A framework to compartmentalize microfluidic surfaces was developed. Substrates are separated from surface modifying agents with an intermediate binding layer (IBL). The IBL is comprised of two compounds which bind together using a non-covalent interaction; a host compound is immobilized on the substrate, and a guest compound is conjugated to the surface modifying agent. The primary benefit of the IBL architecture is adaptability: substrates and surface compounds become modular components with standard connectors. Beta-Cyclodextrin (BCD) and adamantane (AD) were selected as the model immobilized host and conjugated guest, respectively. A quartz crystal microbalance (QCM) was assembled and developed to study the BCD/AD complexation interaction. Kinetic, thermodynamic, and Langmuir isotherm data were reported for AD-derivatives binding with immobilized BCD. QCM was also used to investigate neutravidin (NA) binding onto AD-PEG and AD-PEG-biotin coatings immobilized to t-BCD surfaces. QCM was an effective platform to validate the use of BCD/AD as the IBL interaction prior to microfluidic implementation. The BCD/AD IBL was successfully demonstrated in a microfluidic environment. Microfluidic devices were fabricated using the soft-lithographic technique. Adapted surface modifications were visualized using fluorescein isothiocyanate (FITC) probes within the microfluidic device and detected using confocal laser scanning microscopy (CLSM). Surface modifications were applied to demonstrate the fundamental functions of surface passivation, specific binding, and visualization using the IBL architecture. Consistent with QCM data, AD-PEG passivated the surface and AD-PEG-biotin specifically bound NA to the BCD surface. Thus, an adaptable surface modification architecture for microfluidic applications was developed and demonstrated.

A framework to compartmentalize microfluidic surfaces was developed. Substrates are separated from surface modifying agents with an intermediate binding layer (IBL). The IBL is comprised of two compounds which bind together using a non-covalent interaction; a host compound is immobilized on the substrate, and a guest compound is conjugated to the surface modifying agent. The primary benefit of the IBL architecture is adaptability: substrates and surface compounds become modular components with standard connectors. Beta-Cyclodextrin (BCD) and adamantane (AD) were selected as the model immobilized host and conjugated guest, respectively. A quartz crystal microbalance (QCM) was assembled and developed to study the BCD/AD complexation interaction. Kinetic, thermodynamic, and Langmuir isotherm data were reported for AD-derivatives binding with immobilized BCD. QCM was also used to investigate neutravidin (NA) binding onto AD-PEG and AD-PEG-biotin coatings immobilized to t-BCD surfaces. QCM was an effective platform to validate the use of BCD/AD as the IBL interaction prior to microfluidic implementation. The BCD/AD IBL was successfully demonstrated in a microfluidic environment. Microfluidic devices were fabricated using the soft-lithographic technique. Adapted surface modifications were visualized using fluorescein isothiocyanate (FITC) probes within the microfluidic device and detected using confocal laser scanning microscopy (CLSM). Surface modifications were applied to demonstrate the fundamental functions of surface passivation, specific binding, and visualization using the IBL architecture. Consistent with QCM data, AD-PEG passivated the surface and AD-PEG-biotin specifically bound NA to the BCD surface. Thus, an adaptable surface modification architecture for microfluidic applications was developed and demonstrated.

Microfluidic chips have gained wide applications in various fields, including medicine, environmental sciences and forensic investigations. They are used for the separation of proteins, blood, bacterial cell suspensions, antibody solutions, and drugs. Microfluidic chips display significant advantages, which include faster analysis time, reduced amounts of samples and reagents volumes, flexibility in design and increased separation efficiency. Whole column imaging detection (WCID) exhibits significant advantages compared to other detection methods that are widely used for detecting analytes after the separation of these analytes using isoelectric focusing. With these other methods, there is a need to mobilize the focused sample bands past the detector after separation but with WCID, there is no need for mobilization step. The aim of this research is further development of WCID by characterizing microfluidic chips fabricated for the detection system, to enhance its detection so that high efficiency can be obtained. The chips were fabricated using soft lithography technology at the Microfluidic laboratory, University of Waterloo and they were used to perform isoelectric focusing of various proteins in our laboratory. The fabricated chips with straight channel design were used to carry out isoelectric focusing of some proteins and the results obtained were compared with the results obtained using commercial cartridges. The chips with tapered channel design were used to carry out isoelectric focusing of proteins in which thermally generated pH gradient principle was employed. The samples after separation were sprayed into a mass spectrometer using nano-electrospray interface to obtain their molecular masses. Compatible cartridges for nano-electrospray mass spectrometer were developed and these cartridges were used to carry out capillary isoelectric focusing of low molecular pI markers and proteins. These cartridges were also connected to the nano-electrospray mass spectrometer to obtain the mass to charge ratios of some proteins. The fabricated microfluidic chips with straight channel design were also used to investigate the interaction between drugs and protein.

Microfluidic chips have drawn great attention and interest due to their broad applications in chemical, biological and biomedical fields. These kinds of miniaturized devices offer many advantages over the traditional analysis instruments, such as reduced cost, shortened time, increased throughput, improved integration/automation/portability, etc. However, the concept of integrating multiple labs on a single chip to perform micro total analysis hasn’t been realized yet because of the lack of fundamental knowledge and systematic design of each component, especially for some particular applications. A thorough understanding and grasp of the basic physical phenomenon is the theoretical basis to develop functional devices to utilize them. In this study, we intend to investigate the electrokinetic fluid flow and coherent species transport processes in microchannels, and then try to effectively control them for designing related lab-on-a-chip devices. Rather than expensive experiments, numerical studies are performed to simulate the different processes involved in various electrokinetic chip applications. In the theoretical models, applied potential field, flow field and species concentration field are considered and corresponding governing equations with initial/boundary conditions are numerically solved by computational fluid dynamics techniques. The flow field is obtained by the developed SIMPLE algorithm and a slip-wall velocity boundary condition is applied in simulating electroosmotic flow. Grid independence tests and convergence studies are performed to ensure economic computation with adequate accuracy and stability. For every application with typical channel layout, parametric studies are performed to investigate different effects through the controlling parameters linked to them. For surface patterning or microfabrication using laminar flows, various operational parameters are investigated to explore the optimized configurations for multi-stream flow and mass transport control in cross-linked microchannels. Through a series of numerical simulations, it is found that applied potentials, electroosmotic mobilities of solutions and channel dimensions have significant effects on the flow and mass transport after converging in the intersection of channel network. Diffusion coefficient has less influence than the other parameters due to the presence of high Peclet number for such applications. For the microwashing with two different electrolyte solutions, a three-dimensional model is numerically solved to reveal the flow structure change. In a straight microchannel with a rectangle cross section, KCl solution and LaCl3 solution are mainly employed for tests. Displacement processes between two solutions in both orders are tested and analyzed. The observed flow structures such as back flow in channel center and distortion of plug-like velocity profile are noticed and discussed. The distortion of the flow field results from the induced pressure gradient, which is due to the non-uniformity of electroosmotic mobilities and electrical conductivities of two replaced solutions. The bigger difference two solutions have in chemical properties, the stronger effects on flow they have. Effect of applied potential field strength is also studied and the approximate linear influences are concluded. Finally, the unsteady on-chip sample injection and separation processes involved in microchip capillary electrophoresis are studied. Species’ electrophoretic migration effect is included and the theoretical model is non-dimensionalized in a unique manner with the key fundamental parameters: the Re Sci , species’ non-dimensional electrophoretic mobility and applied potentials. The species transport characteristics are revealed numerically and well understood for future effective control and innovative chip design. Species front movement during injection and sample plug development in separation are examined with diffusion effect; results include concentration profiles and contour plots over a range of injection and separation time. The influence of i Re Sc which characterizes the relative role of convection versus diffusion is examined over the commonly encountered range and the diffusion effect is found to have an essentially negligible effect. Through three species, the electrophoretic mobilities difference is demonstrated to be the reason for separation. Real-time monitoring of different species’ movements is performed for injection guidance.

Microfluidic chips have gained wide applications in various fields, including medicine, environmental sciences and forensic investigations. They are used for the separation of proteins, blood, bacterial cell suspensions, antibody solutions, and drugs. Microfluidic chips display significant advantages, which include faster analysis time, reduced amounts of samples and reagents volumes, flexibility in design and increased separation efficiency. Whole column imaging detection (WCID) exhibits significant advantages compared to other detection methods that are widely used for detecting analytes after the separation of these analytes using isoelectric focusing. With these other methods, there is a need to mobilize the focused sample bands past the detector after separation but with WCID, there is no need for mobilization step. The aim of this research is further development of WCID by characterizing microfluidic chips fabricated for the detection system, to enhance its detection so that high efficiency can be obtained. The chips were fabricated using soft lithography technology at the Microfluidic laboratory, University of Waterloo and they were used to perform isoelectric focusing of various proteins in our laboratory. The fabricated chips with straight channel design were used to carry out isoelectric focusing of some proteins and the results obtained were compared with the results obtained using commercial cartridges. The chips with tapered channel design were used to carry out isoelectric focusing of proteins in which thermally generated pH gradient principle was employed. The samples after separation were sprayed into a mass spectrometer using nano-electrospray interface to obtain their molecular masses. Compatible cartridges for nano-electrospray mass spectrometer were developed and these cartridges were used to carry out capillary isoelectric focusing of low molecular pI markers and proteins. These cartridges were also connected to the nano-electrospray mass spectrometer to obtain the mass to charge ratios of some proteins. The fabricated microfluidic chips with straight channel design were also used to investigate the interaction between drugs and protein.

Microfluidic chips have drawn great attention and interest due to their broad applications in chemical, biological and biomedical fields. These kinds of miniaturized devices offer many advantages over the traditional analysis instruments, such as reduced cost, shortened time, increased throughput, improved integration/automation/portability, etc. However, the concept of integrating multiple labs on a single chip to perform micro total analysis hasn’t been realized yet because of the lack of fundamental knowledge and systematic design of each component, especially for some particular applications. A thorough understanding and grasp of the basic physical phenomenon is the theoretical basis to develop functional devices to utilize them. In this study, we intend to investigate the electrokinetic fluid flow and coherent species transport processes in microchannels, and then try to effectively control them for designing related lab-on-a-chip devices. Rather than expensive experiments, numerical studies are performed to simulate the different processes involved in various electrokinetic chip applications. In the theoretical models, applied potential field, flow field and species concentration field are considered and corresponding governing equations with initial/boundary conditions are numerically solved by computational fluid dynamics techniques. The flow field is obtained by the developed SIMPLE algorithm and a slip-wall velocity boundary condition is applied in simulating electroosmotic flow. Grid independence tests and convergence studies are performed to ensure economic computation with adequate accuracy and stability. For every application with typical channel layout, parametric studies are performed to investigate different effects through the controlling parameters linked to them. For surface patterning or microfabrication using laminar flows, various operational parameters are investigated to explore the optimized configurations for multi-stream flow and mass transport control in cross-linked microchannels. Through a series of numerical simulations, it is found that applied potentials, electroosmotic mobilities of solutions and channel dimensions have significant effects on the flow and mass transport after converging in the intersection of channel network. Diffusion coefficient has less influence than the other parameters due to the presence of high Peclet number for such applications. For the microwashing with two different electrolyte solutions, a three-dimensional model is numerically solved to reveal the flow structure change. In a straight microchannel with a rectangle cross section, KCl solution and LaCl3 solution are mainly employed for tests. Displacement processes between two solutions in both orders are tested and analyzed. The observed flow structures such as back flow in channel center and distortion of plug-like velocity profile are noticed and discussed. The distortion of the flow field results from the induced pressure gradient, which is due to the non-uniformity of electroosmotic mobilities and electrical conductivities of two replaced solutions. The bigger difference two solutions have in chemical properties, the stronger effects on flow they have. Effect of applied potential field strength is also studied and the approximate linear influences are concluded. Finally, the unsteady on-chip sample injection and separation processes involved in microchip capillary electrophoresis are studied. Species’ electrophoretic migration effect is included and the theoretical model is non-dimensionalized in a unique manner with the key fundamental parameters: the Re Sci , species’ non-dimensional electrophoretic mobility and applied potentials. The species transport characteristics are revealed numerically and well understood for future effective control and innovative chip design. Species front movement during injection and sample plug development in separation are examined with diffusion effect; results include concentration profiles and contour plots over a range of injection and separation time. The influence of i Re Sc which characterizes the relative role of convection versus diffusion is examined over the commonly encountered range and the diffusion effect is found to have an essentially negligible effect. Through three species, the electrophoretic mobilities difference is demonstrated to be the reason for separation. Real-time monitoring of different species’ movements is performed for injection guidance.

The objective of this research is to develop a three-dimensional (3-D) microfluidic/ electronic interface system for sustaining and monitoring 3-D neuronal networks. This research work is divided into two parts. One is the development of a 3-D multi-electrode array (MEA) with integrated microfluidic channels. The other is a microneedle array with embedded microelectrodes and microfluidic channels. The 3-D MEA is composed of three elements that are essential for the development and monitoring of 3-D cultures of neurons. These components consist of scaffolds for cellular growth and structural stability, microfluidic channels for cell maintenance and chemical stimulation, and electrodes for electrical stimulation and recording. Two kinds of scaffold structures have been fabricated. The first scaffolding scheme employs a double exposure technique that embeds SU-8 towers into an SU-8 substrate. The second scaffolding mechanism introduces interconnects between towers for the purpose of mechanically supporting 3-D cell cultures and facilitating 3-D synaptic connections. Microfluidic channels are combined for fine control of the cellular microenvironment by means of diffusive and convective fluidic processes. Hollow towers with three-layer side ports were developed by using double exposure techniques and excimer laser ablation. The electrodes are combined into an integrated system that is capable of monitoring electrical activities and the cellular impedances of neurons which are attached to the electrodes. The second part of this research is to fabricate a microneedle array for monitoring brain slices, which will directly detect electrical signals from living brain slices. Although the microneedle array is targeting different 3-D neuronal networks, it also has three components and the fabrication steps are the same as those for the 3-D MEA. To generate the sharp tip, isotropic reactive ion etching (RIE) is performed on tapered SU-8 towers. High aspect ratio tower structures can be effectively generated with SU-8 and tapered shapes are created by backside exposure. The resulting systems will enable a new field of neurobiological research, in which the collective properties of 3-D neuronal circuits can be observed and manipulated with unprecedented detail and precision, and at a level of control not possible in living animals.

This study developed a microfluidic flow sensor for the detections of velocity and viscosity, especially for ultra-low viscosity detection. An etched optic fiber with the diameter of 9 £gm is embedded in a microfluidic chip to couple green laser light into the microfluidic channel. The flow induced vibration causes periodic flapping motion of the optic fiber cantilever because of the pressure difference from two sides of fiber cantilever. Through the frequency analysis, the fluidic properties including the flow rate and the viscosity can be detected and identified. Results show that this developed sensor is capable of sensing liquid samples with the flow rates from 0.17 m/s to 68.81 m/s and the viscosities from 0.306 cP to 1.200 cP. In addition, air samples (0.0183 cP) with various flow rates can also be detected using the developed sensor. Although the detectable range for flow rate sensing is not wide, the sensitivity is high of up to around 3.667 mm/(s¡EHz) in test liquid in DI water, and when detecting air the sensitivity is 6.190 mm/(s¡EHz). The developed flow sensor provides a simple and straight forward method for sensing flow characteristics in a microfluidic channel.

Integrated microfluidic devices for biomedical analysis attract lots of interest in the MEMS (Micro-Electro-Mechanical-Systems) research field. However, the characteristic Reynolds number for liquids flowing in these microchannels is very small (typically less than 10). At such low Reynolds numbers, turbulent mixing does not occur and homogenization of the solutions occurs through diffusion processes alone. Hence, a satisfactory mixing performance generally requires the use of extended flow channels and takes longer to accomplish such that the practical benefits of such devices are somewhat limited. Consequently, accomplishing the goal of u¡VTAS requires the development of enhanced mixing techniques for microfluidic structures. This study first presents a microfluidic mixer utilizing alternatively switching electroosmotic flow and proposes two microchannel designs of T-form and double-T-form micromixer. Switching DC field is used to generate the electroosmotic force to drive the fluid and also used for mixing of the fluids simultaneously, such that moving parts in the microfluidic device and delicate external control system are not required for the mixing purpose. Furthermore, this study also proposed a novel pinched-switching mode in the T-form microfluidic mixer, which could be effectively increase the perturbation within the fluid to promote the mixing efficiency. In this study, computer simulation for the operation conditions is used to predict the mixing outcomes and the mixing performance is also confirmed experimentally. Result shows the mixing performance can be as larger as 95% within the mixing distance of 1 mm downstream the common boundary between the different sample fluids. The novel method proposed in this study can be used for solving the mixing problem in a simple way in the field of micro-total-analysis-systems. Furthermore, in order to demonstrate the proposed micromixer is feasible for on-line bio-reaction, this study designs a fully integrated device for demonstration of DNA/enzyme reaction within the microfluidic chip. The microchip device contains a pre-column concentrating region, a micro mixer for DNA-enzyme mixing, an adjustable temperature control system and a post-column concentration channel. The integrated microfluidic chip has been used to implement the DNA digestion and extraction. Successfully digestion of £f-DNA using EcoRI restriction enzyme in the proposed device is demonstrated utilizing large-scale gel electrophoresis scheme. Results show that the reaction speed doubled while using the microfluidic system. In addition, on-line DNA digestion and capillary electrophoresis detection is also successfully demonstrated using a standard DNA-enzyme system of $X-174 and Hae III. Finally, this reasearch also proposes a novel cell/microparticle manipulation platform by integrating an optical tweezer system and a micro flow cytometer. During operation, electrokinetically driven sheath flows are utilized to focus microparticles to flow in the center of the sample stream then pass through an optical manipulation area. An IR diode laser is focused to generate force gradient in the optical manipulation area to manipulate the microparticles in the microfluidic device. Moving the particles at a static condition is demonstrated to confirm the feasibility of the home-built optical tweezer. The trapping force of the optical tweezer is measured using a novel method of Stocks-drag equilibrium. The proposed system can continuously catch moving microparticles in the flowing stream or switch them to flow into another sample flow within the microchannel. Target particles can be separated from the sample particles with this high efficient approach. More importantly, the system demonstrates a continuously manipulation of microparticles using non-contact force gradient such that moving parts and delicate fabrication processes can be excluded. The proposed system is feasible of high-throughput catching, moving, manipulation and sorting specific microparticles/cells within a mixed sample and results in a simple solution for cell/microparticle manipulation in the field of micro-total-analysis-systems. In this thesis, low-cost soda-lime glass substrates are adopted for the microchip fabrication using a simple and reliable fabrication process. Three kinds of novel microfluidic devices including an electrokinetically-driven microfluidic mixer, a high throughput DNA/enzyme reactor and an optically cell manipulation platform are successfully demonstrated. It is the author¡¦s believes that the results of this study will give important contributions in the development of micro-total-analysis-systems in the future. With the success of this study, we have a further step approaching to the dream of lab-on-a-chip system for bio-analytical applications.

This study develops and demonstrates a microfluidic module for investigating the mechanism of inorganic fouling caused by the precipitation of calcium sulfate (CaSO4) on nanofiltration membranes. The developed microfluidic module enables sensitive system responses, rapid detection and real time observation of inorganic fouling commonly encountered in water treatment industries. For this development, CaSO4 is selected as the model salt due to its unique fouling characteristics. The effect of the operating conditions, such as pressure and permeate flux, was on the fouling behavior is investigated. A plate-frame type microfluidic chip was fabricated and employed in a dead-end filtration mode for constant-flux fouling experiments. The nanofiltration chip module has a dimension of 50 mm ¡Ñ 25 mm ¡Ñ 12 mm. It is consisted of a polymeric nanofilter, a pressure acquisition unit, a C.C.D., and micro electrodes on the nanofilter for investigating the relationships among trans-membrane pressure, conductivity on membrane surface and permeate fluxes. With the microfluidic system, real-time concentration polarization, bulk nucleation of CaSO4 and surface crystal accumulation were observed in terms of the variations of pressure and conductivity on membrane surface, which were verified with scanning electron micrographs to confirm the corresponding fouling stage. It is found that membrane surface conductivity increases with trans-membrane pressure before bulk crystallization of CaSO4, then slightly decreases after the formation of bulk nuclei due to the removal of solute in the aqueous phase. The conductivity remains relatively constant during cake formation stage while trans-membrane pressure steadily increases. This study successfully integrates microfluidic technology with pressure and electrical measurements for detecting the dynamic transition during CaSO4 fouling, and reports for the first time the experimental measurement of the initiation of inorganic cake formation.