In many sensitive assays, target molecules are tagged using fluorescently labeled probes and captured using magnetic beads. Here, we introduce an optical modulation biosensing (OMB) system, which aggregates the beads into a small detection area and separates the signal from the background noise by manipulating the laser beam in and out of the cluster of beads. Using the OMB system to detect human interleukin-8, we demonstrated a limit of detection of 0.02 ng/L and a 4-log dynamic range. Using Zika-positive and healthy individuals' serum samples, we show that the OMB-based Zika IgG serological assay has 96% sensitivity and 100% specificity.
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