Before the Morning After

This paper presents a wearable biopatch prototype for body surface potential measurement. It combines three key technologies, including mixed-signal system on chip (SoC) technology, inkjet printing technology, and anisotropic conductive adhesive (ACA) bonding technology. An integral part of the biopatch is a low-power low-noise SoC. The SoC contains a tunable analog front end, a successive approximation register analog-to-digital converter, and a reconfigurable digital controller. The electrodes, interconnections, and interposer are implemented by inkjet-printing the silver ink precisely on a flexible substrate. The reliability of printed traces is evaluated by static bending tests. ACA is used to attach the SoC to the printed structures and form the flexible hybrid system. The biopatch prototype is light and thin with a physical size of 16 cm x 16 cm. Measurement results show that low-noise concurrent electrocardiogram signals from eight chest points have been successfully recorded using the implemented biopatch.QC 20130805. Updated from accepted to published.</p

Mechanical durability of screen-printed flexible silver traces for wearable devices

There is increased usage of flexible electronics recently in various applications such as wearable devices, flexible displays and sensors. Studies on the durability of conductive metal traces under cyclic mechanical loading is crucial since these conductors will be subjected to repeated bending. In this work, the mechanical and electrical behavior of silver printed conductors was tested using cyclic three-point bend test. The samples were flexible polymer thick film (PTF) silver (Ag) ink printed on a flexible polyethylene terephthalate (PET) substrate. The durability of this PTF Ag ink, which has a hyper-elastic binder and Ag flakes, was studied by performing cyclic bending tests. Four-point resistivity measurements and imaging of the sample both before and after bending were performed. A custom tester machine was used to apply strain to the circuit and measure the resistivity of the silver trace. The results of the bending test show that the silver trace does not undergo significant deformation and the change in resistance is less than 0.6% under both tensile and compressive tests. Fatigue tests were also performed by cyclic bending tests for three trials in which batches of 10,000 cycles were completed. The printed silver wire withstood 30,000 cycles of bend tests and produced only 2.64% change in resistance. This indicates that the printed wires are very durable even after 30,000 cycles of outer bending. Imaging was also conducted on these samples to study the effect of repeated bending on the morphology of the silver conductive trace. Although there was an increase in surface roughness before and after cyclic bending, there was no obvious deformation or delamination observed in the samples

Electrocardiogram Monitoring Wearable Devices and Artificial-Intelligence-Enabled Diagnostic Capabilities: A Review

Worldwide, population aging and unhealthy lifestyles have increased the incidence of high-risk health conditions such as cardiovascular diseases, sleep apnea, and other conditions. Recently, to facilitate early identification and diagnosis, efforts have been made in the research and development of new wearable devices to make them smaller, more comfortable, more accurate, and increasingly compatible with artificial intelligence technologies. These efforts can pave the way to the longer and continuous health monitoring of different biosignals, including the real-time detection of diseases, thus providing more timely and accurate predictions of health events that can drastically improve the healthcare management of patients. Most recent reviews focus on a specific category of disease, the use of artificial intelligence in 12-lead electrocardiograms, or on wearable technology. However, we present recent advances in the use of electrocardiogram signals acquired with wearable devices or from publicly available databases and the analysis of such signals with artificial intelligence methods to detect and predict diseases. As expected, most of the available research focuses on heart diseases, sleep apnea, and other emerging areas, such as mental stress. From a methodological point of view, although traditional statistical methods and machine learning are still widely used, we observe an increasing use of more advanced deep learning methods, specifically architectures that can handle the complexity of biosignal data. These deep learning methods typically include convolutional and recurrent neural networks. Moreover, when proposing new artificial intelligence methods, we observe that the prevalent choice is to use publicly available databases rather than collecting new data

Development of 3-D RF microsystems using additive manufactruing technology

This work intends to explore advanced 3-D integration for state-of-the-art components in wireless systems using various 3-D printing technologies. Several packaging techniques are discussed that utilize the inherent benefits of the 3-D printing techniques. The compatible materials of the 3-D printing system are assessed for their large processing format and compatibility with the build-up process. Single layer and multilayer interconnects, transmission lines are investigated at RF and millimeter-wave (mm-wave) to explore the benefits of each in terms of convenience, reliability, cost, and performance. For the first time，the operation frequency fabricated by 3-D printing is up to D band. A novel vertical via interconnect is applied to the integration of state-of-the-art SoP. Additionally, interconnects that route the signal directly from the chip interface to matching networks are implemented on novel flexible organic material PEN are designed. This work also investigates the possible applications for cavity structures where the benefits of 3-D printing can be exploited for highly integrated receiver systems. Active and passive components are incorporated on LCP using a system-on-package approach to improve performance and enhance capability of the antenna. Wire bond interconnects are utilized as a convenient, low-cost packaging solution, ideal for prototype development.Ph.D

Doctor of Philosophy

dissertationHands are so central to the human experience, yet we often take for granted the capacity to maneuver objects, to form a gesture, or to caress a loved-one’s hand. The effects of hand amputation can be severe, including functional disabilities, chronic phantom pain, and a profound sense of loss which can lead to depression and anxiety. In previous studies, peripheral-nerve interfaces, such as the Utah Slanted Electrode Array (USEA), have shown potential for restoring a sense of touch and prosthesis movement control. This dissertation represents a substantial step forward in the use of the USEAs for clinical careâ€"ultimately providing human amputees with widespread hand sensation that is functionally useful and psychologically meaningful. In completion of this ultimate objective, we report on three major advances. First, we performed the first dual-USEA implantations in human amputees; placing one USEA in the residual median nerve and another USEA in the residual ulnar nerve. Chapter 2 of this dissertation shows that USEAs provided full-hand sensory coverage, and that movement of the implant site to the upper arm in the second subject, proximal to nerve branch-points to extrinsic hand muscles, enabled activation of both proprioceptive sensory percepts and cutaneous percepts. Second, in Chapter 3, we report on successful use of USEA-evoked sensory percepts for functional discrimination tasks. We provide a comprehensive report of functional discrimination among USEA-evoked sensory percepts from three human subjects, including discrimination among multiple proprioceptive or cutaneous sensory percepts with different hand locations, sensory qualities, and/or intensities. Finally, in Chapter 4, we report on the psychological value of multiple degree of freedom prosthesis control, multisensor prosthesis sensation, and closed-loop control. This chapter represents the first report of prosthesis embodiment during closed-loop and open-loop prosthesis control by an amputee, as well as the most sophisticated closed-loop prosthesis control reported in literature to-date, including 5-degree-of-freedom motor control and sensory feedback from 4 hand locations. Ultimately, we expect that USEA-evoked hand sensations may be used as part of a take-home prosthesis system which will provide users with both advanced functional capabilities and a meaningful sense of embodiment and limb restoration

Detección precoz de la cardiopatía isquémica

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

Nanobiosensors: towards real-time human monitoring in aerospace medicine and other extreme conditions

Οι βιοαισθητήρες είναι υποσχόμενα εργαλεία προς την επίτευξη παρακολούθησης της ανθρώπινης υγείας και επίδοσης σε πραγματικό χρόνο και στο σημείο της παρεχόμενης φροντίδας. Η νανοτεχνολογία μπορεί να καταλύσει την διαδικασία της σμίκρυνσης των βιοαισθητήρων ή μπορεί να χρησιμοποιηθεί για την επινόηση εντελώς νέων τύπων αυτών. Η ανάπτυξη των βιοαισθητήρων, σε συνδυασμό με την ωρίμανση της τεχνητής νοημοσύνης και του διαδικτύου των πραγμάτων, μπορεί να εγκαινιάσει μία νέα εποχή για επιτόπου προβλεπτική διαγνωστική, τηλεϊατρική και γενικότερη επαύξηση της επιστημονικής γνώσης. Αυτή η δυναμική είναι άκρως ενδιαφέρουσα για τους κλάδους της ιατρικής που ασχολούνται με την διασφάλιση της ανθρώπινης υγείας, ασφάλειας και επίδοσης σε ακραίες συνθήκες με χαρακτηριστικότερο παράδειγμα τις επανδρωμένες διαστημικές πτήσεις και την ενδεχόμενη πλανητική εποίκιση. Η παρούσα ανασκόπηση επικεντρώνεται σε προσπάθειες βιοανίχνευσης στο διάστημα, αλλά επεκτείνεται και σε περαιτέρω εφαρμογές βιοαισθητήρων στην αεροπορική και την στρατιωτική ιατρική, την αθλητιατρική, καθώς και σε άλλες καταστάσεις με ακραίες περιβαλλοντικές συνθήκες για το ανθρώπινο σώμα. Τέλος, αναφέρονται μερικοί διαφόρου τύπου καινοτόμοι βιοαισθητήρες, με σκοπό να παρασχεθεί μια καλύτερη οπτική για την δυναμική των μελλοντικών συστημάτων βιοαισθητήρων. Αυτή η εργασία έχει ως στόχο να ενθαρρύνει τις επιστημονικές ομάδες που αναπτύσσουν βιοαισθητήρες να συνεργαστούν στενότερα με τους τελικούς χρήστες έτσι, ώστε να επιτευχθεί η απαιτούμενη ποιότητα εκ σχεδιασμού και, δια τούτου, να απελευθερωθεί η πλήρης δυναμική αυτής της επερχόμενης τεχνολογίας.Biosensors are promising tools for achieving point-of-care, real-time, human health, and performance monitoring. Nanotechnology can catalyze the process of biosensors miniaturization or can be used for inventing whole-new types of biosensors. The development of nanobiosensors, along with the maturation of artificial intelligence and Internet-of-Things applications, can inaugurate a new era for in-situ predictive diagnostics, telemedical practice, and general scientific understanding. This potential is of particular interest for medical fields responsible to ensure human health, safety, and performance in extreme environments, with utmost example: manned spaceflight and planets habitation. This review focuses on biosensing approaches in space, but extends further to biosensing applications in aviation, military, and sports, as other situations of extreme environmental conditions for the human body. Lastly, some miscellaneous types of nanobiosensors are mentioned, in order to provide an insight of the potential that future biosensing systems hold. Hopefully, this work will encourage nanobiosensor developers to work closely with the end-users, so that quality-by-design can be achieved, and thus the full potential of this next-generation technology can be harvested

Diagnóstico temprano de la isquemia cardiaca

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

Layer-by-Layer deposition of bioactive polyelectrolytes with incorporation of antimicrobial agents as a new strategy to develop bioactive textiles

Polyelectrolyte multilayer coatings have become a new and general way to functionalize a variety of materials. Particularly, the Layer-by-Layer (LbL) method is a technique developed for the coating of solid surfaces. The LbL technique presents a unique mean to construct surface coatings that can conform to a variety of biomaterial surfaces and serve as matrices enabling controlled delivery of bioactive molecules from surface. As the deposition process is achieved in aqueous medium, incorporation of active agents is possible since the coatings obtained by LbL are less densely packed and this is advantageous for diffusion through the coating. The coating is constructed by the alternate adsorption of oppositely charged polyelectrolytes at the surface of the material, easily obtained when it is dipped in polyelectrolyte solutions. A deposition cycle creates a layer, and these cycles can be repeated as often as needed. This study aims to obtain novel bioactive textiles with potential application as wound-dressings. The biopolymers chosen for the functionalization of cotton (substrate), were chitosan (CH) and alginate (ALG). The multilayer coating of cotton with CH and ALG is constructed by the adsorption of CH and ALG with opposite charge on the surface of cotton substrates. The successive deposition of multilayers of CH and ALG was analyzed by three different techniques. Contact angle between a water droplet and the surface of the sample, cationic dye staining method and analysis by ATR-FTIR (Fourier Transform Infrared spectroscopy with Attenuated Total Reflection). These techniques showed that there was alternating deposition between CH and ALG and the presence of electrostatic bonds between the layers. In order to evaluate the antibacterial activity of the functionalized cotton, the Japanese standard JIS L 1902:2002 for the halo method (qualitative assay), and the absorption method (quantitative test) were assessed. These tests revealed an antibacterial effect on the functionalized cotton for both Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Klebsiella pneumoniae). In addition a method was optimized for incorporating L-cysteine (L-cys) between the layers of CH and ALG deposited on cotton samples by the LbL, in order to obtain a better antimicrobial effect. Several strategies were used and the best results were obtained by the method where the ALG turns into a gel in the presence of calcium, since L-cys can be incorporated directly between the layers of CH and ALG without any covalent bond. Thus, the bioactive L-cys agent was immobilized without losing its bioactive characteristics. These new samples were analyzed for the antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae according with the previously used standard, and the results showed an increase in the antibacterial effect due to the presence of L-cys. This new coating method has the great advantage to able to select other types of bioactive agents without needing further optimization. In this way, L-Cys was replaced by antimicrobial peptides (AMPs). The reason for the use of AMPs is related with the continuous use of antibiotics which resulted in multiresistant bacterial strains all over the world. Consequently, there is an urgent need to search for alternatives for antibiotics. The AMPs are the new generation of antimicrobials. Four AMPs of different features were used. The depth in which each AMPs is incorporated between the layers was determined by energy dispersive analysis of X-rays (Energy Dispersive X-ray EDS). Results showed, that all AMPs used have a higher antimicrobial effect when compared with previous samples (with and without L-Cys) for both microorganisms and are non-cytotoxic to normal human dermal fibroblasts at the tested Concentrations. This confirms that this new functionalization approach of cotton coated with layers of CH and ALG by the LbL technique with incorporated AMPs leads to good antibacterial and cytotoxicity results, which make them suitable to be used as wound dressings.Nos últimos anos, o uso de têxteis com capacidade antimicrobiana tem vindo a aumentar significativamente. Compostos sintéticos antimicrobianos utilizados em artigos têxteis são muito eficazes face a uma grande gama de microrganismos. Mas o uso de têxteis antimicrobianos de forma contínua pode levar à resistência bacteriana e sensibilização dos utilizadores, bem como causar problemas ao meio ambiente. Para minimizar estes riscos existe atualmente uma grande procura de têxteis antimicrobianos produzidos com compostos naturais não tóxicos e amigos do ambiente. A baixa incidência de efeitos adversos com origem em compostos naturais relativamente aos compostos sintéticos pode ser explorada como uma alternativa atraente e promissora para aplicações têxteis. O método de funcionalização por camada sobre camada (Layer-by-Layer, LbL) pode fornecer novos tipos de revestimentos em materiais têxteis. Esta técnica LbL tem ganho uma grande aceitação na investigação académica e a nível industrial. Foi proposta por Decher e seus colaboradores no início dos anos 90 e desde então o seu impacto positivo pode ser comprovado através do crescente número de trabalhos publicados. Revestimentos por multicamadas de polieletrólitos naturais bioativos tornam-se num processo novo de funcionalização de superfícies. Esta técnica é desenvolvida em meio aquoso e envolve tipicamente a adsorção alternada de polieletrólitos de cargas opostas. A possibilidade de fabricar tais camadas, graças às interações eletrostáticas, permite a funcionalização de superfícies de praticamente qualquer tamanho e forma. Este conceito não é novo para algumas aplicações como seja a libertação de fármacos, mas é relativamente novo para aplicações têxteis. Na revisão da literatura foram encontrados alguns, mas poucos, trabalhos de investigação relativamente à aplicação do LbL em substratos têxteis naturais, como seja o caso do algodão. O uso de polímeros naturais para obter estas camadas pode auxiliar na resolução de problemas que ocorrem com os polímeros sintéticos. Relativamente aos polímeros naturais mais utilizados encontram-se o quitosano (CH) e o alginato (ALG) que são polissacarídeos bastante conhecidos por serem biocompatíveis, biodegradáveis, antimicrobianos e não tóxicos. Neste trabalho apresentam-se os resultados sobre a viabilidade e sucesso da deposição de camadas de polieletrólitos de CH e de ALG pela técnica do LbL em fibras de algodão. O revestimento do algodão por multicamadas de CH e ALG é construído através da adsorção de CH de carga positiva e oposta à carga da superfície do algodão, seguida pela adsorção de ALG de carga negativa, ou seja oposta á carga do CH. O substrato de algodão utilizado para a deposição das várias camadas foi pré-tratado antes da deposição dos polieletrólitos, de forma a ativar a sua superfície deixando-a com cargas negativas. A deposição sucessiva das multicamadas de polieletrolitos foi analisada por 3 técnicas diferentes. Cálculo do ângulo de contacto entre uma gota de água e a superfície da amostra, coloração com um corante catiónico e análise por ATR-FTIR (Fourier Transform Infrared Spectroscopy with Attenuated Total Reflection). Estas técnicas indicaram que houve uma deposição alternada entre o CH e o ALG e também a presença de ligações eletrostáticas entre as camadas. Ficou assim demonstrado o sucesso na deposição de CH e ALG pela técnica do LbL em substrato têxtil de origem natural, neste caso o algodão. Com o fim de avaliar a atividade antibacteriana das amostras de algodão funcionalizadas, seguiu-se a norma Japonesa JIS L 1902:2002 para o método do halo (teste qualitativo) e método de absorção (teste quantitativo). Estes testes revelaram um efeito antibacteriano das amostras funcionalizadas, tanto para bactérias Gram-positivas (Staphylococcus aureus) como Gramnegativas (Klebsiella pneumoniae). Com estes resultados verificou-se que era possível preparar estruturas com propriedades específicas. Este método permite assim a possibilidade de desenvolver novos produtos têxteis funcionais para aplicações biomédicas, podendo também com este método do LbL obter amostras que tenham um papel no desenvolvimento de um sistema de libertação de fármacos no local pretendido. As amostras anteriores foram ainda analisadas por microscopia eletrónica de varrimento (Scanning Electron Microscopy, SEM). Esta análise teve como objetivo visualizar o grau do dano sofrido na estrutura das bactérias testadas por ação do CH e ALG. A fase seguinte consistiu em otimizar um método para incorporação de L-cisteína (L-cys), que é um agente antimicrobiano, entre as camadas de CH e ALG depositadas em amostras de algodão pelo método do LbL. Entre os diversos métodos utilizados para incorporar a L-cys, o que melhores resultados produziu foi aquele onde se fez uso da propriedade do ALG em formar gel na presença de cálcio. Verificamos que a L-cys pode ser incorporada diretamente entre as camadas de CH e ALG sem que ocorra qualquer ligação covalente entre a L-cys e os polieletrólitos de CH e ALG. Desta forma o agente bioativo (L-cys) ficou imobilizado sem perder as suas características bioativas e tem como grande vantagem a possibilidade de podermos selecionar outros tipos de agentes bioativos sem a necessidade de nova otimização do método de incorporação. Nestas novas amostras foram analisadas as propriedades antibacterianas para o Staphylococcus aureus e para Klebsiella pneumoniae segundo a norma já referida anteriormente, e os resultados mostraram um aumento no efeito antibacteriano devido à presença da L-cys. Por último, a L-cys foi substituída por péptidos antimicrobianos (antimicrobial peptides, AMPs), já que são a nova geração de antimicrobianos. Foram utilizados 4 AMPs de características diferentes. A profundidade em que cada AMPs se encontra incorporado entre as camadas foi determinada por análise de energia dispersiva de raios X (Energy Dispersive X ray, EDS). Para estas últimas amostras foram feitos os testes antibacterianos e analisada a citotoxicidade para o valor das concentrações usadas. Foram também analisadas as curvas de libertação para o exterior dos AMPs incorporados no algodão funcionalizado. Com os resultados obtidos confirma-se que esta nova funcionalização de algodão revestido com camadas de CH e ALG pela técnica do LbL e com incorporação de AMPs, conduz a bons resultados antimicrobianos e de citotoxicidade, podendo assim estas amostras ser utilizadas na área da saúde, especificamente como compressas

HICPAC Meeting Minutes

Publication date from document properties.2016-March-HICPAC-meeting.pdf2016895