Digitally controllable large-scale integrated microfluidic systems.

Lam Raymond Hiu-wai.Thesis (M.Phil.)--Chinese University of Hong Kong, 2005.Includes bibliographical references (leaves 87-91).Abstracts in English and Chinese.Abstract --- p.iiAbstract (Chinese) --- p.ivAcknowledgment --- p.vContents --- p.viiList of Figures --- p.ixIntroduction --- p.1Chapter 1-1 --- Overview of MEMS and Microfluidic Technologies --- p.1Chapter 1-1-1 --- Microelectromechanical Systems (MEMS) --- p.1Chapter 1-1-2 --- Microfluidic Systems --- p.2Chapter 1-2 --- Literture Review on Microfluidic Devices --- p.4Chapter 1-2-1 --- Micropumps --- p.4Chapter 1-2-2 --- Microvalves --- p.5Chapter 1-2-3 --- Micromixers --- p.5Chapter 1-2-3 --- Integration of Multiple Devices: Microfluidic Systems --- p.6Chapter 1-3 --- Motivation and Research Objectives --- p.7Chapter 1-4 --- Thesis Outline --- p.9Fluid Flow in MicroChannel --- p.11Chapter 2-1 --- Velocity Profile in a MicroChannel --- p.11Chapter 2-2 --- Pressure Dissipation by Laminar Friction --- p.16Chapter 2-3 --- Bubble Filtering --- p.20Microfluidic Centrifugal Pumping --- p.23Chapter 3-1 --- Vortex Micropump --- p.23Chapter 3-1-1 --- Operation Principle and Device Design --- p.23Chapter 3-1-2 --- Alternative Pump Design --- p.25Chapter 3-2 --- Micropump Fabrication --- p.27Chapter 3-2-1 --- Electroplated Impeller --- p.27Chapter 3-2-2 --- SU-8 Impeller --- p.30Chapter 3-2-3 --- Micropump Fabricated by Micro Molding Replication Technique --- p.32Chapter 3-2-4 --- Inverted-chamber Vortex Micropump --- p.35Chapter 3-3 --- Elementary Centrifugal Pump Theory --- p.36Chapter 3-3-1 --- Pumping Pressure and Discharge --- p.36Chapter 3-3-2 --- Fluid Horsepower --- p.38Chapter 3-3-3 --- Effect of Blade Angle --- p.40Chapter 3-4 --- Pumping Specification --- p.41Mixing Based on Mechanical Vibration --- p.47Chapter 4-1 --- Micromixer Design --- p.47Chapter 4-1-1 --- Oscillating Diaphragm Actuated Microfluidic Mixing --- p.47Chapter 4-1-2 --- Flat-surface Diaphragm Active Micromixer --- p.48Chapter 4-1-3 --- Mixing Enhancement by Pillared Chamber Profile --- p.50Chapter 4-2 --- Fabrication Process --- p.52Chapter 4-2-1 --- Flat-surface Diaphragm Active Micromixer --- p.52Chapter 4-2-2 --- Pillared-surface Diaphragm Active Micromixer --- p.54Chapter 4-3 --- Experimental Analysis of Mixing Performance --- p.56Microfluidic Flow Planning System --- p.63Chapter 5-1 --- System Design --- p.63Chapter 5-1-1 --- Chip Design and Fabrication --- p.63Chapter 5-1-2 --- Digital Controlling System --- p.65Chapter 5-1-3 --- Operation Mechanism --- p.67Chapter 5-2 --- Experimental Results --- p.69Microfluidic Mixing Module Array --- p.70Chapter 6-1 --- System Configuration --- p.70Chapter 6-1-1 --- Microfluidic Chip Design --- p.70Chapter 6-1-2 --- Backward Flow Elimination by Tesla Valve --- p.72Chapter 6-1-3 --- System Controller and Operation Mechanism --- p.75Chapter 6-2 --- Fabrication --- p.76Chapter 6-3 --- Mixing Ratio Estimation --- p.78Chapter 6-4 --- Experimental Results --- p.79Conclusion --- p.81Future Work --- p.83Chapter 8-1 --- Self Driven Microfluidic Flow Planning System --- p.83Chapter 8-2 --- Mixing Enhancement by Cavitation Microstreaming --- p.84References --- p.87Bonding Test on UV-curing Epoxy Resin --- p.92Circuit Schematic of Digital Controller --- p.94Advanced Digital Microfluidic Controller --- p.9

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

Microfluidics is an emerging and promising interdisciplinary technology which offers powerful platforms for precise production of novel functional materials (e.g., emulsion droplets, microcapsules, and nanoparticles as drug delivery vehicles- and drug molecules) as well as high-throughput analyses (e.g., bioassays, detection, and diagnostics). In particular, multiphase microfluidics is a rapidly growing technology and has beneficial applications in various fields including biomedicals, chemicals, and foods. In this review, we first describe the fundamentals and latest developments in multiphase microfluidics for producing biocompatible materials that are precisely controlled in size, shape, internal morphology and composition. We next describe some microfluidic applications that synthesize drug molecules, handle biological substances and biological units, and imitate biological organs. We also highlight and discuss design, applications and scale up of droplet- and flow-based microfluidic devices used for drug discovery and delivery. © 2013 Elsevier B.V. All rights reserved

Microscale Strategies for Generating Cell-Encapsulating Hydrogels

Hydrogels in which cells are encapsulated are of great potential interest for tissue engineering applications. These gels provide a structure inside which cells can spread and proliferate. Such structures benefit from controlled microarchitectures that can affect the behavior of the enclosed cells. Microfabrication-based techniques are emerging as powerful approaches to generate such cell-encapsulating hydrogel structures. In this paper we introduce common hydrogels and their crosslinking methods and review the latest microscale approaches for generation of cell containing gel particles. We specifically focus on microfluidics-based methods and on techniques such as micromolding and electrospinning.National Science Foundation (U.S.) (DMR0847287)National Institutes of Health (U.S.) (EB008392)National Institutes of Health (U.S.) (DE019024)National Institutes of Health (U.S.) (HL099073)National Institutes of Health (U.S.) (AR057837)National Institutes of Health (U.S.) (HL092836)United States. Army Research Office (contract W911NF-07-D-0004)United States. Army Research Office (Institute for Soldier Nanotechnology)United States. Army. Corps of EngineersInnovative Med Tech (Postdoctoral fellowship

Development of an autonomous lab-on-a-chip system with ion separation and conductivity detection for river water quality monitoring

This thesis discusses the development of a lab on a chip (LOC) ion separation for river water quality monitoring using a capacitively coupled conductivity detector (C⁴D) with a novel baseline suppression technique.Our first interest was to be able to integrate such a detector in a LOC. Different designs (On-capillary design and on-chip design) have been evaluated for their feasibility and their performances. The most suitable design integrated the electrode close to the channel for an enhanced coupling while having the measurement electronics as close as possible to reduce noise. The final chip design used copper tracks from a printed circuit board (PCB) as electrodes, covered by a thin Polydimethylsiloxane (PDMS) layer to act as electrical insulation. The layer containing the channel was made using casting and bonded to the PCB using oxygen plasma. Flow experiments have been conduced to test this design as a detection cell for capacitively coupled contactless conductivity detection (C⁴D).The baseline signal from the system was reduced using a novel baseline suppression technique. Decrease in the background signal increased the dynamic range of the concentration to be measured before saturation occurs. The sensitivity of the detection system was also improved when using the baseline suppression technique. Use of high excitation voltages has proven to increase the sensitivity leading to an estimated limit of detection of 0.0715 μM for NaCl (0.0041 mg/L).The project also required the production of an autonomous system capable of operating for an extensive period of time without human intervention. Designing such a system involved the investigation of faults which can occur in autonomous system for the in-situ monitoring of water quality. Identification of possible faults (Bubble, pump failure, etc.) and detection methods have been investigated. In-depth details are given on the software and hardware architecture constituting this autonomous system and its controlling software

A Modular design framework for Lab-On-a-Chips

This research discusses the modular design framework for designing Lab-On-a-Chip (LoC) devices. This work will help researchers to be able to focus on their research strengths, without needing to learn details of LoCs design, and they can reuse existing LoC designs

Building droplet-based microfluidic systems for biological analysis

Abstract In the present paper, we review and discuss current developments and challenges in the field of dropletbased microfluidics. This discussion includes an assessment of the basic fluid dynamics of segmented flows, material requirements, fundamental unit operations and how integration of functional components can be applied to specific biological problems

Optical Printing of Multiscale Hydrogel Structures

Hydrogel has been a promising candidate to recapitulate the chemical, physical and mechanical properties of natural extracellular matrix (ECM), and they have been widely used for tissue engineering, lab on a chip and biophotonics applications. A range of optical fabrication technologies such as photolithography, digital projection stereolithography and laser direct writing have been used to shape hydrogels into structurally complex functional devices and constructs. However, it is still greatly challenging for researchers to design and fabricate multiscale hydrogel structures using a single fabrication technology. To address this challenge, the goal of this work is the design and develop novel multimode optical 3D printing technology capable of printing hydrogels with multiscale features ranging from centimeter to micrometer sizes and in the process transforming simple hydrogels into functional devices for many biomedical applications. Chapter 2 presents a new multimode optical printing technology that synergistically combined large-scale additive manufacturing with small-scale additive/subtractive manufacturing. This multiscale fabrication capability was used to (i) align cells using laser induced densification in Chapter 3, (ii) develop diffractive optics based on changes in refractive indices in Chapter 4, (iii) print diffractive optical elements in Chapter 5, and (iv) digitally print complex microfluidic devices and other 3D constructs in Chapter 6. Overall, this work open doors to a new world of fabrication where multiscale functional hydrogel structures are possible for a range biomedical application

Towards rapid 3D direct manufacture of biomechanical microstructures

The field of stereolithography has developed rapidly over the last 20 years, and commercially available systems currently have sufficient resolution for use in microengineering applications. However, they have not as yet been fully exploited in this field. This thesis investigates the possible microengineering applications of microstereolithography systems, specifically in the areas of active microfluidic devices and microneedles. The fields of micropumps and microvalves, stereolithography and microneedles are reviewed, and a variety of test builds were fabricated using the EnvisionTEC Perfactory Mini Multi-Lens stereolithography system in order to define its capabilities. A number of microneedle geometries were considered. This number was narrowed down using finite element modelling, before another simulation was used to optimise these structures. 9 × 9 arrays of 400 μm tall, 300 μm base diameter microneedles were subjected to mechanical testing. Per needle failure forces of 0.263 and 0.243 N were recorded for the selected geometries, stepped cone and inverted trumpet. The 90 μm needle tips were subjected to between 30 and 32 MPa of pressure at their failure point - more than 10 times the required pressure to puncture average human skin. A range of monolithic micropumps were produced with integrated 4 mm diameter single-layer 70 μm-thick membranes used as the basis for a reciprocating displacement operating principle. The membranes were tested using an oscillating pneumatic actuation, and were found reliable (>1,000,000 cycles) up to 2.0 PSIG. Pneumatic single-membrane nozzle/diffuser rectified devices produced flow rates of up to 1,000 μl/min with backpressures of up to 375 Pa. Another device rectified using active membrane valves was found to self-prime, and produced backpressures of up to 4.9 kPa. These devices and structures show great promise for inclusion in complex, fully integrated and active microfluidic systems fabricated using microstereolithography alone, with implications for both cost of manufacture and lead time

Development of a microfluidic device for gaseous formaldehyde sensing = Développement d\u27un dispositif microfluidique pour la détection de formaldéhyde à l\u27état gazeux

Formaldehyd (HCHO) ist eine chemische Verbindung, die bei der Herstellung einer großen Zahl von Haushaltsprodukten verwendet wird.Charakteristisch ist seine hohe Flüchtigkeit aufgrund einer niedrigen Siedetemperatur ($T = - 19\ ℃$). Daher ist HCOH fast überall als Luftschadstoff in Innenräumen vorhanden. Die Miniaturisierung analytischer Systeme zu Handheld-Gerät hat das Potenzial, nicht nur effizientere, sondern auch empfindlichere Instrumente für die Echtzeitüberwachung dieses gefährlichen Luftschadstoffs zu ermöglichen. Die vorliegende Doktorarbeit präsentiert die Entwicklung eines Mikrofluidik-Geräts für die Erfassung von HCHO basierend auf der Hantzsch-Reaktion.Hierbei wurde der Schwerpunkt auf die Komponente für Fluoreszenzdetektion gelegt. Es wurde eine umfangreiche Literaturrecherche durchgeführt, die es erlaubt, den Stand der Technik auf dem Gebiet der Miniaturisierung des Fluoreszenzsensors zusammenzufassen. Auf Grund dieser Studie wurde ein modulares Fluoreszenzdetektionskonzept vorgeschlagen, das um einen CMOS-Bildsensor (CIS) herum entwickelt wurde. Zwei dreischichtige Fluidikzellenkonfigurationen (Konfiguration 1: Quarz - SU-8 3050 - Quarz und Konfiguration 2: Silizium - SU-8 3050 - Quarz) wurden in Betracht gezogen und parallel unter den gleichen experimentellen Bedingungen getestet. Die Verfahren der Mikrofabrikation der fluidischen Zellen wurden detailliert beschrieben, einschließlich des Integrationsprozesses der Standardkomponenten und der experimentellen Verfahren. Der CIS-basierte Fluoreszenzdetektor bewies seine Leistungsfähigkeit, eine anfängliche HCHO-Konzentration von 10 µg/L vollständig in 3,5-Diacetyl-1,4-dihydrolutidin (DDL- derivatisiert) sowohl für die Quarz- als auch für die Silizium-Fluidikzellen zu detektieren. Beide Systemewiesenein Abfragevolumen von 3,5 µL auf. Ein offensichtlich höheres Signal-Rausch-Verhältnis (SNR) wurde für die Silizium-Fluidzelle ($\text{SNR}_{\text{silicon}} = 6.1$) im Vergleich zur Quarz-Fluidzelle ($\text{SNR}_{\text{quartz}} = 4.9$) beobachtet. Die Verstärkung der Signalintensität in der Silizium-Fluidzelle ist wahrscheinlich auf den Silizium-Absorptionskoeffizienten bei der Anregungswellenlänge zurückzuführen,$a\left( \lambda_{\text{abs}} = 420\ nm \right) = 5 \bullet 10^{4}\text{cm}^{- 1}$. Dieser Koeffizient ist ungefähr fünfmal höher als der Absorptionskoeffizient bei der Fluoreszenzemissionswellenlänge $a\left(\lambda_{\text{em}} = 515\ nm \right) = 9.25 \bullet 10^{3}\text{cm}^{- 1}$. HCHO wird aufgrund seiner relativ hohen Konstanten für das Henry-Gesetz sehr schnell in ein flüssiges Reagenz aufgenommen. Somit hängt die Auswahl des molekularen Einfangverfahrens (Schwallströmung, Ringströmung oder membranbasierte Strömungswechselwirkung) von derLeistungsfähigkeit des Fluoreszenzdetektors ab. Ein vorläufiges Konzept, das auf der Verwendung einer Gas-Flüssigkeitsmembran-basierten Wechselwirkung zum ständigen Abfangen des gasförmigen HCHO basiert, wurde eingeführt. Hierzu wurden kompatible Materialien und Herstellungsmethoden identifiziert. Darüber hinaus wurden CFD-Simulationen durchgeführt, um die Mikrokanallänge unter verschiedenen hydrodynamischen Bedingungen abzuschätzen, die für eine vollständige HCHO-Derivatisierung erforderlich sind. Eine Verbesserung und Vereinfachung auf der Grundlage von sehrnempfindlichen Fluoreszenzdetektoren mit niedrigen Detektionsgrenzen könnte zukünftig basierend z. B. auf Schwallströmung oder Ringströmung möglich sein