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Magnetic protein chips for detection of radiation exposure and neonatal diseases [electronic resource]

This dissertation presents the basic principles of the magnetic protein chip immunoassay and applications of the magnetic protein chip for the detection of protein biomarkers. The magnetic protein chip is based on the giant magnetoresistive (GMR) spin-valve sensors, and electrical resistance changes of the sensors are measured as signals. Immunoassays were developed using the magnetic protein chips to quantitate protein biomarkers with high sensitivity. The magnetic protein chip immunoassay has several advantages over conventional non-magnetic techniques, such as multiplex capability, smaller sample volume requirement, enhanced signal-to-noise ratio, and facile integration with electronics. Ionizing radiation is high energy radiation that can remove electrons from atoms, and it causes various cellular damages some of which are lethal. Using an in vivo mouse radiation model, we developed protocols for measuring fms-related tyrosine kinase 3 ligand (Flt3lg) and serum amyloid A1 (Saa1) in small amounts of blood collected during the first week after X-ray exposures of sham, 0.1, 1, 2, 3, or 6 Gy. Flt3lg concentrations showed excellent dose discrimination at ≥ 1 Gy in the time window of 1 to 7 days after exposure except 1 Gy at day 7. Saa1 dose response was limited to the first two days after exposure. A discriminant analysis using both proteins could show improved dose classification accuracy. Our magnetic protein chip immunoassay demonstrated the dose and time responses and low-dose sensitivity that have important advantages in radiation triage biodosimetry. Necrotizing enterocolitis (NEC) is an inflammatory bowel disease often observed in pre-term babies and has high mortality rate. However, timely diagnosis of NEC has been hampered due to its unspecific symptoms and ineffective clinical tests currently available. We developed a magnetic protein chip immunoassay for the validation of NEC biomarkers. Three biomarkers, C-reactive protein (CRP), matrix metalloproteinase-7 (MMP7), and epithelial cell adhesion molecule (EpCAM) were quantitated using a small amount of blood samples. Receiver operating characteristic (ROC) curve analysis combined with bootstrapping technique showed excellent discrimination of NEC from healthy control and NEC from sepsis. Given the generality of the detection scheme used in the magnetic protein chip immunoassay, the magnetic protein chips are expected to hold great potential for medical diagnosis and clinical research.