Nucleic acid hybridization is fundamental to many molecular biology applications, and is expected to grow in significance as nanomedicine joins molecular medicine at the cutting edge of research (28) . In particular, biomedical applications of hybridization such as detection of variable viral target sequences are highly dependent on a precise understanding of the process involved. A probe that has a broad detection spectrum should be as specific as current narrower probes while retaining the ability to cover the biologically or clinically relevant sequence variants of specific microbes. The design of long mismatch-tolerant probes demands knowledge about hybridization in the presence of mismatches, degeneracy and nt analogs.