Imperial College London

ProfessorDarylWilliams

Faculty of EngineeringDepartment of Chemical Engineering

Professor of Particle Science
 
 
 
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Contact

 

+44 (0)20 7594 5611d.r.williams Website

 
 
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Location

 

439ACE ExtensionSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

106 results found

Duralliu A, Matejtschuk P, Williams DR, 2019, Measuring the specific surface area (SSA) of freeze-dried biologics using inverse gas chromatography., Eur J Pharm Biopharm, Vol: 142, Pages: 216-221

The specific surface area (SSA) of freeze-dried biologics (FD) is usually measured via a Brunauer-Emmett-Teller (BET) analysis of volumetric nitrogen adsorption isotherms. However, this technique has accuracy limitations for materials <0.5 m2/g, requires dry samples, must be measured at 77 K and has slow sample preparation times (drying/degassing). Inverse gas chromatography (IGC) is chromatographic characterization technique which can be used to analyse the SSA (down to ≈0.1 m2/g) of various solid-state materials including powders using organic molecules such as octane at ambient temperatures/pressure for a range of relative humidities. This study presents a comprehensive comparison between the N2 BET adsorption versus octane BET adsorption using IGC methods for determining the SSA's for a range of freeze dried biological materials. These include IgG 5% w/w, an influenza antigen standard, sucrose 5% w/w and trehalose 5% w/w. IGC provided comparable SSA values to the N2 BET method with better reproducibility (lower RSDs %). Large variations in average SSA within manufactured FD batches were observed for both IGC and volumetric determinations. IGC was also used to measure the change in SSA with increasing humidity, with FD cakes shrinking and losing their structural integrity with increasing moisture content. Such information highlights the importance of moisture content in determining the physical stability of FD cakes as exemplified by their SSA. In conclusion, IGC is a suitable alternative method for determining the SSA of freeze-dried biological materials which are generally strongly dependent on their moisture content.

Journal article

Hedberg SHM, Brown LG, Meghdadi A, Williams DRet al., 2019, Improved adsorption reactions, kinetics and stability for model and therapeutic proteins immobilised on affinity resins, Adsorption, Vol: 25, Pages: 1177-1190, ISSN: 0929-5607

Protein adsorption on solid state media is important for the industrial affinity chromatography of biotherapeutics and for preparing materials for self-interaction chromatography where fundamental protein solution thermodynamic properties are measured. The adsorption of three model proteins (lysozyme, catalase and BSA) and two antibodies (a monoclonal and a polyclonal antibody) have been investigated on commercial affinity chromatography media with different surface functionalities (Formyl, Tresyl and Amino). Both the extent of protein immobilised (mg protein/ml media) and the reaction kinetics are reported for a range of reaction conditions, including pH, differing buffers as well as the presence of secondary reactants (glutaraldehyde, sodium cyanoborohydride, EDC and NHS). Compared to the reaction conditions recommended by manufacturers as well as those reported in previous published work, significant increases in the extent of protein immobilisation and reaction kinetics are reported here. The addition of glutaraldehyde or sodium cyanoborohydride was found to be especially effective even when not directly needed for the adsorption to happen. For mAb and pIgG, immobilisation levels of 50 and 31 mg of protein/ml of resin respectively were achieved, which are 100% or more than previously reported. Enhanced levels were achieved for lysozyme of 120 mg/ml with very rapid reaction kinetics (< 1 h) with sodium cyanoborohydride. It can be concluded that specific chromatography resins with Tresyl activated support offered enhanced levels of protein immobilisation due to their ability to react to form amine or thio-ether linkages with proteins. Additionally, glutaraldehyde can result in higher immobilisation levels whilst it can also accelerate immobilisation reaction kinetics.

Journal article

Duralliu A, Matejtschuk P, Dubey S, Koroma H, Gubinelli F, Williams DRet al., 2019, The influence of the closure format on the storage stability and moisture content of freeze-dried influenza antigen, VACCINE, Vol: 37, Pages: 4485-4490, ISSN: 0264-410X

Journal article

Antonio Zarate J, Sanchez-Gonzalez E, Williams DR, Gonzalez-Zamora E, Martis V, Martinez A, Balmaseda J, Maurin G, Ibarra IAet al., 2019, High and energy-efficient reversible SO2 uptake by a robust Sc(III)-based MOF, JOURNAL OF MATERIALS CHEMISTRY A, Vol: 7, Pages: 15580-15584, ISSN: 2050-7488

Journal article

Ngeow YW, Heng JYY, Williams DR, Davies RT, Lawrence KME, Chapman AVet al., 2019, TEM observation of silane coupling agent in silica-filled rubber tyre compound, Journal of Rubber Research, Vol: 22, Pages: 1-12, ISSN: 1511-1768

The microdispersion of silica in filled elastomer vulcanisates was evaluated by transmission electron microscopy (TEM)—network visualisation analysis. In this study, the silica is modified with a wide range of coupling and non-coupling silanes. The silica-filled elastomer samples were microtomed using a glass knife. The resulting TEM micrographs were interpreted and characterised based on aggregates with a cross-sectional area larger than 100 nm2. The study showed that silica surface modification has reduced the silica aggregate size by approximately 30–40% compared to an untreated silica-filled elastomer vulcanisate. The TEM micrographs showed evidence of coupling between silica and the elastomer phase and demonstrated a good estimation of silica microdispersion in the elastomer phase. This study has shown that the presence of different surface functionalities has an effect on the silica microdispersion.

Journal article

Hedberg SHM, Devi S, Duralliu A, Williams DRet al., 2019, Mechanical behavior and structure of freeze-dried cakes, Methods in Pharmacology and Toxicology, Pages: 327-351

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Freeze-drying or the lyophilization of biopharmaceuticals is a standard method for product manufacture in order to increase product shelf-life and minimize the tendency of re-constituted products to aggregate. However, the physical and or mechanical stability of freeze-dried cakes can be problematic, which can directly result in financial losses due to unusable or damaged products. Currently, there is very limited systematic knowledge of the relationship between lyophilization process conditions and the cake-specific physical structure, mechanical performance, and stability. This Chapter reviews the detailed mechanical properties and structure of freeze-dried cakes formed from aqueous solutions with concentrations from 1 to 40% w/v of common excipients, mannitol, sucrose, and trehalose in some detail. In addition, the mechanical properties of commercial freeze-dried products as well as effects of moisture content and ingress into freeze-dried cakes are also reported. Both experimentally measured Young’s moduli and yield stress data scale well with reduced cake density, in line with theoretical predictions from classical cellular solids theory. A novel compressive indentation method is reviewed which can accurately determine a cake’s Young’s modulus and yield stress within 1 min, allowing the potential future use of these mechanical cake attributes as Critical Quality Attributes (CQAs).

Book chapter

Hedberg S, Rapley J, Haigh JM, Williams Det al., 2018, Cross-interaction chromatography as a rapid screening technique to identify the stability of new antibody therapeutics, European Journal of Pharmaceutics and Biopharmaceutics, Vol: 133, Pages: 131-137, ISSN: 0939-6411

Protein aggregation can be a major problem in the manufacturing of new biopharmaceuticals and there is a desirability for development of techniques that can predict the behaviour of new biopharmaceuticals early on in the development process. A technique that can be used to predict aggregation is self-interaction chromatography that is used to determine the second virial coefficient, B22, but one of the limitations includes the need to immobilise every protein of interest. In this study a related technique, cross interaction chromatography (CIC), is evaluated which overcomes this limitation. Three antibodies were studied across a range of NaCl concentrations with each antibody being studied as both a mobile phase and as the stationary phase - in total 6 different stationary-mobile phase combinations. The B22 values obtained for all three proteins correlated strongly with the B23 results obtained for the same protein in the mobile phase, and were significantly independent of the protein immobilised on the stationary phase. This observation allows the use of pre-prepared columns with known immobilised model proteins such as a polyclonal antibody or mAb, with other unknown monoclonal antibodies in the mobile phase. Preliminary experiments using a series of known immobilised mAbs columns with an unknown mAb in the mobile phase resulted in at least a 50 fold reduction in the amount of unknown protein needed and a rapid semi-quantitative assessment of aggregation propensity. CIC can speed up the screening process with minimum preparation time and therefore more rapidly be able to identify the aggregation stability of new antibody formulations.

Journal article

Sadeek SA, Williams DR, Campbell KLS, 2018, Using sodium thiosulphate for carbon steel corrosion protection against monoethanolamine and 2-amino-2-methyl-1-propanol, INTERNATIONAL JOURNAL OF GREENHOUSE GAS CONTROL, Vol: 78, Pages: 125-134, ISSN: 1750-5836

Journal article

Ali N, Marsh J, Godfrey S, Williams DRet al., 2018, Aqueous MEA and Ammonia Sorption-Induced Damage in Keratin Fibers, ACS OMEGA, Vol: 3, Pages: 14173-14180, ISSN: 2470-1343

Journal article

Sadeek SA, Williams DR, Campbell KLS, 2018, Using sodium thiosulphate for carbon steel corrosion protection against monoethanolamine and methyldiethanolamine, INTERNATIONAL JOURNAL OF GREENHOUSE GAS CONTROL, Vol: 74, Pages: 206-218, ISSN: 1750-5836

Journal article

Ngeow YW, Chapman AV, Heng JYY, Williams DR, Mathys S, Hull CDet al., Characterization of silica modified with silanes by using thermogravimetric analysis combined with infrared detection, Rubber Chemistry and Technology, ISSN: 0035-9475

Tire treads with reduced rolling resistance and increased wet grip can be achieved by coupling hydrophilic silica to hydrocarbon rubber by using an alkoxysilane. The silica surface was modified by reaction with a wide range of coupling and non-coupling silanes. The chemistry and extent of these silanizations were elucidated using thermogravimetric analysis (TGA) combined with infrared detection. The silane grafting efficiencies were typically 52–72%, but efficiencies were lower in the bulkier [3-(di-(tridecyloxypenta(ethyleneoxy))ethoxysilyl]propyl mercaptan. However, the silica surface coverage increases with increasing size of the silane. Grafting efficiencies were lower with higher silane loadings. In the TGA, ethoxy and methoxy groups are displaced from the grafted silanes mainly at moderate temperatures (up to about 495 °C) to form siloxane bridges. Over a similar temperature range, the weaker S–S bonds present in bis(3-triethoxysilylpropyl) tetrasulfide (TESPT)- or bis[3-(triethoxysilyl)propyl] disulfide (TESPD)-modified silica are cleaved, leading to weight losses from TESPT or TESPD bound at one end to the silica and from TESPT bound at both ends. The remaining weight losses from bound silanes occurred mainly at higher temperatures. In the commercial silanized silica Coupsil 8113, TGA indicates that about two of three ethoxy groups in each triethoxysilane were lost during the silanization process.

Journal article

Williams DR, Mapping the mAb Aggregation Propensity Using Self-InteractionChromatography as a Screening Tool, Analytical Chemistry, ISSN: 0003-2700

Journal article

Duralliu A, Matejtschuk P, Williams DR, 2018, Humidity Induced Collapse in Freeze Dried Cakes: A Direct Visualization Study using DVS., European Journal of Pharmaceutics and Biopharmaceutics, Vol: 127, Pages: 29-36, ISSN: 0939-6411

Maintaining low moisture content is seen as crucial to sustaining long term stability in freeze dried (FD) cakes as higher moisture could lead to cake collapse, degradation and loss in biological potency. Using a combination of gravimetric data and video images captured from a Dynamic Vapour Sorption instrument the onset humidity Collapse Point (RHcp), the humidity Onset Crystallisation (RHc) and Onset Glass Transition (RHg) points for a series of freeze dried cakes at 10, 25 and 40°C have been determined. The moisture sorption behavior with respect to cake collapse and other morphological phase transitions are reported for a two freeze drying excipients and one product formulation; sucrose, trehalose (both 5% w/w) and an influenza antigen (A/Wisconsin/15/2009 H3N2 NYMCX-183, formulated with 1.1% w/w sucrose). Stability maps for all three formulations tested were reported as a function of %RH and temperature using the methods described in this work, thus direct visualization of collapse behavior for any FD cake can now be standardized and routinely determined, facilitating the formulation of FD products with improved stability and storage performance.

Journal article

Sadeek SA, Williams DR, Sedransk Campbell KL, 2017, Use of green inhibitors and pre-treated carbon steel for reduced corrosion in post-combustion capture infrastructure, EUROCORR 2017

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. All rights reserved. Development of strategies to implement carbon steel (CS) infrastructure in lieu of stainless steel (SS) in post-combustion CO2 capture plants will advance wide-scale deployment of this technology. Herein two proposed techniques were investigated: 1) pre-treatment of CS with 5 M methyldiethanolamine (MDEA), 2) green (i.e. low-toxicity) inhibitors: sodium thiosulphate (STS), copper carbonate (CC), and 2-mercaptobenzimidazole (MBI). Coupons (CS) were immersed for seven days in industry standard solvent 5 M monoethanolamine (MEA) to test these proposals. Pre-treated coupons demonstrated good corrosion protection with the development of a dense layer of siderite crystals, significantly reducing oxidation of the underlying Fe substrate. Copper carbonate exhibited good inhibition performance with no surface change evident after immersion. The inhibitor STS provided some corrosion protection through surface adsorption, while MBI proved least effective. The combination of a siderite layer (generated by MDEA pre-treatment) with each inhibitor was also tested. However, the integrity of the protective siderite layer was compromised in the presence of an inhibitor, ranging from nearly complete removal to some destruction.

Conference paper

Campbell KLS, Yu LCY, Williams DR, 2017, Using pre-treated carbon steel for post-combustion carbon capture infrastructure, 13th International Conference on Greenhouse Gas Control Technologies (GHGT), Publisher: ELSEVIER SCIENCE BV, Pages: 1991-1997, ISSN: 1876-6102

The reduction of capital cost in building post-combustion CO2 capture is necessary to realize its widespread use. Cheaper steels, e.g. carbon steel, are attractive but lack the necessary corrosion resistance. To protect from corrosion, one approach is to implement a protective coating on the surface. Particularly, a coating like siderite (FeCO3) is appealing because it can be formed by amines and therefore could be regenerated. This study investigates the formation, over seven days at 40 and 80 °C, of such siderite layers formed in methyldiethanolamine (MDEA), 2-amino-2-methyl-1-propanol (AMP), and a K2CO3 solution. When tested against 2.5 M monoethanolamine for 28 days, the coatings formed at 80 °C in MDEA and AMP appear the most resilient. There is a substantial siderite crystal layer remaining on the surface and only minimal weight loss.

Conference paper

Yu LCY, Sadeek S, Williams DR, Campbell KLSet al., 2017, Investigating the corrosion due to high capacity and uptake promoter amine blends on carbon steel, 13th International Conference on Greenhouse Gas Control Technologies (GHGT), Publisher: ELSEVIER SCIENCE BV, Pages: 1998-2008, ISSN: 1876-6102

The continued development of amine solvents for post-combustion CO2 capture is essential to the large-scale success of this technology, with particular interest in high capacity and uptake promoter blends. Some of these solutions also show reduced corrosive tendencies in the presence of carbon steel, a significantly cheaper alternative to the stainless steels generally employed. Optimization of the solution composition and reduced corrosion could yield both a decrease in capital and operating costs. Solutions (30% by weight) of monoethanolamine (MEA) or piperazine (PZ) were blended with either methyldiethanolamine (MDEA) or 2-amino-2-methyl-1-propanol (AMP). At 120 °C, Solutions containing PZ outperformed those with MEA showing the formation of good protective siderite (FeCO3) crystal layers, reducing continued oxidation of Fe from the surface and therefore corrosion.

Conference paper

Campbell KLS, Yu LCY, Williams DR, 2017, Siderite corrosion protection for carbon steel infrastructure in post-combustion capture plant, INTERNATIONAL JOURNAL OF GREENHOUSE GAS CONTROL, Vol: 58, Pages: 232-245, ISSN: 1750-5836

Journal article

Yu LCY, Campbell KLS, Williams DR, 2016, Carbon steel corrosion in piperazine-promoted blends under CO2 capture conditions, International Journal of Greenhouse Gas Control, Vol: 55, Pages: 144-152, ISSN: 1750-5836

Aqueous amine promoter blends have improved CO2 absorption capacity and uptake. Tertiary (3°) and sterically-hindered (SH) amines are favoured for their molar absorption ratio, (i.e. CO2 absorption capacity). With a promoter, namely piperazine (PZ), the ordinarily slow reaction kinetics of a 3°/SH amine is accelerated. Amine blends of 30 and 50% by weight, MDEA + PZ and AMP + PZ, were tested using immersion corrosion techniques at 120 °C. In all cases, a siderite (FeCO3) product layer was formed on the surface of the carbon steel coupons. Aqueous PZ solutions produced thin layers with comparatively lower Fe ion concentrations than blended solutions. The fast CO2 capture kinetics of PZ, and therefore carbonate formation, makes the rapid reaction possible due to readily available Fe ions oxidised on the surface. The replacement of PZ content in a blend, by MDEA or AMP, resulted in slower formation of siderite and variably poorer corrosion protection. Critically, the use of AMP in the blend offers better protection against corrosion, shown by lower concentration of Fe ions in the bulk solution than parallel MDEA solutions. This can be attributed to the faster formation of carbonate species by AMP, as a SH amine, which also results in more imperfect crystals.

Journal article

Shah UV, Jahn NH, Huang S, Yang Z, Williams DR, Heng JYYet al., 2016, Crystallisation via novel 3D nanotemplates as a tool for protein purification and bio-separation, Journal of Crystal Growth, Vol: 469, Pages: 42-47, ISSN: 1873-5002

This study reports an experimental validation of the surface preferential nucleation of proteins on the basis of a relationship between nucleant pore diameter and protein hydrodynamic diameter. The validated correlation was employed for the selection of nucleant pore diameter to crystallise a target protein from binary, equivolume protein mixture. We report proof-of-concept preliminary experimental evidence for the rational approach for crystallisation of a target protein from a binary protein mixture on the surface of 3D nanotemplates with controlled surface porosity and narrow pore-size distribution selected on the basis of a relationship between the nucleant pore diameter and protein hydrodynamic diameter. The outcome of this study opens up an exciting opportunity for exploring protein crystallisation as a potential route for protein purification and bio-separation in both technical and pharmaceutical applications.

Journal article

Yu LCY, Sedransk Campbell KL, Williams DR, 2016, Using carbon steel in the stripper and reboiler for post-Combustion CO2 capture with aqueous amine blends, International Journal of Greenhouse Gas Control, Vol: 51, Pages: 380-393, ISSN: 1750-5836

Aqueous amine solutions loaded with CO2 show a range of corrosion behaviour when in contact with carbon steels. Primary (1°) and secondary (2°) amines undergo corrosion, including the formation of iron oxide surface layers. By contrast, tertiary (3°) and sterically-hindered (SH) amines produce an excess of carbonate ions, leading to FeCO3 formation, and thereby reducing corrosion. Four amines were tested under challenging conditions (1–5 M at 120 °C) to confirm these behaviors. Due to recent interest in blended amine solvents (1° or 2° with 3° or SH) for improved reaction kinetics, CO2 absorption capacity and recoverability, four binary amine combinations (MEA + MDEA, MEA + AMP, AEPZ + MDEA, AEPZ + AMP) were tested in a range of compositions. Blends containing low concentrations of 1° or 2° amine show promise for use with carbon steel due to the formation of a siderite product layer and low corrosion levels. An increase in concentration of 1° or 2° amines, shows higher Fe ion concentrations initially as well as significant weight change to the coupon. However, the formation of more diverse product layers at longer time intervals reduces the Fe ion concentration in the bulk. Blends generally offer reduced corrosion compared to 1° or 2° amines alone, another benefit towards deployment.

Journal article

Quigley A, Williams DR, 2016, Similar interaction chromatography of proteins: a cross interaction chromatographic approach to estimate the osmotic second virial coefficient, Journal of Chromatography A, ISSN: 0412-3425

Self-interaction chromatography (SIC) has established itself as an important experimental technique for the measurement of the second osmotic virial coefficients B22. B22 data are critical for understanding a range of protein solution phenomena, particularly aggregation and crystallisation. A key limitation to the more extensive use of SIC is the need to develop a method for immobilising each specific protein of interest onto a chromatographic support. This requirement is both a time and protein consuming constraint, which means that SIC cannot be used as a high throughput method for screening a wide range of proteins and their variants. Here an experimental framework is presented for estimating B22 values using Similar Interaction Chromatography (SimIC). This work uses experimental B23 and B32 data for lysozyme, lactoferrin, catalase and concanavalin A to reliably estimate B22 using arithmetic mean field approximations and is demonstrated to give good agreement with SIC measurements of B22 for the same proteins. SimIC could form the basis of a rapid protein variant screening methods to assess the developability of protein therapeutic candidates for industrial and academic researchers with respect to aggregation behaviour by eluting target proteins through a series of well-characterised protein immobilized reference columns.

Journal article

Campbell KLS, Zhao Y, Hall JJ, Williams DRet al., 2016, The effect of CO2-loaded amine solvents on the corrosion of a carbon steel stripper, International Journal of Greenhouse Gas Control, Vol: 47, Pages: 376-385, ISSN: 1750-5836

The corrosive behaviour of loaded amine solvents was evaluated under stripper operating conditions, for post-combustion carbon capture, to determine the feasibility of using carbon steel in plant construction. In addition to monoethanolamine, three alternative amine solvents: methyldiethanolamine (MDEA), 2-amino-2-methyl-1-propanol (AMP), 1-(2-aminoethyl)piperazine (AEPZ), and the common additive K2CO3 were studied when in contact with carbon steel (C1018) over a 28-day period. Corrosive behaviour was evaluated using carbon steel coupons: gravimetric method for weight change, surface imaging (SEM) and analytical techniques (EDX and XRD), and Fe ion concentration in solution (ICP–OES). The results demonstrated that MDEA and AMP as well as K2CO3 develop a significant siderite (FeCO3) layer on the carbon steel surface. The presence of this layer is attributed to the preferred reaction pathway with CO2 for tertiary and sterically hindered amines. The FeCO3 layer formed in the case of MDEA provides superior protection from continued corrosion of the carbon steel. By contrast, MEA and AEPZ show significant corrosion to the carbon steel surface. In conclusion, MDEA, AMP, and K2CO3 can preferentially produce sufficient surface FeCO3 layers to reduce corrosion levels in carbon steels for use under stripper conditions in post-combustion carbon capture plants.

Journal article

Hedberg SHM, Heng JYY, Williams DR, Liddell JMet al., 2015, Micro scale self-interaction chromatography of proteins: a mAb case-study, Journal of Chromatography A, Vol: 1434, Pages: 57-63, ISSN: 0412-3425

Self-interaction chromatography is known to be a fast, automated and promising experimental technique for determination of B22, but with the primary disadvantage of needing a significant amount of protein (>50 mg). This requirement compromises its usage as a technique for the early screening of new biotherapeutic candidates. A new scaled down SIC method has been evaluated here using a number of micro LC columns of different diameters and lengths, using typically 10 times less stationary phase than traditional SIC. Scale-down was successfully accomplished using these micro-columns, where the SIC results for a range of differing columns sizes were in agreement, as reflected by k′, B22 and column volumes data. The results reported here demonstrate that a scaled down version of SIC can be easily implemented using conventional liquid chromatography system where the final amount of mAbs used was 10 times less than required by conventional SIC methodologies.

Journal article

Hedberg SHM, Heng JYY, Williams DR, Liddel JMet al., 2015, Self-interaction chromatography of mAbs: accurate measurement of dead volumes, Pharmaceutical Research, Vol: 32, Pages: 3975-3985, ISSN: 1573-904X

Purpose: Measurement of the second virial coefficient B22 for proteins using self-interaction chromatography (SIC) is becoming an increasingly important technique for studying their solution behaviour. In common with all physicochemical chromatographic methods, measuring the dead volume of the SIC packed column is crucial for accurate retention data; this paper examines best practise for dead volume determination.Method: SIC type experiments using catalase, BSA, lysozyme and a mAb as model systems are reported, as well as a number of dead column measurements. Results: It was observed that lysozyme and mAb interacted specifically with Toyopearl AF-Formyl dead columns depending upon pH and [NaCl], invalidating their dead volume usage. Toyopearl AF-Amino packed dead columns showed no such problems and acted as suitable dead columns without any solution condition dependency. Dead volume determinations using dextran MW standards with protein immobilised SIC columns provided dead volume estimates close to those obtained using Toyopearl AF-Amino dead columns. Conclusion: It is concluded that specific interactions between proteins, including mAbs, and select SIC support phases can compromise the use of some standard approaches for estimating the dead volume of SIC columns. Two other methods were shown to provide good estimates for the dead volume.

Journal article

Williams DR, Quigley A, 2015, The Second Virial Coefficient as a Predictor of Protein Aggregation Propensity: A Self-Interaction Chromatography Study, European Journal of Pharmaceutics and Biopharmaceutics, Vol: 96, Pages: 282-290, ISSN: 1873-3441

The second osmotic virial coefficients (b2) of four proteins – lysozyme, recombinant human lactoferrin, concanavalin A and catalase were measured by self-interaction chromatography (SIC) in solutions of varying salt type, concentration and pH. Protein aggregate sizes basedon the initial hydrodynamic radius of the protein solution species present were measured using dynamic light scattering, and the relationship between b2 and protein aggregate size studied. A linear correlation was established between b2 values and protein aggregate hydrodynamic size for all proteins, and for almost all solution conditions. Aggregate sizes of< ~10nm, indicative of non-aggregated protein systems, were consistently observed to have b2 values > 0. The observed b2 trends as a function of solution conditions were very much protein dependent, with notable trends including the existence of attractive interactions (negative b2 values) at low ionic strengths for catalase and concanavalin A, and the highly positive b2 values observed for lactoferrin over a wide range of solution conditions, reflecting lactoferrin’s innately high stability. It is concluded that the quantification of protein-protein interactions using SIC based b2 data is a potentially valuable screening tool for predicting protein aggregation propensity.

Journal article

Campbell KLS, Lapidot T, Williams DR, 2015, Foaming of CO2-loaded amine solvents degraded thermally under stripper conditions, Industrial & Engineering Chemistry Research, Vol: 54, Pages: 7751-7755, ISSN: 1520-5045

Foaming of amine solutions remains a problem for natural gas sweetening and post-combustion carbon capture. New amine-based solutions are being developed to replace monoethanolamine (MEA). This work tested the foaminess of MEA and three alternatives (methyldiethanolamine (MDEA), 1-(2-aminoethyl)piperazine (AEPZ), and 2-amino-2-methyl-1-propanol (AMP)) before and after thermal degradation; two methods were used to describe the foaminess. Foam was only formed after thermal degradation. The first method suggests foaminess, where AEPZ > MDEA > MEA; AMP, by contrast, did not conform to this model and formed a stable foam. The second method, using liquid physical properties, found that solutions that contained more degradation products (MEA, MDEA, AMP) showed different foaminess than those that did not (i.e., changing the chemistry during degradation strongly impacts the foaminess, which is observed). The foaming of these degraded samples demonstrates complexity that cannot be replicated by simple model solutions. Therefore, this study is more representative of the foaming behavior that is observed in industrial cases.

Journal article

Cheung PCW, Williams DR, 2015, Separation of transition metals and chelated complexes in wastewaters, Environmental Progress & Sustainable Energy, Vol: 34, Pages: 761-783, ISSN: 1944-7442

This review responds to the ongoing needs of wastewater engineers tasked with treating aqueous solutions containing chelated complexes of metal ions, of which nickel citrate in electrodeless plating and copper–EDTA in electronic chip board manufacturing are two key examples. Because of the presence of these sequestering agents, metallic ions cannot be readily precipitated by alkalinity, making a compelling case for the discovery of alternative methods of treatment. This review is a critical appraisal of the varying degrees of success in separation process strategies deployed for the recovery of metallic ions under such challenging chemical conditions. Guidance is provided on making progress toward satisfactory industrial solutions to surmount these difficulties.

Journal article

Shah UV, Parambil JV, Williams DRM, Hinder SJ, Heng Jet al., 2015, Preparation and characterisation of 3D nanotemplates for protein crystallisation, Powder Technology, Vol: 282, Pages: 10-18, ISSN: 0032-5910

Heterogeneous template nucleants are gaining pace as a favoured tool for crystallisation of proteins that may be otherwise difficult to crystallise. A systematic understanding on protein-nucleant interactions has to be developed to enable the development of nucleants for a wide spectrum of biological macromolecules. Thorough characterisation of the nucleants is the key starting point to achieve this aim. This report focuses on the method to produce and characterise functionalised 3D nanotemplates with controlled porosity in the range of 3-22. nm and surface chemistry that can vary from highly hydrophilic to highly hydrophobic in nature. BET and TEM are used to study porosity and pore size distribution while contact angle, XPS and zeta potential are used to investigate surface chemistry of the nucleants. These functionalised 3D nanotemplates are hereby reported to produce protein crystals (concanavalin A and catalase) of different habits without changing any other crystallisation parameters other than the surface chemistry of the templates. This emphasises the potential of 3D nanotemplates with well-ordered porosity and chemistry for further development in protein crystallisation experiments.

Journal article

Williams DR, 2015, Particle Engineering in Pharmaceutical Solids Processing: Surface Energy Considerations, CURRENT PHARMACEUTICAL DESIGN, Vol: 21, Pages: 2677-2694, ISSN: 1381-6128

Journal article

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