This study describes the use of an acrylic acid containing random copolymer (polyethylene-co-acrylic acid, PEAA) as quartz crystal microbalance (QCM) coatings for electrode shielding and covalent tethering of DNA oligonucleotides. Commercially available silver-coated QCM was used as reaction carriers, onto which PEAA was coated to protect the electrode from undesirable effects of oxidation. AFM and SEM/EDX were used to analyze the topology and coverage of the polymer coatings. Carbodiimide chemistry was applied to attach a 17-mer single-stranded DNA probe with a C-12-alkylamino tail on the 5'-end. Seventy-mer single-stranded DNA (ss-DNA) fragments containing complementary or noncomplementary sequences were hybridized to the end-attached probes. With the use of A high stringency hybridization buffer (2 x SSC with 2% SDS), the QCM-based DNA sensor was able to detect and differentiate single-base mismatches in the 70-mer DNA target sequence. The response to the single-base mismatches near the 5' end or at the center of the immobilized probe was only similar to60% and similar to50% of that to the fully complementary sequence, respectively. The carbodiimide chemistry responsible for DNA immobilization creates a strong covalent bond that allows the probe modified surface to be reused upon, denaturing the hybrids.