The One Health approach highlights the intrinsic interconnectedness of human, animal, and environmental health, promoting collaboration across sectors like public health, veterinary medicine, and environmental science. It integrates the exposome concept, which assesses the cumulative effect of lifetime environmental exposures and their impact on health. Biosensing and nanoelectronic technologies can play a key role in real-time environmental monitoring and early detection and accurate quantification of pollutants to support the definition of improved policy standards. Ultimately, they enable the comprehensive evaluation of the health status of populations and individuals. In particular, advancements in nanoelectronics are driving the growth of emerging (bio)sensing applications by enabling ultra-sensitive measurement technologies for point-of-care, lab-on-a-chip, portable devices, etc. A special focus is on CMOS integration for sensors, which allows for improved measurement capabilities, low limit of detection, miniaturized designs, integration with modern electronics, massive production, and low costs. In this work, three emerging applications are analyzed. First, microplastics and nanoplastics are recognized as threatening pollutants for ecosystems, human, and animal health. Their risks, pathways, and measurement standards remain undefined, while traditional analytical methods face challenges in resolution, complexity, and cost. Second, titanium dioxide (TiO2) nanotubes are receiving considerable attention for their unique properties for, among others, biomedical implants, solar cells, supercapacitors, and gas sensors. The characterization of these analytes, particularly in the single-nanotube form, remains challenging and unsatisfactory. Lastly, electrical characterization of individual cells can provide unique physiological information and enable early pathology detection. Red blood cells are particularly noteworthy due to their unique physical and electrical properties, which are essential for oxygen transport. Through experimental results corroborated by physics-based numerical simulations, this work explores the use of high-frequency impedance spectroscopy measured at CMOS nanoelectrode arrays for nanoplastics and microplastics monitoring, TiO2 nanotubes characterization, and single-cell impedance cytometry. In particular, a methodology for nanoplastics and microplastics monitoring in water has been developed, enabling real-time measurements. Debye screening due to the electrical double layer, which severely impairs the spatial sensitivity of traditional impedimetric sensors, is overcome in the high-frequency regime. This work proposes a method for calculating the sensing volume by considering the 3D electric field distribution, identifying areas where beads generate a detectable response. This methodology enables concentration estimations across varying salinity, particle sizes, and concentrations. Algorithms for 3D particle tracking and nanoscale size estimation using simple models and machine learning have also been tailored for the application. As regards TiO2 nanotubes, experimental high-frequency impedance spectra were measured for the first time and directly compared to physics-based numerical simulations. The results corroborate the existing literature on the electrical characteristics of TiO2 and address the discrimination between single and cluster of nanotubes. Finally, regarding red blood cells, investigations have been conducted for cell characterization, paving the way toward advanced electrical imaging and hyperspectral analysis of the single-erythrocytes morphological and electrical characteristics.
L'approccio One Health evidenzia l'intrinseca interconnessione della salute umana, animale e ambientale, promuovendo la collaborazione tra settori come la salute pubblica, la medicina veterinaria e le scienze ambientali. Esso integra il concetto di esposoma, che valuta l'effetto cumulativo delle esposizioni ambientali nel corso della vita e il loro impatto sulla salute. Le tecnologie di (nano)-biosensing possono svolgere un ruolo chiave nel monitoraggio ambientale in tempo reale e nella rilevazione precoce e quantificazione accurata degli inquinanti, per supportare la definizione di standard normativi. In ultima analisi, queste tecnologie consentono una valutazione dello stato di salute delle popolazioni e degli individui. In particolare, i progressi nella nanoelettronica stanno promuovendo applicazioni di (bio)sensing emergenti, grazie all'abilitazione di tecnologie di misurazione ultra-sensibili per dispositivi portatili, lab-on-a-chip, ecc. Un focus speciale è sull'integrazione CMOS per i sensori, che consente migliorate capacità di misurazione, avanzata risoluzione, design miniaturizzati, integrazione con l’elettronica moderna, produzione massiva e bassi costi. In questa tesi sono analizzate tre applicazioni emergenti. Innanzitutto, le microplastiche e le nanoplastiche sono inquinanti minacciosi per gli ecosistemi, la salute umana e animale. I loro rischi e standard di misurazione rimangono indefiniti, mentre i metodi analitici tradizionali sono limitati per risoluzione, complessità e costo. In secondo luogo, i nanotubi di TiO2, grazie alle loro proprietà uniche, sono utilizzati per impianti biomedici, celle solari, supercondensatori e sensori di gas. La caratterizzazione di questi analiti, in particolare nella forma di nanotubi singoli, rimane una sfida. Infine, la caratterizzazione elettrica di singole cellule può fornire informazioni fisiologiche uniche e consentire una diagnosi precoce di patologie. I globuli rossi sono particolarmente degni di nota a causa delle loro proprietà fisiche ed elettriche, essenziali per il trasporto dell'ossigeno. Attraverso risultati sperimentali corroborati da simulazioni numeriche, questa tesi esplora l'uso della spettroscopia di impedenza ad alta frequenza misurata su un array di nanoelettrodi per il monitoraggio delle nanoplastiche e microplastiche, la caratterizzazione dei nanotubi di TiO2 e la citometria di impedenza. In particolare, è stata sviluppata una metodologia per il monitoraggio delle nanoplastiche e microplastiche nell'acqua per misurazioni in tempo reale. Il Debye screening, che compromette la sensibilità spaziale dei sensori impedimetrici tradizionali, viene mitigato nel regime ad alta frequenza. Questa tesi propone un metodo per calcolare il volume di rilevamento considerando la distribuzione del campo elettrico, identificando aree in cui le particelle generano una risposta rilevabile. Questa metodologia consente stime di concentrazione al variare della salinità, alle dimensioni delle particelle e alle concentrazioni. Sono stati inoltre sviluppati algoritmi per il tracciamento di particelle e la stima delle dimensioni su scala nanometrica utilizzando modelli semplici e intelligenza artificiale. Per quanto riguarda i nanotubi di TiO2, gli spettri di impedenza ad alta frequenza sono stati misurati per la prima volta e confrontati direttamente con simulazioni. I risultati corroborano la letteratura esistente sulle caratteristiche elettriche del TiO2 e indagano la discriminazione tra nanotubi singoli e cluster. Infine, riguardo ai globuli rossi, sono state condotte indagini per la caratterizzazione cellulare, aprendo la strada verso immagini elettriche avanzate e analisi iperspettrali delle caratteristiche morfologiche ed elettriche degli eritrociti.
Applicazioni ambientali e biomedicali emergenti di un'avanzata piattaforma integrata ad array di nanoelettrodi.
GOLDONI, DANIELE
2025
Abstract
The One Health approach highlights the intrinsic interconnectedness of human, animal, and environmental health, promoting collaboration across sectors like public health, veterinary medicine, and environmental science. It integrates the exposome concept, which assesses the cumulative effect of lifetime environmental exposures and their impact on health. Biosensing and nanoelectronic technologies can play a key role in real-time environmental monitoring and early detection and accurate quantification of pollutants to support the definition of improved policy standards. Ultimately, they enable the comprehensive evaluation of the health status of populations and individuals. In particular, advancements in nanoelectronics are driving the growth of emerging (bio)sensing applications by enabling ultra-sensitive measurement technologies for point-of-care, lab-on-a-chip, portable devices, etc. A special focus is on CMOS integration for sensors, which allows for improved measurement capabilities, low limit of detection, miniaturized designs, integration with modern electronics, massive production, and low costs. In this work, three emerging applications are analyzed. First, microplastics and nanoplastics are recognized as threatening pollutants for ecosystems, human, and animal health. Their risks, pathways, and measurement standards remain undefined, while traditional analytical methods face challenges in resolution, complexity, and cost. Second, titanium dioxide (TiO2) nanotubes are receiving considerable attention for their unique properties for, among others, biomedical implants, solar cells, supercapacitors, and gas sensors. The characterization of these analytes, particularly in the single-nanotube form, remains challenging and unsatisfactory. Lastly, electrical characterization of individual cells can provide unique physiological information and enable early pathology detection. Red blood cells are particularly noteworthy due to their unique physical and electrical properties, which are essential for oxygen transport. Through experimental results corroborated by physics-based numerical simulations, this work explores the use of high-frequency impedance spectroscopy measured at CMOS nanoelectrode arrays for nanoplastics and microplastics monitoring, TiO2 nanotubes characterization, and single-cell impedance cytometry. In particular, a methodology for nanoplastics and microplastics monitoring in water has been developed, enabling real-time measurements. Debye screening due to the electrical double layer, which severely impairs the spatial sensitivity of traditional impedimetric sensors, is overcome in the high-frequency regime. This work proposes a method for calculating the sensing volume by considering the 3D electric field distribution, identifying areas where beads generate a detectable response. This methodology enables concentration estimations across varying salinity, particle sizes, and concentrations. Algorithms for 3D particle tracking and nanoscale size estimation using simple models and machine learning have also been tailored for the application. As regards TiO2 nanotubes, experimental high-frequency impedance spectra were measured for the first time and directly compared to physics-based numerical simulations. The results corroborate the existing literature on the electrical characteristics of TiO2 and address the discrimination between single and cluster of nanotubes. Finally, regarding red blood cells, investigations have been conducted for cell characterization, paving the way toward advanced electrical imaging and hyperspectral analysis of the single-erythrocytes morphological and electrical characteristics.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.14242/202171
URN:NBN:IT:UNIMORE-202171