Tuning stamp surface energy for soft lithography of polar molecules to fabricate bioactive small-molecule microarrays

Soft-lithography-based techniques are widely used to fabricate microarrays. Here, the use of microcontact insertion printing is described, a soft-lithography method specifically developed for patterning at the dilute scales necessary for highly selective biorecognition. By carefully tuning the polar surface energy of polymeric stamps, problems associated with patterning hydrophilic tether molecules inserted into hydrophilic host self-assembled monolayers (SAMs) are surmounted. Both prefunctionalized tethers and on-chip functionalization of SAMs patterned by microcontact insertion printing enable the fabrication of small-molecule microarrays. Substrates patterned with the neurotransmitter precursor 5-hydroxytryptophan selectively capture a number of different types of membrane-associated receptor proteins, which are native binding partners evolved to recognize free serotonin. These advances provide new avenues for chemically patterning small molecules and fabricating small molecule microarrays with highly specific molecular recognition capabilities.