156 results found
Mitchell HM, Jovannus D, Rosbottom I, et al., 2023, Process modelling of protein crystallisation: A case study of lysozyme, Chemical Engineering Research and Design, Vol: 192, Pages: 268-279, ISSN: 0263-8762
With the rise in interest of protein crystallisation as a purification step in downstream processing, there is significant interest in the process modelling of these crystallisation steps. Herein, we demonstrate and compare the applicability of “traditional” nucleation and growth models, commonly used to model small molecule crystallisation, for the successful population balance modelling of lysozyme crystallisation at the 100 mL and 1 L scales. Results show that both empirical power-law and first-principles models for nucleation and growth provide good fits to experimental data. Results from parameter estimation highlight a high degree of model sensitivity to initial guesses and stress the importance of providing particle size estimates in order to extract sensible data from the models. Estimates obtained for the 100 mL scale provided suitable initial guesses for the 1 L scale, despite significant differences in the final values obtained at each scale. For future work, further investigation into model validation upon scale-up is recommended. The work performed demonstrates the effectiveness of population balance modelling in the prediction of protein crystallisation behaviour, regardless of the underlying physical phenomena.
Guo M, Jones MJ, Goh R, et al., 2023, The Effect of Chain Length and Conformation on the Nucleation of Glycine Homopeptides during the Crystallization Process., Cryst Growth Des, Vol: 23, Pages: 1668-1675, ISSN: 1528-7483
To explore the effect of chain length and conformation on the nucleation of peptides, the primary nucleation induction time of glycine homopeptides in pure water at different supersaturation levels under various temperatures has been determined. Nucleation data suggest that longer chains will prolong the induction time, especially for chains longer than three, where nucleation will occur over several days. In contrast, the nucleation rate increased with an increase in the supersaturation for all homopeptides. Induction time and nucleation difficulty increase at lower temperatures. However, for triglycine, the dihydrate form was produced with an unfolded peptide conformation (pPII) at low temperature. The interfacial energy and activation Gibbs energy of this dihydrate form are both lower than those at high temperature, while the induction time is longer, indicating the classical nucleation theory is not suitable to explain the nucleation phenomenon of triglycine dihydrate. Moreover, gelation and liquid-liquid separation of longer chain glycine homopeptides were observed, which was normally classified to nonclassical nucleation theory. This work provides insight into how the nucleation process evolves with increasing chain length and variable conformation, thereby offering a fundamental understanding of the critical peptide chain length for the classical nucleation theory and complex nucleation process for peptides.
Gosiamemang T, Heng JYY, 2023, Sodium hydroxide catalysed silica sol-gel synthesis: Physicochemical properties of silica nanoparticles and their post-grafting using C8 and C18 alkyl-organosilanes, Powder Technology, Vol: 417, ISSN: 0032-5910
Sodium hydroxide (NaOH) has been shown to result in fast nucleation of highly monodispersed silica nanoparticles (SNPs). However, limited work has been reported on the physicochemical properties of the resulting SNPs and their surface modification. Herein, we demonstrate that NaOH results in poor hydrolysis of silica precursor, SNPs with adsorbed sodium ions and thermally unstable siloxane cross-linkage. The sodium ions are removed by refluxing SNPs in a 4 vol% hydrochloric acid solution. This step was also found to significantly improve the thermal stability of SNPs. The surface chemistry of the SNPs was easily modified with 0.74 mmol/g of octyltrimethoxysilane and 0.42 mmol/g of octadecyltrimethoxysilane. Functionalised SNPs exhibited superhydrophobicity (water contact angle ≥150°) and displayed a decrease between 2.46% to 3.03% in moisture sorption at 95% relative humidity. The results reveal that the acid treatment will be crucial in the design of hydroxylated and thermally stable SNPs from NaOH-catalysed synthesis.
Bade I, Verma V, Rosbottom I, et al., 2023, Crystal regeneration - a unique growth phenomenon observed in organic crystals post breakage, MATERIALS HORIZONS, ISSN: 2051-6347
Karde V, Khala MJ, Hare C, et al., 2023, Use of shear sensitive coloured guest component to track powder mixing in adhesive binary mixtures, POWDER TECHNOLOGY, Vol: 414, ISSN: 0032-5910
Bian H, Ai L, Heng JYY, et al., 2023, Effects of chemical potential differences on methane hydrate formation kinetics, Chemical Engineering Journal, Vol: 452, Pages: 1-11, ISSN: 1385-8947
To underpin the increasing interest in practical applications of gas hydrates, for gas storage and separation for instance, the formation and growth of hydrates at liquid-gas interfaces are of fundamental importance. Although the thermodynamics of hydrate formation has been widely studied and is well understood, the kinetics of these processes is not well characterised. In this work, a high-pressure, low-temperature stirred reactor was used to conduct hydrate formation kinetic studies in a temperature range from 276.5 to 283.5 K and a pressure range from 5 to 10.5 MPa, with a special focus on 1) the impact of agitation conditions on the available water-gas interfacial surface area for mass transfer and growth rate during hydrate formation, and 2) the effect of the chemical potential driving force on the formation rate. Five hydrate growth regimes were identified, with varying degrees of gas mass transfer control across the gas-water interface depending on the extent to which hydrate layers built up at this interface, gas needed to move through solid hydrate layers, and the extent to which the gas was entrained within the water phase. The formation rate in the initial linear growth regime, before the onset of solid hydrate gas mass transfer effects, was found to depend in an essentially exponential manner on the chemical potential difference from the equilibrium state. Semi-empirical models related to Arrhenius-type kinetic models were used to correlate the data, the best of which reproduced the formation rates from the chemical potential differences to within ± 5 %. The approach has general applicability to help determine the balance between kinetic and thermodynamic factors in identifying the optimum pressure-temperature conditions for processes for gas storage, gas separation and other hydrate applications.
Morgeneyer M, Feise HJ, Heng J, et al., 2022, Particle technology's contributions to the major challenges of the 21st century A predictive retrospective as a particular birthday present of IChemE, Chemical Engineering Research and Design, Vol: 188, Pages: 447-452, ISSN: 0263-8762
In 2122, IChemE - Institution of Chemical Engineers – will celebrate its bicentenary. This article presents as a retrospective the years 2022–2122 and summarizes the progresses (to be) made in the field of particle technology until 2122, i.e. during the second century in the life of the yet young IChemE. A century earlier, in 2008, the U.S. National Academy of Engineering (NAE) announced the grand challenges for engineering in the 21st century. The list has been compiled by a committee under the chair of William Perry1 and comprises a series of challenges to which particle technology will obviously make a sound contribution, such as … • Make solar energy affordable • Provide energy from fusion • Develop carbon sequestration methods • Provide access to clean water • Engineer better medicines • Engineer the tools for scientific discovery Particles are everywhere, be it due to natural or human activities and their formulation, production, handling and characterization has a major influence on the quality of many aspects of life. We summarized the visions of leading scientists and practitioners in the field of particle technology (and around) in order to discover their opinions summarizing the progresses in this field (to be) made in the 21st century – and the societal impact related to these. We allowed them to dream, to wish, to be forward-looking, to be optimistic2 in the framework of a bicentenary.
Heng JYY, 2022, Emerging stars special issue, CHEMICAL ENGINEERING RESEARCH & DESIGN, Vol: 188, Pages: 861-867, ISSN: 0263-8762
Klitou P, Rosbottom I, Karde V, et al., 2022, Relating Crystal Structure to Surface Properties: A Study on Quercetin Solid Forms, CRYSTAL GROWTH & DESIGN, Vol: 22, Pages: 6103-6113, ISSN: 1528-7483
Errington E, Guo M, Heng JYY, 2022, Synthetic amorphous silica: environmental impacts of current industry and the benefit of biomass-derived silica, GREEN CHEMISTRY, ISSN: 1463-9262
Ouyang J, Xing X, Zhou L, et al., 2022, Cocrystal design of vanillin with amide drugs: Crystal structure determination, solubility enhancement, DFT calculation, Chemical Engineering Research and Design, Vol: 183, Pages: 170-180, ISSN: 0263-8762
Vanillin (VAN) is widely used in medicine, food and optoelectronics, but its low solubility leads to the decrease of bioavailability and increase of application costs. Three APIs-nicotinamide (NIC), isonicotinamide (INM) and isoniazid (INH) were chosen to form cocrystals with VAN, aiming at improving the solubility of VAN and APIs simultaneously. Two cocrystals (VAN-NIC, VAN-INM) were obtained through cocrystallization while VAN reacted with INH to form one novel compound (VAN-INH). The crystal structures were characterized by single-crystal X-ray diffraction (SCXRD), Powder X-ray diffraction (PXRD), Fourier-Transform Infrared Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC). The melting temperatures of VAN-NIC and VAN-INM cocrystals are between this of VAN and APIs. Compared with pure VAN and APIs, the solubility and dissolution rate of VAN-NIC and VAN-INM are significantly increased. The melting temperature of VAN-INH is greater than that of VAN and INH, and the solubility and dissolution rate is not increased significantly. The intermolecular energy between VAN and APIs as well as lattice energies of cocrystals/novel compound were computed to elucidate the formation mechanism and stability. The present investigation opens a new pathway for the development of natural product-drug cocrystals to improve solubility and dissolution rate of natural product.
Gerard CJJ, Briuglia ML, Rajoub N, et al., 2022, Template-Assisted Crystallization Behavior in Stirred Solutions o the Monoclonal Antibody Anti-CD20: Probability Distributions of Induction Times, CRYSTAL GROWTH & DESIGN, Vol: 22, Pages: 3637-3645, ISSN: 1528-7483
Link FJ, Heng JYY, 2022, Unraveling the Impact of pH on the Crystallization of Pharmaceutical Proteins: A Case Study of Human Insulin, CRYSTAL GROWTH & DESIGN, Vol: 22, Pages: 3024-3033, ISSN: 1528-7483
- Author Web Link
- Citations: 1
Bhute V, Sengupta S, Campbell J, et al., 2022, Effectiveness of a large-scale implementation of hybrid labs for experiential learning at Imperial College London, Education for Chemical Engineers, Vol: 39, Pages: 58-66, ISSN: 1749-7728
Experiential learning is an integral component of engineering education. The Chemeng Remote Experience Augmented through TEchnology (CREATE) labs concept was implemented in the academic year 2020–21 in response to COVID19 for first-, second-, and third-year chemical engineering undergraduate students studying at Imperial College London. Using a range of technologies including pan-tilt-zoom cameras and Microsoft HoloLens 2 to provide real-time views of the lab environment from anywhere in the world. Students could control the experiments remotely while graduate teaching assistants (GTAs) operated the equipment based on the students’ instructions. This study is aimed at assessing the effectiveness of this implementation with a focus on student communication and confidence. Students and GTAs were surveyed at the end of labs, and a year-dependent response was observed. The majority of students (>70%) reported experiencing effective communication with team members and GTAs and there was a strong positive correlation between communication and confidence in applying engineering concepts in the labs (χ2 = 79.96; p = 1.69 ×10−10). 5–10% of students from all year groups reported that they disliked the lack of in-person activities. The majority (>90%) of GTAs assisting with experiments stated that they associated their role in the CREATE labs with that of a facilitator. The overall delivery of CREATE labs during academic year 2020–21 was positively received by both students and GTAs with recommendations for in-person activities for first- and second-year students. With minor modifications, CREATE labs has the potential to prepare students for effective remote communication and gain experience in using smart technologies which are key components of Industry 4.0.
Yang P, Rosbottom I, Li Z, et al., 2022, The heterogeneous nucleation of pimelic acid under the effect of a template: experimental research and molecular simulation, CRYSTENGCOMM, Vol: 24, Pages: 2825-2835
Guo M, Chang ZH, Liang E, et al., 2022, The effect of chain length and side chains on the solubility of peptides in water from 278.15 K to 313.15 K: A case study in glycine homopeptides and dipeptides, JOURNAL OF MOLECULAR LIQUIDS, Vol: 352, ISSN: 0167-7322
- Author Web Link
- Citations: 1
Errington E, Guo M, Heng JYY, 2022, Environmental Impacts of Rice Husk-Derived Silica under Uncertainty: Is “Bio” better?, Computer Aided Chemical Engineering, Pages: 1615-1620
Millions of tonnes of rice husk (RH) are produced annually as an agricultural waste. One area of interest for RH valorisation is to use rice husk ash (RHA, a by-product of RH combustion) as a replacement for mineral-derived synthetic amorphous silica (M-SAS). However, little information is available on the environmental benefit of this approach. This study details the first evaluation of the environmental benefits of producing RH-derived synthetic amorphous silica (RH-SAS). This is done by describing the life cycle of RH-SAS in terms of stages for which existing life cycle inventories can be linked and aggregated in a modular way. It is then shown how the physical meaning of linkages between modules are governed by both the characteristics of the RH feedstock and efficiencies of processes across the life cycle. To provide more robust findings, the sensitivity of predictions to model uncertainty are also considered. Finally, a case is provided for the benefit of RH-SAS production within the Asia-Pacific (APAC) SAS market.
Quijano Velasco P, Karde V, Ito Y, et al., 2022, Rational synthesis of polymer coated inorganic nanoparticles-MWCNT hybrids via solvophobic effects, Carbon Trends, Vol: 6
The efficient synthesis of inorganic nanoparticle-carbon nanotube hybrids requires the development of models and synthetic guidelines that can be used to maximise the interactions between both nanomaterials. Herein we report the application of the Hansen surface energy based solubility parameter theory as a model for the selection of solvents that can maximise the interactions between iron oxide nanoparticles and MWCNTs. To achieve this, we synthesized iron oxide nanoparticle-MWCNT hybrid materials in three different solvents and characterized their composition with TGA. The solvent was found to have a significant impact in the final amount of iron oxide composition of the hybrids. The Hansen surface energy based solubility parameters of MWCNTs were characterized via inverse gas chromatography and were used to evaluate the interactions between the MWCNTs and the solvent media. Under this model we expected that large differences between the Hansen surface energy based solubility parameters of solvents and MWCNTs would be correlated with larger incorporation of iron oxide nanoparticles in the hybrids. The amount of iron oxide nanoparticles found in the hybrids were indeed consistent with the predictions of the Hansen surface energy based solubility parameter theory making it a powerful tool for the design of nanoparticle-carbon nanotube hybrids.
Verma V, Mitchell H, Guo M, et al., 2021, Studying the impact of the pre-exponential factor on templated nucleation, FARADAY DISCUSSIONS, Vol: 235, Pages: 199-218, ISSN: 1359-6640
Karde V, Jefferson AE, Hebbink GA, et al., 2021, Investigating sizing induced surface alterations in crystalline powders using surface energy heterogeneity determination, POWDER TECHNOLOGY, Vol: 395, Pages: 645-651, ISSN: 0032-5910
- Author Web Link
- Citations: 2
Li X, Heng JYY, 2021, Protein crystallisation facilitated by silica particles to compensate for the adverse impact from protein impurities, CRYSTENGCOMM, Vol: 23, Pages: 8386-8391
- Author Web Link
- Citations: 2
Ouyang J, Xing X, Chen J, et al., 2021, Effects of solvent, supersaturation ratio and silica template on morphology and polymorph evolution of vanillin during swift cooling crystallization, PARTICUOLOGY, Vol: 65, Pages: 93-104, ISSN: 1674-2001
- Author Web Link
- Citations: 11
Guo M, Rosbottom I, Zhou L, et al., 2021, Triglycine (GGG) adopts a polyproline II (pPII) conformation in its hydrated crystal form: revealing the role of water in peptide crystallization, Journal of Physical Chemistry Letters, Vol: 12, Pages: 8416-8422, ISSN: 1948-7185
Polyproline II (pPII) is a left-handed 31-helix conformation, which has been observed to be the most abundant secondary structure in unfolded peptides and proteins compared to α-helix and β-sheet. Although pPII has been reported as the most stable conformation for several unfolded short chain peptides in aqueous solution, it is rarely observed in their solid state. Here, we show for the first time a glycine homopeptide (gly-gly-gly) adopting the pPII conformation in its crystalline dihydrate structure. The single crystal X-ray structure with molecular dynamic simulation suggests that a network of water and the charged carboxylate group is critical in stabilizing the pPII conformation in solid state, offering an insight into the structures of unfolded regions of proteins and the role of water in peptide crystallization.
Li X, Heng JYY, 2021, The critical role of agitation in moving from preliminary screening results to reproducible batch protein crystallisation, Chemical Engineering Research and Design, Vol: 173, Pages: 81-88, ISSN: 0263-8762
This study investigated the important role of agitation in obtaining consistent and reproducible results when moving from preliminary qualitative screenings for protein crystallisation to quantitative batch crystallisation experiments. Lysozyme-thaumatin binary protein mixture was used as the model protein system in this study. Poor reproducibility between batches were observed for non-agitated crystallisation conditions even if the same sampling timing and frequency applied. With agitation, from 0 to 200 rpm investigated in this study, improved reproducibility of protein crystallisation was observed with increased agitation. Additionally, agitation also had impacts on supersaturation exhaustion rate, yield and crystal size. Moreover, in agitated batch crystallisation, it was found that target protein crystallisation process was decelerated in the presence of protein impurity. In conclusion, we emphasised the essential role of agitation in protein crystallisation experiments else misleading conclusions with inconsistency might be drawn from non-agitated systems.
Chen W, Li X, Guo M, et al., 2021, Biopurification of monoclonal antibody (mAb) through crystallisation, Separation and Purification Technology, Vol: 263, Pages: 1-15, ISSN: 1383-5866
Therapeutics based on monoclonal antibody (mAb) represent the most advanced biopharmaceuticals, being able to treat a wide range of challenging diseases such as cancers and arthritis. As the scale of mAb production steadily increases with the demand for mAb-based therapeutics, the downstream biopurification continues to experience significant bottleneck due to the throughput limited nature of the current purification technology. Over the last decades, significant advances have been made in protein (and especially mAb) crystallisation as an alternative biopurification technology that offers high product stability and purity as well as scalability. This review starts with the discussion of general physicochemical properties of mAb before moving on to the in-depth discussion of the distinct phase behaviour of mAb in comparison with conventional globular proteins such as lysozyme. The final part of this review presents a summary of successful demonstrations of crystallisation scale-ups of mAb and discusses the critical factors (i.e. mixing and temperature control) to be considered.
Link FJ, Heng JYY, 2021, Enhancing the crystallisation of insulin using amino acids as soft-templates to control nucleation, CrystEngComm, Vol: 23, Pages: 3951-3960, ISSN: 1466-8033
Amino acids have been widely used in protein formulations to increase the protein's stability. In this study, amino acids have been introduced as soft-templates to control the nucleation of proteins. L-Arginine, L-glycine or L-leucine with concentrations between 0.01 M and 0.1 M were used in a hanging drop vapor diffusion set-up to investigate their role in the crystallisation of human insulin as a model protein at low supersaturation. All amino acids were in a dissolved state. Here we show that L-arginine and L-leucine clearly enhance the nucleation significantly. On the other hand, L-glycine does not enhance nucleation of human insulin at low supersaturation. We hypothesize that it is the intermolecular interaction between the protein's residues and the amino acid's residues that results in an enhancement in the formation of the initial protein nuclei. To prove that the enhanced nucleation is of a kinetic nature, the solubility of insulin in amino acid rich solution was also investigated. The solubility results show that amino acids increase insulin solubility. From that we derive that the enhancement in nucleation is not due to a change in the thermodynamic equilibrium between the crystalline and bulk-liquid phase. As this approach of using amino acids to enhance nucleation is based on a dissolved state in solution, we introduce here the concept of protein crystallisation by soft-templating.
Bian H, Ai L, Hellgardt K, et al., 2021, Phase behaviour of methane hydrates in confined media, Crystals, Vol: 11, Pages: 1-16, ISSN: 2073-4352
In a study designed to investigate the melting behaviour of natural gas hydrates which are usually formed in porous mineral sediments rather than in bulk, hydrate phase equilibria for binary methane and water mixtures were studied using high-pressure differential scanning calorimetry in mesoporous and macroporous silica particles having controlled pore sizes ranging from 8.5 nm to 195.7 nm. A dynamic oscillating temperature method was used to form methane hydrates reproducibly and then determine their decomposition behaviour—melting points and enthalpies of melting. Significant decreases in dissociation temperature were observed as the pore size decreased (over 6 K for 8.5 nm pores). This behaviour is consistent with the Gibbs–Thomson equation, which was used to determine hydrate–water interfacial energies. The melting data up to 50 MPa indicated a strong, essentially logarithmic, dependence on pressure, which here has been ascribed to the pressure dependence of the interfacial energy in the confined media. An empirical modification of the Gibbs–Thomson equation is proposed to include this effect.
Salehi H, Karde V, Hajmohammadi H, et al., 2021, Understanding flow properties of mannitol powder at a range of temperature and humidity, INTERNATIONAL JOURNAL OF PHARMACEUTICS, Vol: 596, ISSN: 0378-5173
- Author Web Link
- Citations: 7
Ouyang J, Chen J, Rosbottom I, et al., 2021, Supersaturation and solvent dependent nucleation of carbamazepine polymorphs during rapid cooling crystallization, CrystEngComm, Vol: 23, Pages: 813-823, ISSN: 1466-8033
Polymorphic nucleation behavior of carbamazepine (CBZ) was investigated in terms of supersaturation in several solvents: nitromethane, acetonitrile, acetone, ethanol, 2-propanol and toluene. The solubility was measured and the effects of interaction between the solvent and CBZ on solubility and polymorphic nucleation were discussed. It was found that the polymorphic forms of CBZ largely depended on the solvent type and supersaturation ratio. The carbonyl group in acetone blocked the NH⋯O interaction between the dimer in form II by mimicking the same interaction with CBZ, then favored the nucleation of form III. The aromatic–aromatic interaction between CBZ and the solvent like toluene decreased the solute–solute interaction and favored the formation of form II. The nucleation domains of CBZ polymorphs (forms II and III) were separated as a function of supersaturation ratio range in each solvent, and the effects of solvents and supersaturation ratios on the induction time and transformation process were also explored. The interfacial energies of forms II and III in different solvents were calculated, and it was found that, at all investigated supersaturation ratios, the interfacial energy of form II in all solvents except acetone was always lower than that of form III, indicating that nucleation kinetics preferably favored the formation of form II. However, at lower supersaturation ratios, thermodynamics was critical and form III was obtained.
Ouyang J, Chen J, Chen W, et al., 2021, Application of phenyl-functionalized porous silica for the selective crystallization of carbamazepine metastable form II, Industrial and Engineering Chemistry Research, Vol: 60, Pages: 939-946, ISSN: 0888-5885
Polymorphic nucleation of carbamazepine (CBZ) in several solvents (ethanol, 2-propanol, acetone, acetonitrile, toluene, and nitromethane) was investigated with different functionalized porous silica templates. It was found that the introduction of silica templates with different surface chemistries such as −OH, −NH2, and −phenyl affected the polymorphic outcomes. At a low supersaturation ratio, stable form III of CBZ was prone to nucleate as expected. However, the results in this work confirmed that a phenyl-functionalized porous silica template could crystallize and maintain metastable form II of CBZ at a low supersaturation ratio for a long time. In terms of the underlying mechanism, the aromatic–aromatic interaction between the surface of phenyl-functionalized silica and the CBZ molecule played an important role in stabilizing metastable form II. The influence of the amount of silica templates on the polymorph formation was also investigated. Our results will help to crystallize and maintain metastable materials, even at a low supersaturation ratio.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.