Scientists at EPFL and the University of Geneva have developed a microfluidic device smaller than a domino that can simultaneously measure up to 768 biomolecular interactions.
Inside our cells in the body, molecules are constantly binding and separating from one another. It’s this game of constant flux that drives gene expression asides essentially every other biological process. Understanding the specific details of how these interactions take place is thus crucial to our overall understanding of the fundamental mechanisms of living organisms. There are millions of possible combinations of molecules, however; determining all of them would be a Herculean task.
Various tools have been developed to measure the degree of affinity between a strand of DNA and its transcription factor. They provide an indication of the strength of the affinity between them. Commercial devices, however, have one main drawback: many preliminary manipulations are necessary before an experiment can be carried out, and even then, the experiment can only focus on a dozen interactions at a time.
As part of his doctoral research at the California Institute of Technology (Caltech), Sebastian Maerkl designed a device that he named “MITOMI” — a small device containing hundreds of microfluidic channels equipped with pneumatic valves. The new version, “k-MITOMI,” was developed in the context of the SystemsX.ch RTD DynamiX in cooperation with the University of Geneva.
k-MITOMI has 768 chambers, each one with a valve that allows DNA and transcription factors to interact in a very carefully controlled manner. “In traditional methods, we generally manage to determine if an interaction takes place or not, and then we restart the experiment with another gene or another transcription factor,” Maerkl explains. “Our device goes much further, because it allows us to measure the affinity and kinetics of the interaction.”
The strength of the device lies in a sort of “push-button” in its microreactors. A protein substrate is immobilized on the device; above it circulates a solution containing DNA moelcules. The push-button is activated at regular intervals of a few milliseconds, trapping protein-DNA complexes that form on the surface of the device. “Then we close the lid, and fluorescence reveals the exact number of bound molecules,” explains Maerkl. “We can also observe how long these molecules remain bound.”