Zeolites are porous aluminosilicates that occur both naturally and synthetically, having numerous applications in catalysis, adsorption and separations. Despite over a half century of characterization and synthetic optimization of hundreds of frameworks, the exact mechanism of synthesis remains highly contested, with crystallization typically occurring under transport-limited regimes. In this work, a microcrystallization reactor working under segmented oscillatory flow has been designed to produce a semi-continuous flow of zeolite A. The fast injection of the reactants in a mixing section forms droplets of aqueous precursors in a stream of paraffin, dispersing microdroplets and avoiding any clog from occurring in the system. The crystallization occurred in the system at atmospheric pressure and isothermal conditions (65ºC). This allowed for a rather slow crystallization kinetics which was important to study and highlight the different crystallization mechanisms between flow and batch synthesis. The morphology, size distributions, crystallinity, and porosity were examined by ex-situ characterization of the samples by scanning electron microscopy, X-ray diffraction, Raman spectroscopy, and N2 Physisorption to support the conclusions drawn. The size distribution of the particles achieved in the flow reactor was conclusively narrower than the distribution achieved in the batch reactor. The average size of the crystals for both synthesis methods is reported as 400 nm and the crystallinity achieved was comparable between the two. However, the morphology was quite different between the two systems, the flow products having a much higher mesoporosity due to the presence of crystal aggregates at high crystallinity when compared to the batch crystals. Finally, extended crystallization times leads to a decline of the crystallinity of the product, which might be explained by the metastable state of zeolites in solution.

Point-of-care (POC) tests can improve the management of infectious diseases and clinical outcomes, through prompt diagnosis and appropriate delivery of treatments for preventable and treatable diseases, especially in resource-limited settings where health care infrastructure is weak, and access to quality and timely medical care is challenging. Microfluidics or lab-on-chip technology is appropriate for POC tests when general design constraints such as integration, portability, low power consumption, automation, and ruggedness are met. Although many POC tests have been designed for use in developed countries, they might not be readily transferable to resource-limited settings. These new technologies need to be accessible, affordable and practical to be implemented at resource-limited settings to save lives in developing countries. The overall goal of this dissertation is to develop microfluidic diagnostic devices which are practical and reliable for global health. We first focused on immunoassays, an important class of diagnostic tests which utilize antibodies to quantify host immunity or pathogen protein markers. We developed and evaluated a rapid, accurate, multiplexed, and portable microfluidic immunoassay for diagnosis of HIV and syphilis on hundreds of archived specimens (whole blood, plasma, and sera). Our assay exhibited performance equal to lab-based immunoassays in less than 20 minutes. In addition, our technique quantified signals using a handheld instrument, allowing for objective measurements as opposed to current rapid HIV tests which require subjective interpretation of band intensities. We further integrated three important off-chip processes in a diagnostic test - liquid handling, optical signal detection, and data communication – in a low-cost, versatile, handheld instrument capable of performing immunoassays on reagent-loaded (i.e. “ready-to-run”) cassettes at high analytical performance characteristic of ELISA but with the speed, portability and ease-of-use of a rapid test. We also evaluated this immunoassay device in Rwanda on archived samples and achieved analytical performance comparable to that of benchtop standards. To simplify the user interface and reduce the cost of the diagnostic device, we integrated our microfluidic immunoassay with a smartphone to replace computers or high-cost processors for diagnostic devices in low-resource settings. Our low-cost ($34), smartphone-supported device for a multiplexed immunoassay detected three antibody markers from HIV, treponemal- and non-treponemal syphilis from fingerstick whole blood simultaneously in 15 minutes. This device was designed to eliminate the number of manual steps, through the use of lyophilized secondary antibodies and anti-coagulant, preloaded reagents on cassette, and an automatic result readout. A step-by-step user guide was included on the smartphone to make the device simple enough to be used by an untrained operator. The analytical performance of the device was evaluated in Rwanda by local health care workers. We also accessed user experiences for improvement of the device in future. While immunoassays offer rapid and accurate diagnosis for infectious diseases, various infections cannot be confirmed using protein markers. Due to increasing clinical demand for detection of DNA and RNA signatures for diagnosis and monitoring of patients in resource-limited settings, we also explored how microfluidic and nanoparticle technologies can improve nucleic acid amplification test at the point of care. Nucleic acid tests are arguably some of the most challenging assays to develop due to additional steps required for sample pre-treatment (e.g. cell sorting, isolation, and lysis, as well as nucleic acid extraction), signal amplification (due to low physiological concentrations, target contamination, and instability) and product detection. Here we developed a sputum processor to isolate and lyse mycobacteria (M.smegmatis) from a more complex sample matrix, using magnetic beads-based target isolation to replace the need of a centrifuge or other complicated sample preparation technique. We also investigated a technique to detect Mycobacterium tuberculosis using multiplex polymerase chain reaction (PCR) and silver-gold amplification detection.

Precision medicine represents a shift in medicine where large datasets are gathered for massive patient groups to draw correlations between disease cohorts. An individual patient can then be compared to these large datasets to determine the best treatment strategy. While electronic health records and next generation sequencing techniques have enabled much of the early applications for precision medicine, the human genome only represents a fraction of the information present and important to a person’s health. A person’s proteome (peptides and proteins) and glycome (glycans and glycosylation patterns) contain biomarkers that indicate health and disease; however, tools to detect and analyze such biomarkers remain scarce. Thus, precision medicine databases are lacking a major source of phenotypic data due to the absence of available methods to explore these domains, despite the potential of such data to allow further stratification of patients and individualized therapeutic strategies. Available methods to detect non-nucleic acid biomarkers are currently not well suited to address the needs of precision medicine. Mass spectrometry techniques, while capable of generating high throughput data, lack standardization, require extensive preparative steps, and have many sources of errors. Immunoassays rely on antibodies which are time consuming and expensive to produce for newly discovered biomarkers. Aptamers, analogous to antibodies but composed of nucleotides and isolated through in vitro methods, have potential to identify non-nucleic acid biomarkers but methods to isolate aptamers remain labor and resource intensive and time consuming. Recently, microfluidic technology has been applied to the aptamer discovery process to reduce the aptamer development time, while consuming smaller amounts of reagents. Methods have been demonstrated that employ capillary electrophoresis, magnetic mixers, and integrated functional chambers to select aptamers. However, these methods are not yet able to fully integrate the entire aptamer discovery process on a single chip and must rely on off-chip processes to identify aptamers. In this thesis, new approaches for aptamer selection are developed that aim to integrate the entire process for aptamer discovery on a single chip. These approaches are capable of performing efficient aptamer selection and polymerase chain reaction based amplification while utilizing highly efficient bead-based reactions. The approaches use pressure driven flow, electrokinetic flow or a combination of both to transfer aptamer candidates through multiple rounds of affinity selection and PCR amplification within a single microfluidic device. As such, the approaches are capable of isolating aptamer candidates within a day while consuming <500 µg of a target molecule. The utility of the aptamer discovery approach is then demonstrated with examples in precision medicine over a broad spectrum (small molecule to protein) of molecular targets. Seeking to demonstrate the potential of the device to generate probes capable of accessing the human glycome (an emerging source of precision medicine biomarkers), aptamers are isolated against gangliosides GM1, GM3, and GD3, and a glycosylated peptide. Finally, personalized, patient specific aptamers are isolated against a multiple myeloma patient serum sample. The aptamers have high affinity only for the patient derived antibody.

Xiao, Zigang. / "October 2010." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 62-66). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgement --- p.vi / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Microfluidic Technology --- p.2 / Chapter 1.1.1 --- Continuous Flow Microfluidic System --- p.2 / Chapter 1.1.2 --- Digital Microfluidic System --- p.2 / Chapter 1.2 --- Pin-Constrained Biochips --- p.4 / Chapter 1.2.1 --- Droplet-Trace-Based Array Partitioning Method --- p.5 / Chapter 1.2.2 --- Broadcast-addressing Method --- p.5 / Chapter 1.2.3 --- Cross-Referencing Method --- p.6 / Chapter 1.2.3.1 --- Electrode Interference in Cross-Referencing Biochips --- p.7 / Chapter 1.3 --- Computer-Aided Design Techniques for Biochip --- p.8 / Chapter 1.4 --- Placement Problem in Biochips --- p.8 / Chapter 1.5 --- Droplet Routing Problem in Cross-Referencing Biochips --- p.11 / Chapter 1.6 --- Our Contributions --- p.14 / Chapter 1.7 --- Thesis Organization --- p.15 / Chapter 2 --- Literature Review --- p.16 / Chapter 2.1 --- Introduction --- p.16 / Chapter 2.2 --- Previous Works on Placement --- p.17 / Chapter 2.2.1 --- Basic Simulated Annealing --- p.17 / Chapter 2.2.2 --- Unified Synthesis Approach --- p.18 / Chapter 2.2.3 --- Droplet-Routing-Aware Unified Synthesis Approach --- p.19 / Chapter 2.2.4 --- Simulated Annealing Using T-tree Representation --- p.20 / Chapter 2.3 --- Previous Works on Routing --- p.21 / Chapter 2.3.1 --- Direct-Addressing Droplet Routing --- p.22 / Chapter 2.3.1.1 --- A* Search Method --- p.22 / Chapter 2.3.1.2 --- Open Shortest Path First Method --- p.23 / Chapter 2.3.1.3 --- A Two Phase Algorithm --- p.24 / Chapter 2.3.1.4 --- Network-Flow Based Method --- p.25 / Chapter 2.3.1.5 --- Bypassibility and Concession Method --- p.26 / Chapter 2.3.2 --- Cross-Referencing Droplet Routing --- p.28 / Chapter 2.3.2.1 --- Graph Coloring Method --- p.28 / Chapter 2.3.2.2 --- Clique Partitioning Method --- p.30 / Chapter 2.3.2.3 --- Progressive-ILP Method --- p.31 / Chapter 2.4 --- Conclusion --- p.32 / Chapter 3 --- CrossRouter for Cross-Referencing Biochip --- p.33 / Chapter 3.1 --- Introduction --- p.33 / Chapter 3.2 --- Problem Formulation --- p.34 / Chapter 3.3 --- Overview of Our Method --- p.35 / Chapter 3.4 --- Net Order Computation --- p.35 / Chapter 3.5 --- Propagation Stage --- p.36 / Chapter 3.5.1 --- Fluidic Constraint Check --- p.38 / Chapter 3.5.2 --- Electrode Constraint Check --- p.38 / Chapter 3.5.3 --- Handling 3-pin net --- p.44 / Chapter 3.5.4 --- Waste Reservoir --- p.45 / Chapter 3.6 --- Backtracking Stage --- p.45 / Chapter 3.7 --- Rip-up and Re-route Nets --- p.45 / Chapter 3.8 --- Experimental Results --- p.46 / Chapter 3.9 --- Conclusion --- p.47 / Chapter 4 --- Placement in Cross-Referencing Biochip --- p.49 / Chapter 4.1 --- Introduction --- p.49 / Chapter 4.2 --- Problem Formulation --- p.50 / Chapter 4.3 --- Overview of the method --- p.50 / Chapter 4.4 --- Dispenser and Reservoir Location Generation --- p.51 / Chapter 4.5 --- Solving Placement Problem Using ILP --- p.51 / Chapter 4.5.1 --- Constraints --- p.53 / Chapter 4.5.1.1 --- Validity of modules --- p.53 / Chapter 4.5.1.2 --- Non-overlapping and separation of Modules --- p.53 / Chapter 4.5.1.3 --- Droplet-Routing length constraint --- p.54 / Chapter 4.5.1.4 --- Optical detector resource constraint --- p.55 / Chapter 4.5.2 --- Objective --- p.55 / Chapter 4.5.3 --- Problem Partition --- p.56 / Chapter 4.6 --- Pin Assignment --- p.56 / Chapter 4.7 --- Experimental Results --- p.57 / Chapter 4.8 --- Conclusion --- p.59 / Chapter 5 --- Conclusion --- p.60 / Bibliography --- p.62

Chau, Long Ho. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 73-82). / Abstract also in Chinese. / ABSTRACT --- p.III / 摘要 --- p.IV / PUBLICATIONS CORRESPOND TO THIS THESIS --- p.V / ACKNOWLEDGEMENTS --- p.VI / TABLE OF CONTENTS --- p.VII / LIST OF FIGURES --- p.IX / LIST OF TABLES --- p.XI / ABBREVIATIONS AND NOTATIONS --- p.XII / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Background --- p.1 / Chapter 1.1.1 --- Types of Biofuel Cells --- p.1 / Chapter 1.1.2 --- Properties of Using Enzymes in Bio-energy Generation Systems --- p.2 / Chapter 1.1.3 --- Application of Bio-energy Generation Systems --- p.3 / Chapter 1.2 --- Objectives of the Project --- p.4 / Chapter 1.3 --- Organization of the Thesis --- p.5 / Chapter CHAPTER 2 --- LITERATURE REVIEW --- p.7 / Chapter 2.1 --- Working Principle of a Typical Fuel Cell --- p.7 / Chapter 2.2 --- Introduction of Enzymes and Co-enzymes --- p.9 / Chapter 2.3 --- Functions and Activities of Glucose Dehydrogenase (GDH) --- p.10 / Chapter 2.4 --- Functions and Activities of Laccase --- p.11 / Chapter 2.5 --- Introduction of Carbon Nanotubes (CNTs) --- p.12 / Chapter 2.6 --- Introduction of Gold Nanoparticles (AuNPs) --- p.13 / Chapter 2.7 --- Introduction of PdNPs --- p.14 / Chapter 2.8 --- Summary of Literature Review --- p.15 / Chapter CHAPTER 3 --- WORKING PRINCIPLE OF AN ENZYMATIC BIOFUEL CELL --- p.16 / Chapter 3.1 --- Enzymatic Biofuel Cell Using Glucose as a Fuel --- p.16 / Chapter 3.2 --- Deterministic Factors of the Fuel Cell´ةs Performance --- p.19 / Chapter 3.3 --- Energy --- p.22 / Chapter 3.3 --- Chapter Conclusion --- p.23 / Chapter CHAPTER 4 --- ENZYMATIC BIOFUEL CELL DESIGN --- p.24 / Chapter 4.1 --- Engineering Structure of the EBFC --- p.24 / Chapter 4.2 --- Chemical Structures of the EBFCs --- p.25 / Chapter 4.2.1 --- 1st Structure of EBFC - Au-Ll-CNTs-Ll-AuNPs-L2-{(GDH-NAD)/Laccase} --- p.26 / Chapter 4.2.2 --- 2nd Structure of EBFC - Au-Ll-CNTs-Ll-AuNPs-L2-{GDH/Laccase} --- p.28 / Chapter 4.2.3 --- 3rd Structure of EBFC- Pd-Ll-CNTs-Ll-AuNPs-L2-{(GDH-NAD)/Laccase} --- p.28 / Chapter 4.2.4 --- 4th Structure of EBFC - Pd-Ll -A uNPs-L2-{(GDH~NAD)/Laccase} --- p.29 / Chapter 4.2.5 --- 5th Structure of EBFC- Au-Ll-CNTs~L4'{(GDH-NAD)/Laccase} --- p.30 / Chapter 4.2.6 --- 6th Structure ofEBFC 一 Au-Ll-CNTs-{L3- NAD-GDH/L4-Laccase} --- p.31 / Chapter 4.3 --- Chapter Conclusion --- p.33 / Chapter CHAPTER 5 --- FABRICATION AND CHARACTERIZATION OF EBFCS --- p.34 / Chapter 5.1 --- Materials Preparation --- p.34 / Chapter 5.1.1 --- Preparation of Linker 1 --- p.34 / Chapter 5.1.2 --- Preparation of Linker 2 --- p.35 / Chapter 5.1.3 --- Preparation of Linker 4 --- p.35 / Chapter 5.1.4 --- Purification of Linkers --- p.35 / Chapter 5.1.5 --- Verification of Linkers --- p.36 / Chapter 5.2 --- 3-D Micro Electrode Fabrication --- p.37 / Chapter 5.3 --- Electrode Modification --- p.40 / Chapter 5.3.1 --- 1st Structure of EBFC --- p.40 / Chapter 5.3.2 --- 2nd Structure of EBFC --- p.41 / Chapter 5.3.3 --- 3rd Structure of EBFC --- p.41 / Chapter 5.3.4 --- 4th Structure of EBFC --- p.42 / Chapter 5.3.5 --- 5th Structure of EBFC --- p.42 / Chapter 5.3.6 --- 6th Structure of EBFC --- p.42 / Chapter 5.4 --- Characterization --- p.43 / Chapter 5.4.1 --- Atomic Force Microscopy (AFM) --- p.43 / Chapter 5.4.2 --- Scanning Electron Microscopy (SEM) & Energy-Disperse X-ray Spectroscopy (EDX) --- p.46 / Chapter 5.4.3 --- Cyclic Voltammetry (CV) --- p.47 / Chapter 5.5 --- Chapter Conclusion --- p.52 / Chapter CHAPTER 6 --- RESULTS OF EBFCS --- p.53 / Chapter 6.1 --- Experimental Setup --- p.53 / Chapter 6.2 --- Results --- p.55 / Chapter 6.2.1 --- Results of 1st EBFC --- p.55 / Chapter 6.2.2 --- Results of 2nd EBFC --- p.57 / Chapter 6.2.3 --- Results of 3rd EBFC --- p.58 / Chapter 6.2.4 --- Results of 4th EBFC --- p.60 / Chapter 6.2.5 --- Results of 5th EBFC --- p.60 / Chapter 6.2.6 --- Results of 6th EBFC --- p.65 / Chapter 6.3 --- Chapter Conclusion --- p.67 / Chapter CHAPTER 7 --- CONCLUSION --- p.69 / Chapter 7.1 --- Conclusion --- p.69 / Chapter 7.2 --- Future Work for the Biofuel Cell Project --- p.70 / Chapter 7.2.1 --- Study the Effect of Temperature Change --- p.70 / Chapter 7.2.2 --- Study the Effect of the Change of pH in Substrates --- p.70 / Chapter 7.2.3 --- Further Modified the Electrodes to Enhance the Output Power --- p.70 / APPENDIX --- p.71 / BIBLIOGRAPHY --- p.73

Han, Zuoyan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 43-46). / Abstracts in English and Chinese. / Abstract (Chinese) --- p.i / Abstract (English) --- p.ii / Acknowledgements --- p.iv / Glossary --- p.vi / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Physics parameter viscosity --- p.1 / Chapter 1.2 --- PDMS microfluidics device --- p.4 / Chapter Chapter 2 --- PDMS viscometer for microliter Newtonian fluid / Chapter 2.1 --- Introduction --- p.5 / Chapter 2.2 --- Configuration of the PDMS Viscometer --- p.8 / Chapter 2.3 --- Mechanism of passive pumping --- p.10 / Chapter 2.4 --- Theory of the PDMS viscometer --- p.11 / Chapter 2.5 --- Viscosity Measurement in PDMS Viscometer --- p.15 / Chapter 2.5.1 --- Preparation of Blood Plasma --- p.16 / Chapter 2.5.2 --- Measurements of Glycerol Solutions --- p.16 / Chapter 2.5.3 --- Measurements of Protein Solution and Blood Plasma --- p.19 / Chapter 2.5.4 --- Measurements of Organic Solvents --- p.19 / Chapter 2.6 --- Data Analysis --- p.21 / Chapter 2.7 --- Dynamic Contact Angle --- p.22 / Chapter 2.8 --- Conclusions --- p.23 / Chapter Chapter 3 --- PDMS viscometer for microliter Non-Newtonian fluid / Chapter 3.1 --- Introduction --- p.25 / Chapter 3.2 --- Configuration of the PDMS viscometer --- p.29 / Chapter 3.3 --- Theory for non-Newtonian fluid --- p.31 / Chapter 3.4 --- Viscosity Measurement of non-Newtonian fluids --- p.35 / Chapter 3.4.1 --- Preparation of Blood Plasma --- p.36 / Chapter 3.4.2 --- Measurement of starch solutions --- p.36 / Chapter 3.5 --- Data analysis --- p.37 / Chapter 3.6 --- Conclusion --- p.41 / References --- p.43

Han, Zuoyan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 75-81). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

<p>The presence of <i>Escherichia coli</i> in water is an environmental indicator that the water is contaminated with faeces. Approximately, 30% of the world population drink water from sources contaminated with human faeces. Consequently, this percentage comprises of people that are highly vulnerable to <i>Escherichia coli</i> infection. While most strains of <i>Escherichia coli</i> are harmless or maintain a symbiotic relationship with humans, the pathogenic strains are responsible for injurious health effects, such as diarrhoea and kidney failure. The traditional method of detecting <i>Escherichia coli</i> takes about 24 – 48 hours, does not detect viable but non-culturable cells, and requires advanced equipment and great technical skills. Most other available detection techniques lack specificity, as observed with enzyme-based techniques, or are not very sensitive, as observed with most impedance-based techniques with clogged surfaces.</p> <p> </p> <p>As a result of the health effects due to this microorganism and the basic limitations of available detection techniques, there is need for a specific, sensitive and rapid detection technique to ensure a sustained and timely access to <i>E. coli</i>- free water. Therefore, the aim of this research work is to develop a detection technique devoid of the basic limitations of available methods. In this study, the antibody-antigen relationship was taken advantage of to ensure the specificity of the technique is guaranteed. This was achieved using <i>Escherichia coli</i> polyclonal antibodies that target the O and K antigens found in most pathogenic strains. These antibodies were functionalized on carboxyl group modified superparamagnetic fluorescent microparticles immobilized with streptavidin. The sensitivity of the technique was ensured by utilizing the low detection limit feature offered by the use of microfluidic devices. Two microfluidic devices, glass-based and PDMS-based, were fabricated with easily accessible materials. </p> <p> </p> <p>On introducing the sample reagents and test samples into the microfluidic devices, and passing an alternating current frequency through the system, the antibodies specifically isolated the target organisms from the pool of water contaminants and a drop in the device electric potential proportional to the bacteria concentration was observed. The success of this procedure depends on the identification of the alternating current frequency beyond which manipulation of the samples would not be easily carried out. As a result, the flow field analysis of the microparticles was carried out to study the particle behavior by varying the alternating current frequency from 15 kHz – 75 kHz. </p> <p> </p> <p>The optimum frequency observed was 35 kHz. Using the glass-based microfluidic device, the voltage drop observed for the serial dilutions, 10¹ to 10⁶ ranged from 200 mV to 420 mV while that for the serial dilutions, 10^-7 to 10^-1 ranged from 90 mV to 285 mV. To ascertain if a lower detection limit could be obtained, the PDMS-based microfluidic device, with a channel with of 300 µm, was used to analyze the response of the device to 10^-7 to 10^-1<b> </b>serial dilutions. The result ranged from 10 mV to 30 mV respectively. A comparative analysis with the conventional detection method showed that it was able to detect less than 300 <i>Escherichia coli</i> colony-forming units. This result indicates that an optimized PDMS-based microfluidic device with higher resolution microchannel could potential detect tens of bacteria colony-forming units. These results were obtained in about 60 secs of introducing the sample in the device.</p> <p> </p> <p>The rapidity and consistency of the results observed by the continuous increase in voltage drop with increasing concentrations of <i>Escherichia coli</i> indicate that this detection technique has great potential in addressing the time, specificity and sensitivity issues observed with most available detection methods.</p><br>

Thèse soutenue en Anglais

Microfluidic devices could find applications in many areas, such as BioMEMs, miniature fuel cells and microfluidic cooling of electronic circuitry. One of the important considerations of microfluidic device in analytical and bioanalytical chemistry is the dispersion of solute. In this study, we have developed an analytical solution, which considers the axial dispersion of a solute along the flow direction, to simulate convection and diffusion transport in a pressure driven creeping flow for a rectangular shape slit. During flow, the balance of competing effects of diffusion (especially cross-section diffusion) and convective diffusion in the flow direction are investigated. / Singapore-MIT Alliance (SMA)