Steven Lee

Royal Astronomical Society

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Carter Van Waes

National Institute on Deafness and Other Communication Disorders

Ru Wang

University of Science and Technology of China

Jianhong Chen

Roswell Park Comprehensive Cancer Center

ÖK

Özlem Keskin

Hacettepe University

Ruth Nussinov

Frederick National Laboratory for Cancer Research

Anthony Saleh

National Institute on Deafness and Other Communication Disorders

Attila Gürsoy

Koç University

Emine Guven‐Maiorov

National Cancer Institute

Hui Cheng

Virginia Commonwealth University

Han Si

Hulunbuir University

Cooperative Institutions

Royal Astronomical Society

108

John Wiley & Sons (United Kingdom)

John Wiley & Sons (United States)

RELX Group (Netherlands)

Liechtenstein Institute

Middle East Institute

Institute of Entomology

Harvard University

Walter de Gruyter (Germany)

Claremont McKenna College

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Issue Information

Insect Molecular Biology (2023)

Jennifer A. Brisson Sassan Zhijian Tu Reviews Shahid Karim Jane H. Hill

10.1111/imb.12789

Cite

Citations (0)

Development of a stem cell gene therapy for Sanfilippo syndrome type B

Molecular Genetics and Metabolism (2017)

Don Clarke Valentina Sanguez Shih Kan Steven Lee Michelina Iacovino

Economic shortage

Rural Health

Thematic Analysis

10.1016/j.ymgme.2016.11.068

Cite

Citations (1)

INTEGRATED POLISHING STEPS FOR MONOCLONAL ANTIBODY PURIFICATION

Sanchayita Ghose Mi Sun Jin Jia Liu John L. S. Hickey Steven Lee

This chapter presents an overview of the polishing steps most frequently used in antibody manufacturing and discusses the considerations to be kept in mind while integrating these steps into the overall purification scheme. Some of the chromatography strategies discussed in the chapter, such as anion exchange (AEX) in weak partitioning mode, the use of mixed-mode resins, or the use of membrane chromatography, might help to achieve that vision. Ion-exchange (IEX) chromatography is widely used in the biopharmaceutical industry for the process-scale purification of mAbs, fusion proteins, and other protein therapeutics. Hydrophobic interaction chromatography (HIC) is based on the interaction between hydrophobic ligands (aliphatic or aromatic) and hydrophobic residues on the protein surface. Hydroxyapatite (HA) chromatography is a very selective polishing step in antibody manufacturing and is able to remove HCP, aggregates, and leached Protein A.

Ion chromatography

Biopharmaceutical

Hydrophobic effect

10.1002/9781119126942.ch14

Cite

Citations (1)

Scale‐up analysis for a CHO cell culture process in large‐scale bioreactors

Biotechnology and Bioengineering (2009)

Zizhuo Xing Brian Kenty Zheng Jian Li Steven Lee

Bioprocess scale-up is a fundamental component of process development in the biotechnology industry. When scaling up a mammalian cell culture process, it is important to consider factors such as mixing time, oxygen transfer, and carbon dioxide removal. In this study, cell-free mixing studies were performed in production scale 5,000-L bioreactors to evaluate scale-up issues. Using the current bioreactor configuration, the 5,000-L bioreactor had a lower oxygen transfer coefficient, longer mixing time, and lower carbon dioxide removal rate than that was observed in bench scale 5- and 20-L bioreactors. The oxygen transfer threshold analysis indicates that the current 5,000-L configuration can only support a maximum viable cell density of 7 x 10(6) cells mL(-1). Moreover, experiments using a dual probe technique demonstrated that pH and dissolved oxygen gradients may exist in 5,000-L bioreactors using the current configuration. Empirical equations were developed to predict mixing time, oxygen transfer coefficient, and carbon dioxide removal rate under different mixing-related engineering parameters in the 5,000-L bioreactors. These equations indicate that increasing bottom air sparging rate is more efficient than increasing power input in improving oxygen transfer and carbon dioxide removal. Furthermore, as the liquid volume increases in a production bioreactor operated in fed-batch mode, bulk mixing becomes a challenge. The mixing studies suggest that the engineering parameters related to bulk mixing and carbon dioxide removal in the 5,000-L bioreactors may need optimizing to mitigate the risk of different performance upon process scale-up.

Sparging

Scale-up

10.1002/bit.22287

Cite

Citations (196)

TOC

Journal of Voice (2023)

Jan Miller Harm Svec C Schutte I.-Min A. Chen Achuth Rao

10.1016/s0892-1997(23)00113-3

Cite

Citations (0)

Optimizing Collection of Trace Biological Samples from Vehicle Headrests

Themis Research Journal of Justice Studies and Forensic Science (2017)

Kevin Tang Jesse Ramirez John Bond Jocelyn R. Weart Yvette DeLaTorre

Tape-lifting and swabbing are two methods commonly used for collecting biological samples in the United Kingdom and United States to investigate vehicle crimes. Determining the optimal collection method may lead to an increase in generating DNA profiles and crime-solving. The objective of this study is to evaluate the efficiency of adhesive tape and the double-swab collection methods for investigating vehicle crimes with possible touch DNA samples. Two experiments were conducted to evaluate the use of tape-lifts and swabs on spiked common vehicle fabric materials. The efficiency of recovery between the two collection methods was performed using qPCR. The results from the collection of fabric materials indicated tape-lifts outperformed swabbing on cloth and vinyl substrates, while swabbing resulted in comparable recovery on leather substrates. By optimizing sample collection techniques, we aim to aid not only investigations involving vehicles but also other crimes with touch DNA evidence present.

Sample (material)

10.31979/themis.2017.0507

Cite

Citations (1)

Demonstration of Robust Host Cell Protein Clearance in Biopharmaceutical Downstream Processes

Biotechnology Progress (2008)

Abhinav A. Shukla Canping Jiang Junfen Ma Michael Rubacha Lisa Flansburg

Residual host cell protein impurities (HCPs) are a key component of biopharmaceutical process related impurities. These impurities need to be effectively cleared through chromatographic steps in the downstream purification process to produce safe and efficacious protein biopharmaceuticals. A variety of strategies to demonstrate robust host cell protein clearance using scale-down studies are highlighted and compared. A common strategy is the "spiking" approach, which is widely employed in clearance studies for well-defined impurities. For HCPs this approach involves spiking cell culture harvest, which is rich in host cell proteins, into the load material for all chromatographic steps to assess their clearance ability. However, for studying HCP clearance, this approach suffers from the significant disadvantage that the vast majority of host cell protein impurities in a cell culture harvest sample are not relevant for a chromatographic step that is downstream of the capture step in the process. Two alternative strategies are presented here to study HCP clearance such that relevance of those species for a given chromatographic step is taken into consideration. These include a "bypass" strategy, which assumes that some of the load material for a chromatographic step bypasses that step and makes it into the load for the subsequent step. The second is a "worst-case" strategy, which utilizes information obtained from process characterization studies. This involves operating steps at a combination of their operating parameters within operating ranges that yield the poorest clearance of HCPs over that step. The eluate from the worst case run is carried forward to the next chromatographic step to assess its ability to clear HCPs. Both the bypass and worst-case approaches offer significant advantages over the spiking approach with respect to process relevance of the HCP impurity species being studied. A combination of these small-scale validation approaches with large-scale HCP clearance data from clinical manufacturing and manufacturing consistency runs is used to demonstrate robust HCP clearance for the downstream purification process of an Fc fusion protein. The demonstration of robust HCP clearance through this comprehensive strategy can potentially be used to eliminate the need for routine analytical testing or for establishing acceptance criteria for these impurities as well as to demonstrate robust operation of the entire downstream purification process.

Downstream processing

Clearance

Biopharmaceutical

Process development

10.1021/bp070396j

Cite

Citations (77)

Identifying Inhibitory Threshold Values of Repressing Metabolites in CHO Cell Culture Using Multivariate Analysis Methods

Biotechnology Progress (2008)

Zizhuo Xing Zheng Jian Li Vincent Chow Steven Lee

Elevation of lactate, ammonia, osmolality, and carbon dioxide to inhibitory levels was reported to have adverse effects on cell growth and protein productivity in mammalian cell culture. Multivariate analysis methods were used to investigate the roles of these repressing metabolites in a fed-batch CHO cell culture for antibody fusion protein B1 (B1) production. Principal Factor Analysis methodology was applied to manufacturing-scale data of 112 cell culture runs, which identified threshold values of four repressing metabolites as follows: (1) ammonium levels above 5.1 mM inhibit cell growth; (2) both lactate and osmolality levels above 58 mM and 382 mOsm/kg affect cell viability; and (3) carbon dioxide levels at or above 111 mmHg reduce protein quality. These threshold values were then verified by simulations using Monod-type equations and Canonical Correlation. These results suggest that adverse effects on cell growth, productivity, and product quality may be minimized under the ideal cell culture condition, in which the peak values of all four repressing metabolites are maintained below the threshold values. This strategy was evaluated in 45 cell culture runs in 50-L bioreactors. Eight out of 45 runs were operated under the ideal condition, while the remaining 37 runs had at least one repressing metabolite with peak value at or above the threshold. In comparison to the remaining runs, the eight cell culture runs under the ideal condition had 17%, 40%, and 11% higher values in peak viable cell density, final B1 titer, and quality attribute, respectively. The unique methodology used in this study may be generally applicable in characterizing cell culture processes.

10.1021/bp070466m

Cite

Citations (50)

Towards high-throughput autonomous infrared spectromicroscopy

Acta Crystallographica Section A Foundations and Advances (2021)

Petrus H. Zwart Liang Chen Marcus M. Noack Steven Lee Patricia Valdespino Castillo

10.1107/s0108767321095945

Cite

Citations (0)

AMPLIFICATION AND DIRECT SEQUENCING OF FUNGAL RIBOSOMAL RNA GENES FOR PHYLOGENETICS

Elsevier eBooks (1990)

T. J. White Thomas D. Bruns Steven Lee John W. Taylor

10.1016/b978-0-12-372180-8.50042-1

Cite

Citations (31,945)