A novel deoxyribonucleic acid (DNA) sequencing method is described that uses peptide nucleic acid (PNA) biosensor chips. PNA is a synthesized DNA analog in which both the phosphate and the deoxyribose of the DNA backbone are replaced by polypeptides. The hybridization properties of PNA to DNA are comparable to those of DNA to DNA. PNA can thus be used in the same applications as DNA. We have used TOF-SIMS to investigate its ability to detect DNA fragments hybridized to complementary PNAs. The data show that hybridized DNA could be readily identified by detecting the PO2- and PO3- masses. A good discrimination between complementary and non-complementary sequences could be achieved. It can be concluded that TOF-SIMS is a very useful technique for investigating the complexities of the immobilization and hybridization processes and that SIMS has the potential for providing a rapid method for genetic diagnostics. (C) 2002 Elsevier Science B.V. All rights reserved.