Fiber-enhanced Raman spectroscopy in aqueous media

Abstract

This dissertation focuses on the investigation and development of an optical biosensor based on fiber-enhanced Raman spectroscopy (FERS) that provides chemical selective and sensitive label-free detection of biomolecules. FERS has been achieved by using various types of liquid core optical fibers, which guide the light within the liquid sample and increase the interaction length with the analyte molecules. The first part of this dissertation explains the FERS technique in detail and describes the current state of research of FERS. Several essential characteristics, such as fiber length, attenuation, material and refractive index, are thoroughly discussed in considerations of Raman intensity enhancement. Liquid-core fibers formed with hollow-core photonic-crystal fibers (HC-PCFs) and polymer fibers are introduced and discussed, as they are the most important breakthroughs. The objective of this research is to develop a robust optical fiber platform based on Raman spectroscopy that shows potential for use in bio-analytical and clinical applications. In this work, I demonstrate a combination of UV-resonance Raman spectroscopy (UV-RRS) and liquid-core fibers, to increases the sensitivity for the detection of low-concentrated pharmaceuticals tremendously. This combined enhancement technique was applied for the detection of bile pigments for monitoring of diseases related to hyperbilirubinemia and hyperbiliverdinemia. Their poor optical quality strongly limits the performances of the polymer-based liquid-core fibers. Therefore, the implementation of HC-PCFs was explored in two different types of optical guiding. Waveguiding in the visible range is achieved for the first time in both kinds of liquid-filled HC-PCFs, and therefore the Raman scattering wavelengths are not anymore limited to the insensitive NIR range. In order to achieve easy-to-use and stable FERS devices for further development, the performance of HC-PCFs in the aspect of light-confinement was studied with the help of a specially designed multi-channel Raman chemical imaging. The optimal fiber length, spatial filtering, and optical coupling were thoroughly analyzed, and an automatic coupling system was developed. With the development of optical fibers, FERS shows increasing potential as a robust, fast, chemical selective and sensitive tool for the detection of biomolecules in clinical, pharmaceutical, and biological applications.