Label‐Free Bioanalysis Based on Low‐Q Whispering Gallery Modes: Rapid Preparation of Microsensors by Means of Layer‐by‐Layer Technology

Low‐Q‐whispering gallery modes (low‐Q‐WGM) can be used for label‐free detection of interactions between biomolecules, measuring their binding and release kinetics or for analysis of changes in the medium in real‐time. The main advantage of the low‐Q‐WGM approach over other label‐free methods is the possibility of measurements in small cavities as the method uses microparticles down to 6 µm as sensors. Commercially available dye‐doped microparticles that are used as low‐Q‐WGM sensors exhibit several drawbacks. Therefore, alternative particle types are developed and optimized as low‐Q‐WGM sensors. First, dye‐doped particles made of different materials are screened. The most critical parameter for WGM performance is the refractive index (RI) of sensor particles. Furthermore, surface roughness of particles, determined by scanning electron microscopy and atomic force microscopy, affects their performance as WGM microsensors. In the second test, fluorescent dyes immobilized on nonfluorescent particles by means of nanometer thick layer‐by‐layer (LbL) films are shown to generate a strong WGM signal. The LbL‐coated particles show remarkably less background fluorescence than dye‐doped particles and are easier to prepare. Finally, this article proposes rapid preparation methods for WGM microparticle sensors based on various parameters such as material type, RI, surface roughness, and number of coated polymer layers.