Abstract

Detection of neurotransmitters is an analytical challenge and essential to understand neuronal networks in the brain and associated diseases. However, most methods do not provide sufficient spatial, temporal, or chemical resolution. Near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWCNTs) have been used as building blocks for sensors/probes that detect catecholamine neurotransmitters, including dopamine. This approach provides a high spatial and temporal resolution, but it is not understood if these sensors are able to distinguish dopamine from similar catecholamine neurotransmitters, such as epinephrine or norepinephrine. In this work, the organic phase (DNA sequence) around SWCNTs was varied to create sensors with different selectivity and sensitivity for catecholamine neurotransmitters. Most DNA-functionalized SWCNTs responded to catecholamine neurotransmitters, but both dissociation constants (Kd) and limits of detection were highly dependent on functionalization (sequence). Kd values span a range of 2.3 nM (SWCNT-(GC)15 + norepinephrine) to 9.4 μM (SWCNT-(AT)15 + dopamine) and limits of detection are mostly in the single-digit nM regime. Additionally, sensors of different SWCNT chirality show different fluorescence increases. Moreover, certain sensors (e.g., SWCNT-(GT)10) distinguish between different catecholamines, such as dopamine and norepinephrine at low concentrations (50 nM). These results show that SWCNTs functionalized with certain DNA sequences are able to discriminate between catecholamine neurotransmitters or to detect them in the presence of interfering substances of similar structure. Such sensors will be useful to measure and study neurotransmitter signaling in complex biological settings.

Highlights

  • Neurotransmitters are essential for basic functions of the human body and especially for chemical signaling in neuronal circuits of the brain

  • We address remaining challenges of neurotransmitter detection with carbon nanotube-based sensors by varying the organic phase around the single-walled carbon nanotubes (SWCNTs) scaffold and evaluating the resulting dissociation constants and limits of detection for relevant neurotransmitters

  • Our results show fluorescence increases for all three neurotransmitters but the magnitude and the onset of saturation varies by orders of magnitude

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Summary

Introduction

Neurotransmitters are essential for basic functions of the human body and especially for chemical signaling in neuronal circuits of the brain. Their mode of action is widely unexplored due to a lack of tools to measure their concentration profiles in a spatiotemporal manner. In the past decades several analytical methods have been developed to measure neurotransmitter concentrations [1,2,3,4,5]. The most prominent release sites, i.e., synapses, are very small

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