Design and construction of a distributed sensor NET for biotelemetric monitoring of brain energetic metabolism using microsensors and biosensors

Neurochemical pathways involved in brain physiology or disease pathogenesis are mostly unknown either in physiological conditions or in neurodegenerative diseases. Nowadays the most frequent usage for biotelemetry is in medicine, in cardiac care units or step-down units in hospitals, even if virtually any physiological signal could be transmitted (FCC, 2000; Leuher, 1983; Zhou et al., 2002). In this chapter we present a wireless device connected with microsensors and biosensors capable to detect real-time variations in concentrations of important compounds present in central nervous system (CNS) and implicated in brain energetic metabolism (Bazzu et al., 2009; Calia et al., 2009)

An Overview of Carbon Fiber Electrodes Used in Neurochemical Monitoring

Neurochemistry has always been a topic that many scientists are interested in researching because the brain is such a fascinating and complex organ. Electrochemical methods have proven to be a successful tool for scientists to use for their brain-researching endeavors. Many types of probes and analytical devices have been invented and used in conjunction with electrochemical methods over the past several decades to investigate the inner workings of the brain. In particular, the carbon fiber electrode has become a popular device among scientists due to its favorable qualities.The carbon fiber electrode has several unique characteristics to give it an advantage over other techniques. Carbon fiber electrodes have the ability to monitor in a subsecond time frame and record in real time. Because they are so small, carbon fiber electrodes are also able to sample very small environments, such as a single cell or vesicular volumes, where other devices cannot because they are too big. Evidence has shown that carbon fiber electrodes appear to cause less disruptive tissue damage when implanted into a brain than other devices, for instance a microdialysis probe. On top of that, carbon fiber electrodes are also excellent devices for those seeking greater sensitivity and selectivity by making electrode modifications tailored for the analyte of interest. In addition, carbon fiber electrodes provide a wider range of detectable species, again by simply making slight modifications. One can clearly see that the future for neurochemical monitoring lies heavily in the hands of the carbon fiber electrode. Its advantages over other devices make it superior in many aspects. Researchers will no doubt continue to use the carbon fiber electrode and keep improving it to make it suitable for countless more experiments

Encapsulation of implantable microsensors

Heart function monitoring by attaching an accelerometer directly to the heart ventricle has been established as an effective way of diagnosing ischemia. The method holds a number of advantages over conventional monitoring techniques: high specificity and accuracy surpassing that of electrocardiography, and the ability to conduct non-stop monitoring unlike x-ray imaging. To this date, the drawback has been that the accelerometer-based devices have been too large to be used in the postoperative period, when the patient’s chest is closed. This period is of great interest.The PhD project has focused on developing a heart monitoring device intended to be used on patients recovering from a Coronary Artery Bypass Graft. The device is intended to be used during surgery and for the subsequent recovery period (3-5 days). The project has employed commercial 3-axis accelerometers.This PhD project has contributed to four different generations of devices, each one featuring incremental improvements. The first generation validated the concept, the second outlined the form factor of the device, and the third added extra functionality and revised the form of the implant. The fourth generation device also featured a newer, more compact sensor, which in turn, allowed to further miniaturize the device and evaluate different implant shapes. This evolutionary approach allowed us to formulate testing methodology for the devices. The latest generation devices underwent tests of: leakage current according to IEC60601 standard (current below 0.01 mA), including after cyclical loading of the capsule-cable joint, pull-out force measurements, implant stability evaluation that yielded tilt of no more than 4 degrees

The Real-Time Measurements of Blood Nitric Oxide (NO) and Hydrogen Peroxide (H2O2) Levels under Acute Hyperglycemia

Vascular endothelial dysfunction is one of the earliest recognizable events under hyperglycemic conditions. It is characterized by decreased endothelium-derived nitric oxide (NO) bioavailability and increased oxidative stress, such as superoxide and hydrogen peroxide (H2O2) overproduction. However, the real-time changes in blood NO and H2O2 levels under acute hyperglycemia have not been evaluated. In this study, acute hyperglycemia (200 mg/dl, 400 mg/dL, and 600 mg/dL) was induced by intravenous infusion of 20%, 30%, and 50% D-glucose respectively for 180 min. Infusion of saline or 30% L-glucose serve as controls. Blood NO or H2O2 levels were measured at real-time by inserting calibrated NO or H2O2 microsensors (100 μm diameter) into each femoral vein, respectively. In the saline group, blood NO levels remained stable and only slightly decreased by 17.61±8.04 nM (n=7) at 180 min compared to baseline. By contrast, hyperglycemia significantly decreased blood NO levels from 100-160 min to the end of the experiment. At 180 min, blood NO levels in 200 mg/dL, 400 mg/dL, and ≥600 mg/dL groups were 71.3±17.9 nM (n=7), 112.15±15.28 nM (n=6), and 105.98±23.45 nM (n=6) lower than that in saline group, respectively (all p2O2 levels, which is not principally due to hyperosmolarity

Control and readout electronics for miniaturized temperature sensors integrated with an organ-on-a-chip

Dissertação de mestrado em Engenharia Eletrónica Industrial e ComputadoresDe acordo com um estudo realizado pelo instituto de biomateriais e engenharia biomédica da Universidade de Toronto nos Estados Unidos da América, 4 em cada 1000 pacientes sofreram de efeitos adversos provocados por fármacos. Este problema surge devido ao facto de o teste de fármacos serem realizados em animais e, posteriormente em humanos. A utilização dos organ-on-a-chip aumentam a eficácia quando se inicia os testes em humanos porque são mais representiativos do que os testes em animais. A tecnologia organ-on-a-chip (OOC) surgiu com o objetivo de ser possível replicar aspetos importantes da fisiologia humana e deste modo poder superar as limitações dos procedimentos tradicionais, aumentando assim a segurança e eficácia de quem os toma. Apesar da tecnologia OOC fornecer uma série de vantagens comparativamente com as técnicas convencionais, esta ainda carece de sistemas para monitorização de multiparâmetros capazes de fornecer informações à microescala durante os testes de cultura de células bem como na testagem de novos fármacos. Neste sentido, torna-se muito importante o desenvolvimento de microssensores integrados em sistemas microfluídicos para monitorizar os diversos parâmetros celulares de modo a perceber que efeitos os fármacos provocam nas células. Parâmetros como temperatura, oxigénio, pH, nível de nutrientes, entre outros, são variáveis de interesse para a perceção global do metabolismo criado pela combinação de fármacos com células de múltiplos órgãos. Assim, o trabalho desenvolvido nesta dissertação tem como objetivo estudar e desenvolver a eletrónica de leitura e atuação de um microssensor de temperatura, baseado em resistance temperature detector (RTD), que será integrado na tecnologia OOC. O sistema desenvolvido para além de fornecer portabilidade e baixo custo, permite realizar leitura de vários microssensores com uma sensibilidade de 15mV/0.1°C. Foi também implementada uma componente gráfica que permite ao utilizador selecionar o sensor e acompanhar os resultados em tempo real.According to a study conducted by the Institute of Biomaterials and Biomedical Engineering at the University of Toronto in the United States of America, 4 out of every 1,000 patients suffered from drug-related adverse effects. This problem arises because the drug test mostly performed on animals and, therefore, does not faithfully question the phenomena that occur at the level of the human being. Thus, the use of these drugs can lead to complications for humans as well as damage to the pharmaceutical industry. Organ-on-a-chip (OOC) technology has emerged with the aim of replicating important aspects of human physiology and thus being able to overcome the limitations of traditional procedures, thereby increasing the safety and efficacy of those who take them. Although OOC technology provides several advantages compared to conventional techniques, it still lacks multiparameter monitoring systems capable of providing microscale information during cell culture testing as well as testing for new drugs. In this sense, it is very important to develop microsensors integrated in microfluidic systems to monitor the various cellular parameters in order to understand what effects the drugs have on cells. Parameters such as temperature, oxygen, pH, number of nutrients, among others, are variables of interest for the overall perception of metabolism created by the combination of drugs with multiple organ cells. Thus, the work developed this dissertation aims to study and develop the electronic reading and actuation of a micro temperature sensor, based on resistance temperature detector (RTD), which will be integrated into OOC technology. The system developed in addition to providing portability and low cost, allows to perform reading of several micro sensors with a sensitivity of 15mV/0.1°C. A graphical component has also been implemented that allows the user to select the sensor and track the results in real time.This work results partially of the project NORTE-01-0145-FEDER-029394, RTChip4Theranostics, supported by Programa Operacional Regional do Norte - Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and by Fundação para a Ciência e Tecnologia (FCT), IP, project reference PTDC/EMD-EMD/29394/2017

Effects of NOX-1 Inhibition on Real-Time Blood Nitric Oxide and Hydrogen Peroxide in Acute Hyperglycemia

Hyperglycemia has been associated with vascular endothelial dysfunction in part by a reduction in nitric oxide (NO) production and increased oxidative stress (e.g., increased superoxide (SO) and hydrogen peroxide (H2O2). Endothelial-derived NO can be significantly reduced by increased SO/H2O2 in part by the activation of NADPH oxidase during hyperglycemia. Of the 7 NADPH oxidase isoforms, NADPH oxidase isoform 1 (NOX1) is mainly expressed in the vasculature and may play a major role in hyperglycemia induced oxidative stress and vascular endothelial dysfunction. This hypothesis was tested by measuring blood NO and H2O2 levels in real time via NO and H2O2 microsensors inserted into femoral veins of rats. Hyperglycemia (e.g., 200 mg/dl) was maintained by an i.v. infusion of 30% glucose solution for 3 hours with or without a selective NOX1 inhibitor, ML171. Hyperglycemia for 3 hours resulted in significantly higher blood H2O2 levels (3.06±0.4 μM, n=9) compared to the saline infused control (P2O2 levels by 1.86±0.61 μM (

Future of smart cardiovascular implants

Cardiovascular disease remains the leading cause of death in Western society. Recent technological advances have opened the opportunity of developing new and innovative smart stent devices that have advanced electrical properties that can improve diagnosis and even treatment of previously intractable conditions, such as central line access failure, atherosclerosis and reporting on vascular grafts for renal dialysis. Here we review the latest advances in the field of cardiovascular medical implants, providing a broad overview of the application of their use in the context of cardiovascular disease rather than an in-depth analysis of the current state of the art. We cover their powering, communication and the challenges faced in their fabrication. We focus specifically on those devices required to maintain vascular access such as ones used to treat arterial disease, a major source of heart attacks and strokes. We look forward to advances in these technologies in the future and their implementation to improve the human condition

Sensing Movement: Microsensors for Body Motion Measurement

Recognition of body posture and motion is an important physiological function that can keep the body in balance. Man-made motion sensors have also been widely applied for a broad array of biomedical applications including diagnosis of balance disorders and evaluation of energy expenditure. This paper reviews the state-of-the-art sensing components utilized for body motion measurement. The anatomy and working principles of a natural body motion sensor, the human vestibular system, are first described. Various man-made inertial sensors are then elaborated based on their distinctive sensing mechanisms. In particular, both the conventional solid-state motion sensors and the emerging non solid-state motion sensors are depicted. With their lower cost and increased intelligence, man-made motion sensors are expected to play an increasingly important role in biomedical systems for basic research as well as clinical diagnostics

High-Resolution Dynamics of Hydrogen Peroxide on the Surface of Scleractinian Corals in Relation to Photosynthesis and Feeding

We developed and used a microsensor to measure fast (<1 s) dynamics of hydrogen peroxide (H2O2) on the polyp tissue of two scleractinian coral species (Stylophora pistillata and Pocillopora damicornis) under manipulations of illumination, photosynthesis, and feeding activity. Our real-time tracking of H2O2 concentrations on the coral tissue revealed rapid changes with peaks of up to 60 mu M. We observed bursts of H2O2 release, lasting seconds to minutes, with rapid increase and decrease of surficial H2O2 levels at rates up to 15 mu M s(-1). We found that the H2O2 levels on the polyp surface are enhanced by oxygenic photosynthesis and feeding, whereas H2O2 bursts occurred randomly, independently from photosynthesis. Feeding resulted in a threefold increase of baseline H2O2 levels and was accompanied by H2O2 bursts, suggesting that the coral host is the source of the bursts. Our study reveals that H2O2 levels at the surface of coral polyps are much higher and more dynamic than previously reported, and that bursts are a regular feature of the H2O2 dynamics in the coral holobiont