9 research outputs found

    High-Density Neurochemical Microelectrode Array to Monitor Neurotransmitter Secretion

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    Neuronal exocytosis facilitates the propagation of information through the nervous system pertaining to bodily function, memory, and emotions. Using amperometry, an electrochemical technique that directly detects electroactive molecules, the sub-millisecond dynamics of exocytosis are revealed and the modulation of neurotransmitter secretion due to neurodegenerative diseases or pharmacological treatments can be studied. The method of detection using amperometry is the exchange of electrons due to a redox reaction at an electrochemically sensitive electrode. As electroactive molecules, such as dopamine, undergo oxidation, electrons are released from the molecule to the electrode and an oxidation current is generated and recorded. Despite the significance of traditional single-cell amperometry, it is a costly, labor-intensive, and low-throughput, procedure. The focus of this dissertation is the development of a monolithic CMOS-based neurochemical sensing system that can provide a high-throughput of up to 1024 single-cell recordings in a single experiment, significantly reducing the number of experiments required for studying the effects of neurodegenerative diseases or new pharmacological treatments on the exocytosis process. The neurochemical detection system detailed in this dissertation is based on a CMOS amplifier array that contains 1024 independent electrode-amplifier units, each of which contains a transimpedance amplifier with comparable noise performance to a high-quality electrophysiology amplifier that is used for traditional single-cell amperometry. Using this novel technology, single exocytosis events are monitored simultaneously from numerous single-cells in experiments to reveal the secretion characteristics from groups of cells before and after pharmacological treatments which target the modulation of neurotransmitters in the brain, such as drugs for depression or Parkinson\u27s disease

    Development of a Dual-Mode CMOS Microelectrode Array for the Simultaneous Study of Electrochemical and Electrophysiological Activities of the Brain

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    Medical diagnostic devices are in high demand due to increasing cases of neurodegenerative diseases in the aging population and pandemic outbreaks in our increasingly connected global community. Devices capable of detecting the presence of a disease in its early stages can have dramatic impacts on how it can be treated or eliminated. High cost and limited accessibility to diagnostic tools are the main barriers preventing potential patients from receiving a timely disease diagnosis. This dissertation presents several devices that are aimed at providing higher quality medical diagnostics at a low cost. Brain function is commonly studied with systems detecting the action potentials that are formed when neurons fire. CMOS technology enables extremely high-density electrode arrays to be produced with integrated amplifiers for high-throughput action potential measurement systems while greatly reducing the cost per measurement compared to traditional tools. Recently, CMOS technology has also been used to develop high-throughput electrochemical measurement systems. While action potentials are important, communication between neurons occurs by the flow of neurotransmitters at the synapses, so measurement of action potentials alone is incapable of fully studying neurotransmission. In many neurodegenerative diseases the breakdown in neurotransmission begins well before the disease manifests itself. The development of a dual-mode CMOS device that is capable of simultaneous high-throughput measurement of both action potentials and neurotransmitter flow via an on-chip electrode array is presented in this dissertation. This dual-mode technology is useful to those studying the dynamic decay of the neurotransmission process seen in many neurodegenerative diseases using a low-cost CMOS chip. This dissertation also discusses the development of more traditional diagnostic devices relying on PCR, a method commonly used only in centralized laboratories and not readily available at the point-of-care. These technologies will enable faster, cheaper, more accurate, and more accessible diagnostics to be performed closer to the patient

    Development of an autonomous lab-on-a-chip system with ion separation and conductivity detection for river water quality monitoring

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    This thesis discusses the development of a lab on a chip (LOC) ion separation for river water quality monitoring using a capacitively coupled conductivity detector (C⁴D) with a novel baseline suppression technique.Our first interest was to be able to integrate such a detector in a LOC. Different designs (On-capillary design and on-chip design) have been evaluated for their feasibility and their performances. The most suitable design integrated the electrode close to the channel for an enhanced coupling while having the measurement electronics as close as possible to reduce noise. The final chip design used copper tracks from a printed circuit board (PCB) as electrodes, covered by a thin Polydimethylsiloxane (PDMS) layer to act as electrical insulation. The layer containing the channel was made using casting and bonded to the PCB using oxygen plasma. Flow experiments have been conduced to test this design as a detection cell for capacitively coupled contactless conductivity detection (C⁴D).The baseline signal from the system was reduced using a novel baseline suppression technique. Decrease in the background signal increased the dynamic range of the concentration to be measured before saturation occurs. The sensitivity of the detection system was also improved when using the baseline suppression technique. Use of high excitation voltages has proven to increase the sensitivity leading to an estimated limit of detection of 0.0715 μM for NaCl (0.0041 mg/L).The project also required the production of an autonomous system capable of operating for an extensive period of time without human intervention. Designing such a system involved the investigation of faults which can occur in autonomous system for the in-situ monitoring of water quality. Identification of possible faults (Bubble, pump failure, etc.) and detection methods have been investigated. In-depth details are given on the software and hardware architecture constituting this autonomous system and its controlling software

    Biosensors

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    A biosensor is defined as a detecting device that combines a transducer with a biologically sensitive and selective component. When a specific target molecule interacts with the biological component, a signal is produced, at transducer level, proportional to the concentration of the substance. Therefore biosensors can measure compounds present in the environment, chemical processes, food and human body at low cost if compared with traditional analytical techniques. This book covers a wide range of aspects and issues related to biosensor technology, bringing together researchers from 11 different countries. The book consists of 16 chapters written by 53 authors. The first four chapters describe several aspects of nanotechnology applied to biosensors. The subsequent section, including three chapters, is devoted to biosensor applications in the fields of drug discovery, diagnostics and bacteria detection. The principles behind optical biosensors and some of their application are discussed in chapters from 8 to 11. The last five chapters treat of microelectronics, interfacing circuits, signal transmission, biotelemetry and algorithms applied to biosensing

    Development of biomedical devices for the extracorporeal real-time monitoring and perfusion of transplant organs

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    The goal of this Thesis is to develop a range of technologies that could enable a paradigm shift in organ preservation for renal transplantation, transitioning from static cold storage to warm normothermic blood perfusion. This transition could enable the development of novel pre-implantation therapies, and even serve as the foundation for a global donor pool. A low-hæmolysis pump was developed, based on a design first proposed by Nikola Tesla in 1913. Simulations demonstrated the theoretical superiority of this design over existing centrifugal pumps for blood recirculation, and provided insights for future avenues of research into this technology. A miniature, battery-powered, multimodal sensor suite for the in-line monitoring of a blood perfusion circuit was designed and implemented. This was named the ‘SmartPipe’, and proved capable of simultaneously monitoring temperature, pressure and blood oxygen saturations over the biologically-relevant ranges of each modality. Finally, the Thesis details the successful implementation and optimisation of a combined microfluidic and microdialysis system for the real-time quantitation of creatinine in blood or urine through amperometric sensing, to act as a live renal function monitor. The range of detection was 4.3μM – 500μM, with the possibility of extending this in both directions. This work also details and explores a novel methodology for functional monitoring in closed-loop systems which avoids the need for sensor calibration, and potentially overcomes the problems of sensor drift and desensitisation.Open Acces

    Smart Embedded Systems for Biomedical Applications

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    L'abstract è presente nell'allegato / the abstract is in the attachmen
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