  Rapid, sensitive detection of biomolecules is important for improved testing
methods for viruses as well as biomarkers and environmental hormones. For
example, testing for SARS-CoV-2 is essential in the fight against the COVID-19
pandemic. Reverse-transcription polymerase chain reaction (RT-PCR) is the
current standard for COVID-19 testing; however, it is hampered by the long
testing process. Shortening the testing process while achieving high
sensitivity would facilitate sooner quarantine and thus presumably prevention
of the spread of SARS-CoV-2. Here, we aim to achieve rapid, sensitive detection
of the SARS-CoV-2 nucleocapsid protein by enhancing the performance of optical
biosensing with a dual-comb configuration of optical frequency combs. The
virus-concentration-dependent optical spectrum shift is transformed into a
photonic RF shift by frequency conversion between the optical and RF regions,
facilitating mature electrical frequency measurements. Furthermore,
active-dummy temperature-drift compensation enables very small changes in the
virus-concentration-dependent signal to be extracted from the large, variable
background signal. This dual-comb biosensing technique has the potential to
reduce the COVID-19 testing time to 10 min while maintaining sensitivity close
to that of RT-PCR. Furthermore, this system can be applied for sensing of not
only viruses but also various biomolecules for clinical diagnosis, health care,
and environmental monitoring.
