The past two decades have been a heyday for the field of microfluidics, which has adapted highly accurate etching methods from the information technology industry to create miniaturized arrays where reactions can occur with minimal amounts of reagents. The resulting “lab on a chip” has set the stage for entirely new categories of analytical hardware, such as hand-held sensors capable of conducting intricate chemistry in an isolated field setting.
Despite the progress and promise of this novel approach, however, the limits of microfluidics have become apparent in some areas of the life sciences. Mixtures containing relatively rigid organic components, such as living cells, can undergo significant shear stress within the narrow channels carved into a chip. The ensuing forces can interfere with flow rates and compromise the ability to model the behaviour of a living system. Researchers have therefore been exploring the potential of an “open space” alternative, in which fluid flows are manipulated at the same fine scale but with nothing physically touching them.
Illustration of the mathematical transforms used, first on the image of a chessboard, then on microfluidic multipoles.
Credit: Polytechnique Montréal and McGill University
Among the pioneers of this field is David Juncker, who now holds the Canada Research Chair in Bioengineering at McGill University. Fifteen years ago, he developed a microfluidic probe that operates much like the probe on a scanning microscope, in this case using the hydrodynamic forces of a constant flow of fluid to replace the solid boundaries of a conventional chip with liquid boundaries that can be established on any kind of surface.
Thomas Gervais, a professor of engineering physics at Montreal’s École Polytechnique, has been collaborating with Juncker to enhance way in which a microfluidic probe could be used. Gervais, whose background is in physics and bioengineeging, recalls how his interest in this technology was piqued after comparing the behaviour of the probe with that of classical dipoles that define electrostatic behaviour.
“We showed that there was a very strong mathematical analogy between these fluidic multipoles and electrostatic multipoles,” he explains. ““The electrostatic analogy works because the electric field lines are mathematically analogous to the velocity field lines in a very low Reynolds Number flow or Stokes flow. It’s the same math — if you know one you know the other.”
The strong mathematical analogy between electrostatics and hydrodynamics further enabled the use of an old trick developed to obtain analytical solutions from seemingly impossible to solve geometries, called conformal mapping. The technique was used by James Clerk Maxwell himself in his famous exact calculation of the field near the edges of a parallel plate capacitor. It also permits the same kind of transformations that project the spherical globe onto a flat surface to create maps of the world. Similar transforms, developed by Gervais’ students, can calculate the exact shape, not only of streamlines in complex multipolar flow pattern, but even more interestingly, of reagent concentration profiles inside them. They used the model to guide a multipole reagent delivery system to create complex interactions on a surface using several reagents at once, which could then be tailored in much the same way that microfluidic channels are designed to mimic reaction steps in a laboratory. In this case, Gervais observes, reagents could be arranged on the surface of a particular medium, such as a layer of cells arranged in a petri dish. The device could deposit active agents on this layer and then manipulate them in specific ways that will yield observations as efficiently as traditional microfluidic chips, but without the complications posed by physically touching any of the components.
The process makes for some exotic imagery, too, as can be seen in a recent Nature Communications paper that Gervais and Juncker co-authored with their students, Pierre-Alexandre Goyette, Étienne Boulais, Frédéric Normandeau, and Gabriel Laberge, who developed transforms to define the patterns created by a probe with eight or more apertures. The group employed a 3D printer to create its own version of the necessary hardware, which then generated a variety of these patterns using fluorescent reagents.
Although the technique is in its earliest stages of development, Gervais anticipates that it represents a proof of principle that will attract the interest of industry researchers.
“It’s a matter of placing the probe, filling the syringes, press ‘play’ and in the end you just have to dip your slide in water and put it in a fluorescent scanner,” he says. “We view this technology as something that could be used to automate assays in the life sciences.”