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Rapid, sensitive detection of biomolecules is important for improved testingmethods for viruses as well as biomarkers and environmental hormones. Forexample, testing for SARS-CoV-2 is essential in the fight against the COVID-19pandemic. Reverse-transcription polymerase chain reaction (RT-PCR) is thecurrent standard for COVID-19 testing; however, it is hampered by the longtesting process. Shortening the testing process while achieving highsensitivity would facilitate sooner quarantine and thus presumably preventionof the spread of SARS-CoV-2. Here, we aim to achieve rapid, sensitive detectionof the SARS-CoV-2 nucleocapsid protein by enhancing the performance of opticalbiosensing with a dual-comb configuration of optical frequency combs. Thevirus-concentration-dependent optical spectrum shift is transformed into aphotonic 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 thevirus-concentration-dependent signal to be extracted from the large, variablebackground signal. This dual-comb biosensing technique has the potential toreduce the COVID-19 testing time to 10 min while maintaining sensitivity closeto that of RT-PCR. Furthermore, this system can be applied for sensing of notonly viruses but also various biomolecules for clinical diagnosis, health care,and environmental monitoring.

Rapid, high-sensitivity detection of biomolecules using dual-comb biosensing: application to the SARS-CoV-2 nucleocapsid protein