Single-stranded DNA (ssDNA)-functionalized single-wall carbon nanotubes (SWCNTs) exhibit exceptional optical sensitivity to catecholamines, including dopamine and norepinephrine—key signaling molecules that play vital roles in brain function. This unique capability positions SWCNTs as powerful tools for advancing our understanding of neurochemical processes involving dopaminergic and noradrenergic neurons. In this presentation, I will highlight how our lab has leveraged SWCNT nanosensors to push the boundaries of dopamine neuroscience. For studies in cultured neurons, we developed a composite nanofilm strategy that enabled us to visualize dopamine release with exceptional resolution, capturing single bouton activity with quantal sensitivity while monitoring thousands of release sites simultaneously in large imaging fields of view. By combining SWCNT-based activity imaging with immunofluorescence, electron microscopy, and cutting-edge molecular, cellular and genetic techniques, we have gained new insights into neurobiological properties of dopamine release sites in dopaminergic neurons that had heretofore been inaccessible with conventional methods of inquiry. Building on these advances, I will discuss recent progress in the development of in vivo-compatible dopamine nanosensors. These innovations have allowed us to monitor dopamine dynamics in awake and behaving mice, bridging the gap between molecular-scale imaging and real-time behavior analysis. Furthermore, I will discuss methodological developments that enabled the deployment of these nanosensors in vivo. Looking ahead, these SWCNT-enabled technological advancements hold potential for the study of neurochemical signaling, offering deeper insights into both normal brain function and the pathophysiology of disorders involving catecholamines. Future work aims to expand the applications of these nanosensors to other neural circuits and neuromodulators, ultimately advancing our ability to decode the brain’s chemical language.

Genetically encoded fluorescent calcium indicators allow cellular-resolution recording of physiology. However, bright, genetically targetable indicators that can be multiplexed with existing tools in vivo are needed for simultaneous imaging of multiple signals. Here we describe WHaloCaMP, a modular chemigenetic calcium indicator built from bright dye-ligands and protein sensor domains. Fluorescence change in WHaloCaMP results from reversible quenching of the bound dye via a strategically placed tryptophan. WHaloCaMP is compatible with rhodamine dye-ligands that fluoresce from green to near-infrared, including several that efficiently label the brain in animals. When bound to a near-infrared dye-ligand, WHaloCaMP shows a 7× increase in fluorescence intensity and a 2.1-ns increase in fluorescence lifetime upon calcium binding. We use WHaloCaMP1a to image Ca responses in vivo in flies and mice, to perform three-color multiplexed functional imaging of hundreds of neurons and astrocytes in zebrafish larvae and to quantify Ca concentration using fluorescence lifetime imaging microscopy (FLIM).

Fluorescent carbon nanomaterials have broadly useful chemical and photophysical attributes that are conducive to applications in biology. In this review, we focus on materials whose photophysics allow for the use of these materials in biomedical and environmental applications, with emphasis on imaging, biosensing, and cargo delivery. The review focuses primarily on graphitic carbon nanomaterials including graphene and its derivatives, carbon nanotubes, as well as carbon dots and carbon nanohoops. Recent advances in and future prospects of these fields are discussed at depth, and where appropriate, references to reviews pertaining to older literature are provided.