T-ray biosensing: a versatile tool for studying low-frequency intermolecular vibrations

Abstract

The terahertz (or T-ray) spectra of many small molecules of biological relevance show very characteristic, specific features that are sensitive to small changes of the molecular structure and even isomerization. On the other hand, most packaging materials like plastics, paper or even clothing are transparent for T-rays. Therefore, it is possible to differentiate and identify different substances by their spectral fingerprints, even through their packaging. This supports the potential of this technique in a wide range of applications from safety and security applications, via biosensing, through to pharmaceutical quality control. However, most of the molecular vibrations that give rise to the characteristic features in the T-ray spectra are phonon-like intermolecular vibrations of weakly bound crystalline compounds. This can be easily demonstrated by comparing the spectra of different crystals of the same molecule. Whereas this sensitivity on the intermolecular structure can be used to probe the crystalline structure and detect phase transitions, it is a hurdle when it comes to identify samples that lack such a well defined intermolecular structure. Yet, we have recently shown that a comparison of the absolute absorption values can still be used to differentiate between complex biomolecules such as RNA. In this paper we will demonstrate, based on a wide range of spectra, the potential of T-ray spectroscopy for biosensing and will show examples where this technique can be used to probe the crystalline configuration and probe phase transitions and will discuss the feasibility of using this technique for biosensing.