Life Sciences. Little droplets make the ocean of drug discovery

Imagine a valiant king, skilled in combat and raring to go to battle, waiting droopily on the steps of his palace for his charioteer and horses, who are delayed at lunch!

In drug discovery, there are many such ‘horses’ that are meant to take the drug to the right cell in the body. They transport cells and chemicals to the target region. In a process already fraught with uncertainty and high chances of contamination, these ‘horses’ should ideally be on-demand — ready to move or retire instantaneously.

While trying to discover a drug, you are essentially getting thousands of different molecules to react with thousands of cells, to find out which molecule works best on which cell — to pick a winner.

The conventional way is to put the cells in thousands of “micro-wells” to react with different molecules. But that is laborious, expensive.

Prof Ashish Kumar Sen of the Department of Mechanical Engineering, IIT Madras, working in collaboration with the Lund University of Sweden, has come up with a novel method — generating droplets using sound waves. Each droplet (about a trillionth of a litre) is like a micro-well — so, at one go, you have thousands of droplets containing the cell and a molecule; you take the droplets past a detector, you will be able to see which molecule works best. While the ‘droplet’ method itself is not new, Prof Sen’s innovation is in using sound waves to produce them.

Conventionally, a droplet is made of a minuscule volume of a liquid surrounded by another immiscible fluid, and is generally produced by adjusting the volume flow rates of the two parallel streams of fluids in contact with one another. The formation of droplets in such a process is due to an instability caused by the minimisation of interfacial energy, related to interfacial tension and hydrodynamic force.

The IIT Madras researchers have, for the first time, produced droplets through an alternative way: exposing the parallel streams of fluids to sound waves.

Sound-induced on-demand droplets can be produced within 10 milliseconds, as compared to 100 milliseconds in the conventional process. Do the few tens of milliseconds make such a difference? On a scale of 1,000 by 1,000 imponderables, it does.

And this, Prof Sen believes, could cut the time taken to discover new drugs. “The typical cycle for a new drug to hit the market is 10 years. This could be significantly reduced with technology like sound-induced droplets.”

Chemical reactions take place inside droplets. Droplets carrying different types of cells and others carrying different types of chemicals can be merged in various combinations to facilitate reactions for high throughput screening in an automated fashion, he explains.

The use of sound to control droplet formation, rate and size is also well suited for applications that require on-demand and fast transition, such as microfluidics, emulsification, and encapsulation.

The team is now working towards using their sound-based droplet generation to encapsulate biological cells in droplets. This would enable single-cell analysis techniques, which, in turn, would help in designing improved diagnostic and therapeutic processes.

Not only drug discovery, droplets are useful in drug delivery, too. For example, they are used in timed-release tablets. When the time taken to create these droplets is cut by a tenth, and it is also ‘on-demand’, Prof Sen says the whole process could likely be speeded up for the manufacture of drop-encapsulated drugs. “There is a good chance (of that happening)... we haven’t really noticed studies, in that sense. The technology is here as a proof of concept.”

The icing on the cake is that labs don’t need sophisticated equipment to produce sound to induce droplets. “We used a simple piezoelectric transducer; any average lab can procure it for a couple of thousand rupees.”