News and Events for the Department of Chemical and Biochemical Engineering in the College of Engineering and Information Technology at UMBC.
March 2, 2014
December 19, 2013
Congratulations to Bill Moss (mentor Mark Marten) and Aditi Bhaskar (mentor Claire Welty), both of whom graduated with their Ph.D. Degrees.
December 12, 2013
Congratulations to Nuno Dos Santos Pinto, who successfully defended his Ph.D. on December 8th, 2013. His research was performed int the Frey Lab; the title of his dissertation was Novel hybrid chromatofocusing methods for protein purification
December 6, 2013
Date: Sunday, Dec. 8th, 2013
Time: 10:00 am
Location: TRC 206
Light refreshments will be served at 9:45 am
Dissertation title: Novel hybrid chromatofocusing methods for protein purification
The efforts made to-date to alleviate the downstream challenges faced by the biopharmaceutical industry have been mainly focused on developing novel chromatographic column packings with either higher ligand densities to accommodate larger production capacity requirements or novel ligand groups that exhibit more than one interaction mode to increase selectivity. However, despite this earlier work, there are still unexploited interactions associated with the functional groups present on the column packings that, if optimized, may lead to novel chromatographic separation techniques. Thus, the rational behind the studies investigated here is to provide innovative separation methods based on hybrid chromatofocusing techniques and employ these unexploited interactions which may be useful in protein purification process development for the biopharmaceutical industry.
A comprehensive optimization method capable of exploiting the synergetic effects both the pH and ionic strength on ion-exchange column packing has not yet been developed. Consequently, one primary research objective of this study is to establish the usefulness of employing combined pH and ionic strength gradients to obtain elements of “orthogonal” two-dimension chromatography in one ion-exchange column that is suitable for the preparative purification of proteins in both dilute and non-dilute regimes. Another main objective is to take the concepts developed in this study for ion-exchange chromatography and apply them in affinity and mixed-mode chromatography, where the ligands on the column packings may exhibit electrostatic interactions as well as hydrophobic, hydrogen bonding and/or affinity interactions, and where pH gradients play a major role in the protein adsorption/desorption process. Lastly, this work aims to increase the understanding of the technique of chromatofocusing based on the use of modern theoretical and experimental tools, and to use this understanding to develop novel hybrid chromatofocusing methods. For this purpose, the development of a computer-aided optimization methodology was also performed which allows efficient chromatographic system identification and optimized design. In this way, the computer simulation methods described here go well beyond any previous attempts at simulations in this area.
November 13, 2013
Aditi Bhaskar successfully defended her Ph.D. on November 12th, 2013. Her research was performed in the Welty Lab.
Shaunak Uplekar successfully defended his Ph.D. on November 12th, 2013. His dissertation was entitled "Impact of process parameters on product titer and quality attributes during cell culture scale down."
November 7, 2013
Date: Tuesday, Nov. 12th, 2013
Time: 12:00 pm
Location: TRC 206
Light refreshments will be served at 11:45 am
Dissertation title: Impact of process parameters on product titer and quality attributes during cell culture scale down
Quality by Design and Process Analytical Technology regulatory initiatives aim to achieve consistent production of biopharmaceutical products of predefined quality. Extensive process development studies are imperative to establish such a production process. Currently, these studies are primarily being carried out in bench scale systems. However, bench scale bioreactor studies are costly, tedious and time consuming to set up. An in-house developed, novel high-throughput minibioreactor system shows a significant potential to improve and streamline process development studies. However, in order to fully qualify this system as a scale down model, comparability between the two scales needs to be established. Comparability of product titers and product quality aspects such as glycosylation profile, which is considered to be one of the major product quality attributes, would be of greatest relevance.
Here, we investigate cell culture scale down on monoclonal antibody titers and their N-glycan profiles produced by serum free mammalian cell culture in these two systems. Methods for purification of monoclonal antibody using protein-A chromatography followed by ion exchange chromatography and N-glycan analysis using high pH anion exchange chromatography (HPAEC) with pulsed amperometric detection (PAD) were developed. Structural determination of glycans was done using MALDI TOF mass spectrometry. A comparability experiment indicated that DO (dissolved oxygen) and pH profiles, cell growth, glucose and lactate profiles were similar in bench scale bioreactors and minibioreactors. Although the relative areas of major N-glycans obtained by HPAEC were found to be comparable in two systems, antibody titers in bench scale bioreactor were about 50% higher than in minibioreactor. While investigating this, a noticeable difference in the glutamine consumption in two systems was observed. Evidence in the literature related glutamine consumption to pCO2 levels. In order to investigate the role of pCO2, a novel pCO2 sensor patch was modified for use in mammalian cell culture. This sensor revealed a difference between the pCO2 profiles in both systems. CO2 stripping studies were conducted in order to have comparable pCO2 stripping rate. A comparability study conducted at comparable pCO2 stripping rate showed similar pCO2 profiles and a significant improvement in product titers in minibioreactors was achieved. Finally, the effect of dissolved oxygen (DO) in minibioreactors and bench scale bioreactors was investigated. Effects of DO on cell growth, viability, glucose and lactate profiles, product titers and their N-glycan profiles were found to be comparable. This project attempted to understand the changes that occur during scale down in the cell culture environment, that are significant enough to impact critical process outcomes such as product titer and product quality . This understanding proved to be crucial to provide the comparability of these miniaturized systems with the bench scale systems and to establish them as a scaled down model.
Mid-Atlantic Biosolids Association and the Department of Chemical, Biochemical, and Environmental Engineering present:
The Science of Biosolids: Current Research and Implications for Management
Tuesday, November 19th, 2013
University Center Ballroom
8:00 AM - 4:00 PM
For more information and to register, visit "http://www.mabiosolids.org/index.php?page=events-calendar"
November 1, 2013
Alba Torrents, Professor
Environmental Engineering Program
Civil and Environmental Engineering
University of Maryland, College Park
Date: November 11, 2013
Time: 12:00pm - 1:00pm
Location: TRC 206
Title: Re-Use of Wastewater Effluents: Benefits and Concerns
Through the natural water and nutrient cycle, the earth has recycled and reused water and nutrients for millions of years. Currently, 1.6 billion people live in countries and regions with water and food scarcity and, with population growth and climate change, the number is expected to rise to 2.8 billion people by 2025. Traditional urban wastewater systems need to be transformed in a sustainable, closed-loop urban wastewater management based in the conservation of water and nutrients. There is concern that along with organic matter, nutrients and micronutrients, biosolids could be a source of anthropogenic microconstituents. For over 15 years, our group has been developing methodologies to assess the fate of organic micro pollutants introduced in the environment. We know that many of such micro pollutants are endocrine disruptors and they make their way into the environment, yet many questions remain on their fate and potential risks. A combination of “in-pant”; controlled and field scale studies will be presented and discussed.
October 28, 2013
A recent article on the Smithsonian Science website highlights the work of CBEE professor Upal Ghosh, along with Cynthia Gilmour from the Smithsonian Environmental Research Center, and their colleagues. These researchers have found a new low-cost, nonhazardous way to reduce the toxicity of hot spots polluted with mercury by using charcoal to trap it in the soil.
The complete Smithsonian Science article can be found at this link and the study "Activated Carbon Mitigates Mercury and Methylmercury Bioavailability in Contaminated Sediments," published in the journal Environmental Science & Technology, can be found here
October 11, 2013
Christopher Kistler, Associate Principle Scientist for Merck
Date: Monday, October 21
Time: 12:00pm - 1:00pm
Location: TRC 206
Title: Technology Improvements to Accelerate Process Development of Biologics
Christopher Kistler, Krista Alvin, Rachel Bareither, and David Pollard
Biologics New and Enabling Technologies, Merck & Co., Inc., 126 E. Lincoln Ave, Rahway, NJ
Pressures continue to reduce the time from discovery to product launch and minimize the costs of not only manufacturing but also process development. This is particularly difficult for upstream development where large DOE designs in lab scale reactors, provides a significant equipment and resource constraint. The presentation will show how innovation through automation and single-use technology has led to more efficient process development. This includes the creation of multi use tools to handle both cell culture and microbial expression platforms. Improvements will be shown for end to end development focusing on upstream processing followed by purification and analytics. Examples include the use of cell line development automation for the elimination of manual shakeflask stages and increase throughput of clonal evaluation. For more advanced process development a novel small scale single use prototype bioreactor is evaluated. This system is designed for automated multi tank experimentation with robotic sampling, feeding and control. This is integrated with high throughput purification and analytics using a systematic approach of statistical design of experiments in combination with 'omics' technologies. This allows for a rapid end to end process development and builds a fundamental understanding of the impact of process operations to control process consistency and product quality.