# Highly sensitive multispecies spectroscopic breath analysis for real-time health monitoring and diagnosis

## Importance

Determining the identity and concentration of molecules in the breath is a powerful tool in assessing a person’s overall health, much like blood tests in clinical medicine, but in a faster and less invasive manner. The presence of a particular molecule (or a combination of molecules) can indicate the presence of a certain health problem or infection, thus facilitating a diagnosis. Monitoring the concentration of molecules of interest over time can help track the development (or recurrence) of a condition, as well as the effectiveness of the treatment given. To make breath analysis more accessible and widely adopted, we are exploring a technique to perform breath analysis with high resolution, wide spectral coverage, high specificity and high sensitivity.

## Abstract

Breath analysis enables rapid, non-invasive diagnosis, as well as long-term human health monitoring, through the identification and quantification of exhaled biomarkers. Here, we demonstrate the remarkable capabilities of Cavity Enhanced Direct Frequency Comb Spectroscopy (CE-DFCS) applied to breath analysis. We simultaneously detect and monitor four respiratory biomarkers over timeâ€”

$VSH3$

OH,

$VSH4$

,

$H2$

O, and HDO â€” as well as illustrate the feasibility of detecting at least six others (

$H2$

CO,

$VS2H6$

, OCS,

$VS2H4$

,

$VSS2$

, and

$NOTH3$

) without modification of the experimental set-up. We achieve ultra-high detection sensitivity at the parts per trillion level. This is made possible by the combination of the broadband spectral coverage of a frequency comb, the high spectral resolution offered by the individual comb teeth, and the improved sensitivity resulting from a high fineness cavity. By exploiting recent advances in frequency comb, optical coating and photodetector technologies, we can access a wide variety of biomarkers with strong spectral signatures of carbon-hydrogen bonding in the mid-IR.

## Footnotes

• Accepted August 30, 2021.
• Author contributions: research designed by QL, Y.-CC, PBC, DJN, JY and JT; QL, Y.-CC and JT carried out research; QL, Y.-CC, PBC, DJN, JY and JT contributed new reagents / analysis tools; QL, Y.-CC and JT analyzed the data; and QL, Y.-CC, PBC, DJN, JY and JT wrote the article.

• The authors declare no competing interests.