Physiologically Relevant Changes in Serotonin Resolved by Fast Microdialysis

Online microdialysis is a sampling and detection method that enables continuous interrogation of extracellular molecules in freely moving subjects under behaviorally relevant conditions. A majority of recent publications using brain microdialysis in rodents report sample collection times of 20–30 min. These long sampling times are due, in part, to limitations in the detection sensitivity of high performance liquid chromatography (HPLC). By optimizing separation and detection conditions, we decreased the retention time of serotonin to 2.5 min and the detection threshold to 0.8 fmol. Sampling times were consequently reduced from 20 to 3 min per sample for online detection of serotonin (and dopamine) in brain dialysates using a commercial HPLC system. We developed a strategy to collect and to analyze dialysate samples continuously from two animals in tandem using the same instrument. Improvements in temporal resolution enabled elucidation of rapid changes in extracellular serotonin levels associated with mild stress and circadian rhythms. These dynamics would be difficult or impossible to differentiate using conventional microdialysis sampling rates

Small-Molecule Arrays for Sorting G‑Protein-Coupled Receptors

Precise self-assembled monolayer chemistries and microfluidic technology are combined to create small-molecule biorecognition arrays. Small-molecule neurotransmitters or precursors are spatially encoded on monolayer-modified substrates. This platform enables multiplexed screening of G-protein-coupled receptors (GPCRs) from complex media via protein–ligand interactions. Preserving access to all epitopes of small molecules is critical for GPCR recognition. The ability to address multiple small molecules on solid substrates and to sort protein mixtures based on specific affinities is a critical step in creating biochips for proteomic applications