Publications
169 results found
Gosiamemang T, Heng JYY, 2024, Simple one-pot fabrication of durable superhydrophobic cotton wool using octadecyltrimethoxysilane modified silica-sol for oil-water separation, Separation and Purification Technology, Vol: 336, ISSN: 0950-4214
A fluorine-free superhydrophobic cotton is successfully fabricated using a simple and cost-effective one-pot synthesis method, employing octadecyltrimethoxysilane (ODTMS) as a modifying silane in a silica-sol. Unlike conventional techniques that utilise coupling agents or post-synthesis curing methods to enhance coating stability, this approach eliminates the need for extra chemicals thus saving time and reducing fabrication cost. The prepared cotton demonstrates remarkable superhydrophobicity, as evidenced by a water contact angle of 159°. Additionally, it exhibits exceptional durability and stability when exposed to harsh acidic and alkaline solutions, as well as during laundering test. Moreover, the cotton displays excellent oil–water separation efficiency (>99.0 %) and maintains consistent performance throughout 20 reuse cycles, highlighting its high reusability. Furthermore, the modified cotton is highly effective for separating oil-in-water emulsions, even for highly stable emulsions, achieving separation efficiencies above 90.0 %. The fabrication process is simple and environmentally safe, offering an economical and viable solution for industries handling oily wastewater. Overall, this fluorine-free superhydrophobic cotton presents a promising and cost-effective option for various industrial applications.
Chadha D, Heng J, 2024, A scoping review of professional skills development in engineering education from 1980-2020, Cogent Education, Vol: 14, ISSN: 2331-186X
Engineering students are expected to develop their professional skills throughout the course of their degrees. Yet, there is no clear consensus among educators of which skills are being developed or how this is done effectively. This scoping review has been produced to draw together and disseminate information on effective techniques for developing six specific professional skills (communication, teamwork, problem solving, leadership, project management and entrepreneurship) and tracing the evolution of these skills in engineering education. Using search engines and backwards and forwards snowballing, a scoping literature review on skills development in engineering was conducted, encompassing a 40-year time span (1980–2020). Specified search terms, and inclusion criteria were applied, and findings have been presented quantitatively and qualitatively. In total, 165 studies were included. Key findings indicate skills are more nuanced and accepted today than they were in 1980, with an increased focus on specific skill areas. Additionally, more sophisticated integrated delivery methods are used to teach skills, although short courses remain popular. By synthesising data in this way, professional educators can identify what skill areas to focus on, and how to teach these skills for effective development among students. Gaps in knowledge are also identified through this review. This study is significant in that it has created an exceptionally useful roadmap of skills development, which is of benefit to the engineering community and beyond.
Khala M, Hare C, Karde V, et al., 2023, A regime map for dry powder coating: the influence of material properties and process parameters, Frontiers in Chemical Engineering, Vol: 5, ISSN: 2673-2718
A numerical study is carried out to investigate the combined influence of material properties and process parameters on coating quality in a high shear mixer (specifically an FT4 Powder Rheometer) to construct a regime map. The Discrete Element Method (DEM) is employed to simulate a range of material properties (size, density, and surface energy) and process parameters (impeller speed and mixing time) via Design of Experiments (DoE). A robust regime map is proposed for prediction of dry coating performance based on dimensionless Stokes deformation number (Stdef) and granular Bond number (Bo). The regime map provides insight on the optimal range of material properties and process parameters to achieve high coating levels in a high-shear bladed mixer. Furthermore, the minimum energy required to achieve optimal coating performance as well as regions of poor coating quality due to guest detachment exacerbated by excessive energy input can be identified from the regime map, thus reducing wastage of energy and coating material required. The regime map enables the required mixing time for optimal coating to be determined so long as particle size distributions and surface energies are known.
Rajoub N, Gerard CJJ, Pantuso E, et al., 2023, A workflow for the development of template-assisted membrane crystallization downstream processing for monoclonal antibody purification, Nature Protocols, Vol: 18, Pages: 2998-3049, ISSN: 1750-2799
Monoclonal antibodies (mAbs) are commonly used biologic drugs for the treatment of diseases such as rheumatoid arthritis, multiple sclerosis, COVID-19 and various cancers. They are produced in Chinese hamster ovary cell lines and are purified via a number of complex and expensive chromatography-based steps, operated in batch mode, that rely heavily on protein A resin. The major drawback of conventional procedures is the high cost of the adsorption media and the extensive use of chemicals for the regeneration of the chromatographic columns, with an environmental cost. We have shown that conventional protein A chromatography can be replaced with a single crystallization step and gram-scale production can be achieved in continuous flow using the template-assisted membrane crystallization process. The templates are embedded in a membrane (e.g., porous polyvinylidene fluoride with a layer of polymerized polyvinyl alcohol) and serve as nucleants for crystallization. mAbs are flexible proteins that are difficult to crystallize, so it can be challenging to determine the optimal conditions for crystallization. The objective of this protocol is to establish a systematic and flexible approach for the design of a robust, economic and sustainable mAb purification platform to replace at least the protein A affinity stage in traditional chromatography-based purification platforms. The procedure provides details on how to establish the optimal parameters for separation (crystallization conditions, choice of templates, choice of membrane) and advice on analytical and characterization methods.
Link FJ, Errington E, Verma V, et al., 2023, The role of mixing and surface hydrophobicity on the operation of a continuous tubular slug flow crystalliser for lysozyme, Chemical Engineering Journal, Vol: 471, Pages: 1-13, ISSN: 1385-8947
Continuous crystallisation is currently seen as a more economic and efficient alternative compared to standard techniques for the purification of biopharmaceutical proteins. Despite being promising as continuous crystalliser platforms, tubular slug flow crystallisers pose their challenges due to the tendency of proteins to accumulate at solid surfaces, to form amorphous precipitates at high protein concentrations and to undergo slow diffusive mass transport. This work investigates the effect of equipment surface chemistry and physical mixing on the design and operability of a tubular slug flow crystalliser for lysozyme under laminar flow conditions (Re ∼ 1). Firstly, glass tubes with different surface functional groups, –OH or –CH3, with water contact angles between 9° and 99°, were investigated. CH3 surfaces resulted in a up to 33% delayed onset of nucleation, demonstrating lower heterogeneous nucleation rates, and therefore are better suited to prevent fouling. However, a surface chemistry-independent deposition of lysozyme was found, altering the water contact angle by up to 56°, resulting in an unstable slug flow and a reduction of the onset of nucleation by up to 11.5-fold. To achieve a stable slug flow and controlled nucleation, the surface functional groups were recovered by implementing surface-specific cleaning protocols comprising NaOH or liquid detergent. To overcome poor mixing and amorphous precipitation, a two-step mixing approach, consisting of an intermediate mixing step was developed. This novel mixing approach reduced the mixing time from > 10 min to < 10 s, allowing the achievement of an instantaneous homogeneous solution under laminar flow conditions. Overall, the findings of this study are therefore of crucial relevance to the future design and operation of tubular slug flow crystallisers as purification platforms for biopharmaceutical proteins.
Kaur A, Darvill D, Xiang S, et al., 2023, Development of nanopackaging for storage and transport of loaded lipid nanoparticles, Nano Letters, Vol: 23, Pages: 6760-6767, ISSN: 1530-6984
Easily deploying new vaccines globally to combat disease outbreaks has been highlighted as a major necessity by the World Health Organization. RNA-based vaccines using lipid nanoparticles (LNPs) as a drug delivery system were employed to great effect during the recent COVID-19 pandemic. However, LNPs are still unstable at room temperature and agglomerate over time during storage, rendering them ineffective for intracellular delivery. We demonstrate the suitability of nanohole arrays (nanopackaging) as patterned surfaces to separate and store functionalized LNPs (fLNPs) in individual recesses, which can be expanded to other therapeutics. Encapsulating calcein as a model drug, we show through confocal microscopy the effective loading of fLNPs into our nanopackaging for both wet and dry systems. We prove quantifiably pH-mediated capture and subsequent unloading of over 30% of the fLNPs using QCM-D on alumina surfaces altering the pH from 5.5 to 7, displaying controllable storage at the nanoscale.
Jia L, Heng JYY, Cui P, et al., 2023, Isostructurality or not: a deep insight into the selective formation of spironolactone solvates, Crystal Growth and Design, Vol: 23, Pages: 4721-4727, ISSN: 1528-7483
Isostructurality is a potential tool to design crystals with tailored arrangements, especially for multicomponent systems, but research into its formation mechanism is still limited to date. Herein, a family of spironolactone (SPI) isostructural and non-isostructural solvates was investigated to explore the selective formation of isostructural crystals. The SPI framework, dominated by van der Waals forces, is robust and flexible, with different solvent molecules in its channels playing the same structural role. The formation of the SPI isostructural solvate is a delicate energy balance between the energy loss caused by the expansion of the SPI framework and the addition of SPI···solvent interactions. Besides the size and functional groups of solvent molecules, the directionality of the SPI···solvent interactions should also be carefully considered in the isostructurality-based crystal design. In addition, weak interactions seem to be regarded as potential design elements for organic host architectures.
Chadha D, Heng JYY, Sun E, 2023, Equality, Diversity and Inclusion (EDI) in the Chemical Engineering Curriculum: Working in Partnership with Students to Create Sustainable Practices
Having suitable provisions in place to support equality, diversity and inclusion (EDI) has become increasingly important throughout higher education. In our chemical engineering department, we are currently exploring strategies that would actively enhance and promote EDI whilst aligning the provisions to the curriculum. In this paper, we discuss some of the work we have been doing in partnership with our student body on developing sustainable practices - that builds on earlier work which focused on defining and identifying EDI practices. We have identified 5 key areas of particular interest to us: improvements to our student-to-student peer review system, a departmental charter for staff and students, constructive changes to the programme handbook, a resource developed by students for students, and changes to the content and delivery of certain modules that could accommodate EDI, or the identification of modules/courses that do. As part of the research/verification process, a limited amount of survey data was collected from students to help us establish underlying issues and how suggested sustainable changes might be perceived. In conducting this work, certain challenges have arisen as well as opportunities.
Errington E, Guo M, Heng JYY, 2023, Synthetic amorphous silica: environmental impacts of current industry and the benefit of biomass-derived silica, Green Chemistry, Vol: 25, Pages: 4244-4259, ISSN: 1463-9262
The production of Synthetic Amorphous Silica (SAS) is a billion-dollar industry. However, very little is shared publicly on the environmental impact of SAS production. This work provides the first complete treatment for the environmental impacts of SAS produced via the existing ‘dry’ and ‘wet’ industrial methods using Life Cycle Assessment (LCA). To provide a more robust method, this includes an evaluation of 8 environmental impact indicators and consideration for uncertainty during process comparison. Predictions are then used to compare the impact of the existing dry and wet methods as well as theoretical methods in which rice husk (RH) is used as a biomass-derived feedstock alternative. Results highlight cases in which using RH as an alternative feedstock is likely to be beneficial. However, it is demonstrated that these benefits are highly dependent on specifics of the process, region, and feedstock characteristics rather than the inherent “green-ness” of RH alone. Findings are therefore of significance to those interested in the existing SAS industry and the sustainable development of SAS. Moreover, findings also have potential implications for wider policy.
Verma V, Mitchell H, Errington E, et al., 2023, Templated crystallization of glycine homopeptides: experimental and computational developments, Chemical Engineering and Technology, Vol: 46, Pages: 1271-1278, ISSN: 0930-7516
The usage of glass beads as heterogeneous additives for the crystallization of glycine homopeptides is investigated, whereby glass beads are shown experimentally to increase the rate of crystallization. Induction time analysis indicates that the presence of glass beads acts enhances the kinetic factor for nucleation. These results are compared to those previously obtained by the authors for glycine and diglycine, and it is demonstrated that the increase in nucleation rate is proportional to the peptide chain length. Molecular dynamics simulations confirm that larger molecules exhibit faster nucleation in the presence of glass beads due to an increased number of interactions as observed with the longest hydrogen bond lifetime for triglycine, followed by diglycine and glycine.
Khala MJ, Hare C, Karde V, et al., 2023, A numerical analysis of the influence of material properties on dry powder coating performance, Chemical Engineering Research and Design, Vol: 193, Pages: 158-167, ISSN: 0263-8762
Dry powder coating is a preferable surface modification technique over the traditional aqueous coating technique due to reduced energy waste and less environmental impact. Despite the benefits of dry powder coating, excessive amount of coating powder energy input is often applied to ensure sufficient coating is achieved. In this study, the Discrete Element Method (DEM) is utilised to assess the influence of material properties on dry coating efficiency in a blade-driven system. Granular Bond number is used to predict coating performance based on multiple simulations with varied material properties. This provides insight on the optimal range of material properties (size ratio, density ratio and surface energy) to achieve uniformly distributed coatings, thus providing precise control of the quantity of coating material required and minimising energy consumption.
Verma V, Bade I, Karde V, et al., 2023, Experimental elucidation of templated crystallization and secondary processing of peptides, Pharmaceutics, Vol: 15, Pages: 1-13, ISSN: 1999-4923
The crystallization of peptides offers a sustainable and inexpensive alternative to the purification process. In this study, diglycine was crystallised in porous silica, showing the porous templates' positive yet discriminating effect. The diglycine induction time was reduced by five-fold and three-fold upon crystallising in the presence of silica with pore sizes of 6 nm and 10 nm, respectively. The diglycine induction time had a direct relationship with the silica pore size. The stable form (α-form) of diglycine was crystallised in the presence of porous silica, with the diglycine crystals obtained associated with the silica particles. Further, we studied the mechanical properties of diglycine tablets for their tabletability, compactability, and compressibility. The mechanical properties of the diglycine tablets were similar to those of pure MCC, even with the presence of diglycine crystals in the tablets. The diffusion studies of the tablets using the dialysis membrane presented an extended release of diglycine through the dialysis membrane, confirming that the peptide crystal can be used for oral formulation. Hence, the crystallization of peptides preserved their mechanical and pharmacological properties. More data on different peptides can help us produce oral formulation peptides faster than usual.
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., Crystal Growth and Design, 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, Pages: 1-8, 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, Vol: 10, Pages: 1425-1430, ISSN: 2051-6347
Crystal regeneration has been observed in macroscopic paracetamol crystals post breakage along their cleavage plane. High resolution imaging confirmed regeneration rates to be 3-fold faster than growth prior to breakage. Further analysis of the solute-solvent interactions is required to elucidate the process which currently lacks linearity with traditional growth theories.
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, Pages: 1-9, ISSN: 0032-5910
The mixing performance in binary powder blends with components exhibiting guest and host type interactions was assessed by tracking the colour change of the mixture. The operation parameters like mixing time and speed were studied in compositions containing lactose monohydrate as host and iron oxide nanoparticle as coloured guest components. The mixing characteristics were analysed through visual imaging and colorimetric estimations. Furthermore, surface analytical techniques like scanning electron microscope (SEM) for surface area coverage (SAC) determination and Finite Dilution Inverse Gas chromatography (FD-IGC) for surface energy heterogeneity characterisation were employed. The mixing sensitivity of the coloured tracer and the consequent colour transitions under different conditions helped in validating the mixing performance and operation conditions. The FD-IGC results showed a lowering of the energetic heterogeneity for better quality mixtures. Thus, a shear sensitive coloured nano-tracer can be utilised for a simple, quick and cost-effective estimation of the mixture quality and for the validation of mixing process.
Ramli SS, Nizar NNA, Heng JYY, et al., 2023, Gelatin Substitute, Innovation of Food Products in Halal Supply Chain Worldwide, Pages: 87-98, ISBN: 9780323985239
Partially hydrolyzed collagen from animal bones, skins, and connective tissues yields gelatin, a water-soluble protein. Gelatin has a wide range of applications due to its unique functional qualities, particularly in the food, pharmaceutical, and cosmetics industries. However, in the modern world with different acceptance and food behavior, it is regarded one of the most contentious components. The acceptability of gelatin-based goods is determined by the origin of the gelatin. The primary sources that are commonly used for gelatin production raise concerns among certain groups due to health and religious issues. Fortunately, the advancement of food science and technology unveiled gelatin replacements or alternatives that are mostly plant based. The present review intends to provide an updated and short overview on gelatin substitutes, with special highlights on the presently available types, development, functional properties (surface and gelling behavior), and suitable application of gelatin substitutes. Moreover, misconception of plant-based gelatin along with regulations on gelatin under the purview of food and halal standards will be discussed.
Errington E, Guo M, Heng J, 2023, Environmental Impacts of Bio-derived Silicon: Uncertainty in the Benefit of Industrial Transition, Computer Aided Chemical Engineering, Pages: 2255-2260
Millions of tonnes of silicon are produced each year as part of a global supply chain supporting the manufacture of steel, automobiles, electronics and silicones. However, the supply chain does have its challenges – particularly the high energy intensity of silicon purification methods, and the lack of global supply chain diversity. Consequently, this study investigates the benefit of producing high purity silicon metals (>98 wt% Si) from agricultural biomass wastes from an environmental perspective using Life Cycle Assessment methodology. Taking rice husk as a case study, findings show a reduction in carbon emissions is achievable for co-recovery of silicon with bio-energy. The robustness of these findings is also addressed through uncertainty modelling, which provides further confidence in the major findings. Future agricultural sources of biomass-derived silicon have also been projected for staple crops including corn, sugarcane and wheat.
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<i> particular</i> birthday present of IChemE, CHEMICAL ENGINEERING RESEARCH & DESIGN, Vol: 188, Pages: 447-452, ISSN: 0263-8762
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 and Design, Vol: 22, Pages: 6103-6113, ISSN: 1528-7483
The surface energy and surface chemistry of a crystal are of great importance when designing particles for a specific application, as these will impact both downstream manufacturing processes as well as final product quality. In this work, the surface properties of two different quercetin solvates (quercetin dihydrate and quercetin DMSO solvate) were studied using molecular (synthonic) modeling and experimental techniques, including inverse gas chromatography (IGC) and contact angle measurements, to establish a relationship between crystal structure and surface properties. The attachment energy model was used to predict morphologies and calculate surface properties through the study of their growth synthons. The modeling results confirmed the surface chemistry anisotropy for the two forms. For quercetin dihydrate, the {010} facets were found to grow mainly by nonpolar offset quercetin–quercetin stacking interactions, thus being hydrophobic, while the {100} facets were expected to be hydrophilic, growing by a polar quercetin–water hydrogen bond. For QDMSO, the dominant facet {002} grows by a strong polar quercetin–quercetin hydrogen bonding interaction, while the second most dominant facet {011} grows by nonpolar π–π stacking interactions. Water contact angle measurements and IGC confirmed a greater overall surface hydrophilicity for QDMSO compared to QDH and demonstrated surface energy heterogeneity for both structures. This work shows how synthonic modeling can help in the prediction of the surface nature of crystalline particles and guide the choice of parameters that will determine the optimal crystal form and final morphology for targeted surface properties, for example, the choice of crystallization conditions, choice of solvent, or presence of additives or impurities, which can direct the crystallization of a specific crystal form or crystal shape.
Verma V, Mitchell H, Guo M, et al., 2022, Studying the impact of the pre-exponential factor on templated nucleation, Faraday Discussions, Vol: 235, Pages: 199-218, ISSN: 1359-6640
Traditionally, the enhancement of nucleation rates in the presence of heterogeneous surfaces in crystallisation processes has been attributed to the modification of the interfacial energy of the system according to the classical nucleation theory. However, recent developments have shown that heterogeneous surfaces instead alter the pre-exponential factor of nucleation. In this work, the nucleation kinetics of glycine and diglycine in aqueous solutions have been explored in the presence and absence of a heterogeneous surface. Results from induction time experiments show that the presence of a heterogeneous surface increases the pre-exponential factor by 2-fold or more for both glycine and diglycine, while the interfacial energy remains unchanged for both species. This study suggests that the heterogeneous surface enhances the nucleation rate via hydrogen bond formation with both glycine and diglycine. This is verified by hydrogen bond propensity calculations, molecular functionality analysis, and calculation of the time taken for a solute molecule to attach to the growing nucleus, which is an order of magnitude shorter than the estimated lifetime of the hydrogen bond. The effect of the heterosurface is of greater magnitude for diglycine than for glycine, which may be due to the heightened molecular complementarity between the hydrogen bond donor and acceptor sites on diglycine and the heterosurface.
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 of the monoclonal antibody Anti-CD20: probability distributions of induction times, Crystal Growth and Design, Vol: 22, Pages: 3637-3645, ISSN: 1528-7483
We present a method to determine the template crystallization behavior of proteins. This method is a statistical approach that accounts for the stochastic nature of nucleation. It makes use of batch-wise experiments under stirring conditions in volumes smaller than 0.3 mL to save material while mimicking larger-scale processes. To validate our method, it was applied to the crystallization of a monoclonal antibody of pharmaceutical interest, Anti-CD20. First, we determined the Anti-CD20 phase diagram in a PEG-400/Na2SO4/water system using the batch method, as, to date, no such data on Anti-CD20 solubility have been reported. Then, the probability distribution of induction times was determined experimentally, in the presence of various mesoporous silica template particles, and crystallization of Anti-CD20 in the absence of templates was compared to template-assisted crystallization. The probability distribution of induction times is shown to be a suitable method to determine the effect of template particles on protein crystallization. The induction time distribution allows for the determination of two key parameters of nucleation, the nucleation rate and the growth time. This study shows that the use of silica particles leads to faster crystallization and a higher nucleation rate. The template particle characteristics are shown to be critical parameters to efficiently promote protein crystallization.
Ouyang J, Xing X, Chen J, et al., 2022, 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
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Link FJ, Heng JYY, 2022, Unraveling the impact of pH on the crystallization of pharmaceutical proteins: a case study of human insulin, Crystal Growth and Design, Vol: 22, Pages: 3024-3033, ISSN: 1528-7483
One of the most crucial parameters in protein crystallization is pH, as it governs the protein’s electrostatic interactions. However, the fundamental role of pH on crystallization still remains unknown. Here, we systematically investigated the crystallization of human insulin (isoelectric point 5.3) at various pHs between 6.0 and 6.7 at different supersaturation ratios, up to 20.9. Our results demonstrate that the pH has an opposing effect on solubility and nucleation rate as a shift in pH toward a more basic milieu increases the solubility by 5-fold while the onset of nucleation was accelerated by a maximum of 8.6-fold. To shed light on this opposing effect, we evaluated the protein–protein interactions as a function of pH by measuring the second virial coefficient and hydrodynamic radius and showed that a change in pH of less than one unit has no significant impact on the protein–protein interactions. As it is widely understood that the increase in protein solubility as a function of pH is due to the increase in the repulsive electrostatic interactions, we have demonstrated that the increase in insulin solubility and decrease in the onset of nucleation are independent of the protein–protein interactions. We hypothesize that it is the electrostatic interactions between both ions and solvent molecules and the protein residues that are governing the crystallization of human insulin. The findings of this study will be of crucial importance for the design of novel crystallization pathways.
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, ISSN: 1466-8033
The nucleation experiments of pimelic acid were investigated in the absence and presence of a template. The results show that the template, malonamide, can selectively induce the nucleation of metastable form II of pimelic acid, while only stable form I of pimelic acid crystallizes under blank conditions. Furthermore, the nucleation of pimelic acid induced by a single crystal template was carried out and the induced crystals were characterized by Fourier transform infrared and micro-Raman spectroscopy. The lattice parameters and functional groups of the template and pimelic acid were analyzed, and it is inferred that functional groups play a critical role in the selective nucleation of pimelic acid. In addition, the surface structure of the template crystal was analyzed, and the result shows that the amide groups at both ends of the template molecules are exposed on the (111) and (011) faces, making these faces more likely to induce the nucleation of pimelic acid. The interaction energy, adsorption energy and mean square displacement analysis further verified the induction effect of the template faces on the pimelic acid molecules. The simulation results show that the interaction between the (111)/(011) faces and pimelic acid molecules is obviously stronger than that for other crystal faces. This study investigates the mechanism of heterogeneous nucleation at the molecular level, especially from the perspective of the effective faces, which may provide guidance about the control of polymorphs and selection of templates.
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.
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