Biochemical and Biomolecular Engineering Commons^™

Elucidating The Effects Of Metabolic State On Nanoparticle Distribution In Mice And In Vitro Uptake, Kevin James Quigley

Doctoral Dissertations

Since almost 70% of the U.S. population over 20 years old is overweight and 30% is obese, with much of the western world following suit, many patients that will potentially be administered circulating nanoparticles designed to localize to tumors and avoid non-target areas will have significant amounts of white adipose tissue (WAT), enlarged livers, and additional metabolic complications such as type 2 diabetes. However, studies on nanoparticle biodistribution and efficacy take place almost without exception in lean rodents with healthy metabolic states. In this work, I determined the biodistribution of model nanoparticles – neutral filomicelles and polystyrene spheres both carrying …

Characterization Of Molecular Communication Based On Cell Metabolism Through Mutual Information And Flux Balance Analysis, Zahmeeth Sayed Sakkaff

Department of Computer Science and Engineering: Dissertations, Theses, and Student Research

Synthetic biology is providing novel tools to engineer cells and access the basis of their molecular information processing, including their communication channels based on chemical reactions and molecule exchange. Molecular communication is a discipline in communication engineering that studies these types of communications and ways to exploit them for novel purposes, such as the development of ubiquitous and heterogeneous communication networks to interconnect biological cells with nano and biotechnology-enabled devices, i.e., the Internet of Bio-Nano Things. One major problem in realizing these goals stands in the development of reliable techniques to control the engineered cells and their behavior from the …

Lignin Maximization: Analyzing The Impact Of Different Feedstocks And Feedstock Ratios Using Organosolv Fractionation, Marc Banholzer

Masters Theses

Over-exploitation of fossil fuels coupled with increasing pressure to reduce carbon emissions are prompting a transition from conventional petrochemical feedstocks to sustainable and renewable sourced carbon. The use of lignocellulosic biomass as a feedstock for integrated biorefining is of current high interest, as separation into its component parts affords process streams of cellulose, hemicellulose and lignin, each of which can serve as a starting point for the production of biobased chemicals and fuels. Given the large number of potential sources of lignocellulosic feedstocks, the biorefinery will need to adapt to the supplies available over a normal growing season. Of particular …

Membrane Chromatography For Bioseparations: Ligand Design And Optimization, Zizhao Liu

Graduate Theses and Dissertations

Membrane chromatography, or membrane adsorber, represents an attractive alternative to conventional packed bed chromatography used in downstream processing. Membrane chromatography has many advantages, including high productivity, low buffer consumption and ease to scale up. This doctoral dissertation focuses on developing novel polymeric ligands for protein separations using membrane chromatography. Atom transfer radical polymerization (ATRP), known as a controlled radical polymerization technique, has been used to control the architecture of grafted polymeric ligands. The center theme of this dissertation is to develop new polymeric ligands and investigate how the polymer’s property (e.g. flexibility, hydrophobicity) and architecture (e.g. chain density, chain length) …

Conformationally Superarmed S-Ethyl Glycosyl Donors As Effective Building Blocks For Chemoselective Oligosaccharide Synthesis In One Pot, Mithila Bandara, Jagodige Yasomanee, Nigam Rath, Christian Pedersen, Mikael Bols, Alexei Demchenko

Chemistry & Biochemistry Faculty Works

A new series of superarmed glycosyl donors has been investigated. It was demonstrated that the S-ethyl leaving group allows for high reactivity, which is much higher than that of equally equipped S-phenyl glycosyl donors that were previously investigated by our groups. The superarmed S-ethyl glycosyl donors equipped with a 2-O-benzoyl group gave complete β-stereoselectivity. Utility of the new glycosyl donors has been demonstrated in a one-pot one-addition oligosaccharide synthesis with all of the reaction components present from the beginning.

Label-Free And Aptamer-Based Surface Enhanced Raman Spectroscopy For Detection Of Food Contaminants, Shintaro Pang

Doctoral Dissertations

The development of analytical methods to detect food contaminants is a critical step for improving food safety. Surface enhanced Raman spectroscopy (SERS) is an emerging detection technology that has the potential to rapidly, accurately and sensitively detect a wide variety of food contaminants. However, SERS detection becomes a challenge in real complex matrix, such as food, since non-specific matrix signals have the potential to drown out target associated Raman peaks. In this dissertation, we focused on the development and application of label-free, aptamer-based SERS in order to improve the accuracy and specificity of target contaminant detection in food. To accomplish …

Co-Substrate Fermentation Of Jerusalem Artichoke Tubers And Crude Glycerol To Butanol With Integrated Product Recovery, Tahereh Sarchami

Electronic Thesis and Dissertation Repository

Butanol has long been considered a potential advanced liquid biofuel, in addition to its current application as an industrial solvent. It can be produced biologically; however, the conventional ABE fermentation suffers from many limitations, including low butanol titer, high cost of traditional raw materials, end-product inhibition and high butanol recovery costs. Possible solutions are the use of renewable low-cost feedstocks, genetic manipulations of Clostridia spp. to improve the strains’ butanol titer and tolerance, advanced fermentation techniques, and in-situ product recovery technologies.

In order to overcome some of these limitations, the overall goal of this thesis was to develop a process …

Subcellular And In-Vivo Nano-Endoscopy, Surya Venkatasekhar Cheemalapati, John Winskas, Hao Wang, Karthik Konnaiyan, Arseny Zhdanov, Alison Roth, Swamy Rakesh Adapa, Andrew Deonarine, Rays H. Y. Jiang, Anna Pyayt

Chemical, Biological and Materials Engineering Faculty Publications

Analysis of individual cells at the subcellular level is important for understanding diseases and accelerating drug discovery. Nanoscale endoscopes allow minimally invasive probing of individual cell interiors. Several such instruments have been presented previously, but they are either too complex to fabricate or require sophisticated external detectors because of low signal collection efficiency. Here we present a nanoendoscope that can locally excite fluorescence in labelled cell organelles and collect the emitted signal for spectral analysis. Finite Difference Time Domain (FDTD) simulations have shown that with an optimized nanoendoscope taper profile, the light emission and collection was localized within ~100 nm. …

Fabrication And Cross-Linking Of L-Aspartic Acid Functionalized Poly(Ester Amide)-Based Tissue Engineering Scaffolds, Shuyu Liu

Electronic Thesis and Dissertation Repository

Scaffold fabrication is essential in tissue engineering. Amino acid based poly(ester amide)s (PEAs) have been investigated as scaffold materials due to their non-toxic degradation byproducts, and easily tunable mechanical and biological properties. However, L-aspartic acid functionalized PEAs showed poor morphological stability when immersed in buffer. This work focuses on the further functionalization of L-aspartic acid based PEAs, scaffold fabrication and cross-linking of the scaffold to improve morphological stability. Photo-cross-linkable and thermally cross-linkable PEAs were synthesized successfully and characterized. Two scaffold fabrication methods were applied: 1) electrospinning was applied to photo-cross-linkable PEAs, followed by UV treatment to cross-link electrospun scaffolds; 2) …

Abe Fermentation From Low Cost Substrates, Kai Gao

Electronic Thesis and Dissertation Repository

The high cost of substrate and product inhibition in the fermentation broth remains two major problems associated with bio-butanol production. This thesis aims to solve these problems by examining abundant lignocellulosic biomass as potential feedstocks and exploring novel substrates such as carbohydrates derived from microalgae for ABE fermentation. The commonly observed toxic effect after pretreatment of lignocelluslosic biomass was removed by resin adsorption, where the resin could also serve as an in-situ butanol recvoery devices.

Corn cobs (an agricultural waste), switchgrass (an energy crop) and phragmites (an invasive plant in North America) were investigated as substrates for ABE fermentation by …

Materials And Techniques Used In Cranioplasty Fixation: A Review, Basel A. Khader, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Cranioplasty is the surgical repair of a deficiency or deformity of the skull. The purpose of cranioplasty is to provide protection for the brain following cranial surgery, and to offer relief to psychological disadvantages while increasing social performance. There are several materials that had been used for cranioplasty, but an ideal product has yet to be developed, hence the ongoing research into biologic and non-biologic alternatives to the existing materials. This article critiques the products currently used for cranioplasty in order to facilitate the development of new materials, which can improve patient outcomes.

Methanol And Dimethyl Ether From Renewable Hydrogen And Carbon Dioxide: Alternative Fuels Production And Life-Cycle Assessment, Michael J. Matzen, Yaşar Demirel

Yaşar Demirel Publications

In this work we investigate two renewably based alternative fuels; methanol and dimethyl ether. The ultimate feedstocks for production are wind-based electrolytic hydrogen and carbon dioxide captured from an ethanol fermentation process. Dimethyl ether production was modeled in ASPEN Plus using a previously simulated methanol production facility. The facilities use 18.6 metric tons (mt) of H₂ and 138.4 mt CO₂ per day. Methanol is produced at a rate 96.7 mt/day (99.5 wt%) and dimethyl ether is produced at a rate of 68.5 mt/day (99.6 wt%). A full comparative life-cycle assessment (cradle-to-grave) of both fuels was conducted to investigate …

Biohydrogen And Biomethane Production From Lignocellulosic Biomass, Chinaza Okeoghene Akobi

Electronic Thesis and Dissertation Repository

The main purpose of this study was to investigate the impact of furfural on mixed cultures during fermentative hydrogen production from lignocellulosic biomass. Small batch studies using synthetic lignocellulosic hydrolysate grown on mesophilic mixed cultures, revealed a threshold furfural concentration of greater than 1 g/L with enhancement to the yields (from the control) observed at 0.5 g/L furfural (at initial substrate-to–biomass (S°/X°) ratios of 0.5 and 1 gCOD/gVSS) and at both 0.5 g/L and 1 g/L furfural (at S°/X° of 2 and 4 gCOD/gVSS). This study was scaled-up from 200 mL to 11 L working volume batches, using half the …

Ginseng Polysaccharides Nanoparticles - Synthesis, Characterization, And Biological Activity, Kazi Farida Akhter

Electronic Thesis and Dissertation Repository

North American (NA) ginseng is a widely used medicinal plant. Polysaccharides (PS), the major medicinal fractions derived from NA ginseng root, have been shown several biological activities including anti-carcinogenic, anti-aging, immunostimulatory and antioxidant activity. This work focused on nanoprocessing of ginseng PS for enhancing their immunostimulation. Herein, we have developed a novel microfluidic approach to synthesize ginseng PS nanoparticles (NPs) from NA ginseng root. The microfluidics was found to provide unimodal PS spheres down to 20 nm with very narrow particle size distributions. In addition, the immunostimulating effect was investigated on Murine macrophage cell lines, with the results revealing an …

Direct Conversion Of Wet Microalgae And Oleaginous Yeast To Biodiesel Using Ionic Liquids, Valerie Orr

Electronic Thesis and Dissertation Repository

This thesis examined the development of an oleaginous yeast or microalgae based biorefinery process. First, improvements were made to the Nile Red assay, a high-throughput method for monitoring lipid accumulation in oleaginous organisms resulting in a significantly more reproducible and accurate assay. This assay was then used to optimize lipid production during heterotrophic cultivation of microalgae on glucose using response surface methodology resulting in microalgae with high lipid content (37.6% wt.). In order to improve the renewability of heterotrophic lipid production, both oleaginous yeast and microalgae were cultivated using pyrolytic sugars, produced via fast pyrolysis of pinewood waste. The effects …

Hydrothermal Liquefaction Of High-Water Content Biomass And Waste Materials For The Production Of Biogas And Bio-Crude Oil, Laleh Nazari

Electronic Thesis and Dissertation Repository

Growing interest in renewable energies due to shrinking reserves of fossil fuels and climate change concerns have led to extensive research towards gaseous and liquid fuels production from renewable energy resources such as biomass and wastes. Energy generation from municipal and industrial wastes such as wastewater sludge is also environmental friendly way to deal with large volume of waste disposal with the additional advantage of eliminating part of the indirect greenhouse gas emissions from energy crops-derived biofuels.

In this thesis, a novel process for co-production of biogas and bio-crude oil from high-water-content wastewater sludge through hydrothermal liquefaction (HTL) treatments is …

Development And Characterization Of Oxygen Sensitive Microbial Biosensors, Jonathan Lee

Rose-Hulman Undergraduate Research Publications

Microbial biosensors are useful in detecting suboptimal conditions in a bioreactor. This detection can help in development of improved mixing methods to reduce the occurrence of these conditions. In this research, the activities of 3 promoters known to have activity under anaerobic conditions, the gadB promoter, an FNR protein activated promoter, and the pfl promoter, were tested for activity under anaerobic conditions by connecting them to a green fluorescent protein (GFP) gene. Using two types of media, Luria-Bertani (LB) and Wilms-Reuss media, the activity of these promoters under aerobic and anaerobic conditions were tested. Results indicate that while the FNR …

Studies On Nanocomposite Coating Produced By Laser-Assisted Process To Prevent Silicone Hydrogels From Bio-Fouling, Vishnuvardhana Wuppaladhodi

Electronic Thesis and Dissertation Repository

In this thesis, silver nanoparticles incorporated into polyvinylpyrrolidone (PVP) were deposited on silicone hydrogel to improve the hydrophilicity of the silicone hydrogel and prevent the growth of bacteria. Two different processes were employed to produce Ag nanoparticles: (1) Process-A is a photochemical reduction; (2) Process-B is laser ablation in liquid. Following that, MAPLE process was employed to deposit the Ag-PVP nanocomposites on the surface of silicone hydrogel. A solid-state pulsed laser (Nd:YAG) with a wavelength of 532 nm at a fluence of 50.4 mJ/cm² was used in the MAPLE system to deposit Ag-PVP nanocomposite coating. Our results indicate that …

Fermentative Processes Requiring Low Solubility Feed Gases: An Investigation Into Gas-Dependent Microorganisms, Eric W. Doerr

Electronic Thesis and Dissertation Repository

Two bioprocesses were separately investigated based on their common interest of using gaseous substrates that have low solubility. The first process involved the development of a mixed culture using two organisms capable of utilizing glycerol and carbon monoxide separately to increase biobutanol production, while the second process involved an investigation of different production media used in aerobic xanthan production of Xanthomonas campestris with pressurization effects. It was determined that Clostridium pasteurianum should be used with an organism like Clostridium carboxidivorans or Eubacterium limosum in order for butyrate uptake at 3 g/L to occur with a minimum 0.1 g/L butyrate production. …

Alginate Hydrogels As Three-Dimensional Scaffolds For In Vitro Culture Models Of Growth Plate Cartilage Development And Porcine Embryo Elongation, Taylor D. Laughlin

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

The establishment of in vitro culture models utilizes tissue engineering principles to design functional mimics of in vivo environments in vitro. Advantages for the use of in vitro culture models include ethical alleviation of animal models for therapeutic testing, cost efficiency, and a greater ability to study specific mechanisms via a systematic, ground-up approach to development. In this thesis, alginate hydrogels are utilized in the development of in vitro culture models of porcine embryo elongation and growth plate cartilage development. First, the effect of scaffold and modifications to the scaffold were explored in both projects. In order to modulate …

Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen

Doctoral Dissertations

The tumor extracellular matrix (ECM) plays an important role in facilitating tumor growth and mediating tumor cells' resistance to drugs. However, during drug development, potential chemotherapeutics are screened in plastic plates, which lack relevant ECM physicochemical cues. In order to improve drug development process, this dissertation includes the development of relevant 2D and 3D biomaterial systems that can be used to study carcinoma cell response to drug treatment. A novel poly(ethylene glycol)-phosphorylcholine (PEG-PC) high-throughput biomaterial platform was developed to study how the ECM mechanochemical properties affect cancer cells' response to drug. The PEG-PC biomaterial is optically transparent, has a mechanical …

Hydrothermal Synthesis And Characterisation Of Bioactive Glass-Ceramic Nanorods, Ehsan Zeimaran, Sara Pourshahrestani, Seyed Farid Seyed Shirazi, Belinda Pingguan-Murphy, Nahrizul Adib Kadri, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

In this study fabrication of rod-like bioactive glass-ceramics (BGCs) using hydrothermal treatment based on a sol-gel precursor is reported for the first time. BGCs with composition 58 wt% SiO₂, 33 wt% CaO and 9 wt% P₂O₅ were synthesized in different thermal conditions (200 and 220 °C) and characterised with regard to morphology, chemical composition and crystallinity. The bioactivity of the materials was assessed by immersion in simulated body fluid for up to 7 days. The results revealed that as the reaction temperature increased from 200 to 220 °C, the diameter of rods was reduced from …

Raman Spectroscopic Analysis Of Fingernail Clippings Can Help Differentiate Between Postmenopausal Women Who Have And Have Not Suffered A Fracture, James R. Beattie, Niamh M. Cummins, Clare Caraher, Olive M. O'Driscoll, Aruna T. Bansal, Richard Eastell, Stuart H. Ralston, Michael D. Stone, Gill Pearson, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Raman spectroscopy was applied to nail clippings from 633 postmenopausal British and Irish women, from six clinical sites, of whom 42% had experienced a fragility fracture. The objective was to build a prediction algorithm for fracture using data from four sites (known as the calibration set) and test its performance using data from the other two sites (known as the validation set). Results from the validation set showed that a novel algorithm, combining spectroscopy data with clinical data, provided area under the curve (AUC) of 74% compared to an AUC of 60% from a reduced QFracture score (a clinically accepted …

In Silico Driven Metabolic Engineering Towards Enhancing Biofuel And Biochemical Production, Richard Adam Thompson

Doctoral Dissertations

The development of a secure and sustainable energy economy is likely to require the production of fuels and commodity chemicals in a renewable manner. There has been renewed interest in biological commodity chemical production recently, in particular focusing on non-edible feedstocks. The fields of metabolic engineering and synthetic biology have arisen in the past 20 years to address the challenge of chemical production from biological feedstocks. Metabolic modeling is a powerful tool for studying the metabolism of an organism and predicting the effects of metabolic engineering strategies. Various techniques have been developed for modeling cellular metabolism, with the underlying principle …

Targeted Drug Delivery Using Peptoid Based Nanospheres, Kaylee J. Smith

Chemical Engineering Undergraduate Honors Theses

While medicine has improved greatly in the last couple of decades, there are negative side effects that accompany many drugs. Undesirable side effects could be greatly reduced if non-systemic drug delivery systems were used because the medicine would harm diseased cells at a much higher rate than it does healthy cells. One possible non-systemic drug delivery system is peptoid nanospheres. These nanospheres will then be linked to another peptoid that is engineered to attach almost exclusively to diseased cells.

This research project is focused on designing peptoids that will form nanospheres in solution. Four specific peptoids were synthesized and tested …

Local Delivery Of Ctla-4 Blockade Inhibits Growth Of Pancreatic Tumors, Jack Baltz

Biomedical Engineering Undergraduate Honors Theses

Immune checkpoint blockade has demonstrated great potential in activating antitumor immunity. Ipilimumab is a monoclonal antibody which targets cytotoxic T-lymphocyte antigen-4. CTLA-4 belongs to the CD28 class of receptors and is found on the surface of CD4⁺ and CD8⁺ T cells. CTLA-4 acts to suppress the immune system when bound to CD80 and CD86 receptors on antigen presenting cells. Ipilimumab, or anti-CTLA-4, has shown to be effective in significantly extending the survival of patients with metastatic melanoma. However, systemic delivery of Ipilimumab also induces significant side effects such as: colitis, dermatitis, uveitis, and hypophysitis. In order to minimize …

Development Of A Simple Handheld Biosensor For Waterborne Pathogens, Bryce C. Jones

Chemical Engineering Undergraduate Honors Theses

Current methods of detecting waterborne pathogens involve testing strips which take 24-48 hours to yield results, or require expensive equipment in order to function. In minimalist environments, these two technologies are not always applicable to test water quality. With the emergence of a new method of PCR, named LAMP PCR, it is possible to quickly and accurately detect pathogen DNA in a water sample. In order to scale this technique into a simple device, the aspects of the reaction must be accommodated, and a visual detection method chosen. A handheld device which keeps the isothermal LAMP PCR stable for the …

Investigating The Modulation Of Aggregating Amyloid Beta 40, Marlee J. Motes

Chemical Engineering Undergraduate Honors Theses

Amyloid beta protein has been linked to the formation of Alzheimer’s disease in patients.¹ Plaques form from amyloid beta fibrils. The formation of these plaques between neural connections in the brain are associated with Alzheimer’s disease.² The reduction of the formation of fibrils can be linked to utilizing protein mimics. The protocols that are used to reproduce the simulation of amyloid beta in the brain can be very important. Also, the structure of the protein mimic that is being used to inhibit the formation of fibrils can determine how the amyloid beta plaques are reduced.

The structure of sequence KLLFFLFFLLK …

Model Validation And Transition To Turbulence In Orbiting Culture Dishes., Jonathan Michael D. Thomas

Electronic Theses and Dissertations

Wall shear stress (WSS) is commonly accepted as the primary influence affecting characteristics of anchored endothelial cells when subjected to fluid flow. Orbital shakers are commonly used to study cellular responses due to their ease of use, ability to run several experiments simultaneously, and since they exert physiologically relevant oscillatory shear. These studies require comprehensive resolution of WSS, however the fluid dynamics inside orbiting culture dishes has not yet been well described since the flow is complex and difficult to quantify analytically. A computational fluid dynamics (CFD) model of flow in an orbiting dish has been developed that yields detailed …

Cloning, Fed-Batch Expression And Purification Of A Novel Anti-Candida Peptide And Development Of A Cleavage Resistant Variant Of Green Fluorescence Protein, Rudra Palash Mukherjee

Graduate Theses and Dissertations

This work illustrates that the intelligent design of a bioprocess for the production of peptides of various length is possible by having a prior knowledge of desired product, cell line, fermentation conditions, and choices for downstream recovery. Cloning, expression, and recovery of a novel 12-mer anti-Candida peptide served as an illustrative case for a proposed Escherichia coli platform. The antifungal peptide, expressed as a fusion to GFPUV during high call density fed-batch, was recovered from cell lysate, concentrated using ion exchange chromatography, and finally cleaved with cyanogen bromide. The platform was capable of producing active peptide capable of arresting the …