Exploring Brain Chemistry: Developing Raman Optophysiology with Optogenetics for Enhanced Neurotransmitter Sensing

Combining SWIR-SERS, neuroscience, and AI we push neurotransmitter detection limits in live brain tissue.

Abstract Text:

In situ detection of neurotransmitters within neuronal networks is crucial for understanding brain function and disease. Chemical gradients around neurons and the extracellular space are critical for maintaining normal biological functions, and their dysregulation can lead to neurological diseases like Parkinson’s disease (PD). Traditional methods such as fluorescence microscopy and electrochemistry have been valuable for studying molecular activity, but they fall short in capturing the dynamic complexity of these systems. Surface-enhanced Raman scattering (SERS) optophysiology with optogenetics is a novel approach pioneered by the Masson and Trudeau groups.¹ It makes use of a microneedle functionalised with plasmonic nanomaterials and a laser to provide information on molecular vibrations present in a physiological sample, which is combined with optogenetics to control neuron activity via light-sensitive proteins, enabling both real-time sensing and manipulation of neural processes.

Recent advances in imaging and biomolecule detection are shifting towards the short-wave IR (SWIR) region.³ SERS in biological samples or live tissue when carried out in the SWIR region allows light to penetrate deeper into tissue, reduces background fluorescence and causes less laser damage.² Our current research is expanding our near IR optimised technology into the SWIR region, aiming to unlock huge potential for in vivo imaging due to this high biocompatibility. Our newly developed SWIR enabled Raman microscope combined with optimisation of the available SERS nanostructures and the incorporation of a novel machine learning (ML) based algorithm^1,4 will help to fully realize the potential of this innovative technique. The SWIR-SERS optophysiology will then be carried out on a novel live mouse brain model in development by the Trudeau group. This project is pushing the boundaries of what is possible at the intersection of Raman and chemical gradient sensing in brain research. In the near future, we will test this on Parkinson’s disease models to uncover the complex pathways that drive the neurodegeneration.

References:
1. Lussier, F. et al, ACS Nano 2019, 13 (2), 1403–1411.
2. Deriu, C. et al, Nanoscale Adv. 2023, 5 (8), 2132-2166.
3. Zhu, B. et al, Sensors 2024, 24 (11), 3539.
4. Masson, J.-F. et al, Nat. Nanotechnol. 2023, 18, 111-123.