Protein Microarrays offer an efficient and economic way for high-throughput analysis of the expression, function and interaction of proteins. Though successful application of this technology will have a powerful impact to biomedical sciences, many problems remain to be solved. Two of these problems include immobilizing proteins onto surfaces while maintaining their in vivo activities, while also limiting non-specific adsorption of other biomolecules. We have used surface chemistry to design biocompatible materials to overcome these challenges. While designing these materials we have uncovered the science behind nonuniform spot profiles of immobilized biomolecules deposited from microdroplets. We have also investigated surface tethered macromolecules. Both have implications in the understanding, designing and applying of protein microarrays.