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

Energy Academic Group Compilation of Abstracts 2012-2016

This report highlights the breadth of energy-related student research at NPS and reinforces the importance of energy as an integral aspect of today's Naval enterprise. The abstracts provided are from theses and a capstone project report completed by December 2012-March 2016 graduates.http://archive.org/details/energyacademicgr109454991

Smart Material Wing Morphing for Unmanned Aerial Vehicles.

Morphing, or geometric adaptation to off-design conditions, has been considered in aircraft design since the Wright Brothers’ first powered flight. Decades later, smooth, bio-mimetic shape variation for control over aerodynamic forces still remains elusive. Unmanned Aerial Vehicles are prime targets for morphing implementation as they must adapt to large changes in flight conditions associated with locally varying wind or large changes in mass associated with payload delivery. The Spanwise Morphing Trailing Edge (SMTE) concept is developed to locally vary the trailing edge camber of a wing or control surface, functioning as a modular replacement for conventional ailerons without altering the wing’s spar box. The SMTE design was realized utilizing alternating active sections of Macro Fiber Composites (MFCs) driving internal elastomeric compliant mechanisms and passive sections of anisotropic, elastomeric skin with tailorable stiffness, produced by additive manufacturing. Experimental investigations of the modular design via a new scaling methodology for reduced-span test articles revealed that increased use of more MFCs within the active section did not increase aerodynamic performance due to asymmetric voltage constraints. The comparative mass and aerodynamic gains for the SMTE concept are evaluated for a representative finite wing as compared with a conventional, articulated flap wing. Informed by a simplistic system model and measured control derivatives, experimental investigations identified a reduction in the adaptive drag penalty up to 20% at off-design conditions. To investigate the potential for augmented aeroelastic performance and actuation range, a hybrid multiple-smart material morphing concept, the Synergistic Smart Morphing Aileron (SSMA), is introduced. The SSMA leverages the properties of two different smart material actuators to achieve performance exceeding that of the constituent materials. Utilizing the relatively higher work density and phase transformation of Shape-Memory Alloys combined with the larger bandwidth and conformal bending of MFCs, the resultant design is demonstrated to achieve the desired goals while providing additional control authority at stall and for unsteady conditions through synergistic use of reflex actuation. These advances highlight and motivate new morphing structures for the growing field of UAVs in which adaptation involves advanced compliance tailoring of complex geometry with synergistic actuation of embedded, smart materials.PhDAerospace EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111533/1/alexmp_1.pd

Flexible and Stretchable Electronics

Flexible and stretchable electronics are receiving tremendous attention as future electronics due to their flexibility and light weight, especially as applications in wearable electronics. Flexible electronics are usually fabricated on heat sensitive flexible substrates such as plastic, fabric or even paper, while stretchable electronics are usually fabricated from an elastomeric substrate to survive large deformation in their practical application. Therefore, successful fabrication of flexible electronics needs low temperature processable novel materials and a particular processing development because traditional materials and processes are not compatible with flexible/stretchable electronics. Huge technical challenges and opportunities surround these dramatic changes from the perspective of new material design and processing, new fabrication techniques, large deformation mechanics, new application development and so on. Here, we invited talented researchers to join us in this new vital field that holds the potential to reshape our future life, by contributing their words of wisdom from their particular perspective

Clinical, Safety, and Engineering Perspectives on Wearable Ultrasound Technology: A Review.

Wearable ultrasound has the potential to become a disruptive technology enabling new applications not only in traditional clinical settings, but also in settings where ultrasound is not currently used. Understanding the basic engineering principles and limitations of wearable ultrasound is critical for clinicians, scientists, and engineers to advance potential applications and translate the technology from bench to bedside. Wearable ultrasound devices, especially monitoring devices, have the potential to apply acoustic energy to the body for far longer durations than conventional diagnostic ultrasound systems. Thus, bioeffects associated with prolonged acoustic exposure as well as skin health need to be carefully considered for wearable ultrasound devices. This article reviews emerging clinical applications, safety considerations, and future engineering and clinical research directions for wearable ultrasound technology