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When trying to extract a tiny entity intact from a delicate biological sample, how best to proceed? "Blast it out", according to Ling Ren and her colleagues in Germany and Canada. Their approach uses a newly developed picosecond infrared laser (PIRL) to excite the water molecules in the biological tissue until they propel the specimen intact.

"You can think of it like a cannon ball,” says Ling Ren. “The gun powder is the water molecule and the cannon ball is the biological entity – a protein, virus or cell. The gunpowder shoots out the cannon ball, but the cannon ball stays intact."

The work is the result of a collaboration of researchers at Max Planck Institute for the Structure and Dynamics of Matter, Leibniz Institute for Experimental Virology and Biozentrum Klein Flottbek in Germany, as well as the University of Toronto in Canada. The group has already successfully used the approach to extract a small protein (green fluorescent protein), a large protein (ferritin), a virus (tobacco mosaic virus) and complete yeast cells (S. cerevisiae) from tissue samples. These extractions demonstrate the technique’s potential for minimally invasive biopsies that may help biological diagnosis and disease control.

PIRL - a gem for versatility

The researchers had previously shown that their PIRL could be used for minimally invasive surgery in macroscopic dimensions. They then began to investigate microscopic interactions with biomolecules in samples extracted with the PIRL, which led to the current work. “In the very beginning, the work was driven by scientific curiosity, but when I could see that this extraction method works for so many types of biological entities it was a nice surprise,” says Ling Ren.

Ling Ren and her colleagues chose to look at proteins because of their importance as enzymes and in other biological processes. Viruses are also interesting for dealing with disease and Ling Ren sees promise for the technique for extracting and then analysing and diagnosing suspected pathogens. The success of the technique in extracting whole cells intact was a further surprise as these are much larger entities.

"The general concept of laser extraction is not new," says Ling Ren. Other similar work includes use of CO2 lasers to cut out samples, but there the extractions are often much larger than is needed for analysis, and the sample is also damaged in the process or extracted in parts. "What is new in our work is the type of laser and the very intrinsic effect that the extracted biological entity remains intact."

Next steps

The technique functions effectively because of the rich water content of biological tissues and the high absorption of water molecules at the laser’s 3μm operational wavelength. The laser excites vibrational modes in the hydrogen bonds in water molecules, providing a very efficient conversion of optical into mechanical energy. However, the high tissue absorption at 3μm also means that it can only be used at the surface. Techniques using optical fibres to apply the technique deeper beneath the skin surface may be possible.

The researchers are now planning to combine the laser extraction method with spatial imaging and mass spectrometry to structurally and chemically map biosamples. "Mass spectrometry is the most precise way to analyse molecules so in this way we will have a very accurate idea of the chemical composition of the biological entity we are looking at - some of my colleagues are already looking into this," adds Ling Ren. A further possible development is to combine laser extraction with analysis that would allow a surgeon using the technology in a handheld device to distinguish whether the tissue being removed is healthy or not.

Full details are available at Nanotechnology, the first article to feature in the new Nanotechnology Select. More articles will follow fortnightly.