Microscale Enzymatic Optical Biosensors Using Mass Transport Limiting Nanofilms. 2. Response Modulation by Varying Analyte Transport Properties

Microscale implantable fluorescent sensors that can be transdermally interrogated using light are being pursued as a minimally invasive biochemical monitoring technology for in vivo applications. Previously, we reported the development of an enzymatic-based sensing platform characterized using glucose as a model biochemical analyte for minimally invasive diabetic monitoring. In this work, surface-adsorbed polyelectrolyte nanofilms were employed to modulate the relative fluxes of glucose and oxygen into the sensor, allowing response characteristics, namely, analytical range and sensitivity, to be tuned. Modulation of substrate transport properties were obtained by varying surface-adsorbed nanofilm thicknesses, ionic strength of assembly conditions, and outermost constituents. In general, increasing film thickness through additional cycles of adsorption resulted in consistently decreased glucose flux, correspondingly decreasing sensitivity and increasing range. While the two components of the nanofilms remained the same [poly(allylamine hydrochloride), PAH; poly(sodium 4-styrenesulfonate)}, the assembly conditions and terminal layer were found to strongly influence sensor behavior. Specifically, without added salt in assembly conditions, glucose diffusion was significantly decreased when films were capped with PAH, resulting in reduced sensitivity and extended range of response. With added salt, however, sensor response was the same for films of the same thickness but different terminal materials. These findings demonstrate that sensor response may be customized to cover the hypo- (0−80 mg/dL), normo- (80−120 mg/dL), and hyperglycemic levels (>120 mg/dL) from a single batch of particles through appropriate selection of coating structure and assembly conditions. Furthermore, the results indicate nanofilms of only 12-nm thickness could significantly affect response behavior, confirming predicted behavior by models of sensor reaction−diffusion kinetics. These findings demonstrate the ability to engineer sensor response properties using a simple, cost-effective means and lay the groundwork for developing additional highly sensitive biochemical monitors.