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. © 2013 American Chemical Society.