Unusual case of myocardial injury induced by Escherichia coli sepsis

The typical symptoms and signs of myocardial infarction are well known. Alterations in electrocardiogram (ECG), echocardiography or biochemical markers of myocardial necrosis are usually helpful to confirm the diagnosis. Some of these features, however, also occur in myocarditis, which is a potential differential diagnosis. We describe an unusual case of bacterial sepsis due to Escherichia coli that caused myocardial damage (myocarditis) with ECG changes mimicking acute myocardial infarction. The possible pathophysiological mechanisms of myocardial injury in sepsis are also reviewed

U-CHANGE Project: a multidimensional consensus on how clinicians, patients and caregivers may approach together the new urothelial cancer scenario

IntroductionAdvanced urothelial carcinoma remains aggressive and very hard to cure, while new treatments will pose a challenge for clinicians and healthcare funding policymakers alike. The U-CHANGE Project aimed to redesign the current model of care for advanced urothelial carcinoma patients to identify limitations (“as is” scenario) and recommend future actions (“to be” scenario).MethodsTwenty-three subject-matter experts, divided into three groups, analyzed the two scenarios as part of a multidimensional consensus process, developing statements for specific domains of the disease, and a simplified Delphi methodology was used to establish consensus among the experts.ResultsRecommended actions included increasing awareness of the disease, increased training of healthcare professionals, improvement of screening strategies and care pathways, increased support for patients and caregivers and relevant recommendations from molecular tumor boards when comprehensive genomic profiling has to be provided for appropriate patient selection to ad hoc targeted therapies.DiscussionWhile the innovative new targeted agents have the potential to significantly alter the clinical approach to this highly aggressive disease, the U-CHANGE Project experience shows that the use of these new agents will require a radical shift in the entire model of care, implementing sustainable changes which anticipate the benefits of future treatments, capable of targeting the right patient with the right agent at different stages of the disease

Printed Sensors on Non-Conventional Substrates

L'industria 4.0 sta trasformando radicalmente i processi e i sistemi di produzione con l'adozione di tecnologie abilitanti, come l'Internet of Things (IoT), il Big Data, l'Additive Manufacturing (AM) e il Cloud Computing. I principi di queste tecnologie possono anche essere tradotti in qualsiasi aspetto della vita quotidiana grazie all'uso dell'elettronica stampata (PE), offrendo tecniche per produrre sensori e sistemi non convenzionali o per rendere "intelligenti" oggetti convenzionali. Con la PE a giocare un ruolo chiave nella progettazione di oggetti di nuova generazione, gli oggetti intelligenti adempiono alla loro funzione originale, e possono misurare quantità fisiche nell'ambiente circostante, essendo in grado di comunicare con altri oggetti o unità remote. Diverse tecnologie facenti parte della PE potrebbero essere adottate, ma soprattutto l'Aerosol Jet Printing (AJP) con le sue caratteristiche può essere considerata per tale scopo essendo in grado di stampare su qualsiasi tipo di superficie un'enorme varietà di materiali funzionali. In combinazione con il Flash Lamp Annealing (FLA), un processo termico a bassa temperatura, è possibile completare la produzione di sensori e circuiti su qualsiasi tipo di substrato. Lo scopo di questo lavoro di tesi è quello di identificare metodi e processi innovativi che permettano di incorporare direttamente sensori, circuiti ed elettronica sulla superficie degli oggetti e di analizzarne le caratteristiche metrologiche. A tal fine, sono stati effettuati studi di compatibilità considerando diversi materiali, sia in termini di substrati che di inchiostri per la realizzazione di sensori e oggetti intelligenti. Inoltre, è stata analizzata la progettazione, la fabbricazione e il test di sensori e circuiti in diversi campi. Il capitolo 1 fornirà il background e lo schema di questa tesi. Gli oggetti intelligenti possono essere fabbricati con numerose tecnologie e materiali diversi a seconda delle prestazioni richieste e dell'applicazione specifica. Lo scopo del capitolo 2 è di fornire un'analisi delle tecnologie di elettronica stampata 3D che permettono la stampa di sensori su superfici complesse. In primo luogo, viene fornita una spiegazione delle tecnologie in esame. Poi, concentrandosi sulle tecnologie utilizzate, verrà fornita un'analisi approfondita di AJP e FLA nel capitolo 3. Gli esempi svolti sono suddivisi in quattro macro-aree, dispositivi indossabili, packaging su carta, applicazioni di wet laboratory analysis (rilevamento di cellule e biomolecole), per dimostrare l'applicabilità delle metodologie proposte nella realizzazione di sensori e oggetti intelligenti. A partire dal capitolo 4 verranno riportati esempi applicativi. I prototipi testati sono stati coinvolti in diversi contesti lavorativi, dall'industria alimentare alla riabilitazione medica, passando per le analisi di laboratorio, mantenendo un tratto comune: misurare grazie a sensori non convenzionali. Questo fatto sottolinea l'applicabilità delle metodologie proposte a qualsiasi tipo di richiesta, dando la possibilità di trasformare gli oggetti quotidiani in oggetti intelligenti, dimostrando così la flessibilità dei metodi individuati e la pervasività dei sensori e degli oggetti intelligenti così realizzati.Industry 4.0 has radically been transforming the production processes and systems with the adoption of enabling technologies, such as Internet of Things (IoT), Big Data, Additive Manufacturing (AM), and Cloud Computing. The principles of these technologies can be also translated into any aspect of everyday life thanks to the usage of printed electronics (PE), offering techniques to produce unconventional sensors and systems or to make conventional objects “smart”. With PE playing a key role in the design of next-generation objects, smart objects fulfill their original function, and they can measure physical quantities in the surrounding environment, being able to communicate with other objects or remote units. Many PE technologies could be adopted, but above all, Aerosol Jet Printing (AJP) with its characteristics can be considered for such a purpose being able to print on any kind of surface a huge variety of functional materials. In combination with Flash Lamp Annealing (FLA), a low-point temperature thermal process, it is possible to complete the production of sensors and circuits on any kind of substrate. The aim of this thesis work is to identify innovative methods and processes allowing to directly embed sensors, circuits and electronics on the surface of objects and to analyze the metrological characteristics. To this end, compatibility studies have been carried out considering different materials, both in terms of substrates and inks for the realization of smart sensors and objects. Furthermore, design, fabrication and test of sensors and circuits has been analyzed in different fields. Chapter 1 will provide the background and the outline of this dissertation. Smart objects can be manufactured with numerous different technologies and materials depending on the performance required and on the specific application. The purpose of chapter 2 is to provide an analysis of 3D PE technologies that enable sensors printing on complex surfaces. First, an explanation of the technologies under consideration is provided. Then focusing on the used technologies, a deep analysis of AJP and FLA will be provided in chapter 3. Examples carried out are divided into four macro-areas, wearable devices, paper-based packaging, wet laboratories applications (cells and biomolecules sensing), to demonstrate the applicability of the proposed methodologies in the realization of sensors and smart objects. Starting from chapter 4, applicative examples will be reported. The tested prototypes were involved in different working contexts, from food industry to medical rehabilitation, passing through laboratory analysis, keeping a common trait: measuring thanks to unconventional sensors. This fact underlines the applicability of the proposed methodologies to any kind of request, giving the possibility to turn everyday objects into smart ones, thus demonstrating the flexibility of the methods identified and the pervasiveness of sensors and smart objects made this way

Aerosol Jet Printed 3D Electrochemical Sensors for Protein Detection

The use of electrochemical sensors for the analysis of biological samples is nowadays widespread and highly demanded from diagnostic and pharmaceutical research, but the reliability and repeatability still remain debated issues. In the expanding field of printed electronics, Aerosol Jet Printing (AJP) appears promising to bring an improvement in resolution, miniaturization, and flexibility. In this paper, the use of AJP is proposed to design and fabricate customized electrochemical sensors in term of geometry, materials and 3D liquid sample confinement, reducing variability in the functionalization process. After an analysis of geometrical, electrical and surface features, the optimal layout has been selected. An electrochemical test has been then performed quantifying Interleukin-8, selected as reference protein, by means of Anodic Stripping Voltammetry. AJP sensors have been compared with standard screen-printed electrodes in terms of current density and relative standard deviation. Results from AJP sensors with Ag-based Anodic Stripping Voltammetry confirmed nanostructures capability to reduce the limit of detection (from 2.1 to 0.3 ng/mL). Furthermore, AJP appeared to bring an improvement in term of relative standard deviation from 50 to 10%, if compared to screen-printed sensors. This is promising to improve reliability and repeatability of measurement techniques integrable in several biotechnological applications

Preliminary Study on a Strain Sensor Printed on 3D-plastic Surfaces for Smart Devices

Nowadays, the increasing demand to realize plastic objects and devices equipped with sensors and electronics in the field of Internet of Things (IoT) and Industry 4.0 has required new fabrication methods. The best approach is to realize the sensors directly onto the object surface, which is usually 3-dimensional (3D) or non-planar. In this way, sensors and electronics could be perfectly integrated with the objects, avoiding the use of adhesive materials. The printed electronics represents a viable solution for producing smart devices in term of costs, variety of functional materials, throughput and reliability. Among the different printing methods, the aerosol jet printing (AJP) allows producing electronics and sensors directly onto non-planar and 3D surfaces. The photonic sintering cures the deposited metallic films, reducing the process time and avoiding the overheating of substrates characterized by low thermal stability. In this way, combining with photonic sintering, the AJP can be adopted for a wide variety of substrates, like paper, plastic, fabric and tissue. In this work, a first example of strain gauge printed directly on a PVC tube with the AJP and treated with photonic sintering is presented. The silver-based sensor was designed, realized and characterized. The thickness of the silver film (8 μm in average) was measured with a profilometer. The tube was bent in a cantilever configuration up to 0.5%. The relationship between mechanical deformation and electrical resistance is linear, with a gauge factor of 1.04. The decay over time of the resistance change under constant strain is about 0.05%. The proposed method is a promising fabrication solution for smart devices in IoT and Industry 4.0 applications

Aerosol jet printed 3D electrochemical sensors for protein detection

The use of electrochemical sensors for the analysis of biological samples is nowadays widespread and highly demanded from diagnostic and pharmaceutical research, but the reliability and repeatability still remain debated issues. In the expanding field of printed electronics, Aerosol Jet Printing (AJP) appears promising to bring an improvement in resolution, miniaturization, and flexibility. In this paper, the use of AJP is proposed to design and fabricate customized electrochemical sensors in term of geometry, materials and 3D liquid sample confinement, reducing variability in the functionalization process. After an analysis of geometrical, electrical and surface features, the optimal layout has been selected. An electrochemical test has been then performed quantifying Interleukin-8, selected as reference protein, by means of Anodic Stripping Voltammetry. AJP sensors have been compared with standard screen-printed electrodes in terms of current density and relative standard deviation. Results from AJP sensors with Ag-based Anodic Stripping Voltammetry confirmed nanostructures capability to reduce the limit of detection (from 2.1 to 0.3 ng/mL). Furthermore, AJP appeared to bring an improvement in term of relative standard deviation from 50 to 10%, if compared to screen-printed sensors. This is promising to improve reliability and repeatability of measurement techniques integrable in several biotechnological applications

Printed Smart Devices on Cellulose-Based Materials by means of Aerosol-Jet Printing and Photonic Curing

Printed electronics is an expanding research field that can reach the goal of reducing the environmental impact on electronics exploiting renewable and biodegradable materials, like paper. In our work, we designed and tested a new method for fabricating hybrid smart devices on cellulose substrates by aerosol jet printing (AJP) and photonic curing, also known as flash lamp annealing (FLA), capable to cure low temperature materials without any damage. Three different cellulose-based materials (chromatographic paper, photopaper, cardboard) were tested. Multilayer capability and SMDs (surface mount devices) interconnections are possible permitting high flexibility in the fabrication process. Electrical and geometrical tests were performed to analyze the behavior of printed samples. Resulted resistivities are 26.3 × 10−8 Ω⋅m on chromatographic paper, 22.3 × 10−8 Ω⋅m on photopaper and 13.1 × 10−8 Ω⋅m on cardboard. Profilometer and optical microscope evaluations were performed to state deposition quality and penetration of the ink in cellulose materials (thicknesses equal to 24.9, 28.5, and 51 μm respectively for chromatographic paper, photopaper, and cardboard). Furthermore, bending (only chromatographic paper did not reach the break-up) and damp environment tests (no significant variations in resistance) where performed. A final prototype of a complete functioning multilayer smart devices on cellulose 3D-substrate is shown, characterized by multilayers, capacitive sensors, SMDs interconnections

Aerosol Jet Printed and Photonic Cured Paper-based Ammonia Sensor for Food Smart Packaging

In this work, we report the manufacturing and experimental analysis of low-cost and eco-friendly paper-based gas sensors for food smart packaging. The hygroscopic properties of paper help detect the presence of water-soluble gases in an environment provided with relative humidity (RH) above a given threshold (RH >75 %) and discovering the presence of gaseous markers of the food spoilage process, such as ammonia. Carbon interdigitated electrodes were printed by aerosol jet printing (AJP) and sintered by flash lamp annealing on chromatographic paper, obtaining a mean resistance value of ( 231±20 ) kΩ and ( 249±28 ) kΩ for the left and right electrodes, respectively. After being tested at different RH values (75, 80, 90, and 100%), and once stabilized, they were tested with different ammonia concentrations (3, 6, 9, and 12 ppm). A proportional resistance decrease was evidenced in increasing ammonia concentration. Considering the baseline at a constant value of RH =75 %, the sensors showed a resistance variation of 12% in the presence of the lowest concentration of 3 ppm. Three different temperatures were considered during the tests, 5 ∘C , 15 °C, and 25 °C, evidencing no primary influence of this parameter. Ethanol and acetone were investigated as representatives of interfering compounds such as alcohols and ketones that may be developed during food spoilage. Good selectivity was observed both by studying these compounds individually and together with ammonia. Experimental results showed that 48 ppm of acetone induced a resistance change lower than 3 ppm of ammonia, while 240 ppm of ethanol induced a resistance change comparable to 12 ppm of ammonia

Support-Material-Free Microfluidics on an Electrochemical Sensors Platform by Aerosol Jet Printing

Printed electronics have led to new possibilities in the detection and quantification of a wide range of molecules important for medical, biotechnological, and environmental fields. The integration with microfluidics is often adopted to avoid hand-deposition of little volumes of reagents and samples on miniaturized electrodes that strongly depend on operator’s skills. Here we report design, fabrication and test of an easy-to-use electrochemical sensor platform with microfluidics entirely realized with Aerosol Jet Printing (AJP). We printed a six-electrochemical-sensors platform with AJP and we explored the possibility to aerosol jet print directly on it a microfluidic structure without any support material. Thus, the sacrificial material removal and/or the assembly with sensors steps are avoided. The repeatability observed when printing both conductive and ultraviolet (UV)-curable polymer inks can be supported from the values of relative standard deviation of maximum 5% for thickness and 9% for line width. We designed the whole microfluidic platform to make the sample deposition (20 μL) independent from the operator. To validate the platform, we quantified glucose at different concentrations using a standard enzyme-mediated procedure. Both mediator and enzyme were directly aerosol jet printed on working electrodes (WEs), thus the proposed platform is entirely fabricated by AJP and ready to use. The chronoamperometric tests show limit of detection (LOD) = 2.4 mM and sensitivity = 2.2 ± 0.08 µA/mM confirming the effectiveness of mediator and enzyme directly aerosol jet printed to provide sensing in a clinically relevant range (3–10 mM). The average relative standard inter-platform deviation is about 8%. AJP technique can be used for fabricating a ready-to-use microfluidic device that does not need further processing after fabrication, but is promptly available for electrochemical sample analysis

A Review on Biomaterials for 3D Conductive Scaffolds for Stimulating and Monitoring Cellular Activities

During the last years, scientific research in biotechnology has been reporting a considerable boost forward due to many advances marked in different technological areas. Researchers working in the field of regenerative medicine, mechanobiology and pharmacology have been constantly looking for non-invasive methods able to track tissue development, monitor biological processes and check effectiveness in treatments. The possibility to control cell cultures and quantify their products represents indeed one of the most promising and exciting hurdles. In this perspective, the use of conductive materials able to map cell activity in a three-dimensional environment represents the most interesting approach. The greatest potential of this strategy relies on the possibility to correlate measurable changes in electrical parameters with specific cell cycle events, without affecting their maturation process and considering a physiological-like setting. Up to now, several conductive materials has been identified and validated as possible solutions in scaffold development, but still few works have stressed the possibility to use conductive scaffolds for non-invasive electrical cell monitoring. In this picture, the main objective of this review was to define the state-of-the-art concerning conductive biomaterials to provide researchers with practical guidelines for developing specific applications addressing cell growth and differentiation monitoring. Therefore, a comprehensive review of all the available conductive biomaterials (polymers, carbon-based, and metals) was given in terms of their main electric characteristics and range of applications