Biomedical Engineering and Bioengineering Commons^™

Molecular Separation By Using Active And Passive Microfluidic Chip Designs: A Comprehensive Review, A. Ebrahimi, K. Icoz, R. Didarian, C.-H. Shih, A. Akpek, Berivan Cecen, Sabanci A. Bal-Ozturk, K. Güleç, Y.-C.E Li, S. Shih, B. Sirma Tarim, H.C. Tekin, E. Alarçin, H. Ghorbanpoor, C. Özel, A. Eker Sarıboyacı, Guzel F. Dogan, N. Bassous, S.R. Shin, H. Avci

Henry M. Rowan College of Engineering Faculty Scholarship

Separation and identification of molecules and biomolecules such as nucleic acids, proteins, and polysaccharides from complex fluids are known to be important due to unmet needs in various applications. Generally, many different separation techniques, including chromatography, electrophoresis, and magnetophoresis, have been developed to identify the target molecules precisely. However, these techniques are expensive and time consuming. “Lab-on-a-chip” systems with low cost per device, quick analysis capabilities, and minimal sample consumption seem to be ideal candidates for separating particles, cells, blood samples, and molecules. From this perspective, different microfluidic-based techniques have been extensively developed in the past two decades to separate …

A Microfluidic Assay For Single Cell Bacterial Adhesion Studies Under Shear Stress, Amanda Trusiak

Electronic Theses and Dissertations

The study of bacterial adhesion to host cells is important in understanding bacterial pathogenesis and developing new therapeutic approaches. Here, we studied bacterial adhesion under shear stress using a novel microfluidic method. Specifically, the adhesion of a uropathogenic E. coli strain (FimHOn, ATCC 700928/CFT073) to mannose-modified substrates was studied under flow conditions. The FimHOn E. coli strain expresses FimH which is a mannose-specific adhesin found on the fimbriae that binds to glycoproteins on the epithelium. We developed a microfluidic method that mimics bacterial adhesion to urothelial cells. First, the microfluidic channels were modified by sequentially adsorbing BSA-mannose and BSA onto …

Novel Microfabricated Systems To Elucidate The Role Of Anisotropic Stiffness In The Tumor Microenvironment, Jiten Narang

Theses and Dissertations

Cancer is the second leading cause of death in women and late stage (metastatic) cancers have abysmal survival rates compared to early stage regional cases (27% vs 86%). As a tumor grows, the surrounding extracellular matrix (ECM) is reorganized into a dense, collagen rich matrix. The new matrix of aligned collagen fibers provides unique mechanical cues such as anisotropic stiffness and contact guidance. Matrix turnover also constricts local vasculature and restricts delivery of key nutrients and signaling molecules to malignant cells to outside the tumor creating a chemotactic gradient from outside to inside. In this work, we developed a novel …

The Development Of A Novel Blood-Brain Barrier, Organ-On-A-Chip System And The Identification Of Erythrocytes As A Key Contributor To Age-Associated Neurological Decline, Payam Amiri

KGI Theses and Dissertations

Advancements in modern medicine have greatly extended human life expectancy. However, with the onset of age-associated conditions such as Alzheimer’s disease, autoimmune disorders, and certain cancers, healthy aging is becoming an increasingly pressing issue. Blood exchanges between young and old partners demonstrate old blood can cause detrimental effect to the young animal, notably on the brain tissue. However, the complexity of blood makes it difficult to identify what role the individual factors play in the aggregate observed effect. This dissertation seeks to explore the potential effects of erythrocytes on the brain as we age. Erythrocyte morphology and rigidity changes as …

Evaluation Of Cell Concentration And Viability By Impedance Spectroscopy On Microfluidic Devices, Jason Eades

LSU Master's Theses

This document describes two distinct platforms that implement electrochemical impedance spectroscopy (EIS) within microfluidic devices for rapid, label-free cell analysis. Each study provides proof-of-concept evaluations of these devices for cell counting and viability analysis applications to mitigate some of the challenges associated with conventional methods. Chapter one includes background information on each version of EIS selected and motivations for the studies conducted. Chapter two describes the design and fabrication of a modular, reusable microfluidic device. Additionally, the methodology for and results from the application of this platform for the measurement of zebrafish sperm cell concentrations are presented. Chapter three describes …

Micro-Physiological Models To Mimic Mucosal Barrier Complexity Of The Human Intestine In Vitro, Abhinav Sharma

Doctoral Dissertations

The mucosal barrier in the intestine is vital to maintain selective absorption of nutrients while protecting internal tissues and maintaining symbiotic relationship with luminal microbiota. This bio-barrier consists of a cellular epithelial barrier and an acellular mucus barrier. Secreted mucus regulates barrier function via in situ biochemical and biophysical interaction with luminal content that continually evolves during digestion and absorption. Increasing evidence suggests that a mucus barrier is indispensable to maintain homeostasis in the gastrointestinal tract. However, the importance of mucus barrier is largely underrated for in vitro mucosal tissue modeling. The major gap is the lack of experimental material …

Mathematical Characterization Of A Microfluidic Ultrasound Driven Transfection Device., Chris J. Holton

Electronic Theses and Dissertations

The objective of this thesis is to develop a mathematical model characterizing the behavior of a microfluidic sonoporation device in order to understand how standing wave conditions influence molecular delivery to cells and determine whether the model predicts device performance. A prior model based on an ultrasonic separation cell that uses standing waves to separate particles is adapted for translation to the microfluidic device. This study generates data on acoustic pressure profiles across the cell as well as identifying optimal driving frequencies. This model is validated and the equations and methods for developing this model are translated to the microfluidic …

Automated Microscope Stage, Corin Nishimoto, Alison Flesch, Theo Anastos

Biomedical Engineering

This document seeks to describe the background information, customer requirements, design specifications, indications for use, selected materials, proposed budget, prototypes, final design, manufacturing processes, and testing methods regarding the CellOptimizer automated microscope stage product.

Mechanical Stresses On Nasal Mucosa Using Nose-On-Chip Model, Zachary Edward Brooks

Browse all Theses and Dissertations

The objective of this research was to design and fabricate a nose-on-chip device and bi-directional airflow system that models flow within the nasal cavity to investigate how airflow induced mechanical stresses impact nasal secretion rates and cytoskeletal remodeling. This research hypothesizes that the airflow induced shear stresses on the nasal mucosa will influence mucus production and the cytoskeleton of the cells. The RPMI 2650 cell line was used to model the nasal mucosa. The system was used to replicate the wall shear stresses (WSS) and wall shear forces (WSF) present in the anterior region of the nose. The WSS and …

Thermally-Assisted Acoustofluidic Separation For Bioanalytical Applications, Ata Dolatmoradi

FIU Electronic Theses and Dissertations

Changes in the biomechanical properties of cells accompanying the development of various pathological conditions have been increasingly reported as biomarkers for various diseases and as a predictor of disease progression stages. For instance, cancer cells have been found to be less stiff compared to their healthy counterparts due to the proteomic and lipidomic dysregulations conferred by the underlying pathology. The separation and selective recovery of cells or extracellular vesicles secreted from such cells that have undergone these changes have been suggested to be of diagnostic and prognostic value.

This dissertation first describes the implementation of a stiffness-based separation of phosphatidylcholine-based …

A Drosophila Model To Examine Collective Migration During Retinogenesis, Caroline Pena, Stephanie Zhang, Mildred Kamara, Tadmiri Venkatesh, Maribel Vazquez

Publications and Research

Retinal dysfunction is often caused by aberrant neural cell migration during development. In this study, we observed the migration of neural cells of the Drosophila melanogaster after marking cells of the 3rd instar larvae with the GAL4-UAS expression system when exposed to a concentration gradient of FGF-8 through the use of a microfluidic device. The glial and neuronal cell ratio in the developing brain was determined through immunofluorescent staining and observation. In future studies, a microfluidic device that mimics the developing Drosophila brain and retina will be designed in order to better understand the biological factors that affect the migration …

Sub-Picogram, Inline Detection Of Proteins Using Microfluidic Drop Generators And Shape-Based Detection, Razieh Kebriaei

Wayne State University Dissertations

Proteomic workflows rely on sensitive and precise methods for purifying and detecting proteins, and one of the most popular methods is liquid chromatography (LC) followed by an inline detector. However, the most commonly used method, UV-Vis absorbance, provides relatively low sensitivity and requires long path lengths in the flow cell. In this thesis, we present a highly sensitive, label-free method to detect proteins in continuous flow, using a pressure-driven microfluidic droplet generator. The system consists of a cross junction or flow focusing structure where the flowing stream of proteins is combined with two coflowing streams of oil which break up …

Microengineering The Neural Tube, Christopher Demers

Electronic Theses and Dissertations

Early embryonic development is a complex and highly regulated orchestra of instructive cues that collectively guide naïve stem cells towards progressively more specialized fates. In the neural tube, the precursor structure to the brain and spinal cord, these signals emanate from ‘organizing centers’ surrounding the neural tube. These organizing centers send out soluble cues or morphogens that diffuse tens to hundreds of microns to recipient cells residing in the neural tube. Re-creating this dynamic landscape of cues in vitro is impossible using standard cell culture tools and techniques. However, microfluidics is perfectly suited to fill this gap, allowing precise control …

Microfluidic Generated Egf-Gradients Induce Chemokinesis Of Transplantable Retinal Progenitor Cells Via The Jak/Stat And Pi3kinase Signaling Pathways., Uchenna J. Unachukwu, Moira Sauane, Maribel Vazquez, Stephen Redenti

Publications and Research

A growing number of studies are evaluating retinal progenitor cell (RPC) transplantation as an approach to repair retinal degeneration and restore visual function. To advance cell-replacement strategies for a practical retinal therapy, it is important to define the molecular and biochemical mechanisms guiding RPC motility. We have analyzed RPC expression of the epidermal growth factor receptor (EGFR) and evaluated whether exposure to epidermal growth factor (EGF) can coordinate motogenic activity in vitro. Using Boyden chamber analysis as an initial high-throughput screen, we determined that RPC motility was optimally stimulated by EGF concentrations in the range of 20-400 ng/ml, with decreased …

A New Computational Model To Augment The Design Of Microfluidic Separations: Electric Field Assisted, Hydrodynamic Chromatography, Jeffrey D. Wells

Master's Theses

This project encompasses the implementation of a computational model to simulate the microfluidic separation of like-charged particles in a continuous flow environment. By accomplishing this task the model can be used to optimize future fractionations by tailoring the process parameters to the properties of the target particles. The primary goal of this project is to develop a vectorized code within Matlab® that captures a sufficient quantity of the physics in separations to assist with the optimization and design of microfluidic systems.

This project differs from other computational models in that it utilizes a personal computer to run the simulation in …

An Inexpensive Method For Creating Paste To Be Used In Paper-Based Microfluidic Devices, Kirra Marie Sankey

Biomedical Engineering

Microfluidic devices are diagnostic tools that are small, portable, and inexpensive. This makes them ideally suited for resource-limited settings. To construct a 3D device, each layer of patterned paper is stacked using double-sided tape with holes corresponding to the pattern. It is necessary to have a paste to fill the holes in the tape and provide a medium for the fluid to wick through. The powder used to make the paste is very expensive and must be bought in bulk (an estimated $1121 - $1231), so it is not convenient for the Biomedical (BMED) department to use. This project was …

A Pmma Conductivity Pretreatment Microfluidics Device For The Optimization Of Electrokinetic Manipulations, Cameron Paul Purcell

Master's Theses

This project encompasses the design and development of a pretreatment microfluidic device for samples of physiological conductivity, namely a saline solution. The conductivity was reduced through the combination of dilution and ion removal using electric fields to enable downstream electro kinetic manipulations. The two major parts of this project include (1) designing a pretreatment protocol to reduce the conductivity of the sample solution to an acceptable level and (2) designing /fabricating a microchip that will effectively allow aim (1) to be performed on chip.

This project is one of the first to observe the effects of an electric field, used …

A Microfluidic Device To Establish Concentration Gradients Using Reagent Density Differences, Qingjun Kong, Richard A. Able, Jr., Veronica Dudu, Maribel Vazquez

Publications and Research

Microfabrication has become widely utilized to generate controlled microenvironments that establish chemical concentration gradients for a variety of engineering and life science applications. To establish microfluidic flow, the majority of existing devices rely upon additional facilities, equipment, and excessive reagent supplies, which together limit device portability as well as constrain device usage to individuals trained in technological disciplines. The current work presents our laboratory-developed bridged microLane system, which is a stand-alone device that runs via conventional pipette loading and can operate for several days without need of external machinery or additional reagent volumes. The bridged microLane is a two-layer polydimethylsiloxane …

A Pdms Sample Pretreatment Device For The Optimization Of Electrokinetic Manipulations Of Blood Serum, Timothy J. Abram

Master's Theses

This project encompasses the design of a pretreatment protocol for blood serum and adaption of that protocol to a microfluidic environment in order to optimize key sample characteristics, namely pH, conductivity, and viscosity, to enable on-chip electrokinetic separations. The two major parts of this project include (1) designing a pretreatment protocol to optimize key parameters of the sample solution within a target range and (2) designing /fabricating a microchip that will effectively combine the sample solution with the appropriate buffers to replicate the same bench-scale protocol on the micro-scale.

Biomarker detection in complex samples such as blood necessitates appropriate sample …

Creation Of Defined Single Cell Resolution Neuronal Circuits On Microelectrode Arrays, Russell Pirlo

All Dissertations

The way cell-cell organization of neuronal networks influences activity and facilitates function is not well understood. Microelectrode arrays (MEAs) and advancing cell patterning technologies have enabled access to and control of in vitro neuronal networks spawning much new research in neuroscience and neuroengineering. We propose that small, simple networks of neurons with defined circuitry may serve as valuable research models where every connection can be analyzed, controlled and manipulated.
Towards the goal of creating such neuronal networks we have applied microfabricated elastomeric membranes, surface modification and our unique laser cell patterning system to create defined neuronal circuits with single-cell precision …