Open Access Publications

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Open access publications by faculty, postdocs, and graduate students in the Department of Chemical and Biomolecular Engineering

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A color prediction model for mending materials of the Yuquan Iron Pagoda in China based on machine learning
(Heritage Science, 2024-06-06) Liu, Xuegang; Liu, Yuhang; Wang, Ke; Zhang, Yang; Lei, Yang; An, Hai; Wang, Mingqiang; Chen, Yuqiu
During the restoration of iron cultural relics, the removal of rust from these artifacts is necessary. However, this rust removal process may lead to inconsistent local color on the iron relics. To address this, mending materials are applied to treat the surface, ensuring consistent local color. In the surface treatment of iron cultural relics, a significant challenge lies in modulating the color of these mending materials. The corrosion products of Yuquan Iron Pagoda are mainly Fe3O4, γ-FeO(OH), α-FeO(OH) and α-Fe2O3, with contents of 13.1, 16.1, 40.2 and 30.6%, respectively. Due to their structural stability and suitable color characteristics, Fe3O4 and α-Fe2O3 are selected as the primary raw materials for the repair material. This study employs machine learning methods to predict the color of mending materials corresponding to varying contents of α-Fe2O3, Fe3O4, and epoxy resin. The Artificial Neural Network (ANN), eXtreme Gradient Boosting (XGBoost), and Light Gradient Boost Machine (LightGBM) algorithms are utilized to develop the model, and the predictive performance of these three algorithms is compared. XGBoost exhibits the best prediction performance, achieving a square correlation coefficient (R2) of 0.94238 and a mean absolute error (MAE) of 0.68485. Additionally, the SHapley Additive exPlanations (SHAP) method is employed to analyze the most crucial raw material affecting the color of mending materials, which is identified as Fe3O4. The study illustrates the specific process of employing this model by applying it to the surface treatment of the Yuquan Iron Pagoda, demonstrating the practicality of the model. This model can be applied to assist in the surface treatment of other iron cultural relics.
Effect of Dynamic and Preferential Decoration of Pt Catalyst Surfaces by WOx on Hydrodeoxygenation Reactions
(Journal of the American Chemical Society, 2024-05-22) Marlowe, Justin; Deshpande, Siddharth; Vlachos, Dionisios G.; Abu-Omar, Mahdi M.; Christopher, Phillip
Catalysts containing Pt nanoparticles and reducible transition-metal oxides (WOx, NbOx, TiOx) exhibit remarkable selectivity to aromatic products in hydrodeoxygenation (HDO) reactions for biomass valorization, contrasting the undesired aromatic hydrogenation typically observed for metal catalysts. However, the active site(s) responsible for the high selectivity remains elusive. Here, theoretical and experimental analyses are combined to explain the observed HDO reactivity by interrogating the organization of reduced WOx domains on Pt surfaces at sub-monolayer coverage. The SurfGraph algorithm is used to develop model structures that capture the configurational space (∼1000 configurations) for density functional theory (DFT) calculations of a W3O7 trimer on stepped Pt surfaces. Machine-learning models trained on the DFT calculations identify the preferential occupation of well-coordinated Pt sites (≥8 Pt coordination number) by WOx and structural features governing WOx–Pt stability. WOx/Pt/SiO2 catalysts are synthesized with varying W loadings to test the theoretical predictions and relate them to HDO reactivity. Spectroscopy- and microscopy-based catalyst characterizations identify the dynamic and preferential decoration of well-coordinated sites on Pt nanoparticles by reduced WOx species, consistent with theoretical predictions. The catalytic consequences of this preferential decoration on the HDO of a lignin model compound, dihydroeugenol, are clarified. The effect of WOx decoration on Pt nanoparticles for HDO involves WOx inhibition of aromatic ring hydrogenation by preferentially blocking well-coordinated Pt sites. The identification of preferential decoration on specific sites of late-transition-metal surfaces by reducible metal oxides provides a new perspective for understanding and controlling metal–support interactions in heterogeneous catalysis.
Biphasic Plasma Microreactor for Oxyfunctionalization of Liquid Hydrocarbons
(Industrial & Engineering Chemistry Research, 2024-05-22) Nguyen, Darien K.; Cameli, Fabio; Dimitrakellis, Panagiotis; Vlachos, Dionisios G.
Oxyfunctionalization of linear alkanes is important but challenging to achieve. Herein, we demonstrate a biphasic gas–liquid modular plasma microreactor utilizing Ar/O2 gas to selectively oxidize liquid n-dodecane (C12) in an electrified, catalyst-free fashion. C12 secondary alcohols and ketones are the major products, with selectivities of 45–60% and a maximum yield of 23%. Fine-tuning gas and liquid flow rates enhance the plasma–liquid interfacial area, leading to a conversion of >50%. Difunctional and oligomerized oxygenates, alongside lighter hydrocarbons stemming from carbon–carbon cleavage, form at higher conversions. The energy efficiency (0.189 μmol/J) of the modular microreactor is the highest reported among plasma systems. Alkane conversion can be further improved by increasing the length of the plasma region while maintaining excellent energy efficiencies. Similarly, sequential processing/recirculation can enhance the extent of the reaction. This system is also amenable to treating mixtures of liquid n-alkanes, where smaller hydrocarbons are oxidized preferentially to a certain extent. The vapor pressure and liquid temperature are the key parameters. The chemistry occurs primarily in the gas phase for the lighter hydrocarbons and switches to interfacial reactions for the larger ones.
CKineticsDB─An Extensible and FAIR Data Management Framework and Datahub for Multiscale Modeling in Heterogeneous Catalysis
(Journal of Chemical Information and Modeling, 2023-07-24) Lambor, Siddhant M.; Kasiraju, Sashank; Vlachos, Dionisios G.
A great advantage of computational research is its reproducibility and reusability. However, an enormous amount of computational research data in heterogeneous catalysis is barricaded due to logistical limitations. Sufficient provenance and characterization of data and computational environment, with uniform organization and easy accessibility, can allow the development of software tools for integration across the multiscale modeling workflow. Here, we develop the Chemical Kinetics Database, CKineticsDB, a state-of-the-art datahub for multiscale modeling, designed to be compliant with the FAIR guiding principles for scientific data management. CKineticsDB utilizes a MongoDB back-end for extensibility and adaptation to varying data formats, with a referencing-based data model to reduce redundancy in storage. We have developed a Python software program for data processing operations and with built-in features to extract data for common applications. CKineticsDB evaluates the incoming data for quality and uniformity, retains curated information from simulations, enables accurate regeneration of publication results, optimizes storage, and allows the selective retrieval of files based on domain-relevant catalyst and simulation parameters. CKineticsDB provides data from multiple scales of theory (ab initio calculations, thermochemistry, and microkinetic models) to accelerate the development of new reaction pathways, kinetic analysis of reaction mechanisms, and catalysis discovery, along with several data-driven applications. Abstract Graphic available at: https://doi.org/10.1021/acs.jcim.3c00123
Vaccine process technology—A decade of progress
(Biotechnology and Bioengineering, 2024-05-06) Buckland, Barry; Sanyal, Gautam; Ranheim, Todd; Pollard, David; Searles, Jim A.; Behrens, Sue; Pluschkell, Stefanie; Josefsberg, Jessica; Roberts, Christopher J.
In the past decade, new approaches to the discovery and development of vaccines have transformed the field. Advances during the COVID-19 pandemic allowed the production of billions of vaccine doses per year using novel platforms such as messenger RNA and viral vectors. Improvements in the analytical toolbox, equipment, and bioprocess technology have made it possible to achieve both unprecedented speed in vaccine development and scale of vaccine manufacturing. Macromolecular structure-function characterization technologies, combined with improved modeling and data analysis, enable quantitative evaluation of vaccine formulations at single-particle resolution and guided design of vaccine drug substances and drug products. These advances play a major role in precise assessment of critical quality attributes of vaccines delivered by newer platforms. Innovations in label-free and immunoassay technologies aid in the characterization of antigenic sites and the development of robust in vitro potency assays. These methods, along with molecular techniques such as next-generation sequencing, will accelerate characterization and release of vaccines delivered by all platforms. Process analytical technologies for real-time monitoring and optimization of process steps enable the implementation of quality-by-design principles and faster release of vaccine products. In the next decade, the field of vaccine discovery and development will continue to advance, bringing together new technologies, methods, and platforms to improve human health.
Nozzle Innovations That Improve Capacity and Capabilities of Multimaterial Additive Manufacturing
(ACS Engineering Au, 2024-05-13) McCauley, Patrick J.; Bayles, Alexandra V.
Multimaterial additive manufacturing incorporates multiple species within a single 3D-printed object to enhance its material properties and functionality. This technology could play a key role in distributed manufacturing. However, conventional layer-by-layer construction methods must operate at low volumetric throughputs to maintain fine feature resolution. One approach to overcome this challenge and increase production capacity is to structure multimaterial components in the printhead prior to deposition. Here we survey four classes of multimaterial nozzle innovations, nozzle arrays, coextruders, static mixers, and advective assemblers, designed for this purpose. Additionally, each design offers unique capabilities that provide benefits associated with accessible architectures, interfacial adhesion, material properties, and even living-cell viability. Accessing these benefits requires trade-offs, which may be mitigated with future investigation. Leveraging decades of research and development of multiphase extrusion equipment can help us engineer the next generation of 3D-printing nozzles and expand the capabilities and practical reach of multimaterial additive manufacturing.
A Benign Synthesis Route to Terephthalic Acid via Two-Step Electrochemical Oxidation of P-xylene
(Journal of The Electrochemical Society, 2024-05-31) Ding, Haoran; Orazov, Marat; Oliveira, Nicholas; Yan, Yushan
Terephthalic acid is conventionally synthesized through the AMOCO process under harsh conditions, making milder electrosynthesis routes desirable. Electrooxidation of p-xylene has been demonstrated but the degree of oxidation is limited, resulting in low terephthalic acid yields. Here, we demonstrate a process with two electrochemical steps enabling the complete oxidation of p-xylene into terephthalic acid. The first electrochemical step achieves C-H activation of p-xylene using electrochemically generated bromine as a mediator, while the second electrochemical step does alcohol oxidation of 1,4-benzenedimethanol into terephthalate on NiOOH. The divided cell in the first step simultaneously generates acid and base that are utilized subsequently, negating the need of external acid and base addition and thus offering a cost competitive synthesis route. The competing bromide oxidation in the second step is suppressed by using constant voltage electrolysis at 0.50 V, where an optimal yield of terephthalic acid of 81% is achieved.
Lignin-derivable, thermoplastic, non-isocyanate polyurethanes with increased hydrogen-bonding content and toughness vs. petroleum-derived analogues
(Materials Advances, 2024-04-02) Mahajan, Jignesh S.; Hinton, Zachary R.; Nombera Bueno, Eduardo; Epps, Thomas H. III; Korley, LaShanda T. J.
The functionality inherent in lignin-derivable bisguaiacols/bissyringols can improve the processability and performance of the resulting polymers. Herein, non-isocyanate polyurethanes (NIPUs) were synthesized from bisguaiacols/bissyringols with varying degrees of methoxy substitution and differing bridging groups. Notably, the presence of increasing numbers of methoxy groups (0, 2, and 4) in bisphenol F (BPF)-, bisguaiacol F (BGF)-, and bissyringol F (BSF)-NIPUs led to higher percentages of hydrogen-bonded –OH/–NH groups (i.e., ∼65%, ∼85%, ∼95%, respectively). Increased hydrogen bonding between chains improved the elongation-at-break (εbreak) and toughness of lignin-derivable NIPUs over their petroleum counterparts without a reduction in Young's moduli and tensile strengths. For example, BSF-NIPU exhibited the highest εbreak ∼210% and toughness ∼62 MJ m−3, followed by BGF-NIPU (εbreak ∼185% and toughness ∼58 MJ m−3), and then BPF-NIPU (εbreak ∼140% and toughness ∼42 MJ m−3). Similar trends were found in the dimethyl-substituted analogues, particularly for the bisphenol A-NIPU and bisguaiacol A-NIPU. Importantly, the melt rheology of the lignin-derivable NIPUs was comparable to that of the petroleum-derived analogues, with a slightly lower viscosity (i.e., improved melt flow) for the bio-derivable NIPUs. These findings suggested that the added functionalities (methoxy groups) derived from lignin precursors improved thermomechanical stability while also offering increased processability. Altogether, the structure–property-processing relationships described in this work can help facilitate the development of sustainable, performance-advantaged polymers.
Using Bulky Dodecaborane-Based Dopants to Produce Mobile Charge Carriers in Amorphous Semiconducting Polymers
(Chemistry of Materials, 2024-05-17) Wu, Yutong; Salamat, Charlene Z.; Ruiz, Alex León; Simafranca, Alexander F.; Akmanşen-Kalayci, Nesibe; Wu, Eric C.; Doud, Evan; Mehmedović, Zerina; Lindemuth, Jeffrey R.; Phan, Minh D.; Spokoyny, Alexander M.; Schwartz, Benjamin J.; Tolbert, Sarah H.
Conjugated polymers are a versatile class of electronic materials featured in a variety of next-generation electronic devices. The utility of such polymers is contingent in large part on their electrical conductivity, which depends both on the density of charge carriers (polarons) and on the carrier mobility. Carrier mobility, in turn, is largely controlled by the separation between the polarons and dopant counterions, as counterions can produce Coulombic traps. In previous work, we showed that large dopants based on dodecaborane (DDB) clusters were able to reduce Coulombic binding and thus increase carrier mobility in regioregular (RR) poly(3-hexylthiophene-2,5-diyl) (P3HT). Here, we use a DDB-based dopant to study the effects of polaron–counterion separation in chemically doped regiorandom (RRa) P3HT, which is highly amorphous. X-ray scattering shows that the DDB dopants, despite their large size, can partially order the RRa P3HT during doping and produce a doped polymer crystal structure similar to that of DDB-doped RR P3HT; Alternating Field (AC) Hall measurements also confirm a similar hole mobility. We also show that use of the large DDB dopants successfully reduces Coulombic binding of polarons and counterions in amorphous polymer regions, resulting in a 77% doping efficiency in RRa P3HT films. The DDB dopants are able to produce RRa P3HT films with a 4.92 S/cm conductivity, a value that is ∼200× higher than that achieved with 3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ), the traditional dopant molecule. These results show that tailoring dopants to produce mobile carriers in both the amorphous and semicrystalline regions of conjugated polymers is an effective strategy for increasing achievable polymer conductivities, particularly in low-cost polymers with random regiochemistry. The results also emphasize the importance of dopant size and shape for producing Coulombically unbound, mobile polarons capable of electrical conduction in less-ordered materials.
Macrophage variance: investigating how macrophage origin influences responses to soluble and physical cues with immortalized vs. primary cells in 2D and 3D culture
(Frontiers in Biomaterials Science, 2024-05-22) Graf, Jodi; Bomb, Kartik; Trautmann-Rodriguez, Michael; Jarai, Bader M.; Gill, Nicole; Kloxin, April M.; Fromen, Catherine A.
Macrophages are phagocytic innate immune cells capable of phenotypical switching in response to the local microenvironment. Studies often use either primary macrophages or immortalized cell lines for hypothesis testing, therapeutic assessment, and biomaterial evaluation without carefully considering the potential effects of cell source and tissue of origin, which strongly influence macrophage response. Surprisingly, limited information is available about how, under similar stimuli, immortalized cell lines and primary cells respond in both phenotypical and functional changes. To address this need, in this work, we cultured immortalized macrophage cell lines derived from different origins (i.e., blood, lung, peritoneal) to understand and compare macrophage phenotypical responses, including polarization and plasticity, morphological changes, and phagocytic functionalities, as well as compared primary macrophages extracted from peritoneal and bone marrow to their immortalized cell line counterparts. We found significant differences in baseline expression of different markers (e.g., CD86, MHCII, CD206, and EGR2) amongst different cell lines, which further influence both polarization and repolarization of the cells, in addition to their phagocytic functionality. Additionally, we observed that, while RAW 264.7 cells behave similarly to the primary bone marrow-derived macrophages, there are noticeable phenotypical and functional differences in cell line (IC-21) and primary peritoneal macrophages, highlighting tissue-specific differences in macrophage response amongst cell lines and primary cells. Moving to three-dimensional (3D) culture in well-defined biomaterials, blood-derived primary and cell line macrophages were encapsulated within hydrogel-based synthetic extracellular matrices and their polarization profiles and cell morphologies were compared. Macrophages exhibited less pronounced polarization during 3D culture in these compliant, soft materials compared to two-dimensional (2D) culture on rigid, tissue culture plastic plates. Overall, our findings highlight origin-specific differences in macrophage response, and therefore, careful considerations must be made to identify the appropriate cell source for the application of interest.
Advective Assembler-Enhanced Support Bath Rotational Direct Ink Writing
(Advanced Materials Technologies, 2024-05-01) Pleij, Tazio; Bayles, Alexandra V.; Vermant, Jan
Manufacturing intricately controlled, hierarchically distributed structures poses significant fabrication challenges, but is crucial for enhancing functionality in synthetic systems. A 3D printing technique combining advective assembly with rotational direct ink writing is developed and exploited to build topologically complex, multimaterial structures with high precision. A modular advective assembler printhead is fabricated and employed in the process. This flow-structuring device is designed with a complex network of internal channels that patterns flowing hydrogel-based inks, creating multi-layered filaments whose structures go well beyond conventional nozzle shape and size limitations. The composite filaments are extruded into a rotating support bath of Polyacrylic acid microgels. The rheology of the inks and support bath are critical to maintain print fidelity and integrity, and are characterized by linear and nonlinear bulk rheometry. Optimization of the materials creates a platform where curvilinear, multimaterial architectures are constructed without being constrained to slicing across X, Y, and Z axes. The versatility of this manufacturing platform is demonstrated by printing helical structures that undergo swelling-induced actuation. This processing method has the potential to significantly enhance additive manufacturing by enabling the production of intricate, multiscale composite structures with broad applicability in fields such as bioengineering, soft robotics, and functional composite materials.
Ionic liquid binary mixtures: Machine learning-assisted modeling, solvent tailoring, process design, and optimization
(AIChE Journal, 2024-04-15) Chen, Yuqiu; Ma, Sulei; Lei, Yang; Liang, Xiaodong; Liu, Xinyan; Kontogeorgis, Georgios M.; Gani, Rafiqul
This work conducts a comprehensive modeling study on the viscosity, density, heat capacity, and surface tension of ionic liquid (IL)-IL binary mixtures by combining the group contribution (GC) method with three machine learning algorithms: artificial neural network, XGBoost, and LightGBM. A large number of experimental data from reliable open sources is exhaustively collected to train, validate, and test the proposed ML-based GC models. Furthermore, the Shapley Additive Explanations technique is employed to quantify the influential factors behind all the studied properties. Finally, these ML-based GC models are sequentially integrated into computer-aided mixed solvent design, process design, and optimization through an industrial case study of recovering hydrogen from raw coke oven gas. Optimization results demonstrate their high computational efficiency and integrability in solvent and process design, while also highlighting the significant potential of IL-IL binary mixtures in practical applications.
Bioderived silicon nano-quills: synthesis, structure and performance in lithium-ion battery anodes
(Green Chemistry, 2024-03-12) Chen, Nancy; Sabet, Morteza; Sapkota, Nawraj; Parekh, Mihir; Chiluwal, Shailendra; Koehler, Kelliann; Clemons, Craig M.; Ding, Yi; Rao, Apparao M.; Pilla, Srikanth
Cellulose nanocrystals (CNCs) are bioderived one-dimensional species with versatile surface chemistry and unique self-assembling behavior in aqueous solutions. This work presents a scientific approach to leverage these characteristics for creating CNC network templates and processing them to engineer a novel silicon (Si)-based material called silicon nano-quill (SiNQ) for energy storage applications. The SiNQ structure possesses a porous, tubular morphology with a substantial ability to store lithium ions while maintaining its structural integrity. The presence of Si suboxides in the SiNQ structure is demonstrated to be crucial for realizing a stable cycling performance. One of the defining attributes of SiNQ is its water dispersibility due to Si–H surface bonds, promoting water-based Si-graphite electrode manufacturing with environmental and economic benefits. The incorporation of only 17 wt% SiNQ enhances the capacity of graphitic anodes by ∼2.5 times. An initial coulombic efficiency of 97.5% is achieved by employing a versatile pre-lithiation. The SiNQ-graphite anodes with high active loading, when subjected to accelerated charging/discharging conditions at 5.4 mA cm−2, exhibit stable cycling stability up to 500 cycles and average coulombic efficiency of >99%. A generalized physics-based cyclic voltammetry model is presented to explain the remarkable behavior of SiNQs under fast-charging conditions.
Electrophoretic Deposition as a Versatile Low-Cost Tool to Construct a Synthetic Polymeric Solid-Electrolyte Interphase on Silicon Anodes: A Model System Investigation
(ACS Applied Materials and Interfaces, 2024-02-14) Mou, Rownak J.; Barua, Sattajit; Prasad, Ajay K.; Epps, Thomas H. III; Yao, Koffi P. C.
The cycling of next-generation, high-capacity silicon (Si) anodes capable of 3579 mAh·g–1 is greatly hindered by the instability of the solid-electrolyte interphase (SEI). The large volume changes of Si during (de)lithiation cause continuous cracking of the SEI and its reconstruction, leading to loss of lithium inventory and extensive consumption of electrolyte. The SEI formed in situ during cell cycling is mostly composed of molecular fragments and oligomers, the structure of which is difficult to tailor. In contrast, ex situ formation of a synthetic SEI provides greater flexibility to deposit long-chain, polymeric, and elastomeric components potentially capable of maintaining integrity against the large ∼350% volume expansion of Si while also enabling electronic passivation of the surface for longer cycling and calendar life. Furthermore, polymers are amenable to structural modifications, and the desired elasticity can be targeted by selection of the SEI polymer feedstock. Herein, electrophoretic deposition (EPD) is used to apply chitosan as a synthetic SEI on model Si thin film electrodes. Comparison of synthetic SEIs obtained without (Si/Chit) and with CH3COOLi (Si/Chit+CH3COOLi) added during EPD is performed to demonstrate a facile route to tuning of the polymer SEI chemistry. Atomic force and scanning electron microscopy reveal that addition of CH3COOLi at EPD assists in conformal deposition of the synthetic SEI. During electrochemical cycling, the Chit+CH3COOLi coating nearly doubles the capacity retention versus the reference bare Si thin film. X-ray photoelectron and Fourier transform infrared spectroscopy reveal that CH3COOLi caps the −NH2 groups of chitosan through amidation during EPD, which suppresses the catalytic reduction of the electrolyte. The presented approach demonstrates and validates EPD as a low-capital route to achieving and chemistry-tuning synthetic SEIs on Si electrodes. More broadly, the method is a promising avenue toward controlled and tailored polymeric SEIs on various conversion-type electrodes with high particle volumetric expansion.
A novel digital lifecycle for Material-Process-Microstructure-Performance relationships of thermoplastic olefins foams manufactured via supercritical fluid assisted foam injection molding
(Polymer Engineering and Science, 2024-03-15) Pradeep, Sai Aditya; Deshpande, Amit M.; Lavertu, Pierre‐Yves; Zheng, Ting; Yerra, Veera Aditya; Shimabukuro, Yiro; Li, Gang; Pilla, Srikanth
This research significantly enhances the applicability of thermoplastic olefins (TPOs) in the automotive industry using supercritical N2 as a physical foaming agent, effectively addressing the limitations of traditional chemical agents. It merges experimental results with simulations to establish detailed material-process-microstructure-performance (MP2) relationships, targeting 5–20% weight reductions. This innovative approach labeled digital lifecycle (DLC) helps accurately predict tensile, flexural, and impact properties based on the foam microstructure, along with experimentally demonstrating improved paintability. The study combines process simulations with finite element models to develop a comprehensive digital model for accurately predicting mechanical properties. Our findings demonstrate a strong correlation between simulated and experimental data, with about a 5% error across various weight reduction targets, marking significant improvements over existing analytical models. This research highlights the efficacy of physical foaming agents in TPO enhancement and emphasizes the importance of integrating experimental and simulation methods to capture the underlying foaming mechanism to establish material-process-microstructure-performance (MP2) relationships. Highlights - Establishes a material-process-microstructure-performance (MP2) for TPO foams - Sustainably produces TPO foams using supercritical (ScF) N2 with 20% lightweighting - Shows enhanced paintability for TPO foam improved surface aesthetics - Digital lifecycle (DLC) that predicts both foam microstructure and properties - DLC maps process effects & microstructure onto FEA mesh for precise prediction
Modeling scalability of impurity precipitation in downstream biomanufacturing
(Biotechnology Progress, 2024-03-27) Guo, Jing; Traylor, Steven J.; Agoub, Mohamed; Jin, Weixin; Hua, Helen; Diemer, R. Bertrum; Xu, Xuankuo; Ghose, Sanchayita; Li, Zheng Jian; Lenhoff, Abraham M.
Precipitation during the viral inactivation, neutralization and depth filtration step of a monoclonal antibody (mAb) purification process can provide quantifiable and potentially significant impurity reduction. However, robust commercial implementation of this unit operation is limited due to the lack of a representative scale-down model to characterize the removal of impurities. The objective of this work is to compare isoelectric impurity precipitation behavior for a monoclonal antibody product across scales, from benchtop to pilot manufacturing. Scaling parameters such as agitation and vessel geometry were investigated, with the precipitate amount and particle size distribution (PSD) characterized via turbidity and flow imaging microscopy. Qualitative analysis of the data shows that maintaining a consistent energy dissipation rate (EDR) could be used for approximate scaling of vessel geometry and agitator speeds in the absence of more detailed simulation. For a more rigorous approach, however, agitation was simulated via computational fluid dynamics (CFD) and these results were applied alongside a population balance model to simulate the trajectory of the size distribution of precipitate. CFD results were analyzed within a framework of a two-compartment mixing model comprising regions of high- and low-energy agitation, with material exchange between the two. Rate terms accounting for particle formation, growth and breakage within each region were defined, accounting for dependence on turbulence. This bifurcated model was successful in capturing the variability in particle sizes over time across scales. Such an approach enhances the mechanistic understanding of impurity precipitation and provides additional tools for model-assisted prediction for process scaling.
Factors affecting product association as a mechanism of host-cell protein persistence in bioprocessing
(Biotechnology and Bioengineering, 2024-01-19) Oh, Young Hoon; Becker, Matthew L.; Mendola, Kerri M.; Choe, Leila H.; Min, Lie; Lee, Kelvin H.; Yigzaw, Yinges; Seay, Alexander; Bill, Jerome; Li, Xuanwen; Roush, David J.; Cramer, Steven M.; Menegatti, Stefano; Lenhoff, Abraham M.
Product association of host-cell proteins (HCPs) to monoclonal antibodies (mAbs) is widely regarded as a mechanism that can enable HCP persistence through multiple purification steps and even into the final drug substance. Discussion of this mechanism often implies that the existence or extent of persistence is directly related to the strength of binding but actual measurements of the binding affinity of such interactions remain sparse. Two separate avenues of investigation of HCP-mAb binding are reported here. One is the measurement of the affinity of binding of individual, commonly persistent Chinese hamster ovary (CHO) HCPs to each of a set of mAbs, and the other uses quantitative proteomic measurements to assess binding of HCPs in a null CHO harvested cell culture fluid (HCCF) to mAbs produced in the same cell line. The individual HCP measurements show that the binding affinities of individual HCPs to different mAbs can vary appreciably but are rarely very high, with only weak pH dependence. The measurements on the null HCCF allow estimation of individual HCP-mAb affinities; these are typically weaker than those seen in affinity measurements on isolated HCPs. Instead, the extent of binding appears correlated with the initial abundance of individual HCPs in the HCCF and the forms of the HCPs in the solution, i.e., whether HCPs are present as free molecules or as parts of large aggregates. Separate protein A chromatography experiments performed by feeding different fractions of a mAb-containing HCCF obtained by size-exclusion chromatography (SEC) showed clear differences in the number and identity of HCPs found in the protein A eluate. These results indicate a significant role for HCP-mAb association in determining HCP persistence through protein A chromatography, presumably through binding of HCP-mAb complexes to the resin. Overall, the results illustrate the importance of considering more fully the biophysical context of HCP-product association in assessing the factors that may affect the phenomenon and determine its implications. Knowledge of the abundances and the forms of individual or aggregated HCPs in HCCF are particularly significant, emphasizing the integration of upstream and downstream bioprocessing and the importance of understanding the collective properties of HCPs in addition to just the biophysical properties of individual HCPs.
Dissipation in nonequilibrium thermodynamics and its connection to the Rayleighian functional
(Physics of Fluids, 2024-01-04) Beris, Antony N.; Edwards, Brian J.
We examine quantitatively the role of dissipation in nonequilibrium thermodynamics and its connection to variational principles and the Rayleighian functional. The extremum of the Rayleighian is sometimes used to describe the inertialess (dissipation-dominated) dynamics of continuum systems, and it has been applied recently for the modeling of soft matter dynamics. We discuss how dissipation is considered within one of the modern complete descriptions of nonequilibrium thermodynamics, namely the single generator bracket formalism. Within this formalism, dissipation is introduced through the use of the dissipation bracket, describing irreversible dynamics, which is added to a Poisson bracket that describes the reversible dynamics of the system. A possible connection with the Rayleighian functional is then demonstrated that in all cases considered herein, the Rayleighian is equal to minus one half of the effective dissipation rate of the Lagrangian functional. The effective dissipation rate is obtained starting with an inertial (i.e., flux-based or velocity-based) system description, involving the Poisson bracket and the primitive part (i.e., without the entropy correction term) of the dissipative bracket. Several examples are discussed in detail, ranging from an algebraic model (damped oscillator) to continuum ones: modeling of fluid flow in porous particle media, viscous Newtonian compressible and incompressible fluid flows, and more interestingly, flow of a nematic liquid-crystalline material.
Ethylene production: process design, techno-economic and life-cycle assessments
(Green Chemistry, 2024-01-29) Chen, Yuqiu; Kuo, Mi Jen; Lobo, Raul; Ierapetritou, Marianthi
Replacing the steam cracking process with oxidative dehydrogenation for ethylene production offers potential energy and environmental benefits. To evaluate these possibilities, a study combining conceptual process design, techno-economic analysis, and life cycle assessments of the oxidative dehydrogenation of ethane (ODHE) for producing ethylene at an industrial scale is performed. For comparison, the conventional steam cracking process of ethane is also simulated and optimized. The techno-economic analysis results for ODHE with a boron-containing zeolite chabazite (B-CHA) catalyst, as developed in our group, demonstrate that it is economically competitive ($790 per t ethylene production) compared to the steam cracking process ($832 per t ethylene production). However, a “cradle-to-gate” life-cycle assessment shows that the ODHE process emits more greenhouse gases (2.42 kg CO2 equiv. per kg ethylene) compared to the steam cracking counterpart (1.34 kg CO2 equiv. per kg ethylene). The discrepancy between the initial hypothesis and the results arises from the significant refrigerant input required by the ODHE process to recover ethylene from byproducts such as CO, CH4, and unreacted oxygen and ethane. Further scenario analysis reveals that plausible improvements in the C2H6 conversion per pass, the selectivity to ethylene and the ratio of ethane to oxygen in the current ODHE process could render it both economically and environmentally viable as a replacement for the steam cracking process.
Neutron Scattering Analysis of Cryptococcus neoformans Polysaccharide Reveals Solution Rigidity and Repeating Fractal-like Structural Patterns
(Biomacromolecules, 2024-02-12) Wang, Ziwei; Teixeira, Susana C. M.; Strother, Camilla; Bowen, Anthony; Casadevall, Arturo; Cordero, Radamés J. B.
Cryptococcus neoformans is a fungal pathogen that can cause life-threatening brain infections in immunocompromised individuals. Unlike other fungal pathogens, it possesses a protective polysaccharide capsule that is crucial for its virulence. During infections, Cryptococcus cells release copious amounts of extracellular polysaccharides (exo-PS) that interfere with host immune responses. Both exo-PS and capsular-PS play pivotal roles in Cryptococcus infections and serve as essential targets for disease diagnosis and vaccine development strategies. However, understanding their structure is complicated by their polydispersity, complexity, sensitivity to sample isolation and processing, and scarcity of methods capable of isolating and analyzing them while preserving their native structure. In this study, we employ small-angle neutron scattering (SANS) and ultra-small-angle neutron scattering (USANS) for the first time to investigate both fungal cell suspensions and extracellular polysaccharides in solution. Our data suggests that exo-PS in solution exhibits collapsed chain-like behavior and demonstrates mass fractal properties that indicate a relatively condensed pore structure in aqueous environments. This observation is also supported by scanning electron microscopy (SEM). The local structure of the polysaccharide is characterized as a rigid rod, with a length scale corresponding to 3–4 repeating units. This research not only unveils insights into exo-PS and capsular-PS structures but also demonstrates the potential of USANS for studying changes in cell dimensions and the promise of contrast variation in future neutron scattering studies. Graphical abstract available at: https://doi.org/10.1021/acs.biomac.3c00911

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