Ultrasensitive Detection of Biomarkers in a Color‐Switchable Microcavity‐Reactor Laser

Abstract Early detection and diagnosis are vitally important in reducing the mortality rate of fatal diseases but require highly sensitive detection of biomarkers. Presently, detection methods with the highest sensitivity require in vitro processing, while in vivo compatible fluorescence detections require a much higher concentration of biomarkers or limit of detection (LOD). In this paper, a fundamentally new strategy for ultrasensitive detection based on color‐switchable lasing with a cavity‐enhanced reduction of LOD is demonstrated, down to 1.4 × 10⁻¹⁶ mg ml⁻¹ for a quantitative detection, lower than both the fluorescence method and plasmonic enhanced method. For a qualitative or a yes/no type of detection, the LOD is as low as 10^–17 mg ml⁻¹. The approach in this work is based on a dye‐embedded, in vivo compatible, polystyrene‐sphere cavity, penetrable by biomarkers. A polystyrene sphere serves the dual roles of a laser cavity and an in vivo bio‐reactor, in which dye molecules react with a biomarker, reporting biomarker information through lasing signals. The cavity‐enhanced emission and lasing with only a single biomarker molecule per cavity allow improved visual distinguishability via color changes. Furthermore, when combined with a narrow‐band filter, the color‐switchable lasers act as an “on‐off” logic signal and can be integrated into multiplexing detection assay biochips.