Broadband THz time-domain spectroscopy of biomolecules : a comprehensive study of the dielectric properties of biomaterials in the far-infrared

Since the introduction of THz-time-domain spectroscopy (THz-TDS) in the late 1980's, the technique, based on the generation and detection of subpicosecond terahertz pulses, has found widespread use as a simple and versatile experiment technique for obtaining the low frequency response of gases, solids and liquids. Since then there has been an increased interest in the exploitation of the THz-region in all fields of basic natural science as well as medicine. Recently commercial interest in the THz technology has also been growing, spurred by the potential for THz technology in the safety and security sector. Parallel, an increase of public interest in these 'T-rays' is noticeable. However, it appears that in many cases reporters but also research groups overestimate the potential of THz-TDS. Therefore we hope that this comprehensive study of the dielectric properties of biomaterials in the far-infrared will contribute to clearly outline the prospects but also the hurdles of THz spectroscopy of samples of biological relevance. <br>The increased interest in THz spectroscopy is also reflected by the number of collaborations that arose from this work. In a project sponsored by the Bundesministerium für Bildung und Forschung (BMBF), the potential of THz TDS for marker-free detection of the hybridisation of DNA was evaluated. Further collaborations with the with the pharmaceutical department of the University Freiburg, the chemistry department of the University Regensburg, the photronics group of the University Ulm and the department of microwave engineering and high frequency technology at the University of Erlangen-Nürnberg demonstrate the interdisciplinary character of this work. <br>This thesis is structured in the following way: <br>In Chapter 1 the basic aspects of vibrational spectroscopy in the far-infrared are reviewed. Chapter 2 outlines theoretical and technical concepts of terahertz time-domain spectroscopy. <br>In the following four chapters we give a broad overview of the capabilities and potentials of far-infrared spectroscopy of bio-molecules at the hand of specific samples which we studied. In chapter 3 the high sensitivity of the far-infrared spectra to small changes in the molecular or crystalline structure will be demonstrated, based on the spectra of saccharides and DNA components. <br>The vibrational origins that give rise to the characteristic fingerprints in far-infrared spectra are topic of Chapter 4, where examples of computational and experimental approaches in order to characterise and to identify the spectra will be given. In Chapter 5 the potential THz-TDS holds for applications based on chemical recognition will be demonstrated. For this we present characteristic spectra of pharmaceuticals, illicit drugs and explosives and introduce a contrast mechanism that allows a distinction between different chemicals hidden in sealed containers by the use of spatially resolved THz-TDS. In Chapter 6 we examine the spectra of larger, complex bio-molecules such as polysaccarides and polynucleotides. The lack of long-range intermolecular order in these materials and the consequent absence of characteristic features in the far-infrared spectra of these molecules prohibits applications based on the identification of characteristic far-infrared fingerprints. Yet we can show that under controlled conditions it is possible to use THz imaging to distinguish between the two RNA strands. We will further discuss the requirements to sample preparation imposed by the lack of sharp spectral features in the absorption spectra. <br>Some samples such as polar liquids or ionic crystals show very strong absorptions in the far-infrared and are thus not suitable for studies in a transmission <br>THz-TDS-spectrometer. Therefore a new spectrometer in reflection geometry was set up. In Chapter 7 we review the similarities and differences of THZ-TDS in reflection and transmission geometry and we present spectra of a selection of solid samples and water. In order to allow spectroscopy of the wide variety of samples in liquid, amorphous, and solid state form presented in this work the use of different window and filling materials is required. Although most plastic materials can be considered to be transparent for THz radiation compared to the strong absorptions occurring in the biomolecular samples, there are significant differences in the chemical and optical properties of commonly used window and filling materials. We review and present new data for this subject in Chapter 8. In Chapter 9 we will present the spectroscopic data of dioxane-water mixtures where we are in particular interested in the dielectric properties of water itself and its binding properties to the solvent dioxane. A large number of additional details were studied and evaluated in the course of this work. <br>These studies are collected in the appendix as most of these have by now appeared in print.

Author dc:creator

• Fischer, Bernd Michael

Contributors dc:contributor

• Helm, Hanspeter

• far-infrared
• THz-TDS
• biomolecules

Repository record source_url

https://freidok.uni-freiburg.de/data/2342

OAI identifier oai:identifier

oai:freidok.uni-freiburg.de:2342