Laser-based sensor can ‘see’ what’s in any gas sample

An expert sommelier can tell a lot about what’s in a glass of wine from the merest smell and now a team of physicists at University of Colorado, Boulder (CU) and the US National Institute of Standards and Technology (NIST) have achieved a similar feat of sensing – and for a much wider range of substances.

The group has developed a new laser-based device that can take any sample of gas and identify a huge variety of the molecules within it. It is sensitive enough to detect molecules at minute concentrations – at levels which are parts per trillion.

The design is simple enough that researchers could employ the method quickly – and at a low cost – in a range of settings, from diagnosis of illness in humans to tracking greenhouse gas emissions from factories.

The study was led by scientists at JILA, a joint research institute established between CU and NIST.

“Even today I still find it unbelievable that the most capable sensing tool can in fact be built with such simplicity, using only mature technical ingredients but tied together with a clever computation algorithm,” said Qizhong Liang, lead author of the research and a doctoral student at JILA.

To show what the tool is capable of, Liang and his colleagues drilled down on an important question in medicine: What’s in the air you breathe out?

The team analysed breath samples from human subjects and showed that they could, for example, identify the types of bacteria living in peoples’ mouths. The technique could one day help doctors diagnose lung cancer, diabetes, chronic obstructive pulmonary disease (COPD) and much more.

Physicist Jun Ye, senior author of the study, said that the work builds on around three decades of research into quantum physics at CU and NIST – especially around a type of specialised device known as a frequency comb laser.

“The frequency comb laser was originally invented for optical atomic clocks, but very early on, we identified its powerful application for molecular sensing,” said Ye, a fellow of JILA and NIST and professor adjoint of physics at CU Boulder.

“Still, it took us 20 years to mature this technique, finally allowing universal applicability for molecular sensing.”

All gases, from pure carbon dioxide to your stinky breath after you eat garlic, carry an identifiable ‘fingerprint’.

JILA’s Jan Hall pioneered these lasers, winning the Nobel Prize in Physics for his work in 2005.

Examining those gases with a laser that spans multiple ‘optical frequencies’ – colours –molecules in a gas sample will absorb light at different frequencies. In a previous study, Liang et al used this laser absorption detection principle to screen human breath samples for signs of infection with SARS-CoV-2.

Frequency combs are well suited to that technique because, unlike traditional lasers, they emit pulses of light in thousands to millions of colours at the same time.

“We enclose the gas sample with a pair of high-reflectivity mirrors, forming an ‘optical cavity’. The comb light can now bounce between those mirrors several thousand times to effectively increase its absorption path length with the molecules.” Liang said.

‘Optical cavities’ are tricky to work with and eject laser beams if they aren’t properly matched to the resonant modes of the cavity. As a result, scientists previously could only use a narrow range of comb light – and therefore only detect a narrow range of molecules – per test.

In their study, Liang et al overcame this longstanding challenge with novel technique they have named Modulated Ringdown Comb Interferometry – MRCI and pronounced ‘mercy’.

Rather than keep the optical cavity in a steady state, the study parameters changed its size, periodically. This jiggling, in turn, allowed the cavity to accept a much wider range of frequencies of light. The team then deciphered the complicated laser intensity patterns emerging from the cavity with computational algorithms to determine the samples’ chemical contents.

“We can now use mirrors with even larger reflectivity and send in comb light with even broader spectral coverage,” Liang said. “But this is just the beginning. Even better sensing performance can be established using MRCI.”

The team is now turning its new gas sniffer on human breath.

“Exhaled breath is one of the most challenging gas samples to be measured, but characterising its molecular compositions is highly important for its powerful potential for medical diagnostics,” said Apoorva Bisht, co-author of the research and a doctoral student in Ye’s lab.

Bisht, Liang and Ye are now collaborating with researchers at the hospitals of CU Anschutz Medical Campus and the Children’s Hospital, Colorado, to use MRCI to analyse a range of breath samples. They are examining whether MRCI can distinguish samples taken from children with pneumonia from those taken from children with asthma.

The group is also analysing the breath of lung cancer patients before and after tumour removal surgery and is exploring whether the technology can diagnose people in early stages of chronic obstructive pulmonary disease.

“It will be tremendously important to validate our approach on real world subjects,” Ye said. “Through close collaboration with our medical colleagues we are committed to developing the full potential of this technique for medical diagnosis.”

For further reading please visit: 10.1038/s41586-024-08534-2