A PORTABLE, MODULAR DEVICE FOR OBJECTIVE OR FIBER-BASED FLUORESCENCE AND LABEL-FREE BIOMOLECULAR SPECTROSCOPY OF THE MOUSE BRAIN

The development of optical approaches for neural monitoring based on genetically encoded fluorescent reporters has enabled functional readouts with high spatio-temporal resolution^​. In parallel, label-free strategies based on Raman spectroscopy have emerged as powerful tools to obtain in situ chemical information. The combination of labeled and label-free approaches may therefore enable a more comprehensive picture of the links between functional and biomolecular brain states.
Nonetheless, the adoption of label-free monitoring remains marginal compared with fluorescence-based approaches, largely due to the unsuitability of conventional Raman systems for experiments in small animal models, such as rodents. While extensive vibrational imaging studies have been carried out on ex vivo specimens, in vivo neuroscience applications still call for versatile, deployable platforms.
Here, we present a compact device designed to capture biomolecular signatures of the living mouse brain using spontaneous Raman spectroscopy in combination with conventional fluorescence readouts. The system is based on a modular opto-mechanical architecture combining a near-infrared spectroscopy path with a visible imaging path compatible with fluorescence intensity and lifetime measurements, operating with either a microscope objective or an optical fiber probe.
We show that our setup detects spectral signatures in ex vivo mouse brain slices, benchmarked against commercial systems, potentially enabling the simultaneous acquisition of chemical, structural, and functional information with a single device.
Owing to its flexibility and ease of assembly, this platform represents a promising tool for broadening the accessibility of label-free spectroscopy in neuroscience and lays the ground for further miniaturization toward head-mounted systems for freely behaving animals.