Article
Chemistry, Medicinal
Thomas B. Fanthom, Christopher Wilson, David Gruber, Daniel G. Bracewell
Summary: Peristaltic pumping during bioprocessing can cause therapeutic protein loss and aggregation, and the root cause of protein loss is the mechanism of solid-solid contact.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Chemistry, Physical
Inseok Chae, Andy Han, Jagan Sundaram, Seung-Wuk Lee
Summary: This study investigates the molecular interactions of therapeutic proteins at a liquid-glass interface and finds that reducing electrostatic attractions in the solution can significantly reduce the aggregation and adsorption of the proteins. The study also shows that PEGylation enhances the stability of the therapeutic proteins at the interface.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Javad Eshraghi, Zhongwang Dou, Jean-Christophe Veilleux, Galen Shi, David Collins, Arezoo M. Ardekani, Pavlos P. Vlachos
Summary: Understanding the interface motion and hydrodynamic shear induced by liquid sloshing during the insertion stage of an autoinjector is important for improving drug product administration. The experiments showed that reducing the air gap volume and syringe acceleration/deceleration can decrease the interface area and effective shear.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Chemistry, Multidisciplinary
Peichao Zou, Chunyang Wang, Yubin He, Huolin L. Xin
Summary: This study presents a universal solid electrolyte design that allows for a wide range of ceramic LICs to be used in solid-state lithium batteries. The design eliminates the need for electronic insulation or chemical stability in ceramic LICs.
ENERGY & ENVIRONMENTAL SCIENCE
(2023)
Article
Chemistry, Physical
Artashes A. Khachatrian, Timur A. Mukhametzyanov, Ramazan Z. Salikhov, Marat Safin, Dmitry G. Yakhvarov, Zufar N. Gafurov, Bulat F. Garifullin, Ilnaz T. Rakipov, Diana A. Mironova, Boris N. Solomonov
Summary: This work investigates the impact of imidazolium- and cholinium-based ionic liquids (ILs) on the thermal stability, binding, and aggregation of bovine serum albumin (BSA). The study evaluates various ILs including choline chloride [Ch][Cl], choline dihydrogenphosphate [Ch][DHP], and others. The presence of ILs enhances the thermal stability of BSA except for [OMIM][BF4]. Molecular docking is used to identify the probable binding modes of ILs with BSA. The findings suggest that ILs with short alkyl chain length promote the aggregation and thermal stability of BSA.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Chemistry, Medicinal
Kohei Soeda, Masakazu Fukuda, Masaya Takahashi, Hirotaka Imai, Kengo Arai, Satoshi Saitoh, Ravuri S. K. Kishore, Nuria Sancho Oltra, Jeremy Duboeuf, Daisuke Hashimoto, Yuji Yamanaka
Summary: This study demonstrates the importance of hydrophobicity of Poloxamer 188 (PX188) in controlling visible particle (VP) formation in biotherapeutic formulations. The variability in hydrophobicity among different PX188 lots can affect surfactant function and VP formation. Monitoring lot-to-lot variability of PX188 is crucial for improving and controlling its material attributes in liquid biotherapeutic formulations.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Medicinal
Takaki Nakajima, Kazuya Nagano, Yuka Fukuda, Yu Ishima, Hiroko Shibata, Ryo Isaka, Tian-qi Zhang, Yuya Haga, Kazuma Higashisaka, Hirofumi Tsujino, Tatsuhiro Ishida, Akiko Ishii-Watabe, Yasuo Tsutsumi
Summary: Bioconjugation with polyethylene glycol (PEG) is important for protein drug development, but proteins including PEGylated ones are prone to aggregation or subvisible particle formation under dropping stress. In this study, different lengths and numbers of PEG-OVA molecules were prepared and analyzed under dropping stress, revealing that 20 kDa PEG-OVA formed approximately three times the aggregated particle concentration compared to regular OVA solution, leading to the production of anti-PEG antibodies and clearance of PEG-OVA.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Biophysics
Karim Chouchane, Thibaut Frachon, Laurent Marichal, Laurent Nault, Charlotte Vendrely, Antoine Maze, Franz Bruckert, Marianne Weidenhaupt
Summary: This study analyzes the effects of agitation on insulin aggregation and investigates the contribution of different agitation-induced effects on the rate of aggregation. The results show that strong agitation is necessary for the onset of insulin aggregation, and the presence of dynamic triple interfaces affects the rate of aggregation.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Engineering, Environmental
Yang Li, Selim Halacoglu, Varun Shreyas, William Arnold, Xiaolin Guo, Qianqian Dou, Jacek B. Jasinski, Badri Narayanan, Hui Wang
Summary: This study demonstrates the use of an ionic liquid interlayer to address interfacial issues in sulfide-based solid-state sodium batteries (SSSBs). The interlayer stabilizes the Na metal/SSE interface, enabling the formation of a stable solid electrolyte interphase (SEI) and preventing harmful reactions and Na dendrite growth. Experimental and simulation results reveal that the stable SEI is composed of reduced products of TFSI-. Symmetric cells and FeS2||Na quasi-solid-state batteries exhibit stable cycling performance and high specific capacity.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Guangfei Duan, Yanqin Li, Meimei Ye, Hexin Liu, Ning Wang, Shizhong Luo
Summary: Transthyretin (TTR) aggregation and amyloid formation in ATTR diseases involve liquid-liquid phase separation (LLPS) and subsequent liquid-to-solid phase transition. Electrostatic interactions mediate LLPS of TTR, and pathogenic mutations and heparin promote the process of phase transition and aggregate formation. Post-translational modifications of TTR, such as S-cysteinylation and S-sulfonation, affect the stability and aggregation propensity of TTR. These findings provide molecular insights into the mechanism of TTR aggregation and suggest potential therapeutic targets for ATTR diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Cheng Zhang, Nuria Codina, Jiazhi Tang, Haoran Yu, Nesrine Chakroun, Frank Kozielski, Paul A. Dalby
Summary: The research findings highlighted the different destabilizing pathways of protein structure under low pH and high temperature stress conditions, revealing the potential for stabilizing mutations in the CL domain and C-L-C(H)1 interface. The analysis also identified key salt bridge losses as a cause of conformational changes under different stresses, with implications for future engineering efforts to enhance stability.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Chemistry, Physical
M. Mohib Ur Rehman, Gyoko Nagayama
Summary: In this study, it was found that the presence of micro/nanostructured surfaces significantly affects the evaporation rate of droplets, with the wettability and volume of the droplets further influencing this effect. Theoretical and experimental results showed agreement when the scale of the solid-liquid-vapor interface (slv) was negligible. For microstructured surfaces, the scale of the slv interface could reach 253-940 μm, and the evaporation rate at the slv interface accounted for 16-48% of the total evaporation rate. The scale and rate of the slv interface increased with a decrease in the initial contact angle or an increase in the droplet volume. These findings are important for practical engineering and medical applications involving droplet evaporation on micro/nanostructured surfaces.
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
(2023)
Article
Biochemistry & Molecular Biology
Javed Masood Khan, Ajamaluddin Malik, Prerna Sharma, Sadaf Fatima
Summary: In this study, the impact of the negatively charged detergent sodium dodecyl sulfate (SDS) on insulin amyloid fibrillation was investigated. It was found that SDS can accelerate insulin aggregation at pH 2.0, but not at pH 7.4.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Thermodynamics
Rupak Kumar, Arup Kumar Das
Summary: The numerical study focused on the boiling of LN2 on solid and liquid surfaces, discussing flow instabilities, bubble characteristics, and heat flux. The research also investigated the asymmetry in bubble growth and departure time during multi-mode boiling. Additionally, the study compared vapor film thickness and evaporation rate to understand the impact of film collapse during boiling on liquid surfaces.
INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER
(2022)
Article
Chemistry, Medicinal
Caitlin Wood, Vladimir Razinkov, Wei Qi, Eric M. Furst, Christopher J. Roberts
Summary: This study introduces a rapid method to evaluate protein aggregation propensity at air-water interfaces (AWI). Temperature had minimal effect under this technique's rapid interface turnover time scales, while electrostatic protein-protein interactions mediated by pH changes were more influential for particle formation via AWI. Nonionic surfactants substantially reduced particle formation for monoclonal antibodies, but not for a globular protein.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Michael Martinez, Gareth Mannall, Mari Spitali, Edith L. Norrant, Daniel G. Bracewell
Summary: This study established a micro-mixing model for monoclonal antibody precipitation in continuous tubular reactors, finding that increased micro-mixing led to smaller particle sizes and high antibody yields independent of mixing. Precipitates were easily clarified at small scale, but less so at pilot-scale.
JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY
(2022)
Article
Biochemical Research Methods
Alexander Armstrong, Kieran Horry, Tingting Cui, Martyn Hulley, Richard Turner, Suzanne S. Farid, Stephen Goldrick, Daniel G. Bracewell
Summary: This paper critically reviews industrial chromatography control systems, highlighting the limitations of traditional control strategies and introducing promising monitoring and control techniques. Novel control strategies that combine rapid online data capture with enhanced process understanding improve the capabilities of industrial chromatography systems to meet product quality standards.
JOURNAL OF CHROMATOGRAPHY A
(2021)
Article
Medicine, Research & Experimental
Elsa Noaks, Carlotta Peticone, Ekaterini Kotsopoulou, Daniel G. Bracewell
Summary: The removal of monocytes from leukapheresis has been shown to enhance the activation level and transduction efficiency of CAR T cells, leading to improved production consistency and increased CAR expression levels.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Review
Biotechnology & Applied Microbiology
Elizabeth Edwards, Maria Livanos, Anja Krueger, Anne Dell, Stuart M. Haslam, C. Mark Smales, Daniel G. Bracewell
Summary: Glycosylation plays a critical role in the quality and characteristics of therapeutic monoclonal antibodies in biologic manufacturing. Advances have been made in upstream processing, such as mammalian cell line engineering, to improve the predictability of glycosylation. Downstream processing strategies, including the use of novel technologies, are also being explored to control glycosylation. However, more research is needed to establish holistic and consistent manufacturing processes for antibody therapies.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Biotechnology & Applied Microbiology
Louisa J. Wilson, Will Lewis, Richard Kucia-Tran, Daniel G. Bracewell
Summary: Improvements in upstream processing have increased antibody productivity, but the recovery of harvest material has become more challenging. Integrating upstream and downstream process development can address product purification issues early in the optimization process, reducing the need for costly downstream clearance strategies. Longer cell culture durations were found to negatively impact product quality, with an increase in post-protein A HCPs and a decrease in product monomer percentage.
BIOTECHNOLOGY PROGRESS
(2022)
Article
Biotechnology & Applied Microbiology
Maria Parau, Thomas F. Johnson, James Pullen, Daniel G. Bracewell
Summary: Titer improvement in mAb manufacture has led to increased cell densities and associated process-related impurities. New depth filter materials offer the potential to remove these impurities at an early stage, but understanding their mechanism of impurity removal is essential.
BIOTECHNOLOGY PROGRESS
(2022)
Article
Biotechnology & Applied Microbiology
Amber R. Peswani, Jaraspim Narkpuk, Anja Krueger, Daniel G. Bracewell, Porntippa Lekcharoensuk, Stuart M. Haslam, Anne Dell, Peera Jaru-Ampornpan, Colin Robinson
Summary: This study presents a new production workflow for an updated and cost-effective PCV2d vaccine candidate, showing high yields of purified PCV2d-based antigen from E. coli fermentation systems and a chimeric PCV2d-PCV3 capsid construct. The recombinant protein effectively induced capsid-specific and PCV2d-neutralizing antibodies in immunized animals, suggesting significant potential as a new vaccine candidate that can be easily manufactured at commercial scale.
FOOD AND BIOPRODUCTS PROCESSING
(2022)
Article
Biochemical Research Methods
Braulio Carrillo Sanchez, Matthew Hinchliffe, Daniel G. Bracewell
Summary: Extracellular vesicles (EVs) are considered as nano-scale molecular messengers due to their ability to deliver bioactive cargos. This study presents the use of GFP-tagged EVs for rapid quantification and monitoring of EVs production, highlighting the utility of this approach for accelerated process development.
BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemical Research Methods
Benjamin Barnes, Thomas Caws, Samantha Thomas, Alex P. Shephard, Randolph Corteling, Paul Hole, Daniel G. Bracewell
Summary: The purification of extracellular vesicles (EVs) is a major challenge in fundamental research and commercial applications. The study investigates the potential of heparin affinity chromatography (HAC) in purifying neural stem cell-derived EVs. HAC demonstrates high efficiency in removing residual protein and DNA, and it can also separate EVs into different subgroups.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Chemistry, Medicinal
John M. Hickey, Shaleem I. Jacob, Andrew S. Tait, Fatemeh Dastjerdi Vahid, Joseph Barritt, Sarah Rouse, Alexander Douglas, Sangeeta B. Joshi, David B. Volkin, Daniel G. Bracewell
Summary: Adenovirus vectors have become important vaccines, and electron microscopy and mass spectrometry can be used to analyze virus morphology and proteins, which helps to understand the product heterogeneity and purity, and contributes to the monitoring of viral vaccine quality during the process.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Maria Parau, James Pullen, Daniel G. Bracewell
Summary: Upstream advances in biotechnology have resulted in higher monoclonal antibody (mAb) titers and cell densities in fed-batch cell cultures, but this has also led to increased process-related impurities such as DNA and Host Cell Protein (HCP). Depth filtration is commonly used for harvesting CHO cell cultures, but there is a need to understand its effectiveness in removing impurities. This study investigates the effect of depth filter material and loading on the Protein A resin lifetime and reveals the impact of loading on DNA breakthrough and foulant formation.
BIOTECHNOLOGY PROGRESS
(2023)
Article
Biochemical Research Methods
Sushobhan Bandyopadhyay, Vasos Pavlika, Daniel G. Bracewell, Darren N. Nesbeth
Summary: We constructed a three-input biological logic gate, S OR (G XNOR M), to optimize co-expression of two transgenes in Komagataella phaffii using batch-mode carbon source switching. This logic gate functionality enabled use of CSS to accumulate approximately 80% of total virus-like particle (VLP) yield before cells were burdened with lipase expression in 250 mL DasGip bioreactor cultivation.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Biochemical Research Methods
Thomas F. Johnson, Mariachiara Conti, Francesco Iacoviello, Paul R. Shearing, James Pullen, Simone Dimartino, Daniel G. Bracewell
Summary: This study applied X-ray computed tomography to image and characterize 3D-printed gyroids for bioseparation. It visualized structures from the overall geometry down to individual nanopores and achieved digital representations across multiple length scales for geometric analysis and flow simulation. Comparisons between the imaged samples and the original designs were made to analyze printing fidelity, and parameters such as porosity, tortuosity factor, and pore size were measured.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
George Pamenter, Lee Davies, Carol Knevelman, James Miskin, Kyriacos Mitrophanous, Duygu Dikicioglu, Daniel G. Bracewell
Summary: The use of Lentiviral vectors (LVs) in clinical Cell and Gene Therapy applications is increasing, but there is a significant challenge of product loss during capture chromatography. A study demonstrates that the recovery of HIV-1-LV on quaternary-amine membrane adsorbents is dependent on the time in the adsorbed state. Kinetic data shows a rapid drop in functional recovery due to increased irreversible binding, and gradient elution reveals two distinct binding subpopulations.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Chemistry, Medicinal
Thomas B. Fanthom, Christopher Wilson, David Gruber, Daniel G. Bracewell
Summary: Peristaltic pumping during bioprocessing can cause therapeutic protein loss and aggregation, and the root cause of protein loss is the mechanism of solid-solid contact.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
