Modular integration and on-chip sensing approaches for tunable fluid control polymer microdevices

228 p.Doktore tesi honetan mikroemariak kontrolatzeko elementuak diseinatu eta garatuko dira, mikrobalbula eta mikrosentsore bat zehazki. Ondoren, gailu horiek batera integratuko dira likido emari kontrolatzaile bat sortzeko asmotan. Helburu nagusia gailuen fabrikazio arkitektura modular bat frogatzea da, non Lab-on-a-Chip prototipoak garatzeko beharrezko fase guztiak harmonizatuz, Cyclic-Olefin-Polymer termoplastikozko mikrogailu merkeak pausu gutxi batzuetan garatuko diren, hauen kalitate industriala bermatuz. Ildo horretan, mikrogailuak prototipotik produkturako trantsizio azkar, erraz, errentagarri eta arriskurik gabeen bidez lortu daitezkeenetz frogatuko da

Mems (Micro-Electro-Mechanical-Systems) Based Microfluidic Platforms for Magnetic Cell Separation

Microfluidic platforms for magnetic cell separation were developed and investigated for isolation of magnetic particles and magnetically tagged cells from a fluidic sample. Two types of magnetic separation platforms were considered: an Isodynamic Open Gradient Magnetic Sorter (OGMS) and a multistage bio-ferrograph. Miniaturized magnets were designed using magnetostatic simulation software, microfluidic channels were fabricated using microfabrication technology and magnetic separation was investigated using video microscopy and digital image processing. The isodynamic OGMS consisted of an external magnetic circuit and a microfabricated channel (biochip) with embedded magnetic elements. The biochip is placed inside the magnetic field of the external circuit to obtain nearly constant energy density gradient in the portion of the channel used for separation. The microfabrication process involved improving adhesion of thick SU-8 to Pyrex, forming enclosed channels using a low temperature SU-8 adhesive bonding, and fabricating patterned plating molds on both sides of the bonded wafers. Adhesion of SU-8 to Pyrex was improved by using a highly crosslinked thin SU-8 adhesion layer, and enclosed microchannels were fabricated using selectively exposed SU-8 bond formation layers. Electroplating molds were fabricated using KMPR photoresists and were integrated on both sides of the bonded wafers. The multistage bio-ferrograph consisted of a microfabricated enclosed channel placed on the surface of a multi-unit magnet (4 trapezoidal magnets placed in series) assembly such that magnetic cells from a flowing stream would be deposited on designated locations. The OGMS was able to deflect magnetic particles by 500-1000 microns and the capture efficiencies of magnetic particles and cells with the multistage bio-ferrograph were 80-85 percent and 99.5 percent, respectivel

Mems (Micro-Electro-Mechanical-Systems) Based Microfluidic Platforms for Magnetic Cell Separation

Microfluidic platforms for magnetic cell separation were developed and investigated for isolation of magnetic particles and magnetically tagged cells from a fluidic sample. Two types of magnetic separation platforms were considered: an Isodynamic Open Gradient Magnetic Sorter (OGMS) and a multistage bio-ferrograph. Miniaturized magnets were designed using magnetostatic simulation software, microfluidic channels were fabricated using microfabrication technology and magnetic separation was investigated using video microscopy and digital image processing. The isodynamic OGMS consisted of an external magnetic circuit and a microfabricated channel (biochip) with embedded magnetic elements. The biochip is placed inside the magnetic field of the external circuit to obtain nearly constant energy density gradient in the portion of the channel used for separation. The microfabrication process involved improving adhesion of thick SU-8 to Pyrex, forming enclosed channels using a low temperature SU-8 adhesive bonding, and fabricating patterned plating molds on both sides of the bonded wafers. Adhesion of SU-8 to Pyrex was improved by using a highly crosslinked thin SU-8 adhesion layer, and enclosed microchannels were fabricated using selectively exposed SU-8 bond formation layers. Electroplating molds were fabricated using KMPR photoresists and were integrated on both sides of the bonded wafers. The multistage bio-ferrograph consisted of a microfabricated enclosed channel placed on the surface of a multi-unit magnet (4 trapezoidal magnets placed in series) assembly such that magnetic cells from a flowing stream would be deposited on designated locations. The OGMS was able to deflect magnetic particles by 500-1000 microns and the capture efficiencies of magnetic particles and cells with the multistage bio-ferrograph were 80-85 percent and 99.5 percent, respectivel

Development and application of microtechnologies in the design and fabrication of cell culture biomimetic systems

“Lab-On-a-chip” systems have proved to be a promising tool in the field of biology. Currently, cell culture is performed massively on Petri dishes, which have traditionally been used in cell culture laboratories and tissue engineering. However, having proved to be a widely used tool until now, the scientific community has largely described the lack of correlation between the results obtained in the laboratory and the clinical results. This lack of connection between what has been studied in the laboratories and what has been observed in the clinic has led to the search for more advanced alternative tools that allow results to be obtained closer to reality. Thus, the use of microtechnologies in the field of biomedical engineering, presents itself as the perfect tool as an alternative to obsolete traditional media. Thanks to the low volumes of liquid it presents for its use, it also makes it an essential technology for the testing of drugs, new compounds and materials. By being able to more accurately reproduce the biomimetic environment of cell cultures and tissues, they make this technique fundamental as an intermediate step between basic in vitro laboratory tests and preclinical animal tests, resulting from this way in the best alternative for the reduction of both the use of animal models, as in times and costs. For a biomimetic system to be as such, it also needs another series of complementary devices for its better functioning. Micro-valves, micro pumps, flow sensors, O2 sensors, pH, CO2 are fundamental for the correct functioning andsophistication of biomimetic systems. This complexity, on the other hand, is often not perceived by the user since the miniaturization of all these components makes “Lab-On-a-Chip” systems smaller every day, despite numerous control components that can be incorporated.This thesis presents some examples of different microfluidic devices designed and manufactured through the use of microtechnologies, with all applications, focused on their use in biomimetic systems.<br /

SU-8 microprobes for biomedical applications

152 p. : il.[ES]La presente tesis doctoral aborda el diseño, fabricación, encapsulado, y caracterización de microagujas de SU-8 para aplicaciones médicas. En la actualidad existe una amplia variedad de agujas para el registro, estimulación y dispensado de drogas, pero se han observado algunas limitaciones en relación a su diseño y material estructural utilizados. En este trabajo se han desarrollado microagujas basadas en la tecnología de SU-8 como alternativa a las agujas actuales. Primeramente se diseñan las agujas para cada tipo de aplicación, después se determinan los procedimientos de fabricación y finalmente se desarrollan los encapsulados para conectar la aguja miniaturizada con el exterior macroscópico. La aplicación de las agujas se ha centrado en dos campos biomédicos: 1) la monitorización de órganos tal como el riñón, y 2) el registro de la actividad neuronal, añadiendo la posibilidad de realizar dispensado de drogas de forma simultánea. El primer objetivo es crear microagujas que causen el menor daño posible en el tejido biológico. Las mediciones eléctricas que se llevan a cabo para conocer el estado real del tejido pueden resultar modificadas, debilitadas o destruidas si las células que constituyen el tejido han sido previamente dañadas. En este trabajo, se desarrollan microagujas basadas en la tecnología MEMS (micro electromechanical systems) para evitar daños profundos en el tejido y poder así realizar mediciones fidedignas. La tecnología MEMS integra elementos y dispositivos eléctricos, mecánicos y electrónicos miniaturizados, los cuales están basados en la industria consolidada de los Circuitos Integrados (IC). Generalmente, las dimensiones de los elementos basados en MEMS son de entre 1 y 100 micras y los dispositivos pueden variar entre 20 micras y 1 milímetro. Las técnicas base de esta tecnología son la deposición de materiales en láminas, la fotolitografía y el grabado. El silicio es el material más utilizado para crear los múltiples dispositivos MEMS, sin embargo, su rigidez y fragilidad ha motivado el estudio de otros materiales tales como los polímeros. En esta tesis se ha utilizado el polímero SU-8 como material estructural debido a sus propiedades favorables para la fabricación de microagujas. Además, la fabricación de microagujas con este polímero permite el uso de procesos de bajo coste. Esta fotoresina presenta una baja absorción a la luz UV, posibilitando exposiciones uniformes en función del espesor del polímero. Así, se obtienen perfiles verticales y un buen control dimensional para toda la estructura. Además, estudios recientes muestran una adecuada biocompatibilidad del polímero SU-8. El segundo objetivo es obtener la más alta relación señal-ruido posible en las mediciones eléctricas. Para ello se han integrado microelectrodos en las agujas y se ha estudiado la constitución física, la configuración espacial y los tratamientos superficiales de los mismos. Un determinado diseño para cada aplicación y la modificación de las técnicas de fabricación han dado como resultado una óptima capacidad sensora de los electrodos. Así, se ha demostrado su uso a través de la monitorización de episodios de isquemia y reperfusión en riñón de rata. En cuanto a las aplicaciones neuronales, se han registrado potenciales de acción con una amplitud de hasta 400-500 ¿V en hipocampo de rata. Además, se ha demostrado que los microelectrodos son capaces de discriminar diferentes fuentes neuronales. Todos estos resultados han demostrado la versatilidad del polímero para crear dispositivos sensores con aplicación en diversas áreas biomédicas. El último objetivo de esta tesis ha sido integrar canales microfluídicos en la aguja para poder dispensar drogas en aplicaciones neuronales y como resultado, detectar cambios en la actividad neuronal. Finalmente, se han llevado a cabo los primeros experimentos fluídicos in vivo en hipocampo de rata como prueba de concepto. Se dispensan 0.5 ¿l de una disolución de kainato y a continuación se registra un incremento en la actividad neuronal. Los resultados preliminares han demostrado la funcionalidad de la aguja para dispensar y monitorizar de forma simultánea aunque se tienen que realizar más experimentos y optimizar el protocolo experimental para verificar el buen funcionamiento de la aguja. En estos momentos, se están realizando más experimentos neuronales para llegar a establecer la tecnología desarrollada en esta tesis

MEMS micropump for a Micro Gas Analyzer

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2009.Cataloged from PDF version of thesis.Includes bibliographical references (p. 164-177).This thesis presents a MEMS micro-vacuum pump designed for use in a portable gas analysis system. It is designed to be pneumatically-driven and as such does not have self-contained actuation (the focus of future work). This research was carried out through a series of modeling, design, fabrication, and experimental testing tasks. Non-linear stress modeling tools characterizing the structural deformations of the micropump pistons and tethers, and fluid-flow modeling tools characterizing the vacuum generation and pumping rates were developed. A systematic design procedure based on these tools enabled the design and prediction of different valve and pump layouts to satisfy the stress limitations, and flow and power consumption requirements set forth by the MIT Micro Gas Analyzer project. The micropumps were fabricated using MEMS fabrication techniques, comprised of silicon and pyrex micromachining and bonding. Fabrication challenges, in particular the deep-reactive ion etching (DRIE) of the drive pistons and membrane structures, were overcome, and a completely computer controlled pneumatic testing platform for the rapid characterization of valve and micropump performance at different actuation pressures and frequencies was developed. Valve leakage data for various valve designs was collected and compared with models, and a micropump capable of generating 258Torr of vacuum below atmosphere was demonstrated at 0.75Hz operation. The maximum frequency of operation for these devices was experimentally measured to be just above 2Hz, which was consistent with fluid flow models.(cont.) This thesis presents vacuum generating micropump performance that comparables well with the best published to date, and explores future micropump designs and modeling/testing approaches that could improve overall performance and bring us closer to meeting the specifications set forth by the MGA project. Finally, general guidelines for micropump design and fabrication for any application are also presented.by Vikas Sharma.Ph.D