Hydrogen-Bonding Surfaces for Ice Mitigation

Ice formation on aircraft, either on the ground or in-flight, is a major safety issue. While ground icing events occur predominantly during the winter months, in-flight icing can happen anytime during the year. The latter is more problematic since it could result in increased drag and loss of lift. Under a Phase I ARMD NARI Seedling Activity, coated aluminum surfaces possessing hydrogen-bonding groups were under investigation for mitigating ice formation. Hydroxyl and methyl terminated dimethylethoxysilanes were prepared via known chemistries and characterized by spectroscopic methods. These materials were subsequently used to coat aluminum surfaces. Surface compositions were based on pure hydroxyl and methyl terminated species as well as mixtures of the two. Coated surfaces were characterized by contact angle goniometry. Receding water contact angle data suggested several potential surfaces that may exhibit reduced ice adhesion. Qualitative icing experiments performed under representative environmental temperatures using supercooled distilled water delivered via spray coating were inconclusive. Molecular modeling studies suggested that chain mobility affected the interface between ice and the surface more than terminal group chemical composition. Chain mobility resulted from the creation of "pockets" of increased free volume for longer chains to occupy

Development of microfluidic tools for cancer single cell encapsulation and proliferation in microdroplets

The role of microfluidics in liquid biopsy as a more capable solution to address the monitoring of cancer progression in patients is gaining increasing attention. One out of the several difficulties in can-cer monitoring resides with the offset between current cell growth techniques in vitro and the influence of the cellular microenvironment in proliferation. One application of microfluidics consists in the use of microdroplets to replicate the complex dynamic microenvironment that can accurately describe factual 3D models of cancer cell growth. The goal of this thesis was to develop a set of microfluidic-based tools that would enable the encapsulation, proliferation and monitoring of single cancer cells in micro-droplets. For this, a set of microfluidic devices made of PDMS for droplet generation and containment were developed by photo- and soft-lithography techniques, being tested and optimized to ensure single cancer cell encapsulation. After the optimization of the droplet generation parameters in terms of droplet size and long-term stability on-chip, the best performance conditions were selected for cell growth ex-periments. Different densities of MDA-MB-435S cancer cells were combined with various percentages of Matrigel®, an extracellular matrix supplement, to promote cell proliferation. As a result, it was possi-ble to monitor droplets with cancer cells for a range of 1-20 days. A preliminary observation showed signs of cell aggregation, indicating that the tools developed during the thesis have the potential of developing 3D cancer spheroids from cancer single cells

DEVELOPMENT OF MICROFLUIDIC PLATFORMS AS A TOOL FOR HIGH-THROUGHPUT BIOMARKER SCREENING

Droplet microfluidic platforms are in the early stages of revolutionizing high throughput and combinatorial sample screening for bioanalytical applications. However, many droplet platforms are incapable of addressing the needs of numerous applications, which require high degrees of multiplexing, as well as high-throughput analysis of multiple samples. Examples of applications include single nucleotide polymorphism (SNP) analysis for crop improvement and genotyping for the identification of genes associated with common diseases. My PhD thesis focused on developing microfluidic devices to extend their capabilities to meet the needs of a wide array of applications

Developing an Optomechanical Approach for Characterizing Mechanical Properties of Single Adherent Cells

Mechanical properties of a cell reflect its biological and pathological conditions including cellular disorders and fundamental cellular processes such as cell division and differentiation. There have been active research efforts to develop high-throughput platforms to mechanically characterize single cells. Yet, many of these research efforts are focused on suspended cells and use a flow-through configuration. Therefore, adherent cells are detached prior to the characterization, which seriously perturbs the cellular conditions. Also, methods for adherent cells are limited in their throughput. My study is aimed to fill the technical gap in the field of single cell analysis, which is a high-throughput and non-invasive mechanical characterization of single adherent cells. I developed a multi-modal platform to mechanically characterize single adherent cells. The platform is based on optomechanical principle, which induces least perturbation on the cells and does not require cell detachment. Besides, multiple measurements can be performed on a single cell to track its mechanical behavior over time. Proposed platform can expand our understanding on the relationship between mechanical properties and cellular status of adherent cells. Single adherent cells are characterized optomechanically using the vibration-induced phase shift (VIPS). VIPS is a phase shift of apparent velocity of a vertically vibrating substrate measured with laser Doppler vibrometer (LDV), when the measurement laser passes through an adherent cell or any transparent objects on the substrate. The VIPS and height oscillation of a single cell on a vibrating substrate have negative correlation with the cell stiffness. An analytical model is established which demonstrates relationship between cell’s mechanical properties and its VIPS. With the VIPS measurements, at multiple frequencies on large population of cells, the statistical significant difference in the cell stiffness is confirmed after exposure to various drugs affecting cytoskeleton network. Also, a 3-dimensional finite element model is developed to extract the cell stiffness from VIPS. VIPS technique is used to reconstruct the detailed oscillation pattern of transparent objects such as water microdroplets and intracellular lipid droplets on a vibrating substrate, which can give us better understanding of mechanical behavior of biological transparent objects. In addition, using VIPS measurement mechanical interaction between extracellular matrixes (ECMs) and adherent cells is studied. Statistical significant difference in bonding straight of single cells and different ECMs is demonstrated

Bubble Dynamics and Acoustic Droplet Vaporization in Gas Embolotherapy.

Gas embolotherapy is a twist on traditional catheter based embolotherapy approaches. Localized gas bubbles generated are used in place of solid emboli normally used to restrict blood flow. The gas bubbles are formed through targeted vaporization of intravenously injected liquid microdroplets using focused ultrasound, also known as acoustic droplet vaporization (ADV). A greater understanding of the ADV process, bubble transport, and acoustic interactions are essential to devising a safe and effective therapy. This dissertation delves into the dynamics at various time-scales throughout the ADV process from the phase-change process to bubble transport in vessels. The dissertation has been divided into five time-scale events that may occur throughout the ADV process. First, ultra-high speed imaging investigating the initial gas nucleus formation within liquid microdroplets is compared against a numerical model of the acoustic field within the droplet to determine the mechanism behind ADV. The effects of pulse length and acoustic power are correlated with the likelihood of collapsing the newly formed bubble possibly resulting in vessel damage. Next, influences from channel resistance on the ADV bubble expansion rates and wall stress are estimated in idealized microvessels. Once the bubbles have completed expansion, transport phenomena and additional acoustic pulses may influence bubble dynamics and treatment outcomes. The scenario of a finite-sized bubble attached to a vessel wall approaching a bifurcation point is modeled using the boundary element method in order to understand the influences of sticking conditions and bifurcation geometry on bubble lodging or dislodging. Finally, an instability resulting from short acoustic pulses impinging on a bubble attached to a solid boundary resulting in droplet atomization of the bulk liquid in the bubble is characterized. The implications from all of these dynamics are discussed in the context of gas embolotherapy and extended to other ultrasound therapies. It is concluded that potential sources of damage include bubble torus formation, rapid expansion in small vessels, and contact line motion. However, it is revealed that the level of damage can be addressed through the careful choice of acoustic parameters and droplet distribution and functionalization. Furthermore, controlled stress levels can be leveraged for enhanced therapeutic benefits.PhDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/107251/1/shicheng_1.pd

A General Purpose Programmable Microfluidic Platform for Screening and Optimization of Biological Assays

Screening is a fundamental process in today’s medicine and clinical diagnostics, comprising of several processes ranging from finding new target molecules having the desired therapeutic potential to identifying biomarkers for accurate diagnosis of a spectrum of diseases. Current high throughput screening (HTS) platforms leverage sophisticated robotics to perform a large number of experiments very quickly, an otherwise unmanageable task with manual labor. However, these systems are capital intensive which limit their use to large pharmaceutical companies or larger research labs. Additionally, reagent consumption is of the order of 10-100 µL per assay, which leads to substantial consumables cost. Recently proposed droplet microfluidic technologies have the potential to substantially reduce assay costs by performing reactions using nanoliter volumes at very rapid rates. However, their incorporation into screening workflows is limited owing to various technological challenges such as on-chip droplet storage for long incubation assays, fluid waste due to large dead volumes, lack of programmable control over individual assay droplets, etc

Materials jetting for advanced optoelectronic interconnect: technologies and application

This report covers the work carried out on Teaching Company Scheme No. 2275 "Materials Jetting for Advanced Interconnect" between February 1998 and February 2000. The project was conducted at the Harlow laboratories of Nortel Networks with the support of the Department of Manufacturing Engineering of Loughborough University. Technical direction and supervision has been provided by Mr Paul Conway, Reader, at Loughborough University, Professor Ken Snowdon and Mr Chris Tanner of Nortel Networks. The aim of the project was to produce and deposit minute and precise volumes of a range of materials, such as metallic alloys, glasses and polymers, onto a variety of substrates commonly used in the electronics and optoelectronics fields. The technology, which is analogous to ink-jet printing, firstly had to be refined to accommodate higher processing temperatures of up to 350°C. The ultimate project deliverable was to produce a specification for jetting equipment suited towards volume manufacturing. [Continues.

Experimental and Theoretical Investigation of Droplet Evaporation on Heated Hydrophilic and Hydrophobic Surfaces

The evaporation characteristics of sessile droplets on heated hydrophobic and hydrophilic surfaces are investigated. Results are reported for the evaporation of water droplet volumes covering a range of shapes dominated by surface tension or gravity and over a range of temperatures between 40 and 60 °C. The weight evolution and total time of evaporation is measured using a novel self-contained heating stage on a high resolution analytical balance, which has advantages over visualization measurement techniques as it allows free choice of the initial droplet size and surface and the ability to record the droplet evaporation right through to the final stages of droplet life. Evaporation is modeled through a combination of a constant contact area and a constant contact angle model with the switch from the former to the latter occurring when the contact angle falls below its predetermined receding value. Theoretical results compare well with the experimental results for the hydrophobic substrate. However, a significant deviation is observed for the hydrophilic substrate due to the combined effects of the droplet surface cooling due to evaporation and buoyancy effects that are not included in the model. The proposed method of using the stick–slip model offers a convenient means of modeling droplet evaporation by mimicking the drying modes based on initial measurements of the static and receding contact angles

Protein Crystallization in Droplet-based Microsystems

The central focus of protein crystallization has been on the production of high quality (large well diffracting) protein crystals for protein structure determination by X-ray crystallography, being a complex and multiparametric process. The successful crystallization of a protein is determined both by thermodynamic and kinetic considerations, involving the optimization of several variables. In this context, the main goal of this work is to improve our understanding of protein crystallization, namely study the influence of some parameters on the process. For this, we propose a more rational screening strategy to the traditional trial-and-error approach. The latter is based in the use of phase diagrams at an early stage to analyse protein solubility. Further, an easy-to-use and cheap droplet-based microreactor will be explored to perform multiple protein crystallization trials. In fact, microreactors have been reported to provide a unique platform for investigating fundamental protein crystallization mechanisms, since they permit a large number of experiments under identical conditions, using small quantities of samples.status: accepte