Dissertations / Theses on the topic 'Microfluidic optical chip'

This dissertation develops technology for microfluidic point-of-care (POC) immunoassay devices, divided into three papers, and explores the use of a quartz crystal microbalance for real time monitoring of blood coagulation in a fourth paper. The concept of POC testing has been well established around the world. With testing conveniently brought to the vicinity of the patient or testing site, results can be obtained in a much shorter time. There has been a global push in recent years to develop POC molecular diagnostics devices for resource-limited regions where well equipped centralized laboratories are not readily accessible. POC testing has applications in medical/veterinary diagnostics, environmental monitoring, as well as defense related testing. In the first paper, we demonstrated the use of latex immunoagglutination assays within a microfluidic chip to be an effective and sensitive method for detecting the bovine viral diarrhea virus. In the second paper the feasibility and general ease of integrating liquid core optical components onto a microfluidic lab-on-a-chip type device, for point-of-care AI diagnosis is demonstrated. In the third paper particle agglutination assays, utilizing light scattering measurements at a fixed angle from incident light delivery, for pathogen detection are explored in both Rayleigh and Mie scatter regimes through scatter intensity simulations and compared to experimental results. In the fourth paper a quartz crystal microbalance was used for real-time monitoring of fibrinogen cross-linking on three model biomaterial surfaces.

Integration and miniaturisation in electronics has undoubtedly revolutionised the modern world. In biotechnology, emerging lab-on-a-chip (LOC) methodologies promise all-integrated laboratory processes, to perform complete biochemical or medical synthesis and analysis encapsulated on small microchips. The integration of electrical, optical and physical sensors, and control devices, with fluid handling, is creating a new class of functional chip-based systems. Scaled down onto a chip, reagent and sample consumption is reduced, point-of-care or in-the-field usage is enabled through portability, costs are reduced, automation increases the ease of use, and favourable scaling laws can be exploited, such as improved fluid control. The capacity to manipulate single cells on-chip has applications across the life sciences, in biotechnology, pharmacology, medical diagnostics and drug discovery. This thesis explores multiple applications of optical manipulation within microfluidic chips. Used in combination with microfluidic systems, optics adds powerful functionalities to emerging LOC technologies. These include particle management such as immobilising, sorting, concentrating, and transportation of cell-sized objects, along with sensing, spectroscopic interrogation, and cell treatment. The work in this thesis brings several key applications of optical techniques for manipulating and porating cell-sized microscopic particles to within microfluidic chips. The fields of optical trapping, optical tweezers and optical sorting are reviewed in the context of lab-on-a-chip application, and the physics of the laminar fluid flow exhibited at this size scale is detailed. Microfluidic chip fabrication methods are presented, including a robust method for the introduction of optical fibres for laser beam delivery, which is demonstrated in a dual-beam optical trap chip and in optical chromatography using photonic crystal fibre. The use of a total internal reflection microscope objective lens is utilised in a novel demonstration of propelling particles within fluid flow. The size and refractive index dependency is modelled and experimentally characterised, before presenting continuous passive optical sorting of microparticles based on these intrinsic optical properties, in a microfluidic chip. Finally, a microfluidic system is utilised in the delivery of mammalian cells to a focused femtosecond laser beam for continuous, high throughput photoporation. The optical injection efficiency of inserting a fluorescent dye is determined and the cell viability is evaluated. This could form the basis for ultra-high throughput, efficient transfection of cells, with the advantages of single cell treatment and unrivalled viability using this optical technique.

This dissertation develops technology for microfluidic point-of-care immunoassay devices. This research (2004–2007) improved microfluidic immunoassay performance by reducing reagent consumption, decreasing analysis time, increasing sensitivity, and integrating processes using a lab-on-a-chip. Estimates show that typical hospital laboratories can save $1.0 million per year by using microfluidic chips. Our first objective was to enhance mixing in a microfluidic channel, which had been one of the main barriers to using these devices. Another goal of our studies was to simplify immunoassays by eliminating surfactants. Manufacturers of latex immunoassays add surfactants to prevent non-specific aggregation of microspheres. However, these same surfactants can cause false positives (and negatives) during diagnostic testing. This work, published in Appendix A (© 2006 Elsevier) shows that highly carboxylated polystyrene (HCPS) microspheres can replace surfactants and induce rapid mixing via diffusion in microfluidic devices. Our second objective was to develop a microfluidic device using fiber optics to detect static light scattering (SLS) of microspheres in Appendix B (© 2007 Elsevier). Fiber optics were used to deliver light emitting diode (LED) or laser light. A miniature spectrometer was used to measure 45° forward light scattering collected by optical fiber. Latex microspheres coated with PR3 proteins were used to test for the vasculitis marker, anti-PR3. No false negatives or positives were observed. A limit of detection (LOD) of 50 ng mL⁻¹ was demonstrated. This optical detection system works without fluorescence or chemiluminescence markers. It is cost effective, small, and re-usable with simple rinsing. The final objective in this dissertation, published in Appendix C (© 2007 Elsevier), developed a multiplex immunoassay. A lab-on-a-chip was used to detect multiple antibodies using microsphere light scattering and quantum dot (QD) emission. We conjugated QDs onto microspheres and named this configuration “nano-on-micro” or “NOM”. Upon radiation with UV light, strong light scattering is observed. Since QDs also provide fluorescent emission, we are able to use increased light scattering for detecting antigen-antibody reactions, and decreased QD emission to identify which antibody is present.

The past few years have seen great interest and advances in scientific research on fluorescence-based microfluidic optical sensors for clinical/medical applications. In particular, the growing demand for point-of-care-testing (POCT) devices to be applied near the patient’s bed, has driven the development of simple to use, reliable and low cost microfluidic optical platforms. The main objective of the research project presented in this thesis is the development of a novel fluorescence-based microfluidic optical chip for the simultaneous analysis of different analytes and its integration into a stand-alone POCT device. The work was undertaken in the framework of the EU project NANODEM (NANOphotonic Device for Multiple therapeutic drug monitoring - FP7-ICT-2011) that aims at developing a POCT device for the measurement of immunosuppressants in transplanted patients, characterized by a narrow therapeutic range and serious potential side effects. The benefit of this device will be an optimized dosage of the therapeutic drugs to support patient management in a clinical environment. In particular, the system will accurately measure the patient blood drug free fraction, which is considered the active fraction in terms of both drug effect and toxicity. In order to reach the low limit of detection required by the clinicians and enable the detection of the therapeutic drug free fraction, a heterogeneous binding inhibition immunoassay has been developed which makes use of antibody-coated fluorescent and magnetic nanoparticles. The microfluidic optical chip, which exploits total internal reflection fluorescence (TIRF) and fluorescence anisotropy, is constituted by an array of microfluidic channels whose surface is chemically modified with the analyte derivative. The excitation light, coming from an external source, is properly coupled and confined by total internal reflection into the optical waveguide constituting the chip, and is guided towards the sensing area. After binding with the analyte derivative immobilised on the microchannel surface, the fluorescent-magnetic nanoparticles, coated with the analyte-specific antibodies, can be excited by means of the evanescent field, which arises at the waveguide/chip surface, and the emitted fluorescence can be collected by means of large area photodiodes. A thorough study on the excitation and emission of a fluorophore near a dielectric interface was undertaken theoretically and experimentally in order to optimize the microfluidic chip design for the best fluorescence collection efficiency. Different materials have been also investigated and several chip prototypes have been realized and characterized. The final microfluidic optical chip consists of three different polymeric parts bonded together: a thin Zeonor foil (188 µm thick, R.I. = 1.53) which is used as excitation waveguide, a double side adhesive tape (140 µm thick, R.I. = 1.49), in which ten channels are structured by laser cutting and in which the heterogeneous inhibition binding immunoassay is performed, and a Zeonex slide (1 mm thick, R.I = 1.51). The developed microfluidic optical chip is capable of performing the simultaneous analysis of three different selected analytes (Tacrolimus, Cyclosporin A and Mycophenolic acid), each of them measured three times in three different channels with an additional channel for waste flowing. One of the main challenges of the work is to make the microfluidic optical chip easy to use and easy to integrate with different functional elements into a POCT device. These elements include the optoelectronic system (for both the excitation and the detection of the fluorescent signal), the magnetic trapping system (for the attraction and confinement of magnetic and fluorescent nanoparticles within the sensing area), and the fluidic system (for the automatic management of samples and reagents). Specifically, for the optoelectronic excitation system, different laser sources and different optical arrangements for the in-coupling of the light into the excitation waveguide have been experimentally evaluated and tested. An optimized butt-coupling illumination system based on an optical fibre bundle has been finally developed and integrated with the microfluidic chip. As second step of integration, the optical acquisition system, constituted of amorphous large area silicon (a-Si:H) photodiodes, absorption optical filters and readout electronics, has been properly developed in collaboration with the partners of the project. In order to favour the interaction between the fluorescent magnetic nanoparticles and the sensing layer, two magnetic trapping strategies based on current line structures (magnetic coils) and on permanent magnets have been evaluated, and a permanent magnet platform has been properly designed to be finally coupled with the microfluidic optical chip. The automatic management of the fluidics is an essential requirement for the development of POCT devices: from this point of view a fluidic system has been optimized for the implementation of the heterogeneous assay into the channels of the chip. A laboratory version of the integrated system has been developed and it can be considered as a transition setup. The final NANODEM POCT device has been finally manufactured and its functionality has been evaluated.

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.

Les laboratoires sur puce visent à miniaturiser et à intégrer les fonctions couramment utilisées dans les laboratoires d'analyse afin de cibler des applications en santé avec un impact prometteur sur le diagnostic médical au lit du patient. Les membranes poreuses sont d'un grand intérêt pour la préparation et l'analyse d'échantillon sur puce car elles permettent la séparation par taille/charge de molécules, mais également leur pré-concentration. Parmi les matériaux disponibles pour constituer des membranes poreuses, le silicium poreux présente de nombreux avantages tels que le contrôle précis de la taille des pores et de la porosité, une chimie de surface pratique et des propriétés optiques uniques. Les membranes de silicium poreux sont généralement intégrées dans des puces fluidiques en les montant entre deux couches comportant des micro-canaux, formant ainsi des réseaux fluidiques à trois dimensions, peu pratiques et peu adaptés à l'observation directe par microscopie. Dans ces travaux de thèse, nous avons développé deux méthodes de fabrication de membranes de silicium à pores latéraux qui permettent leur intégration monolithique dans des systèmes microfluidiques planaires. Le premier procédé est fondé sur l'utilisation d'électrodes localement structurées afin de guider la formation de pores de manière horizontale, en combinaison avec des substrats type silicium sur isolant (SOI) pour localiser spatialement la formation de silicium poreux dans la profondeur du canal. La deuxième méthode repose sur le fait que la formation de silicium poreux par anodisation est fortement dépendante du type de dopant et de sa concentration. Bien que nous utilisons encore le même type d'électrodes structurées sur les parois latérales de la membrane pour injecter le courant lors de l'anodisation, le dopage par implantation permet de confiner la membrane, de façon analogue mais à la place de l'oxyde enterré du SOI. Des membranes à pores latéraux ont été fabriquées par ces deux méthodes et leur fonctionnalité a été démontrée en réalisant des expériences de filtrage. En plus de la filtration d'échantillon, les membranes ont été utilisées pour étudier la possibilité d'effectuer de la pré-concentration électrocinétique et de la détection interférométrique. La sélectivité ionique des membranes microporeuse permet la pré-concentration moléculaire avec des facteurs de concentration pouvant atteindre jusqu'à 103 en 10 min en appliquant moins de 9 V. Ces résultats sont comparables à ceux rapportés dans la littérature à l'aide par exemple de nanocanaux avec une consommation d'énergie beaucoup plus faible. Enfin, nous avons pu détecter une variation de l'indice de réfraction du silicium poreux par le décalage du spectre d'interférence lors du chargement de différents liquides injectés dans les membranes. Le travail présenté dans cette thèse constitue la première étape dans la démonstration de l'intérêt du silicium poreux pour la préparation d'échantillon et la biodétection dans des laboratoires sur puce planaires
Lab on a chip devices aim at integrating functions routinely used in medical laboratories into miniaturized chips to target health care applications with a promising impact foreseen in point-of-care testing. Porous membranes are of great interest for on-chip sample preparation and analysis since they enable size- and charge-based molecule separation, but also molecule pre-concentration by ion concentration polarization. Out of the various materials available to constitute porous membranes, porous silicon offers many advantages, such as tunable pore properties, large porosity, convenient surface chemistry and unique optical properties. Porous silicon membranes are usually integrated into fluidic chips by sandwiching fabricated membranes between two layers bearing inlet and outlet microchannels, resulting in three-dimensional fluidic networks that lack the simplicity of operation and direct observation accessibility of planar microfluidic devices. To tackle this constraint, we have developed two methods for the fabrication of lateral porous silicon membranes and their monolithic integration into planar microfluidics. The first method is based on the use of locally patterned electrodes to guide pore formation horizontally within the membrane in combination with silicon-on-insulator (SOI) substrates to spatially localize the porous silicon within the channel depth. The second method relies on the fact that the formation of porous silicon by anodization is highly dependent on the dopant type and concentration. While we still use electrodes patterned on the membrane sidewalls to inject current for anodization, the doping via implantation enables to confine the membrane analogously to but instead of the SOI buried oxide box. Membranes with lateral pores were successfully fabricated by these two methods and their functionality was demonstrated by conducting filtering experiments. In addition to sample filtration, we have achieved electrokinetic pre-concentration and interferometric sensing using the fabricated membranes. The ion selectivity of the microporous membrane enables to carry out sample pre-concentration by ion concentration polarization with concentration factors that can reach more than 103 in 10 min by applying less than 9 V across the membrane[TL1]. These results are comparable to what has already been reported in the literature using e.g. nanochannels with much lower power consumption. Finally, we were able to detect a change of the porous silicon refractive index through the shift of interference spectrum upon loading different liquids into the membrane. The work presented in this dissertation constitutes the first step in demonstrating the interest of porous silicon for all-in-one sample preparation and biosensing into planar lab on a chip

Microfluidic systems can be considered as nonlinear dynamical systems. In the perspective of control systems toward the development of highly integrated and portable Lab on a Chip systems (LOC), is of primary importance the identification of the nonlinear processes involved in such phenomena. The main aims achieved in this PhD thesis are: the identification of input-output relation maps for the two-phase flow patterns, the design of innovative PDMS micro-optical systems for microfluidics' monitoring, the parameters estimation of a mathematical model by means of synchronization of two dynamical systems. These experimental studies open the way for the control of two-phase microfluidic flows through signal processing.

Rolled-up nanotechnology based on strain-engineering is a powerful tool to manufacture three-dimensional hollow structures made of virtually any kind of material on a large variety of substrates. The aim of this thesis is to address the key features of different on- and off-chip applications of rolled-up microtubes through modification of their basic framework. The modification of the framework pertains to the tubular structure, in particular the diameter of the microtube, and the material which it is made of, hence achieving different functionalities of the final rolled-up structure. The tuning of the microtube diameter which is adjusted to the individual size of an object allows on-chip studies of single cells in artificial narrow cavities, for example. Another modification of the framework is the addition of a catalytic layer which turns the microtube into a self-propelled catalytic micro-engine. Furthermore, the tuneability of the diameter can have applications ranging from nanotools for drilling into cells, to cargo transporters in microfluidic channels. Especially rolled-up microtubes based on low-cost and easy to deposit materials, such as silicon oxides, can enable the exploration of novel systems for several scientific topics. The main objective of this thesis is to combine microfluidic features of rolled-up structures with optical sensor capabilities of silicon oxide microtubes acting as optical ring resonators, and to integrate these into a Lab-on-a-Chip system. Therefore, a new concept of microfluidic integration is developed in order to establish an inexpensive, reliable and reproducible fabrication process which also sustains the optical capabilities of the microtubes. These integrated microtubes act as optofluidic refractrometric sensors which detect changes in the refractive index of analytes using photoluminescence spectroscopy. The thesis concludes with a demonstration of a functional portable sensor device with several integrated optofluidic sensors
Die auf verspannten Dünnschichten basierende „rolled-up nanotechnologie“ ist eine leistungsfähige Methode um dreidimensionale hohle Strukturen (Mikroröhrchen) aus nahezu jeder Art von Material auf einer großen Vielfalt von Substraten herzustellen. Ausgehend von der Möglichkeit der Skalierung des Röhrchendurchmessers und der Modifikation der Funktionalität des Röhrchens durch Einsatz verschiedener Materialien und Oberflächenfunktionalisierungen kann eine große Anzahl an verschiedenen Anwendungen ermöglicht werden. Eine Anwendung behandelt unter anderem on-chip Studien einzelner Zellen wobei die Mikroröhrchen, an die Größe der Zelle angepasste, Reaktionscontainer darstellen. Eine weitere Modifikation der Funktionalität der Mikroröhrchen kann durch das Aufbringen einer katalytischen Schicht realisiert werden, wodurch das Mikroröhrchen zu einem selbstangetriebenen katalytischen Mikro-Motor wird. Hauptziel dieser Arbeit ist es Mikrometer große optisch aktive Glasröhrchen herzustellen, diese mikrofluidisch zu kontaktieren und als Sensoren in Lab-on-a-Chip Systeme zu integrieren. Die integrierten Glasröhrchen arbeiten als optofluidische Ringresonatoren, welche die Veränderungen des Brechungsindex von Fluiden im inneren des Röhrchens durch Änderungen im Evaneszenzfeld detektieren können. Die Funktionsfähigkeit eines Demonstrators wird mit verschiedenen Flüssigkeiten gezeigt, dabei kommt ein Fotolumineszenz Spektrometer zum Anregen des Evaneszenzfeldes und Auslesen des Signals zum Einsatz. Die entwickelte Integrationsmethode ist eine Basis für ein kostengünstiges, zuverlässiges und reproduzierbares Herstellungsverfahren von optofluidischen Mikrochips basierend auf optisch aktiven Mikroröhrchen

Dans cette thèse, deux dispositifs de culture in vitro de cellules ont été développés selon des technologies de microfabrication, qui offrent de nouveaux niveaux de contrôle sur le microenvironnement de la culture cellulaire. Les applications des dispositifs développés dans la recherche sur le cancer et la neurobiologie ont été démontrées, notamment pour l'étude fondamentale de métastases du cancer et le pathfinding axonal de neurones. La puce microfluidique dédiée à la transmigration comprend des microcanaux utilisées pour mimer les capillaires des tissus le long de la trajectoire des cellules cancéreuses lors de la métastase. La transparence optique du dispositif a permis une bonne observation de la déformation et de la migration des cellules dans les capillaires artificiels. Les résultats ont montré que la déformation du noyau de la cellule rigide était une des étapes les fastidieuses du processus de transmigration. Les restrictions physiques modifient la morphologie des cellules, mais elles affectent aussi de manière significative leur profil de migration. D'autres études sur le contenu moléculaire et les propriétés biologiques des cellules transmigrées ont montré que le blocage des modifications des histones par un médicament spécifique peut inhiber la transmigration des cellules cancéreuses dans le microcanal, ce qui pourrait avoir des implications sur la prévention et le traitement du cancer. La puce microfluidique peut également être utilisée pour évaluer la déformabilité de la cellule, qui est un marqueur pronostique potentiel pour le diagnostic du cancer. La puce de la culture de neurones permet la culture de cellules dans un microenvironnement au sein duquel de protéines sont imprimées selon des motifs géométriques précis. Les somas et axones des neurones mis en culture dans le dispositif peuvent être polarisés dans différents environnements fluidiquement isolés sur une longue période. L'extension des axones peut être guidée par des protéines immobilisées sur le substrat de verre. La croissance axonale orientée peut en outre être modulée par un traitement médicamenteux localisé. Les études sur le mécanisme moléculaire sous-jacent ont révélé que ces processus ont été étroitement associés à des protéines synthétisées localement dans les extrémités d'axones en croissance
In this PhD project, two in vitro cell culture devices were developed via microfabrication technologies, which provided entirely new levels of controls over the cell culture microenvironment. The applications of the developed devices in cancer and neurobiology researches were demonstrated, specifically for the fundamental study of cancer metastasis and neural axonal pathfinding. The microfluidic transmigration chip used microchannel structures to mimic the tissue capillaries along the path of cancer cell metastasis. The transparent optical qualities of the device allowed good observation of the deformation and migration of cells in the artificial capillaries. Results showed that deformation of the stiff cell nucleus were the most time-consuming steps during the transmigration process. The physical restrictions not only changed the morphology of the cells, but also significantly affect their migration profile. Further studies on the molecular contents and biological properties of the transmigrated cells showed that blocking the histone modifications by specific drug can inhibit the transmigration of cancer cells in the microchannel, which might have implications on cancer prevention and treatment. The microfluidic chip can also be used to evaluate cell deformability, which is a potential prognostic marker for cancer diagnosis. The neural culture chip integrated microfluidic cell culture and protein patterning techniques. The somas and axons of neurons cultured in the device can be polarized into different fluidically isolated environments for long period, and the extension of the axons can be guided by proteins immobilized on the glass substrate into specific patterns. The oriented axon growth can be further modulated by localized drug treatment. Studies on the underlying molecular mechanism revealed that these processes were closely associated with the proteins synthesized locally in the tips of growing axons

Optical biosensors are increasingly being considered for lab-on-a-chip applications due to their benefits such as small size, biocompatibility, passive behaviour and lack of the need for fluorescent labels. The light guiding mechanisms used by many of them result in poor overlap of the optical field with the target molecules, reducing the maximum sensitivity achievable. This thesis presents a new platform for optical biosensors, namely slotted photonic crystals, which engender higher sensitivities due to their ability to confine, spatially and temporally, the peak of optical mode within the analyte itself. Loss measurements showed values comparable to standard photonic crystals, confirming their ability to be used in real devices. A novel resonant coupler was designed, simulated, and experimentally tested, and was found to perform better than other solutions within the literature. Combining with cavities, microfluidics and biological functionalization allowed proof-of-principle demonstrations of protein binding to be carried out. High sensitivities were observed in smaller structures than most competing devices in the literature. Initial tests with cellular material for real applications was also performed, and shown to be of promise. In addition, groundwork to make an integrated device that includes the spectrometer function was also carried out showing that slotted photonic crystals themselves can be used for on-chip wavelength specific filtering and spectroscopy, whilst gas-free microvalves for automation were also developed. This body of work presents slotted photonic crystals as a realistic platform for complete on-chip biosensing; addressing key design, performance and application issues, whilst also opening up exciting new ideas for future study.

In this master thesis I have been dealt with the design and construction of an instrumental platform that used positioning focused laser beam (so-called optical tweezers) for manipulation with living cells without their damage.

Optofluidic flow-through biosensor devices have been in development for fast bio-target detection. Utilizing the fabrication processes developed by the microelectronics industry, these biosensors can be fabricated into lab-on-a-chip devices with a degree of platform portability. This biosensor technology can be used to detect a variety of targets, and is particularly useful for the detection single molecules and nucleic acid strands. Microfabrication also offers the possibility of production at scale, and this will offer a fast detection method for a range of applications with promising economic viability. The development of this technology has advanced to now warrant a descriptive model that will aid in the design of future iterations. The biosensor consists of multiple integrated waveguides and a microfluidic channel. This platform therefore incorporates multiple fields of study: fluorescence, optical waveguiding, microfluidics, and signal counting. This dissertation presents a model theory that integrates all these factors and predicts a biosensor design's sensitivity. The model is validated by comparing simulated tests with physical tests done with fabricated devices. Additionally, the model is used to investigate and comment on designs that have not yet been allocated time and resources to fabricate. Tangentially, an improvement to the fabrication process is investigated and implemented.

Ce travail s'inscrit dans le contexte du retraitement du combustible irradié dans l'industrie nucléaire. La gestion du combustible usé fait partie des enjeux majeurs de l'industrie nucléaire aujourd'hui. Ses vastes implications sont de nature économique, politique et écologique. Puisque le combustible irradié contient 97 % des matières valorisables, de nombreux pays ont choisi de retraiter le combustible, non tant pour des raisons économiques que pour le besoin de réduire la quantité en déchets radiotoxiques. Le procédé de séparation le plus répandu est connu sous le nom PUREX et consiste à diluer le combustible dans une solution d'acide nitrique afn d'en extraire les matières valorisables, comme notamment l'uranium et le plutonium. Le procédé est soumis à des strictes contrôles qui s'effectuent au présent par prélèvement et analyse manuel des flux radiotoxiques. Il n'existe cependant peu d'outils pour la supervision du procédé en ligne. Ces travaux visent alors à développer un capteur adapté à cet environnement de mesure à la fois acide et ionisant. Les verres borosilicates étant répandus pour leur inertie chimique, nous proposons l'étude d'un capteur optique fondé sur le substrat de verre Borofloat 33 de Schott. Le capteur étudié et réalisé a été fabriqué grâce à deux technologies différentes : l'optique intégrée sur verre par échange d'ions pour la fabrication de fonction de guidage optique, et la microfluidique pour la gestion des flux acides au sein du capteur. L'approche optique permet de répondre aux besoins de polyvalence, de sensibilité et d'immunité au rayonnement électromagnétique. La microfluidique permet, quant à elle, de travailler sur des très faibles volumes d'échantillon, réduisant ainsi la radiotoxicité des flux d'analyse. Le principe de mesure du capteur repose sur l'effet photothermique, induit dans le fluide par absorption optique d'un faisceau laser d'excitation. L'absorption entraîne un changement de l'indice de réfraction du fluide qui est sondé par un interféromètre de Young, intégré sur la puce. Le volume sondé au sein du canal était de (33,5 ± 3,5) pl. Le changement d'indice de réfraction à la limite de détection était de ∆n_min = 1,2 × 10−6 , nous permettant de détecter une concentration minimale de cobalt(II) dans de l'éthanol de c_min = 6 × 10−4 mol/l, équivalent à un coefficient d'absorption de alpha_min = 1,2 × 10−2 cm−1. À la limite de détection du capteur, une quantité de N_min = (20 ± 2) fmol de cobalt(II) peut être détectée. La longueur d'interaction était de li = 14,9 µm et par conséquent l'absorbance minimale détectable égal K_min = (1,56±0,12)×10−5.

1-Microevaporation - Microfluidics is the branch of fluid mechanics dedicated to the study of flows in the channel withdimensions between 1 micron and 100 micron. The object of this chapter is to illustrate the basicprinciples and possible applications of microfluidic chip, called microevaporator. In the first part ofthe chapter, we present a detailed description of the physics of microevaporators using analyticalarguments, and describe some applications. In the second part of the chapter, we present theexperimental protocol of engineering of micro evaporator and different type of microfluidics device.2- On-chip microspectroscopy - The object of this chapter is to illustrate a method to measure absorption spectra during theprocess of growth of our materials in our microfluidic tools. The aim is to make an opticalcharacterization of our micro materials and to carry-out a spatio-temporal study of kineticproperties of our dispersion under study. This instrumental chapter presents the theoretical basis !of the method we used.3-Role of colloidal stability in the growth of micromaterials - We used combined microspectroscopy and videomicroscopy to follow the nucleation and growth ofmaterials made of core-shell Ag@SiO2 NPs in micro evaporators.!We evidence that the growth is actually not always possible, and instead precipitation may occurduring the concentration process. This event is governed by the concentration of dispersion in thereservoir and we assume that its origin come from ionic species that are concentrated all togetherwith the NPs and may alter the colloidal stability en route towards high concentration. 4-Microfluidic-induced growth and shape-up of three-dimensional extended arrays of denselypacked nano particles - In this chapter I present in details microfluidic evaporation experiments to engineer various denselypacked 3D arrays of NPs.5-Bulk metamaterials assembled by microfluidic evaporation - In this chapter I introduced the technique we used (microspot ellipsometry) in close collaborationswith V.Kravets and A.Grigorenko(University of Manchester) and with A.Aradian, P.Barois, A.Baron,K.Ehrhardt(CRPP, Pessac) to characterized the solids made of densely packed NPs. I describe theconstraints that emerge from the coupling between the small size of our materials and the opticalrequirements, the analysis and interpretation of the ellipsometry experiments show that for thematerial with high volume fraction of metal exists the strong electrical coupling between the NPsand the materials display an extremely high refraction index in the near infra-red regime.

As the microelectronics industry pushes microfabrication processes further, the lab-on-a-chip field has continued to piggy-back off the industry's fabrication capabilities with the goal of producing total chemical and biological systems on small chip-size platforms. One important function of such systems is the ability to perform single molecule detection. There are currently many methods being researched for performing single molecule detection, both macro and micro in scale. This dissertation focuses on an optofluidic, lab-on-a-chip platform called the ARROW biosensor, which possesses several advantages over macro-scale single molecule detection platforms. These advantages include an amplification-free detection scheme, cheap parallel fabrication techniques, rapid single molecule detection results, and extremely low volume sample probing, which leads to ultra-sensitive detection. The ARROW biosensor was conceived in the early 2000s; however, since then it has undergone many design changes to improve and add new functionality to the lab-on-a-chip; however, water absorption in the plasma enhanced chemical vapor deposited silicon dioxide has been a problem that has plagued the biosensor platform for some time. Moisture uptake in the oxide layer of the ARROWs leads to loss of waveguiding confinement and drastically decreases the overall sensitivity of the ARROW biosensors. New ARROW designs were investigated to alleviate the negative water absorption effects in the ARROWs. The new waveguide designs were tested for resiliency to water absorption and the buried ARROW (bARROW) design was determined to be the most successful at preventing negative water absorption effects from occurring in the PECVD oxide waveguides. The bARROWs were integrated into the full biosensor platforms and used to demonstrate high sensitivity single molecule detection without any signs of water absorption affecting the bARROWs' waveguiding capabilities. The bARROW biosensors are not only water resistant, they also proved to be the most sensitive biosensors yet fabricated with average signal-to-noise ratios around 80% higher than any previously fabricated ARROW biosensors.

The rise of superbugs, including antibiotic-resistant bacteria, and virus outbreaks, such as the recent coronavirus scare, illustrate the need for rapid detection of disease pathogens. Widespread availability of rapid disease identification would facilitate outbreak prevention and specific treatment. The ARROW biosensor microchip can directly detect single molecules through fluorescence-based optofluidic interrogation. The nature of the microfluidic channels found on optofluidic sensor platforms sets some of the ultimate sensitivity and accuracy limits and can result in false negative test results. Yet higher sensitivity and specificity is desired through hydrodynamic focusing. Novel 3D hydrodynamic focusing designs were developed and implemented on the ARROW platform, an optofluidic lab-on-a-chip single-molecule detector device. Microchannels with cross-section dimensions smaller than 10 μm were formed using sacrificial etching of photoresist layers covered with plasma-enhanced chemical-vapor-deposited silicon dioxide on a silicon wafer. Buffer fluid carried to the focusing junction enveloped an intersecting sample fluid, resulting in 3D focusing of the sample stream. The designs which operate across a wide range of fluid velocities through pressure-driven flow were integrated with optical waveguides in order to interrogate fluorescing particles and confirm 3D focusing, characterize diffusion, and quantify optofluidic detection enhancement of single viruses on chip.

The rapid development of optofluidics, the combination of microfluidics and integrated optics, since its formal conception in the early 2000's has aided in the advance of single-molecule analysis. The optofluidic platform discussed in this dissertation is called the liquid core anti-resonant reflecting optical waveguide (LC-ARROW). This platform uses ARROW waveguides to orthogonally intersect a liquid core waveguide with solid core rib waveguides for the excitation of specifically labeled molecules and collection of fluorescence signal. Since conception, the LC-ARROW platform has demonstrated its effectiveness as a lab-on-a-chip fluorescence biosensor. However, until the addition of optical multiplexing excitation waveguides, the platform lacked a critical functionality for use in rapid disease diagnostics, namely the ability to simultaneously detect different types of molecules and particles. In disease diagnostics, the ability to multiplex, detect and identify multiple biomarkers simultaneously is paramount for a sensor to be used as a rapid diagnostic system. This work brings optofluidic multiplexing to the sensor through the implementation of three specific designs: (1) the Y-splitter was the first multi-spot excitation design implemented on the platform, although it did not have the ability to multiplex it served as a critical stepping stone and showed that multi-spot excitation could improve the signal-to-noise ratio of the platform by ~50,000 times; (2) a multimode interference (MMI) waveguide which took the multi-spot idea and then demonstrated spectral multiplexing capable of correctly identifying multiple diverse biomarkers simultaneously; and, (3) a Triple-Core design which incorporates excitation and collection along multiple liquid cores, enabling spatial multiplexing which increases the number of individual molecules to be identified concurrently with the MMI waveguide excitation. In addition to describing the development of optical multiplexing, this dissertation includes an investigation of another LC-ARROW based design that enables 2D bioparticle trapping, the Anti-Brownian Electrokinetic (ABEL) trap. This design demonstrates two-dimensional compensation of a particle's Brownian motion in solution. The capability to maintain a molecule suspended in solution over time enables the ability to gain a deeper understanding of cellular function and therapies based on molecular functions.

碩士
國立臺灣大學
光電工程學研究所
101
In the past decades, miniaturization has been the driving force for the development of technology. For the medical or biological research, traditionally they have to perform with bulky instruments and have to wait a long time to analyze the results. The research on lab-on-chip devices may lead to portable medical inspection devices. A lab-on-chip device is a versatile chip that integrates different kinds of functionalities into a small area ranging from millimeters to a few centimeters in size. The development of a lab-on-chip device can not only shrinks the experiment area to a small size but also enable a fast and reliable analysis. Recently, the research on single cells analysis is thriving. For this purpose, it is important to distinguish and to sort the cells based on their physical or chemical features. We want to develop a setup that is operating in a miniaturized area and that is able to hold a sample for a certain time so that we can gather its information. The technique of counter propagating dual fiber optical trap is appropriate to our demands, because the divergency of the optical fibers makes them possible to hold a larger sample in an optical trap. Besides, the optical fibers are flexible so that they can be easily integrated. To quantify the optical trapping performance on a chip, we have to establish a model to calculate the forces exerted by a light beam when it interacts with matter. The model is based on a ray tracing approach with the use of a non-sequential ray tracing software. The non-sequential ray tracing method allows for the considerations of any order of the interactions due to the “child rays” caused by reflection, refraction, etc at the interface between the light propagating medium and the trapped object. The model provides a powerful tool that can be used to design and optimize a microfluidic chip. The optical trapping will be operated in a microfluidic environment. Therefore, the trapping forces in the direction of the flow should be higher to resist the forces induced by the flow. The basic design of the fiber trapping on chip can be further improved by implementing microlenses in the chip. The design of the microfluidic chip is limited by the boundary conditions of the fabrication technique. It limits the minimum diameter of the microfluidic channel and the distance between the fiber facet and the trapped position. By considering the limitations and with the aid of the ray tracing model, the radius of curvature and the height of the lenses can be optimized towards the maximum transverse trapping force. The improvement results from the use of the microlenses can be shown by comparing the modeling results of the two optical trapping schemes. In order to show the validity of the ray tracing model, the proof of concept optical setup is under construction. The motions of the trapped object in its equilibrium position should be recorded and analyzed for the quantification of the trapping forces exerted by the laser beam. The novelty of our design, to our knowledge, lies in the use of the integrated microlenses to enhance the performance of an dual fiber optical trap in a microfluidic chip.

Data acquisition and diagnostics for chemical and biological analytes are critical to medicine, security, and the environment. Miniaturized and portable sensing systems are especially important for medical and environmental diagnostics and monitoring applications. Chip scale integrated planar photonic sensing systems that can combine optical, electrical and fluidic functions are especially attractive to address sensing applications, because of their high sensitivity, compactness, high surface specificity after surface customization, and easy patterning for reagents. The purpose of this dissertation research is to make progress toward a chip scale integrated sensing system that realizes a high functionality optical system integration with a digital microfluidics platform for medical diagnostics and environmental monitoring.

This thesis describes the details of the design, fabrication, experimental measurement, and theoretical modeling of chip scale optical sensing systems integrated with electrowetting-on-dielectric digital microfluidic systems. Heterogeneous integration, a technology that integrates multiple optical thin film semiconductor devices onto arbitrary host substrates, has been utilized for this thesis. Three different integrated sensing systems were explored and realized. First, an integrated optical sensor based upon the heterogeneous integration of an InGaAs thin film photodetector with a digital microfluidic system was demonstrated. This integrated sensing system detected the chemiluminescent signals generated by a pyrogallol droplet solution mixed with H2O2 delivered by the digital microfluidic system.

Second, polymer microresonator sensors were explored. Polymer microresonators are useful components for chip scale integrated sensing because they can be integrated in a planar format using standard semiconductor manufacturing technologies. Therefore, as a second step, chip scale optical microdisk/ring sensors integrated with digital microfluidic systems were fabricated and measured. . The response of the microdisk and microring sensing systems to the change index of refraction, due to the glucose solutions in different concentrations presented by the digital microfluidic to the resonator surface, were measured to be 95 nm/RIU and 87nm/RIU, respectively. This is a first step toward chip-scale, low power, fully portable integrated sensing systems.

Third, a chip scale sensing system, which is composed of a planar integrated optical microdisk resonator and a thin film InGaAs photodetector, integrated with a digital microfluidic system, was fabricated and experimentally characterized. The measured sensitivity of this sensing system was 69 nm/RIU. Estimates of the resonant spectrum for the fabricated systems show good agreement with the theoretical calculations. These three systems yielded results that have led to a better understanding of the design and operation of chip scale optical sensing systems integrated with microfluidics.

Dissertation

碩士
中原大學
機械工程研究所
104
This study presents a novel microfluidic blood typing chip. The blood sample and reagents are driven by the capillary force, surface tension and gravity, without requiring any apparatuses for fluid manipulation. Chip fabrication was based on the photolithography process to produce a mold, followed by casting PDMS into the mold. Finally, the PDMD layer was bonded with a glass substrate. For blood typing measurement, an oscillator was used to reduce the precipitation time of blood agglutination. At the bottom of reaction vessel, a V-shape was designed. In addition, a vent connecting to the V-shaped vessel was used to release gas and prevent the occurrence of bubbles. Bioassay was based on the test protocol of manual polybrene (MP) technique. However, we used diluted whole blood in our experiments instead of centrifuged 3%-diluted red blood cells (RBC), which is used in the MP method. After the assay, the light intensity was detected to determine the result of blood typing.The experimental results show in this proposed chip the sample and reagents can be manipulated for the blood reaction without extra forces. The blood agglutination can be effectively precipitated. The diluted whole blood gives the same assay result as the centrifuged 3%-diluted RBC. We also concluded the optimal position for measurement in this proposed chip.

An all-optical micromanipulation technique is presented in the framework of precise cell selection within a cell culture and multiplexed transport capabilities for microfluidic single cell analysis applications. The technique was developed by combining an optical tweezer setup with a novel integrated waveguide cell propulsion method referred to as end-face waveguide propulsion (EFWP). The EFWP technique delivers optical forces to a particle generating thrust. The thesis is divided into two sections: simulation and experimental validation. In the first section a new simulation technique based on ray optics theory (ROT) and the beam propagation method (BPM) is used to predict particle velocity and trajectory along a microfluidic propagation channel. In this work, the ROT-BPM technique is used to analyse and optimize the waveguide geometry to maximize particle velocity. Analysis of the impact of common microchip manufacturing limitations on velocity is performed to determine acceptable fabrication process tolerances. The second section presents experimental results of polymer microspheres and acute myeloid leukemia (AML) cells as biological targets. The experimental results are compared with simulations performed in the first section. Correction factors are added to the simulations to reflect the experimental device parameters. Thermal e_ects due to photon absorption within the fluidic channels are also investigated and corrected for. The final analysis indicates that the ROT-BPM technique developed in this work can be used to adequately predict particle velocity and trajectory path. EFWP currently delivers the fastest particle velocities compared to other optical micromanipulation techniques currently available in microfluidic applications. While the technique is focused on addressing chemical cytometry precise particle selectivity and high throughput needs, EFWP can also be used in many other single cell applications.

碩士
國立成功大學
工程科學系碩博士班
96
Fiber-dual-beam optical trap has been widely used for many applications such as the trapping or manipulation of micro-particles and cell biomechanics study. However, for these applications, precise alignment of a pair of optical fibers still remains a challenge. To tackle this issue, this study proposes a two-axis active optical-fiber manipulator for on-chip fiber alignment and optical dual beam trap applications. The chip comprising of a flow channel, air chambers, fiber channels, controllable moving walls and membrane microstructures were fabricated by using micro-electro-mechanical-systems (MEMS) technology. By adjusting air pressures to control the deflection of the pneumatic chambers placed orthogonal to and underneath the fiber channels, accurate alignment of a pair of co-axial optical-fibers, which was indicated by maximizing fiber-to-fiber coupling efficiency measured in real-time, has been achieved. A maximum displacement of a buried fiber as large as 13 μm at an applied pressure of 40 psi for one air chamber has been demonstrated. The maximum coupling efficiency for two single-mode optical-fibers facing each other at a distance of 200 μm was measured to be 4.1%. The multiple cells trapping manipulation by using the proposed chip also has been demonstrated. In addition, this study also developed a new microfluidic chip integrating the proposed fiber alignment device, cell transportation and pre-positioning systems utilizing MEMS techniques. The developed microfluidic chip is capable of delivering and pre-positioning cells in a predefined trapping zone, followed by manipulation of buried optical fibers and dual beam lasers for optical trapping, manipulation and stretcher. Experimental results showed that by integrating three micropumps connected in series, the cell samples were automatically delivered into the flow focusing area and then transported to the trapping zone. A single cell can be confined by micro-valves and then elevated towards the optical axis by a negative-DEP force operated at 20 Vp-p and 900 KHz. Finally, a red blood cell was successfully trapped, manipulated and stretched by active fiber manipulators and dual beam optical trap using the proposed microfluidic system. The developed microfluidic chip is promising for further applications that require trapping, manipulation and biomechanical analysis of a single cell or particle. Furthermore, the developed fibers alignment system is not only promising for applications requiring co-axial fibers for in-line optical analysis, but can also be easily integrated with other microfluidic systems such as capillary electrophoresis or micro flow cytometers for cell, protein, and DNA analysis.

碩士
國立清華大學
動力機械工程學系
103
Cell fusion is a critical course for all sort of biomedical applications including cell reprogramming, hybridoma formation, cancer immunotherapy, and tissue regeneration. It can be realized by using biological, chemical, or physical methods. However, efficiency and yields are limited by unstable cell contact and random cell pairings in traditional methods. Hence, improving cell contact and cell pairing are the two key factors to enhance efficiency and yields of cell fusion. This study therefore reported a new approach called optically-induced cell fusion (OICF) which integrates cell-pairing microstructures and optically-induced, localized electrical field to achieve precise cell fusion with high yields and high efficiency. By projecting light patterns on a photoconductive film (hydrogen-rich amorphous silicon, a-Si: H) coated on an indium-tin-oxide (ITO) glass while an alternating-current (AC) electric field was applied on the top and bottom ITO glasses, “virtual” electrodes would be constructed accordingly. In fact, this method could be used on several biomedical applications, including cell manipulation, cell separation, cell lysis and electroporation. Therefore, a locally enhanced electric field would be induced and the pairing cells could be precisely fused by the virtual electrodes. In this study, 57% cell paring rate and 87% fusion efficiency were achieved. Therefore, OICF is a promising method to succeed in cell fusion with high efficiency and high yields.

碩士
輔仁大學
物理學系碩士班
104
In this thesis, we combined the surface plasmon resonance (SPR) based side-polished D-type optical fiber sensor with microfluidic chips to measure the refractive indices of different liquids. The D-type OFS is based on the Kretchmann’ s configuration. By using the optical fiber to guide the light source to the side-polished region with deposited gold film, surface evanescent wave excites the gold film to attain the SPR phenomenon. A CO2 laser scriber was used to ablate polymethylmethacrylate (PMMA) substrates for making the microfluidic chips. These chips are cheap and easy to be fabricated. We combined the microfluidic chip with the D-type optical fiber to measure the spectrum peak of liquids with different refractive indices. We changed a variety of refractive indices for observing the difference in the spectrum peak and calculate the corresponding sensitivity. In our experiments, four sets of samples were measured: 1.ethanol mixed with water; 2.methanol mixed with water; 3.ethanol and methanol mixed with water; 4.different concentrations of glucose solution. Liquids with different refractive indices were flowed into the microfluidic chip for observing their effects on the spectrum peak. The sensitivity of the present OFS was calculated to be in the order of 10-6 RIU. We believed that, in the future, this microfluidic chip-integrated OFS can serve as a biosensor to monitor subtle changes in biological samples such as blood glucose, allergen, and biomolecular interactions.

博士
國立交通大學
機械工程學系
99
This study presents a microfluidic platform fabricated by optical disc process for microcapsules generation. In the previous reports, the generation of microemulsion adopted microfluidic methods. The microfluidic chips were fabricated by casting process or by adopting CO2 laser engraving on plastic sheet. However, microfluidic chip of PDMS material is too soft, and can easily induce microchannel clogged. Furthermore, the cycle time for manufacturing the microfluidic substrate is over 3~4 hours. As for CO2 laser engraving, the surface of the microfluidic channels was too rough, uneven, deformed and different from the original designs. Besides, the size of the channels was limited by laser machine, and the cycle time for manufacturing the microfluidic substrate is over 10 minutes. The cycle time for both casting process and CO2 laser engraving process is too long. The long cycle time will be a drawback for mass production. Therefore, we present a new process of optical disc to fabricate microchannels of mold insert and adopt the micromolding technique of optical disc to prevent roughness, unevenness, deformation, and clog of microchannels. This paper is divided into three sections. (1) a design of microfluidic chip; (2) the fabrication of microfluidic mold insert and microfluidic chip; (3) generation of microemulsion droplet. In the design of microfluidic chip section, the depth of microchannels were 50/200 μm respectively and CFD-RC simulation software was adopted to simulate the motion of fluids and emulsions in microfluidic channels. In the fabrication of microfluidic mold insert, we propose a new process of optical disc to manufacture microfluidic mold insert. This new process can prevent the damage on the mirror plate of the mold caused by the traditional process of optical disc. The mold system is composed of a mold insert (stamper) holder and a vacuum system, which is used to join the mold insert with the mold. In this way, the time to change the stamper is drastically decreased. Therefore, it can improve the utility rate of injection molding. In the microfluidic chips of injection molding, we investigate the influence of controlled factors on the quality properties (depth of replication rate, width deviation, birefringence, tilt and surface roughness) of microfluidic chips. Those controlled factors include mold temperature, cylinder temperature, clamping force and injection speed. In the microemulsion generation, we use cross-junction microchannel to form uniform water-in-oil (w/o) emulsions. We prove that the size of these emulsion drops can be easily controlled by adjusting the ratio of disperser phase flow / continue phase flow. These emulsion drops, consisting of 1.5% (w/v) sodium alginate (Na-alginate), are then dripped into a solution containing 20% (w/v) calcium chloride (CaCl2) to create Ca-alginate microcapsules in an efficient manner. We apply Taguchi method to investigate the influence of controlled factors on the size of microemulsion drops which include the flow rate of dispersed phase flow, flow rate ratio, viscosity and surfactant concentration. The simulation results demonstrate that the bigger the flow rate ratio (continue phase flow /dispense phase flow) is, the smaller the size of microemulsion drops is, and the faster the speed of the generation microemulsion will become. In the fabrication mold insert, we successfully fabricate two layer of microfluidic mold insert, 300 um in thickness and the back side of mold insert is smooth and even. The proposed method will not damage the mirror of the mold. In the fabrication of microfluidic chips, we adopt DOE method to investigate the influence of controlled factors on the quality properties. The results indicated 2nd clamping force and injection speed have a greater effect on depth replication rate, width deviation and surface roughness. The injection speed and cylinder temperature have a greater effect on birefringence and the mold temperature has a greater effect on vertical deviation. The cycle time of injection molding is 4 seconds. It can be reduced to more than tenfold compared with the traditional ones. In the generation of microemulsion drops, we apply Taguchi method to investigate the influence of controlled factors on the size of microemulsion drops. The results show that the smallest size is 19.58 μm and coefficient of deviation of emulsion drop is 1.95%, the size of emulsion drop is 23.46% lower and the size deviation of drop is 20.73% lower than original design. We demonstrate that the Au nanoparticles and Immunoglobulins are encapsulated into Ca-alginate microcapsules. In this paper, we successfully devise the new method of optical disc process to fabricate microfluidic chips. The cycle time of microfluidic chips is 4 seconds. It is faster than traditional methods. The proposed microfluidic platform is capable of generating relatively uniform emulsions and has the advantages of active control of the emulsions diameter, a simple and low cost process, and a high throughput, highly efficient and suitable for mass production.

碩士
國立臺灣科技大學
機械工程系
106
This study aims to develop an automated optical inspection system for measuring microchannel dimension. Research about microfluidic chip has flourished in recent years. There will be more and more related products which are important for dimension appearing. Therefore we developed a non-destructive and non-contact measurement for bonded microfluidic chip to verify whether the microchannel dimension meets the tolerance specification. The data measured with measurement system we’ve developed is compared with the reference value measured with toolmaker microscope. The error obtained after comparing reaches ± 2 %.

The three-dimensional (3-D) writing capability of a high repetition rate (1 MHz) fiber-amplified femtosecond laser with a wavelength of 522 nm was harnessed together with wet-chemical etching for laser-patterning of 3-D optofluidic microsystems in fused silica glass, by the method of Femtosecond Laser Irradiation followed by Chemical Etching (FLICE). Selective chemical etching of laser irradiated glass with dilute hydrofluoric acid (HF) enabled micro-fabrication of high aspect-ratio embedded micro-channels and fine-period 3-D glass meshes in a 3-D inverted woodpile (IWP) arrangement that permitted high density lab-on-a-chip (LOC) integration of flow channels, reservoirs, glass chromatography columns, and optical circuit devices. Optical waveguides, reservoirs, micro-channels, and IWP structures were first laser patterned and followed by selective wet etching controlled by the polarization orientation of the writing laser. With the laser polarization perpendicular to the scanning direction, the volume nanogratings were aligned perpendicular to glass surfaces to facilitate HF etching and thus created designer shaped micro-channels with the smoothest sidewall surfaces measured at present and terminated with open reservoirs. An array of vertical access holes spaced periodically apart facilitated etching of continuous and highly uniform buried channels of unrestricted length in the glass to interconnect flow channels and reservoirs. Alternatively, laser polarization parallel to the scan direction provided low-loss optical waveguides with nanograting walls resisting the acid etching, providing a convenient one-step laser scanning process of optofluidic microsystems prior to wet etching. For the first time, dual-channel capillary electrophoresis was demonstrated by simultaneous fluorescent detection of separating dyes in a 3-D microsystem having over- and under-passing crossed channels in fused silica. In addition, an on-chip particle counting device based on capillary force to drive analytes through an embedded micro-channel into a calibrated reservoir for particle counting was designed and demonstrated. Further, a new type of glass mesh structure is presented where a 3-D IWP micro-channel array with diamond-like symmetry was integrated inside a micro-channel for capillary electrophoretic chromatography. The FLICE technique thus enables rapid prototyping of fully integrated 3-D optofluidic systems in bulk fused silica glasses for numerous applications, and these provide the groundwork and open new 3-D design approaches for advanced microsystems in the future.

碩士
國立臺北科技大學
工業工程與管理系碩士班
102
In recent years, the emerging technologies such as DNA sequencing, protein analysis and micro-electronics draw a lot of research attention. The application of the micro-electronics is among the most important ones. The sensitivity of machine has reached a certain level. Due to lengthy inspecting time, difficulty of carrying, expensive cost, some inspecting devices are not universal. The concept of miniaturization becomes very critical to the development of micro-electronic technology which integrates the sampling, pretreatment, detachment, testing process into the micro-fluidic chip that gives an impetus to the sample to move between the micro channels of the parts to detect by centrifugal force and impressed voltage. The main advantage of micro-fluidic chip is to increase the performance, quality, reliabilityand reduce the sample consumption and cost. The applications of micro-fluidic chip include new medicine development, disease examination, DNA sequencing, protein analysis, infection cause of disease, blood sieves examines, environment examination, food examination and so on. A lot of cost may happen if the micro-fluidic chip manufacturing process does not result in high quality and yield rate.In this project, we proposed a model which tries to optimize the parameters of the manufacturing process of micro-fluidic chips.The Taguchi method is used to reduce the number of experiments. Genetic algorithm, differential evolution algorithm and grey theory are utilized to optimize the parameters of manufacturing process. The result of gray relational analysis obtains the optimize the parameters of the manufacturing process of micro-fluidic chips and the effect of each parameters.the most important parameters of the manufacturing process of micro-fluidic chips is the embossing temperature. The result of the algorithms are apparently improved the result of the original process.