Test analysis & fault simulation of microfluidic systems

This work presents a design, simulation and test methodology for microfluidic systems, with particular focus on simulation for test. A Microfluidic Fault Simulator (MFS) has been created based around COMSOL which allows a fault-free system model to undergo fault injection and provide test measurements. A post MFS test analysis procedure is also described.A range of fault-free system simulations have been cross-validated to experimental work to gauge the accuracy of the fundamental simulation approach prior to further investigation and development of the simulation and test procedure.A generic mechanism, termed a fault block, has been developed to provide fault injection and a method of describing a low abstraction behavioural fault model within the system. This technique has allowed the creation of a fault library containing a range of different microfluidic fault conditions. Each of the fault models has been cross-validated to experimental conditions or published results to determine their accuracy.Two test methods, namely, impedance spectroscopy and Levich electro-chemical sensors have been investigated as general methods of microfluidic test, each of which has been shown to be sensitive to a multitude of fault. Each method has successfully been implemented within the simulation environment and each cross-validated by first-hand experimentation or published work.A test analysis procedure based around the Neyman-Pearson criterion has been developed to allow a probabilistic metric for each test applied for a given fault condition, providing a quantitive assessment of each test. These metrics are used to analyse the sensitivity of each test method, useful when determining which tests to employ in the final system. Furthermore, these probabilistic metrics may be combined to provide a fault coverage metric for the complete system.The complete MFS method has been applied to two system cases studies; a hydrodynamic “Y” channel and a flow cytometry system for prognosing head and neck cancer.Decision trees are trained based on the test measurement data and fault conditions as a means of classifying the systems fault condition state. The classification rules created by the decision trees may be displayed graphically or as a set of rules which can be loaded into test instrumentation. During the course of this research a high voltage power supply instrument has been developed to aid electro-osmotic experimentation and an impedance spectrometer to provide embedded test

Design, Fabrication and Characterization of Electrokinetically Pumped Microfluidic Chips for Cell Culture Applications

Continuous perfusion cell culture chips offer the biomedical researcher unprecedented control over the microenvironment surrounding the cell which is not feasible with conventional static cell culture procedures. Applying microfluidics technology to these devices provides several benefits including increased fluid and media control, reduced consumption of reagents, continuous monitoring of cells and the potential for massively parallel experiments. In this work a new continuous perfusion cell culture chip is studied that utilizes electroosmotic pumping to control fluid flow. Problems associated with EOF and cells are solved by incorporating electroosmotic pumps (EO pumps) which generate an induced pressure driven flow in regions with cells. Several advantages of EO pumps include pulse free flow, quick flow control and precise movement of minute volumes of fluid. However, the high salt concentration in cell culture medium creates significant problems for EO pumps such as decreased flow rate due to low zeta potential, increased electrolysis due to large current draw, significant joule heating, bubble formation and polarization. Attempts to solve these problems with the proposed microfluidic chip are discussed. The microfluidic chip is fabricated using soft lithography techniques developed as part of this work. The designs were modelled using a combination of numerical simulations with a commercial software program and compact circuit modelling. The pumps were integrated on-chip into a cell culture perfusion chip. The chip is adaptable due to the flexibility of the EO pumps to work as both pressure sources and virtual valves for regulating the fluid flow. Experiments with rainbow trout gill cells (RT-gill W1) were performed in order to validate the use of EO pumps for cell culture. Results show that the cells are not affected by the presence of the EO pumps as the electric field is isolated from the cells. However, the pumps were only able to operate continuously for eight hours before electrolysis effects stopped fluid flow. As a proof of concept, this shows that it is feasible to use EO pumps within a cell culture network

Droplet Production and Transport in Microfluidic Networks with Pressure Driven Flow Control

Droplet based microfluidics is a developing technology with great potential towards improving large scale combinatorial studies that require high throughput and accurate metering of reagents. Each droplet can be thought of as a miniature microreactor where complex reactions can be performed on the micro-scale by mixing, splitting and combining droplets. This thesis investigates the operation and control of droplet microfluidic devices operating using constant pressure sources to pump fluids where feedback from the droplets influences the overall performance of the device. For this purpose, a model system consisting of a single T-junction droplet generator and a single network node is used to understand how pressure source control effects droplet generation and transport through microfluidic networks. The first part of this thesis focuses on the generation of Newtonian liquid-liquid droplets from a microfluidic T-junction operating within the squeezing-to-transition regime with stable flow rates. An experimental study was performed to characterize the effects of geometry (height/width ratio, channel width ratio) and flow parameters (Capillary number, flow rate ratio, viscosity ratio) on the droplet size, spacing and rate of production. Three stages of droplet formation were identified (lag, filling and necking), including the newly defined lag stage that appears at the beginning of the formation cycle once the interface pulls back after a droplet detaches. Based on the experimental observations, a model was developed to describe the formation process which incorporates a detailed geometric description of the drop shape with a force balance in the filling stage and a control volume analysis of the necking stage. The model matches well with the experimental results as data falls within 10% of the predicted values. Subsequently, the effect of surfactants on the formation process was investigated. Surfactant transport occurs on a timescale comparable to the production rate of droplets resulting in dynamic interfacial tension effects. This causes strong coupling between the mass transport of surfactants and the drop production process. Using the previously defined force balance, the apparent interfacial tension at the end of the filling stage was measured. The results show that there is a significant deviation from the equilibrium interfacial tension at normal operating conditions for the T-junction generators due to the rapid expansion of the interface. A model was developed to calculate the dynamic interfacial tension for pre and post micellar solutions, which was then incorporated into the overall model for droplet formation in T-junction generators. Next, the behaviour of microfluidic droplet generators operating under pressure source control was investigated. Coupling between the changing interface and hydrodynamic resistance of the droplets and the flow rate of the two phases creates fluctuations in the output of the droplet generator. Oscillations were found to occur over the short term (one droplet formation cycle) and long term (many formation cycles). Two metrics were developed to quantify these oscillations. Short term oscillations were quantified by tracking droplet speed in the output channel and long term oscillation were quantified by measuring changes in droplet spacing. Analysis of experimental and numerical data shows that long term oscillations have a periodicity that matches the residence time of droplets in the system. A simple model is developed to determine the influence of Laplace pressure, droplet resistance, T-junction generator design and network architecture on the magnitude of these oscillations. From the model a set of design rules are developed to improve the overall operation of T-junction generators using pressure driven flow. The final part of this thesis studies the transport of droplets through a single microchannel junction under various geometric and flow conditions applied to the two outlet channels. Droplets alter the hydrodynamic resistance of the channel they travel within which creates a feedback effect where the decision of preceding droplets influences the trajectory of subsequent droplets. Multifaceted behaviour occurs where sometimes the trajectory of droplets follows a repeatable pattern and other times it is chaotic. As part of this work, a discrete analytical model was developed that predicts droplet transport through the junction including transitions between filtering and sorting, bifurcation in the patterns, composition of the patterns, and an estimation of when patterns will disintegrate into chaos. The model was validated by comparing it to compact numerical simulations and microfluidic experiments with good agreement.The complex behaviour of a simple junction emphasizes the challenge that remains for more highly integrated droplet microfluidic networks operating with pressure driven flow