In this study, we demonstrated a simple immobilization technique to prepare nucleic acid sensor based on piezoelectric crystal microbalance system. The results showed that the QCM sensors can be fabricated by using relatively inexpensive quartz piezoelectric crystals having silver electrodes. Crystals can be effectively coated with a very thin EDA/plasma film in a simple glow/discharge system at a discharge power of 15 W and a treatment time of 2.5 min. Then the amino groups can be converted satisfactorily to aldehyde groups by treating the surfaces with glutaraldehyde (concentration: 2.5%) at 4 8C in about 2 h. For oligonucleotide immobilization, the double strand DNA composed ofa strand to be identified (P2) and its complementary strand having one extra base at 5?-end (P1) is dissolved in a buffer (carbonate, pH 9.2) with an ionic strength of 0.1, at a concentration of 1 mg/ml, and only incubated with the GA-attached crystals for about 3 h. The reaction with the amino groups of the 5?-end of the oligonucleotide and surface aldehyde groups allows covalent bonding of the oligonucleotide molecules onto crystal surfaces through only the probe strand (P1). The P2 strand can easily be removed from the surface and the QCM sensor is brought to its final form. Oligonucleotide immobilization can be followed with the QCM system by measuring frequency shifts of the crystal, which was 1269 /12 Hz under optimal condition. This frequency shift is sufficient for sensitive measurements. The response time for equilibrium in the hybridization experiments were obtained about 5 min, which is quite satisfactory. We also obtained a good correlation between the concentration of the strand to be identified and the measured frequency shifts, which may be applied for quantitative determination of the oligonucleotides within aqueous media. STM images supported the QCM results where oligonucleotide chains are attached onto the crystal surfaces.