Multinozzle to speed up lab-on-a-chip proteomics

The pace of proteomics research is set to increase, thanks to the development of a new device that interfaces lab-on-a-chip technology with a conventional mass spectrometer. The multinozzle nanoelectrospray emitter array, developed by Daojing Wang and colleagues at the US Department of Energy’s Lawrence Berkeley National Laboratory, is easily microfabricated via silicon lithography in a five-step process that requires only one mask.

Proteomics is the large-scale study of protein structure and function and, after genomics, is the next step in understanding biological systems. But while a gene remains fairly constant, proteomics varies from cell to cell and is constantly changing. One of the most effective ways to study protein mixtures is mass spectroscopy. This breaks proteins into small fragments whose masses can be exactly measured. Lab-on-a-chip, or microfluidics, refers to devices with a variety of miniaturised and integrated conventional laboratory functions on a single chip up to a few centimetres across. The chips can handle liquid volumes down to less than a pico-litre.

’The problem has been how to marry chip-based analysis systems with conventional electrospray mass spectrometers,’ said microfluidics expert Andrew deMello at Imperial College London. Polymer-based systems have been tried but they tend to have a high affinity for proteins and are incompatible with some organic solvents, leading to microfluidic flow problems. Nozzle-clogging has also been a problem with these systems. Thus, there has been a lack of cheap readily available enabling technology for a high quality interface.

The Lawrence Berkeley team’s solution was to use a novel but simple silicon microfabrication process that can mass-produce multi-nozzle emitters from silicon wafers. This allowed the dimensions and number of free-standing nozzles to be systematically and precisely controlled during the fabrication process so that they could be integrated with a microfluidic channel.

The new nozzles achieved resolutions, sensitivities and stabilities of peptide and protein detection during mass spectroscopic analysis comparable with commercial electrospray tips.

’This is an interesting first step towards integrating microfluidics with mass spectroscopy’, said deMello. ’The nice thing about the US team’s approach is that making the microfluidic channel, the nozzles, and integrating with a conventional mass spectrometer is simple. The performance in comparison with commercial electrospray tips looks very good. What would be interesting now is to see how this new system performs in real proteomic studies.’

Lionel Milgrom

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