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Tiny droplets help separate tiny samples


25 September 2009

UK scientists have solved a crucial problem in proteomics: how to transfer protein samples between separation apparatus without mixing them up. 

Andrew deMello and colleagues at Imperial College London used microdroplets to couple two microfluidic separation techniques - high performance liquid chromatography (HPLC) and capillary electrophoresis. The process could enable high throughput separation of proteins, they claim, ideal for bioanalytical chemistry. 

a microfluidic droplet connector coupling two separation techniques

Droplets transfer separated components from the HPLC column to the capillary electrophoresis channel

To separate complicated mixtures of proteins, such as all those found in a cell, scientists use 2D gel electrophoresis. This separates the proteins first by their isoelectric point (the pH at which they have no net electric charge) followed by their mass. Because it is unlikely that two proteins share both of these characteristics, each protein is localised to a different position on the gel and can be analysed. But the method doesn't work well with very small samples, such as those used in proteomics. 

"With the potential for high-throughput afforded by the droplet technology, 3D information will soon also be achievable"
- Jon Cooper, University of Glasgow, UK
Many scientists have been trying to transfer 2D separation techniques to a microfluidic format. Until now, the problem has been transferring the proteins separated by the first apparatus to the second apparatus without re-mixing the samples and losing the results of the first separation. deMello's innovation is to suspend the samples as droplets in oil as they come out of the HPLC column. The oil is pumped along a microchannel to the second stage of separation, carrying the samples but not allowing them to mix. Then the oil is removed and the droplets are loaded onto the capillary electrophoresis channel for the second stage of separation. 

Jon Cooper, an expert on lab-on-a-chip technologies at the University of Glasgow, UK, describes the work as 'exciting'. 'With the potential for high-throughput afforded by the droplet technology, 3D information will soon also be achievable,' he predicts. 'This may lead to exciting new technologies for the post-genomic and analytical sciences.' 

deMello agrees: 'We expect that droplet-based interfaces could become key components in 2D or multi-dimensional separations' he says, adding that he hopes that new work on controlling droplet size will help improve the system. 

Laura Howes 

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Link to journal article

Droplet-based compartmentalization of chemically separated components in two-dimensional separations
X. Z. Niu, B. Zhang, R. T. Marszalek, O. Ces, J. B. Edel, D. R. Klug and A. J. deMello, Chem. Commun., 2009, 6159
DOI: 10.1039/b918100h

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