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.

The development of microneedles that penetrate the skin barrier, but are small enough not to stimulate nerves, has the potential to deliver drugs across skin in a painless way. Controlled injection by convective flow into skin using hollow microneedles, however, has remained a challenge. To address this challenge, the goals of this study were (i) to provide experimental measurements coupled with numerical simulations to quantitatively describe fluid mechanics of flow within microneedles over a range of experimental conditions and needle geometries, (ii) to demonstrate and study the effects of diffusion-based delivery of insulin to diabetic rats in vivo using solid and hollow microneedles and (iii) to determine the effect of experimental parameters on microinfusion through hollow microneedles into skin to optimize drug delivery protocols and identify rate-limiting barriers to flow. Experimentally, we quantified the relationship between pressure drop and flow rate through microneedles as a function of fluid viscosity and microneedle length, diameter, and cone half-angle. Microneedle tip diameter and taper angle were the primary controlling parameters for flow through conically tapered microneedles as shown by numerical simulations. Flow rates over a range of 1.4 56 l/s were achieved through microneedles (in the absence of skin) with pressure drops in the range of 4.6 196.5 kPa. This work also studied the use of solid and hollow microneedle arrays to insert into the skin of diabetic animals for transdermal delivery of insulin. Blood glucose levels dropped by as much as 80% in diabetic rats in vivo. Larger drops in blood glucose level and larger plasma insulin concentrations were shown due to higher donor solution insulin concentration, shorter microneedles insertion time and fewer repeated insertions. The final scope of this work was to determine the effect of microneedle geometry and infusion protocols on microinfusion flow rate into skin in vitro. Infusion flow rates ranged from 21 to 1130 l/h was demonstrated using glass microneedles. The presence of a bevel at the microneedle tip, larger retraction distance and insertion depth, larger infusion pressure and the presence of hyaluronidase led to larger infusion flow rates.

Recent advances in microfluidic technologies have enabled integration of the functional units for biological and chemical analysis onto miniaturized chips, called Labon- a-Chip (LOC). However, the effective manipulation and control of colloidal particles suspended in fluids are still challenging tasks due to the lack of clear characterization of particle control mechanisms. The aim of this dissertation is to develop microfluidic techniques and devices for manipulating colloids and biological particles with the utilization of alternating current (AC) electric fields and acoustic waves. The dissertation presents a simple theoretical tool for predicting the motion of colloidal particles in the presence of AC electric field. Dominant electrokinetic forces are explained as a function of the electric field conditions and material properties, and parametric experimental validations of the model are conducted with particles and biological species. Using the theoretical tool as an effective framework for designing electrokinetic systems, a dielectrophoresis (DEP) based microfluidic device for trapping bacterial spores from high conductivity media is developed. With a simple planar electrode having well defined electric field minima that can act as the targetattachment/ detection sites for integration of biosensors, negative DEP trapping of spores on patterned surfaces is successfully demonstrated. A further investigation of DEP colloidal manipulation under the effects of electrothermal flow induced by Joule heating of the applied electric field is conducted. A periodic structure of the electrothermal flow that enhances DEP trapping is numerically simulated and experimentally validated. An acoustic method is investigated for continuous sample concentration in a microscale device. Fast formation of particle streams focused at the pressure nodes is demonstrated by using the long-range forces of the ultrasonic standing waves (USW). High frequency actuation suitable for miniaturization of devices is successfully applied and the device performance and key parameters are explained. Further extension and integration of the technologies presented in this dissertation will enable a chip scale platform for various chemical and biological applications such as drug delivery, chemical analyses, point-of-care clinical diagnosis, biowarfare and biochemical agent detection/screening, and water quality control.

Thesis (M.S.)--Rochester Institute of Technology, 2009. / Typescript. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 73-79).

Fast mixing remains a major challenge in droplet-based microfluidics. The low Reynolds number operating regime typical of most microfluidic devices signify laminar and orderly flows that are devoid of any inertial characteristics. To increase mixing rates in droplet-based devices, a novel technique is presented that uses a high Reynolds number gaseous phase for droplet generation and transport and promotes mixing through binary droplet collisions at velocities near 1m/s. Control of multiple gas and liquid streams is provided by a newly constructed microfluidic test bed that affords the stringent flow stability required for generating liquid droplets in gaseous flows. The result is droplet production with size dispersion and generation frequencies not previously achievable. Limitations of existing mixing diagnostic methods have led to the development of a new measurement technique for measuring droplet collision mixing in confined microchannels. The technique employs single fluorophore laser-induced fluorescence, custom image processing, and meaningful statistical analysis for monitoring and quantifying mixing in high-speed droplet collisions. Mixing information is revealed through three governing statistics that that separate the roles of convective rearrangement and molecular diffusion during the mixing process. The end result is a viewing window into the rich dynamics of droplet collisions with spatial and temporal resolutions of 1μm and 25μs, respectively. Experimental results obtained across a decade vi of Reynolds and Peclet numbers reveal a direct link between droplet mixing time and the collision convective timescale. Increasing the collision velocity or reducing the collision length scale is the most direct method for increasing droplet mixing rates. These characteristics are complemented by detaching droplets under inertial conditions, where increasing the Reynolds number of the continuous gaseous phase generates and transports smaller droplets at faster rates. This work provides valuable insight into the emerging field of two-phase gas-liquid microfluidics and opens the door to fundamental research possibilities not offered by traditional oil-based architectures. / text

This work presents the first electrochemical observation of single polystyrene microbead collisions with an electrode within a microchannel. We have observed that detecting single microbead collisions is facile with this system. Additionally, we have shown that by increasing flow within the channel, one can increase both the frequency and magnitude of collision signals. This technique may provide a means of signal amplification in future sensing work. / text

published_or_final_version / Mechanical Engineering / Doctoral / Doctor of Philosophy

The development of microdevices for applications related to bioanalysis is described. There are two types of microdevices involved in this study: DNA (or RNA) microarrays and bead-based microfluidic devices. First, a new method to fabricate DNA microarrays is developed: replication of DNA microarrays. It was shown that oligonucleotides immobilized on a glass master can hybridize with their biotin-modified complements, and then the complements can be transferred to a streptavidinfunctionalized replica surface. This results in replication of the master DNA array. Several innovative aspects of replication are discussed. First, the zip code approach allows fabrication of replica DNA arrays having any configuration using a single, universal master array. It is demonstrated that this approach can be used to replicate master arrays having three different sequences (spot feature sizes as small as 100 [mu]m) and that master arrays can be used to prepare multiple replicas. Second, it is shown that a surface T4 DNA polymerase reaction improves the DNA microarray replication method by removing the requirement for using presynthesizd oligonucleotides. This in-situ, enzymatic synthesis approach is used to replicate DNA master arrays consisting of 2304 spots and arrays consisting of different oligonucleotide sequences. Importantly, multiple replica arrays prepared from a single master show consistent functionality to hybridization-based application. It is also shown that RNA microarrays can be fabricated utilizing a surface T4 DNA ligase reaction, which eliminates the requirement of modified RNA in conventional fabrication schemes. This aspect of the work shows that the replication approach may be broadly applicable to bioarray technologies. A different but related aspect of this project focuses on biosensors consisting of microfluidic devices packed with microbeads conjugated to DNA capture probes. The focus here is on understanding the parameters affecting the hybridization of DNA onto the probeconjugated microbeads under microfluidic flow conditions. These parameters include the surface concentration of the probe, the flow rate of the solution, and the concentration of the target. The simple microfluidic device packed with probe-conjugated microbeads exhibits efficient target capture resulting from the inherently high surface-area-to-volume ratio of the beads, optimized capture-probe surface density, and good mass-transfer characteristics. Furthermore, the bead-based microchip is integrated with a hydrogel preconcentrator enhancing the local concentration of DNA in a icrochannel. The integration of the preconcentrator into the bead-based capture chip allows significantly lower limit of detection level (~10-fold enhancement in the sensitivity of the microbeadbased DNA detection). / text

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