A new device developed at California Institute of Technology and Ecole Polytechnique Federale de Lausanne in Switzerland may help research conduct large scale studies of biomolecular interactions at a rapid rate.
Known as k-MITOMI, the current version of the microfluidic device features 768 chambers within which DNA strings and transcription factors that can stick onto them are carefully brought together. While this is happening, the k-MITOMI is able to measure the attraction between the compounds and the kinetics involved.
Some details from Ecole Polytechnique Federale de Lausanne:
This microfluidic device 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.”
In addition to providing quantitative kinetic information, the k-MITOMI device can work in a “massively parallel” manner. Each of the 768 independent chambers can simultaneously analyze different molecule pairs. It can also be used to synthesize proteins in vitro, with a massive reduction in time and number of manipulations compared to the traditional method, which involves producing proteins inside a living organism such as a bacterium, purifying, and putting them in contact with the genes to be studied.
“The number of protein-protein and protein-DNA interactions that remain to be characterized is phenomenal. Our device not only allows us to accelerate the acquisition of this information, which is crucial to our understanding of living organisms, but it also meets a need for the production of specific proteins,” adds Maerkl.
Press release: Hundreds of biochemical analyses on a single device
Open access article in PNAS: Massively parallel measurements of molecular interaction kinetics on a microfluidic platform