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


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.


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 time—






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




, OCS,




, and


) 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.


    • 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.

  • This article is a direct PNAS submission.

  • This article contains additional information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2105063118/-/DCSupplemental.

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