Engineering Commons^™

Key Engineering Challenges In The Biomanufacturing Of Lentiviral Viral Vectors, Peter Jones

Advancing Manufacture of Cell and Gene Therapies VI [2019]

No Abstract.

Tangential Flow Filtration And Scalability In Viral Vector Purification, Eni Sterjanaj, Heather Mall, Rachel Legmann, Jacky Dang

Advancing Manufacture of Cell and Gene Therapies VI [2019]

Pall Biotech has linearly scalable tangential flow filtration technology that can cover processing volume ranges from less than a liter to over 2000 liters. Manual assemblies can be used with Pall TFF filters in scales under 20L and programmable skids are available for larger scales. In this document TFF linear scalability of up to 200 liters is covered starting from a 7L initial volume and maintaining similar pressures, processing times and yields at all scales. Using this scalable technology Pall biotech can help biologics companies go to clinical trials and to commercial scale manufacturing successfully.

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Conference Program, Dolores Baksh, Rod Rietze, Ivan Wall

Advancing Manufacture of Cell and Gene Therapies VI [2019]

No abstract provided.

Workshop Agenda, Fernanda Masri

Advancing Manufacture of Cell and Gene Therapies VI [2019]

No abstract provided.

Development Of A Closed Car-T Manufacturing Process, Loo-Yong Steven Kee, Calley Hirsch, Devina Ramsaroop, Elizabeth Csaszar, Danylo Sirskyj, Aaron Dulgar-Tulloch

Advancing Manufacture of Cell and Gene Therapies VI [2019]

The field of immunotherapy has emerged as a promising new type of treatment for cancer with the approval of the first two CAR-T therapies. The clinical success of T-cell based immunotherapies necessitates a robust manufacturing process for these products to be consistently produced at commercial scale. Our CAR-T workflow combines unit operation specific solutions for thaw of an apheresis unit, wash, CD3 selection, T-cell activation, lentiviral transduction, incubator- and reactor-based expansion culture, harvest, formulation, cryopreservation and thaw of CAR-T product. We have evaluated the impact of both serum-containing and xeno-free culture media, commercially available T-cell selection and activation reagents, closed …

Scale-Up Study For Ex-Vivo Expansion Of Allogeneic Natural Killer Cells In Stirred-Tank Bioreactor, Juyoung Kim, Hyung Jin Nam, Sang Hyun Lee, Jong Beom Ku, Seung Ryel Han, Hye Jin Shin, Yu Kyeong Hwang, Sang Hoon Paik

Advancing Manufacture of Cell and Gene Therapies VI [2019]

Natural killer (NK) cells are a type of lymphocyte in the blood that are responsible for innate and adaptive immune response, and they mature in the liver and bone marrow. Being a key role in host defense system with direct and indirect killing of virus-infected cells or cancer cells, NK cell has been considered an attractive candidate for cancer therapy. Peripheral blood shows the low frequency of NK cells, so ex vivo expansion method is important to obtain sufficient NK cells for therapeutic use. Currently, we successfully developed bioreactor process for NK cell expansion on lab-scale. Stirred-tank bioreactor could be …

Single Use Disposable Biosettler Removes The Dead Cells And Cell Debris Selectively To Increase The Viability Percentage Of Mammalian Cells (E.G., Car-T) During Expansion, Dhinakar Kompala

Advancing Manufacture of Cell and Gene Therapies VI [2019]

Current challenge in a FDA approved cell therapy product for adult B-cell leukemia is reported to be the percentage of viable cells after manufacturing is sometimes out of specified range. As the head of a large contract development and manufacturing organization observed, this fall in viability percentage during CAR-T cell manufacturing is a challenge to the whole industry.

We present a simple and powerful off-the-shelf solution to this big challenge in all mammalian cell culture expansion bioreactor system. Our single use disposable BioSettler has been demonstrated to be uniquely capable of removing dead cells and cell debris selectively from the …

Disciplinary Learning From An Authentic Engineering Context, Catherine Langman, Judith Zawojewski, Patricia Mcnicholas, Ali Cinar, Eric Brey, Mustafa Bilgic, Hamidreza Mehdizadeh

Journal of Pre-College Engineering Education Research (J-PEER)

This small-scale design study describes disciplinary learning in mathematical modeling and science from an authentic engineeringthemed module. Current research in tissue engineering served as source material for the module, including science content for readings and a mathematical modeling activity in which students work in small teams to design a model in response to a problem from a client. The design of the module was guided by well-established principles of model-eliciting activities (a special class of problem-solving activities deeply studied in mathematics education) and recently published implementation design principles, which emphasize the portability of model-eliciting activities to many classroom settings.

Two …

The Effect Of Electrospun Fiber Diameter On Astrocyte-Mediated Neurite Guidance And Protection, Christopher D.L. Johnson, Jonathan M. Zuidema, Kathryn R. Kearns, Alianna B. Maguire, Gregory P. Desmond, Deanna M. Thompson, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

The topography of electro spun fiber scaffolds modifies astrocytes toward in vivo-like morphologies and behaviors. However, little is known about how electro spun fiber diameter influences astrocyte behavior. In this work, aligned fibers with two distinct nanoscale fiber diameters (808 and 386 nm) were prepared, and the astrocyte response was measured over time. Astrocytes on the large diameter fibers showed significantly increased elongation as early as 2 h after seeding and remained significantly more elongated for up to 4 days compared to those on small diameter fibers. Astrocytes extending along larger diameter fibers were better equipped to support long neurite …

Coatings On Mammalian Cells: Interfacing Cells With Their Environment, Kara A. Davis, Pei-Jung Wu, Calvin F. Cahall, Cong Li, Anuhya Gottipati, Brad J. Berron

Chemical and Materials Engineering Faculty Publications

The research community is intent on harnessing increasingly complex biological building blocks. At present, cells represent a highly functional component for integration into higher order systems. In this review, we discuss the current application space for cellular coating technologies and emphasize the relationship between the target application and coating design. We also discuss how the cell and the coating interact in common analytical techniques, and where caution must be exercised in the interpretation of results. Finally, we look ahead at emerging application areas that are ideal for innovation in cellular coatings. In all, cellular coatings leverage the machinery unique to …

Ensuring Scientific Publishing Credibility In Translational Biomedical Optics., Brian W. Pogue

Dartmouth Scholarship

Optics has consistently been the largest singular technology sector used in medicine, and major advances in biomedical optics are documented daily in peer-reviewed publications. However, the academic stature of this field can be damaged by weaknesses in scientific publishing, where a “credibility crisis” has emerged as a popularized and increasingly studied dialogue. While there are still relatively few overt cases of fraud or erroneous research, more insidious aspects are seen in papers with results that have either low statistical power, selective reporting of observations, or data or computer codes that cannot be independently verified. Interestingly, the same solutions that improve …

3d Microwave Tomography Using The Soft Prior Regularization Technique: Evaluation In Anatomically-Realistic Mri-Derived Numerical Breast Phantoms, Amir H. Golnabi, Paul M. Meaney, Shireen D. Geimer, Keith D. Paulsen

Department of Mathematics Faculty Scholarship and Creative Works

Objective: Fusion of magnetic resonance imaging (MRI) breast images with microwave tomography is accomplished through a soft prior technique, which incorporates spatial information (from MRI), i.e. accurate boundary location of different regions of interest, into the regularization process of the microwave image reconstruction algorithm. Methods: Numerical experiments were completed on a set of 3D breast geometries derived from MR breast data with different parenchymal densities, as well as a simulated tumor to evaluate performance over a range of breast shapes, sizes and property distributions. Results: When the soft prior regularization technique was applied, both permittivity and conductivity relative root mean …

Injectable, Magnetically Orienting Electrospun Fiber Conduits For Neuron Guidance, Christopher D.L. Johnson, Debmalya Ganguly, Jonathan M. Zuidema, Thomas J. Cardinal, Alexis M. Ziemba, Kathryn R. Kearns, Simon M. Mccarthy, Deanna M. Thompson, Ganpati Ramanath, Diana A. Borca-Tasciuc, Silvio Dutz, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

Magnetic electro spun fibers are of interest for minimally invasive biomaterial applications that also strive to provide cell guidance. Magnetic electro spun fibers can be injected and then magnetically positioned in situ, and the aligned fiber scaffolds provide consistent topographical guidance to cells. In this study, magnetically responsive aligned poly-l-lactic acid electro spun fiber scaffolds were developed and tested for neural applications. Incorporating oleic acid-coated iron oxide nanoparticles significantly increased neurite outgrowth, reduced the fiber alignment, and increased the surface nano topography of the electro spun fibers. After verifying neuron viability on two-dimensional scaffolds, the system was tested as an …

Terpene Synthase Genes Originated From Bacteria Through Horizontal Gene Transfer Contribute To Terpenoid Diversity In Fungi, Qidong Jia, Xinlu Chen, Tobias G. Kollner, Jan Rinkel, Jianyu Fu, Jessy Labbe, Wangdan Xiong, Jeroen S. Dickschat, Jonathan Gershenzon, Feng Chen

Nebraska Center for Biotechnology: Faculty and Staff Publications

Fungi are successful eukaryotes of wide distribution. They are known as rich producers of secondary metabolites, especially terpenoids, which are important for fungi-environment interactions. Horizontal gene transfer (HGT) is an important mechanism contributing to genetic innovation of fungi. However, it remains unclear whether HGT has played a role in creating the enormous chemical diversity of fungal terpenoids. Here we report that fungi have acquired terpene synthase genes (TPSs), which encode pivotal enzymes for terpenoid biosynthesis, from bacteria through HGT. Phylogenetic analysis placed the majority of fungal and bacterial TPS genes from diverse taxa into two clades, indicating ancient …

The Effect Of Impact Location On Brain Strain, Stephen Tiernan, Gary Byrne Mr

Articles

Objective: To determine the effect of impact direction on strains within the brain.

Research design: Laboratory drop tests of hybrid III head-form and finite element simulation of impacts.

Methods and procedures: A head-form instrumented with accelerometers and gyroscopes was dropped from 10 different heights in four orientations: front, rear, left and right hand side. Twelve impacts with constant impact energy were chosen to simulate, to determine the effect of impact location. A finite element head model was used to simulate these impacts, using 6 degrees of freedom. Following this a further set of simulations were performed, where the same acceleration …

Communication Of Deaf People Based On Myoware Muscle Sensor, Mohamad Ataya

Research Opportunities for Engineering Undergraduates (ROEU) Program 2018-19

The current project aims to create a product that enhances communication of deaf people. The developed product has the following features:

• a muscle sensor that transcribes sign language into actual letters

• a voice detector that translates speech into actual words

• the ability to receive and send emergency alerts.

Exploring The Challenges To Sustainable Rural Drinking Water Services In Chile, Jami Nelson-Nuñez, Jeffrey P. Walters, Denisse Charpentier

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Many countries around the world now face the dual challenges of closing the remaining gaps in access to drinking water in rural areas while further addressing the issues of equity, quality, and sustainability outlined in the new Sustainable Development Goals (SDGs). Our research explores the key factors for sustainability in rural drinking water services in Chile, an important example not only due to its success in rural water access but also because of the new directions the country is taking to achieve the SDGs. Drawing on results from a Delphi study of Chilean rural water experts, we discuss the most …

Progressive Hypoxia-On-A-Chip: An In Vitro Oxygen Gradient Model For Capturing The Effects Of Hypoxia On Primary Hepatocytes In Health And Disease, Young Bok Abraham Kang, Jinsu Eo, Beyza Bulutoglu, Martin L. Yarmush, O. Berk Usta

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Oxygen is vital to the function of all tissues including the liver and lack of oxygen, that is, hypoxia can result in both acute and chronic injuries to the liver in vivo and ex vivo. Furthermore, a permanent oxygen gradient is naturally present along the liver sinusoid, which plays a role in the metabolic zonation and the pathophysiology of liver diseases. Accordingly, here, we introduce an in vitro microfluidic platform capable of actively creating a series of oxygen concentrations on a single continuous microtissue, ranging from normoxia to severe hypoxia. This range approximately captures both the physiologically relevant oxygen gradient …

Cancer Nanotechnology: Enhancing Tumor Cell Response To Chemotherapy For Hepatocellular Carcinoma Therapy, Sun Yongbing, Ma Wen, Yang Yuanyuan, He Mengxue, Li Aimin, Bai Lei, Yu Bin, Yu Zhiqiang

Faculty & Staff Scholarship

Abstract

Hepatocellular carcinoma (HCC) is one of the deadliest cancers due to its complexities, reoccurrence after surgical resection, metastasis and heterogeneity. In addition to sorafenib and lenvatinib for the treatment of HCC approved by FDA, various strategies including transarterial chemoembolization, radiotherapy, locoregional therapy and chemotherapy have been investigated in clinics. Recently, cancer nanotechnology has got great attention for the treatment of various cancers including HCC. Both passive and active targetings are progressing at a steady rate. Herein, we describe the lessons learned from pathogenesis of HCC and the understanding of targeted and non-targeted nanoparticles used for the delivery of small …

Feasibility Of Integrating Microfluidics Into Point-Of-Care Bio-Diagnostics, Swetha Manoharan

Theses

Potassium in the body needs to be maintained in proper levels for the normal functioning of heart and kidneys. The aim of this work is to develop a simple technique to measure the concentration of Potassium present in a bodily fluid sample, which can be used to assess the health condition of extremely sick patients, especially when the patient's condition needs to be diagnosed and results needs to be obtained rapidly under Point-of-Care settings. Microfluidics is one of the platforms used in bio-diagnostics because of several advantages such as low sample volume requirement and integration into high-throughput screening. In this …

Abso2luteu-Net: Tissue Oxygenation Calculation Using Photoacoustic Imaging And Convolutional Neural Networks, Kevin Hoffer-Hawlik, Geoffrey P. Luke

ENGS 88 Honors Thesis (AB Students)

Photoacoustic (PA) imaging uses incident light to generate ultrasound signals within tissues. Using PA imaging to accurately measure hemoglobin concentration and calculate oxygenation (sO₂) requires prior tissue knowledge and costly computational methods. However, this thesis shows that machine learning algorithms can accurately and quickly estimate sO₂. absO₂luteU-Net, a convolutional neural network, was trained on Monte Carlo simulated multispectral PA data and predicted sO₂ with higher accuracy compared to simple linear unmixing, suggesting machine learning can solve the fluence estimation problem. This project was funded by the Kaminsky Family Fund and the Neukom Institute.

Bioelectrical Circuits: Lecture 7, Jacek P. Dmochowski, Luis Cardoso

Open Educational Resources

No abstract provided.

Assessing The Role Of Polyphenols As A Vascular Protectant Against Drug Induced Vascular Injury, Anson Jacob Oommen

Browse all Theses and Dissertations

Vascular injury is identified during pre-clinical toxicity testing within certain pharmacological classes of drug candidates and induces degenerative and hyperplastic changes in endothelial (ECs) and vascular smooth muscle (VSMCs) cells. This drug-induced vascular injury has been show as a side-effect caused by various classes of drugs, including, antibacterial (e.g., azithromycin), anti-malarial (e.g., quinoline), anti-viral (e.g., anti-hepatitis C virus interferons) and nonsteroidal anti-inflammatory drugs (e.g., ibuprofen), and affects normal cardiovascular function and can further lead to various cardiovascular conditions like arrhythmia, cardiac arrest, high blood pressure, and even heart attack. The search for agents capable of reducing vascular injury side-effects by …

Impact In Practice, Maria Garman

ENGS 88 Honors Thesis (AB Students)

Medial Tibial Stress Syndrome (Shin splits) is an overuse injury caused by repetitive impact. If ignored it can lead to stress reactions and then stress fractures in the shins. This nagging injury is something that plagues many track athletes especially as they start to wear their competition shoes more frequently at practice to work on technical aspects of their events.

This paper investigates the relationship between ground reaction forces experienced by the athletes in each stride and what shoes they are wearing on their feet. Due to the fact that repetitive impact is a cause for shin splints, the conclusion …

Characterization Of In-Vivo Damage In Implantable Cardiac Devices And The Lead Residual Properties, Anmar Mahdi Salih

Browse all Theses and Dissertations

Approximately, 92.1 million patients in the US suffer from cardiovascular diseases with an estimated healthcare cost of over $300 billion; out of which at least one million patients have Cardiac Implantable Electronics Devices (CIED). CIED represented by pacemakers, Implantable Cardioversion Defibrillator (ICD), and Cardiac Resynchronization Therapy (CRT) are exposed to in-vivo damage. These damages are complex and composed on multiple levels and present challenges while assessing their combined extent. Since 2004, more than one hundred recalls were reported for cardiac devices. ICD devices had the majority with 40.8% recalls, pacemaker recall percentage was 14.5%, CRT recall percentage was12.7%, leads recalls …

Inception Modules Enhance Brain Tumor Segmentation., Daniel E Cahall, Ghulam Rasool, Nidhal Carla Bouaynaya, Hassan M Fathallah-Shaykh

Henry M. Rowan College of Engineering Departmental Research

Magnetic resonance images of brain tumors are routinely used in neuro-oncology clinics for diagnosis, treatment planning, and post-treatment tumor surveillance. Currently, physicians spend considerable time manually delineating different structures of the brain. Spatial and structural variations, as well as intensity inhomogeneity across images, make the problem of computer-assisted segmentation very challenging. We propose a new image segmentation framework for tumor delineation that benefits from two state-of-the-art machine learning architectures in computer vision, i.e., Inception modules and U-Net image segmentation architecture. Furthermore, our framework includes two learning regimes, i.e., learning to segment intra-tumoral structures (necrotic and non-enhancing tumor core, peritumoral edema, …

Biomarker-Performance Associations During Nutritional And Exercise Intervention In Air Force Personnel, Jennifer Jurcsisn

Browse all Theses and Dissertations

This study evaluated the combined effects of an exercise intervention and nutritional supplement on biomarkers of stress and resilience, and the relationships of those markers with physical and cognitive performance. 130 healthy Active-Duty Air Force (AF) personnel were recruited to participate in a double-blind, placebo controlled 12-week exercise and nutritional intervention. Serum was collected at basal and high stress conditions pre- and post-intervention to track the following biomarkers: cortisol, dehydroepiandrosterone-sulfate (DHEA-S), norepinephrine (NE), neuropeptide Y (NPY), and serotonin. The exercise intervention significantly attenuated the cortisol response and peak stress cortisol levels. The nutritional intervention decreased peak stress NE. The selected …

Ultrasound Calibration For Unique 2.5d Conical Images, Hareem Nisar, John Moore, Natasha Alves, Germain Hwang, Terry Peters, Elvis Chen

Robarts Imaging Publications

Intracardiac echocardiography (ICE) systems are routinely used in percutaneous cardiac interventions for inter-ventional and surgical navigation. Conavi’s Foresight ICE is a new ICE system that uses a mechanically rotatingtransducer to generate a 2D conical surface image in 3D space, in contrast to the more typical side-firing phasedarray. When combined with magnetic tracking technology, this unique imaging geometry poses new calibrationchallenges and opportunities. Existing ultrasound calibration methods are designed for 2D planar images andcannot be trivially applied to unique 2.5D conical surface images provided by the Foresight ICE system. In thiswork a spatial and temporal calibration technique applied to the unique …

A Virtual-Reality Training Simulator For Cochlear Implant Surgery, Blake Jones, Seyed Alireza Rohani, Nelson Ong, Tarek Tayeh, Hanif M. Ladak, Ahmad Chalabi, Sumit K. Agrawal

Electrical and Computer Engineering Publications

No abstract provided.

Three-Dimensional Human Neural Stem Cell Culture For High-Throughput Assessment Of Developmental Neurotoxicity, Pranav Joshi

ETD Archive

Only a few hundred of compounds, among tens of thousands of commercially available compounds, have been tested for developmental neurotoxicity (DNT) due to the limitations of current guidelines for DNT which are based entirely on in vivo experiments. In vivo studies are highly expensive and time-consuming, which often do not correlate to human outcomes. There is a key gap in our ability to predict in vivo outcomes accurately and robustly using in vitro assays. This is particularly the case for predicting the toxicity of chemicals on the developing human brains. Conventional in vitro assays are typically performed in two-dimensional (2D) …