Breath analysis by ultra-sensitive broadband laser spectroscopy detects SARS-CoV-2 infection

Abstract

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

Theory of rotationally resolved two-dimensional infrared spectroscopy including polarization dependence and rotational coherence dynamics

“…These computer resources have been made freely available for download here [29]. We expect in the future that machine learning will be applied to deciphering RR2DIR spectra, as has been applied to linear multi-species spectra [57,58]. The first-principles framework and computer simulation tools presented here can be used for generating spectra for training machine learning algorithms for interpreting RR2DIR spectra and extracting species concentrations.…”

Controlling rotationally-resolved two-dimensional infrared spectra with polarization

“…In the current era, many new developments in spectroscopy are being driven by rapid progress in optical frequency combs. For example, frequency combs are now used in precision metrology [1,2], searches for new physics beyond the standard model [3], discovery of extrasolar planets [4,5], advanced spectroscopy and imaging in the research laboratory [6][7][8], and breath analysis in clinical settings [9], to name just a few applications.…”

Mid-Infrared Upconversion Time-Stretch Spectroscopy

“…We demonstrate high-resolution mid-infrared spectroscopy of gas-phase methane molecules with a high resolution of 0.017 cm -1 . This unprecedentedly high-speed vibrational spectroscopy technique would satisfy various unmet needs in experimental molecular science, e.g., measuring ultrafast dynamics of irreversible phenomena 12,13,20 , statistically analyzing a large amount of heterogeneous spectral data 21,22 , or taking broadband hyperspectral images at a high frame rate [23][24][25] .Broadband mid-infrared (MIR) spectroscopy is a powerful non-invasive tool for identifying molecular species and sensing subtle changes in molecular structures that reflect environmental conditions, and various applications have been widely investigated, such as environmental gas monitoring 14,26,27 , combustion analysis 20,28 , photoreactive protein analysis 12 , liquid biopsy 21,29 , breath diagnosis 30,31 , etc. One of the promising directions of instrumental development of broadband MIR spectroscopy is increasing the measurement speed because normal vibration modes of molecules have huge MIR absorption cross-sections, which are orders of magnitude larger than Raman scattering cross-sections.…”

“…Broadband mid-infrared (MIR) spectroscopy is a powerful non-invasive tool for identifying molecular species and sensing subtle changes in molecular structures that reflect environmental conditions, and various applications have been widely investigated, such as environmental gas monitoring 14,26,27 , combustion analysis 20,28 , photoreactive protein analysis 12 , liquid biopsy 21,29 , breath diagnosis 30,31 , etc. One of the promising directions of instrumental development of broadband MIR spectroscopy is increasing the measurement speed because normal vibration modes of molecules have huge MIR absorption cross-sections, which are orders of magnitude larger than Raman scattering cross-sections.…”