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Ultrahigh-throughput droplet microfluidics:
Scalable liquid handling

Liquid handling is the foundation of cellular/molecular assays – from blood tests to DNA sequencing to growing cells – liquid handling is an indispensable part of the workflow. However, the way we traditionally perform these operations (pipettes and plastic tubes) is difficult to scale.


Rather than using pipetting robots, we leverage microfluidics technology to perform liquid handling with tiny droplets that act analogously to plastic tubes – except scaled down 1 million fold! This fundamentally changes the scalability of reactions. For example, using the same volume of reagents used in a tube-based PCR reaction, we can conduct millions of independent PCR reactions within tiny droplets.

Below are some examples of how we can manipulate these droplets using microfluidic devices.

We can encapsulate single cells in the droplets to conduct single-cell assays at ultrahigh-throughput. Typically, cells enter the droplet making nozzle in a random manner. But leveraging inertial forces of microfluidic flow, we can arrange the cells in an orderly fashion, resulting in higher encapsulation efficiency.

Video from Edd et. al Lab on a Chip 8, 1262-1264 (2008)

Droplets are stable under normal conditions, but can be destabilized by electric fields. Leveraging this property, we can use microfluidic channels to pair droplets and subject them to electric fields to merge droplets in a controlled fashion. This allows us to combine different samples or add new reagents to already formed droplets.

Microfluidic channels allow us to precisely control the hydrodynamic forces acting on the droplets. In this case, the channels of the splitting array are the same length and size, and therefore the hydrodynamic resistance for all paths are equal. The result is perfect splitting of droplets into equal sized smaller droplets. Controlled splitting of droplets can be used to further increase the throughput of droplet making or to remove reagents from droplets.

Droplets can be sorted into different channels by providing an external force as they flow through a junction. In this video, when (clear) fluorescent droplets are detected (white flashes) as they flow through the channel, an electric field pulls the droplets towards the lower channel. When the droplets are not fluorescent, the electric field is not actuated and they flow towards the upper channel. This can be used to screen through large numbers of droplets for those containing samples with desired properties.

Video from Agresti et. al, PNAS (2010)

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