The use of digital microfluidics (DMF) for sample handling in a microarray immunoassay was investigated. A two plate DMF device was used, with the top plate being used for the immobilization of antibodies for a sandwich immunoassay. A patterning procedure was developed for the top plate to expose patches of glass that were chemically modified, using silane chemistry, to allow for the covalent immobilization of antibodies. For creating microarrays, a set of parallel microchannels were used for the high density patterning of proteins onto the functionalized surface of the top plate. This patterning procedure was optimized to ensure the reproducibility of the immobilization and the physical integrity of the top plate. Preliminary work for a multiplexed immunoassay such as verification of cross-reactivity and detection schemes was also conducted. This work represents the initial efforts towards a microarray immunoassay on DMF, which has the potential to improve high throughput analysis.

The use of digital microfluidics (DMF) for sample handling in a microarray immunoassay was investigated. A two plate DMF device was used, with the top plate being used for the immobilization of antibodies for a sandwich immunoassay. A patterning procedure was developed for the top plate to expose patches of glass that were chemically modified, using silane chemistry, to allow for the covalent immobilization of antibodies. For creating microarrays, a set of parallel microchannels were used for the high density patterning of proteins onto the functionalized surface of the top plate. This patterning procedure was optimized to ensure the reproducibility of the immobilization and the physical integrity of the top plate. Preliminary work for a multiplexed immunoassay such as verification of cross-reactivity and detection schemes was also conducted. This work represents the initial efforts towards a microarray immunoassay on DMF, which has the potential to improve high throughput analysis.

Digital Microfluidics (DMF) is a new field of science and technology that introduces movement of nanoliter to microliter size droplets on patterned electrodes. Droplets can be moved, dispensed, merged, and split on devices. Sequential chemical reaction, and DNA extraction are examples of biological applications of DMF. In this thesis, sol-gel technology has been used as a coating method for thin film fabrication. Sol-gel is suitable for coating thin films with flexible shapes. BaTiO3 was used as a dielectric material for coating the insulator layer of the device. The material was spin coated on glass substrates. Devices were coated spinning at 500 rpm for 45 s, and annealed at 600 °C for 2hrs. The ceramic layer obtained, had a thickness of ~1 µm and average roughness of 60 nm. Nanoliter size droplets of water of ~400 nl were moved on the surface of the devices applying minimum voltage of 30 Volts.

Digital Microfluidics (DMF) is a new field of science and technology that introduces movement of nanoliter to microliter size droplets on patterned electrodes. Droplets can be moved, dispensed, merged, and split on devices. Sequential chemical reaction, and DNA extraction are examples of biological applications of DMF. In this thesis, sol-gel technology has been used as a coating method for thin film fabrication. Sol-gel is suitable for coating thin films with flexible shapes. BaTiO3 was used as a dielectric material for coating the insulator layer of the device. The material was spin coated on glass substrates. Devices were coated spinning at 500 rpm for 45 s, and annealed at 600 °C for 2hrs. The ceramic layer obtained, had a thickness of ~1 µm and average roughness of 60 nm. Nanoliter size droplets of water of ~400 nl were moved on the surface of the devices applying minimum voltage of 30 Volts.

Microfluidic based miniature lab-on-a-chip devices integrate different laboratory functionality in microscale. Microarray technology is evolving as a powerful tool for biomedical and pharmaceutical applications to identify gene sequences or to determine gene expression levels. Preparation of samples and spotting the arrays are the two major steps required for making microarrays. The microfluidic components developed in this research would facilitate performing the above-mentioned steps by a single lab-on-a-chip. Three microfluidic modules were developed: a non-contact microdispenser, an interface connecting the microdispenser with planar Electrowetting on Dielectric (EWOD) sample manipulator and a microvalve that controls the flow at the interface. An electrostatically actuated non-contact type drop-on-demand based microdispenser was developed. The dispenser was designed using finite element modeling technique that solved electrostatically actuated dispensing process. Prototypes were fabricated and tested verifying stable droplet dispensing with error in subsequent droplet generation was less than 15% between each droplet. The frequency of stable generation was 20 Hz and the average volume of dispensed droplet was 1 nL. A closed-channel EWOD actuated interface was developed that allowed a series of droplets to merge inside at the interface converting droplet flow to a continuous flow. An innovative design modification allowed series of droplet merging inside closed-channel. The interface allows integration of pressure driven devices such as: pumps, dispensers, and valves with droplet based planar EWOD devices. A novel EWOD based microvalve was developed that utilizes a thermo-responsive polymer to block and unblock a pressurized continuous flow. EWOD actuation was used to control the positioning of the valving polymer at location of interest. The valve also isolated a pressurized flow from an integrated planar EWOD device. Valves with zero leak rates were demonstrated. Such a valve will be useful in controlling microflows in EWOD to pressure driven flows such as dispensers.

Microfluidic based miniature lab-on-a-chip devices integrate different laboratory functionality in microscale. Microarray technology is evolving as a powerful tool for biomedical and pharmaceutical applications to identify gene sequences or to determine gene expression levels. Preparation of samples and spotting the arrays are the two major steps required for making microarrays. The microfluidic components developed in this research would facilitate performing the above-mentioned steps by a single lab-on-a-chip. Three microfluidic modules were developed: a non-contact microdispenser, an interface connecting the microdispenser with planar Electrowetting on Dielectric (EWOD) sample manipulator and a microvalve that controls the flow at the interface. An electrostatically actuated non-contact type drop-on-demand based microdispenser was developed. The dispenser was designed using finite element modeling technique that solved electrostatically actuated dispensing process. Prototypes were fabricated and tested verifying stable droplet dispensing with error in subsequent droplet generation was less than 15% between each droplet. The frequency of stable generation was 20 Hz and the average volume of dispensed droplet was 1 nL. A closed-channel EWOD actuated interface was developed that allowed a series of droplets to merge inside at the interface converting droplet flow to a continuous flow. An innovative design modification allowed series of droplet merging inside closed-channel. The interface allows integration of pressure driven devices such as: pumps, dispensers, and valves with droplet based planar EWOD devices. A novel EWOD based microvalve was developed that utilizes a thermo-responsive polymer to block and unblock a pressurized continuous flow. EWOD actuation was used to control the positioning of the valving polymer at location of interest. The valve also isolated a pressurized flow from an integrated planar EWOD device. Valves with zero leak rates were demonstrated. Such a valve will be useful in controlling microflows in EWOD to pressure driven flows such as dispensers.

Digital microfluidics is a new technology that permits manipulation of liquid droplets on an array of electrodes. Using this technology, nanoliter to microliter size droplets of different samples and reagents can be dispensed from reservoirs, moved, split, and merged together. Digital microfluidics is poised to become an important and useful tool for biomedical applications because of its capacity to precisely and automatically carry out sequential chemical reactions. In this thesis, a set of tools is presented to accelerate the integration of digital microfluidics into Lab-on-a-Chip platforms for a wide range of applications. An important contribution in this thesis is the development of three rapid prototyping techniques, including the use of laser printing to pattern flexible printed circuit board (PCB) substrates, to make the technology accessible and less expensive. Using these techniques, both digital and channel microfluidic devices can be produced in less than 30 minutes at a minimal cost. These rapid prototyping techniques led to a new method for manipulating liquid droplets on non-planar surfaces. The method, called All Terrain Droplet Actuation (ATDA), was used for several applications, including DNA enrichment by liquid-liquid extraction. ATDA has great potential for the integration of different physico-chemical environments on Lab-on-a-Chip devices. A second important contribution described herein is the development of a new microfluidic format, hybrid microfluidics, which combines digital and channel microfluidics on the same platform. The new hybrid device architecture was used to perform biological sample processing (e.g. enzymatic digestion and fluorescent labeling) followed by electrophoretic separation of the analytes. This new format will facilitate complete automation of Lab-on-a-Chip devices and will eliminate the need for extensive manual sample processing (e.g. pipetting) or expensive robotic stations. Finally, numerical modeling of droplet actuation on single-plate digital microfluidic devices, using electrodynamics, was used to evaluate the droplet actuation forces. Modeling results were verified experimentally using an innovative technique that estimates actuation forces based on resistive forces against droplet motion. The results suggested a list of design tips to produce better devices. It is hoped that the work presented in this thesis will help introduce digital microfluidics to many of the existing Lab-on-a-Chip applications and inspire the development of new ones.

<p>A digital microfluidic biochip (DMFB) is a device that digitizes fluidic samples into tiny droplets and operates chemical processes on a single chip. Movement control of droplets can be realized by using electrowetting-on-dielectric (EWOD) technology. DMFBs have high configurability, high sensitivity, low cost and reduced human error as well as a promising future in the applications of point-of-care medical diagnostic, and DNA sequencing. As the demands of scalability, configurability and portability increase, a new DMFB architecture called Microelectrode Dot Array (MEDA) has been introduced recently to allow configurable electrodes shape and more precise control of droplets.</p> <p>The objective of this work is to investigate a routing algorithm which can not only handle the routing problem for traditional DMFBs, but also be able to route different sizes of droplets and incorporate diagonal movements for MEDA. The proposed droplet routing algorithm is based on 3D-A* search algorithm. The simulation results show that the proposed algorithm can reduce the maximum latest arrival time, average latest arrival time and total number of used cells. By enabling channel-based routing in MEDA, the equivalent total number of used cells can be significantly reduced. Compared to all existing algorithms, the proposed algorithm can achieve so far the least average latest arrival time.</p>

Digital microfluidics is a new technology that permits manipulation of liquid droplets on an array of electrodes. Using this technology, nanoliter to microliter size droplets of different samples and reagents can be dispensed from reservoirs, moved, split, and merged together. Digital microfluidics is poised to become an important and useful tool for biomedical applications because of its capacity to precisely and automatically carry out sequential chemical reactions. In this thesis, a set of tools is presented to accelerate the integration of digital microfluidics into Lab-on-a-Chip platforms for a wide range of applications. An important contribution in this thesis is the development of three rapid prototyping techniques, including the use of laser printing to pattern flexible printed circuit board (PCB) substrates, to make the technology accessible and less expensive. Using these techniques, both digital and channel microfluidic devices can be produced in less than 30 minutes at a minimal cost. These rapid prototyping techniques led to a new method for manipulating liquid droplets on non-planar surfaces. The method, called All Terrain Droplet Actuation (ATDA), was used for several applications, including DNA enrichment by liquid-liquid extraction. ATDA has great potential for the integration of different physico-chemical environments on Lab-on-a-Chip devices. A second important contribution described herein is the development of a new microfluidic format, hybrid microfluidics, which combines digital and channel microfluidics on the same platform. The new hybrid device architecture was used to perform biological sample processing (e.g. enzymatic digestion and fluorescent labeling) followed by electrophoretic separation of the analytes. This new format will facilitate complete automation of Lab-on-a-Chip devices and will eliminate the need for extensive manual sample processing (e.g. pipetting) or expensive robotic stations. Finally, numerical modeling of droplet actuation on single-plate digital microfluidic devices, using electrodynamics, was used to evaluate the droplet actuation forces. Modeling results were verified experimentally using an innovative technique that estimates actuation forces based on resistive forces against droplet motion. The results suggested a list of design tips to produce better devices. It is hoped that the work presented in this thesis will help introduce digital microfluidics to many of the existing Lab-on-a-Chip applications and inspire the development of new ones.

<p>A digital microfluidic biochip (DMFB) is a device that digitizes fluidic samples into tiny droplets and operates chemical processes on a single chip. Movement control of droplets can be realized by using electrowetting-on-dielectric (EWOD) technology. DMFBs have high configurability, high sensitivity, low cost and reduced human error as well as a promising future in the applications of point-of-care medical diagnostic, and DNA sequencing. As the demands of scalability, configurability and portability increase, a new DMFB architecture called Microelectrode Dot Array (MEDA) has been introduced recently to allow configurable electrodes shape and more precise control of droplets.</p> <p>The objective of this work is to investigate a routing algorithm which can not only handle the routing problem for traditional DMFBs, but also be able to route different sizes of droplets and incorporate diagonal movements for MEDA. The proposed droplet routing algorithm is based on 3D-A* search algorithm. The simulation results show that the proposed algorithm can reduce the maximum latest arrival time, average latest arrival time and total number of used cells. By enabling channel-based routing in MEDA, the equivalent total number of used cells can be significantly reduced. Compared to all existing algorithms, the proposed algorithm can achieve so far the least average latest arrival time.</p>