Biochemical and Biomolecular Engineering Commons^™

Continuous, Platform Purification Of Viral Products Using Aqueous Two-Phase Extraction, Natalie M. Nold

Dissertations, Master's Theses and Master's Reports

Cell and gene therapies, a ground-breaking class of drugs that can heal genetic diseases and cure cancer, often have treatment costs over $1 million. Most cell and gene therapies are delivered using virus-based delivery vectors, which are incredibly expensive to manufacture. Liquid chromatography is the favored method of viral vector purification since it is easily scalable and can be functionalized to purify by biospecificity, charge, hydrophobicity, or size. However, chromatography-based purification processes are highly expensive and usually only recover 20-50% of the viral vectors. There is currently no platform purification strategy for viral vectors due to differences in their surface …

Optimizing Diabetes Diagnostics: Electrophoretic Separation And Detection Of Hemoglobin A1c With Boronate, Rixlie Fozilova

Dissertations, Master's Theses and Master's Reports

Diabetes affects 537 million people worldwide, while 136 million Americans have diabetes or prediabetes; roughly 22.6% of individuals are undiagnosed. Diabetes is the inability to regulate blood sugar levels. Hemoglobin A1c (HbA1c) is glycosylated hemoglobin and indicates average blood sugar levels over the past three months.

We adapted the selective boronic acid binding to the HbA1c sugar moieties from boronate affinity chromatography and translated it into a portable microchip paper-based electrophoresis platform. We explored a range of boronate concentrations at a steady voltage and sample volume to determine the optimal HbA1c binding and subsequent electrophoretic separation. A pH above 11 …

Exploring Ph Gradient Phenomena In Non-Linear Electrokinetic Microfluidic Devices, Azade Tahmasebi

Dissertations, Master's Theses and Master's Reports

Electrokinetic microfluidics is a versatile technology utilized within lab on a chip (LOC) devices for diagnostic and analytical applications; advantages include reduced resource demands, flexibility, and simplicity of use. Dielectrophoresis (DEP) is a precision nonlinear electrokinetic tool utilized within microfluidic microdevices to induce polarization and control bioparticle motions for applications that range from hemoglobin separations to cancer cell isolation and detection. Despite promising results, undesired side phenomena can occur in electrokinetic systems which impede reproducibility and accuracy. These unfavorable phenomena have not been comprehensively explored in the literature. Prior preliminary research suggests the fundamental phenomena originate from microelectrodes utilized in …

Chemical Decomposition Of Flexible Polyurethane Foam To Generate A Media For Microbial Upcycling, Kaushik Baruah

Dissertations, Master's Theses and Master's Reports

Polyurethane waste is becoming a global concern as a large amount is being disposed of in landfills every year, and only a fraction is being recycled. Several polyurethane recycling techniques exist, of which ammonolysis and base-catalyzed hydrolysis is the least explored. Flexible polyurethane foam (FPUF) decomposition can generate amines that can act as a carbon source for the growth of microbial consortia. This study aims to generate a novel media capable of microbial upcycling via ammonolysis and base-catalyzed hydrolysis of flexible polyurethane foams (FPUFs) using ammonium hydroxide and subsequently determine the reaction conditions for maximum solubilization of polyurethane foam in …

Microscopic And Laboratory Scale Characterization Methods To Evaluate Biomass Deconstruction, Meenaa Chandrasekar

Dissertations, Master's Theses and Master's Reports

Renewable fuels from lignocellulosic biomass are an appealing option because they can seamlessly integrate into the existing fuel distribution infrastructure. Lignocellulosic biomass constitutes nonedible plant material obtained from plant cell walls. The natural recalcitrance of lignocellulosic biomass poses a challenge in accessing the cell wall carbohydrates during biochemical conversion. Despite various approaches, enzymatic hydrolysis of lignocellulosic biomass remains economically impractical due to incomplete knowledge about biomass recalcitrance and the influence of environmental factors on biomass quality.

The first goal of this dissertation was to construct a microfluidic imaging reactor to better understand the tissue-specific deconstruction of plant materials. Confocal laser …

The Extraction Of Waxes And Lipids From Sorghum Using Green And Renewable Solvents Followed By Conversion To Biofuels Using Gamma-Valerolactone Pretreatment, Marissa Gallmeyer

Dissertations, Master's Theses and Master's Reports

Plant matter contains waxes and lipids that can be extracted and used or sold as a value-added product prior to conversion of the remaining plant material to biofuels. Wax and lipid extraction of plant materials is currently performed using volatile, non-renewable hydrocarbons, primarily hexane, which is produced from fossil fuels and can pose a health and safety hazard. The purpose of this study is to compare the amount and characteristics of waxes extracted by hexane with those extracted using organic solvents that are less toxic and can be produced from renewable sources.

Sorghum samples were extracted separately with hexane, 2-methyltetrahydrofuran …

Effects Of Microporous Structure On The Enzymatic Conversion Of Biomass Using A Multiscale Model, Saketh Merugu

Dissertations, Master's Theses and Master's Reports

The generation of biofuels from lignocellulosic biomass involves innovative process technology that is being investigated worldwide. Enzymatic hydrolysis is a major step in the contemporary process of the generation of biofuels. Guided by pore size distribution measured using NMR cryoporometry, we developed pore-enzyme diffusion and adsorption models at the particle level coupled with a kinetic model for cellulose, cellobiose, and glucose production at flask level. By simulating these models in MATLAB, COMSOL, and Polymath software packages, we investigate the effects of various biomass particle-related parameters (particle dimensions, porosity, enzyme accessibility) on the characteristic time of enzyme diffusion and adsorption and …

Virus Purification Framework And Enhancement In Aqueous Two-Phase System, Pratik Umesh Joshi

Dissertations, Master's Theses and Master's Reports

Viral infections regularly pose detrimental health risks to humans. Preventing viral infections through global immunization requires the production of large doses of vaccines. The increasing demand for vaccines, especially during pandemics such as COVID-19, has challenged current manufacturing strategy to develop advanced unit operations with high throughput capability. Over the decade, the upstream processing responsible for synthesizing viral products in cell cultures has shown significant success in yielding high titers of viruses and virus-like particles. The progress in the upstream stage has now shifted the bottleneck to the downstream processing (DSP). Overlooked for decades, the DSP responsible for viral product …

Innovative Sustainable Wood Preservatives From Pulp And Paper Industry Byproduct, Raisa Carmen Andeme Ela

Dissertations, Master's Theses and Master's Reports

In the modern forest industry, the need for bio-based, renewable, and environmentally-benign wood preservatives is increasing. Preservatives are used to prevent or limit decay and there has been an increasing interest in developing wood preservatives from renewable materials. To support the need for bio-based, environmentally-friendly preservatives, this work employed kraft lignin as a raw material to produce a novel bio-based wood preservative.

For the first project, a statistical design of experiments approach in Minitab® was used to study how fractionation process variables during acid precipitation of lignin influence the lignin mass yield and characteristics. After precipitating lignin from black liquor, …

Systems Analysis For Sustainability Assessment Of Biogas And Bio-Ch4 Production From Food Waste And Dairy Manure Mixtures In The Us, Sharath Kumar Ankathi

Dissertations, Master's Theses and Master's Reports

The purpose of the dissertation is to relate systems analysis for bioenergy to identify optimum configurations for improved scenarios and to make better decisions in a systems perspective.

Chapter 1 is a review of the literature to identify the state of the knowledge in terms of systems analysis for anaerobic digestion (AD) bioenergy systems. The key outcomes from this review showed that anaerobic digestion of mixtures of food waste and animal manure has great potential to achieve economic and environmental benefits compared to other treatments of organic waste materials, such as landfilling or conventional manure management.

Chapter 2 focuses on …

Mechanisms Of Pathogen Inactivation In Wastewater And Pharmaceutical Applications, Christa L. Meingast

Dissertations, Master's Theses and Master's Reports

Infectious diseases are a significant threat to public health. Though society enacts practices to prevent the spread of these dangerous diseases, challenges remain. Therefore, continual advancements in treatment and prevention are required. Wastewater treatment and viral clearance in pharmaceutical applications are two key health measures that prevent the spread of infections.

A low-cost, low-technology biosolids treatment process was developed to improve wastewater treatment by collecting key information on storage temperature, ammonia, volatile solids, moisture content, pH, and pathogen inactivation in biosolids over long-term storage at two wastewater treatment plants located in northern climates of the United States. Inactivation of pathogens …

Detection And Thermal Stabilization Of Virus Based On Surface Properties, Xue Mi

Dissertations, Master's Theses and Master's Reports

Viral diseases take the lives of millions of people each year. The most effective methods to prevent viral disease outbreak are viral detection to reduce contact with viral pathogens and vaccines to prevent disease. To reduce the costs of the detection of viruses and improve vaccine formulation, we explored viral surface properties. The properties we have focused on are viral hydrophobicity and surface charge using chemical force microscopy (CFM). CFM is a single-particle technique that measures the adhesion force of a functionalized atomic force microscopy (AFM) probe, and in this study, a virus covalently bound to a surface. The non-enveloped …

Continuous Viral Vaccine Manufacturing And Viral Detection Strategies, Dylan G. Turpeinen

Dissertations, Master's Theses and Master's Reports

Viruses are responsible for many human diseases that lead to suffering and death. Acquired immunodeficiency syndrome (AIDS), influenza, and coronavirus disease 2019 (COVID-19) have claimed the lives of millions of people. Two methods have been created to reduce the suffering caused by these diseases. The first is the manufacturing of vaccines that prevent disease and the second is the development of virus detection tests that lead to treatment. The work summarized in this dissertation discusses the development of a continuous virus purification process using an aqueous two-phase system for use in vaccine manufacturing. Additionally, two novel virus detection methods were …

Exploring The Role And Impact Of Microscale Phenomena On Electrode, Microdevice, And Cellular Function, Sanaz Habibi

Dissertations, Master's Theses and Master's Reports

Microfluidic technologies enable the development of portable devices to perform multiple high-resolution unit operations with small sample and reagent volumes, low fabrication cost, facile operation, and quick response times. Microfluidic platforms are expected to effectively interpret both wanted and unwanted phenomena; however, a comprehensive evaluation of the unwanted phenomena has not been appropriately investigated in the literature. This work explored an attenuative evaluation of unwanted phenomena, also called here as secondary phenomena, in a unique approach.

Upon electric field utilization within microfluidic devices, electrode miniaturization improves device sensitivity. However, electrodes in contact with medium solution can yield byproducts that can …

Molecular Biogeochemistry Of A Poor Fen, Zhimin Song

Dissertations, Master's Theses and Master's Reports

Variations in climate may rapidly change the carbon balance of peatlands and increase greenhouse gas emissions through accelerated decomposition of peat and dissolved organic matter (DOM). In this study, porewater samples were collected monthly from May to October in 2017 to study the effects of plant functional groups (PFGs) on DOM, dissolved inorganic and organic nitrogen through the season in a poor fen with replicate plots dominated by different PFGs in Nestoria, Michigan, USA (46.34˚N 88.16˚W). The composition of the peat porewater showed strong statistical significance with plot type and season.The observed PFG and season impact on the composition of …

Identification Of Developmental Stage And Anatomical Fraction Contributions To Cell Wall Recalcitrance In Switchgrass, Jacob D. Crowe, Nicholas Feringa, Sivakumar Pattathil, Brian Merritt, Cliff Foster, Dayna Dines, Rebecca Ong, David B. Hodge

Department of Chemical Engineering Publications

Background

Heterogeneity within herbaceous biomass can present important challenges for processing feedstocks to cellulosic biofuels. Alterations to cell wall composition and organization during plant growth represent major contributions to heterogeneity within a single species or cultivar. To address this challenge, the focus of this study was to characterize the relationship between composition and properties of the plant cell wall and cell wall response to deconstruction by NaOH pretreatment and enzymatic hydrolysis for anatomical fractions (stem internodes, leaf sheaths, and leaf blades) within switchgrass at various tissue maturities as assessed by differing internode.

Results

Substantial differences in both cell wall composition …

Surface Enabled Lab-On-A-Chip (Loc) Device For Protein Detection And Separation, Zhichao Wang

Dissertations, Master's Theses and Master's Reports

Sensitive and selective chemical/biological detection/analysis for proteins is essential for applications such as disease diagnosis, species phenotype identification, product quality control, and sample examination. Lab-on-a-chip (LOC) device provides advantages of fast analysis, reduced amount of sample requirements, and low cost, to magnificently facilitate protein detection research. Isoelectric focusing (IEF) is a strong and reliable electrophoretic technique capable of discerning proteins from complex mixtures based on the isoelectric point (pI) differences. It has experienced plenty of fruitful developments during previous decades which has given it the capability of performing with highly robust and reproducible analysis. This progress has made IEF devices …

Purification And Recovery Of Infectious Virus Particles Using Osmolyte Flocculation, Ashish Saksule

Dissertations, Master's Theses and Master's Reports

Viral infectious diseases cause millions of deaths and severe illness all around the world affecting public health and economics. Viral vaccines are helping to fight against viral diseases, but current vaccines are expensive and unavailable, especially in poor and developing countries. When measuring the entire manufacturing processing, the downstream processing of vaccines is the major cost of production. Our goal for this research is to develop a low-cost alternative downstream processing platform for new vaccine manufacturing infrastructures. We have developed a novel osmolyte flocculation method for viral particles. To create a platform purification for several types of viral particles, we …

Life-Cycle Energy And Ghg Emissions Of Forest Biomass Harvest And Transport For Biofuel Production In Michigan, Fengli Zhang, Dana M. Johnson, Jinjiang Wang

College of Business Publications

High dependence on imported oil has increased U.S. strategic vulnerability and prompted more research in the area of renewable energy production. Ethanol production from renewable woody biomass, which could be a substitute for gasoline, has seen increased interest. This study analysed energy use and greenhouse gas emission impacts on the forest biomass supply chain activities within the State of Michigan. A life-cycle assessment of harvesting and transportation stages was completed utilizing peer-reviewed literature. Results for forest-delivered ethanol were compared with those for petroleum gasoline using data specific to the U.S. The analysis from a woody biomass feedstock supply perspective uncovered …

Mechanistic Models On Enzymatic Hydrolysis And Anaerobic Digestion, Yang Zhang

Dissertations, Master's Theses and Master's Reports

For enzymatic hydrolysis, a mechanistic model on enzymatic hydrolysis of pure cellulosic substrates was improved to consider oligomer reactions with beta-glucanases, inhibition of oligomers to cellulases and enzyme decay. Then a novel and general modeling framework was developed for enzymatic hydrolysis of hemicellulose-cellulosic substrates. This mechanistic model, for the first time, took into consideration explicitly the time evolution of morphologies of intertwining cellulose and hemicelluloses. This novel mechanistic model was applied to optimize the composition of enzyme mixtures for substrate conversion and monosaccharides yield during simultaneous enzymatic hydrolysis of different lignocellulosic substrates. For anaerobic digestion, the original "Anaerobic Digestion Model …

Bacteriorhodopsin-Based Sensors, Craig Friedrich, Donald Lueking, Mark Griep

Michigan Tech Patents

A sensor comprising a membrane containing bacteriorhodopsin. In one embodiment, the sensor comprises a layer of purple membrane between a first and a second electrode, wherein the electrodes are connected to a circuit such that a signal is produced when a charge is transferred across the membrane. In another embodiment, the sensor comprises a field effect transistor with a layer of purple membrane deposited on the gate. The layer of purple membrane may be further functionalized by adding fluorophores to the layer of purple membrane. The fluorophores may be deposited adjacent to the layer of purple membrane, or the fluorophores …