Towards the development of flexible substrate materials for label-free Surface Enhanced Raman Spectroscopy (SERS) and Photo-induced Enhanced Raman Spectroscopy (PIERS)

This thesis is concerned with the label-free detection of small molecules and macromolecules using enhanced Raman spectroscopic techniques: Surfaceenhanced Raman Spectroscopy (SERS) and photo-induced enhanced Raman spectroscopy (PIERS). The work focuses on the development of reproducible and stable plasmonic nanoparticles (NPs) incorporated into flexible substrates to realise their SERS potential. The materials have been designed to fulfil the criteria of flexible and sensitive substrates in many applications with an emphasis in the biomedical field, especially within wound healing. A number of measurements on varying molecules were conducted to assess the SERS efficacy of the substrates. Most of the novel research presented in this thesis is proof-of-concept, laying the framework for further work. Chapter I highlights the importance of SERS and potential of PIERS with a thorough evaluation of the literature. Motivations behind the research as well as the aims of this work are addressed. Theoretical concepts are introduced with a touch on the mathematical background. Key principles and parameters influencing SERS and considerations are all covered to give a complete outline of the topic. The next few chapters focus on the results of this thesis. Chapter II provides synthetic routes for gold nanoparticles and includes a comparative study on the influence on nanoparticle shape on their subsequent SERS function. The effects of capping agents on the shape, size and stability of the NPs are examined. These are fully characterised and functional SERS testing is carried out using a range of molecules to fully evaluate their SERS ability. Surface modification is also attempted in this work with great concern given to overpowering solvent effects. Several biomarkers are introduced with qualitative SERS analysis. Duplex testing was performed to determine the specificity and sensitivity of the gold NPs. Chapter III starts investigating flexible materials as SERS substrates. These are readily available, low cost and biocompatible materials with gold NPs incorporated into them to become SERS active. Simple methods for synthesis 4 and data collection are presented as well as their SERS results. Paper and PDMS, whilst having some advantages lack clear Raman enhancement with inherent material signals dominating the spectra. Gelatine based hydrogels are chosen as an ideal candidate for SERS substrates. Many gelatine/polymer blends are synthesised and characterised to find the optimum gel regarding both mechanical and chemical permanence as well as SERS capability. Studies looking into cross-linking agents to establish the best synthetic protocol are executed. There is always a trade-off between highest functional efficiency and a more 'green' and sustainable approach. The PVA/hydrogel nanocomposite material exhibits valuable SERS whilst maintaining a facile methodology for synthesis and data acquisition. Chapter IV extends the SERS studies to biological macromolecules such as proteins and wound biomarkers. Both colloidal NPs and hydrogels are used as substrates. Concentration studies are conducted and attempts at correlating intensity with concentration are made, to limited realization. Real samples from patients are probed with patterns and trends hypothesised. These are corroborated against photographic evidence of the wound. Preliminary machine learning is employed to help classify the data with suggestive, positive results. Chapter V inspects PIERS on biomolecules with varying degrees of enhancements, but low concentration detection of glucose is reported. Different TiO2 substrates are investigated for their influence in the PIERS effect and are characterised appropriately. The preparation method, film thickness and wetting behaviour of the property are likely parameters that can impact the PIERS property of the substrate. Comparisons between SERS and PIERS reveal complex mechanistic considerations between the two phenomena. As a novel technique the possibilities to fully realise the potential of PIERS is yet to be explored, but there is a lot more research to be done to fully understand the effect. This thesis concludes with a summary of the key findings from the experimental work and presents possible avenues for further research to consolidate and advance the current work.