Magnetic Nanoparticle Mediated Enhancement of Localized Surface Plasmon Resonance for Ultrasensitive Bioanalytical Assay in Human Blood Plasma

We demonstrate that Fe₃O₄ magnetic nanoparticle (MNP) can greatly enhance the localized surface plasmon resonance (LSPR) of metal nanoparticle. The high refractive index and molecular weight of the Fe₃O₄ MNPs make them a powerful enhancer for plasmonic response to biological binding events, thereby enabling a significant improvement in the sensitivity, reliability, dynamic range, and calibration linearity for LSPR assay of small molecules in a trace amount. Rather than using fluorescence spectroscopy or magnetic resonance imaging, this study marks the first use of the label-free LSPR nanosensor for a disease biomarker in physiological solutions, providing a low cost, clinical-oriented detection. This facile and ultrasensitive nanosensor with an extremely light, robust, and low-cost instrument is attractive for miniaturization on a lab-on-a-chip system to deliver point-of-care medical diagnostics. To further evaluate the practical application of Fe₃O₄ MNPs in the enhancement of LSPR assay, cardiac troponin I (cTnI) for myocardial infarction diagnosis was used as a model protein to be detected by a gold nanorod (GNR) bioprobe. MNP-captured cTnI molecules resulted in spectral responses up to 6-fold higher than direct cTnI adsorption on the GNR sensor. The detection limit (LOD) was lowered to ca. 30 pM for plasma samples which is 3 orders lower than a comparable study. To the best of our knowledge, this marks the lowest LOD for a real plasma protein detection based on label-free LSPR shift without complicated instrumentation. The observed LSPR sensing enhancement by Fe₃O₄ MNPs is independent of nonspecific binding