Magnetic modulation biosensing: How it works and how it can be used to detect the Zika virus

Current serological diagnostic tests for Zika virus (ZIKV) suffer from reduced sensitivity, high cross-reactivity, low specificity, and lengthy protocols. Here, we begin by reviewing serological and antigenemia assays that are either commercially available or under development. We then focus on a new technology, named magnetic modulation biosensing (MMB), that enables rapid detection of ZIKV immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies. The MMB system utilizes magnetic beads that are conjugated to recombinant ZIKV nonstructural 1 (NS1) protein, which specifically captures Zika IgM/IgG antibodies. A second fluorescently labeled antibody is then added, forming a “sandwich” with the analyte and the capture protein. An oscillating magnetic field gradient concentrates the beads within the sample volume and transports them in a periodic motion in and out of a laser beam, producing an oscillating signal that is detected and demodulated. Compared with EUROIMMUN enzyme-linked immunosorbent assay (ELISA), MMB exhibits a much higher clinical sensitivity (88%-97% vs 38%-74%), a much longer time after symptom onset in which the IgM antibodies can be detected (5-180 vs 7-29 days post symptom onset), and a lower false positive rate. Additionally the specificity is 100%, and the cross-reactivity with West Nile and dengue viruses is minimal (0%-4%). The sensitivity, specificity, and simplicity of the MMB assays can significantly improve Zika diagnosis and provide accurate results for public health agencies.