Biomedical spectroscopy

We extend the Nobel Prize-winning concept of optical frequency combs to the infrared portion of the electromagnetic spectrum to rapidly and reliably detect hundreds of biomarker molecules in exhaled human breath, unlocking a goldmine of data on the body’s metabolism and medical conditions. Mapping biomarker patterns to specific diseases paves the way for new non-invasive, breath-based, precision medical diagnostics that operate in real time at the point of care. We use ultra-wideband (> one octave) optical frequency combs that operate in the mid-infrared (3-12 µm) “molecular fingerprint” region of the spectrum, where biomarker molecules exhibit their strongest fundamental vibrational-rotational resonances. We employ two novel frequency comb generation methods: optical subharmonic generation and intrapulse difference frequency generation, both of which use ultrafast lasers as the pump source. The detection method, dual-comb spectroscopy, provides an unprecedented combination of broadband coverage and, at the same time, superior spectral resolution, high speed and massive parallelism of data acquisition. With the ability to detect about a million spectral data points with comb-line resolution in real time with the absolute accuracy of the optical frequency scale through coupling to a rubidium atomic clock, the system can simultaneously identify hundreds of molecular species in a mixture  with a sensitivity of one part per billion. This provides the basis for matching biomarker patterns with specific diseases in future medical research and has the potential to revolutionize modern medicine by enabling early diagnosis of many health conditions.