The use of terahertz spectroscopy for biomolecular analysis

  • Thomas Harwood

Student thesis: Doctoral Thesis


Terahertz radiation occupies part of the electromagnetic spectrum between the mid-infraredand microwave bands (approximately 0.1 - 20 THz). Within this range, spectroscopic analysis of biological molecules can detect low-frequency vibrational modes that arise from intermolecular as well as intramolecular interactions and can provide significant information regarding structure and function. For example, the spectra of small biomolecules is dominated by individual modes and hydrogen bonds that can produce a distinctive spectral 'fingerprint',whereas the spectra of macromolecules, such as protein and DNA, can reveal information regarding conformation and dynamics. However, terahertz spectroscopy has habitually been underutilised as an investigative tool in biochemistry due to lack of terahertz sources and the strong absorbance of terahertz radiation by liquid water. The aim of this study was to bridge the gap between terahertz spectroscopy and biomolecular analysis by utilising three techniques to investigate a range of biomolecules of varying complexity. The bulk of this work employed terahertz Optical Kerr Effect (OKE) Spectroscopy as a novel means to study biomolecules in solution - This Raman based technique has the advantage that it does not suffer the same water absorption as conventional terahertz spectroscopies. We analysed a variety of small biomolecules, such as amino acids and nucleotides, and identified a variety of terahertz modes that are influenced by structure and interactions with the solvent. Additionally, we have identified spectral features in proteins molecules that are indicative of conformation and also identified novel vibrational modes that mediate protein-ligand binding in solution. Analysis of DNA and its components has also lead us to identify a multitude of previously undetected modes, some of which are attributed to phonons in the double helix and also hydrogen bonded interactions. We also utilised two common methods of terahertz spectroscopy - Terahertz Time DomainSpectroscopy (THz-TDS) and Fourier Transform Infrared (FTIR) Spectroscopy - to create the first comprehensive database of small biomolecules in the terahertz range and also developed a novel membrane method for the simple and rapid analysis of biomolecules.
Date of Award6 May 2016
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde & M Squared Lasers Ltd
SupervisorGail McConnell (Supervisor) & Patricia Connolly (Supervisor)

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