The brain is a complex organ, with billions of neurons and more than 30 distinct neurochemicals (possibly up to 100), involved in all aspects of a human life, including cognition, movement, sleep, appetite, and fear responses. For some neurological diseases/conditions, changes in neurochemical concentrations could be predictors of early onset disease or disease progression. While there are a variety of sampling techniques which can detect neurotransmitters in biofluids at low concentrations, these techniques often involve multi-step sample preparations coupled with long measurement times, and are not suited for in vivo detection. There is a need for the development of sensors for the detection of neurotransmitters that are selective, rapid, and label-free with little to no sample processing. Our group focuses on the detection of biomarkers for neurological activity in biofluids and through the skull.
Our approach is to apply surface enhanced Raman spectroscopy (SERS), a highly specific and selective vibrational spectroscopy, for the detection of neurochemicals. Raman scattering is an inherently weak phenomenon. To enhance the weak Raman scattering signal, we incorporate noble metal nanoparticles in our sensors, which when excited with a laser generate an oscillating electric field, referred to as the localized surface plasmon resonance (LSPR), at the surface of the nanoparticles. The molecules of interest are adsorbed to the nanoparticle surface, and the Raman scattered light is enhanced by the LSPR of the nanoparticles. SERS is surface selective, highly sensitive, rapid, label-free and requires little to no sample processing. We are developing SERS-based sensors for in vitro neurotransmitter sensing at physiologically relevant concentrations in biofluids. For in vivo detection, we combine SERS with spatially offset Raman spectroscopy (SORS), where Raman scattering spectra is obtained from subsurface layers of turbid media. We demonstrate low concentration detection of neurotransmitters in the micromolar (µM) to nanomolar (nM) concentration ranges with SESORS in a brain tissue mimic through the skull.