This work describes progress towards the development of a point-of-care chemical sensor for cortisol. This sensor will function according to a novel design of "nano-brighteners" that should allow for high sensitivity of detection based on fluorescence enhancement.

Chapter 1 gives a brief background on sensor classifications and cortisol. It also describes the components and physical phenomena featured in the sensor, including DNA aptamers, silver nanoparticles, metal-enhanced fluorescence and dithiocarbamates as surface anchors.

Chapter 2 describes the main synthetic effort toward the modular sensor platform, focusing on development of the signal transducer component. A pyridylthiazole-based fluorophore (BPT) was synthesized and used in the nucleophilic substitution of a 1,3,5-triazine core, which also served as a hub for the conjugation of two amine-terminated ssDNA oligomers.

In Chapter 3, the assembly of the nanosensor construct is described, focusing on the coating of silver nanoparticles (AgNPs) with ssDNA aptamers. Amine-terminated DNA oligomers can be anchored onto AgNP surfaces by in situ DTC ligation. Interestingly, this functionalization does not always produce an increase in hydrodynamic size, which spurred an investigation into surface chemistry using several passivating agents. This ultimately led to the incorporation of the quencher Dabcyl as a secondary coating agent, both to promote radial ssDNA projection and to reduce background fluorescence. With these components in hand, testing and optimization of the proposed sensor may be fully investigated.