The non-specific adsorption of dissolved analytes strongly reduces the sensitivity and reliability in polymer microanalytical systems. Here, a one-step aqueous phase procedure modifies polymer material surfaces to strongly reduce their non-specific adsorption of a broad range of organic analytes including hydrophobic and hydrophilic drugs (0.23 < ClogP < 8.95), small and large proteins (insulin, albumin, IgG), and DNA. The coating is shown to limit the adsorption of even highly hydrophobic drugs (ClogP > 8) in their pharmaceutically relevant concentration range ≤100 nM. The low adsorption is mediated by photochemical conjugation, where polyethylene glycol (PEG) polymers in aqueous solution are covalently bound to the surface by UV illumination of dissolved benzophenone and a functionalized PEG. The method can coat the interior of polymer systems made from a range of materials commonly used in microanalytical systems, including polystyrene (PS), cyclic olefin copolymer (COC), liquid crystalline polymer (LCP), and polyimide (PI).