Novel (bio) analytical tools based on nanomaterials for point of care clinical diagnosis
- Autores: Celia Toyos Rodríguez
- Directores de la Tesis: Alfredo de la Escosura Muñiz (dir. tes.), Francisco Javier García Alonso (dir. tes.)
- Lectura: En la Universidad de Oviedo ( España ) en 2023
- Idioma: español
- Tribunal Calificador de la Tesis: María Jesús Lobo Castañón (presid.), Felipe Lombó Brugos (secret.), Ravinash Krishna Kumar (voc.), Susana Campuzano (voc.), Maria del Pilar Marco Colas (voc.)
- Programa de doctorado: Programa de Doctorado en Análisis Químico, Bioquímico y Estructural y Modelización Computacional por la Universidad de Oviedo
- Materias:
- Enlaces
- Tesis en acceso abierto en: RUO
- Resumen
The development of (bio)analytical tools is a field of great interest within analytical chemistry, given the simplicity, sensitivity, and low cost of these devices, which allows their use at the point of care. Their applicability is especially relevant in the biomedical field, where obtaining a quick and reliable clinical diagnosis is essential. Nanomaterials have been incorporated into them to improve the performance of these (bio)analytical tools.
Therefore, the objectives of this PhD Thesis are the study of novel (bio)analytical strategies, mainly based on electrochemical detection, integrating nanomaterials. In particular, the objectives were to: 1) synthesise nanoparticles with new electrocatalytic properties, and 2) apply them as electrocatalytic labels; 3) develop magnetic microparticles with high magnetisation and, 4) employ them as a sensing platform; 5) study the use of nanoporous alumina membranes, and particularly the electrostatic effects governing them and; 6) use them for biomarker detection; 7) integrate these membranes as platform for testing new antimicrobials, as well as 8) study new strategies, such as 3D printing to understand microbial interactions.
First, a general Introduction to point-of-care devices, focusing on biosensors and detailing their classification is provided. In addition, the advantages, and uses of nanomaterials in these devices are explained. Finally, a bibliographical review is made of the clinical cases studied in this PhD Thesis: Alzheimer's disease and the detection and study of chronic wound infection.
The main results are divided into four chapters. The first one presents the synthesis and characterisation of gold-palladium bimetallic nanoparticles (Pd-AuNPs) and the evaluation of their electrocatalytic activity against the oxygen reduction reaction. From this work it is concluded that Au/Pd ratio is essential to maximise the catalytic effect and that these particles are optimal as an electrochemical tag at neutral pH, allowing the detection of hyaluronidase, a marker enzyme for wound infections.
In the second, the synthesis and characterisation of magnetic nanoparticles and their encapsulation in polymeric matrices forming magnetic microparticles is studied. The performance of these microparticles is compared with that of commercial alternatives, and it is concluded that their performance is superior. These microparticles are used in a sandwich immunosensor, successfully detecting Tau protein, a biomarker of Alzheimer's disease.
The third chapter introduces the use of nanoporous alumina membranes as a sensing platform, concluding their usefulness in real samples, without the need of tags. In the first work included in this Chapter, the importance of electrostatic effects in the blocking of the analytical signal by direct antigen-antibody detection of a biomarker of Alzheimer's disease is demonstrated. The second work studies the opposite strategy, the unblocking of the analytical signal for the detection of an enzymatic biomarker, paying special attention to steric effects, concluding that these are also relevant in terms of the total blocking achieved. These studies are completed in a final work, which evaluates how the thickness of the membrane affects the sensitivity achieved, demonstrating that they are directly related.
In the last chapter, preliminary studies of new strategies for infection management are presented. In a first study, carried out during an international stay, 3D printing has been used for preliminary studies of the mechanisms of toxicity and interactions between bacterial species, showing that these outperform traditional techniques, making it possible to increase the sensitivity achieved. In a second study included in this Chapter, a (bio)analytical platform was developed for testing new antimicrobial compounds. First, the toxicity of the redox indicators used in electrochemistry was studied, concluding that some of them can affect bacterial growth.
