Tagless and universal biosensor for point detection of pathogens

We demonstrate the use of terahertz time domain spectroscopy for determination of ligand binding for biomolecules. Vibrational modes associated with tertiary structure conformational motions lay in the THz frequency range. We examine the THz dielectric response for hen egg white lysozyme (HEWL): free and bound with tri-N-acetyl-D-glucosamine. Transmission measurements on thin films show that there is a small change in the real part of the refractive index as a function of binding and a sizable decrease in the absorbance. A phenomenological model is used to determine the source of the absorbance change. A change in the vibrational mode density of states and net dipole moment changes will necessarily happen for all biomolecule-ligand binding, thus THz dielectric measurements may provide an universally applicable method to determine probe-target binding for biosensor applications.