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Asthma is a chronic disease affecting over 300 million people worldwide. Airway inflammation is a central feature of asthma. Quantitative sputum cytometry is the most validated method to assess this and to adjust anti-inflammatory therapy, yet it is underutilized due to rigorous processing that requires expensive specialized technicians. To address these limitations, this thesis focuses on the development of several point of need biosensors that rapidly quantify respiratory biomarkers as alternatives to traditional laboratory tests. The project began by developing a paper based sensor for detection of myeloperoxidase (MPO), a neutrophil biomarker. A test was developed using commercially available antibodies, showing direct correlation between the test line colour intensity and total neutrophils. This work was expanded to include a second protein target, eosinophil peroxidase (EPX), for identification of eosinophils. Although the test performed well using neat samples, it failed to identify EPX in clinical sputum samples. Analyzing pre-treatment methods identified that a quick immunoprecipitation technique using protein A/G beads followed by syringe filtration allowed for the device to successfully quantify EPX, eliminating the need for a centrifuge. However, the limited supply of commercial anti-EPX antibodies combined with the need for sample pre-treatment prompted investigation into alternative detection avenues. Nucleic acid aptamers were explored, with aptamer selection for EPX producing several aptamer candidates. Binding affinity and specificity tests were performed, with the T1-5 aptamer emerging. T1-5 was capable of selectively binding EPX over MPO with high affinity. This aptamer was integrated into a simple pull-down assay, capable of detecting EPX with an order of magnitude lower limit of detection than the antibody test. Overall this work has developed multiple sensors with the potential to overcome the limitations of accessibility to sputum cytometry, rapidly identify the presence and type of airway inflammation, and deliver personalized treatment strategies that not only reduce the global healthcare burden, but also greatly improve a patient’s quality of life. / Thesis / Doctor of Philosophy (PhD)

<p dir="ltr">The emergence of infectious diseases like HIV, influenza, and COVID-19 highlights the urgent need for highly scalable testing methods that can be deployed outside traditional laboratory settings. Despite decades of research in point-of-care (POC) diagnostics, the main challenge remains the limited performance of assays, especially in terms of sensitivity. Furthermore, most POC assays originating from academic research struggle to transition beyond the laboratory due to manufacturability issues. This dissertation aims to enhance the effectiveness of viral molecular detection platforms for POC diagnostics by improving analytical and clinical sensitivity and facilitating the practical adaptation of academic-developed POC devices for use outside laboratory settings.</p><p dir="ltr">Each aim addresses a separate aspect of device development. The first aim addresses the need for clinical accuracy during test interpretation, especially in POC or at-home diagnostic tests, by developing an internal amplification control (IAC). Here, I develop a one-pot duplex reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay for detecting SARS-CoV- 2 along that incorporates a housekeeping gene as an IAC to ensure the quality of collected samples and the validity of assay reagents. The valid results can be easily visualized in triple-line lateral flow immunoassay (LFIA). The second aim makes progress towards overcoming the limited analytical sensitivity of existing rapid diagnostic tests for acute HIV infection screening. Here, I introduce a novel antibody-initiated LAMP assay targeting the HIV p24 capsid protein that combines LAMP sensitivity with the specificity of HIV p24 and its antibody. There are 3000 p24 capsid proteins present in the virion compared to only 2 viral RNA copies. In the assay, two DNA- conjugated antibody probes will each bind to p24 and their proximity will allow the DNA overlaps to generate a complete DNA target that acts as a trigger for the LAMP reaction. An LFIA is integrated into this design to enable simple result visualization. The third aim improves manufacturability and assembly of our existing nucleic acid detection platform by simplifying the platform components while maintaining the user-friendly sample-to-answer concept. Here, I validate material compatibility testing, assess chamber fabrication methods amenable to large-scale manufacturing, evaluate alternative heating units, and examine fluid flow control mechanisms of the redesigned wax valve. These combined aims demonstrate promising outcomes for practical implementation of molecular diagnostics to the POC.</p>

<p dir="ltr">Phosphatidylethanol (PEth) species are emerging as promising biomarkers for alcohol consumption due to their specificity and stability in biological samples. This thesis employs a quadrupole ion trap mass spectrometer to comprehensively profile 25 PEth analogs in dried blood spot (DBS) samples. The study adopts a semi-quantitative approach utilizing tandem mass spectrometry (MS/MS) to assess relative PEth analog abundances based on ion intensities without inducing fragmentation except that declustering is achieved. This method provides rapid data acquisition compared to absolute concentration determinations, with the potential to provide additional insights into individual metabolic and/or alcohol consumption patterns.</p><p dir="ltr">Initial analysis focuses on precursor ion intensities at unit mass resolution, revealing distinctive distribution patterns of PEth analogs across eight patient samples. Utilizing a heatmap generated from PEth analysis, significant patterns and similarities were identified among certain patient groups. Patient 2 and Patient 8 exhibit similar PEth profiles, while Patient 3, Patient 4, and Patient 5 form another group with comparable PEth analog intensities. Similarly, Patient 6 and Patient 7 also show analogous profiles, whereas Patient 1 stands out with a distinctly unique PEth profile. These observed groupings indicate that, despite the variability in individual responses to alcohol consumption, there are commonalities that can be leveraged to form supergroups based on PEth analysis.</p><p dir="ltr">Subsequent MS/MS analysis elucidates the structural diversity of the top five most abundant PEth analogs (<i>m/z </i>723.5, 751.5, 753.5, 773.5, and 775.5) by fragmenting isolated ions and recording product ion spectra. This approach facilitates the identification of multiple isomeric PEth molecules at specific precursor <i>m/z</i> values, enhancing the characterization of PEth species.</p><p dir="ltr">Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) are employed to interpret MS/MS data, revealing distinct clustering patterns among patient samples based on their PEth profiles. These analyses highlight the discriminatory potential of PEth analogs in delineating alcohol consumption behaviors within a limited cohort.</p><p dir="ltr">Despite limitations related to sample size and cohort specificity, this study underscores the utility of LTQ mass spectrometry in rapid and comprehensive PEth analog profiling. The findings contribute to validating PEth species as reliable biomarkers for alcohol consumption, with implications for clinical diagnostics and forensic applications.</p>

Tesis por compendio / [EN] The determination of genetic biomarkers is progressively becoming more extended and popular, being commercialized even in kits for personalized medicine. Establishing specific genotype variations for each patient, such as single nucleotide polymorphisms (SNPs), could be a fundamental tool in the field of diagnosis, prognosis and therapy selection. However, the use of DNA testing is not fully implemented in general healthcare, mainly due to technical and economic barriers associated to the current technologies, which are limited only to specialized centers and large hospitals. In this thesis, the main goal was to overcome these obstacles by developing simpler, faster and more affordable point-of-care (POC) genotyping systems. Allele discrimination was achieved by employing isothermal enzymatic reactions, like recombinase polymerase amplification (RPA), ligation of oligonucleotides and loop-mediated isothermal amplification (LAMP). These processes were integrated to colorimetric indicators and immunoenzymatic assays, in a microarray format. Using compact discs and polycarbonate chips as platforms, the detection was achieved through widespread electronics, like disc-reader, flatbed scanner and smartphone. To demonstrate their capacities, the resulting systems were applied for identifying SNPs in human samples, associated to therapies for tobacco smoking cessation, major depression disorder and blood clotting-related diseases. After selecting the proper conditions, all studied strategies discriminated SNPs in samples containing as low as 100 copies of genomic DNA, with an error rate below 15%. Most importantly, the developed methods have reduced assays times varying between 70 and 140 minutes, at a cost similar to a conventional PCR-based analog, but maintaining or raising amplification efficiency and eliminating the need of specialized temperature cyclers and fluorescence scanners. In conclusion, the biosensors based in isothermal reactions and consumer electronics devices greatly improve the competitivity of POC DNA analysis. It was demonstrated that the technologies developed in this thesis could support genotyping assays in low-resource areas, such as primary healthcare centers and emerging countries. Through this democratization of genetic testing and by performing adequate association studies, molecular diagnostics and personalized medicine practices could have their application extended to the clinical routine. / [ES] La determinación de biomarcadores genéticos es cada vez más extensa y popular, estando incluso comercializándose kits para medicina personalizada. Establecer las variaciones específicas en el genotipo de cada paciente, como los polimorfismos de un solo nucleótido (SNP) podría ser una herramienta fundamental en el campo del diagnóstico, pronóstico y selección de la terapia. Sin embargo, el uso de pruebas de ADN no se encuentra completamente implementado en la atención médica general, principalmente debido a las barreras técnicas y económicas asociadas a las tecnologías actuales, limitadas solamente a centros especializados y grandes hospitales. En esta tesis, el objetivo principal fue superar estos obstáculos mediante el desarrollo de sistemas de genotipado point-of-care (POC), más simples, rápidos y asequibles. La discriminación alélica se logró mediante el uso de reacciones enzimáticas isotermas, como la amplificación de la recombinasa polimerasa (RPA), la ligación de oligonucleótidos y la amplificación isotérmica mediada por bucle (LAMP). Estos procesos se integraron a indicadores colorimétricos y ensayos inmunoenzimáticos en formato de micromatriz. Utilizando discos compactos y chips de policarbonato como plataforma de ensayo, se ha logrado la detección mediante dispositivos electrónicos de consumo, como un lector de discos, escáner documental y teléfono móvil. Para demostrar sus capacidades, los sistemas resultantes se aplicaron a la identificación de SNPs en muestras humanas, asociados a terapias antitabaquismo, para depresión y enfermedades relacionadas con la coagulación de la sangre. Tras seleccionar las condiciones adecuadas, todas las estrategias estudiadas discriminaron SNPs en muestras conteniendo tan solo 100 copias de ADN genómico, con una tasa de error inferior al 15%. Más importante, los métodos desarrollados han reducido los tiempos de ensayo a valores entre 70 y 140 minutos, a un coste similar a un análogo convencional basado en la reacción en cadena de la polimerasa (PCR), pero manteniendo o aumentando la eficiencia de amplificación y eliminando la necesidad de termocicladores y escáneres de fluorescencia. En conclusión, los biosensores basados en reacciones isotérmicas y dispositivos de electrónica de consumo mejoran en gran medida la competitividad del análisis POC de ADN. Se ha demostrado que las tecnologías desarrolladas en esta tesis podrían apoyar los ensayos de genotipado en áreas de recursos escasos, como centros de atención primaria y países emergentes. A través de esta democratización de las pruebas genéticas y realización estudios de asociación adecuados, el diagnóstico molecular y las prácticas en medicina personalizada podrían extender su aplicación a la rutina clínica. / [CA] La determinació de biomarcadors genètics és cada vegada més extensa i popular, estant fins i tot comercialitzant-se kits per a medicina personalitzada. Establir les variacions específiques en el genotip de cada pacient, com els polimorfismes d'un sol nucleòtid (SNP) podria ser una eina fonamental en el camp del diagnòstic, pronòstic i selecció de la teràpia. No obstant això, l'ús de proves d'ADN no es troba completament implementat en l'atenció mèdica general, principalment a causa de les barreres tècniques i econòmiques associades a les tecnologies actuals, limitades solament a centres especialitzats i grans hospitals. En aquesta tesi, l'objectiu principal va ser superar aquests obstacles mitjançant el desenvolupament de sistemes de genotipat point-of-care (POC), més simples, ràpids i assequibles. La discriminació al·lèlica es va aconseguir mitjançant l'ús de reaccions enzimàtiques isotermes, com l'amplificació de la recombinasa polimerasa (RPA), la lligació de oligonucleòtids i l'amplificació isotèrmica mediada per bucle (LAMP). Aquests processos es van integrar a indicadors colorimètrics i assajos inmunoenzimàtics en format de micromatriu. Utilitzant discos compactes i xips de policarbonat com a plataforma d'assaig, s'ha conseguit la detecció mitjançant dispositius electrònics de consum, com un lector de discos, escàner documental i telèfon mòbil. Per a demostrar les seues capacitats, els sistemes resultants es van aplicar a la identificació de polimorfismes en mostres humanes, associats a teràpies antitabaquisme, per a depressió i malalties relacionades amb la coagulació de la sang. Després de seleccionar les condicions adequades, totes les estratègies estudiades van ser capaces de discriminar SNPs en mostres contenint tan sols 100 còpies d'ADN genòmic, amb una taxa d'error inferior al 15%. Més important, els mètodes desenvolupats han reduït els temps d'assaig a valors entre 70 i 140 minuts, a un cost similar a un anàleg convencional basat en la reacció en cadena de la polimerasa (PCR), però mantenint o augmentant l'eficiència d'amplificació i eliminant la necessitat de termocicladors i escàners de fluorescència. En conclusió, els biosensors basats en reaccions isotèrmiques i dispositius d'electrònica de consum milloren en gran manera la competitivitat de l'anàlisi POC del ADN. S'ha demostrat que les tecnologies desenvolupades en aquesta tesi podrien donar suport als assajos de genotipat en àrees de recursos escassos, com a centres d'atenció primària i països emergents. A través d'aquesta democratització de les proves genètiques i realització estudis d'associació adequats, el diagnòstic molecular i les pràctiques en medicina personalitzada podrien estendre la seua aplicació a la rutina clínica. / [PT] A determinação de biomarcadores genéticos está tornando-se cada vez mais extensa e popular, sendo comercializada até em kits para medicina personalizada. O estabelecimento de variações específicas de genotipo para cada paciente, tais como os polimorfismo de nucleotídeo único, pode ser uma ferramenta fundamental no campo do diagnóstico, prognóstico e seleção de terapias. No entanto, o uso de testes de DNA ainda não encontra-se totalmente implementado na área de saúde geral, principalmente devido às barreiras técnicas e econômicas associadas às tecnologias atuais, limitadas apenas a centros especializados e grandes hospitais. Nesta tese, o principal objetivo foi superar esses obstáculos desenvolvendo sistemas de genotipagem point-of-care (POC) de DNA, mais simples, rápidos e acessíveis. A discriminação de alelos foi alcançada empregando reações enzimáticas isotérmicas, como amplificação por recombinase polimerase (RPA), ligação de oligonucleotídeos e amplificação isotérmica mediada por loop (LAMP). Tais processos foram integrados a indicadores colorimétricos e ensaios imunoenzimáticos, em formato micromatriz. Usando discos compactos e chips de policarbonato como plataforma de ensaio, os analitos foram detectados através de dispositivos eletrônicos de consumo, como leitor de disco, scanner de mesa e smartphone. Para demonstrar suas capacidades, os sistemas resultantes foram aplicados para identificação de polimorfismos em amostras de DNA humano, associados a terapias antitabagismo, para depressão e doenças relacionadas à coagulação do sangue. Após a seleção das condições adequadas, todas as estratégias estudadas foram capazes de discriminar SNPs em amostras contendo até 100 cópias de DNA genômico, com uma taxa de erro inferior a 15%. Mais importante, os métodos desenvolvidos reduziram o tempo de ensaio a valores entre 70 e 140 minutos, com um custo similar a um método análogo baseado em reação em cadeia da polimerase (PCR), mas mantendo ou aumentando a eficiência da amplificação e eliminando a necessidade de cicladores de temperatura e scanners de fluorescência especializados. Em conclusão, os biosensores baseados em reações enzimáticas isotérmicas e dispositivos eletrônicos de consumo incrementam grandemente a competitividade da análise POC de DNA. Foi demonstrado que as tecnologias desenvolvidas nesta tese poderiam dar suporte a ensaios de genotipagem em lugares com poucos recursos, como centros de atenção primária e países emergentes. Através desta democratização dos testes genéticos e com a realização de estudos de associação adequados, o diagnóstico molecular e as práticas de medicina personalizada poderiam ter sua aplicação extendida à rotina clínica. / The authors acknowledge the financial support received from the Generalitat Valenciana (GVA-PROMETEOII/2014/040 Project and GRISOLIA/2014/024 PhD grant) and the Spanish Ministry of Economy and Competitiveness (MINECO CTQ2013-45875-R project) / Yamanaka, ES. (2020). Isothermal-based DNA biosensors for application in pharmacogenetics [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/148366 / Compendio

Tesis por compendio / This thesis explores new analytical advances using compact disk biosensing technologies, and comprises six scientific publications distributed along four chapters. Special attention is herein payed to Thermochromic Etching Disks (TED) technology (Chapter 1), rational design of disk-based biorecognition assays (Chapter 2), and label-free detection systems for point-of-need analysis (Chapters 3 and 4). First, insights into a novel light-mediated signal developing system for biorecognition assays (based on TED disks and drives) are provided together with an overview of the state-of-the art and future trends in photo- and thermochromic biosensing. This signal developing approach exploits photo- and thermochromism for biosensing in an original manner and represents a potential strategy to simplify signaling processes in bioanalytical systems. Then, how to transform TED technology into lab-on-a-disk systems is addressed. TED has proven to be a very versatile tool to perform sensitive analysis of biorecognition assays, using platforms and scanners easily obtained from regular disks and drives, respectively. Biologically relevant assays of different nature (microarray, cell culture, immunofiltration, turbidimetry, etc.) have been arrayed in a single disk and sensitively analyzed by imaging. Regarding rational design, a theoretical-experimental method (INSEL) based on kinetics and mass-transport modelling for optimizing biorecognition assays and exploring their behavior is presented. INSEL has been implemented as an in silico tool that enables to characterize biointeractions with minimal experimentation, to perform optimizations directed towards custom objectives defined by the user, and to easily compute the effect of critical variables without further experiments. In another study included in this thesis, polycarbonate grooved structures obtained from standard recordable disks (CD-R and DVD-R) were coated with silver and tailored to become SERS-active. This strategy represents a cost-effective and industrially scalable alternative to the SERS substrates typically used for bioanalysis. These disk-based materials have presented tunable plasmonic responses, significant Raman enhancement, and have allowed complex biological targets (such as proteins and exosomes) to be analyzed by SERS without using labeled reagents as tracers. In addition to introduce inexpensive and large-scale SERS substrates for biosensing, this study also suggests the development of prospective Raman scanners based on disk drives. Another approach herein presented addresses the implementation of diffraction-based sensing (DBS) in TED technology in order to conceive disk-based label-free biosensors based on standard disks and drives. At first, a comprehensive experimental assessment of the analytical possibilities offered by DBS is presented. Then, the fabrication of arrays of diffractive protein networks on TED disks is investigated, with which sensitive analysis of antibodies in label-free conditions has been demonstrated, using adapted drives as scanners. This investigation provides important insights into cost-effective and industrially scalable functional materials and detection setups that exploit consumer electronics for label-free biosensing. / Esta tesis explora nuevos avances en química analítica usando tecnologías de biosensado basadas en sistemas de disco compacto y comprende seis publicaciones científicas distribuidas a lo largo de cuatro capítulos. Los estudios se han centrado en la tecnología Thermochromic Etching Disks (TED) (Capítulo 1), el diseño racional de ensayos de bioreconocimiento en discos compactos (Capítulo 2), y la detección sin marcaje para realizar análisis in situ (Capítulos 3 y 4). Primero, enmarcado en una discusión del estado del arte y futuras tendencias en biosensado foto y termocrómico, se presenta un nuevo sistema (basado en discos y lectores TED) mediado por luz para el desarrollo de señales en ensayos de bioreconocimiento. Ésta constituye una estrategia novedosa para aprovechar el foto y termocromismo en biosensado, y presenta un gran potencial para simplificar los procesos de desarrollo de señal en sistemas bioanalíticos. A continuación, se aborda cómo transformar la tecnología TED en sistemas analíticos integrados basados en discos compactos. TED ha demostrado ser una herramienta muy versátil para analizar, de forma sensible, ensayos de bioreconocimiento usando plataformas y escáneres fácilmente obtenidos a partir de discos y lectores convencionales, respectivamente. Un único disco ha mostrado poder albergar varios ensayos biológicos importantes y de distinta naturaleza (micromatriz, cultivos celulares, inmunofiltración, turbidimetría, etc.), para ser analizados de forma sensible a través de imágenes En cuanto al diseño racional, se presenta un método teórico-experimental (INSEL), basado en modelos cinéticos y de transporte de masa, para optimizar ensayos de bioreconocimiento y explorar su comportamiento. INSEL se ha implementado como una herramienta in silico que permite caracterizar biointeracciones mediante mínima experimentación, realizar optimizaciones dirigidas a objetivos particulares definidos por el usuario, y computar el efecto de variables críticas de forma sencilla y sin experimentos adicionales. En otro estudio incluido en esta tesis, nanoestructuras en forma de surco obtenidas a partir de discos regrabables convencionales (CD-R y DVD-R) fueron recubiertas con plata y adaptadas para ser activas en SERS. Esta estrategia supone una alternativa, económicamente efectiva e industrialmente escalable, a los sustratos SERS típicamente usados en bioanálisis. Estos materiales han mostrado respuestas plasmónicas sintonizables, una amplificación Raman significativa, y han permitido analizar muestras biológicas complejas (como proteínas y exosomas) mediante SERS sin usar marcadores. Además de introducir sustratos SERS grandes y baratos, este trabajo también sugiere el desarrollo de escáneres Raman basados en lectores de disco. Otra aproximación presentada en esta tesis aborda la implementación de DBS (diffraction-based sensing) en tecnologías TED, con el fin de desarrollar biosensores para detección sin marcaje basados en discos y lectores convencionales. Primero, se presenta una amplia evaluación experimental de las posibilidades analíticas ofrecidas por DBS. A continuación, se investiga la fabricación de multitud de redes difractivas de proteínas sobre discos TED, con las que se ha demostrado la determinación sensible y sin marcaje de anticuerpos, usando lectores adaptados como escáneres analíticos. Esta investigación introduce avances importantes que apuntan al desarrollo de materiales funcionales y sistemas de detección, baratos e industrialmente escalables, que aprovechen las tecnologías de consumo para realizar biosensado sin marcaje. / Aquesta tesi explora nous avanços en la química analítica usant tecnologies de biosensat basades en sistemes de disc compacte, i comprèn sis publicacions científiques distribuïdes en quatre capítols. Els estudis s'han centrat en la tecnologia Thermochromic Etching Disks (TED) (Capítol 1), el disseny racional d'assajos de bioreconeixement en discos compactes (Capítol 2), i la detecció sense marcatge per realitzar anàlisi in situ (Capítols 3 i 4). Primer, dins del marc d'una discussió de l'estat de l'art i tendències futures en biosensat foto i termocròmic, es presenta un nou sistema (basat en discos i lectors TED) per al desenvolupament de senyals mitjançant llum, en assajos de bioreconeixement. Aquesta constitueix una nova estratègia per aprofitar el foto i termocromisme en biosensat, mentre que també presenta una gran potencial per simplificar els processos de desenvolupament de senyal en sistemes bioanalítics. Tot seguit, s'aborda com transformar la tecnologia TED en sistemes analítics integrats basats en discos compactes. TED ha demostrat ser una eina molt versàtil per analitzar, de forma sensible, assajos de bioreconeixement usant plataformes i escàners fàcilment obtinguts a partir de discos i lectors convencionals, respectivament. Un únic disc ha mostrat poder albergar diversos assajos biològicament importants i de distinta naturalesa (micromatrius, cultius cel·lulars, immunofiltració, turbidimetria, etc.), per a ser analitzats de forma sensible a través d'imatges. Pel que fa al disseny racional, es presenta un mètode teòric-experimental (INSEL), basat en models cinètics i de transport de massa, per optimitzar assajos de bioreconeixement i explorar el seu comportament. INSEL s'ha implementat com a una eina in silico que permet caracteritzar biointeraccions amb mínima experimentació, realitzar optimitzacions dirigides cap a objectius particulars definits per l'usuari, i computar l'efecte de variables crítiques de forma senzilla i sense experiments addicionals. En un altre estudi inclòs en aquesta tesi, nanoestructures en forma de solc obtingudes a partir de discos compactes regravables convencionals (CD-R i DVD-R) van ser recobertes amb plata i adaptades per a ser actives en SERS. Aquesta estratègia suposa una alternativa, econòmicament efectiva i industrialment escalable, als substrats SERS típicament usats en bioanàlisi. Aquests materials han mostrat respostes plasmòniques sintonitzables, una amplificació Raman significativa, i han permès analitzar mostres biològiques complexes (com proteïnes i exosomes) mitjançant SERS sense usar marcadors. A més d'introduir substrats SERS grans i barats, aquest treball també suggereix el desenvolupament d'escàners Raman basats en lectors de disc. Una altra aproximació presentada en aquesta tesi aborda la implementació de DBS (diffraction-based sensing) en tecnologies TED, per tal de desenvolupar biosensors basats en discos i lectors convencionals que permeten detecció sense marcatge. Primer, es presenta una amplia avaluació experimental de les possibilitats analítiques que ofereix aquesta tècnica. A continuació, s'investiga la fabricació de multitud de xarxes difractives de proteïnes sobre discos TED, amb les quals s'ha demostrat la determinació sensible i sense marcatge d'anticossos, usant lectors adaptats com a escàners analítics. Aquesta investigació introdueix avanços importants que apunten cap al desenvolupament de materials funcionals i sistemes de detecció, barats i industrialment escalables, que aprofiten les tecnologies de consum per dur a terme bioanàlisi sense marcatge. / Avellà Oliver, JM. (2017). Towards label-free biosensing in compact disk technologies f or point-of-need analysis [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/86128 / Compendio