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Optical physics

New laser could spot signs of cancer in exhaled breath

30 Sep 2015
Breathtaking: new laser could help to detect cancer

A new type of compact infrared laser promises to make it easier to identify specific molecules at very low concentrations within complex chemical samples. That is the claim of physicists in Germany and Spain, who have created the high-power, ultrashort-pulsed, broadband laser. They add that the device shows particular promise for spotting molecules within exhaled breath that are indicative of certain kinds of disease.

Molecular spectroscopy, or “molecular fingerprinting”, involves shining a laser beam spanning a certain portion of the electromagnetic spectrum through a liquid or gas and then comparing the beam before and after it travels through the sample – the specific wavelengths absorbed revealing the composition and structure of molecules within the sample. Most molecular vibrations can be stimulated by mid-infrared radiation (2–25 μm), and therefore laser light covering this part of the spectrum is very useful for molecular fingerprinting.

Because no existing lasing media are able to emit light across a broad range of mid-infrared (MIR) wavelengths, current devices operating in this part of the spectrum use nonlinear crystals to shift shorter-wavelength near-infrared (NIR) radiation to longer wavelengths. However, these crystals have significant limitations, and practical fingerprinting systems would benefit from a different approach.

In the latest work, Ioachim Pupeza of the Max Planck Institute of Quantum Optics near Munich and colleagues have created a system that makes use of a different type of nonlinear crystal. NIR radiation is first created in a novel high-power, diode-pumped femtosecond laser “oscillator”, in which a thin disc made from a ytterbium-doped material forms the active medium. The light from the oscillator is compressed into pulses lasting just 20 fs (2 × 10–14 s) and is then converted into the MIR using a nonlinear crystal made from lithium–gallium-sulphide. The current prototype device occupies an area of about 2 m2.

Crucial crystal

“Apart from developing the oscillator, the choice of the nonlinear medium was crucial,” explains Pupeza. “It was not clear that any crystal could be found that fulfils the necessary requirements of low absorption and high damage threshold.”

Pupeza says that the new system combines a number of features that make it useful for molecular fingerprinting – including its power. As Pupeza points out, many molecules studied using the technique exist in minuscule concentrations. Exhaled human breath, for example, containing organic compounds that are present at the level of just a few parts per billion. An intense light source is therefore needed to have a decent chance of detecting such molecules. The average power of the pulse train in the current work is 0.1 W.

The new system also spans a broad range of wavelengths (6.8–16.4 μm), which allows a large number of individual absorption lines to be recorded for any given type of molecule.

Clear identification

This means that a molecule can be more clearly identified against the very high background noise. “It’s the same with one’s fingerprints,” explains Pupeza. “To precisely identify a person, an entire fingerprint is much more useful than just a tiny fraction of it.”

Another useful characteristic of the new laser is its spatial coherence. This increases the distance the beam can travel through a sample without undergoing significant losses, which boosts its sensitivity to low-concentration molecules. In addition, the beam has phase coherence, which means that the electric field of its ultrashort pulses – each less than two wavelengths long – is identical from one pulse to the next.

Phase coherence increases the amount of information that can be extracted from the sample because the phase of the light will change as it interacts with the sample molecules. In addition, the laser’s MIR beam can be combined with a part of the original NIR beam. This allows the laser’s output to be measured using NIR detectors, which have far lower noise levels than their MIR equivalents.

Designed for hospitals

The group has designed its new device so that it can be used for one application in particular: detecting molecular markers of disease. The air we breathe out is believed to contain very small traces of molecules specific to certain types of disease, including some forms of cancer, and Pupeza says that the new laser could help scientists to better understand the cellular processes underpinning those diseases. He also says that such a compact device, being potentially easy to install in hospitals and clinics, could “facilitate a standardized collection of disease-specific molecular fingerprints”.

The researchers are currently working to increase the bandwidth of their device so that it covers the full 2–25 μm band that is relevant to molecular fingerprinting. Other potential applications include detecting explosives or monitoring air quality.

Søren Rud Keiding, a chemist at Aarhus University in Denmark, describes the latest work as “an impressive example of the development of new few-cycle infrared and terahertz sources with extreme brightness”, adding that such sources have “spurred a renewed interest in molecular spectroscopy”. But he notes that the new device is not without precedent. It is, he says, a more powerful version of an ultrashort-pulse source developed by Alfred Leitenstorfer and colleagues at the Technical University of Munich in 2000.

The research is described in Nature Photonics.


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