Ultrasensitive label-free detection and quantitation of DNA hybridization via terahertz spectrometry

Time-domain terahertz (THz) spectrometry has been used to analyze DNA hybridization state and its quantitation in a label-free manner. Time-resolved THz signal (or temporal signal) converted to frequency domain constitutes a signature of a given molecular "event" (e.g., a vibrational or a conformational state). The temporal signal provides a means of probing a molecular event in an appropriate time window. This is a unique ability of this technique because different molecular events exhibit different time response based on their physical and chemical nature. Conformational difference of a given molecule results in different signature with an appropriate time response that can be accurately probed by a terahertz temporal signal. In this work we discriminate between single stranded and double stranded 25-mer oligonucleotides via spectral signature. For each species, different peaks were identified; however, the peaks are distinctly different allowing an easy comparison. Additionally, temporal transmission spectra of the DNA specimens were collected at normal temperature and atmosphere. The peak value extracted from the temporal spectra exhibit a power law behavior over a region spanning from 13.6 femto-molar to 0.136 nano-molar. The results clearly demonstrate the ability of the spectrometer to detect a minute amount of biomolecules in a labelfree fashion. This capability can be used as a diagnostic tool, as well as for studying molecular reactions such as mutation.