Irregularities in neuromodulation can create a variety of diseases. As a result, accurate measurement of neurotransmitter concentrations is imperative to improve clinical diagnostics. Biosensing technologies help by permitting real-time monitoring of these molecules. However, despite intense global focus on optimizing biosensing technologies, their ultimate potential remains limited by inadequate sensitivity and selectivity. The extra requirement for high spatiotemporal resolution in neurochemical sensing imposes barriers that are not yet surmountable with existing biosensor technologies. This has hindered our studies of the complex nature of neurotransmitters and neuromodulators and prevented us from improving our understanding of their role in regulating biological functions. To address these challenges, we present new optical biosensors for serotonin and dopamine using single-walled carbon nanotubes (SWCNTs). The unique physiochemical and optoelectronic properties of SWCNTs can be readily tuned, creating a versatile material for imaging and sensing applications. Their intrinsic near-infrared fluorescence overlaps with the optical transparency window for biological tissue, which coupled with their indefinite photostability, increases their suitability for in vitro and in vivo applications. In this thesis, we systematically explore the use of surfactants, DNA, and xeno nucleic acids (XNAs) to improve the brightness and selectivity of SWCNT sensors. We highlight the trade-offs typically encountered for these approaches and propose new semi-rational methods to overcome these limitations. We begin by examining the impact of exposed surface area on the optical response of SWCNTs. We subsequently use this understanding to achieve previously unreported molecular selectivity through controlled, adsorption-based tuning of the nanotube surface of sub-critical colloidal suspensions of sodium cholate (SC)-SWCNTs. Owing to the increased biocompatibility of DNA, we expand our study to DNA-SWCNTs and demonstrate the impact of the dispersion method on both sensor brightness and responsivity using chemically modified DNA. This thesis culminates in several major findings for improving DNA-SWCNTs in ionically complex environments using XNAs. We introduce locked nucleic acid (LNA) to control the unwanted cation-induced fluorescence changes typically encountered by DNA-SWCNTs and show that this improvement does not come at the expense of their sensing capabilities. Our results suggest that the LNA-SWCNTs may uniquely enable simultaneous monitoring of dopamine and calcium, providing an improved sensor for studying the process of neuromodulation. In the final chapter of this thesis we demonstrate that the LNA-SWCNTs retain their sensing capabilities following extended periods of time in the presence of salts, proteins, antibiotics, and even whole cells. Furthermore, we expand upon the possibilities achievable using XNA-SWCNTs and present a new peptide nucleic acid (PNA) sensor for the rapid detection of an additional biomarker, microRNA. The synthetic biology approaches presented in this work serve as a complementary means for enhancing nanotube optoelectronic behaviour, unlocking previously unexplored possibilities for developing nano-bioengineered sensors with augmented capabilities.