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

Abstract

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.

Machine learning enabled detection of COVID-19 pneumonia using exhaled breath analysis: a proof-of-concept study

“…To our knowledge, this is one of the largest exhaled breath studies to date [8,27,[36][37][38][39][40][41][42] and contains a diverse population of mild to severe SARS-CoV-2 patients. Ibrahim et al previously reported identifying SARS-CoV-2 positive patients using GCMS to identify a set of seven exhaled breath VOCs [8].…”

“…Furthermore, the clinical characteristics including variant type and steroid use were not recorded, and therefore limit the generalisation of their study findings. Liang et al examined exhaled breath utilizing a cavity enhanced direct frequency comb spectroscopy (CE-DFCS) approach to identify SARS-CoV-2 positive from negative university students [42]. The authors found a pattern-based approach (AUC of 0.849) outperformed a molecular-based approach (AUC of 0.769).…”

Compact mid-infrared dual-comb spectrometer over 3–4 μm via intra-pulse difference frequency generation in LiNbO3 waveguides

“…Optical frequency combs are powerful tools for rapid gas sensing. In particular, frequency comb spectroscopy in the mid-infrared (MIR, 3-5 µm) region of the atmospheric window has made significant progress in various applications, such as greenhouse gas monitoring, atmospheric monitoring, green agriculture and breath analysis [1][2][3][4] . Generally, these MIR frequency combs can be obtained via χ (2) and χ (3) nonlinear processes in lithium niobate (LN) [5][6][7][8][9] , which is a widely used optical material that can provide a wide transparency window, high nonlinear coefficient and electro-optical effect for integrated chip-based laser devices [10] .…”