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How to make digital microfluidics suit biological need

Droplet-based microfluidics is a technology that allows for the manipulation of small liquid droplets with a volume ranging from microliters to picolitres. The technology that handles discrete droplets is called digital microfluidics. The small volume offers various advantages such as quick mixing, simple handling, high throughput with a large number of droplets. The small volume also poses a serious challenge to engineering droplet-based microfluidic platforms: evaporation.

To prevent evaporation and protect droplets from contamination, an immiscible liquid such as oil is often used in both continuous-flow droplet-based microfluidics and digital microfluidics. However, the protective oil layer also prevents the much needed gas exchange for biological applications such as cell culture. Coating the droplet with a porous layer of solid particles would protect the droplet content, and at the same time allow for gas exchange. This droplet platform is called liquid marble.

Although the porous particle coating of a liquid marble prevents the liquid content from wetting a solid surface or their unwanted coalescence, it cannot solve the problem of evaporations. Recent research indicated that the porous coating may even accelerate evaporation due to the increase in liquid surface area in the pores. To make liquid marble a practical digital microfluidics platform, the evaporation problem has to be addressed and managed. Keeping a high humidity of the air around the liquid marble or even make it saturated could make this platform last for days, even weeks. We found a solution for making liquid marbles last for a long time by floating them on a liquid water surface.

The liquid bath supplies the saturated condition at its surface and allows the liquid marble to remain intact for days. The floating condition further allows for good mixing inside the liquid marble. The floating liquid marble has served incredibly well as a bioreactor for growing multiple cell spheroids. In contrast to the state-of-the-art hanging drop platform, the cells self-assemble into spheroids with healthy cores. Embedding a hydrogel sphere soaked with growth factors in a liquid marble allows for culturing a donut-shaped tissue called toroid. The unique shape of a cell toroid makes it serve perfectly as a three-dimensional wound model, a serious alternative for the conventional two-dimensional scratch assay on a petri dish.

To make liquid marble-based digital microfluidics commercially viable, ongoing research is looking into various schemes for the generation, manipulation and evaporation control of liquid marbles. Our lab has successfully demonstrated the manipulation of liquid marbles using magnetic and electrostatic forces.

Due to the extremely low friction of a liquid marble floating on a free liquid surface, its manipulation requires a minimum amount of input energy. Including a minute amount of magnetic particles into the liquid marble allows it to be controlled with a magnetic field. Electrostatic force can be used of manipulating liquid marbles, similar to the current concept used for digital microfluidics. Instead of electrowetting, changing the contact angle of a droplet on a solid surface with an applied voltage, we used dielectrophoresis to manipulate the liquid marbles.

Dielectrophoresis is a phenomenon where charged objects are attracted to a region with a high gradient of an electric field such as the tip of an electrode. The manipulation techniques allows the liquid marble to move around, enhancing the circulation and thus mixing inside the liquid marble.

A common manipulation task in digital microfluidics is merging or the coalescence of two or more liquid droplets. As liquid marbles are robust and stable, it is a challenge to merge them. We have demonstrated forced coalesce of liquid marbles by impact. More elegant solutions such as opening up the coating using magnetic particles as the coating material have been demonstrated. We are exploring concepts such as direct injection of sample and chemicals into a liquid marble or coalescence using electrostatic force. However, coalescence of liquid marbles floating on a liquid surface as currently used for cell culture remains an unsolved technical challenge.

Liquid marble based digital microfluidics have proved itself as a feasible and useful platform for biological applications, particularly for cell culture. We recently demonstrated that cells can be directly preserved in a liquid marble using conventional, and subsequently cultured into three-dimensional tissues in the same liquid marble. We envision the development of a desktop based cell culture system that includes the generation, manipulation, preservation of liquid marbles containing cells. Such a system will contribute to advancing engineering of tissues and organ models for cell therapy and drug discovery.

 

Nam-Trung Nguyen is Professor and Director of the Queensland Micro- and Nanotechnology Centre at Griffith University. He will give his presentation “Liquid marble based digital microfluidics: fundamental physics and applications” at the 4BIO Summit: Europe.

 

The 4BIO Summit: Europe will take place in under two weeks time in Rotterdam. Time is running out for you to guarantee your place – book now to avoid disappointment.

 

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