidic device

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KEY FINDINGS

Key contributions of this work include:

1) Firstly, the demonstration that pressure-driven droplet generation enables higher-order patterning of droplets sequences in a controllable manner, with the potential to capture varied combinations of droplets in a hydrodynamic trap array for the study of complex biological processes; and 2) Secondly, the characterization of pressure-driven flow evidencing that pressure-driven flow is sensitive to small changes in resistance, with droplet velocities and size decreasing as traps filled; a characteristic that does not match syringe pump-driven flow where flow rate is constant.

Together, these advances enable rapid formation of complex DIB networks of controllable droplet composition and ordering. To sum up, this work has furthered the understanding of pressure-driven microfluidic droplet generation and hydrodynamic trapping to facilitate the creation of complex microfluidic droplet networks (DIBs) for experiments analyzing complex biosystems.

A video showing live hydrodynamic droplet trapping. Courtesy of Tayler Schimel

References

Timm, A. C., P. G. Shankles, C. M. Foster, M. J. Doktycz and S. T. Retterer (2016). “Toward Microfluidic Reactors for Cell-Free Protein Synthesis at the Point-of-Care.” Small 12(6): 810-817.
Mattern-Schain, S. I., M.-A. Nguyen, T. M. Schimel, J. Manuel, J. Maraj, D. Leo, E. Freeman, S. Lenaghan and S. A. Sarles (2019). Totipotent Cellularly-Inspired Materials. Smart Materials, Adaptive Structures and Intelligent Systems 59131, American Society of Mechanical Engineers.
Zhang, Y., H. Bracken, C. Woolhead and M. Zagnoni (2020). “Functionalisation of human chloride intracellular ion channels in microfluidic droplet-interface-bilayers.” Biosensors and Bioelectronics 150: 111920.

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