SERS-based serodiagnosis of acute febrile diseases using plasmonic nanopopcorn microarray platforms

We report a surface-enhanced Raman scattering (SERS)-based immunoassay platform for the rapid diagnosis of scrub typhus and murine typhus, which are the most common acute febrile diseases in South Korea. A microarray device, composed of multiple gold nanopopcorn substrates capable of detecting ultra-sensitive biomarkers, was used as a multiplex SERS-based assay platform. Sequentially diluted titers of Orientia tsutsugamushi and Rickettsia typhi specific human IgG/IgM antibodies, which are biomarkers of two typhus diseases, were analyzed by Raman spectroscopy, and the peak intensity was plotted against the different titer concentration range (0-2048 and 0-1024 for O. tsutsugamushi IgG/IgM and 0-8192 and 0-256 for R. typhi IgG/IgM) to generate calibration curves. The sensitivities and limits of detection (LODs) determined for four different IgG/IgM antibodies were significantly lower than those for the ELISA method. The LODs of titer concentrations for O. tsutsugamushi IgG/IgM and R. typhi IgG/IgM are determined to be 20.4, 7.03, 16.8 and 12.5, respectively. The LOD values were all lower than the cut-off values (256, 16, 128, and 64) used for clinical diagnosis, which means that this assay platform can diagnose two typhus diseases with high sensitivity. When the microarray sensors are combined with portable Raman spectrophotometers, which are commercially available worldwide, it is also possible to directly diagnose a patient in the field without sending their blood sample to a hospital.