Engineering Commons^™

Continuous Purification Of Hepatitis C Virus-Like Particles By Multi-Column Chromatography, Ricardo Silva, Alex Xenopoulos, Jose Mota, Cristina Peixoto, Manuel Carrondo, Paula Alves

Integrated Continuous Biomanufacturing II

Novel biopharmaceutical products, such as virus-like particles (VLPs) and viral vectors, constitute a challenging task for downstream processing (DSP). Recoveries achieved to reach required purities are significantly inferior compared to more common antibody and other recombinant processes. Therefore, the biopharmaceutical industry is looking for alternative downstream strategies capable of improving purification yields and decreasing cost while maintaining product quality. One of many possible improvements to DSP is to replace single-column batch operation by continuous, or semi-continuous, multi-column chromatography.

A single-column batch chromatographic operation used for capture is limited by the dynamic binding capacity (DBC) of the target product. For high-value …

Innovations In Bioreactor Operational Modes – Hybrid Semi-Continuous Processes To Push Beyond The Limits Of Conventional Fed-Batch Cultures, Gregory Hiller, Matthew Gagnon, Ana Maria Ovalle, Wenge Wang, Elizabeth Eydelman

Integrated Continuous Biomanufacturing II

Due to the limits of feed volume addition and the problem of amino acid counter ion, miscellaneous osmolyte, and cell growth inhibitor accumulation, the fed-batch mode of bioreactor operation for CHO cell production of protein therapeutics is inherently limited with respect to the cell densities and productivities that are achievable. Continuous or perfusion culture with cell retention can overcome some of these limitations, but suffers from the disadvantages of large volume media consumption, long times to reach peak cell densities, and complications with cell retention devices. We will describe hybrid versions of continuous culture that overcome many of these limitations …

Bhk Cells Physiological Response To Spin-Filter Stress Condition, Bruno Labate, Aldo Tonso

Integrated Continuous Biomanufacturing II

Mammalian cells are the preferable platform for secreted pharmaceutical proteins due to the compatibility of posttranslational modifications performed by these cells with therapeutic applications. However, to obtain a desirable quantity of these proteins, high cell concentrations are also needed. Baby hamster kidney BHK-21/C13 cells, adapted to single-cell suspension culture growth were cultivated in batch mode in a Biostat B (Sartorius AG, Germany) bioreactor with a 1,5 L working volume vessel. The temperature was controlled at 37 ºC, pH at 7.2 with CO­₂, agitation at 80 rpm and dissolved oxygen at 50% of air saturation. The culture medium used …

Mab Product Consistency Achieved In Long Duration Microfiltration-Based Cho Perfusion Process, Douglas Rank, Christopher Martin, Lee Madrid, Michael Phillips

Integrated Continuous Biomanufacturing II

Perfusion processes have traditionally been used for the generation of unstable proteins in cell culture systems. The use of perfusion for production of stable proteins has been limited by low product concentration, media costs, and system complexity. However, with the advent of new single-use technology, cell culture media specifically formulated to support high density perfusion, and high-producing cell lines, perfusion processes are gaining widespread industry attention. Additionally, perfusion processes are considered an integral part of the “Factory of the Future” vision through enabling continuous processing while delivering a product effluent with consistent product quality and concentration.

In this study, we …

Evaluation Of A Continuous Chromatography Process Through Process Modeling And Resin Characterization, Ketki Behere, Seongkyu Yoon

Integrated Continuous Biomanufacturing II

Increased product yield at reduced cost and time has been the driving force of any manufacturing process. However, inevitable increase in future demand for biopharmaceutical drugs, along with intensified competition and stringent regulatory laws have exhibited an imperative need for established platform processes. In this regard, the implementation of continuous processing, in whole or in components, has demonstrated to increase the manufacturing productivity with key impact on speed, cost and facility implications. While, upstream operations have confirmed increased productivity by implementation of continuous processing components, such as perfusion culture, similar adaptation for downstream processes has been limited. We have evaluated …

Continuous Production Of Proteins: Integration Of Polishing Using Mcsgp, Fabian Steinebach, Daniel Karst, Massimo Morbidelli

Integrated Continuous Biomanufacturing II

Continuous counter-current processes for polishing steps overcome the purity-yield tradeoff of classical batch chromatography by internal recycling of overlapping regions of the chromatogram. Particularly in the case of challenging separation tasks this leads for the same product quality to significantly higher yields and productivity. Processes using these fundamental principals have been successfully implemented in the chemical industry up to multi-ton production.

In an integrated continuous process, with a perfusion bioreactor and a continuous capture process, the product quality of the capture product is different compared to classical batch processing. The lower residence time in the bioreactor and the higher loading …

Exometabolome Characterization Of High Cell Density Culture Perfusion And Optimization Of The Cell Specific Perfusion Rate, Veronique Chotteau, Leila Zamani, Ye Zhang, Magnus Aberg, Anna Lindahl, Axel Mie

Integrated Continuous Biomanufacturing II

High cell density perfusion has the potential to generate intensified processes. A target for such perfusion process can be to maintain a steady state culture around 100 x 10⁶ cells/mL. A challenge for the development of these processes is to minimize the medium consumption, to reduce the costs associated with this raw material and with the harvest processing. This is particularly true for processes at densities such as 100 x 10⁶ cells/mL for which several reactor volumes per day are typically necessary.

We have shown that cell specific perfusion rate (CSPR) is an approach, which has proven to …

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 …

Engineering Thinking | College Of Engineering, Usu College Of Engineering

College of Engineering News

Nov. 2, 2015 - It’s no surprise: engineering courses are tough. Professors assign complex homework problems that can take hours to solve, and for some the experience feels like drinking from a fire hose.

Most engineering programs begin with a handful of rigorous courses in statics and dynamics that can be stumbling blocks for some. This has engineering education experts looking for retention solutions and rethinking how these difficult courses are taught.

Engineers Without Borders | College Of Engineering, Usu College Of Engineering

College of Engineering News

Nov. 2, 2015 – Members of the Engineers Without Borders Team Mexico have been working with residents in the community of La Salitrera, Mexico for several years to help eliminate arsenic from water supplies using an improved design on a classic tool – the bio-sand water filter.

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 …

A Smarter Baby Monitor | College Of Engineering, Usu College Of Engineering

College of Engineering News

Nate Ruben and Professor of Electrical and Computer Engineering Dr. Jake Gunther can see something on the surface that most people can’t. The two are developing a new technology that uses a video camera to detect a person’s heartbeat. It’s not the first time engineers have tried to remotely measure a heartbeat signal. Medical technology experts have been at it for years with different designs that tether a child or his bedding to an electronic device that alerts parents to the possibility of Sudden Infant Death Syndrome, or SIDS.

Tandemonium | College Of Engineering, Usu College Of Engineering

College of Engineering News

Nov. 2, 2015 — Jay Lindstrom’s love for biking and Laura Birkhold’s enthusiasm for a hands-on project made designing a side-by-side quadricycle perfect for their senior design project. Along with their team members and representatives from Common Ground Outdoor Adventures and Icon Health & Fitness, the group of mechanical engineering students set out to build a unique tandem cycle they dubbed ‘Tandemonium.’

Evaluation Of The Snow Thermal Model (Sntherm) Through Continuous In Situ Observations Of Snow’S Physical Properties At The Crest-Safe Field Experiment, José Alberto Infante Corona, Jonathan Muñoz, Tarendra Lakhankar, Peter Romanov, Reza Khanbilvardi

Publications and Research

Snowpack properties like temperature or density are the result of a complex energy and mass balance process in the snowpack that varies temporally and spatially. The Snow Thermal Model (SNTHERM) is a 1-dimensional model, energy and mass balance-driven, that simulates these properties. This article analyzes the simulated snowpack properties using SNTHERM forced with two datasets, namely measured meteorological data at the Cooperative Remote Sensing Science and Technology-Snow Analysis and Field Experiment (CREST-SAFE) site and the National Land Data Assimilation System (NLDAS). The study area is located on the premises of Caribou Municipal Airport at Caribou (ME, USA). The model evaluation …

Kelvin Probe Electrode For Field Detection Of Corrosion Of Steel In Concrete, Leonidas Philip Emmenegger

USF Tampa Graduate Theses and Dissertations

While the Kelvin Probe (KP) has been used in a variety of surface scanning applications, the use of the KP in reinforced concrete structures to detect corrosion has been pioneered by previous work performed at the University of South Florida. However, in that work, the scale and construction of the probes was not suited to use in the field. This is primarily attributable to the small operating disk-to-concrete gap which would make the probe unable to accommodate road conditions, such as irregularities in the grading of the road, and local pitting of the surface. Therefore, it was important to investigate …

Creep Behavior In Interlaminar Shear Of A Hi-Nicalon™/Sic-B4c Composite At 1200°C In Air And In Steam, Marina B. Ruggles-Wrenn, Matthew T. Pope

Faculty Publications

Creep behavior in interlaminar shear of a non-oxide ceramic composite with a multilayered matrix was investigated at 1200^∘C in laboratory air and in steam environment. The composite was produced via chemical vapor infiltration (CVI). The composite had an oxidation inhibited matrix, which consisted of alternating layers of silicon carbide and boron carbide and was reinforced with laminated Hi-Nicalon^TM fibers woven in a five-harness-satin weave. Fiber preforms had pyrolytic carbon fiber coating with boron carbon overlay applied. The interlaminar shear properties were measured. The creep behavior was examined for interlaminar shear stresses in the 16–22 MPa range. Primary …

Standard For Cold-Formed Steel Framing -- Prescriptive Method For One- And Two-Family Dwellings, 2015 Edition, American Iron And Steel Institute

American Iron and Steel Institute (AISI) Specifications, Standards, Manuals and Research Reports (1946 - present)

No abstract provided.

Tungsten Disulphide Based All Fiber Q-Switching Cylindrical-Vector Beam Generation, J. Lin, K. Yan, Yong Zhou, L. X. Xu, C. Gu, Qiwen Zhan

Electro-Optics and Photonics Faculty Publications

We proposed and demonstrated an all fiber passively Q-switching laser to generate cylindrical-vectorbeam, a two dimensional material,tungsten disulphide (WS2), was adopted as a saturable absorber inside the laser cavity, while a few-mode fiber Bragg grating was used as a transverse mode-selective output coupler. The repetition rate of the Q-switching output pulses can be varied from 80 kHz to 120 kHz with a shortest duration of 958 ns. Attributed to the high damage threshold and polarization insensitivity of the WS2 based saturable absorber, the radially polarized beam and azimuthally polarized beam can be easily generated in the Q-switchingfiber laser.

Final Program, Kathy Chan

Integrated Continuous Biomanufacturing II

No abstract provided.

Energy-Efficient Computational Chemistry: Comparison Of X86 And Arm Systems, Kristopher Keipert, Gaurav Mitra, Vaibhav Sunriyal, Sarom S. Leang, Masha Sosonkina, Alistair P. Rendell, Mark S. Gordon

Computational Modeling & Simulation Engineering Faculty Publications

The computational efficiency and energy-to-solution of several applications using the GAMESS quantum chemistry suite of codes is evaluated for 32-bit and 64-bit ARM-based computers, and compared to an x86 machine. The x86 system completes all benchmark computations more quickly than either ARM system and is the best choice to minimize time to solution. The ARM64 and ARM32 computational performances are similar to each other for Hartree-Fock and density functional theory energy calculations. However, for memory-intensive second-order perturbation theory energy and gradient computations the lower ARM32 read/write memory bandwidth results in computation times as much as 86% longer than on the …

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 …

Science Is Helpful For Engineering Applications: A Theoretical Explanation Of An Empirical Observation, Olga Kosheleva, Vladik Kreinovich

Departmental Technical Reports (CS)

Empirical evidence shows that when engineering design uses scientific analysis, we usually get a much better performance that for the system designed by using a trial-and-error engineering approach. In this paper, we provide a quantitative explanation for this empirical observation.

Radial Strain Behaviors And Stress State Interpretation Of Soil Under Direct Simple Shear, Xin Kang, Yao Cheng, Louis Ge

Civil, Architectural and Environmental Engineering Faculty Research & Creative Works

Radial strain behaviors and stress state interpretation methods of silica sand consolidated at different K0 values under modified direct simple shear were investigated in this research. Consolidated drained triaxial compression test, direct shear box test, and wire reinforced direct simple shear tests were conducted, and the test results were compared and linked with the modified direct simple shear tests. Based on the observed testing data, simple shear specimens with constant lateral stress exhibited relatively small radial strain during shear, especially under small shear strains. After the peak shear resistance has mobilized, radial strain increased rigorously until the specimen failed. Confining …

Geotechnical Effects Of The 2015 Magnitude 7.8 Gorkha, Nepal, Earthquake And Aftershocks, Robb E.S. Moss, Eric M. Thompson, D. Scott Kieffer, Binod Tiwari, Youssef M.A. Hashash, Indra Acharya, Basanta Raj Adhikari, Domniki Asimaki, Kevin B. Clahan, Brian D. Collins, Sachindra Dahal, Randall W. Jibson, Diwakar Khadka, Amy Macdonald, Chris L.M. Madugo, H. Benjamin Mason, Menzer Pehlivan, Deepak Rayamajhi, Sital Uprety

Civil and Environmental Engineering

This article summarizes the geotechnical effects of the 25 April 2015 M 7.8 Gorkha, Nepal, earthquake and aftershocks, as documented by a reconnaissance team that undertook a broad engineering and scientific assessment of the damage and collected perishable data for future analysis. Brief descriptions are provided of ground shaking, surface fault rupture, landsliding, soil failure, and infrastructure performance. The goal of this reconnaissance effort, led by Geotechnical Extreme Events Reconnaissance, is to learn from earthquakes and mitigate hazards in future earthquakes.

Evaluation Of In-Ground Plastic-Hinge Length And Depth For Piles In Marine Oil Terminals, Rakesh K. Goel

Civil and Environmental Engineering

This investigation evaluated the current recommendations for plastic-hinge length and depth for piles in marine oil terminals considering nonlinear pile and soil behavior, as well as two seismic design levels: Level 1 and Level 2. It was found that the plastic-hinge length depends on seismic design level, whereas depth is independent of seismic design level. For pre-stressed concrete piles, the current plastic-hinge length recommendations were generally found to be adequate for seismic design Level 2, but provided much smaller plastic-hinge length for Level 1. For hollow-steel piles, the current plastic-hinge length recommendation was generally found to be adequate for sands, …