Mid-infrared photonic sensors based on metamaterial structures

In this work three different metallic metamaterials (MMs) structures such as asymmetric split ring resonators (A-SRRs), dipole and split H-shaped (ASHs) structures that support plasmonic resonances have been developed. The aim of the work involves the optimization of photonic sensor based on plasmonic resonances and surface enhanced infrared absorption (SEIRA) from the MM structures. The MMs structures were designed to tune their plasmonic resonance peaks in the mid-infrared region. The plasmonic resonance peaks produced are highly dependent on the structural dimension and polarisation of the electromagnetic (EM) source. The ASH structure particularly has the ability to produce the plasmonic resonance peak with dual polarisation of the EM source. The double resonance peaks produced due to the asymmetric nature of the structures were optimized by varying the fundamental parameters of the design. These peaks occur due to hybridization of the individual elements of the MMs structure. The presence of a dip known as a trapped mode in between the double plasmonic peaks helps to narrow the resonances. A periodicity greater than twice the length and diameter of the metallic structure was applied to produce narrow resonances for the designed MMs. A nanoscale gap in each structure that broadens the trapped mode to narrow the plasmonic resonances was also used. A thickness of 100 nm gold was used to experimentally produce a high quality factor of 18 in the mid-infrared region. The optimised plasmonic resonance peaks was used for detection of an analyte, 17β-estradiol. 17β-estradiol is mostly responsible for the development of human sex organs and can be found naturally in the environment through human excreta. SEIRA was the method applied to the analysis of the analyte. The work is important in the monitoring of human biology and in water treatment. Applying this method to the developed nano-engineered structures, enhancement factors of 10^5 and a sensitivity of 2791 nm/RIU was obtained. With this high sensitivity a figure of merit (FOM) of 9 was also achieved from the sensors. The experiments were verified using numerical simulations where the vibrational resonances of the C-H stretch from 17β-estradiol were modelled. Lastly, A-SRRs and ASH on waveguides were also designed and evaluated. These patterns are to be use as basis for future work.

Molecular probes for monitoring mitochondrial movement and function

This thesis explores two distinct parts of mitochondrial physiology: the role of mitochondria in generation of reactive oxygen species (ROS) and mitochondrial morphology and dynamics within cells. The first area of research is covered in Chapters 1-8. Mitochondrial biofunctionality and ROS production are discussed in Chapter 1, followed by the strategy of targeting bioactive compounds to mitochondria by linking them to lipophilic triphenylphosphonium cations (TPP) (Chapter 2). ROS sensors relevant to the research are reviewed in Chapter 3. Chapter 4 presents design and synthesis of novel probes for superoxide detection in mitochondria (MitoNeo-D), cytosol (Neo-D) and extracellular environment (ExCellNeo-D). The results of biological validation of MitoNeo-D and Neo-D performed in the MRC MBU in Cambridge are presented in Chapter 5. A dicationic hydrogen peroxide sensor that utilizes in situ click chemistry is discussed in Chapter 6. Preliminary work on the synthesis of mitochondria-targeted superoxide generators, which led to the development of mitochondria-targeted analogue of paraquat, MitoPQ, is presented in Chapter 7. A set of bifunctional probes (BCN-Mal, BCN-E-BCN and Mito-iTag) for assessing the redox states of protein thiols is discussed in Chapter 8 along with their biological validation. The second part of the thesis is aimed at the study of mitochondrial morphology and dynamics and is presented in Chapters 9-11. Chapter 9 provides background on the classes of fluorophores relevant to the research, the phenomenon of fluorescence quenching and the principle of photoactivation with examples of photoactivatable fluorophores. Next, the background on mitochondrial morphology and heterogeneity is presented in Chapter 10, followed by the ways of imaging and tracking mitochondria within cells by conventional fluorophores and by photoactivatable fluorophores exploiting super-resolution microscopy. Chapter 11 presents the design and synthesis of four photoactivatable fluorophores for mitochondrial tracking, MitoPhotoRhod110, MitoPhotoNIR, Photo-E+, MitoPhoto-E+, along with results of biological validation of MitoPhotoNIR. The results and discussion concludes with Chapter 12, which is a summary and suggestions for future work, followed by the chemistry experimental procedures (Chapter 13), materials and methods for biological experiments (Chapter 14) and references.