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.of the studied molecules with markers. However, these markers alter the intrinsic protein properties, which in turn can affect their interactions and bioactivity. [11] Therefore, label-free methods such as surface plasmon resonance (SPR), [12] whispering gallery mode (WGM), [13][14][15] quartz crystal microbalance (QCM), [16] reflectometric interference spectroscopy (RIfS), [17] biolayer interferometry (BLI), [18] or nanowire sensors [19] have gained popularity with the ultimate aim of replacing current diagnostic assays. In particular, WGM-based devices provide an excellent means of inexpensive and label-free biomolecule detection. The basic operating principle of WGM relies upon total internal reflection (TIR) of light trapped inside a circular resonator, e.g., a microparticle. [20][21][22] Since the trapped light circulates along the microparticle surface over a thousand times before escaping, photons associated with certain wavelengths create a constructive interference. This set of constructive interferences at discrete wavelengths is called WGM. [20][21][22][23][24] These modes are detectable by a high resolution spectrograph as narrow peaks in the optical spectrum. Any modification in optical geometry or refractive index (RI) of the particle as well as in the surrounding environment induces a shift in WGM wavelength positions Δλ, which is the basis of WGM-based sensing.Sensing performance of the WGM resonator is described by two factors. The first factor is the resonator's quality factor (Q-factor = full widths at half maximum (FWHM)/resonance wavelength), which is proportional to the number of recirculati...