We describe the first in a series of studies designed to develop and to characterize self-assembled monolayers containing isolated small-molecule probes. We insert tether molecules into preformed oligo(ethylene glycol) -terminated alkanethiolate monolayer matrices and covalently attach the neurotransmitter serotonin to the tethers. These monolayers selectively recognize serotonin antibodies and resist binding of nonspecific antibodies and proteins. We will use these capture materials for biosensor development and functionally-directed proteomics.