Ultrasensitive Label-free Detection of Human CEACAM5 using a WGM Resonator Based on Thin-walled Capillary

Abstract

Whispering gallery mode (WGM) laser sensors, utilizing the interaction between the in-plane evanescent field and the surface vicinity, provide enhanced sensitivity in label-free sensing for bioanalysis and disease screening. However, the unavoidably excited spiral modes resulting from the weak axial confinement and their sensing potential were overlooked. In this study, a microfluidic biosensor using the localized conical modes of an active resonator based on the thin-walled capillaries was developed, demonstrating ultrasensitive refractive index and biomolecule detection capabilities. This sensor provides nonspecific detection of bovine serum albumin (BSA) and specific detection of Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) with ultra-low detection limits, large sensing range, rapid response, and a cost-effective design, making it a promising candidate for industrial-scale production. The theoretical detection limit for CEACAM5 is as low as 0.38ag/mL (5zM), and the sensitivity in the linear region reaches 0.25nm/(ag/mL). These results are approximately an order of magnitude higher in sensitivity than currently reported active WGM biosensors, demonstrating enormous detection potential for biomarkers.