Dynamic SERS nanosensor for neurotransmitter sensing near neurons

Abstract

Current electrophysiology and electrochemistry techniques have provided unprecedented understanding of neuronal activity. However, these techniques are suited to a small, albeit important, panel of neurotransmitters such as glutamate, GABA and dopamine, and these constitute only a subset of the broader range of neurotransmitters involved in brain chemistry. Surface-enhanced Raman scattering (SERS) provides a unique opportunity to detect a broader range of neurotransmitters in close proximity to neurons. Dynamic SERS (D-SERS) nanosensors based on patch-clamp-like nanopipettes decorated with gold nanoraspberries can be located accurately under a microscope using techniques analogous to those used in current electrophysiology or electrochemistry experiments. In this manuscript, we demonstrate that D-SERS can measure in a single experiment ATP, glutamate (glu), acetylcholine (ACh), GABA and dopamine (DA), among other neurotransmitters, with the potential for detecting a greater number of neurotransmitters. The SERS spectra of these neurotransmitters were identified with a barcoding data processing method and time series of the neurotransmitter levels were constructed. The D-SERS nanosensor was then located near cultured mouse dopaminergic neurons. The detection of neurotransmitters was performed in response to a series of K depolarisations, and allowed the detection of elevated levels of both ATP and dopamine. Control experiments were also performed near glial cells, showing only very low basal detection neurotransmitter events. This paper demonstrates the potential of D-SERS to detect neurotransmitter secretion events near living neurons, but also constitutes a strong proof-of-concept for the broad application of SERS to the detection of secretion events by neurons or other cell types in order to study normal or pathological cell functions.

Dual microelectrodes decorated with nanotip arrays: Fabrication, characterization and spectroelectrochemical sensing

“…They could find a wide range of applications in photonic devices or electro-optical probes for biosensing, among which the detection of neurosecretory processes at single cells. Indeed, as shown recently [73], SERS performed at a nanotip allows one to detect dynamically the cell release of certain neurotransmitters which are not electroactive (glutamate, ATP), others being electroactive (dopamine) could be detectable by the electrode surface simultaneously. The combination of both methodologies on the same probe, of less than 100 μm diameter, would provide unprecedented features for sensing, for instance, in the brain tissue different types of neuronal activities with high spatial accuracy.…”

“…However, this probe can detect freely-diffusing molecules by SERS. Molecules that are released by cells [72,73] or (eletro)generated by a surface [74,75] diffuse and reach the nanotips where they are detected by SERS and/or by electrochemistry. In addition, it renders possible the study of the molecular functionalization and substitution dynamics of surfaces as well as the characterization of cellular release of biomolecules [36,76].…”

In Vitro and In Vivo SERS Biosensing for Disease Diagnosis

“…The probes were later used to demonstrate, in a single experiment, the simultaneous detection of ATP, glutamate, acetylcholine, GABA, and dopamine. The nanosensor was also placed near cultured mouse dopaminergic neurons where a series of K + depolarizations were performed, and the detection of elevated levels of both ATP and dopamine was achieved [ 52 ]. These experiments demonstrate the potential of SERS to monitor neurotransmitter secretion near living neurons.…”

Leveraging the interplay of nanotechnology and neuroscience: Designing new avenues for treating central nervous system disorders

“…Nano-enabled probes are also being developed for quantification of multiple analytes or multiple modes of analysis. Using dynamic surface-enhanced Raman spectroscopy (SERS) and AuNPs coated to glass micropipettes, multiple neurotransmitters including glutamate, acetylcholine, GABA, and dopamine along with ATP can be measured simultaneously [205,206]. Further, dual probes that can sense neurotransmitters and electrochemical signals have also been developed using microelectrode arrays modified with Platinum NPs and Nafion [207].…”

“…1 analyte per probe 2-5 analytes per probe, multiple modalities -n/a graphene quantum dots [197,198], Au SERS probes [205,206] In vitro extracellular sampling 20 sensors per cell 20,000 sensors per cell Hours n/a SWCNTs with corona phase recognition [200][201][202] In vitro intracellular sampling n/a 3-10 probes per cell n/a Days Nanostraw cell culture surface [208]…”