University of Brescia

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    Study of different thermal management systems for traction batteries to obtain vehicle lightweighting

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    Nowadays environmental sustainability is a hot topic, especially with regards to the transportation sector. In fact, political strategies are oriented to the transition towards the cleaner technologies to reduce polluting and climate-altering emissions. However, even fully electric vehicles are not characterized by zero global emissions, due to the production of electricity from sources that are not always renewable. Moreover, this type of vehicle is afflicted by the limited range provided by the battery pack and its long recharging time. So, it is useful to reduce the energy consumption through appropriate strategies, for example by means of the vehicle lightweighting. In this paper we focus on the battery pack lightweighting by considering different passive battery cooling systems as a replacement for the standard active one. The passive systems considered are air and PCM-based (Phase Change Material) cooling systems. In addition to the primary lightweighting given by the replacement of the cooling system, the secondary lightweighting obtained by reducing the capacity of the battery pack to return to the range of the starting reference vehicle has been also considered. Three tools were used for the study: VI-CarRealTime and another consolidate vehicle model to obtain the power demand on a standard driving cycle; and an ad-hoc battery system model, configurable according to the cooling system. The simulations showed that the air-cooled system leads to greater lightweighting, but it makes the battery cells work far from 20 °C (optimal operating temperature) and therefore it could lead to greater battery cell degradation and its field of application must be limited to vehicles operating in fleets, with predictable mission; this can be overcome by using an appropriate PCM-based cooling system, stearyl alcohol. Furthermore, using a PCM, glycerol, with a melting point close to the optimal operating temperature of the batteries, allows to reduce the cell degradation

    Intensity and type of physical activity and semen quality in healthy young men

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    Objective: To study the relationship between intensity of physical activity (PA) and semen quality in healthy young men. Design: A prospective cohort study with repeated measures for each subject. Setting: Not applicable. Patient(s): Healthy high school and university students who did not regularly smoke tobacco, drink alcohol, or take drugs or medicine, with normal body mass index and abdominal circumference. Intervention(s): The participants underwent urologic visit, fasting blood and semen sampling, and anthropometric measurements, and filled in the International Physical Activity Questionnaire, at enrollment and after 4 and 8 months. Duration and frequency of walking, moderate-intensity, and vigorous-intensity activities in the last week were assessed, and a score was computed for total PA. Main outcome measure(s): Semen specimens were taken at each visit through masturbation, after 3-5 days of abstinence, and analyzed by an expert urologist. Sperm concentration, total and progressive motility, and proportion of spermatozoa with normal morphology were measured. Linear and generalized linear mixed models with the Poisson family were fitted to assess the relationships between PA variables and sperm parameters, after adjusting for season, time, and study arm. The shape of the relationship was modeled through restricted cubic spline regression. Result(s): A total of 143 male subjects, aged 18-23 years (median, 20 years), were enrolled. They had a median PA of 1,960 (95% confidence interval, 1,055-3,182) Metabolic Equivalent of Tasks in min/wk. Statistically significant differences were found for total, progressive motility, and percent of cell with normal morphology across categories of total PA; the highest medians of total (47%) and progressive motility (34%) and of the percentage of normal morphology cells (7%) were found for medium PA. Positive associations of sperm total motility and normal morphology with medium levels of PA, and negative associations with walking and vigorous-intensity activity emerged. Spline regression analysis confirmed these findings, showing an inverse U-shape relationship, with the highest value of total motility and normal morphology for medium PA, and the lowest values for lower and higher activity. Conclusion(s): These findings support the present recommendations to practice moderate PA for health improvement, including semen quality

    Moneychangers and the local credit market in late Renaissance Florence. A social network analysis

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    This chapter studies the structure and functioning of the interpersonal credit network in fifteenth-century Florence, focusing particularly on intermediation. To this end, the research centers on a specific professional group, the moneychangers. They were trained accountants and among the few individuals in the city with ready cash, which allowed them to be very active in the credit market. However, the sources show that they were not only lenders, but also intermediaries and guarantors. The chapter uses social network analysis (SNA) to investigate the main characteristics of the credit network and uses a multilevel algorithm to identify and study the communities that compose it. The analysis confirms the strength of professional and geographical homophily in network formation. Moreover, it stresses the important bridging role that moneychangers had in the Florentine credit market and the ways through which they linked various communities of the network with each other. The paper confirms quantitatively and qualitatively the important contribution of moneychangers to the efficiency of the local credit market – identified here as the capacity of the market to match debtors and creditors. They helped to overcome asymmetries of information, spreading trust, and lowering transaction costs

    Unveiling gender equality: assessing the impact of board gender diversity approaches in European Countries

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    The chapter examines the impact of gender inclusivity measures on corporate boards in European countries, focusing on whether these measures drive broader societal change. It analyzes the effectiveness of gender quota laws, recommendations, and disclosure approaches in increasing women's representation in leadership roles. The chapter introduces a comprehensive framework to evaluate outcomes based on these measures and assesses their influence on societal norms and institutional practices. Findings suggest that stricter measures, such as gender quota laws, significantly improve women's representation in business and finance, with varying effects across other institutional domains. Despite progress, the effectiveness of these measures is influenced by contextual factors, highlighting the need for a multifaceted approach to achieving gender equality in governance and management

    ASSESSMENT OF SUSTAINABLE RECOVERY AND RECYCLING POSSIBILITIES OF MATERIALS FROM END-OF-LIFE LI-ION BATTERIES

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    Il recupero urbano dei rifiuti elettronici, in particolare delle batterie al litio (LiB), è fondamentale per soddisfare la domanda di materie prime critiche e ridurre l’impatto ambientale. Questa ricerca esplora il riciclo sostenibile delle LiB attraverso un approccio completo che comprende revisione della letteratura, ottimizzazione dei processi, valutazione del ciclo di vita (LCA) e analisi dei costi del ciclo di vita (LCC) per massimizzare il recupero delle risorse riducendo al minimo l’impronta ambientale. La prima fase esamina sistematicamente le tecnologie di riciclo delle LiB, concentrandosi sullo sviluppo di una linea di pretrattamento decentralizzata per diverse chimiche di batterie. Passaggi chiave, tra cui frantumazione, separazione per densità, riscaldamento con CaO e separazione per flottazione, migliorano il recupero dei materiali e la compatibilità con vari tipi di LiB. La seconda fase indaga tecniche idrometallurgiche per il recupero dei materiali catodici, raggiungendo un recupero superiore all’83% per l’ossido di cobalto, 77% per l’ossido di nichel e 74% per l’ossido di manganese. L’ottimizzazione di processi come lisciviazione, purificazione e calcinazione ha ridotto la domanda energetica e l’impatto ambientale di quattro volte, dimostrando la fattibilità di metodi di recupero sostenibili. Un'analisi comparativa dei metodi di recupero della grafite nella terza fase evidenzia il processo a freddo come il più sostenibile ed economico, con un costo di recupero di -40 /kgeunimpattocomplessivo(SSI)di432μpt.Ilprocessoacaldohaprodottografitedialtaqualitaˋconilminorspaziamentointerstrato(0,345nm),mentreilprocessoaumidohageneratografiteadaltocontenutodicarboniomaconsignificativicompromessiambientali(SSIdi695μpt).Lultimafaseesplorailriutilizzodellagrafiteresiduaneltrattamentodelleacquereflue.Lossidodigrafene(GrO)sintetizzatohadimostratocapacitaˋdiadsorbimentosuperiori,conil97QuestostudioevidenziailpotenzialedelriciclosostenibiledelleLiBpersupportareuneconomiacircolare.Integrandoconsiderazioniambientaliedeconomiche,imetodisviluppatioffronosoluzioniscalabiliperilrecuperourbano,sottolineandoilruolocrucialedelriciclodelleLiBnellagestionesostenibiledellerisorse.Urbanminingofelectronicwaste,particularlylithiumionbatteries(LiBs),iscrucialforaddressingcriticalrawmaterialdemandsandreducingenvironmentalimpact.ThisresearchexploressustainableLiBrecyclingthroughacomprehensiveapproachencompassingliteraturereview,processoptimization,lifecycleassessment(LCA),andlifecyclecosting(LCC)tomaximizeresourcerecoverywhileminimizingtheenvironmentalfootprint.ThefirstphasesystematicallyreviewsLiBrecyclingtechnologies,focusingondevelopingadecentralizedpretreatmentlinefordiversebatterychemistries.Keysteps,includingcrushing,densityseparation,heatingwithCaO,andflotationbasedseparation,enhancematerialrecoveryandcompatibilitywithvariousLiBtypes.Thesecondphaseinvestigateshydrometallurgicaltechniquesforrecoveringcathodematerials,achievingover83Acomparativeanalysisofgraphiterecoverymethodsinthethirdphasehighlightsthecoldprocessasthemostsustainableandcosteffective,witharecoverycostof/kg e un impatto complessivo (SSI) di -432 μpt. Il processo a caldo ha prodotto grafite di alta qualità con il minor spaziamento interstrato (0,345 nm), mentre il processo a umido ha generato grafite ad alto contenuto di carbonio ma con significativi compromessi ambientali (SSI di 695 μpt). L’ultima fase esplora il riutilizzo della grafite residua nel trattamento delle acque reflue. L’ossido di grafene (GrO) sintetizzato ha dimostrato capacità di adsorbimento superiori, con il 97% di rimozione dei coloranti e il 94% dei metalli, superando le alternative commerciali. Questo studio evidenzia il potenziale del riciclo sostenibile delle LiB per supportare un’economia circolare. Integrando considerazioni ambientali ed economiche, i metodi sviluppati offrono soluzioni scalabili per il recupero urbano, sottolineando il ruolo cruciale del riciclo delle LiB nella gestione sostenibile delle risorse.Urban mining of electronic waste, particularly lithium-ion batteries (LiBs), is crucial for addressing critical raw material demands and reducing environmental impact. This research explores sustainable LiB recycling through a comprehensive approach encompassing literature review, process optimization, life cycle assessment (LCA), and life cycle costing (LCC) to maximize resource recovery while minimizing the environmental footprint. The first phase systematically reviews LiB recycling technologies, focusing on developing a decentralized pretreatment line for diverse battery chemistries. Key steps, including crushing, density separation, heating with CaO, and flotation-based separation, enhance material recovery and compatibility with various LiB types. The second phase investigates hydrometallurgical techniques for recovering cathode materials, achieving over 83% cobalt oxide, 77% nickel oxide, and 74% manganese oxide recovery. Optimization of leaching, purification, and calcination reduced energy demand and environmental impact by fourfold, demonstrating the feasibility of sustainable recovery methods. A comparative analysis of graphite recovery methods in the third phase highlights the cold process as the most sustainable and cost-effective, with a recovery cost of -40/kg and a single score impact (SSI) of -432 μpt. The hot process achieved high-quality graphite with the lowest interlayer spacing (0.345 nm), while the wet process produced high-carbon graphite but with significant environmental trade-offs (SSI of 695 μpt). The final phase explores the reuse of residual graphite in wastewater treatment. Graphene oxide (GrO) synthesized from residual graphite demonstrated superior adsorption capacities, achieving 97% dye removal and 94% metal removal, outperforming commercial alternatives. This study highlights the potential of sustainable LiB recycling to support a circular economy. By integrating environmental and economic considerations, the developed methods provide scalable solutions for urban mining, emphasizing LiB recycling's pivotal role in sustainable resource management

    Plasma microRNA Levels After Electroconvulsive Therapy in Treatment-Resistant Depressed Patients

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    Objectives: Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD), even though the molecular mechanisms underlying its efficacy remain largely unclear. This study aimed, for the first time, to analyze plasma levels of miRNAs, key regulators of gene expression, in TRD patients undergoing ECT to investigate potential changes during treatment and their associations with symptom improvement. Methods: The study involved 27 TRD patients who underwent ECT. Plasma samples were collected at baseline (T0) and 1 month after the last ECT session (T1), and miRNA analysis was conducted by qRT-PCR. We also performed gene prediction of miRNAs differentially expressed and KEGG pathway analysis. Results: miR-95-3p, miR-194-5p, miR-324-3p, miR-195-5p, miR-19b-3p, miR-30c-5p, let-7i-5p, and miR-497-5p were nominally downregulated at T1. Changes in miR-324-3p and miR-30c-5p levels between T0 and T1 significantly correlated with symptom improvement. Among the predicted miRNA target genes of these 2 miRNAs, we noticed the presence of VEGF and SIRT1, whose expression regulation has been associated with the ECT mechanism of action in previous studies. Conclusions: The study's most relevant results are related to the correlation between reductions in miR-30c-5p and miR-324-3p and the improvement of symptoms in response to ECT, positioning these miRNAs as promising candidates for further studies. These findings support and extend previous clinical and preclinical research indicating a role of miRNAs in ECT mechanism of action. However, no significant effects in ECT miRNA modulation were observed, highlighting the need for future replications in broader samples to confirm these results

    Bilateral carotid body tumor management: tips, tricks, strategies, and problems

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    Purpose of review Carotid body tumors (CBTs) are rare neuroendocrine tumors with an annual incidence of 1:30000. Bilateral carotid body tumors (BCBTs) account for 3-5% of all CBTs and are more frequently linked to familial syndromes and potential malignancy. BCBT management is still not universally standardized and depends on multiple factors, including patient's age, risk of malignancy, location, growth rate, size, and related Shamblin and Mehanna classifications. Recent findings Options of treatment include active surveillance, external beam radiation, and surgery. Surgery is the first-choice treatment, but it may not always be performed especially in elderly patients. Simultaneous BCBT resection is not suggested due to high intra-operative and postoperative risks. The decision to operate on the larger or smaller tumor first is still debated. Whenever feasible, treatment of the larger tumor first to reduce the tumor burden should be preferred but with higher risks of neurovascular injury. Conversely, starting with the smaller tumor first offers a lower risk at initial surgery but may complicate the management of the larger tumor later. Summary Surgery for BCBTs, whenever feasible, remains the most indicated treatment but poses a significant risk of neurovascular complications. Resection of the larger, often more symptomatic, and potentially problematic or malignant tumor, reduces the overall disease burden and mitigates risks of rapid progression but involves a higher immediate complication hazard. Multidisciplinary evaluation is essential for balancing surgical risks and long-term outcomes, prioritizing neurovascular preservation and reducing morbidity

    From the center to the periphery: untangling the role of NF-κB/c-Rel in Parkinson's disease

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    La Malattia di Parkinson (MP), il più comune disturbo neurodegenerativo del movimento, è caratterizzato dalla progressiva perdita di neuroni dopaminergici nella substantia nigra e si manifesta attraverso sintomi motori come tremore a riposo, rigidità muscolare, bradicinesia e problemi di equilibrio. Oltre ai deficit motori, la MP è associato a disturbi non motori, tra cui disfunzioni gastrointestinali, disturbi del sonno e declino cognitivo, che spesso precedono di anni l'insorgenza dei sintomi motori. Sebbene le cause precise della MP siano ancora sconosciute, l'α-sinucleina sembra svolgere un ruolo chiave, formando aggregati patologici che si accumulano nei neuroni, portando alla formazione di corpi di Lewy, un segno distintivo della malattia. Attualmente, la diagnosi del PD si basa principalmente sulla valutazione clinica, ma l'assenza di strumenti diagnostici precoci e accurati ostacola lo sviluppo di terapie efficaci. Identificare biomarcatori rappresenta quindi una priorità cruciale per permettere una diagnosi precoce, classificare i sottotipi della malattia e monitorare la progressione e l'efficacia delle terapie. Questa tesi esplora il ruolo di NF-κB/c-Rel nella fisiopatologia della MP, concentrandosi sui meccanismi molecolari e le implicazioni per la salute neuronale. Studi precedenti hanno dimostrato che i topi maschi carenti di NF-κB/c-Rel (c-rel−/−) mostrano una diffusione dell'α-sinucleina che parte dai bulbi olfattivi e dal nucleo motore dorsale del vago e progredisce verso la substantia nigra. Questa patologia è accompagnata da sintomi non motori precoci, come iposmia a 2 mesi, ansia e depressione a 12 mesi, seguiti da deficit motori a 18 mesi. Analisi post-mortem su pazienti affetti da MP hanno inoltre rivelato una ridotta attività di legame al DNA di NF-κB/c-Rel sia nel tessuto cerebrale che nelle cellule mononucleate del sangue periferico (peripheral blood mononuclear cells, PBMCs), suggerendo il coinvolgimento di questa disfunzione nella malattia. La tesi è suddivisa in due parti. La Parte I indaga sulla ridotta attività di legame al DNA di NF-κB/c-Rel nei PBMCs di pazienti con MP. Usando due coorti (a digiuno e postprandiale), i risultati mostrano che l’assunzione di cibo aumenta l'attività di NF-κB/c-Rel nei soggetti sani ma non nei pazienti affetti da MP. Lo studio ha poi esaminato le modifiche post-traduzionali (PTMs), in particolare la glicosilazione O-GlcNAc, un processo sensibile ai nutrienti che aggiunge residui di N-acetilglucosamina alle proteine. I pazienti con MP presentano deficit di O-GlcNAc sia generali che specifici per NF-κB/c-Rel. Inoltre, l'analisi degli enzimi coinvolti (OGT e OGA) ha evidenziato una disfunzione di questo pathway sia a digiuno che dopo il pasto. Esperimenti su colture di PBMC trattate con glucosio e inibitori di OGA hanno confermato un processo di O-GlcNAc alterato nei pazienti, indipendentemente dallo stato metabolico. Questi risultati sottolineano il ruolo di O-GlcNAc come possibile meccanismo molecolare e bersaglio terapeutico. La Parte II esamina il ruolo di NF-κB/c-Rel nella sopravvivenza dei neuroni dopaminergici sotto stress metabolico e ossidativo. Colture di neuroni midollari da topi c-rel+/+ e c-rel−/− mostrano che i neuroni c-rel−/− accumulano α-sinucleina endogena in quantità elevate, con ridotta ramificazione neuritica e respirazione mitocondriale. L'aumento di VMAT2 nei neuriti suggerisce un meccanismo compensatorio per contrastare il deficit funzionale. In sintesi, questa tesi dimostra che NF-κB/c-Rel sostiene la resilienza neuronale, regolando l'attività mitocondriale e la maturazione dei neuroni, evidenziando il suo potenziale come biomarcatore e bersaglio terapeutico per il PD.Parkinson’s disease (PD), the most prevalent neurodegenerative movement disorder, is marked by the progressive loss of dopaminergic neurons in the substantia nigra and manifests through motor symptoms such as tremor, rigidity, bradykinesia, and balance issues. Beyond motor impairments, PD is also associated with non-motor disorders, including gastrointestinal dysfunction, sleep disturbances, and cognitive decline, which often precede motor symptoms by years. While the exact causes of PD remain unclear, α-synuclein is believed to be a key player, forming pathological aggregates that accumulate in neurons and result in Lewy bodies, a hallmark of the disease. Currently, PD diagnosis relies on clinical evaluation, but the absence of early, accurate diagnostic tools hinders effective therapeutic development. Identifying biomarkers is therefore a critical priority to enable early diagnosis, subtype classification, and the monitoring of disease progression and therapeutic efficacy. This thesis explores the role of NF-κB/c-Rel in PD pathophysiology, focusing on its molecular mechanisms and implications for neuronal health. Prior research has demonstrated that male NF-κB/c-Rel-deficient mice (c-rel−/−) show an α-synuclein spreading pattern starting in the olfactory bulbs and vagus nerve and progressing to the substantia nigra. This pathology is accompanied by non-motor symptoms such as hyposmia, anxiety, and depression as early as two months, followed by motor deficits at 18 months. Post-mortem analysis of PD patients also revealed reduced NF-κB/c-Rel DNA-binding activity in both brain tissue and peripheral blood mononuclear cells (PBMCs), implicating its dysregulation in PD. The thesis is divided into two parts. Part I investigates the reduced NF-κB/c-Rel DNA-binding activity in PD patient PBMCs. Using two cohorts, fasted and postprandial, results show that food intake increases NF-κB/c-Rel activity in healthy individuals but not in PD patients. This was confirmed in the same individuals pre- and post-meal. The study then explored post-translational modifications (PTMs), particularly O-GlcNAcylation, a nutrient-sensitive process that adds N-acetylglucosamine residues to proteins and is regulated by UDP-GlcNAc synthesis. PD patients exhibited both general and NF-κB/c-Rel-specific O-GlcNAcylation deficits. Furthermore, analysis of enzymes involved in O-GlcNAcylation, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), showed dysregulation in both fasting and postprandial states. Experiments on PBMC cultures treated with high glucose and the OGA inhibitor PUGNAc confirmed impaired O-GlcNAcylation in PD patients, independent of metabolic state. These findings highlight O-GlcNAcylation as a potential molecular mechanism underlying NF-κB/c-Rel dysfunction and a promising therapeutic target. Part II examines NF-κB/c-Rel’s role in dopaminergic neuron survival under metabolic and oxidative stress. Primary midbrain neurons from c-rel+/+ and c-rel−/− mice were exposed to stressors to assess α-synuclein accumulation, neuritic arborization, and mitochondrial respiration. c-rel−/− neurons showed elevated baseline α-synuclein levels that did not increase under stress, reduced neuritic branching, and impaired mitochondrial respiration. Interestingly, increased vesicular monoamine transporter 2 (VMAT2) levels in c-rel−/− neurites suggest a compensatory mechanism for reduced neuronal functionality. In conclusion, the thesis demonstrates that NF-κB/c-Rel deficiency impacts neuronal resilience by disrupting mitochondrial activity and promoting α-synuclein accumulation. The findings underscore the critical role of NF-κB/c-Rel in PD pathogenesis, emphasizing its potential as a biomarker and therapeutic target for the disease

    Advanced Bioelectronic Platforms for Biomedical Engineering and E-Healthcare

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    La ricerca oggetto approfondisce la convergenza tra scienza dei materiali, elettronica e biologia attraverso lo sviluppo di piattaforme bioelettroniche basate su transistor elettrochimici organici (OECT). Adottando un approccio interdisciplinare, l’obiettivo è realizzare dispositivi innovativi che avanzino l’ingegneria biomedica, migliorando l’efficacia e l’accessibilità delle soluzioni di e-healthcare. Tra i vantaggi degli OECT vi sono basse tensioni di funzionamento, stabilità in ambienti acquosi, scalabilità per l'integrazione in sistemi elettronici su larga scala e facilità di fabbricazione. Operando come dispositivi a tre terminali, la conduttività del canale è modulata dal movimento di ioni attraverso il canale, guidato da cambiamenti di tensione all'interfaccia volumetrica tra l'elettrolita e il polimero conduttivo. Imitando i processi di trasporto ionico propri dei sistemi biologici, gli OECT si integrano perfettamente con i tessuti corporei e ambienti fisiologici, rilevando e amplificando i flussi ionici in segnali elettrici misurabili. Il Capitolo 1 fornisce una panoramica sugli OECT, evidenziando come questa tecnologia si allinei con lo sviluppo di piattaforme bioelettroniche per applicazioni biomediche. Il Capitolo 2 introduce un processo fotolitografico scalabile per la produzione di OECT ad alte prestazioni, utilizzando il polimero conduttivo poli(3,4-etilenediossitiophene) drogato con poli(stirene sulfonato) (PEDOT:PSS). Il metodo sfrutta una tecnica basata sulla deposizione di due strati di fotoresist con cross-linking controllato per definire le geometrie del canale e incapsulare gli elettrodi. Inoltre, al fine di ridurre la citotossicità e migliorare le prestazioni dei dispositivi, questo capitolo analizza l’uso di materiali alternativi per il gate polarizzabile, migliorando la sensibilità nella rilevazione degli ioni a basse tensioni di alimentazione. Questi sviluppi delineano una trasformazione nella bioelettronica integrata e nei sistemi neuromorfici. I risultati sono pubblicati nell'articolo "Microfabrication of Organic Electrochemical Transistors for High-Performance Integrated Bioelectronics" su Advanced Materials Technologies. Il Capitolo 3 introduce l’architettura ion-selective floating-gate OECT (ISFG-OECT), per eliminare la complessità e l’ingombro dei dispositivi tradizionali per il rilevamento ionico selettivo. Il nuovo design consente un accoppiamento ionico-elettronico efficiente, permettendo il rilevamento selettivo degli ioni senza l’impiego di serbatoi di liquidi. Questo capitolo evidenzia il potenziale degli ISFG-OECT come soluzione scalabile e affidabile per il monitoraggio degli ioni in settori come la diagnostica medica, l'agricoltura di precisione e il monitoraggio ambientale. I risultati sono stati pubblicati su Advanced Materials Technologies. Nel Capitolo 4, l’obiettivo è sviluppare OECT ad architettura verticale totalmente stampati in 3D (vOECT). Questo capitolo esplora un approccio di stampa 3D additiva che ottimizza la struttura del dispositivo e integra membrane ionoselettive, al fine di realizzare dispositivi miniaturizzati ad alte prestazioni. Viene dimostrato il loro potenziale per l'integrazione in applicazioni biomediche che richiedono alta sensibilità e selettività. Il Capitolo 5 presenta la realizzazione di una piattaforma bioelettronica ad alta efficienza e sensibilità per la quantificazione di vescicole extracellulari (EV). Il sistema integra matrici di OECT funzionalizzati in configurazione 3×4, utilizzando la click-chemistry per rilevare le EV con proteine di membrana, consentendo la quantificazione in tempo reale. Questa configurazione rappresenta una soluzione robusta, ad alta sensibilità e facile da usare per la sanità di precisione, la ricerca sulle EV e l’indagine diagnostica, affrontando le sfide della eterogeneità e la necessità di una quantificazione affidabile dei biomarcatori nelle applicazioni biomedicheThis thesis examines the convergence of materials science, electronics and biology through the development of bioelectronic platforms based on organic electrochemical transistors (OECTs). By fostering interdisciplinary research, it aims to develop innovative devices that advance biomedical engineering and significantly enhance the effectiveness and accessibility of e-healthcare solutions. Among the benefits of OECTs are their low operating voltages, stability in aqueous environments, scalability for integration into large-scale electronic systems and ease of processing and fabrication. Operating as three-terminal devices, OECTs channel conductivity is modulated by driving ions in and out of the channel, which is gated by voltage changes at the volumetric interface between the electrolyte and the conducting polymer film. By mimicking the ion transport processes inherent in biological systems, OECTs can seamlessly integrate with living tissues and physiological environments detecting and amplifying ion fluxes into measurable electrical signals. Chapter 1 details highlighting their unique properties and capabilities that align with the goals of developing advanced bioelectronic platforms for biomedical applications. Chapter 1 highlights the OECTs properties that support the development of advanced bioelectronic platforms for biomedical applications. Chapter 2 introduces a scalable photolithographic fabrication process for high-performance OECTs using the prototypical conductive polymer poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS). The method employs a two-layer photoresist approach with controlled cross-linking to pattern the polymeric channel and encapsulate the electrodes. This work explores alternative polarizable gate materials to mitigate cytotoxicity while enhancing device performance, achieving unprecedented ion detection sensitivity at low supply voltages. These advancements open opportunities for next-generation integrated bioelectronics, and neuromorphics. The results are reported in the paper “Microfabrication of Organic Electrochemical Transistors for High-Performance Integrated Bioelectronics” to be submitted to peer-review on Advanced Materials Technologies. Chapter 3 focuses on advancing ion-selective sensing with the introduction of ion-selective floating-gate OECTs (ISFG-OECTs) architecture. With the aim of overcoming the complexity and bulk of traditional ion-selective sensing devices, the novel architecture paradigm achieves efficient ionic-electronic coupling within a compact design, enabling selective ion detection without liquid reservoirs. Theoretical and practical guidelines for ISFG-OECT implementation are provided. This chapter highlights the ISFG-OECT’s potential as a scalable and reliable solution for ion monitoring in fields such as medical diagnostics, precision agriculture, and environmental sensing. This chapter’s findings are published on Advanced Materials Technologies. In Chapter 4, the objective is to develop fully 3D-printed vertical OECTs (vOECTs). This chapter explores a direct-write additive 3D printing approach that optimizes device structure and integrates ion-selective membranes to yield high-performance, miniaturized devices. It demonstrates their potential for integration in biomedical applications that require high sensitivity and selectivity. Chapter 5 outlines the development of a high-throughput bioelectronic platform for extracellular vesicle (EV) quantification. The system integrates channel-functionalized OECT arrays in a 3×4 matrix configuration, using click chemistry to detect EVs with transmembrane proteins, allowing real-time quantification. This configuration represents a robust, high-sensitivity, and user-friendly solution for precision healthcare, EV research, and screening diagnostics, addressing the challenges of heterogeneity and the need for reliable biomarker quantification in biomedical applications

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