Pilot Application of Magnetic Nanoparticle-Based Biosensor for Necrotizing Enterocolitis. Journal of proteomics & bioinformatics Kim, D., Fu, C., Ling, X. B., Hu, Z., Tao, G., Zhao, Y., Kastenberg, Z. J., Sylvester, K. G., Wang, S. X. 2015


Necrotizing Enterocolitis (NEC) is a major source of neonatal morbidity and mortality. There is an ongoing need for a sensitive diagnostic instrument to discriminate NEC from neonatal sepsis. We hypothesized that magnetic nanopartile-based biosensor analysis of gut injury-associated biomarkers would provide such an instrument.We designed a magnetic multiplexed biosensor platform, allowing the parallel plasma analysis of C-reactive protein (CRP), matrix metalloproteinase-7 (MMp7), and epithelial cell adhesion molecule (EpCAM). Neonatal subjects with sepsis (n=5) or NEC (n=10) were compared to control (n=5) subjects to perform a proof of concept pilot study for the diagnosis of NEC using our ultra-sensitive biosensor platform.Our multiplexed NEC magnetic nanoparticle-based biosensor platform was robust, ultrasensitive (Limit of detection LOD: CRP 0.6 pg/ml; MMp7 20 pg/ml; and EpCAM 20 pg/ml), and displayed no cross-reactivity among analyte reporting regents. To gauge the diagnostic performance, bootstrapping procedure (500 runs) was applied: MMp7 and EpCAM collectively differentiated infants with NEC from control infants with ROC AUC of 0.96, and infants with NEC from those with sepsis with ROC AUC of 1.00. The 3-marker panel comprising of EpCAM, MMp7 and CRP had a corresponding ROC AUC of 0.956 and 0.975, respectively.The exploration of the multiplexed nano-biosensor platform shows promise to deliver an ultrasensitive instrument for the diagnosis of NEC in the clinical setting.

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