Raman-based breathalyzer offers point-of-care Covid diagnosis

08 Feb 2022

Nanyang Technological University designs device able to screen for virus in 5 minutes.

Analysis of exhaled breath is a promising approach for the detection and diagnosis of multiple diseases and conditions, with spectroscopic techniques potentially able to detect different biomarkers rapidly and conveniently.

Recent advances in the optical components employed, such as frequency combs specifically intended to facilitate simultaneous detection of multiple species, along with optimized device architectures, have made this a growing area of study.

Applying the principle to detection of infectious disease has always been an attractive application area, one currently made more significant by its potential use against Covid-19.

A project at Singapore's Nanyang Technological University has now designed a breathalyzer module based around surface-enhanced Raman scattering (SERS), said to allow Covid screening in under 5 minutes and offer a better alternative to nasal swabbing and PCR testing. The results were published in ACS Nano.

"Scientists have developed breathalyzer-type tests for Covid which rely on differences in concentrations of volatile organic compounds exhaled by those infected with the coronavirus, but most require bulky, nonportable instruments for analysis," commented the Nanyang project team. "We wanted to develop a quick, convenient and accurate breathalyzer test that would be suitable for on-site screening of large numbers of people."

The researchers designed a handheld module that contains a chip with three SERS sensor molecules attached to silver nanocubes. When a person exhales into the device for 10 seconds, Covid biomarkers in the breath chemically interact with the sensors. The breathalyzer is then loaded into a portable Raman spectrometer, and the bound compounds are characterized based on changes to the SERS signal.

Next-generation noninvasive breath diagnostics

Raman is one of several spectroscopy modalities that have been brought to bear on the problem of Covid detection. Research at Oxford University has shown how fluorescence spectroscopy and image analysis can identify the virus in a swab sample more reliably than a standard PCR test, and potentially do the same for other viruses beyond Covid.

Elsewhere a US team has studied whether spatial light-interference microscopy paired with deep-learning algorithms can achieve the same end result without the need to label samples first.

SERS is attractive for Covid detection thanks to the chemical specificity of the technique and the unique vibrational signature of the spike protein involved, although real-world application has always faced challenges connected to the low signal strength and the potentially complex Raman response of multi-species environments. Using three individual SERS probe molecules in the Nanyang device, termed MBA, MPY and ATP, all able to bond with volatile organic biomarkers in exhaled breath, is intended to tackle these hurdles.

In trials on 501 people in hospitals and airports in Singapore, the method had a 3.8 percent false-negative and 0.1 percent false-positive rate, said to be comparable to PCR tests, but it could be completed on-site in less than 5 minutes.

"The SERS-based breathalyzer harnesses key variations in vibrational fingerprints arising from interactions between breath metabolites and multiple molecular receptors, to establish a robust partial least-squares discriminant analysis model for high throughput classifications," said the project.

"Our strategy strives to spur the development of next-generation, noninvasive human breath diagnostic toolkits tailored for mass screening purposes."