This PhD research relates to the design, fabrication, characterization, and optimization of on-chip electrochemical microelectrode arrays (MEAs) for measurement of transient concentrations and gradients, focusing on fast transients and physiological applications. In particular, this work presents the determination of kinetic mechanisms taking place at an active interface (either physiological or non-physiological) in contact with a liquid phase using the MEA device to simultaneously estimate the concentration and gradient of the analyte of interest at the surface of the active interface. The design approach of the MEA device and the corresponding measurement methodology to acquire reliable concentration information is discussed. The ability of the MEA device to measure fast (i.e., in sub-second time scale) transient gradients is demonstrated experimentally using a controllable diffusion-reaction system which mimics the consumption of hydrogen peroxide by a 2D cell culture. The proposed MEA device and measurement methodology meet effectively most of the requirements for physiological applications and as a demonstration of this, two physiological applications are presented. In one application, the MEA device was tailored to measure the hydrogen peroxide uptake rate of human astrocytes and glioblastoma multiforme cells in 2D cell culture as a function of hydrogen peroxide concentration at the cell surface; the results allowed to quantitatively determine the uptake kinetics mechanisms which are well-described by linear and Michaelis-Menten expressions, in agreement with the literature. In the other application, further customization of the MEA device was realized to study the glucose uptake kinetics of human bronchial epithelial and small cell lung cancer cells, these latter with and without DDX5 gene knockdown; the results allowed to distinguish mechanistic differences in the glucose uptake kinetics among the three cell lines. These results were complemented with measurements of glycolytic and respiration rates to obtain a bigger picture of the glucose metabolism of the three cell lines. Finally, additional applications, both physiological and non-physiological, are proposed for the developed MEA device.

<div>The link between volatile organic compounds (VOCs) from breath and various diseases and specific conditions has been identified since long by the researchers. Canine studies and breath sample analysis on Gas chromatography/ Mass Spectroscopy has proven that there are VOCs in the breath that can detect and potentially predict hypoglycemia. This project aims at developing a smart nanosensor system to detect hypoglycemia from human breath. The sensor system comprises of 1-Mercapto-(triethylene glycol) methyl ether functionalized goldnanoparticle (EGNPs) sensors coated with polyetherimide (PEI) and poly(vinylidene fluoride -hexafluoropropylene) (PVDF-HFP) and polymer composite sensor made from PVDF-HFP-Carbon Black (PVDF-HFP/CB), an interface circuit that performs signal conditioning and amplification, and a microcontroller with Bluetooth Low Energy (BLE) to control the interface circuit and communicate with an external personal digital assistant. The sensors were fabricated and tested with 5 VOCs in dry air and simulated breath (mixture of air, small portion of acetone, ethanol at high humidity) to investigate sensitivity and selectivity. The name of the VOCs is not disclosed herein but these VOCs have been identified in breath and are identified as potential biomarkers for other diseases as well. </div><div> </div><div> The sensor hydrophobicity has been studied using contact angle measurement. The GNPs size was verified using Ultra-Violent-Visible (UV-VIS) Spectroscopy. Field Emission Scanning Electron Microscope (FESEM) image is used to show GNPs embedded in the polymer film. The sensors sensitivity increases by more than 400% in an environment with relative humidity (RH) of 93% and the sensors show selectivity towards VOCs of interest. The interface circuit was designed on Eagle PCB and was fabricated using a two-layer PCB. The fabricated interface circuit was simulated with variable resistance and was verified with experiments. The system is also tested at different power source voltages and it was found that the system performance is optimum at more than 5 volts. The sensor fabrication, testing methods, and results are presented and discussed along with interface circuit design, fabrication, and characterization.</div>

<div>Glutamate is the principal excitatory neurotransmitter in the central nervous system. As one of the most abundant neurotransmitters, glutamate plays an essential role in many processes of the central nervous system and beyond. As a result, any disruption that causes an abnormal glutamate level can significantly impact the central nervous system's neurological functions. Glutamate excitotoxicity is a neuropathology that persists in many neurodegenerative disorders such as Parkinson's and Alzheimer's disease as well as in the traumatic brain and spinal cord injuries. Thus, the ability to obtain precise information about the extracellular glutamate level in the living brain and spinal cord tissue may provide new insights into the fundamental understanding of glutamate in neurological disorders and neurophysiological phenomena.</div><div><br></div><div>Conventional bioanalytical techniques that characterize glutamate levels <i>in vivo</i> have a low spatiotemporal resolution that has impeded our understanding of this dynamic event. The electrochemical sensor has emerged as a promising solution that can satisfy the requirement for highly reliable and continuous monitoring methods with an excellent spatiotemporal resolution for the characterization of extracellular glutamate concentration. In this thesis, I present various amperometric biosensors fabricated using a simple direct ink writing technique for<i> ex vivo </i>and <i>in vivo</i> glutamate monitoring.</div><div><br></div><div>The amperometric biosensor is fabricated by immobilizing glutamate oxidase on nanocomposite electrodes made of platinum nanoparticles, multiwalled carbon nanotubes, and a conductive polymer. The biosensors demonstrate good sensitivity and selectivity that can be inserted into a spinal cord and measure extracellular glutamate concentration. Additionally, another type of glutamate biosensor is fabricated from commercially available activated carbon with platinum microparticles. We utilize astrocyte cell culture to demonstrate our biosensor's ability to monitor the glutamate uptake process. We also present a direct measurement of glutamate release from optogenetic stimulation in mouse primary visual cortex brain slides. </div><div><br></div><div>Moreover, we explore a new type of material, perovskite nickelate-Nafion heterostructure, to fabricate biosensors and measure glutamate inside the mouse brain. Finally, by utilizing the nanocomposite ink and direct ink writing technique, we also fabricate the gold-ruthenium non-enzymatic glucose biosensor. We apply a modified Butler-Volmer non-linear model to evaluate the impact of geometrical and chemical design parameters of non-enzymatic biosensor performance. </div><div><br></div>

<div>The Internet-of-Things (IoT) is one of the fastest-growing technologies in computing, revolutionizing several application domains such as wearable computing, home automation, industrial manufacturing, <i>etc</i>. This rapid proliferation, however, has given rise to a plethora of new security and privacy concerns. For example, IoT devices frequently access sensitive and confidential information (<i>e.g.,</i> physiological signals), which has made them attractive targets for various security attacks. Moreover, with the hardware components in these systems sourced from manufacturers across the globe, instances of counterfeiting and piracy have increased steadily. Security mechanisms such as device authentication and key exchange are attractive options for alleviating these challenges.</div><div><br></div><div>In this dissertation, we address the challenge of enabling low-cost and low-overhead device authentication and key exchange in off-the-shelf embedded systems. The first part of the dissertation focuses on a hardware-intrinsic mechanism and proposes the design of two Physically Unclonable Functions (PUFs), which leverage the memory (DRAM, SRAM) in the system, thus, requiring minimal (or no) additional hardware for operation. Two lightweight authentication and error-correction techniques, which ensure robust operation under wide environmental and temporal variations, are also presented. Experimental results obtained from prototype implementations demonstrate the effectiveness of the design. The second part of the dissertation focuses on the application of these techniques in real-world systems through a new end-to-end authentication and key-exchange protocol in the context of an Implantable Medical Device (IMD) ecosystem. Prototype implementations exhibit an energy-efficient design that guards against security and privacy attacks, thereby making it suitable for resource-constrained devices such as IMDs.</div><div><br></div>

Indiana University-Purdue University Indianapolis (IUPUI) / Understanding the mechanical properties of peripheral nerves is essential for chronically implanted device design. The work in this thesis aimed to understand the relationship between local deformation responses to global strain changes in peripheral nerves. A custom-built mechanical testing rig and sample holder enabled an improved cyclical uniaxial tensile testing environment on rabbit sciatic nerves (N=5). A speckle was placed on the surface of the nerve and recorded with a microscope camera to track local deformations. The development of a semi-automated digital image processing algorithm systematically measured local speckle dimension and nerve diameter changes. Combined with the measured force response, local and global strain values constructed a stress-strain relationship and corresponding elastic modulus. Preliminary exploration of models such as Fung and 2-Term Mooney-Rivlin confirmed the hyperelastic nature of the nerve. The results of strain analysis show that, on average, local strain levels were approximately five times smaller than globally measured strains; however, the relationship was dependent on global strain magnitude. Elastic modulus values corresponding to ~9% global strains were 2.070 ± 1.020 MPa globally and 10.15 ± 4 MPa locally. Elastic modulus values corresponding to ~6% global strains were 0.173 ± 0.091 MPa globally and 1.030 ± 0.532 MPa locally.

No description available.

La presente tesis tiene por finalidad identificar los obstáculos excesivos que limitan la importación de dispositivos médicos en la subpartida nacional 90.18.39.00.10 con descripción comercial “los demás conjuntos para hemodiálisis, transfusiones o similares” en el periodo 2019. Los productos comprendidos en la subpartida mencionada están dirigidos al tratamiento de la insuficiencia renal dentro del sistema de salud peruano. En el primer capítulo, se detalla el marco teórico, términos relevantes, los antecedentes de investigación nacionales e internacionales, así como el sustento legal en el cual está enmarcada la presente investigación. En el segundo capítulo, se detalla el plan de investigación, lo cual abarca la realidad problemática, los objetivos e hipótesis principales y específicos. Asimismo, contiene también la justificación de la investigación teórica, práctica y metodológica. El tercer capítulo, detalla la metodología de trabajo. Es decir, el enfoque aplicado, siendo en esta ocasión del tipo cualitativo explicativo. Adicionalmente, se menciona las limitaciones, la población, la muestra, la recolección de datos y los aspectos éticos. En el cuarto capítulo, se lleva a cabo el desarrollo y análisis de resultados. En ese sentido, se detalla la información obtenida mediante la técnica de entrevista de profundidad, manejando un programa de atlas TI. Para el presente documento, se ha elaborado una muestra de las empresas representativas y se ha entrevistado al responsable de comercio exterior y al personal químico farmacéutico. Finalmente, en el quinto, sexto y séptimo capítulo, se presentan la discusión, consideraciones finales y recomendaciones. / The purpose of this thesis is to identify the excessive obstacles that limit the importation of medical devices in the national subheading 90.18.39.00.10 with a commercial description "the other sets for hemodialysis, transfusions or similar" in the period 2019. The products included in the mentioned subheading are aimed at the treatment of kidney failure within the Peruvian health system. In the first chapter, the theoretical framework, relevant terms, the national and international research background are detailed, as well as the legal basis in which this research is framed. In the second chapter, the research plan is detailed, which includes the problematic reality, the main and specific objectives and hypotheses. Likewise, it also contains the justification of the theoretical, practical and methodological research. The third chapter details the work methodology. That is to say, the applied approach, this time being of the qualitative explanatory type. Additionally, the limitations, the population, the sample, the data collection and the ethical aspects are mentioned. In the fourth chapter, the development and analysis of results is carried out. In this sense, the information obtained through the in-depth interview technique is detailed, using an Atlas TI program. For this document, a sample of representative companies has been prepared and the person in charge of foreign trade and the chemical-pharmaceutical staff have been interviewed. Finally, in the fifth, sixth and seventh chapters, the discussion, final considerations and recommendations are presented. / Tesis

Objective: Cardiovascular diseases are the leading cause of death. The gold standard for their diagnosis and treatment are angiographic procedures. Clinicians rely on dedicated and specialized equipment for these interventions, e.g. angiography systems. The speed of the associated development is important as better technology enables progress in treatment methods and clinical outcomes. The goal of this article is to show how to optimize the innovation and development process such that it takes minimal time. Methods: 672 data sets on 302 topics were collected over 47 months during a long-term observation of the innovation and development process of angiographic systems. The total data collected is equivalent to efforts worth 30 man-years. This input was used to calculate key process parameters, analyse key process roles, evaluate the use of problem-solving methods and identify key technologies. We also developed a process model comprising the primary innovation sources, important input providers and key processes. This model is characterized by a continuous loop for the innovation and development process. Results: The conducted literature research identifies this closed loop process model as being unique in comparison to the well-established models proposed by Brockhoff, Cooper, Crawford, Durfee, Ebert, Eppinger, Hughes, Pleschak, Thom, Ulrich, Vahs and Witt. According to the best knowledge of the authors no comparable data collection has been performed and presented anywhere else yet. When analysing our 672 data sets, we found that the median process time ( in this data pool (n=672) was to be 10 weeks (p<0,05). The median number of task owners (xPA) per task across all topics was 2. Our data revealed that the number of task owners had a direct impact on the process time. For data sets with up to eight task owners the relationship between process time and task owners can be described as tPd=3.6*xPA^1.4. The median time of owning a topic was determined for Sales (7 weeks), Service (11 weeks), Customer Relationship Management (6 weeks), Product Lifecycle Management (10 weeks) and Research & Development (11 weeks). Main input providers were Sales (53%) and customers (28%). Sales (42%) and PLM (37%) are significant connectors. Problem solvers are PLM (35%), CRM (27%) and R&D (27%). The problem-solving methods were analysed and it was found that clarification (77%) as well as dialog and variation method (both 50%) were used most often. We found that changes to the application software (33%), mechanics, device interfaces and user interface (all 21%) are the four out of six components that were involved in most often. In the analysed datasets a potential of an up to 20% shorter process time was identified. Conclusion: This article proposes a new model for the innovation and development process. Based on our data, we recommend to apply a continuous loop process in the context of innovation and development of medical devices. Our results can, for example, be used for Activity Based Costing Approach or be applied to bring new or upgraded angiography systems faster to market benefitting patient outcome due to improved diagnosis and treatment of cardiovascular diseases.

No description available.

<p>The advent and spread of counterfeit goods in medical supply chains is an opportunistic activity by actors who take advantage of information asymmetry between themselves and the rest of the supply chain. Counterfeiters, fraudsters, and companies who intend to cut corners have asymmetric knowledge of the quality (substandard) of the products they possess and are not obligated, but have a disincentive, to share that asymmetric knowledge. This has led to a medical supply chain that is riddled with asymmetric information from consumers, all the way upstream to manufacturers. The asymmetric information present in the supply chain allows agents to take advantage of the demand and chaos in the system to act contrary to the principal’s, in this case the supply chain, best interest as described in the agent-principal theory. The problem related to information asymmetry in principal-agent relationships, including those encapsulated in supply chains, is well documented in prior literature. The missing piece of research deals with quantification of information asymmetry metrics and assessing supply chain of goods.</p> <p>This research explored current and proposed information asymmetry mitigating activities including the potential applications of technology-based methods of reducing information asymmetry within the medical supply chains including distributed ledger technology. Five data aggregation services were searched for relevant literature generating a final sample for analysis of 90 documents (ndocuments = 90). A qualitative meta-analysis methodology was conducted using Nvivo as exploratory research to analyze content in the corpus of documents and extract key themes relevant to each research question then synthesize frequencies of key themes such that information asymmetry in medical supply chains can be decomposed into agents, conditions, and contributing factors.</p>