Test analysis & fault simulation of microfluidic systems

This work presents a design, simulation and test methodology for microfluidic systems, with particular focus on simulation for test. A Microfluidic Fault Simulator (MFS) has been created based around COMSOL which allows a fault-free system model to undergo fault injection and provide test measurements. A post MFS test analysis procedure is also described.A range of fault-free system simulations have been cross-validated to experimental work to gauge the accuracy of the fundamental simulation approach prior to further investigation and development of the simulation and test procedure.A generic mechanism, termed a fault block, has been developed to provide fault injection and a method of describing a low abstraction behavioural fault model within the system. This technique has allowed the creation of a fault library containing a range of different microfluidic fault conditions. Each of the fault models has been cross-validated to experimental conditions or published results to determine their accuracy.Two test methods, namely, impedance spectroscopy and Levich electro-chemical sensors have been investigated as general methods of microfluidic test, each of which has been shown to be sensitive to a multitude of fault. Each method has successfully been implemented within the simulation environment and each cross-validated by first-hand experimentation or published work.A test analysis procedure based around the Neyman-Pearson criterion has been developed to allow a probabilistic metric for each test applied for a given fault condition, providing a quantitive assessment of each test. These metrics are used to analyse the sensitivity of each test method, useful when determining which tests to employ in the final system. Furthermore, these probabilistic metrics may be combined to provide a fault coverage metric for the complete system.The complete MFS method has been applied to two system cases studies; a hydrodynamic “Y” channel and a flow cytometry system for prognosing head and neck cancer.Decision trees are trained based on the test measurement data and fault conditions as a means of classifying the systems fault condition state. The classification rules created by the decision trees may be displayed graphically or as a set of rules which can be loaded into test instrumentation. During the course of this research a high voltage power supply instrument has been developed to aid electro-osmotic experimentation and an impedance spectrometer to provide embedded test

Microsystems Integration Towards Point-of-Care Monitoring of Clozapine Treatment for Adherence, Efficacy, and Safety

Schizophrenia is a challenging and complex disorder with 30–50% of patients not responding to first line antipsychotic treatment. Clozapine is the only antipsychotic approved by the FDA for treatment-resistant schizophrenia and is the most effective antipsychotic medication currently available. Yet, clozapine remains underutilized because of the requirements for frequent invasive and burdensome monitoring to 1) titrate doses to achieve effective blood levels, as well as 2) monitor white blood cells on a weekly basis for the first six months due to risk of agranulocytosis, a rare but potentially fatal side effect of clozapine. These blood draws, and the time lag in receiving reports from central labs, can add several more visits to the caregivers' treatment plan, which may not be feasible for the patient nor the treatment team. This contributes to a very low prescription rate for clozapine, making it one of the most underutilized evidence-based treatments in the field of mental health. The objective of this work is to progress toward a point-of-care approach to monitor both white blood cells and clozapine within a clinical setting. This would significantly lower the burden associated with clozapine treatment by allowing both tests to be performed rapidly during a single doctor's office visit or at the pharmacy. Specifically, I have developed and studied novel clozapine detection schemes based on electrochemical signal amplification in chitosan-based films. Moreover, I have investigated impedance cytometry coupled with hydrodynamic focusing and osmotic lysis to provide label- and reagent-free differential white blood cell counting capabilities. Finally, I have integrated the components in a microsystem capable of concurrent sensing of both biomarkers in whole blood samples. This proof-of-concept device lays the foundation for a fully integrated and automated lab-on-a-chip for point-of-care or even at-home testing to ensure treatment adherence, efficacy, and safety. This will allow for broader use of clozapine by increasing convenience to patients as well as medical professionals, thus improving the lives of people affected by schizophrenia through personalized medicine

Epidermal sensors for monitoring skin physiology

Wearable sensors are revolutionizing personalised healthcare and have continuously progressed over the years in both research and commercialization. However, most efforts on wearable sensors have been focused on tracking movement, spatial position and continuous monitoring of vital signs such as heart rate or respiration rate. Recently, there is a demand to obtain biochemical information from the body using wearables. This demand stems from an individuals’ desire for improved personal health awareness as well as the drive for doctors to continuously obtain medical information for a patients’ disease management. Epidermal sensors are a sub-class of wearable sensors that can intimately integrate with skin and have the potential for monitoring physical changes as well as detecting biomarkers within skin that can be related to human health. The holy grail for these types of sensors is to achieve continuous real-time monitoring of the state of an individual and the development of these sensors are paving the way towards personalised healthcare. However, skin is highly anisotropic which makes it challenging to keep epidermal sensors in consistent contact with skin. It is important that these sensors remain in contact with skin in order to measure its electrical properties and acquire high fidelity signals. The key objective of this thesis is to develop thin conformable, stretchable epidermal sensors for tracking changes in skin physiology. The initial iteration of the screen printed epidermal sensor comprised of a flexible silver film. Impedance spectroscopy was used to understand the electrical signals generated on skin and it was used to measure relative changes due to varying water content. However, this iteration was more suited for single use. The next chapters explore different ink formulations and adherence methodologies to enhance the epidermal sensors adherence to skin. Impedance spectroscopy was used to characterise the electrical signals from these different epidermal sensor iterations, while tensile testing and on-body assessment was used to characterise its mechanical properties. The final chapter focused on investigating the use of phenyl boronic acid (PBA) functionalized hydrogels to modify the epidermal sensor with responsive hydrogel materials to enable chemical sensing of analytes relevant to skin physiology. Impedance spectroscopy was used to characterise and understand the electrical signals generated by the binding interaction of the PBA and analytes using the sensor. Overall, the work demonstrates the challenges of developing these epidermal sensors as well as presenting their potential for continuous monitoring of human skin in the future

Battery-less near field communications (nfc) sensors for internet of things (iot) applications

L’ implementació de la tecnologia de comunicació de camp proper (NFC) en els telèfons intel·ligents no para de créixer degut a l’ús d’aquesta per fer pagaments, això, junt amb el fet de poder aprofitar l’energia generada pel mòbil no només per la comunicació, sinó també per transmetre energia, el baix cost dels xips NFC, i el fet de que els telèfons tinguin connectivitat amb internet, possibilita i fa molt interesant el disseny d’etiquetes sense bateria incorporant-hi sensors i poder enviar la informació al núvol, dins del creixent escenari de l’internet de les coses (IoT). La present Tesi estudia la viabilitat d’aquests sensors, analitzant la màxima distància entre lector i sensor per proveir la potència necessària, presenta tècniques per augmentar el rang d’operació, i analitza els efectes de certs materials quan aquests estan propers a les antenes. Diversos sensors han estat dissenyats i analitzats i son presentats en aquest treball. Aquests son: Una etiqueta que mesura la humitat de la terra, la temperatura i la humitat relativa de l’aire per controlar les condicions de plantes. Un sensor per detectar la humitat en bolquers, imprès en material flexible que s’adapta a la forma del bolquer. Dues aplicacions, una per estimació de pH i una altre per avaluar el grau de maduració de fruites, basats en un sensor de color. I, per últim, s’estudia la viabilitat de sensors en implants per aplicacions mèdiques, analitzant l’efecte del cos i proposant un sistema per augmentar la profunditat a la que aquests es poden llegir utilitzant un telèfon mòbil. Tots aquests sensors poden ser alimentats i llegits per qualsevol dispositiu que disposin de connexió NFC.La implementación de la tecnología de comunicaciones de campo cercano (NFC) en los teléfonos inteligentes no para de crecer debido al uso de esta para llevar a cabo pagos, esto, junto con el hecho de poder aprovechar la energía generada por el móvil no sólo para la comunicación, sino también para transmitir energía, el bajo coste de los chips NFC, i el hecho que los teléfonos tengan conectividad a internet, posibilita y hace muy interesante el diseño de etiquetas sin batería que incorporen sensores i poder enviar la información a la nube, enmarcado en el creciente escenario del internet de las cosas (IoT). La presente Tesis estudia la viabilidad de estos sensores, analizando la máxima distancia entre lector i sensor para proveer la potencia necesaria, presenta técnicas para aumentar el rango de operación, y analiza los efectos de ciertos materiales cuando estos están cerca de las antenas. Varios sensores han sido diseñados y analizados y son presentados en este trabajo. Estos son: Una etiqueta que mide la humedad de la tierra, la temperatura y la humedad relativa del aire para controlar las condiciones de plantas. Un sensor para detectar la humedad en pañales, impreso en material flexible que se adapta a la forma del pañal. Dos aplicaciones, una para estimación de pH y otra para evaluar el grado de maduración de frutas, basados en un sensor de color. Y, por último, se estudia la viabilidad de sensores en implantes para aplicaciones médicas, analizando el efecto del cuerpo y proponiendo un sistema para aumentar la profundidad a la que estos se pueden leer usando un teléfono móvil. Todos estos sensores pueden ser alimentados y leídos por cualquier dispositivo que disponga de conexión NFC.The implementation of near field communication (NFC) technology into smartphones grows rapidly due the use of this technology as a payment system. This, altogether with the fact that the energy generated by the phone can be used not only to communicate but for power transfer as well, the low-cost of the NFC chips, and the fact that the smartphones have connectivity to internet, makes possible and very interesting the design of battery-less sensing tags which information can be sent to the cloud, within the growing internet of things (IoT) scenario. This Thesis studies the feasibility of these sensors, analysing the maximum distance between reader and sensor to provide the necessary power, presents techniques to increase the range of operation, and analyses the effects of certain materials when they are near to the antennas. Several sensors have been designed and analysed and are presented in this work. These are: a tag that measures the soil moisture, the temperature and the relative humidity of the air to control the conditions of plants. A moisture sensor for diapers, printed on flexible material that adapts to the diaper shape. Two applications, one for pH estimation and another for assessing the degree of fruit ripening, based on a colour sensor. And finally, the feasibility of sensors in implants for medical applications is studied, analysing the effect of the body and proposing a system to increase the depth at which they can be read using a mobile phone. All of these sensors can be powered and read by any NFC enabled device