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Bioimpedance Monitoring System for Pervasive Biomedical Applications

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Bioimpedance Monitoring System for Pervasive Biomedical Applications Bioimpedance monitoring system for pervasive biomedical applications Jaime Punter Villagrasa ADVERTIMENT . La consulta d’aquesta tesi queda condicionada a l’acceptació de les següents condicions d'ús: La difusió d’aquesta tesi per mitjà del servei TDX ( www.tdx.cat ) i a través del Dipòsit Digital de la UB ( diposit.ub.edu ) ha estat autoritzada pels titulars dels drets de propietat intel·lectual únicament per a usos privats emmarcats en ac tivitats d’investigació i docència. No s’autoritza la seva reproducció amb finalitats de lucre ni la seva difusió i posada a disposici ó des d’un lloc aliè al servei TDX ni al Dipòsit Digital de la UB . No s’autoritza la presentació del seu contingut en una finestra o marc aliè a TDX o al Dipòsit Digital de la UB (framing). Aquesta reserva de drets afecta tant al resum de presentació de la tesi com als seus continguts. En la utilització o cita de parts de la tesi és obligat indicar el nom de la persona autora . ADVERTENCIA . La consulta de esta tesis queda condicionada a la aceptación de las siguientes condiciones de uso: La difusión de esta tesis por medio del servicio TDR ( www.tdx.cat ) y a través del Repositorio Digital de la UB ( diposit.ub.edu ) ha sido auto rizada por los titulares de los derechos de propiedad intelectual únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con finalidades de lucro ni su difusión y puesta a disposición desde un si tio ajeno al servicio TDR o al Repositorio Digital de la UB . No se autoriza la presentación de su contenido en una ventana o marco ajeno a TDR o al Repositorio Digital de la UB (framing). Esta reserva de derechos afecta tanto al resumen de presentación de la tesis como a sus contenidos. En la utilización o cita de partes de la tesis es obligado indicar el nombre de la persona autora. WARNING . On having consulted this thesis you’re accepting the following use conditions: Spreading this thesis by the TDX ( www.tdx.cat ) service and by the UB Digital Repository ( diposit.ub.edu ) has been authorized by the titular of the intellectual property rights only for private uses placed in investigation and teaching activities. Reproduction with lucrati ve aims is not aut horized n or its spreading and availability from a site foreign to the TDX service or to the UB Digital Repository . Introducing its content in a window or frame foreign to the TDX service or to the UB Digital Repository is not authorized (framing). Tho s e ri ghts affect to the presentation summary of the thesis as well as to its contents. In the using or citation of parts of the thesis it’s obliged to indicate the name of the author. BIOIMPEDANCE MONITORING SYSTEM FOR PERVASIVE BIOMEDICAL APPLICATIONS. Per Jaime Punter Villagrasa Directors: Pere Lluis Miribel Català i Jordi Colomer Farrarons Tutor: Pere Lluis Miribel Català Memòria per optar al títol de doctor per la Universitat de Barcelona en Enginyeria i Tecnologies Avançades. Departament d’Electrònica, Facultat de Física Universitat de Barcelona, 2015 ii Agradecimientos / Acknowledgements La realización de esta tesis doctoral no habría llegado a buen puerto sin la ayuda de muchas personas e instituciones a las cuales debo agradecer su esfuerzo y su colaboración. Soy una persona de pocas palabras, así que seré escueto. En primer lugar, quiero agradecer al Dr. Pere Lluis Miribel Català toda su dedicación, entusiasmo y motivación, que ha compartido conmigo, para que esta tesis doctoral se haya hecho realidad. Han sido muchos años de trabajo donde nunca me ha faltado su apoyo y su constancia al confiar en mi trabajo, como tampoco ha faltado nunca su apoyo económico para la realización de publicaciones y congresos. También quiero agradecer a mi codirector, Dr. Jordi Colomer Farrarons, el dador de motes y peluches decorativos, cuyo apoyo técnico, sus consejos y su vehemencia a la hora de alentar e impulsar han sido parte fundamental para la elaboración de esta tesis. También quiero mencionar al Dr. Joan Cid Vidal, poro su inmenso apoyo logístico y la oportunidad que me brindó confiando en mi trabajo y compartiendo sus conocimientos. No me quiero tampoco olvidar del Dr. Ginés Escolar Albadalejo y su equipo de trabajo, que me brindaron un espacio de trabajo en su laboratorioy toda la ayuda que pude necesitar. Agradecer al Dr. Josep Samitier Martí y al Institute for Bioengineering of Catalonia su apoyo económico en las primeras fases de esta tesis. También me gustaría agradecer a Beatriz del Moral Zamora por tantos días compartiendo las penas y alegrías que suele brindar este tipo de empresas. Así como su mirada de aprobación, o tal vez de desaprobación, casi maternal para con mis felices devenires investigadores y mi personalidad. Gracias también a Joan Canals y Dr. Oscar Alonso, por el agua barata y de calidad, las cervezas y los cigarros, también baratos y de calidad. Muchísimos agradecimientos para mi familia, a mis padres Laura y Vicente todo el cariño y la buena educación que me han dado, aunque lo más importante para haber llegado hasta aquí ha sido haberme apretado las tuercas cuando ha sido necesario. Mi queridísima hermana Baldesca, la persona que más ha reído y llorado conmigo, compartiendo hasta la parte más infinitesimal de nuestra vida. iii A mis abuelas Celia y Matilde por ser las abuelas cariñosas que todo el mundo necesita, a mi abuelo Bernardino que no ha podido ver este trabajo acabado, y mi abuelo Francisco, el cual me ha reconciliado con la vida. Finalmente quería dedicar un pequeño espacio de agradecimiento a todos mis amigos, aprendices del ejercicio de la vitalidad, compañeros de clase de estética, políticos de barra de bar, y adalides de la música visceral y minoritaria. Y a Merche, por ser lo mejor que me ha pasado. iv Abbreviations PoC Point-of-Care LoC Lab-on-a-Chip ASIC Application Specific Integrated Circuit BioZ Biological Electrical Impedance IA Impedance Analysis IM Impedance Measurement FPGA Field Programmable Gate Array SNR Signal to Noise Ratio THD Total Harmonic Distortion DEP Dielectrophoresis DEPIM Dielectrophoretic Impedance Measurement IDE Interdigitated Electrodes HCT Haematocrit v vi Contents AGRADECIMIENTOS / ACKNOWLEDGEMENTS ................................................. ii ABBREVIATIONS ............................................................................................... iv CONTENTS ........................................................................................................ vi LIST OF FIGURES ................................................................................................ x CHAPTER 1 INTRODUCTION ............................................................................. 1 1.1. APPLICATION OF POC TECHNOLOGIES TO BIOMEDICAL CELLULAR DETECTION AND MONITORING APPLICATIONS: HCT. ....................................................................... 3 1.1.1. Anaemia .................................................................................... 3 1.1.2. Erythrocytosis ............................................................................ 4 1.1.3. Other HCT related diseases. ....................................................... 4 1.2. WHOLE BLOOD MULTIPARAMETRIC POC DEVICES. DIABETES CASE. ................. 7 1.3. IMPEDANCE ANALYSIS FOR CELLULAR DETECTION. ..................................... 10 1.3.1. Biological Electrical Impedance................................................ 11 1.3.2. Instrumentation electronics for 3 electrodes configuration sensing system. Potentiostat. ............................................................................. 12 1.4. BACK-END ELECTRONICS DATA PROCESSING FOR IA. .................................. 19 1.4.1. The Lock-in amplifier analog approach. ................................... 21 1.4.2. The Lock-in Amplifier digital approach. .................................... 25 1.5. CONTRIBUTION OF THIS THESIS. ........................................................... 27 1.6. REFERENCES .................................................................................... 29 CHAPTER 2 DESIGN, TEST AND VALIDATION OF POC DEVICE INSTRUMENTATION. ...................................................................................... 33 2.1. FRONT-END ELECTRONICS DEPENDING ON THE SENSING TOPOLOGY. .............. 33 2.2. BACK-END ELECTRONICS FOR DATA IMPEDANCE SPECTROMETRY POST-PROCESSING AND USER INTERFACE. ...................................................................................... 35 2.3. BACK-END ELECTRONICS TEST. ............................................................. 37 2.4. COMBINED FRONT-END AND BACK-END ELECTRONICS TEST USING PASSIVE COMPONENTS. ............................................................................................... 38 2.5. COMBINED FRONT-END AND BACK-END ELECTRONICS TEST USING A FERROCYANIDE/FERRICYANIDE SOLUTION. ............................................................. 41 2.6. CONCLUSIONS. ................................................................................. 42 2.7. REFERENCES. ................................................................................... 43 CHAPTER 3 A STUDY OF IA FOR CELLULAR DETECTION. HCT DETECTION APPROACH. .................................................................................................... 45 vii 3.1. HCT SCREENING. FOCUS ON ANAEMIA DISEASE AND POC SCREENING DEVICES. 45 3.2. BIOLOGICAL ELECTRICAL IMPEDANCE APPLIED TO HCT, ELECTRODES AND IA. .. 46 3.3. SENSING SYSTEM ..............................................................................
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