To understand how the brain functions and what disruptions underlie diseases and disorders, development of analytical methods to monitor chemical signaling in living brain tissue are critically important. Neurochemical analysis techniques should have the appropriate temporal, spatial, and chemical resolution to study these systems, while minimally perturbing them to allow unconstrained in vivo measurements. To make a direct measurement in functioning, live tissue these methods must be able to selectively measure chemical changes on multiple timescales ranging from milliseconds to months, have spatial resolution on the order of micrometers or less, and be sensitive to concentrations ranging from picomolar to micromolar. The complexity of the brain is staggering and the reductionist approach of breaking down the central nervous system into subsystems with specific functions that rely on specific neurotransmitters has had been successful on the one hand but has also revealed the interconnected nature of the many biochemical pathways involved in neurotransmission and the limitations of this approach. As we grapple with this problem, we must be continuously be afforded new tools for analytical decision-making, and improved methods for performing chemical measurements in vivo.
1. Pioneering techniques bridging disparate timescales to measure tonic (slower changing) neurotransmitter concentrations in situ with high selectivity, sensitivity, and temporal resolution .
2. Advancement of MSn methodology to monitor endogenous neuropeptides and neuropeptide-derived drugs.
3. Engineered novel biocompatible films for selective and sensitive measurements of neurotransmitters both in vitro and in vivo .
4. Developing new data collection and analysis tools