| dc.description.abstract | Preterm birth (PTB) constitutes 10% of births and is the global leading cause of death in children under the age of 5. Unfortunately, a complete understanding of the mechanisms precluding PTB is lacking, making prediction and intervention challenging. Studying concentration changes of known biomarkers during PTB can help elucidate these mechanisms and provide valuable insight towards developing point of care (POC) sensing platforms. This project aims to develop electrochemical biosensors to measure two PTB biomarkers: matrix metalloproteinase-3 (MMP-3) and tumor necrosis factor-α (TNF-α). The biosensor designs investigated in this work aim to improve upon current commercial detection methods by reducing time, sample volumes, and costs. A microfluidic, magnetic bead-based competitive assay faced challenges due to the adherence of magnetic beads in the fluidic device. Next, three chemically modified electrode (CME) sensors were investigated. The first, a regenerable microfluidic competitive assay, yielded promising signal but experienced surface regeneration complications. The second, a disposable carbon-based sensor, exhibited successful competitive binding but suffered replicability issues that were later attributed to the electrochemical readout, p-aminophenol (PAP). The third CME, a single-use gold sensor, had an extensive protocol that was incompatible with the goals for this project. Subsequent sensor designs that utilized magnetic beads statically also faced irreproducibility. Investigation into the redox reporter, PAP, revealed that its adsorption and electropolymerization on electrode surfaces were the source of irreproducibility. A full electrochemical characterization of PAP was conducted. The final sensor design, a sandwich assay utilizing 3,3’,5,5’-Tetramethylbenzidine (TMB) rather than PAP, yielded linear calibrations for MMP-3 and TNF-α from 2 – 10 ng/mL and 25 – 600 pg/mL, respectively. This design’s procedure was more rapid and required smaller sample volumes than commercial methods, successfully accomplishing the goals for this project. Future directions involve streamlining the final design for POC applications and monitoring MMP-3 and TNF-α concentrations before and after infections that are common during pregnancy. Understanding how infection impacts these biomarkers will aid in uncovering the mechanisms precluding PTB. | |
