Laborious optimisation trials could be a thing of the past for scientists trying to create new proteins. A time-saving device developed by US researchers can rapidly screen numerous cell-free protein synthesis experiments and dramatically reduces the amounts of reagents used.

Protein expression occurs at outlets in the microchannel device

Cell-free protein expression uses DNA templates to make proteins without using whole cells. But identifying the ideal conditions for the protein expression can be a time-consuming exercise. The optimum method can vary depending upon the protein, medium, and expression system used. With this in mind a team led by Hugh Fan at the University of Florida in Gainesville and David Beebe from the University of Wisconsin-Madison, has created a lab-on-a-chip style device to rapidly screen experimental conditions.

The system is based on nutrient transfer between two droplets - one formed from a nutrient solution, the other, larger, droplet from a protein expression solution containing a DNA template. The transfer, or passive pumping, occurs because the two droplets are connected by a microchannel. 'As the droplets have different sizes they have different surface tensions,' explains Fan. 'Liquid flows between the droplets to balance the difference in the force.' The nutrients are then transported into the protein expression solution, allowing protein production. 

The team demonstrated its system by optimising the production of a luciferase - an enzyme that catalyses a light-emitting process and so can be easily monitored. Varying the droplets allowed them to tune the expression conditions. They found that the device consumes up to 800 times less reagents than a commercial system and could run nearly 200 experiments in parallel. Also, the passive pumping approach increased the yield by almost five times compared to simply mixing the nutrient and expression solutions within a centrifuge tube.

Mengsu Yang, an expert in microfluidic technology from the City University of Hong Kong, welcomes the research. 'The array technology combined with the passive pumping process provides an exciting new system for the high-throughput chemical or biochemical generation of diverse ranges of products,' he says. 'The technology could also be adopted for other applications such as drug screening and protein crystallisation.' 

Russell Johnson

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