My dissertation work integrates the techniques of microfabrication, micro/nanofluidics, and bioanalytical chemistry to develop miniaturized devices for healthcare applications. Semiconductor processing techniques including photolithography, physical and chemical vapor deposition, and wet etching are used to build these devices in silicon and polymeric materials. On-chip micro-/nanochannels, pumps, and valves are used to manipulate the flow of fluid in these devices. Analytical techniques such as size-based filtration, solid-phase extraction (SPE), sample enrichment, on-chip labeling, microchip electrophoresis (µCE), and laser induced fluorescence (LIF) are utilized to analyze biomolecules. Such miniaturized devices offer the advantages of rapid analysis, low cost, and lab-on-a-chip scale integration that can potentially be used for point-of-care applications.The first project involves construction of sieving devices on a silicon substrate, which can separate sub-100-nm biostructures based on their size. Devices consist of an array of 200 parallel nanochannels with a height step in each channel, an injection reservoir, and a waste reservoir. Height steps are used to sieve the protein mixture based on size as the protein solution flows through channels via capillary action. Proteins smaller than the height step reach the end of the channels while larger proteins stop at the height step, resulting in separation. A process is optimized to fabricate 10-100 nm tall channels with improved reliability and shorter fabrication time. Furthermore, a protocol is developed to reduce the electrostatic interaction between proteins and channel walls, which allows the study of size-selective trapping of five proteins in this system. The effects of protein size and concentration on protein trapping behavior are evaluated. A model is also developed to predict the trapping behavior of different size proteins in these devices. Additionally, the influence of buffer ionic strength, which can change the effective cross-sectional area of nanochannels and trapping of proteins at height steps, is explored in nanochannels. The ionic strength inversely correlates with electric double layer thickness. Overall, this work lays a foundation for developing nanofluidic-based sieving systems with potential applications in lipoprotein fractionation, protein aggregate studies in biopharmaceuticals, and protein preconcentration. The second project focuses on designing and developing a microfluidic-based platform for preterm birth (PTB) diagnosis. PTB is a pregnancy complication that involves delivery before 37 weeks of gestation, and causes many newborn deaths and illnesses worldwide. Several serum PTB biomarkers have recently been identified, including three peptides and six proteins. To provide rapid analysis of these PTB biomarkers, an integrated SPE and µCE device is assembled that provides sample enrichment, on-chip labeling, and separation. The integrated device is a multi-layer structure consisting of polydimethylsiloxane valves with a peristaltic pump, and a porous polymer monolith in a thermoplastic layer. The valves and pump are fabricated using soft lithography to enable pressure-based sample actuation, as an alternative to electrokinetic operation. Porous monolithic columns are synthesized in the SPE unit using UV photopolymerization of a mixture consisting of monomer, cross-linker, photoinitiator, and various porogens. The hydrophobic surface and porous structure of the monolith allow both protein retention and easy flow. I have optimized the conditions for ferritin retention, on-chip labelling, elution, and µCE in a pressure-actuated device. Overall functionality of the integrated device in terms of pressure-controlled flow, protein retention/elution, and on-chip labelling and separation is demonstrated using a PTB biomarker (ferritin). Moreover, I have developed a µCE protocol to separate four PTB biomarkers, including three peptides and one protein. In the future, an immunoaffinity extraction unit will be integrated with SPE and µCE to enable rapid, on-chip analysis of PTB biomarkers. This integrated system can be used to analyze other disease biomarkers as well.

abstract: Dielectrophoresis (DEP) is a technique that influences the motion of polarizable particles in an electric field gradient. DEP can be combined with other effects that influence the motion of a particle in a microchannel, such as electrophoresis and electroosmosis. Together, these three can be used to probe properties of an analyte, including charge, conductivity, and zeta potential. DEP shows promise as a high-resolution differentiation and separation method, with the ability to distinguish between subtly-different populations. This, combined with the fast (on the order of minutes) analysis times offered by the technique, lend it many of the features necessary to be used in rapid diagnostics and point-of-care devices. Here, a mathematical model of dielectrophoretic data is presented to connect analyte properties with data features, including the intercept and slope, enabling DEP to be used in applications which require this information. The promise of DEP to distinguish between analytes with small differences is illustrated with antibiotic resistant bacteria. The DEP system is shown to differentiate between methicillin-resistant and susceptible Staphylococcus aureus. This differentiation was achieved both label free and with bacteria that had been fluorescently-labeled. Klebsiella pneumoniae carbapenemase-positive and negative Klebsiella pneumoniae were also distinguished, demonstrating the differentiation for a different mechanism of antibiotic resistance. Differences in dielectrophoretic behavior as displayed by S. aureus and K. pneumoniae were also shown by Staphylococcus epidermidis. These differences were exploited for a separation in space of gentamicin-resistant and -susceptible S. epidermidis. Besides establishing the ability of DEP to distinguish between populations with small biophysical differences, these studies illustrate the possibility for the use of DEP in applications such as rapid diagnostics. / Dissertation/Thesis / Doctoral Dissertation Chemistry 2019

My research broadly covers various important aspects of microfluidic devices and biosensors. Specifically, this dissertation reports: (1) a new and effective room temperature method of bonding polydimethylsiloxane (PDMS) microfluidics to substrates such as silicon and glass, (2) a new microfluidic pump concept and implementation specifically designed to repeatedly drive a small sample volume (<1 µL) very rapidly (~500 µL/min) through a sensor-containing flow channel to significantly decrease sensor response time through advection-driven rather than diffusion-driven mass transport, (3) use of a new microfluidic material based on polyethylene glycol diacrylate (PEGDA) to implement impedance-based dynamic nanochannel sensors for protein sensing, and (4) an investigation of galvanoluminescence and how to avoid it for conditions important to fluorescence-based dielectrophoresis (DEP) microfluidic biosensors. Over the last decade, the Nordin research group has developed a lab-on-a-chip (LOC) biosensor based on silicon photonic microcantilever arrays integrated with polydimethylsiloxane (PDMS) microfluidics for protein biomarker detection. Integration requires reliable bonding at room temperature with adequate bond strength between the PDMS element and microcantilever sensor substrate. The requirement for a room temperature process is particularly critical because microcantilevers must be individually functionalized with antibody-based receptor molecules prior to bonding and cannot withstand significant heating after functionalization. I developed a new room temperature bonding method using PDMS curing agent as an intermediate adhesive layer. Two curing agents (Sylgard 184 and 182) were compared, as well as an alternate UV curable adhesive (NOA 75). The bond strength of Sylgard 184 was found to be stronger than Sylgard 182 under the same curing conditions. Overnight room temperature curing with Sylgard 184 yields an average burst pressure of 433 kPa, which is more than adequate for many PDMS sensor devices. In contrast, UV curable epoxy required a 12 hour bake at 50 °C to achieve maximum bond strength, which resulted in a burst pressure of only 124 kPa. In many biosensing scenarios it is desirable to use a small sample volume (<1 µL) to detect small analyte concentrations in as short a time as possible. I report a new microfluidic pump to address this need, which we call a reflow pump. It is designed to rapidly pump a small sample volume back and forth in a flow channel. Ultimately, the flow channel would contain functionalized sensor surfaces. The rapid flow permits use of advection-driven mass transport to the sensor surfaces to dramatically reduce sensor response times compared to diffusion-based mass transport. Normally such rapid flow would have the effect of decreasing the fraction of analyte molecules in the volume that would see the sensor surfaces. By configuring the pump to reflow fluid back and forth in the flow channel, the analyte molecules in the small sample volume are used efficiently in that they have many opportunities to make it to the sensor surfaces. I describe a 3-layer PDMS reflow pump that pumps 300 nL of fluid at 500 µL/min for 15 psi actuation pressure, and demonstrate a new two-layer configuration that significantly simplifies pump fabrication. Impedance-based nanochannel sensors operate on the basis of capturing target molecules in nanochannels such that impedance through the nanochannels is increased. While simple in concept, the response time can be quite long (8~12 hours) because the achievable flow rate through a nanochannel is very limited. An approach to dramatically increase the flow rate is to form nanochannels only during impedance measurements, and otherwise have an array of nanotrenches on the surface of a conventional microfluidic flow channel where they are exposed to normal microfluidic flow rates. I have implemented such a dynamic nanochannel approach with a recently-developed microfluidic material based polyethylene glycol diacrylate (PEGDA). I present the design, fabrication, and testing of PEGDA dynamic nanochannel array sensors, and demonstrate an 11.2 % increase in nanochannel impedance when exposed to 7.2 µM bovine serum albumin (BSA) in phosphate buffered saline (PBS). Recently, LOC biosensors for cancer cell detection have been demonstrated based on a combination of dielectrophoresis (DEP) and fluorescence detection. For fluorescence detection it is critical to minimize other sources of light in the system. However, reported devices use a non-noble metal electrode, indium tin oxide (ITO), to take advantage of its optical transparency. Unfortunately, use of non-noble metal electrodes can result in galvanoluminescence (GL) in which the AC voltage applied to the electrodes to achieve DEP causes light emission, which can potentially confound the fluorescence measurement. I designed and fabricated two types of devices to examine and identify conditions that lead to GL. Based on my observations, I have developed a method to avoid GL that involves measuring the impedance spectrum of a DEP device and choosing an operating frequency in the resistive portion of the spectrum. I also measure the emission spectrum of twelve salt solutions, all of which exhibited broadband GL. Finally, I show that in addition to Au, Cr and Ni do not exhibit GL, are therefore potentially attractive as low cost DEP electrode materials.

Depuis les observations par Poiseuille au XVIIIe de réseaux microvasculaires de petits vertébrés,la microcirculation sanguine a fait l'objet d'abondantes études. Une spécificité mise en avant par le médecin français est la forte hétérogénéité de la distribution des globules rouges dans ces réseaux. En dépit du lien étroit qui lie la fraction volumique locale des globules rouges(hématocrite) à l'oxygénation des tissus environnants, le couplage entre l'architecture microvasculaire et la micro-hémodynamique est encore mal compris. Le sang est un fluide complexe composé de globules rouges, cellules très déformables, suspendus dans du plasma.Dans les vaisseaux de petits diamètres, i.e. du même ordre de grandeur voire plus petits que la taille caractéristique d'un globule rouge (~10µm), le sang possède des propriétés rhéologiques atypiques induites par la structuration locale de l'écoulement et les hétérogénéités d'hématocrite qui en résultent dans la section droite. Ces hétérogénéités se traduisent, aux bifurcationsdivergentes, par une répartition non proportionnelle des débits de globules rouges et de plasma entre les deux branches filles. L'hématocrite de l'une d'elles est alors plus élevé que celui de labranche d'entrée, alors qu'il est plus faible dans l'autre branche. Cet effet, connu sous le nom d'effet de séparation de phase, induit une très grande hétérogénéité de l'hématocrite à l'échelle du réseau. L'objectif de cette thèse est d'étudier l'apparition de ces hétérogénéités, de l'échelle du vaisseau à l'échelle du réseau, dans des conditions expérimentales contrôlées et pour des régimes de confinement et d'hématocrite représentatifs des écoulement sanguins de la partie terminale du lit microvasculaire (artérioles, capillaires et veinules de diamètres inférieurs à 20 µm).De nombreuses données expérimentales ont été acquises in vivo, mais elles sont sujettes à de fortes incertitudes quant à la forme et aux dimensions de la section droite des vaisseaux, mais aussi soumises aux effets de régulations physiologiques des débits (e.g. par vasoconstriction ou vasodilatation). A notre connaissance, du fait des contraintes expérimentales inhérentes aux régimes de confinement et d'hématocrite des plus petits vaisseaux de la microcirculation, très peu d'études in vitro dans ces conditions ont été menées. Tout d'abord, nous présentons les profils de vitesse des globules rouges et les profils d'hématocrite obtenus grâce à une nouvelle méthode de mesure de concentration développée pendant ce travail, dans des canaux uniques de taille comprise entre 5 et 20µm, et dans une large gamme d'hématocrite. Nous proposons une paramétrisation générale semi-empirique de ces profils, qui prend en compte la présence d'unecouche d'exclusion plasmatique, observée quelle que soit la taille du canal aux faibleshématocrites. Ensuite, nous présentons une étude paramétrique de l’effet de séparation dephase. Nous montrons que les résultats obtenus sont indépendants, dans les régimes étudiés, de l’angle de la bifurcation et du débit de la branche d’entrée. Ces résultats sont en général en bon accord avec un modèle simple qui s’appuie sur la paramétrisation précédente des profils d'hématocrite et de vitesse des globules rouges et suppose l'existence d'une ligne séparatrice de fluides dans la section droite de la branche mère. Ces résultats suggèrent que les globules rouges peuvent être décrits par un fluide équivalent, y compris dans les conditions de très fortconfinement. Enfin, nous reportons pour la première fois des résultats quantitatifs liés à la distribution de l'hématocrite dans des réseaux modèles. Nous montrons notamment quel'asymétrie des profils d'hématocrite dans les branches amonts distribue les globules rouges en enrichissant le cœur du réseau au détriment des bords. Nous comparons nos résultats à ceux d’un modèle non-linéaire de type réseau classique proposant des corrections prenant en compte cette asymétrie. / Since the very first observations of microvascular networks in small animals by Jean-MariePoiseuille in the XVIIIth century, the blood microcirculation has been extensively studied. One ofthe most striking feature highlighted by the French physicist is the highly heterogeneousdistribution of the red blood cells throughout microvessel networks. Despite the intimate linkbetween local red blood cell volume fraction (hematocrit) and surrounding tissue oxygenation, thecoupling between microvascular architecture and micro-hemodynamics is still poorly understood.Blood is a complex fluid, mainly composed of highly deformable red blood cells suspended inplasma. Thus in vessels with small diameter, i.e. of same order or smaller than the characteristicsize of a single red blood cell (~ 10µm), blood exhibits non-standard rheological propertiesinduced by the structuration of the flow and the heterogeneous distribution of the hematocrit withinthe cross section. This heterogeneity triggers a non propotionnal distribution of red blood cell andplasma flow rates between the daughter branches of a diverging bifurcation. One of the daughterbranch has a higher hematocrit than the feeding branch, while the other has a lower hematocrit.This effect, known as the phase separation effect, leads to hematocrit heterogeneities at networkscale. The goal of this thesis is to study the emergence of these heterogeneities, from the scale ofa single vessel to the scale of a network, in controlled experimental conditions and regimes ofconfinement and hematocrit representative of blood flow in the terminal parts of the microvascularbed (arterioles, capillaries and venules with diameters below 20µm). Many experimental data havebeen obtained textit{in vivo}, but these are subject not only to strong uncertainties regarding theshape and the dimensions of the vessel cross section, but also to physiological flow rate regulation(e.g. through vasoconstriction or vasolidation). To our knowledge, due to the highly challengingexperimental constraints, only very few in vitro studies have been performed. First, we presentred blood cell velocity and hematocrit profiles, obtained thanks to a new measure of red blood cellconcentration developped during this work in single channels of size ranging from 5 to 20 micronsand for a broad range of hematocrit values. We derive a semi-empirical parameterization of theseprofiles that takes into account the presence of a cell-free layer observed at low hematocrit values,for the whole range of channel sizes studied. We then present a parametric study of phaseseparation. Our results show that in the studied regimes, this effect depends neither on thebifurcation angle nor on the entry branch flow rate. These results are in general in good agreementwith a simple model that assumes the existence of a fluid separating streamline in the entrybranch cross section and relies on the above parameterization of the red blood cell velocity andhematocrit profiles. These results suggest that in spite of their cellular nature the red blood cellscan be treated as an equivalent fluid even in very high confinement regimes. Finally, we report forthe first time quantitative results related to the hematocrit distribution in model networks. Wenotably show that asymmetry of the hematocrit profile in the upstream branches leads the redblood cells into the center of the network while its edges are depleted. Our results are comparedwith a classical non-linear network type model corrected to take this asymmetry into account.

This thesis describes the design, fabrication, and testing process for a microfluidic phosphate colorimeter utilized for water quality analysis. The device can be powered by, and interfaced for data collection with, a common cell phone or laptop to dramatically reduce costs. Unlike commercially available colorimeters, this device does not require the user to measure or mix sample and reagent. A disposable poly(dimethylsiloxane) (PDMS) microfluid chip, powered by an absorption pumping mechanism, was used to draw water samples, mix the sample at a specific ratio with a molybdovanadate reagent, and load both fluids into an onboard cuvette for colorimetric analysis. A series of capillary retention valves, channels, and diffusion pumping surfaces passively controls the microfluidic chip so that no user input is required. The microfluidic chip was fabricated using a modified SU-8 soft lithography process to produce a 1.67mm light absorbance pathlength for optimal Beer Lambert Law color absorbance. Preliminary calibration curves for the device produced from standard phosphate solutions indicate a range of detection between 5 to 30mg/L for reactive orthophosphate with a linearity of R²=91.3% and precision of 2.6ppm. The performance of the PDMS absorption driven pumping process was investigated using flow image analysis and indicates an effective pumping rate up to approximately 7µL/min to load a 36µL sample.

The field of microfluidics is expanding into what is known as paper microfluidics. This uses a paper platform rather than materials (i.e. PDMS, PMMA) that are commonly used in microfluidics research. Current devices require an expensive manufacturing process and external sources to power the device. Such devices are not practical in low resource environments. As a consequence, it is the goal of this Thesis to develop a three-dimensional, multiplexed assay chip using nitrocellulose membranes. This device comprises of multiple layers of nitrocellulose membranes with defined fluidic channels. The multiple layers are bound together using double backed tape, and imbedded between the layers are conjugate reagents. In the detection region both antibodies and aptamers were evaluated. The fiberglass pad where conjugate reagents would be contained, were initially saturated in dye. As sample was inputted into the three-dimensional chip, the fluid path could be visualized. Without the use of the conjugate pad the chip’s four detection regions showed detection within one minute of one another. However, the addition of this fibrous pad skewed time points dramatically. The hypothesis that a three-dimensional chip could be designed to detect different biomarkers in a multi-analyte sample was satisfied. However, simultaneous detection was only possible if the conjugate pad was either neglected or, possibly, a different material was used. Additionally, current lateral flow assay technologies, another research area that paper microfluidics spawns from, use antibodies in order to capture biomarkers in sample and provide visual signal to the user. However, antibodies are sensitive to denaturation with pH and temperature, whereas aptamers can withstand much more extreme environmental conditions. A two-dimensional nitrocellulose chip was designed to compare antibodies and aptamers as capture reagents to detect VEGF, using colloidal gold as a particle to visualize detection. Both monoclonal and polyclonal anti-VEGF antibodies were used and showed no signal. On the other hand, the anti-VEGF aptamer produced a visual signal when conjugated to biotin on its 5’ end. This data was further validated by a separate project analyzing the binding kinetics of the antibody and the aptamer using Surface Plasmon Resonance. Therefore, the hypothesis that aptamers could be used as a possible capture reagent in a paper microfluidic chip for the detection of VEGF was satisfied.

Acute Respiratory Distress Syndrome (ARDS) is a lung condition with a mortality rate of 40 % that affects about 225,000 individuals in the U.S. In these patients, epithelial injury can contribute to alveolar flooding and injury to type II cells by disrupting normal epithelial fluid transport, impacting the removal of edema fluid from alveolar space. Mechanical stresses associated with opening occluded airways damages the epithelial lining of the lungs. Prior studies explore the nature of the stresses and damage in straight tube models of airways. Our model presented in this work accounts for the branching in the pulmonary airways. We have developed a scalable microfluidic model of pulmonary airway bifurcations for investigation of reopening near the bifurcation as well as the macroscopic reopening pattern. We utilize a μ-PIV/Shadowgraph system to visualize the flow fields near the interface as a semi-infinite finger of air propagates through the bifurcation model. Further, we utilize μ-PIV for downstream flow-rate monitoring to examine the symmetry of reopening through bifurcating networks. In the absence of surfactant, propagation preferentially opens the low-resistance path, and leads to asymmetric reopening. However, with SDS and albumin inactivated surfactant, interfacial propagation preferentially reopens the pathway with the higher hydraulic resistance. The propagation pattern with pulmonary surfactant stabilizes the system so that the daughter branches of a nearly symmetric bifurcation open simultaneously. Our multiple generation network serves to validate the stability of the single generation. However, the second generation does not mirror the behavior of the first generation. We explore the reasons for this, and also present preliminary studies for the investigation of restoring surfactant function after deactivation by serum proteins. / acase@tulane.edu

Les propriétés électrocinétiques de cellules ou de complexes colloïde-cellule visant leur manipulation individuelle dans une puce microfluidique devrait permettre de proposer de nouveaux types d'application dans le domaine des laboratoires-sur-puce et de la recherche biomédicale. Les travaux présentés dans ce manuscrit visent à créer une nouvelle technologie de puce microfluidique permettant la manipulation électrocinétique tridimensionnelle sans contact de particules colloïdales. Cette technologie innovante associée à la réalisation de particules colloïdales multifonctionnelles (Janus) permet d'étudier et de contrôler les interactions d'un complexe colloïde-cellule. Une technologie originale de puce microfluidique tridimensionnelle transparente présentant des niveaux d'électrodes biplanaires est développée sans couche résiduelle classiquement présente dans les technologies de scellement microfluidique. Parallèlement, de nouveaux types de colloïdes anisotropes (Janus) et multifonctionnels (fluorescents, fonctionnalisés avec des protéines…) sont fabriqués en associant la synthèse colloïdale aux techniques de la microélectronique et à la fonctionnalisation de surface. La compréhension et l'exploitation des forces électrocinétiques créées par un champ électrique alternatif et non-uniforme sur la solution colloïdale confinée dans cette puce permettent de proposer une nouvelle méthode de détermination du facteur de Clausius-Mossotti. Ce facteur est un paramètre intrinsèque à la solution colloïdale qui régit la force diélectrophorétique. La détermination expérimentale de ce facteur, combinée à une analyse théorique pour les solutions colloïdales étudiées, définit les paramètres du champ électrique à appliquer (fréquence, tension) pour localiser, séparer ou manipuler en trois dimensions des particules micrométriques de tout type (particules nu, fonctionnalisées, disymétriques…). Le mélange de ces particules dans des milieux de culture cellulaire contenant des cellules de lignées humaines crée des complexes colloïde-cellule. En fonction du type cellulaire, ces complexes se caractérisent par une cellule ayant internalisé des colloïdes ou une cellule décoré par des colloïdes attachés sur sa membrane. Soumis à des forces électrocinétiques déterminées, ces complexes démontrent des réponses duales des particules et des cellules contrôlables indépendamment. En combinant l'ingénierie des particules colloïdales et la technologie microfluidique de manipulation électrocinétique sans contact, des forces locales peuvent être exercées sur les cellules par l'intermédiaire des particules. / The electrokinetics properties of cells or a particles-cell complex for their individual handling in a microfluidic chip open the way to new applications for lab-on-chip or biomedical research fields. The work presented in this thesis aims to create a new technology of microfluidic chips able to perform 3D electrokinetic contactless handling of colloidal particles. Combined with the microfabrication of multifunctional (Janus) colloidal particles this technological breakthrough allows the study and the control of colloidal particles and cells. An innovative technology of a 3D transparent microfluidic chip that integrates two levels of bi-planar electrodes is developed without any residual layer commonly stacked in microfluidic sealing technology. At the same time, a new type of anisotropic particles (Janus) and multifunctional (fluorescence, functionalized with proteins) are microfabricated by combining colloidal synthesis, microelectronics process and surface functionalization techniques. The understanding and the use of electrokinetic forces that are created by a non-uniform electric field in a colloidal solution confined in this chip enable the access to a new method of determination of the Claussius-Mossotti factor. It is an intrinsic parameter of a colloidal solution that rules the dielectrophoretic force. Its experimental determination, combined with a theoretical analysis of the colloidal solution, defines the parameters of the electric field to apply (frequency, applied voltage) in order to localize, separate or handle in 3D all types of micrometer sized particles (plain, functionalized, dissymmetric). The mixing of particles in cell culture mediums that contain human lines cells creates a particle-cell complex. According to the cellular type, those complexes are characterized by a cell that has internalized particles or is decorated by particles attached on its membrane. Submitted to determined electrokinetic forces, those complexes show dual responses that are controllable on both particles or cell independently. By associating the engineering of colloidal particles and this electrokinetic contactless handling microfluidic technology, local forces can be exerted on cells via those particles.

The aim to provide preventive healthcare and high quality medical diagnostics and treatment to an increasingly ageing population caused a rapidly increasing demand for point-of-care diagnostic devices. Disposables have an advantage over re-usable units as cross-contamination is avoided, no cleaning and sterilising of equipment is required and devices can be used out of centralised laboratories. To remain cost-effective, costs for disposables should be kept low. This makes polymer materials an obvious choice. One method for the realisation of fluidic micro devices is the stacking of several layers of microstructured polymer films. Reel-to-reel manufacturing is a promising technique for high-volume manufacturing of disposable polymer bio-analytical devices. Polyethylene terephthalate (PET) and cycloolefin copolymer (COC) were selected as suitable polymer substrate materials and polydimethyl siloxane (PDMS) as membrane layer. Bonding of polymer films with the help of adhesives carries the risk of channel blocking. Despite this drawback, no other method of bonding PDMS to a structural layer could be identified. Bonding with solvents avoids channel blocking issues, but adversely affects biocompatibility. Thermal diffusion processes enable bonding of COC and PET without the use of any auxiliary material. The extensive process times requires for thermal diffusion bonding can be considerably shortened by pre-treating the material with plasma or UV exposure. Welding with the use of a laser energy absorbing dye was demonstrated to be particularly suitable for selective bonding around channels and reservoirs. None of the assessed bonding methods provide a generic solution to all bonding applications. Instead, the selection of an appropriate technique depends on the intended application and the required level of biocompatibility. Since this selection has implications on the feasibility and reliability of microfluidic structures on the device, design rules which ensure design for production have to be established and followed.

<p>Microsystem interfaces to the macroscopic surroundings and within the microsystems themselves are formidable challenges that this thesis makes an effort to overcome, specifically for enabling a spacecraft based entirely on microsystems. The NanoSpace-1 nanospacecraft is a full-fledged satellite design with mass below 10 kg. The high performance with respect to mass is enabled by a massive implementation of microsystem technology – the entire spacecraft structure is built from square silicon panels that allow for efficient microsystem integration. The panels comprise bonded silicon wafers, fitted with silicone rubber gaskets into aluminium frames. Each module of the spacecraft is added in a way that strengthens and stiffens the overall spacecraft structure.</p><p>The structural integrity of the silicon module as a generic building block has been successfully proven. The basic design (silicon, silicone, aluminium) survived considerable mechanical loads, where the silicon material contributed significantly to the strength of the structural element. Structural modeling of the silicon building blocks enables rapid iterative design of e.g. spacecraft structures by the use of pertinent model simplifications.</p><p>Other microsystem interfaces treats fluidic, thermal, and mechanical functions. First, solder sealing of microsystem cavities was demonstrated, using screen-printed solder and localized resistive heating in the microsystem interface. Second, a dismountable fluidic microsystem connector, using a ridged silicon membrane, intended for monopropellant thruster systems, was developed. Third, a thermally regulated microvalve for minute flows, made by a silicon ridge imprint in a stainless steel nipple, was investigated. Finally, particle filters for gas interfaces to microsystems, or between parts of fluidic microsystems, were made from sets of crossed v-grooves in the interface of a bonded silicon wafer stack. Filter manufacture, mass flow and pressure drop characterization, together with numeric modeling for filter design, was performed.</p><p>All in all this reduces the weight and volume when microsystems are interfaced in their applications.</p>