Functional Microstructures via Direct Laser Writing

In the current thesis novel chemical photoresist systems for the fabrication of functional microstructures via three dimensional lithography are described. Next to in-depth characterization of the produced structures, the selected polymerization procedures during curing allowed for covalent postmodification. For the different curing systems, namely for thiol-ene, thiol-yne, and photoenol chemistry, structures were modified in a single, dual, and spatially resolved manner by click chemistry

MEMS micro-contact printing engines

This thesis investigates micro-contact printing (µCP) engines using micro-electro-mechanical systems (MEMS). Such engines are self-contained and do not require further optical alignment and precision manipulation equipment. Hence they provide a low-cost and accessible method of multilevel surface patterning with sub-micron resolution. Applications include the field of biotechnology where the placement of biological ligands at well controlled locations on substrates is often required for biological assays, cell studies and manipulation, or for the fabrication of biosensors. A miniaturised silicon µCP engine is designed and fabricated using a wafer-scale MEMS fabrication process and single level and bi-level µCP are successfully demonstrated. The performance of the engine is fully characterised and two actuation modes, mechanical and electrostatic, are investigated. In addition, a novel method of integrating the stamp material into the MEMS process flow by spray coating is reported. A second µCP engine formed by wafer-scale replica moulding of a polymer is developed to further drive down cost and complexity. This system carries six complementary patterns and allows six-level µCP with a layer-to-layer accuracy of 10 µm over a 5 mm x 5 mm area without the use of external aligning equipment. This is the first such report of aligned multilevel µCP. Lastly, the integration of the replica moulded engine with a hydraulic drive for controlled actuation is investigated. This approach is promising and proof of concept has been provided for single-level patterning

Design and fabrication of silver microelectrodes for biomedical applications

Tese de doutoramento em Engenharia BiomédicaO cancro é uma das maiores causas de mortalidade e morbilidade em países desenvolvidos em todo o mundo. É geralmente precedido por alterações pré-cancerígenas e a sua deteção precoce, especialmente numa fase de displasia, é um dos grandes objetivos da medicina moderna, visto que as probabilidades de tratamento aumentam consideravelmente nesta fase. Estudos in-vitro demonstraram que alterações no pH a nível do ambiente intra- e extracelular podem estar correlacionadas com a proliferação de células tumorais em diferentes estados. Contudo, medições in-situ das propriedades eletroquímicas das células podem ser desafiantes e requerer equipamento complexo ou dispendioso. A ambição desta tese consiste no desenvolvimento de ferramentas inovadoras para o diagnóstico celular in-vitro e in-situ, com base em elétrodos micrométricos “solid-state” com capacidade de leitura de pH. Este sistema deverá, preferencialmente, ser compatível e permitir a integração de componentes “lab-on-chip” subsequentes, maioritariamente de processos óticos para posterior análise química e biológica. O protótipo proposto consiste numa matriz de 9600 microelétrodos “solid-state” com pontas nanométricas. O processo de fabricação consiste na padronização de um molde negativo para as pontas individuais de cada microelétrodo, seguido de um aumento na altura do perfil (para um maior “aspect-ratio” e capacidade de penetração) através da adição de um Photoresist, preenchimento do molde com Prata através de um processo inovador de Eletrodeposição “Through-Silicon”, e finalmente a transferência do perfil para um substrato de vidro com compatibilidade com processos óticos. Os resultados finais demonstram a prova de conceito da viabilidade do processo e dos múltiplos desenvolvimentos em engenharia de processos, apesar de estudos e otimizações subsequentes serem necessárias em diversas áreas do projeto de forma a melhor compreender os princípios e mecânicas por detrás de alguns aspetos dos processos inovadores.Cancer is one of the major causes of mortality and morbidity in developed countries worldwide. It is usually preceded by precancerous changes and its early detection, especially at the dysplasia stage, is one of the major goals in modern medicine, as the chances of a successful treatment are increased at this stage. In-vitro studies have demonstrated that pH changes in both the intracellular and extracellular environment of a tissue can be correlated with tumor cell proliferation at different stages. However, in-situ measurements of the electrochemical properties of cells can be challenging and require complex or costly equipment. In this thesis, the ambition is to develop a novel tool for in-vitro and in-situ cell diagnosis, based on solid-state micrometric electrodes with pH sensing capabilities. This system should, optimally, be compatible and allow integration with subsequent lab-on-chip components, mainly optical processes for further biological and chemical analysis. The proposed prototype consists in an array of 9600 solid-state microelectrodes with nanometric tips. The fabrication process includes the patterning of a negative mold for the individual microelectrode tips, followed by an increase in height (for higher aspect-ratio and deeper penetration capability) through the addition of a Photoresist, filling of the mold with Silver through a novel Through-Silicon Electrodeposition process, and finally transferring the pattern to a Glass substrate with optical processing compatibility. The end results demonstrates a proof-of-concept of the process feasibility and the multiple achievements in process engineering, although further studies and optimization are required in different areas of the project as to better understand the mechanics and principles behind some of the novel aspects of the processes.This thesis had the support of Fundação para a Ciência e Tecnologia under a Doctoral Scholarship -SFRH/BD/90121/201

Light to Shape the Future: From Photolithography to 4D Printing

Over the last few decades, the demand of polymeric structures with well-defined features of different size, dimension, and functionality has increased from various application areas, including microelectronics, biotechnology, tissue engineering, and photonics, among others. The ability of light to control over space and time physicochemical processes is a unique tool for the structuring of polymeric materials, opening new avenues for technological progress in different fields of application. This article gives an overview of various photochemical reactions in polymers, photosensitive materials, and structuring techniques making use of light, and highlights most recent advances, emerging opportunities, and relevant applications

A Microfluidic Programmable Array for Label-free Detection of Biomolecules

One of the most promising ways to improve clinical diagnostic tools is to use microfluidic Lab-on-a-chip devices. Such devices can provide a dense array of fluidic components and sensors at the micro-scale which drastically reduce the necessary sample volumes and testing time. This dissertation develops a unique electrochemical sensor array in a microfluidic device for high-throughput, label-free detection of both DNA hybridization and protein adsorption experiments. The device consists of a patterned 3 x 3 grid of electrodes which can be individually addressed and microfluidic channels molded using the elastomer PDMS. The channels are bonded over the patterned electrodes on a silicon or glass substrate. The electrodes are designed to provide a row-column addressing format to reduce the number of contact pads required and to drastically reduce the complexity involved in scaling the device to include larger arrays. The device includes straight channels of 100 micron height which can be manually rotated to provide either horizontal or vertical fluid flow over the patterned sensors. To enhance the design of the arrayed device, a series of microvalves were integrated with the platform. This integrated system requires rounded microfluidic channels of 32 micron height and a second layer of channels which act as pneumatic valves to pinch off selected areas of the microfluidic channel. With the valves, the fluid flow direction can be controlled autonomously without moving the bonded PDMS layer. Changes to the mechanism of detection and diffusion properties of the system were examined after the integration of the microvalve network. Protein adhesion studies of three different proteins to three functionalized surfaces were performed. The electrochemical characterization data could be used to help identify adhesion properties for surface coatings used in biomedical devices or for passivating sensor surfaces. DNA hybridization experiments were performed and confirmed both arrayed and sensitive detection. Hybridization experiments performed in the valved device demonstrated an altered diffusion regime which directly affected the detection mechanism. On average, successful hybridization yielded a signal increase 8x higher than two separate control experiments. The detection limit of the sensor was calculated to be 8 nM

Scanning evanescent wave lithography for sub-22nm generations

Current assumptions for the limits of immersion optical lithography include NA values at 1.35, largely based on the lack of high-index materials. In this research we have been working with ultra-high NA evanescent wave lithography (EWL) where the NA of the projection system is allowed to exceed the corresponding acceptance angle of one or more materials of the system. This approach is made possible by frustrating the total internal reflection (TIR) evanescent field into propagation. With photoresist as the frustrating media, the allowable gap for adequate exposure latitude is in the sub-100 nm range. Through static imaging, we have demonstrated the ability to resolve 26 nm half-pitch features at 193 nm and 1.85 NA using existing materials. Such imaging could lead to the attainment of 13 nm half-pitch through double patterning. In addition, a scanning EWL imaging system was designed, prototyped with a two-stage gap control imaging head including a DC noise canceling carrying air-bearing, and a AC noise canceling piezoelectric transducer with real-time closed-loop feedback from gap detection. Various design aspects of the system including gap detection, feedback actuation, prism design and fabrication, software integration, and scanning scheme have been carefully considered to ensure sub-100 nm scanning. Experiments performed showed successful gap gauging at sub-100 nm scanning height. Scanning EWL results using a two-beam interference imaging approach achieved pattern resolution comparable to static EWL imaging results. With this scanning EWL approach and the imaging head developed, optical lithography becomes extendable to sub-22 nm generations

Industrial lab-on-a-chip: Design applications and scale-up for drug discovery and delivery

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3D integration of micro- and nanostructures into bio-analytical devices

This study aims to develop a process which allows 3D integration of micro and nanostructures in microchannels. A fabrication process was established for the large area integration of hierarchical micro and nanostructures in microchannels. This novel process, which is called 3D molding, takes advantage of an intermediate thin flexible stamp such as PDMS from soft lithography and a hard mold such as brass from hot embossing process. However, the use of a thin intermediate polydimethylsiloxane (PDMS) stamp inevitably causes dimensional changes in the 3D molded channel, with respect to those in the brass mold protrusion and the intermediate PDMS stamp structures. We have investigated the deformation behavior of the 3D molded poly(methyl methacrylate) (PMMA) substrate and the intermediate PDMS stamp in 3D molding through both experimentation and numerical simulation. It was found that for high aspect ratio brass mold protrusion, the maximum strain of the intermediate layer occurs in the bottom center of the 3D channels. However, with decreasing the aspect ratio of brass mold protrusion the highest elongation occurs at the bottom corners of the channel causing less elongation of the intermediate PDMS stamp and imprinted structures on the bottom surface of the 3D channel. A modified 3D molding process which is called 3D nanomolding is developed which allows nanopatterning the surface of small microfeatures. Using 3D nanomolding process and solvent assisted bonding microdevices with no side, one side, three sides and four sides patterned were fabricated. To characterize 3D flow patterns induced by the surface structures on microdevices, confocal microscopy was used as dyed water and undyed water injected from separate inlets of micromixer were mixed along the microchannel at flow rates of 10 and 40 μL/min. The standard deviation of the normalized intensity measured in the confocal image of the cross section of the channel was used for quantifying the degree of mixing and evaluating the mixing performance of all four different microdevices. Experimental and simulation results show that by patterning the surface of the micromixer, flow patterns can be manipulated, which can improve mixing through stretching and folding of fluid elements and therefore increasing the interfacial area between fluids and cutting down the diffusion length. The effect of increasing velocity on increasing standard deviation (decreasing mixing) was also found to be less for the micromixers whose surfaces are patterned compared to the plain channel