Engineering Commons^™

Continuous Downstream Processing Of A Monoclonal Antibody Using Periodic Counter Current Chromatography (Pcc) And Straight Through Processing (Stp), Hans Blom, Christer Eriksson, Annika Forss, Helena Skoglar

Integrated Continuous Biomanufacturing II

There is an increased interest to perform process intensification in order to reduce costs and improve throughput in the development and production of monoclonal antibodies (MAbs). One solution to these demands can be to implement continuous or semi-continuous downstream processing. New emerging technologies such as periodic counter-current (PCC) chromatography and straight through processing (STP) are entering the market. Here, these two technologies were evaluated in a continuous three step chromatography MAb process. The capture step was performed with protein A media (resin) on a 3 column PCC chromatography system followed by two polishing steps which were connected in series with …

Integrated Solutions For Continuous Processing In Mobius® Bioreactor Systems, Andrew Clutterbuck

Integrated Continuous Biomanufacturing II

Throughout the bioprocess industry, the use of disposable systems such as bioreactors is playing an increasingly significant role. Manufactures are recognising the strategic benefits of single use systems in both reducing production costs and increasing overall manufacturing throughput.

Over the past few years there has been increasing demand for larger scale disposable bioreactor systems, to satisfy the manufacturing demands and an emphasis on suppliers such as Merck Millipore to demonstrate robust and reproducible scale-up within these systems.

This presentation will explore the design philosophies behind the Mobius^® bioreactors and will also give an overview of the novel SensorReady external …

Optical Enzymatic Sensors For Continuous Monitoring Of Bioreactors, Kenneth Reardon, Brian Heinze, Trenton Danna

Integrated Continuous Biomanufacturing II

Continuous monitoring of biotechnological processes is important for control and optimization of quality and productivity. Typically, samples must be removed from the cultivation and analyzed in a laboratory to determine the concentrations of substrates and products. These time-delayed data cannot be used for real-time process control. The Process Analytical Technology initiative of the FDA supports the use of on-line measurement techniques for process development, production, and quality. An overview of sensors will be presented, focusing on in-situ sensors that contact the biological medium, and external sensors that contact the medium either optically (ex situ) or via a sterile (and disposable) …

Salt-Tolerant Cation Exchange Hd-Sb Hydrogel Membrane: Mab Purification Performance In Flowthrough Mode, Dharmesh Kanani, Daniel Luo, Nirali Paghdal, Navneet Sidhu, Annabel Shang, Jim Stout

Integrated Continuous Biomanufacturing II

Development of Protein A based purification platforms have simplified the downstream processing of monoclonal antibodies (mAb), the largest component of biopharmaceuticals. The ever increasing titer of the cell culture process is putting more pressure on the downstream process to further increase its productivity. The classical Protein A based mAb purification platform consists of two polishing steps, bind and elute cation-exchanger and flowthrough anion-exchanger. Cation-exchange chromatography is very efficient at the separation of HCP, leached Protein A and product-related impurities such as aggregates and fragments in bind and elute mode. However, anion-exchange chromatography is a proven technology to remove DNA, viruses, …

Glycoexpress: A Toolbox For The High Yield Production Of Glycooptimized Fully Human Biopharmaceuticals In Perfusion Bioreactors At Different Scales, Steffen Kreye

Integrated Continuous Biomanufacturing II

Background and Novelty: Glycosylation is one of the major post-translational modifications of biotherapeutics important for bioactivity, bioavailability, immunogenicity and patient coverage. By establishment of the GlycoExpress™ toolbox (GEX™) we have generated a set of glycoengineered human cell lines for the high yield production of fully human glycoproteins to optimize the glycosylation of antibodies and non-antibody biotherapeutics for improvement of the clinical efficacy and side effects. The system is biotechnologically superior in quality, reproducibility and yield compared to other including conventional production systems. All four clinical products derived from GlycoExpress cells are produced using a perfusion bioreactor system in order to …

Designing A Microbial Cultivation Platform For Continuous Biopharmaceutical Production, Nicholas Mozdzierz, Kerry Love, Alan Stockdale, John Clark, Noelle Colant, Christopher Love

Integrated Continuous Biomanufacturing II

The existing biopharmaceutical manufacturing paradigm is poorly suited to produce biologic drugs on demand at a point-of-care. Generally, commercial-scale (~2,000 - 10,000 L) manufacturing using fed-batch cultivation and fixed stainless-steel infrastructure is concentrated in developed nations and results in process cycle times on the order of weeks to months.^1,2 Coupled with the complex logistical challenges associated with continuous “plant-to-patient” cold-chains, the geographically biased nature of therapeutic protein production today can limit access to biologic drugs in developing areas of the world.³ There is an opportunity to create technologies capable of rapidly generating biopharmaceuticals in situ in emergency situations, …

Robust Design And Operation Of Quasi-Continuous Adenovirus Purification By Two-Column, Simulated Moving-Bed, Size-Exclusion Chromatography, Jose Mota, Ricardo Silva, Piergiuseppe Nestolla, Cristina Peixoto, Manuel Carrondo

Integrated Continuous Biomanufacturing II

Adenoviruses (Ads) are considered one of the most suitable platforms for production of viral vaccines and gene therapy vectors. Their broad tissue tropism and large transgene packing capacity make them attractive candidates for innovative virotherapies. Ads can be produced in a complementary cell line in both adherent and suspension culture systems, such as HEK-293 or PER-C6 cells, or A549 for oncolytic therapies.

Liquid chromatography is currently the core technique for vector purification, and its use is often integrated vertically within the downstream processing (DSP) strategy, as it easily fits into the early capture stage as well as into the final …

Final Program, Kathy Chan

Integrated Continuous Biomanufacturing II

No abstract provided.

Gaussian Nonlinear Line Attractor For Learning Multidimensional Data, Theus H. Aspiras, Vijayan K. Asari, Wesam Sakla

Electrical and Computer Engineering Faculty Publications

The human brain’s ability to extract information from multidimensional data modeled by the Nonlinear Line Attractor (NLA), where nodes are connected by polynomial weight sets. Neuron connections in this architecture assumes complete connectivity with all other neurons, thus creating a huge web of connections. We envision that each neuron should be connected to a group of surrounding neurons with weighted connection strengths that reduces with proximity to the neuron. To develop the weighted NLA architecture, we use a Gaussian weighting strategy to model the proximity, which will also reduce the computation times significantly.

Once all data has been trained in …

Computational Characterization Of Exogenous Micrornas That Can Be Transferred Into Human Circulation, Jiang Shu, Kevin Chiang, Janos Zempleni, Juan Cui

School of Computing: Faculty Publications

MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of …

Detection Of Acute Nervous System Injury With Advanced Diffusion-Weighted Mri: A Simulation And Sensitivity Analysis, Nathan P. Skinner, Shekar N. Kurpad, Brian D. Schmit, Matthew D. Budde

Biomedical Engineering Faculty Research and Publications

Diffusion-weighted imaging (DWI) is a powerful tool to investigate the microscopic structure of the central nervous system (CNS). Diffusion tensor imaging (DTI), a common model of the DWI signal, has a demonstrated sensitivity to detect microscopic changes as a result of injury or disease. However, DTI and other similar models have inherent limitations that reduce their specificity for certain pathological features, particularly in tissues with complex fiber arrangements. Methods such as double pulsed field gradient (dPFG) and q-vector magic angle spinning (qMAS) have been proposed to specifically probe the underlying microscopic anisotropy without interference from the macroscopic tissue organization. …

Effect Of Imperceptible Vibratory Noise Applied To Wrist Skin On Fingertip Touch Evoked Potentials – An Eeg Study, Na Jin Seo, Kishor Lakshminarayanan, Leonardo Bonilha, Abigail W. Lauer, Brian D. Schmit

Biomedical Engineering Faculty Research and Publications

Random vibration applied to skin can change the sense of touch. Specifically, low amplitude white-noise vibration can improve fingertip touch perception. In fact, fingertip touch sensation can improve even when imperceptible random vibration is applied to other remote upper extremity areas such as wrist, dorsum of the hand, or forearm. As such, vibration can be used to manipulate sensory feedback and improve dexterity, particularly during neurological rehabilitation. Nonetheless, the neurological bases for remote vibration enhanced sensory feedback are yet poorly understood. This study examined how imperceptible random vibration applied to the wrist changes cortical activity for fingertip sensation. We measured …

Computational Replication Of The Patient-Specific Stenting Procedure For Coronary Artery Bifurcations: From Oct And Ct Imaging To Structural And Hemodynamics Analyses, Claudio Chiastra, Wei Wu, Benjamin Dickerhoff, Ali Aleiou, Gabriele Dubini, Hiromasa Otake, Francesco Migliavacca, John F. Ladisa Jr.

Biomedical Engineering Faculty Research and Publications

The optimal stenting technique for coronary artery bifurcations is still debated. With additional advances computational simulations can soon be used to compare stent designs or strategies based on verified structural and hemodynamics results in order to identify the optimal solution for each individual’s anatomy. In this study, patient-specific simulations of stent deployment were performed for 2 cases to replicate the complete procedure conducted by interventional cardiologists. Subsequent computational fluid dynamics (CFD) analyses were conducted to quantify hemodynamic quantities linked to restenosis.

Patient-specific pre-operative models of coronary bifurcations were reconstructed from CT angiography and optical coherence tomography (OCT). Plaque location and …

An Immersed Boundary Geometric Preprocessor For Arbitrarily Complex Terrain And Geometry, Inanc Senocak, Micah Sandusky, Rey Deleon, Derek Wade, Kyle Felzien, Marianna Budnikova

Mechanical and Biomedical Engineering Faculty Publications and Presentations

There is a growing interest to apply the immersed boundary method to compute wind fields over arbitrarily complex terrain. The computer implementation of an immersed boundary module into an existing flow solver can be accomplished with minor modifications to the rest of the computer program. However, a versatile preprocessor is needed at the first place to extract the essential geometric information pertinent to the immersion of an arbitrarily complex terrain inside a 3D Cartesian mesh. Errors in the geometric information can negatively impact the correct implementation of the immersed boundary method as part of the solution algorithm. Additionally, the distance …

Next-Generation Mrna Sequencing Reveals Pyroptosis-Induced Cd4+ T Cell Death In Early Simian Immunodeficiency Virus-Infected Lymphoid Tissues, Wuxun Lu, Andrew J. Demers, Fangrui Ma, Guobin Kang, Zhe Yuan, Yanmin Wan, Yue Li, Jiangqing Xu, Mark Lewis, Qingsheng Li

Nebraska Center for Biotechnology: Faculty and Staff Publications

Lymphoid tissues (LTs) are the principal sites where human immunodeficiency virus type 1 (HIV-1) replicates and virus-host interactions take place, resulting in immunopathology in the form of inflammation, immune activation, and CD4+ T cell death. The HIV-1 pathogenesis in LTs has been extensively studied; however, our understanding of the virus-host interactions in the very early stages of infection remains incomplete. We investigated virus-host interactions in the rectal draining lymph nodes (dLNs) of rhesus macaques at different times after intrarectal inoculation (days postinoculation [dpi]) with simian immunodeficiency virus (SIV). At 3 dpi, 103 differentially expressed genes (DEGs) were detected using next-generation …

Modeling Viscoelastic Behavior In Compact Bone Through A Distribution Of Collagen D-Spacing: A Finite Element Analysis, Christopher Ha

Master's Theses

Osteoporosis affects nearly 54 million people in the United States. The cost associated with treatment is estimated to be $19 billion per year and is expected to grow yearly. D-spacing is the staggering of collagen molecules found at the nanoscopic level. Previously thought to have a constant value, recent studies have found that D-spacing has a distribution of values throughout the tissue. As part of an ongoing effort in understanding the mechanisms that are affected by osteoporosis, a finite element model was developed to explore the effects of D-spacing distribution on the viscoelastic material properties of bone tissue. The goal …

Biomechanical Investigation Of Elite Place-Kicking, Chase M. Pfeifer

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Many studies aim to understand the fundamentals of kicking commonly displayed by soccer players [4,6,10,16,17,18,24,25,28,29,30,34,36,38,40]. Of those studies, most are limited to a two-dimensional (2D) analysis using high-speed cameras for position tracking or utilizing electromyography to observe the activity of select muscles [4,6,18,25,29,36]. The few studies that investigate kicking using a three-dimensional (3D) model are limited in their position tracking capabilities and focus mainly on joint flexion potentials and foot speed.

This dissertation is a comprehensive biomechanical analysis (kinematic and EMG) of the field-goal place-kicking techniques of four elite kickers in American football. Data were compared and contrasted with ball …

Smartphone Based 3d Printed Colorimeter For Biomedical Applications, Karthik Raj Konnaiyan

USF Tampa Graduate Theses and Dissertations

Here we present a novel Smartphone-based colorimeter and demonstrate its application to the measurements of glucose and protein concentrations in biological samples. The key innovation of our approach was to combine powerful image processing encoded into a mobile phone application with a low cost 3D printed sample holder that allowed to control lighting conditions and significantly improved sensitivity. Different solutions with protein and glucose concentrations ranging from 0 to 2000 mg/dL were prepared and analyzed using our system. The Smartphone-based colorimeter always correctly classified the corresponding reagent strip pads, what confirms that it can be used as a low cost …

Incorporation Of Fibrin Into A Collagen–Glycosaminoglycan Matrix Results In A Scaffold With Improved Mechanical Properties And Enhanced Capacity To Resist Cell-Mediated Contraction, Claire Brougham, Tanya J. Levingstone, Stefan Jockenhoevel, Thomas C. Flanagan, Fergal J. O'Brien

Articles

Fibrin has many uses as a tissue engineering scaffold, however many in vivo studies have shown a reduction in function resulting from the susceptibility of fibrin to cell-mediated contraction. The overall aim of the present study was to develop and characterise a reinforced natural scaffold using fibrin, collagen and glycosaminoglycan (FCG), and to examine the cell-mediated contraction of this scaffold in comparison to fibrin gels. Through the use of an injection loading technique, a homogenous FCG scaffold was developed. Mechanical testing showed a sixfold increase in compressive modulus and a thirtyfold increase in tensile modulus of fibrin when reinforced with …

Department Of Biological Systems Engineering Newsletter, Fall 2015

BSE Department Magazine

No abstract provided.

Underwater Sound Transmission Through Arrays Of Disk Cavities In A Soft Elastic Medium., David C. Calvo, Abel L. Thangawng, Christopher N. Layman, Riccardo Casalini, Shadi F. Othman

All Faculty Articles - School of Engineering and Computer Science

Scattering from a cavity in a soft elastic medium, such as silicone rubber, resembles scattering from an underwater bubble in that low-frequency monopole resonance is obtainable in both cases. Arrays of cavities can therefore be used to reduce underwater sound transmission using thin layers and low void fractions. This article examines the role of cavity shape by microfabricating arrays of disk-shaped air cavities into single and multiple layers of polydimethylsiloxane. Comparison is made with the case of equivalent volume cylinders which approximate spheres. Measurements of ultrasonic underwater sound transmission are compared with finite element modeling predictions. The disks provide a …

Quantification Of Blood Flow Velocity Using Color Sensing, Aditya Deepak Sanghani

Master's Theses

Blood flow velocity is an important parameter that can give information on several pathologies including atherosclerosis, glaucoma, Raynaud’s phenomenon, and ischemic stroke [2,5,6,10]. Present techniques of measuring blood flow velocity involve expensive procedures such as Doppler echocardiography, Doppler ultrasound, and magnetic resonance imaging [11,12]. They cost from $8500-$20000. It is desired to find a low-cost yet equally effective solution for measuring blood flow velocity. This thesis has a goal of creating a proof of concept device for measuring blood flow velocity.

Finger blood flow velocity is investigated in this project. The close proximity to the skin of the finger’s arteries …

Quantifying Cross-Scatter Contamination In Biplane Fluoroscopy Motion Analysis Systems, Janelle A. Cross, Ben Mchenry, Taly Gilat-Schmidt

Biomedical Engineering Faculty Research and Publications

Biplane fluoroscopy is used for dynamic in vivo three-dimensional motion analysis of various joints of the body. Cross-scatter between the two fluoroscopy systems may limit tracking accuracy. This study measured the magnitude and effects of cross-scatter in biplane fluoroscopic images. Four cylindrical phantoms of 4-, 6-, 8-, and 10-in. diameter were imaged at varying kVp levels to determine the cross-scatter fraction and contrast-to-noise ratio (CNR). Monte Carlo simulations quantified the effect of the gantry angle on the cross-scatter fraction. A cadaver foot with implanted beads was also imaged. The effect of cross-scatter on marker-based tracking accuracy was investigated. Results demonstrated …

Lpcoms: Towards A Low Power Wireless Smart-Shoe System For Gait Analysis In People With Disabilities, Ishmat Zerin

Master's Theses (2009 -)

Gait analysis using smart sensor technology is an important medical diagnostic process and has many applications in rehabilitation, therapy and exercise training. In this thesis, we present a low power wireless smart-shoe system (LPcomS) to analyze different functional postures and characteristics of gait while walking. We have designed and implemented a smart-shoe with a Bluetooth communication module to unobtrusively collect data using smartphone in any environment. With the design of a shoe insole equipped with four pressure sensors, the foot pressure is been collected, and those data are used to obtain accurate gait pattern of a patient. With our proposed …

Hockey Skating Kinematics And The Effect Of Skate Design And Technique Training, Rebecca Mae Tidman

Master's Theses (2009 -)

The purpose of this study was to investigate the effects of technique training and hockey skate design on hockey skating performance. Fourteen male subjects, aged 12-16 years, with no recent skate treadmill experience completed ten training sessions on a skating treadmill. Instruction emphasized maximizing stride width by pushing laterally with the skate pointed anteriorly. Subjects were randomly placed into one of two experimental groups based on initial skate type: traditional or Easton Mako. After completion of five sessions, skate type was switched so that skate design effects could be assessed. In contrast to a traditional hockey skate design, the Easton …

Mechanical Characterization Of Carbon Fiber And Thermoplastic Ankle Foot Orthoses, Amanda Wach

Master's Theses (2009 -)

The needs of an increasingly young and active orthotic patient population has led to advancements in ankle foot orthosis (AFO) design and materials to enable higher function. The Intrepid Dynamic Exoskeletal Orthosis (IDEO) is a custom energy-storing carbon fiber AFO that has demonstrated improved clinical function, allowing patients to return to high-intensity activities such as sports and military service. An improved understanding of AFO mechanical function will aid prescription and fitting, as well as assist in design modifications for different patient populations. This study investigated the mechanical properties of AFOs, specifically structural stiffness, rotational motion, and strut deflection, to discern …

Integrating Meal And Exercise Into Personalized Glucoregulation Models: Metabolic Dynamics And Diabetic Athletes, Sofie Schunk

Master's Theses (2009 -)

Diabetes affects nearly 26 million Americans, according to the American Diabetes Association, with as many as three million Americans who have Type 1 Diabetes (ADA, 2015). Type 1 Diabetes (T1D) is autoimmune and characterized by little to no insulin production whereas Type 2 Diabetes (T2D) concerns insulin resistance and inability to use produced insulin. Factors contributing to current diabetes management and regulation include exercise type, daily movement activities, and distinct tissue compartment metabolism, each challenging to model in a robust and comprehensive manner. Past models are highly limited in regard to exercise and varying glucose fluctuations dependent on type, intensity, …

Noninvasive Assessment Of Photoreceptor Structure And Function In The Human Retina, Robert Francis Cooper

Dissertations (1934 -)

The human photoreceptor mosaic underlies the first steps of vision; thus, even subtle defects in the mosaic can result in severe vision loss. The retina can be examined directly using clinical tools; however these devices lack the resolution necessary to visualize the photoreceptor mosaic. The primary limiting factor of these devices is the optical aberrations of the human eye. These aberrations are surmountable with the incorporation of adaptive optics (AO) to ophthalmoscopes, enabling imaging of the photoreceptor mosaic with cellular resolution. Despite the potential of AO imaging, much work remains before this technology can be translated to the clinic. Metrics …

Computational Approaches For Remote Monitoring Of Symptoms And Activities, Ferdaus Kawsar

Dissertations (1934 -)

We now have a unique phenomenon where significant computational power, storage, connectivity, and built-in sensors are carried by many people willingly as part of their life style; two billion people now use smart phones. Unique and innovative solutions using smart phones are motivated by rising health care cost in both the developed and developing worlds. In this work, development of a methodology for building a remote symptom monitoring system for rural people in developing countries has been explored. Design, development, deployment, and evaluation of e-ESAS is described. The system’s performance was studied by analyzing feedback from users. A smart phone …

Biomechanical Characerization And Evaluation Of Conservative Clubfoot Correction, Tamara Loren Cohen

Dissertations (1934 -)

Congential talipes equinovarus, or clubfoot, affects approximately 200,000 newborns worldwide each year and presents with equinovarus of the hindfoot, as well as cavus and adduction of the midfoot. In addition to bone malformation and displacement, soft tissue contractures encapsulate the medial and posterior aspects of the affected foot. The Ponseti method is a conservative treatment that progressively repositions the clubfoot through weekly casting, followed by bracing. Concerns exist regarding the variability in outcomes, resistance to treatment, and risk of relapse, which occur in approximately 10% of the population. Potential factors contributing to variability and resistant clubfoot include cast material performance, …