Breath analysis enables rapid, noninvasive diagnostics, as well as long-term monitoring of human health, through the identification and quantification of exhaled biomarkers. Here, we demonstrate the remarkable capabilities of mid-infrared (mid-IR) cavity-enhanced direct-frequency comb spectroscopy (CE-DFCS) applied to breath analysis. We simultaneously detect and monitor as a function of time four breath biomarkers—CH3OH, CH4, H2O, and HDO—as well as illustrate the feasibility of detecting at least six more (H2CO, C2H6, OCS, C2H4, CS2, and NH3) without modifications to the experimental apparatus. We achieve ultrahigh 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 afforded by the individual comb teeth, and the sensitivity enhancement resulting from a high-finesse cavity. Exploiting recent advances in frequency comb, optical coating, and photodetector technologies, we can access a large variety of biomarkers with strong carbon–hydrogen-bond spectral signatures in the mid-IR.

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Human breath contains hundreds of volatile molecules that can provide powerful, non-intrusive spectral diagnosis of a diverse set of diseases and physiological/metabolic states. To unleash this tremendous potential for medical science, we present a robust analytical method that simultaneously measures tens of thousands of spectral features in each breath sample, followed by efficient and detail-specific multivariate data analysis for unambiguous binary medical response classification. We combine mid-infrared cavity-enhanced direct frequency comb spectroscopy (CE-DFCS), capable of real-time collection of tens of thousands of distinct molecular features at parts-per-trillion sensitivity, with supervised machine learning, capable of analysis and verification of extremely high-dimensional input data channels. Here, we present the first application

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Rapid testing is essential to fighting pandemics such as coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exhaled human breath contains multiple volatile molecules providing powerful potential for non-invasive diagnosis of diverse medical conditions. We investigated breath detection of SARS-CoV-2 infection using cavity-enhanced direct frequency comb spectroscopy (CE-DFCS), a state-of-the-art laser spectroscopic technique capable of a real-time massive collection of broadband molecular absorption features at ro-vibrational quantum state resolution and at parts-per-trillion volume detection sensitivity. Using a total of 170 individual breath samples (83 positive and 87 negative with SARS-CoV-2 based on reverse transcription polymerase chain reaction tests), we report excellent discrimination capability for SARS-CoV-2 infection with an area under the receiver-operating-characteristics curve of 0.849(4). Our results support the development of CE-DFCS as an alternative, rapid, non-invasive test for COVID-19 and highlight its remarkable potential for optical diagnoses of diverse biological conditions and disease states.

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Buckminsterfullerene, C 60 , is the largest molecule for which quantum state resolved spectra have been observed, marking an important step towards quantum control of complex polyatomic systems. The first high resolution experiments, made possible by a combination of cavity-enhanced direct frequency comb spectroscopy and buffer-gas cooling a , revealed detailed insights into the rovibrational structure of C 60 , while also posing several outstanding spectroscopic questions. To address these, we have constructed a new spectrometer targeting the 8.5 µm vibrational band based on a continuous-wave quantum cascade laser (QCL). Linewidth narrowing via optical feedback stabilization is used to efficiently couple QCL light into a high-finesse optical cavity, providing high absorption detection sensitivity and a 100-fold improvement over the previous comb measurements. This talk will focus on new observations of low-J transitions, rovibrational perturbations, and saturated absorption effects. We will also discuss progress towards high resolution measurements of electronically excited C 60. The extraordinarily precise spectroscopic information revealed by such experiments presents new challenges for modern quantum chemistry and high accuracy ab initio spectroscopy of truly many-electron systems.