A Novel Mobile Device for Environmental Hydrocarbon Sensing and Its Applications

abstract: The accurate and fast determination of organic air pollutants for many applications and studies is critical. Exposure to volatile organic compounds (VOCs) has become an important public health concern, which may induce a lot of health effects such as respiratory irritation, headaches and dizziness. In order to monitor the personal VOCs exposure level at point-of-care, a wearable real time monitor for VOCs detection is necessary. For it to be useful in real world application, it requires low cost, small size and weight, low power consumption, high sensitivity and selectivity. To meet these requirements, a novel mobile device for personal VOCs exposure monitor has been developed. The key sensing element is a disposable molecularly imprinted polymer based quartz tuning fork resonator. The sensor and fabrication protocol are low cost, reproducible and stable. Characterization on the sensing material and device has been done. Comparisons with gold standards in the field such as GC-MS have been conducted. And the device’s functionality and capability have been validated in field tests, proving that it’s a great tool for VOCs monitoring under different scenarios.Dissertation/ThesisDoctoral Dissertation Chemical Engineering 201

Design, characterization and validation of integrated bioelectronics for cellular studies: from inkjet-printed sensors to organic actuators

Mención Internacional en el título de doctorAdvances in bioinspired and biomimetic electronics have enabled coupling engineering devices to biological systems with unprecedented integration levels. Major efforts, however, have been devoted to interface malleable electronic devices externally to the organs and tissues. A promising alternative is embedding electronics into living tissues/organs or, turning the concept inside out, lading electronic devices with soft living matters which may accomplish remote monitoring and control of tissue’s functions from within. This endeavor may unleash the ability to engineer “living electronics” for regenerative medicine and biomedical applications. In this context, it remains a challenge to insert electronic devices efficiently with living cells in a way that there are minimal adverse reactions in the biological host while the electronics maintaining the engineered functionalities. In addition, investigating in real-time and with minimal invasion the long-term responses of biological systems that are brought in contact with such bioelectronic devices is desirable. In this work we introduce the development (design, fabrication and characterization) and validation of sensors and actuators mechanically soft and compliant to cells able to properly operate embedded into a cell culture environment, specifically of a cell line of human epithelial keratinocytes. For the development of the sensors we propose moving from conventional microtechnology approaches to techniques compatible with bioprinting in a way to support the eventual fabrication of tissues and electronic sensors in a single hybrid plataform simultaneously. For the actuators we explore the use of electroactive, organic, printing-compatible polymers to induce cellular responses as a drug-free alternative to the classic chemical route in a way to gain eventual control of biological behaviors electronically. In particular, the presented work introduces inkjet-printed interdigitated electrodes to monitor label-freely and non-invasively cellular migration, proliferation and cell-sensor adhesions of epidermal cells (HaCaT cells) using impedance spectroscopy and the effects of (dynamic) mechanical stimulation on proliferation, migration and morphology of keratinocytes by varying the magnitude, frequency and duration of mechanical stimuli exploiting the developed biocompatible actuator. The results of this thesis contribute to the envision of three-dimensional laboratory-growth tissues with built-in electronics, paving exciting avenues towards the idea of living smart cyborg-skin substitutes.En los útimos años los avances en el desarrollo de dispositivos electrónicos diseñados imitando las propiedades de sistemas vivos han logrado acoplar sistemas electrónicos y órganos/tejidos biológicos con un nivel de integración sin precedentes. Convencionalmente, la forma en que estos sistemas bioelectrónicos son integrados con órganos o tejidos ha sido a través del contacto superficial entre ambos sistemas, es decir acoplando la electrónica externamente al tejido. Lamentablemente estas aproximaciones no contemplan escenarios donde ha habido una pérdida o daño del tejido con el cual interactuar, como es el caso de daños en la piel debido a quemaduras, úlceras u otras lesiones genéticas o producidas. Una alternativa prometedora para ingeniería de tejidos y medicina regenerativa, y en particular para implantes de piel, es embeber la electrónica dentro del tejido, o presentado de otra manera, cargar el sistema electrónico con células vivas y tejidos fabricados por ingeniería de tejidos como parte innata del propio dispositivo. Este concepto permitiría no solo una monitorización remota y un control basado en señalizaciones eléctricas (sin químicos) de tejidos biológicos fabricados mediante técnicas de bioingeniería desde dentro del propio tejido, sino también la fabricación de una “electrónica viva”, biológica y eléctricamente funcional. En este contexto, es un desafío insertar de manera eficiente dispositivos electrónicos con células vivas sin desencadenar reacciones adversas en el sistema biológico receptor ni en el sistema electrónico diseñado. Además, es deseable monitorizar en tiempo real y de manera mínimamente invasiva las respuestas de dichos sistemas biológicos que se han añadido a tales dispositivos bioelectrónicos. En este trabajo presentamos el desarrollo (diseño, fabricación y caracterización) y validación de sensores y actuadores mecánicamente suaves y compatibles con células capaces de funcionar correctamente dentro de un entorno de cultivo celular, específicamente de una línea celular de células epiteliales humanas. Para el desarrollo de los sensores hemos propuesto utilizar técnicas compatibles con la bioimpresión, alejándonos de la micro fabricación tradicionalmente usada para la manufactura de sensores electrónicos, con el objetivo a largo plazo de promover la fabricación de los tejidos y los sensores electrónicos simultáneamente en un mismo sistema de impresión híbrido. Para el desarrollo de los actuadores hemos explorado el uso de polímeros electroactivos y compatibles con impresión y hemos investigado el efecto de estímulos mecánicos dinámicos en respuestas celulares con el objetivo a largo plazo de autoinducir comportamientos biológicos controlados de forma electrónica. En concreto, este trabajo presenta sensores basados en electrodos interdigitados impresos por inyección de tinta para monitorear la migración celular, proliferación y adhesiones célula-sustrato de una línea celular de células epiteliales humanas (HaCaT) en tiempo real y de manera no invasiva mediante espectroscopía de impedancia. Por otro lado, este trabajo presenta actuadores biocompatibles basados en el polímero piezoeléctrico fluoruro de poli vinilideno y ha investigado los efectos de estimular mecánicamente células epiteliales en relación con la proliferación, migración y morfología celular mediante variaciones dinámicas de la magnitud, frecuencia y duración de estímulos mecánicos explotando el actuador biocompatible propuesto. Ambos sistemas presentados como resultado de esta tesis doctoral contribuyen al desarrollo de tejidos 3D con electrónica incorporada, promoviendo una investigación hacia la fabricación de sustitutos equivalentes de piel mitad orgánica mitad electrónica como tejidos funcionales biónicos inteligentes.The main works presented in this thesis have been conducted in the facilities of the Universidad Carlos III de Madrid with support from the program Formación del Profesorado Universitario FPU015/06208 granted by Spanish Ministry of Education, Culture and Sports. Some of the work has been also developed in the facilities of the Fraunhofer-Institut für Zuverlässigkeit und Mikrointegration (IZM) and University of Applied Sciences (HTW) in Berlin, under the supervision of Prof. Dr. Ing. H-D. Ngo during a research visit funded by the Mobility Fellows Program by the Spanish Ministry of Education, Culture, and Sports. This work has been developed in the framework of the projects BIOPIELTEC-CM (P2018/BAA-4480), funded by Comunidad de Madrid, and PARAQUA (TEC2017-86271-R) funded by Ministerio de Ciencia e Innovación.Programa de Doctorado en Ingeniería Eléctrica, Electrónica y Automática por la Universidad Carlos III de MadridPresidente: José Antonio García Souto.- Secretario: Carlos Elvira Pujalte.- Vocal: María Dimak

Wearable chemo/bio-sensors for sweat sensing in sports applications: combining micro-fluidics and novel materials

In the last decade, we have witnessed an exponential growth in the area of clinical diagnostic but surprisingly little has been done on the development of wearable chemo/bio-sensors in the field of sports science. In particular, the use of wearable wireless sensors capable of analysing sweat during physical exercise can provide access to new information sources that can be used to optimise and manage athletes’ performance. Lab-on-a-Chip technology provides a fascinating opportunity for the development of such wearable sensors. In this thesis two different colorimetric wearable microfluidic devices for real- time pH sensing were developed and used during athlete training activity. In one case a textile-based microfluidic platform employing cotton capillarity to drive sweat toward the pH sensitive area is presented that avoids the use of bulky fluid handling apparatus, i.e. pumps. The second case presents a wearable micro-fluidic device based on the use of pH responsive ionogels to obtain real-time sweat pH measurements through photo analysis of their colour variation. The thesis also presents the first example of sweat lactate sensing using an organic electrochemical transistor incorporating an ionogel as solid-state electrolyte. In this chapter, optimization of the lactate oxidase stability when dissolved in number of hydrated ionic liquids is investigated. Finally, a new fabrication protocol for paper-based microfluidic technology is presented, which may have important implications for future applications such as low-cost diagnostics and chemical sensing technologies

Development of a Plasmonic On-Chip System to Characterize Changes from External Perturbations in Cardiomyocytes

Today’s heart-on-a-chip devices are hoped to be the state-of-the-art cell and tissue characterizing tool, in clinically applicable regenerative medicine and cardiac tissue engineering. Due to the coupled electromechanical activity of cardiomyocytes (CM), a comprehensive heart-on-a-chip device as a cell characterizing tool must encompass the capability to quantify cellular contractility, conductivity, excitability, and rhythmicity. This dissertation focuses on developing a successful and statistically relevant surface plasmon resonance (SPR) biosensor for simultaneous recording of neonatal rat cardiomyocytes’ electrophysiological profile and mechanical motion under normal and perturbed conditions. The surface plasmon resonance technique can quantify (1) molecular binding onto a metal film, (2) bulk refractive index changes of the medium near (nm) the metal film, and (3) dielectric property changes of the metal film. We used thin gold metal films (also called chips) as our plasmonic sensor and obtained a periodic signal from spontaneously contracting CMs on the chip. Furthermore, we took advantage of a microfluidic module for controlled drug delivery to CMs on-chip, inhibiting and promoting their signaling pathways under dynamic flow. We identified that ionic channel activity of each contraction period of a live CM syncytium on a gold metal sensor would account for the non-specific ion adsorption onto the metal surface in a periodic manner. Moreover, the contraction of cardiomyocytes following their ion channel activity displaces the medium, changing its bulk refractive index near the metal surface. Hence, the real-time electromechanical activity of CMs using SPR sensors may be extracted as a time series we call the Plasmonic Cardio-Eukaryography Signal (P-CeG). The P-CeG signal render opportunities, where state-of-the-art heart-on-a-chip device complexities may subside to a simpler, faster and cheaper platform for label-free, non-invasive, and high throughput cellular characterization

Study of thermochromic nature of VO2 for reconfigurable frequency selection applications

The goal of this project is to investigate the use of vanadium dioxide in reconfigurable microwave devices such as antennas or filters. The second phase would see the creation of a more concrete application. The ability of vanadium dioxide (VO2) to change its structure above a certain temperature is of particular interest. Under 68°C, VO2 behaves like a dielectric, but when it reaches and exceeds that temperature, it behaves like a metal. With this in mind, we wanted to demonstrate the possibility of creating a reconfigurable FSS for spatial filtering by selectively heating the VO2 sample's surface area. A laser was used to select which area of the sample to heat: by shaping the beam, we were able to illuminate, and thus heat, only specific areas. This dissertation also describes the use of the time-resolved microwave conductivity (TRMC) technique to characterise vanadium dioxide to design these FSS images projected on the VO2 surface. We show that TRMC is a versatile technique for determining the electromagnetic material properties and conductivity of VO2 compounds. This was used to compare the behaviour of several VO2 samples of varying thicknesses and fabrication technologies.James Watt Scholarshi

Bio-Inspired Soft Artificial Muscles for Robotic and Healthcare Applications

Soft robotics and soft artificial muscles have emerged as prolific research areas and have gained substantial traction over the last two decades. There is a large paradigm shift of research interests in soft artificial muscles for robotic and medical applications due to their soft, flexible and compliant characteristics compared to rigid actuators. Soft artificial muscles provide safe human-machine interaction, thus promoting their implementation in medical fields such as wearable assistive devices, haptic devices, soft surgical instruments and cardiac compression devices. Depending on the structure and material composition, soft artificial muscles can be controlled with various excitation sources, including electricity, magnetic fields, temperature and pressure. Pressure-driven artificial muscles are among the most popular soft actuators due to their fast response, high exertion force and energy efficiency. Although significant progress has been made, challenges remain for a new type of artificial muscle that is easy to manufacture, flexible, multifunctional and has a high length-to-diameter ratio. Inspired by human muscles, this thesis proposes a soft, scalable, flexible, multifunctional, responsive, and high aspect ratio hydraulic filament artificial muscle (HFAM) for robotic and medical applications. The HFAM consists of a silicone tube inserted inside a coil spring, which expands longitudinally when receiving positive hydraulic pressure. This simple fabrication method enables low-cost and mass production of a wide range of product sizes and materials. This thesis investigates the characteristics of the proposed HFAM and two implementations, as a wearable soft robotic glove to aid in grasping objects, and as a smart surgical suture for perforation closure. Multiple HFAMs are also combined by twisting and braiding techniques to enhance their performance. In addition, smart textiles are created from HFAMs using traditional knitting and weaving techniques for shape-programmable structures, shape-morphing soft robots and smart compression devices for massage therapy. Finally, a proof-of-concept robotic cardiac compression device is developed by arranging HFAMs in a special configuration to assist in heart failure treatment. Overall this fundamental work contributes to the development of soft artificial muscle technologies and paves the way for future comprehensive studies to develop HFAMs for specific medical and robotic requirements

Conducting Polymers as Novel Tools for Biosensing and Tissue Engineering

The field of Bioelectronics deals with the integration of electronics and biology, and possesses a tremendous potential regarding the improvement of the quality of life of millions of people. Thanks to their favorable properties, conjugated polymers have proven to be very suitable materials for the bridging of such diverse worlds. In particular, poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate), or PEDOT:PSS, is nowadays considered a benchmark material for bioelectronics applications. The aim of the present work is to give a detailed characterization of the physical and electrochemical properties of PEDOT:PSS thin films, and to prove the potentialities of this material both for the sensing of bioanalytes, through the development of innovative electrochemical sensors, and for tissue engineering applications, through the development of redox-active substrates that can control the replication of living cells. In this work, the development of all PEDOT:PSS-based organic electrochemical transistors (OECTs) is presented. The sensing efficiency of these devices was optimized in terms of sensitivity and limit of detection (LOD) through the investigation of the effect of device geometry, thickness, and operating voltages. An electrochemical characterization of these devices was carried out as well, in order to clarify the processes involved in the device operation. Furthermore, the operation of these devices as electrochemical sensors was tested on several analytes, obtaining in most cases a performance suitable for real applications. The development and characterization of a different kind of devices realized using the same material, redox-active substrates for applications in tissue engineering, is then presented. The effect of a change in the redox state of these PEDOT:PSS films on cell growth is assessed using two cell lines, human dermal fibroblasts (hDF) and human tumoral glioblastoma multiforme cells (T98G), finding that the cell proliferation rate has a clear dependence on the electrochemical state of its substrate

A hybrid piezoelectric and electrostatic energy harvester for scavenging arterial pulsations

Implantable and wearable biomedical devices suffer from a limited lifespan of on-board batteries which results in a requirement to change the battery or the device itself causing additional physical discomfort. In order to overcome this, various energy harvesters have been developed. The human body possesses several types of energy available for scavenging through appropriately designed energy harvesting devices, while cardiovascular system in particular represents a constant reliable source of mechanical energy from vibration. Most conventional energy harvesters exploit only a single phenomenon, such piezo- or triboelectricity, thus producing reduced power density. As an improvement, hybridisation of energy harvesters intends to negate this drawback by simultaneously scavenging energy by multiple harvesters. In the present work, the reverse electrowetting on dielectric (REWOD) phenomenon is combined with the piezoelectric effect in a proof-of-concept hybrid harvester for scavenging biomechanical energy from arterial or other type pulsations. A mathematical model of the harvester was developed, and a computational investigation using CFD, and fluid-structure interaction simulations were carried out using the COMSOL Multiphysics software. The effect of the materials of piezoelectric film and geometrical features of the harvester on parameters such as the displacement, the frequency of pulsations and the energy produced were studied. An experimental setup that could imitate the displacements caused from arterial pulsations was designed and the produced electrical energy characteristics were analysed. A comparison between experimental and computational data was carried out and demonstrated a good agreement. Dependencies between geometrical parameters and electrical output were obtained, recommendation on piezoelectric materials and design solutions were provided