Recently developed DNA-modified diamond surfaces exhibit excellent chemical stability to high-temperature incubations ill biological buffers. The stability of these surfaces is substantially greater than that of gold or silicon surfaces, using similar surface attachment chemistry. The DNA molecules attached to the diamond surfaces are accessible to enzymes and call be modified ill surface enzymatic reactions. An important application a these surfaces is for surface invasive cleavage reactions, ill which target DNA strands added to the solution may result ill specific cleavage of surface-bound probe oligonucleotides, permitting analysis of single nucleotide polymorphisms (SNPs). Our previous work demonstrated the feasibility, of performing such cleavage reactions oil planar gold surfaces using PCR-amplified human genomic DNA as target. The sensitivity, of detection ill this earlier work was substantially limited by a lack of stability of the gold surface employed. In the present work, detection sensitivity is improved by a factor of similar to100 (100 amole of DNA target compared with 10 fmole ill the earlier work) by replacing the DNA-modified gold surface with a more stable DNA-modified diamond surface. (C) 2004 Wiley Periodicals, Inc.