Protein microarrays are high information density bioassays that, if accurate, provide information valuable in early disease diagnosis and biodefense applications. While elegant patterning methods exist, diagnostic validity is crippled by nonspecific binding and device fouling. Nonspecifically bound biomolecules create false signal, block sensor receptors, and foul detectors. As biomarker detection (electrochemical, gravimetric or optical) is pushed to lower levels, nonspecific binding becomes increasingly problematic. Commonly, nonspecific binding is mitigated by surfactant addition or excessive, repeated washing. These additional steps add complexity to devices promised to be portable, robust, simple and accurate. Using quartz crystal resonators, low affinity proteins were removed from protein microarrays, improving protein spot uniformity and signal reproducibility. Copyright © 2005 by the Transducer Research Foundation, Inc.