MIT technique using electrical manipulation could help screen biological samples while avoiding drawbacks of microfluidic technology.
Microfluidics, where painstakingly-constructed networks of narrow channels and chambers guide small amounts of chemicals or biological materials into contact with each other to carry out sequences of reactions, have proved useful in testing arrays of related materials, especially in screening candidates for drug trials.
The technique, however, is notoriously temperamental so the MIT team, at the institution’s famous Media Laboratory, has developed a technique that uses electrical fields to move droplets of liquid precisely on a flat surface, mixing them together under controlled conditions.
This, they claim, could allow thousands of reactions to be carried out in parallel, and could prove more cost-effective than microfluidics while also allowing reactions to be carried out at larger scales, making the results easier to study.
“Traditional microfluidic systems use tubes, valves, and pumps,” said Udayan Umapathi, who led the development of the new system. “What this means is that they are mechanical, and they break down all the time. I noticed this problem three years ago, when I was at a synthetic biology company where I built some of these microfluidic systems and mechanical machines that interact with them. I had to babysit these machines to make sure they didn’t explode.”
Moreover, Umapathi added, as the interactions studied by the life science industry become more complex, so the microfluidic mechanisms needed to carry out reactions are becoming impractical.
“We need technologies to manipulate smaller and smaller-volume droplets,” he said. “Pumps, valves, and tubes quickly become complicated. In the machine that I built, it took me a week to assemble 100 connections. Let’s say you go from a scale of 100 connections to a machine with a million connections. You’re not going to be able to manually assemble that.”
The new technique does away with all the tubes, valves, and pumps. Instead, Umapathi used a simple printed circuit board: a polymer substrate with an array of copper electrodes and wires deposited on top of it. The surface was then coated with a dense layer of micrometre-diameter spheres of a hydrophobic material. This coating forces any water-based liquid falling on top of it to form into a spherical shape. Charging the electrode underneath the droplet pulls it towards the surface, flattening it out. If the charge is gradually reduced, while the adjacent electrode is activated at the same rate, the droplet is pulled across the surface.
Moving droplets requires high voltages, somewhere between 95 and 200 volts. But 300 times a second, a charged electrode in the MIT researchers’ device alternates between a high-voltage, low-frequency (1-kilohertz) signal and a 3.3-volt high-frequency (200-kilohertz) signal. The high-frequency signal enables the system to determine a droplet’s location, using essentially the same technology as touch-screen phones. The signal generated by the droplet also allows the device to determine its volume.
The software controlling the droplets automatically calculates their paths across the surface and coordinates the timing of successive operations. “The operator specifies the requirements for the experiment — for example, reagent A and reagent B need to be mixed in these volumes and incubated for this amount of time, and then mixed with reagent C,” Umapathi explained. “The operator doesn’t specify how the droplets flow or where they mix. It is all precomputed by the software.”
Umapathi believes this system is well-suited to technologies already widely in use in the pharmaceutical industry, which uses robots equipped with arrays of tiny pipettes to simultaneously drop small amounts of solutions of drug candidates or biological materials into reaction chambers for screening.
“If you look at drug discovery companies, one pipetting robot uses a million pipette tips in one week,” Umapathi said. “That is part of what is driving the cost of creating new drugs. I’m starting to develop some liquid assays that could reduce the number of pipetting operations 100-fold.”
The MIT team’s paper is to be published in the online journal MRS Advances.