Abstract.Many homogeneous assays are complicated by the adsorption of probe molecules by the surface of reaction vessels, which are often made of polypropylene or polystyrene-based plastics. To solve this problem, many protein and surfactant-based blocking agents are used. However, these blockers may interfere with intended assays by sequestering transition metal ions, inducing protein denaturing, generating air bubbles or making pores in membranes. Coating surfaces with polyethylene glycol (PEG) through covalent linkages have been proven to be an effective method to minimize protein adsorption.However, this method is more difficult to apply on plastic surfaces and is quite expensive. While unmodified PEG is often considered as a non-adsorbing polymer, in this Technical Note, we report that PEG at very low ppm can still effectively block plastic surfaces. This method works for DNA, protein and liposome-based assays as long as the molecular weight of PEG is larger than 2000. PEG works due to multivalent hydrophobic interaction from its repeating methylene units. This Technical Note will not only facilitate biosensor development, but also enhance our understanding of the interaction between various molecules and plastic surfaces.3