title: Pilot Application of Magnetic Nanoparticle-Based Biosensor for Necrotizing Enterocolitis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The exploration of the multiplexed nano-biosensor platform shows promise to deliver an ultrasensitive instrument for the diagnosis of NEC in the clinical setting.
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Dokyoon
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Surgery, Stanford University, Stanford, CA 94305, USA.
authors.forename: Changlin
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Surgery, Stanford University, Stanford, CA 94305, USA.
authors.forename: Xuefeng B
authors.initials: XB
authors.lastname: Ling
authors.affiliation: Department of Surgery, Stanford University, Stanford, CA 94305, USA.
authors.forename: Zhongkai
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Surgery, Stanford University, Stanford, CA 94305, USA.
authors.forename: Guozhong
authors.initials: G
authors.lastname: Tao
authors.affiliation: Department of Surgery, Stanford University, Stanford, CA 94305, USA.
authors.forename: Yingzhen
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Surgery, Stanford University, Stanford, CA 94305, USA.
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Kastenberg
authors.affiliation: Department of Surgery, Stanford University, Stanford, CA 94305, USA.
authors.forename: Karl G
authors.initials: KG
authors.lastname: Sylvester
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA.|Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Shan X
authors.initials: SX
authors.lastname: Wang
keywords: Biosensor; Diagnosis; NEC; Nanoparticle; Necrotizing enterocolitis; Sepsis