Synthetic Control and Bioconjugation of Magnetite Nanoparticles for the Development of an in vivo Glucose Sensor

Abstract

In this work, an examination into the synthesis, functionalization, and utility of iron oxide nanoparticles was conducted for the development of an in vivo glucose biosensor based on the catalytic cycle of glucose oxidase and amperometric detection of hydrogen peroxide. While enzyme conjugation to a nanoparticle has been reported in the literature, this study focuses on the role of the nanoparticles as electrophoretic charge carriers for sensor fabrication. The kinetically controlled growth of magnetite (Fe3O4) nanoparticles was investigated utilizing the thermal decomposition method and iron (III) stearate as a readily available and economical precursor. Nucleation periods were observed to be kinetically controlled by and directly proportional to the surfactant concentration, giving a linear relationship between the surfactant concentration and particle diameters below 20 nm. Narrow size distributions were achieved, with standard deviations of particle populations being 2-4 nm. A precise empirical growth model was determined for low surfactant concentrations. As synthesized Fe3O4 nanoparticles presented a hydrophobic surface with no appreciable surface charge as determined by electrophoretic light scattering. Surface functionalization was attempted via base catalyzed condensation of (3-aminopropyl)trimethoxysilane, followed by nucleophilic ring opening of two cyclic anhydrides, yielding an aqueous suspension of particles with æ potentials of approximately -50 mV. Enzyme-particle conjugation was done via known carbodiimide/N-hydroxyl succinimide chemistry. The resulting bioconjugates were electrodeposited onto glass/platinum capillary electrodes, and glucose response was measured. Sub-optimal responses were realized, owing to aggregation of particle cores prior to functionalization as observed by dynamic light scattering. The same aggregation was not observed by transmission electron microscopy.