Theoretical Analysis of Bioassays Based on Microlaser Ensembles

We present a bioassay platform based on microlaser ensembles, offering a sensitive assay method with a high dynamic range. In this platform, microlasers are functionalized to capture analytes. The captured analytes introduce quenchers, thus increasing microlasers' lasing thresholds and even turning off microlaser emission. We develop a theoretical model to count the number of quenchers and hence the number of captured analytes for microlasers by measuring their lasing thresholds. A statistical model is established to link the distribution of captured analytes to the lasing fraction of microlasers. Fundamentally different from digital ELISA, in which a microunit (such as a microbead) saturates when more than one analyte is present, the microlaser-based method can perform multiple quantized signal readouts by scanning over the lasing threshold with a varied external pump. Therefore, this platform does not require the average number of analytes per microlaser be much lower than one, thus achieving a higher dynamic range. The detection limit and the factors that may affect the detection limit are also discussed.