Peptoids are a versatile family of oligomeric synthetic molecules that can be customized for many applications. The submonomer solid-phase synthesis of peptoids allows for quick and inexpensive manufacturing and the selection of side chains is nearly limitless. In addition, peptoids that include chiral, aromatic side chains form stable helical secondary structure that leads to the potential for the formation of supramolecular assemblies. The effects of water solubility, helical content, charge placement, and side chain bulk on microsphere formation were studied for seven peptoid sequences. We found that secondary structure and partial water solubility were essential for microsphere formation. In addition, charge placement and side chain bulk affect both the ability to form microspheres and the diameter of the microspheres.

Peptoids that are helical and partially water soluble have been shown to self-assemble into microspheres when the peptoid solution is dried on a silicon substrate. Such microsphere coatings have great potential for use in biosensor technologies, specifically to increase the surface area for binding. However, in order to be useful, the peptoids must consistently form uniform coatings. In this study we investigated the effects of various coating protocol parameters on the uniformity of the resulting peptoid microsphere coatings, including (i) solvent, (ii) administration technique, and (iii) drying environment. In addition, we investigated the robustness of the coatings as well as the potential for using a glass substrate. These studies show that uniform, robust peptoid microsphere coatings can be formed using protic solvents, a full coverage administration technique, and drying in open air on silicon or glass substrates.