Detección precoz de la cardiopatía isquémica

La cardiopatía isquémica es una de las principales causas de muerte en los países desarrollados, por lo que su prevención, diagnóstico y tratamiento precoz se ha convertido en un objetivo de vital importancia para disminuir su morbi-mortalidad. En esta revisión se mencionan los principales avances conseguidos para mejorar el diagnóstico precoz de esta patología. A nivel electrocardiográfico, además de los signos ya conocidos como desviaciones del segmento ST, alteraciones en la onda T, aumento duración segmento QRS y cambio del eje eléctrico cardíaco, se han desarrollado diversos parámetros como el cálculo del área desviada del segmento ST, un nuevo algoritmo a partir de potenciales eléctricos tardíos, un nuevo biomarcador eléctrico cardíaco, el cálculo del área de la onda Q y la localización del territorio y vasos afectos según criterios electrocardiográficos. Sin embargo el avance más importante es la aplicación de la tecnología QRS-AF, que con un 75% ± 6% de sensibilidad y un 80% ± 6% de especificidad supera a los anteriores test diagnósticos. En los últimos años ha cobrado vital importancia la monitorización ambulatoria del paciente de alto riesgo, por lo que se han desarrollado tecnologías que faciliten esta labor como la creación de electrodos cada vez más cómodos y que originan menos artefactos, chips capaces de registrar la actividad eléctrica cardíaca y métodos de transmisión de esta información. Por último, se revisan los principales marcadores séricos de isquemia y el descubrimiento de nuevos, como el microARN-19a, obtenidos por PCR que son más sensibles y específicos que los anteriores

Diagnóstico temprano de la isquemia cardiaca

1. RESUMEN La cardiopatía isquémica causa más muertes, discapacidad y tiene un costo monetario mayor que cualquier otra enfermedad en los países desarrollados, siendo el infarto agudo de miocardio una de las entidades diagnosticadas con mayor frecuencia, por lo que su diagnóstico precoz ha sido un objetivo ampliamente estudiado durante años. En este trabajo se revisan y comparan los principales avances al respecto, repasando las técnicas y parámetros empleados clásicamente en el diagnóstico de la isquemia cardiaca. El electrocardiograma de 12 derivaciones es un elemento de importancia decisiva en el diagnóstico y clasificación del riesgo de los pacientes con sospecha de síndrome coronario agudo, pero tiene una serie de limitaciones importantes, tanto de sensibilidad (inicialmente del 28-65%), como de especificidad, por lo que han surgido nuevos parámetros electrocardiográficos, como el nuevo biomarcador eléctrico cardiaco (CEB), que con una sensibilidad del 85´3-94´4% ha demostrado tener una exactitud diagnóstica mayor que el ECG clásico, o el HFQRS y sus parámetros derivados, que también superan al ECG convencional con una sensibilidad del 75% ± 6% y una especificidad del 80% ± 6%. Se han estudiado nuevas localizaciones para los electrodos detectándose en 6 de ellas el mayor cambio del segmento ST registrado, de las que 5 no estaban en las posiciones estándar de las derivaciones precordiales. Se han desarrollado tecnologías que facilitan la monitorización ambulatoria del paciente de alto riesgo, como varios modelos de electrodos de cómoda colocación y biochips capaces de registrar la actividad eléctrica cardíaca, que han demostrado tener alta sensibilidad y exactitud diagnóstica mejorando además la capacidad de reducción de los artefactos registrados. Los biomarcadores sanguíneos no sólo complementan la evaluación clínica y electrocardiográfica, sino que juegan un papel diagnóstico esencial en el paciente con sospecha de síndrome coronario agudo. En esta revisión se recuerda la importancia de los biomarcadores empleados clásicamente en la detección de la isquemia cardiaca, siendo la troponina cardiaca I (cTnI) el “gold standard” en el diagnóstico del síndrome coronario agudo con una sensibilidad inicial del 20-50%. Asímismo, se estudian los avances biotecnológicos que han mejorado la capacidad de detección y cuantificación de daño miocárdico, como las troponinas de alta sensibilidad (hs-cTn), en cuyas mediciones seriadas se basan los nuevos algoritmos diagnósticos recomendados por la Sociedad Europea de Cardiología, y las nuevas líneas de investigación basadas en la vía genética de la patogénesis del infarto agudo de miocardio, donde el microRNA-19a, que ha demostrado ser más preciso para la presencia de infarto agudo de miocardio que los biomarcadores empleados clásicamente, y la proteína S100A4, con una sensibilidad del 76,3% y una especificidad del 87,5%, se postulan como nuevos biomarcadores fiables para la detección temprana de infarto agudo de miocardio

Development of a low-cost graphene-based impedance biosensor

PhD ThesisThe current applicability and accuracy of point-of-care devices is limited, with the need of future technologies to simultaneously target multiple analytes in complex human samples. Graphene’s discovery has provided a valuable opportunity towards the development of high performance biosensors. The quality and surface properties of graphene devices are critical for biosensing applications with a preferred low contact resistance interface between metal and graphene. However, each graphene production method currently results in inconsistent properties, quality and defects thus limiting its application towards mass production. Also, post-production processing, patterning and conventional lithography-based contact deposition negatively impact graphene properties due to chemical contamination. The work of this thesis focuses on the development of fully-functional, label-free graphene-based biosensors and a proof-of-concept was established for the detection of prostate specific antigen (PSA) in aqueous solution using graphene platforms. Extensive work was carried out to characterize different graphene family nanomaterials in order to understand their potential for biosensing applications. Two graphene materials, obtained via a laser reduction process, were selected for further investigations: reduced graphene oxide (rGO) and laser induced graphene from polyimide (LIG). Electrically conductive, porous and chemically active to an extent, these materials offer the advantage of simultaneous production and patterning as capacitive biosensing structures, i.e. interdigitated electrode arrays (IDE). Aiming to enhance the sensitivity of these biosensors, a novel, radio-frequency (RF) detection method was investigated and compared with conventional electrochemical impedance spectroscopy (EIS) on a well-known biocompatible material: gold (standard). It was shown that the RF detection methods require careful design and testing setup, with conventional EIS performing better in the given conditions. The method was further used on rGO and LIG IDE devices for the electrochemical impedance detection of PSA to assess the feasibility of the graphene based materials as biosensors. The graphene-based materials were successfully functionalized via the available carboxylic groups, using the EDC-NHS chemistry. Despite the difficulty of producing reproducible graphene-based electrodes, highly required for biosensor development, extensive testing was carried out to understand their feasibility. The calibration curves obtained via successive PSA addition showed a moderate-to-high ii sensitivity of both rGO and LIG IDE. However, further adsorption and drift testing underlined some major limitations in the case of LIG, due to its complex morphology and large porosity. To enable low contact resistance to these biosensors, the electroless nickel coating process is shown to be compatible with various graphene-based materials. This was demonstrated by tuning the chemical nickel bath and method conditions for pristine graphene and rGO for nickel contacts deposition

Conducting metal oxide materials for printed electronics

Printed electronics as a manufacturing process has many advantages, mainly, it allows for the high throughput rapid fabrication of thin, flexible electronic components with minimal waste. There are many printing processes that can be utilised for printing electronics and although each process can differ vastly, the materials currently used in these processes are generally the same, silver and carbon. However, to develop printing as a more mainstream manufacturing method for electronics, a wider variety of materials are required which can provide better stability and longevity of components, new functionality for printed applications and allow for in-situ processing and tuning of components. Conducting metal oxides are a good candidate for integrating into printed electronics processes, these materials are typically semiconductors, they have bandgaps, and properties can be altered via altering the band gap. They are also oxides, so they cannot oxidise further and therefore atmospheric damage is reduced compared to pure metals. They can also be fabricated into a wide range of particle morphologies, all with advantages in different fields and electronic applications. Therefore, the ability to print these materials is valuable to the field. In this thesis, the integration of conducting metal oxide electro-ceramic materials into the field of printed electronics has been explored. This was performed through the completion of five research objectives including, the selection of appropriate materials for the research, the formulation of conductive inks with the materials, the investigation of post-processing techniques for printed films and further research into passive component fabrication and sensor applications. Firstly, following an extensive literature review, four materials were selected including three doped zinc oxide materials synthesised via different methods. The fourth material is commercially sourced indium tin oxide (ITO). A nitrocellulose vehicle was determined to be the most compatible with the oxides and selected for ink formulation. Inks were then formulated with all four materials, with optical and electrical properties analysed. Gallium doped Zinc Oxide (GZO) and ITO were selected for further investigation based on the excellent conductivity of the indium tin oxide (57.77Ω□-1) and the highly transparent optical properties of the gallium doped zinc oxide (>84% transmittance). Laser processing was selected as a post processing method. It was found that the laser processing dramatically increased conductivity. The GZO improving from a non-conductive film to 10.21% of bulk conductivity. The ITO improved from 3.46% to 40.47% of the bulk conductivity. It was also found that the laser processing invoked a carbothermal reduction process allowing for a rapid manufacturing process for converting spherical particles into useful nanoparticle morphologies (nanorods, nanowires etc). Following this, resistive and capacitive applications involving laser processing and conventionally heat-treated conductive oxide inks were developed. Combining the new materials and manufacturing processes, tuneable printed resistors with a tuning range of 50 to 20M could be fabricated. All metal oxide, ITO based capacitors were also fabricated and characterised. These were then developed into humidity sensors which provided excellent humidity sensing properties, showing linearity between 5 and 95% relative humidity (RH) and sensitivities of up to 7.76pF/RH%, demonstrating higher performance than commercial equivalents (0.2 – 0.5pF/RH%). In conclusion, this work provides a breakthrough for conductive metal oxide materials research and its place in Printed Electronics research by providing insight into the processes required to make these materials conduct and by developing useful manufacturing methods, post processing techniques and applications.</div