Identifying selective molecular recognition elements from large combinatorial pools of biomolecules is key to advancing small-molecule sensing. However, uncontrolled small-molecule functionalization of substrates, <i>e.g.</i>, SepharoseÒ beads, to produce biomolecule selection materials leads to high degrees of nonselective recognition and thus, poorly optimized pools of candidate biomolecule “receptors”. We developed a number of methods for controlled placement and ligation of small molecules on self-assembled monolayer substrates. Moreover, we discovered various methods of patterning small-molecule substrates to create negative and positive areas of functionalization with features as small as tens of nanometers and patterns over millimeters. Our findings have enabled a set of design rules that achieve high degrees of specific and selective biomolecule recognition of immobilized small molecules mimicking free solution interactions. Recent advances include identification of surface-bound small molecules by nucleic acid binding partners, and patterning and characterization of pre-functionalized small-molecule tethers. Ongoing efforts are directed at developing substrate-based approaches for determining affinity constants with high throughput.<br/>

Enabling biomolecule selection by small molecule-functionalized substrates: A decade of collaborative progress<br />

249th National Meeting (2015)

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