Biochemical and Biomolecular Engineering Commons^™

Development Of Translational Microscale Systems To Interrogate How Biophysical And Biochemical Cues Alter The Phenotype Of Hormone Positive Breast Cancer, Braulio Ortega Quesada

All Dissertations

Cancer is a complicated disease and one in every three diagnoses are women with breast cancer. Recent research shows that the progression of cancer depends strongly on interactions with other non-cancerous cells and non-cellular components. Metastasis, the spread of cancer to other parts of the body, is a key step in cancer progression and makes treatment harder, leading to poor response to treatments culminating in death in ~90% of patients. This dissertation focused on creating a series of microdevices as novel pre-clinical models of breast cancer. Two different devices were fabricated to (1) study how exposing cancer cells to the …

Fundamental Study Of Nonlinear Electrophoresis, Joseph Armakan Bentor

All Dissertations

Classical electrophoretic theory describes the linear response of particles suspended in Newtonian fluids under weak electric fields. When the electric field exceeds this weak limit, a nonlinear response arises due to non-uniform surface conduction over the curved particles. This nonlinear behavior introduces dependencies on fluid and particle properties not considered in the classical theory, offering potential advantages for microfluidic particle manipulation. While this phenomenon has been extensively studied theoretically and numerically in Newtonian fluids, experimental investigations have been relatively limited.

Fluid rheology can significantly alter particle dynamics under applied electric fields. Rheological properties like shear-thinning and elasticity which are not …

Investigating The Role Of Fluid Shear Stress During Metastasis On Enhanced Breast Cancer Extravasation, Alejandra M. Ham

LSU Master's Theses

In 2022, ~288,000 American women were diagnosed with metastatic breast cancer which was the leading cause of patient mortality with ~43,000 American women succumbing to the disease. Women can be diagnosed with four different molecular subtypes of breast cancer: luminal A, luminal B, human epithelial growth receptor type 2 enriched (HER2+), and triple-negative breast cancer (TNBC). TNBC accounts for ~12% of all breast cancers, yet it has the worst outcomes. TNBC is highly invasive, with ~46% of TNBC patients developing metastatic disease. A further understanding of metastatic TNBC is needed to provide a greater understanding of how to treat this …

Scaffold-Based 3d Cell Culture Models In Cancer Research, Waad H. Abuwatfa, William G. Pitt, Ghaleb A. Husseini

Faculty Publications

Three-dimensional (3D) cell cultures have emerged as valuable tools in cancer research, offering significant advantages over traditional two-dimensional (2D) cell culture systems. In 3D cell cultures, cancer cells are grown in an environment that more closely mimics the 3D architecture and complexity of in vivo tumors. This approach has revolutionized cancer research by providing a more accurate representation of the tumor microenvironment (TME) and enabling the study of tumor behavior and response to therapies in a more physiologically relevant context. One of the key benefits of 3D cell culture in cancer research is the ability to recapitulate the complex interactions …

Liposomes-Encapsulating Double-Stranded Nucleic Acid (Poly I:C) For Head And Neck Cancer Treatment, Vidit Singh, Anna Chernatynskaya, Lin Qi, Hsin Yin Chuang, Tristan Cole, Vimalin Mani Jeyalatha, Lavanya Bhargava, W. Andrew Yeudall, Laszlo Farkas, Hu Yang

Chemical and Biochemical Engineering Faculty Research & Creative Works

Polyriboinosinic acid-polyribocytidylic acid (Poly I:C) serves as a synthetic mimic of viral double-stranded dsRNA, capable of inducing apoptosis in numerous cancer cells. Despite its potential, therapeutic benefits, the application of Poly I:C has been hindered by concerns regarding toxicity, stability, enzymatic degradation, and undue immune stimulation, leading to autoimmune disorders. To address these challenges, encapsulation of antitumor drugs within delivery systems such as cationic liposomes is often employed to enhance their efficacy while minimizing dosages. In this study, we investigated the potential of cationic liposomes to deliver Poly I:C into the Head and Neck 12 (HN12) cell line to induce …

A Microscale Approach To Investigate Breast Cancer Cellular Communication And Migration, Sharif Mohammad Mizanur Rahman

LSU Doctoral Dissertations

Metastatic breast cancer significantly decreases patient survival, with the majority of deaths caused by secondary metastasis. Cancer metastasis is a multi-step process that starts with the detachment of a cancer cell from the primary tumor and ends with establishing a secondary tumor at a distal location. This work's focus was to use an interdisciplinary microscale approach to study how cancer cells respond to neighboring cells and how they migrate in response to chemical gradients. Two distinct devices, a microfluidic device, and a 3D-printed plate insert, were developed to perform co-culture studies to elucidate the impact of ASCs on cancer cell …

Reaction Profiling Of Extracellular Protein Phosphorylation Through A Microfluidic Reactor Coupled With Raman Spectroscopy, Abigail Casey

Theses and Dissertations

Diseases and disorders in the human body are considered abnormalities of proper cellular function. Understanding the signal transduction mechanisms that cause these abnormalities is crucial to developing earlier detection methods, better treatment options and effective cures. While current diagnostic procedures are powerful tools in diagnosing diseases, they are ineffective in informing physicians on the real-time behavior of the signal transduction mechanisms associated with diseases and disorders. Currently, disease progression is monitored over time through routine patient visits and testing by one or more of the above techniques. By developing an approach that can monitor structural and conformational changes of proteins …

Development Of A Comsol Microdialysis Model, Towards Creation Of Microdialysis On A Chip With Improved Geometries And Recovery, Patrick Pysz

Graduate Theses and Dissertations

Microdialysis (µD) sampling is a diffusion-limited sampling method that has been widely used in different biomedical fields for greater than 35 years. Device calibration for in vivo studies is difficult for current non-steady state analytes of interest correlated with both inflammatory response and microbial signaling molecules (QS); which exist in low ng/mL to pg/mL with molecular weights over a wide range of 170 Da to 70 kDa. The primary performance metric, relative recovery (RR), relating the collected sample to the extracellular space concentration varies from 10% to 60% per analyte even under controlled bench-top conditions. Innovations in microdialysis device design …

Direct Quantification Of Deubiquitinating Enzyme Activity In Single Intact Cells, Nora Safabakhsh

LSU Doctoral Dissertations

Challenges in drug efficacy occur during the treatment of most types of cancer due to the heterogeneity of the tumor microenvironment. This has led to the development of personalized medicine. Due to the clinical success of the proteasome inhibitors Bortezomib and Carfilzomib in treatment of multiple myeloma, interest has shifted towards molecularly-targeted chemotherapeutics for ubiquitin-proteasome system (UPS). Deubiquitinating enzymes (DUBs) are an essential part of this pathway which have been found to promote Bortezomib resistance in multiple myeloma patients. Unfortunately, there is a lack of specific, high throughput biochemical assays to characterize DUB activity in patient samples before and after …

The Development Of Microfluidic Devices For The Production Of Safe And Effective Non-Viral Gene Delivery Vectors, Jason Matthew Absher

Theses and Dissertations--Chemical and Materials Engineering

Including inherited genetic diseases, like lipoprotein lipase deficiency, and acquired diseases, such as cancer and HIV, gene therapy has the potential to treat or cure afflicted people by driving an affected cell to produce a therapeutic protein. Using primarily viral vectors, gene therapies are involved in a number of ongoing clinical trials and have already been approved by multiple international regulatory drug administrations for several diseases. However, viral vectors suffer from serious disadvantages including poor transduction of many cell types, immunogenicity, direct tissue toxicity and lack of targetability. Non-viral polymeric gene delivery vectors (polyplexes) provide an alternative solution but are …

Computational And Experimental Determination Of The Mixing Efficiency Of A Microfluidic Serpentine Micromixer, Siril Arockiam

Theses

In microfluidics, efficiency and mixing time are the greatest disadvantages. These parameters hinder the application of microfluidic devices for biochemical and immunological assays. However, once these disadvantages have been overcome by optimizing the parameters of the microfluidic device, it becomes the important analytical tool. In this experiment, various designs of microfluidic devices have been both simulated using COMSOL software, and experimentally verified to obtain the optimized parameter such as depth and velocity for better mixing efficiency. The COMSOL model has been validated by comparing the results with fluorescent images data of the experiment. The microfluidic device is built with Adhesive …

Microfluidic Devices Applied On Enriching Post –Translational Modified Proteins For Proteomics, Hui Xia

Doctoral Dissertations

In this work, microfluidic devices were developed for enriching post-translational modified proteins. Post-translational modifications (PTM) of proteins play essential roles in cellular physiology and disease. The identification of protein substrates and detection of modification site helps understand PTM-mediated regulation in essential biological pathways and functions in various diseases. However, PTM proteins are typically present only at trace levels, making them difficult to identify in mass spectrometry based proteomics. This work study is about the design, fabrication and testing of the microfluidic device for the enrichment of abundant amount of PTMs. Carbonylated protein is used as a representative PTM to illustrate …