350 research outputs found
LTCC packaging for Lab-on-a-chip application
LTCC -pakkaus Lab-on-a-chip -sovellukseen. Tiivistelmä. Tässä työssä suunniteltiin, valmistettiin ja testattiin uusi pakkaustekniikka ”Lab-on-a-chip” (LOC) -sovellukseen. Pakkaus tehtiin pii-mikrosirulle, jolla voidaan mitata solujen kiinnittymistä sirun pintaan solujen elinkelpoisuuden indikaattorina. Luotettavuustestaukset tehtiin daisy-chain -resistanssimittauksilla solunkasvatusolosuhteissa. Lisäksi työssä selvitettiin LTCC- ja ”Lab-on-a-chip” -teknologioiden perusteet teoreettiselta pohjalta.
Mikrosirun pakkauksessa käytettiin joustavaa LTCC-teknologiaa. Sähköisiin kontakteihin ja niiden suojauksiin käytettiin sekä johtavia että eristäviä epoksi-liimoja.
LOC-sovelluksiin on tärkeää kehittää uusia pakkausmenetelmiä jotta näiden laitteiden kaikki ominaisuudet saadaan toimimaan luotettavasti. Pakkaus testattiin samoissa olosuhteissa missä sitä tullaan käyttämään ja pakkaus kesti kaikki nämä haasteet. Lisäksi esitetty valmistusprosessi on sellainen, että sitä voidaan käyttää myös muihin ”Lab-on-a-chip” -sovelluksiin.Abstract. This work presents design, manufacturing and testing of new packaging method for Lab-on-a-chip (LOC) application. Packaging was made for silicon microchip which can measure cell adhesion on chips surface as indication of cell viability. Reliability testing was done with daisy-chain resistance measurement in real conditions. Moreover basic theory of LTCC and Lab-on-a-chip technology is presented.
Resilient LTCC technology was used for packaging material and conductive/insulating epoxies were applied for electrical contacts and barriers against the environment.
It is fundamentally important to develop new packaging methods for LOC applications, so all the properties can be utilized reliably. Packaging was tested under the cell growth conditions and the package showed to withstand all these challenges. Moreover the presented packaging method is possible to use also in other Lab-on-a-chip applications
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
A Surface-Integrated Sensor Network for Personalized Multifunctional Catheters*
Augmenting the sensing/actuating capabilities of multifunctional catheters used for minimally invasive interventions has been fostered by the reduction of transducers’ sizes. However, increasing the number of transducers to benefit from the entire catheter surface is challenging due to the number of connections and/or the required integrated circuits dedicated for multiplexing the transducer signals. Modular concepts enabling personalized catheters are lacking, at all. In this work, we investigated the feasibility of a simple and daisy-chainable transducer node network for active catheters, which overcomes these limitations. Sequentially accessible nodes enabling analog interaction (including signal buffering) with transducers were designed and fabricated using miniature components suited for catheter integration. The effective sampling rate (ESR) per node for acquiring bio-signals from 10 nodes was examined for various signal-to-noise ratios. Thanks to the low circuit complexity, an ESR up to 20 kHz was achieved, which is high enough for many bio-signals.Clinical relevance— Typical daisy-chaining features, namely theoretically indefinite node extension and simple reconfiguration facilitates modularization of the catheter design. The proposed network consequently ensures application and patient-specific requirements while incorporating transducer functions over the entire catheter surface, both may improve minimally invasive interventions
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Developing Next-generation Brain Sensing Technologies - A Review.
Advances in sensing technology raise the possibility of creating neural interfaces that can more effectively restore or repair neural function and reveal fundamental properties of neural information processing. To realize the potential of these bioelectronic devices, it is necessary to understand the capabilities of emerging technologies and identify the best strategies to translate these technologies into products and therapies that will improve the lives of patients with neurological and other disorders. Here we discuss emerging technologies for sensing brain activity, anticipated challenges for translation, and perspectives for how to best transition these technologies from academic research labs to useful products for neuroscience researchers and human patients
Towards CMOS integrated microfluidics using dielectrophoretic immobilization
Dielectrophoresis (DEP) is a nondestructive and noninvasive method which is favorable for point-of-care medical diagnostic tests. This technique exhibits prominent relevance in a wide range of medical applications wherein the miniaturized platform for manipulation (immobilization, separation or rotation), and detection of biological particles (cells or molecules) can be conducted. DEP can be performed using advanced planar technologies, such as complementary metal-oxide-semiconductor (CMOS) through interdigitated capacitive biosensors. The dielectrophoretically immobilization of micron and submicron size particles using interdigitated electrode (IDE) arrays is studied by finite element simulations. The CMOS compatible IDEs have been placed into the silicon microfluidic channel. A rigorous study of the DEP force actuation, the IDE’s geometrical structure, and the fluid dynamics are crucial for enabling the complete platform for CMOS integrated microfluidics and detection of micron and submicron-sized particle ranges. The design of the IDEs is performed by robust finite element analyses to avoid time-consuming and costly fabrication processes. To analyze the preliminary microfluidic test vehicle, simulations were first performed with non-biological particles. To produce DEP force, an AC field in the range of 1 to 5 V (peak-to-peak) is applied to the IDE. The impact of the effective external and internal properties, such as actuating DEP frequency and voltage, fluid flow velocity, and IDE’s geometrical parameters are investigated. The IDE based system will be used to immobilize and sense particles simultaneously while flowing through the microfluidic channel. The sensed particles will be detected using the capacitive sensing feature of the biosensor. The sensing and detecting of the particles are not in the scope of this paper and will be described in details elsewhere. However, to provide a complete overview of this system, the working principles of the sensor, the readout detection circuit, and the integration process of the silicon microfluidic channel are briefly discussed. © 2019 by the authors
Exploiting bioluminescence to enhance the analytical performance of whole-cell and cell-free biosensors for environmental and point-of-care applications
The routine health monitoring of living organisms and environment has become one of the major concerns of public interest. Therefore, there has been an increasing demand for fast and easy to perform monitoring technologies. The current available analytical techniques generally offer accurate and precise results; however, they often require clean samples and sophisticated equipment. Thus, they are not suitable for on site, real-time, cost-effective routine monitoring. To this end, biosensors represent suitable analytical alternative tools. Biosensors are analytical devices integrating a biological recognition element (i.e. antibody, receptor, cell) and a transducer able to convert the biological response into an easily measurable analytical signal. These tools can easily quantify an analyte or a class of analytes of interest even in a complex matrix, like clinical or environmental samples, thanks to the specificity of the biological components. Whole-cell biosensors among others offer unique features such as low cost of production and provide comprehensive functional information (i.e. detection of unclassified compounds and synergistic effects, information about the bioavailable concentration). During this PhD, several bioengineered whole-cell biosensors have been developed and optimized for environmental and point-of-care applications. Analytical performance of biosensors have been improved (i.e. low limit of detection, faster response time and wider dynamic range) thanks to synthetic biology and genetic engineering tools. Bacterial, yeast and 3D cell cultures of mammalian cell lines have been tailored at the molecular level to improve robustness and predictivity. Several reporter genes, i.e. colorimetric, fluorescent and bioluminescent proteins, have been also profiled for finding the best candidate for each point-of-need application. Furthermore, spectral resolution of different optical reporter proteins has been exploited and multiplex detection has been achieved. The inclusion of viability control strains provided a suitable tool for assessing non-specific effects on cell viability, correcting the analytical signal and increasing the analytical performance of ready-to-use cartridges
Transfer print techniques for heterogeneous integration of photonic components
The essential functionality of photonic and electronic devices is contained in thin surface layers leaving the substrate often to play primarily a mechanical role. Layer transfer of optimised devices or materials and their heterogeneous integration is thus a very attractive strategy to realise high performance, low-cost circuits for a wide variety of new applications. Additionally, new device configurations can be achieved that could not otherwise be realised. A range of layer transfer methods have been developed over the years including epitaxial lift-off and wafer bonding with substrate removal. Recently, a new technique called transfer printing has been introduced which allows manipulation of small and thin materials along with devices on a massively parallel scale with micron scale placement accuracies to a wide choice of substrates such as silicon, glass, ceramic, metal and polymer. Thus, the co-integration of electronics with photonic devices made from compound semiconductors, silicon, polymer and new 2D materials is now achievable in a practical and scalable method. This is leading to exciting possibilities in microassembly. We review some of the recent developments in layer transfer and particularly the use of the transfer print technology for enabling active photonic devices on rigid and flexible foreign substrates
Real-Time Bio Sensing Using Micro-Channel Encapsulated MEMS Resonators
This work presents a label-free bio-molecular detection technique based on realtime monitoring of the resonant frequency of micromechanical thermal-piezoresistive rotational mode disk resonators encapsulated in microfluidic channels. Mass loading via adsorption of molecular layers on the surface of such devices results in a frequency shift. In order to provide a reliable platform for sample-resonator interactions and to protect the resonators from contaminants, the resonators were encapsulated in PDMS-based microfluidic channels. Micro-channel encapsulation also allows insulation of electrical signals from the analyte solution. To characterize the performance of such devices as real-time label-free bio-molecular detectors, the strong non-covalent binding of Avidin with its ligand, biotin was utilized. To further validate the measured frequency shifts and confirm that the frequency shifts are due to molecular attachments to the resonator surfaces, fluorescent labeled molecules followed by fluorescent imaging was used confirming the existence of the expected molecular layers on the resonator surfaces
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