Dr Richard Sear


Reader, Soft Matter Group leader

Academic and research departments

Department of Physics, Soft Matter Group.

Biography

Research

Research interests

My teaching

My publications

Publications

Advances in Nanotechnology enable us to structure new materials at the nanoscale and develop novel systems capable of active response of X-rays and sensing humidity. Carbon nanomaterials are two-dimensional sheets of
Crystallisation by precipitation is a very common technique in industry, however the crystals produced are often of poor quality, characterised by broad particle size distribution and morphological inhomogeneities. These problems can be overcome by the use of ultrasound. Sonocrystallisation, or ultrasound-assisted crystallisation, has already demonstrated its general benefits in terms of reduction in crystallisation time, smaller and more homogeneous crystals and repeatability. However, there are many issues still unaddressed, such as poor knowledge of the mechanism of sonocrystallisation and of the governing parameters of the whole system. This is largely attributed to lack of systematic studies, varying frequency and power while using the same equipment, as well as difficulties in comparing results from different systems. Furthermore, ultrasound is still considered uneconomical in industrial scale, due to its high energy demand. Therefore, there is the necessity of optimising the use of ultrasound for guaranteeing a high-quality product with the lowest energy consumption. This thesis therefore focused on studying the effects of sonocrystallisation for two different crystallisation systems by precipitation: the antisolvent crystallisation of sodium chloride and the reactive crystallisation of ZIF-8, a type of Metal-Organic Frameworks (MOFs). In both systems, frequency, power and sonication time was systematically varied, and the effects on the product obtained investigated. The effect of changing supersaturation was also studied. The comparison between a simpler and a more complex system could help on obtaining general conclusions useful for clarifying the mechanism of sonocrystallisation. The antisolvent sonocrystallisation of sodium chloride revealed that sonication caused a reduction of the crystal size up to 10 times with respect to unsonicated conditions. This was achieved within a few seconds of sonication (5 s for high supersaturation and 15 s for low supersaturation), indicating that the effects of ultrasound were on the nucleation, causing the rapid formation of small and regular crystals. Phenomena of sono-fracture was excluded because the crystals formed were morphologically regular, very different from fragments. Adding a subsequent step in silent conditions or using intermittent ultrasound bursts coupled with silent conditions showed a limited crystal growth. Hence, ultrasound uses the majority of the solute forming new small crystals and leaving in the solution only a small amount of sodium chloride. The effects of different frequencies and powers were more evident at lower supersaturations, with lower frequency being more effective at reducing crystal size. However, under these conditions, although a small average crystal size was obtained, the particle size distributions were bimodal at low power. At high supersaturation, this bimodality disappeared even at low powers. For the reactive crystallisation of ZIF-8 at high excess of ligand, it was confirmed that the action of ultrasound caused a reduction of the crystal size up to nanometre. Furthermore, it was demonstrated again that the action of sonication was on the early stages of the crystallisation. However, the effects of ultrasound resembled a lot the results obtained when only mixing was applied, suggesting that sonication was not directly influencing the chemistry of the reaction. In addition, the BET surface area appeared to be related to the power used, reaching a maximum and decreasing beyond a certain power. This suggests that a competition between micromixing, causing an increase of the BET surface area, and shockwaves, responsible of breaking the framework during its formation. On the other hand, when a low excess of ligand was used, it was revealed that the formation of by-products was accelerated when mixing or sonication were applied. However, if shorter reaction time was applied, it was possible to obtain a reasonable quality of ZIF-8 at low excess of ligand. This new insight explains why low excess of ligand was considered unsuitable for ZIF-8 production, as all reported studies in the literature have applied mixing and used long reaction times. Overall, the results from this thesis have demonstrated commonalities between antisolvent and reactive crystallisation, that is reducing the sonication time to a brief interval at the beginning of the crystallisation can achieve the same size reduction as sonicating for the entire process. This is a key result in view of optimising sonocrystallisation processes. In addition, lower supersaturations or excess ligands are more sensitive to the crystallisation condition. The effect of frequency and power is more significant under antisolvent crystallisation, whereas under reactive crystallisation mixing is the dominant effect and therefore no frequency or power effect is observed. These differences may explain why there are inconsistencies in the reported frequency and power effects in the literature.
The phase behaviour of a single large semiflexible polymer immersed in a suspension of spherical particles is studied. All interactions are simple excluded volume interactions and the diameter of the spherical particles is an order of magnitude larger than the diameter of the polymer. The spherical particles induce a quite long ranged depletion attraction between the segments of the polymer and this induces a continuous coil-globule transition in the polymer. This behaviour gives an indication of the condensing effect of macromolecular crowding on DNA.
It is well known amongst molecular biologists that proteins with a common ancestor and that perform the same function in similar organisms, can have rather different amino-acid sequences. Mutations have altered the amino-acid sequences without affecting the function; this is called neutral evolution. A simple model of a protein in which the interactions are encoded by sequences of bits is introduced, and used to study how mutations can change these bits, and hence the interactions, while maintaining the stability of the protein solution. This stability is a simple minimal requirement on our model proteins which mimics part of the requirement on a real protein to be functional. The properties of our model protein, such as its second virial coefficient, are found to vary significantly from one model protein to another. It is suggested that this may also be the case for real proteins in vivo.
Silvia Nalesso, Madeleine J. Bussemaker, Richard P. Sear, Mark Hodnett, Judy Lee (2019)A Review on Possible Mechanisms of Sonocrystallisation in Solution, In: Ultrasonics Sonochemistry Elsevier
Sonocrystallisation is the application of ultrasound to the crystallisation process. The benefits obtained by sonication have been widely studied since the beginning of the 20th century and so far it is clear that ultrasound can be a very useful tool for enhancing crystallisation and controlling the properties of the final product. Crystal size, polymorphs, purity, process repeatability and lower induction time are only some of the advantages of sonocrystallisation. Even though the effects of sonication on crystallisation are quite clear, the physical explanation of the phenomena involved is still lacking. Is the presence of cavitation necessary for the process? Or is only the bubbles surface responsible for enhancing crystallisation? Are the strong local increases in pressure and temperature induced by cavitation the main cause of all the observed effects? Or is it the strong turbulence induced in the system, instead? Many questions still remain and can only be appreciated with an understanding of the complexity behind the individual processes of crystallisation and acoustic cavitation. Therefore, this review will first summarise the theories behind crystallisation and acoustic cavitation, followed by a description of all the current proposed sonocrystallisation mechanisms, and conclude with an overview on future prospects of sonocrystallisation applications.
It has been shown by Stell [J. Stat. Phys. 63, 1203 (1991)] that at low temperature monodisperse sticky spheres collapse to form coexisting close-packed solid and infinitely dilute gases. We show that polydisperse sticky spheres also collapse and calculate the collapse temperature. The polydisperse spheres separate into fractions with narrower polydispersities which can then solidify. This is the first example of a single-peaked polydisperse mixture phase separating. It implies that a mixture of polydisperse large hard spheres with much smaller hard spheres does not show fluid--fluid coexistence.
RP Sear, JA Cuesta (2003)Instabilities in complex mixtures with a large number of components, In: Phys. Rev. Lett.91pp. 245701-?
Inside living cells are complex mixtures of thousands of components. It is hopeless to try to characterise all the individual interactions in these mixtures. Thus, we develop a statistical approach to approximating them, and examine the conditions under which the mixtures phase separate. The approach approximates the matrix of second virial coefficients of the mixture by a random matrix, and determines the stability of the mixture from the spectrum of such random matrices.
RP Sear (2012)Non-self-averaging nucleation rate due to quenched disorder, In: JOURNAL OF PHYSICS-CONDENSED MATTER24(5)ARTN 0pp. ?-? IOP PUBLISHING LTD
RP Sear (1998)Phase separation and crystallisation of polydisperse hard spheres, In: Europhysics Letters44pp. 531-535
Hard spheres with a polydispersity above approximately 8% are shown to crystallise into two phase-separated solid phases. A polydispersity above 8% is too large to be tolerated by a single solid phase but phase separation produces two fractions with polydispersities sufficiently narrow to allow them to crystallise. It may not be possible to observe this in experiment due to the intervention of a glass transition.
Homogeneous nucleation of a new phase near an Ising-like critical point of another phase transition is studied. A scaling analysis shows that the free energy barrier to nucleation contains a singular term with the same scaling as the order parameter associated with the critical point. The total magnetisation of the nucleus scales as the response function and so it diverges. Vapour-liquid critical points are in the Ising universality class and so our results imply that near such a critical point the number of molecules in a nucleus of a another phase, such as a crystalline phase, diverges as the isothermal compressibility. The case where symmetry prevents coupling between the nucleus and the order parameter is also considered.
Andrea Fortini, Ignacio Martin-Fabiani, Jennifer Lesage De La Haye, Pierre-Yves Dugas, Muriel Lansalot, Franck D'Agosto, Elodie Bourgeat-Lami, Joseph Keddie, Richard Sear (2016)Dynamic stratification in drying films of colloidal mixtures, In: Physical Review Letters116(11) American Physical Society
In simulations and experiments, we study the drying of films containing mixtures of large and small colloidal particles in water. During drying, the mixture stratifies into a layer of the larger particles at the bottom with a layer of the smaller particles on top. We developed a model to show that a gradient in osmotic pressure, which develops dynamically during drying, is responsible for the segregation mechanism behind stratification.
In a mixed suspension of rods and small polymer coils, the rods adsorb onto a hard wall in contact with the suspension. This adsorption is studied in the low density of rods limit. It is driven by depletion forces and is much stronger for long rods than for spheres. This is shown by means of exact, numerical, calculations and an approximate theory.
RP Sear (2002)The effects of added salt on the second virial coefficients of the complete proteome of E. coli, In: Journal of Chemical Physics118(11)pp. 5157-5161 AIP
Bacteria typically have a few thousand different proteins. The number of proteins with a given charge is a roughly Gaussian function of charge - centred near zero, and with a width around ten (in units of the charge on the proton). We have used the charges on E. coli's proteins to estimate the changes in the second virial coefficients of all its proteins as the concentration of a 1:1 salt is increased. The second virial coefficient has dimensions of volume and we find that on average it decreases by about twice the average volume of a protein when the salt concentration is increased from 0.2 to 1 Molar. The standard deviation of the decrease is of the same order. The consequences of this for the complex mixture of proteins inside an E. coli cell, are briefly discussed.
RP Sear (2005)Formation of a metastable phase due to the presence of impurities, In: J. Phys.: Condens. Matter17pp. 3997-4004
Phase transitions into a new phase that is itself metastable are common; instead of the equilibrium phase nucleating a metastable phase does so. When this occurs the system is sometimes said to be obeying Ostwald's rule. We show how this can happen when there are impurities present that reduce the barrier to heterogeneous nucleation of the metastable phase. We do so by studying a Potts lattice model using Monte Carlo simulation. Thus, which phase forms depends not only on the properties of the different phases but also on the impurities present. Understanding why systems obey Ostwald's rule may therefore require a study of the impurities present.
As proteins typically have charges of around 10, they will interact strongly with charged surfaces. We calculate the electrostatic contribution to the interaction of crystals of protein with charged surfaces. The surfaces repel like-charged crystals and attract oppositely-charged crystals, with free energies which can be easily several kT per protein molecule brought into contact with the surface. This means that oppositely charged surfaces can act as a nucleant, they can induce nucleation of a protein crystal by lowering the free energy barrier to heterogeneous nucleation of the crystal from a dilute solution.
The effect of adding nonadsorbing polymer to a lamellar phase of surfactant bilayers is studied theoretically. We find that the polymer produces coexistence between two lamellar phases of different layer spacings. The coexistence region is a closed loop, as in the experiments of Ficheux et al. [J. de Physique II 5 823 (1995)]. Within our model the coexistence is driven by depletion.
A simple model of a polymer with long rigid segments which interact via excluded volume repulsions and short ranged attractions is proposed. The coil-globule transition of this model polymer is strongly first order, the globule is crystalline and the coil which coexists with the globule is swollen. A virial expansion truncated at low order is shown to provide a very poor approximation to the free energy and so a cell theory is used to calculate the free energy of the globule.
P Asanithi, E Saridakis, L Govada, I Jurewicz, EW Brunner, R Ponnusamy, JAS Cleaver, AB Dalton, NE Chayen, RP Sear (2009)Carbon-Nanotube-Based Materials for Protein Crystallization, In: ACS APPL MATER INTER1(6)pp. 1203-1210 AMER CHEMICAL SOC
We report on the first use OF carbon-nanotube-based films to produce crystals of proteins. The crystals nucleate on the surface of the film. The difficulty of crystallizing proteins is a major bottleneck in. the determination of the structure and function of biological molecules. The crystallization of two model proteins and two medically relevant proteins was studied. Quantitative data on the crystallization times of the model protein lyozyme are also presented. Two types of nanotube films, one made with the surfactant Triton X-100 (TX-100) and one with gelatin, were tested. Both induce nucleation of the crystal phase at supersaturations at which the protein solution would otherwise remain clear: however, the gelatin-based film induced nucleation down to much lower supersaturations for the two model proteins with which it was used. it appears that the interactions of gelatin with the protein molecules are particularly favorable to nucleation. Crystals of the C I domain of the human cardiac myosin-binding protein-C that diffracted to a resolution of 1.6 angstrom were obtained on the TX-100 film. This is far superior to the best crystals obtained using standard techniques, which only diffracted to 3.0 angstrom. Thus, both of our nanotube-based films are very promising candidates for future work on crystallizing difficult-to-crystallize target proteins.
Ian Williams, Sangyoon Lee, Azzurra Apriceno, Richard P. Sear, Giuseppe Battaglia (2020)Diffusioosmotic and convective flows induced by a non-electrolyte concentration gradient, In: Proceedings of the National Academy of Sciences National Academy of Sciences
Glucose is an important energy source in our bodies, and its consumption results in gradients over lengthscales ranging from the sub-cellular to entire organs. Concentration gradients can drive material transport through both diffusioosmosis and convection. Convection arises because concentration gradients are mass density gradients. Diffusioosmosis is fluid flow induced by the interaction between a solute and a solid surface. A concentration gradient parallel to a surface creates an osmotic pressure gradient near the surface, resulting in flow. Diffusioosmosis is well understood for electrolyte solutes, but is more poorly characterised for nonelectrolytes such as glucose. We measure fluid flow in glucose gradients formed in a millimetre-long thin channel, and find that increasing the gradient causes a crossover from diffusioosmosis-dominated to convection-dominated flow. We cannot explain this with established theories of these phenomena which predict that both scale linearly. In our system, the convection speed is linear in the gradient, but the diffusioosmotic speed has a much weaker concentration dependence, and is large even for dilute solutions. We develop existing models and show that a strong surface-solute interaction, a heterogeneous surface and accounting for a concentration-dependent solution viscosity can explain our data. This demonstrates how sensitive non-electrolyte diffusioosmosis is to surface and solution properties and to surface-solute interactions. A comprehensive understanding of this sensitivity is required to understand transport in biological systems on lengthscales from micrometres to millimetres where surfaces are invariably complex and heterogeneous.
JL Keddie, P Ekanayake, AM Koenig, TG Weerakkody, N Barber, D Johannsmann, RP Sear, PJ McDonald (2007)Influence of the colloidal stability of latex particles on their distribution in drying films, In: ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY234 AMER CHEMICAL SOC
RP Sear (2001)Homogeneous nucleation of a non-critical phase near a continuous phase transition, In: Physical Review E: Statistical, Nonlinear, and Soft Matter Physics63(6)pp. ?-?
Homogeneous nucleation of a new phase near a second, continuous, transition, is considered. The continuous transition is in the metastable region associated with the first-order phase transition, one of whose coexisting phases is nucleating. Mean-field calculations show that as the continuous transition is approached, the size of the nucleus varies as the response function of the order parameter of the continuous transition. This response function diverges at the continuous transition, as does the temperature derivative of the free energy barrier to nucleation. This rapid drop of the barrier as the continuous transition is approached means that the continuous transition acts to reduce the barrier to nucleation at the first-order transition. This may be useful in the crystallisation of globular proteins.
Crystallisation starts off with nucleation, which is rather poorly understood. However, over the last few years there have been important quantitative experiments at constant supersaturation, and the modelling of this data has also advanced. Experiments in which the supersaturation is varying, e.g., those at constant cooling rate, are important but hard to interpret. This review focuses on the state of the art in quantitative studies of nucleation at constant supersaturation. We can now test reliably for heterogeneous nucleation and somewhat less reliably for the rarer case of homogeneous nucleation. In the case of heterogeneous nucleation, we can also obtain at least some information on what is responsible for nucleation. We also now have (unfortunately currently untested) predictions for the scaling of nucleation timescales with system size. These predictions may prove important both for scaling up from small droplets to larger volumes, and for scaling down to crystallisation at the nanoscales relevant for nanotechnology applications. Finally, it is worth noting that in many experiments the dynamic range of nucleation times is too large to be measured. This is presumably due to highly variable impurities, and this problem may need to be addressed in future work. This journal is © the Partner Organisations 2014.
Richard Sear (2018)Stratification of mixtures in evaporating liquid films occurs only for a range of volume fractions of the smaller component, In: Journal of Chemical Physics148(13)134909pp. 134909-1 AIP Publishing
I model the drying of a liquid film containing small and big colloid particles. Fortini et al. [A. Fortini et al, Phys. Rev. Lett. 116, 118301 (2016)] studied these films with both computer simulation and experiment. They found that at the end of drying the mixture had stratified with a layer of the smaller particles on top of the big particles. I develop a simple model for this process. The model has two ingredients: arrest of the diffusion of the particles at high density, and diffusiophoretic motion of the big particles due to gradients in the concentration of the small particles. The model predicts that stratification only occurs over a range of initial concentrations of the smaller colloidal species. At concentrations that are either too low or too high, the concentration gradients due to drying are not enough to push the big particles away and so produce a layer at the top of only small particles. In agreement with earlier work, the model also predicts that large Peclet numbers for drying are needed to see stratification.
AJ Page, RP Sear (2009)Freezing in the bulk controlled by prefreezing at a surface, In: PHYSICAL REVIEW E80(3)ARTN 0pp. ?-? AMER PHYSICAL SOC
The dilute fluid phase of model globular proteins is studied. The model possesses a fluid-fluid transition buried within the fluid-crystal coexistence region, as do some globular proteins. If this fluid-fluid transition is not buried deep inside the fluid-crystal coexistence region the crystalline phase does not nucleate within the dilute fluid. We link this lack of nucleation of the crystal to the interactions in our model and speculate that similar interactions between globular proteins are responsible for the difficulty found in crystallising many globular proteins.
RP Sear (2004)Statistical theory of nucleation in the presence of uncharacterised impurities, In: Physical Review E70(2)pp. ?-? APS
First order phase transitions proceed via nucleation. The rate of nucleation varies exponentially with the free-energy barrier to nucleation, and so is highly sensitive to variations in this barrier. In practice, very few systems are absolutely pure, there are typically some impurities present which are rather poorly characterised. These interact with the nucleus, causing the barrier to vary, and so must be taken into account. Here the impurity-nucleus interactions are modelled by random variables. The rate then has the same form as the partition function of Derrida's Random Energy Model, and as in this model there is a regime in which the behaviour is non-self-averaging. Non-self-averaging nucleation is nucleation with a rate that varies significantly from one realisation of the random variables to another. In experiment this corresponds to variation in the nucleation rate from one sample to another. General analytic expressions are obtained for the crossover from a self-averaging to a non-self-averaging rate of nucleation.
Richard Sear (2013)Generalisation of Levine's prediction for the distribution of freezing temperatures of droplets: A general singular model for ice nucleation, In: Atmospheric Chemistry and Physics13pp. 7215-7223 European Geosciences Union
Models without an explicit time dependence, called singular models, are widely used for fitting the distribution of temperatures at which water droplets freeze. In 1950 Levine developed the original singular model. His key assumption was that each droplet contained many nucleation sites, and that freezing occurred due to the nucleation site with the highest freezing temperature. The fact that freezing occurs due to the maximum value out of large number of nucleation temperatures, means that we can apply the results of what is called extreme-value statistics. This is the statistics of the extreme, i.e., maximum or minimum, value of a large number of random variables. Here we use the results of extreme-value statistics to show that we can generalise Levine's model to produce the most general singular model possible. We show that when a singular model is a good approximation, the distribution of freezing temperatures should always be given by what is called the generalised extreme-value distribution. In addition, we also show that the distribution of freezing temperatures for droplets of onesize, can be used to make predictions for the scaling of the median nucleation temperature with droplet size, and vice versa.
RP Sear (1999)Depletion induced demixing in polydisperse mixtures of hard spheres, In: Physical Review Letters82(21)pp. 4244-4247 American Physical Society
Polydisperse mixtures are those in which components with a whole range of sizes are present. It is shown that the fluid phase of polydisperse hard spheres is thermodynamically unstable unless the density of large spheres decreases at least exponentially as their size increases. The instability is with respect to the large spheres crystallising out into multiple solid phases.
Richard Sear, Patrick B. Warren (2017)Diffusiophoresis in non-adsorbing polymer solutions: the Asakura-Oosawa model and stratification in drying films, In: Physical Review E96pp. 062602-1 American Physical Society
A colloidal particle placed in an inhomogeneous solution of smaller non-adsorbing polymers will move towards regions of lower polymer concentration, in order to reduce the free energy of the interface between the surface of the particle and the solution. This phenomenon is known as diffusiophoresis. Treating the polymer as penetrable hard spheres, as in the Asakura-Oosawa model, a simple analytic expression for the diffusiophoretic drift velocity can be obtained. In the context of drying films we show that diffusiophoresis by this mechanism can lead to stratification under easily accessible experimental conditions. By stratification we mean spontaneous formation of a layer of polymer on top of a layer of the colloid. Transposed to the case of binary colloidal mixtures, this offers an explanation for the stratification observed recently in these systems [A. Fortini et al., Phys. Rev. Lett. 116, 118301 (2016)]. Our results emphasise the importance of treating solvent dynamics explicitly in these problems, and caution against the neglect of hydrodynamic interactions or the use of implicit solvent models in which the absence of solvent back ow results in an unbalanced osmotic force which gives rise to large but unphysical effects.
CAC Abdullah, CL Azad, R Ovalle-Robles, S Fang, MD Lima, X Lepro, S Collins, RH Baughman, AB Dalton, NJ Plant, RP Sear (2014)Primary Liver Cells Cultured on Carbon Nanotube Substrates for Liver Tissue Engineering and Drug Discovery Applications, In: ACS APPLIED MATERIALS & INTERFACES6(13)pp. 10373-10380 AMER CHEMICAL SOC
Laurie Little, Richard Sear, Joseph Keddie (2015)Does the gamma Polymorph of Glycine Nucleate Faster? A Quantitative Study of Nucleation from Aqueous Solution, In: Crystal Growth and Design15(11)pp. 5345-5354 American Chemical Society
We advance the quantitative study of nucleation by combining the study of hundreds of samples, with statistical tests for reproducibility, and for well-defined nucleation rates. Unlike in most previous work, we find that in the samples that nucleate after the first hour of our experiment the equilibrium glycine polymorph predominates over the alpha form.
At low temperature, spheres with a very short-ranged attraction exist as a close-packed solid coexisting with an infinitely dilute gas. We find that the ratio of the interfacial tension between these two phases to the thermal energy diverges as the range of the attraction goes to zero. The large tensions when the interparticle attractions are short-ranged may be why globular proteins only crystallise over a narrow range of conditions.
Proteins must bind to specific other proteins in vivo in order to function. The proteins must bind only to one or a few other proteins of the of order a thousand proteins typically present in vivo. Using a simple model of a protein, specific binding in many component mixtures is studied. It is found to be a demanding function in the sense that it demands that the binding sites of the proteins be encoded by long sequences of bits, and the requirement for specific binding then strongly constrains these sequences. This is quantified by the capacity of proteins of a given size (sequence length), which is the maximum number of specific-binding interactions possible in a mixture. This calculation of the maximum number possible is in the same spirit as the work of Shannon and others on the maximum rate of communication through noisy channels.
IA Bushnak, FH Labeed, RP Sear, JL Keddie (2010)Adhesion of microorganisms to bovine submaxillary mucin coatings: effect of coating deposition conditions, In: BIOFOULING26(4)pp. 387-397 TAYLOR & FRANCIS LTD
The adhesion of Staphylococcus epidermidis, Escherichia coli, and Candida albicans on mucin coatings was evaluated to explore the feasibility of using the coating to increase the infection resistance of biomaterials. Coatings of bovine submaxillary mucin (BSM) were deposited on a base layer consisting of a poly(acrylic acid-b-methyl methacrylate) (PAA-b-PMMA) diblock copolymer. This bi-layer system exploits the mucoadhesive interactions of the PAA block to aid the adhesion of mucin to the substratum, whereas the PMMA block prevents dissolution of the coating in aqueous environments. The thickness of the mucin coating was adjusted by varying the pH of the solution from which it was deposited. Thin mucin coatings decreased the numbers of bacteria but increased the numbers of C. albicans adhering to the copolymer and control surfaces. Increasing the mucin film thickness resulted in a further lowering of the density of adhering S. epidermidis cells, but it did not affect the density of E. coli. In contrast, the density of C. albicans increased with an increase in mucin thickness.
A simple analytic theory for mixtures of hard spheres and larger polymers with excluded volume interactions is developed. The mixture is shown to exhibit extensive immiscibility. For large polymers with strong excluded volume interactions, the density of monomers at the critical point for demixing decreases as one over the square root of the length of the polymer, while the density of spheres tends to a constant. This is very different to the behaviour of mixtures of hard spheres and ideal polymers, these mixtures although even less miscible than those with polymers with excluded volume interactions, have a much higher polymer density at the critical point of demixing. The theory applies to the complete range of mixtures of spheres with flexible polymers, from those with strong excluded volume interactions to ideal polymers.
JL Keddie, DC Andrei, RPL Sear, SG Yeates (1999)Surface flattening of thermosetting powder coatings: Theory and experiment., In: ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY218pp. U626-U626 AMER CHEMICAL SOC
RP Sear (2000)Phase separation in mixtures of colloids and long ideal polymer coils, In: Physical Review Letters v86pp. 4696-4699
Colloidal suspensions with free polymer coils which are larger than the colloidal particles are considered. The polymer-colloid interaction is modeled by an extension of the Asakura-Oosawa model. Phase separation occurs into dilute and dense fluid phases of colloidal particles when polymer is added. The critical density of this transition tends to zero as the size of the polymer coils diverges.
RNA molecules in living cells form what look like liquid droplets formed by liquid/liquid phase separation. But unlike the molecules in conventional phase separating mixtures, RNA molecules are transported by molecular motors that consume energy and so are out of equilibrium. Motivated by this we consider what sort of simple rules for the dynamics of model mRNA molecules lead to liquid/liquid phase separation. We find that dynamics that slow as the local density of molecules increases, drive the formation of liquids. We also look at the analogous separation of the two blocks of a block copolymer, in which the monomers of one block have dynamics that depend on the local density of monomers of that block. We find that this block condenses and separates from the monomers of the other block. This is a simple model of the out-of-equilibrium domain formation found in the chromatin in the nucleus of cells.
RP Sear (2007)Nucleation: theory and applications to protein solutions and colloidal suspensions, In: JOURNAL OF PHYSICS-CONDENSED MATTER19(3)ARTN 03310 IOP PUBLISHING LTD
RP Sear (2006)Interactions in protein solutions, In: CURRENT OPINION IN COLLOID & INTERFACE SCIENCE11(1)pp. 35-39 ELSEVIER SCIENCE LONDON
RP Sear (2002)Distribution of the second virial coefficients of globular proteins, In: Europhysics Letters60pp. 938-944
George and Wilson [Acta. Cryst. D 50, 361 (1994)] looked at the distribution of values of the second virial coefficient of globular proteins, under the conditions at which they crystallise. They found the values to lie within a fairly narrow range. We have defined a simple model of a generic globular protein. We then generate a set of proteins by picking values for the parameters of the model from a probability distribution. At fixed solubility, this set of proteins is found to have values of the second virial coefficient that fall within a fairly narrow range. The shape of the probability distribution of the second virial coefficient is Gaussian because the second virial coefficient is a sum of contributions from different patches on the protein surface.
Richard Sear, M Howard (2006)Modeling dual pathways for the metazoan spindle assembly checkpoint, In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA103(45)pp. 16758-16763 NATL ACAD SCIENCES
Using computational modelling, we investigate mechanisms of signal transduction focusing on the spindle assembly checkpoint where a single unattached kinetochore is able to signal to prevent cell cycle progression. This inhibitory signal switches off rapidly once spindle microtubules have attached to all kinetochores. This requirement tightly constrains the possible mechanisms. Here we investigate two possible mechanisms for spindle checkpoint operation in metazoan cells, both supported by recent experiments. The first involves the free diffusion and sequestration of cell-cycle regulators. This mechanism is severely constrained both by experimental fluorescence recovery data and also by the large volumes involved in open mitosis in metazoan cells. Using a simple mathematical analysis and computer simulation, we find that this mechanism can generate the inhibition found in experiment but likely requires a two stage signal amplification cascade. The second mechanism involves spatial gradients of a short-lived inhibitory signal that propagates first by diffusion but then primarily via active transport along spindle microtubules. We propose that both mechanisms may be operative in the metazoan spindle assembly checkpoint, with either able to trigger anaphase onset even without support from the other pathway.
Mixtures of ideal polymers with hard spheres whose diameters are smaller than the radius of gyration of the polymer, exhibit extensive immiscibility. The interfacial tension between demixed phases of these mixtures is estimated, as is the barrier to nucleation. The barrier is found to scale linearly with the radius of the polymer, causing it to become large for large polymers. Thus for large polymers nucleation is suppressed and phase separation proceeds via spinodal decomposition, as it does in polymer blends.
D Liu, CAC Abdullah, RP Sear, JL Keddie (2010)Cell adhesion on nanopatterned fibronectin substrates, In: SOFT MATTER6(21)pp. 5408-5416 ROYAL SOC CHEMISTRY
The coating of substrates with an extracellular matrix (ECM) protein, such as fibronectin (FN), is often employed to increase cell adhesion and growth. Here, we examine the influence of the size scale and geometry of novel FN nanopatterns on the adhesion and spreading of Chinese Hamster Ovary (CHO) cells. The FN is patterned on the surface of templates created through the self-assembly of polystyrene-block-polyisoprene (PS-b-PI) diblock copolymers. Both ring-like and stripe-like FN nanopatterns are created through the preferential adsorption of FN on PS blocks, as confirmed through the complementary use of atomic force microscopy and secondary ion mass spectrometry. The ring-like FN nanopattern substrate increases the cells' adhesion compared with the cells on homogeneous FN surfaces and the stripe-like FN nanopatterns. Cell adhesion is high when the FN ring size is greater than 50 nm and when the surface coverage of FN is less than ca. 85%. We suggest that the ring-like nanopatterns of FN may be aiding cell adhesion by increasing the clustering of the proteins (integrins) with which cells bind to the nanopatterned substrate. This clustering is required for cell adhesion. In comparison to lithographic techniques, the FN templating method, presented here, provides a simple, convenient and economical way of coating substrates for tissue cultures and should be applicable to tissue engineering.
I Martin-Fabiani, Andrea Fortini, J Lesage de la Haye, ML Koh, Spencer Taylor, E Bourgeat-Lami, M Lansalot, F D’Agosto, Richard Sear, Joseph Keddie (2016)pH-Switchable Stratification of Colloidal Coatings: Surfaces “On Demand”, In: ACS Applied Materials and Interfaces8(50)pp. 34755-34761 American Chemical Society
Stratified coatings are used to provide properties at a surface, such as hardness or refractive index, which are different from underlying layers. Although time-savings are offered by self-assembly approaches, there have been no methods yet reported to offer stratification on demand. Here, we demonstrate a strategy to create self-assembled stratified coatings, which can be switched to homogenous structures when required. We use blends of large and small colloidal polymer particle dispersions in water that self-assemble during drying because of an osmotic pressure gradient that leads to a downward velocity of larger particles. Our confocal fluorescent microscopy images reveal a distinct surface layer created by the small particles. When the pH of the initial dispersion is raised, the hydrophilic shells of the small particles swell substantially, and the stratification is switched off. Brownian dynamics simulations explain the suppression of stratifi-cation when the small particles are swollen as a result of reduced particle mobility, a drop in the pressure gradient, and less time available before particle jamming. Our strategy paves the way for applications in antireflection films and pro-tective coatings in which the required surface composition can be achieved on demand, simply by adjusting the pH prior to deposition.
David Makepeace, Andrea Fortini, A Markov, P Locatelli, C Lindsay, S Moorhouse, R Lind, Richard Sear, Joseph Keddie (2017)Stratification in Binary Colloidal Polymer Films: Experiment and Simulations, In: Soft Matter13pp. 6969-6980 Royal Society of Chemistry
When films are deposited from mixtures of colloidal particles of two different sizes, a diverse range of functional structures can result. One structure of particular interest is a stratified film in which the top surface layer has a composition different than in the interior. Here, we explore the conditions under which a stratified layer of small particles develops spontaneously in a colloidal film that is cast from a binary mixture of small and large polymer particles that are suspended in water. A recent model, which considers the cross-interaction between the large and small particles (Zhou et al., Phys. Rev. Lett. (2017) 118, 108002), predicts that stratification will develop from dilute binary mixtures when the particle size ratio (), initial volume fraction of small particles ( s), and Péclet number are high. In experiments and Langevin dynamics simulations, we systematically vary and s in both dilute and concentrated suspensions. We find that stratified films develop when  s is increased, which is in agreement with the model. In dilute suspensions, there is reasonable agreement between the experiments and the Zhou et al. model. In concentrated suspensions, stratification occurs in experiments only for the higher size ratio  = 7. Simulations using a high Péclet number, additionally find stratification with  = 2, when  s is high enough. Our results provide a quantitative understanding of the conditions under which stratified colloidal films assemble. Our research has relevance for the design of coatings with targeted optical and mechanical properties at their surface.
Colloidal particles are not simple rigid particles, in general an isolated particle is a system with many degrees of freedom in its own right, e.g., the counterions around a charged colloidal particle.The behaviour of model colloidal particles, with a simple phenomenological model to account for these degrees of freedom, is studied. It is found that the interaction between the particles is not pairwise additive. It is even possible that the interaction between a triplet of particles is attractive while the pair interaction is repulsive. When this is so the liquid phase is either stable only in a small region of the phase diagram or absent altogether.
Phase transformations such as freezing typically start with heterogeneous nucleation. Heterogeneous nucleation near a wetting transition, of a crystalline phase is studied. The wetting transition occurs at or near a vapour-liquid transition which occurs in a metastable fluid. The fluid is metastable with respect to crystallisation, and it is the crystallisation of this fluid phase that we are interested in. At a wetting transition a thick layer of a liquid phase forms at a surface in contact with the vapour phase. The crystalline nucleus is then immersed in this liquid layer, which reduces the free energy barrier to nucleation and so dramatically increases the nucleation rate. The variation in the rate of heterogeneous nucleation close to wetting transitions is calculated for systems in which the longest-range forces are dispersion forces.
We study the electrical double layer at the interface between a protein crystal and a salt solution or a dilute solution of protein, and estimate the double layer's contribution to the interfacial tension of this interface. This contribution is negative and decreases in magnitude with increasing salt concentration. We also consider briefly the interaction between a pair of protein surfaces.
RP Sear (2000)Nucleation of a non-critical phase in a fluid near a critical point, In: Journal of Chemical Physics v114pp. 3170-3173
Phase diagrams of some globular proteins have a fluid-fluid transition as well as a fluid-crystal transition. Homogeneous nucleation of the crystal from the fluid phase near the critical point of the fluid-fluid transition is examined. As the fluid-fluid critical point is approached, the number of molecules in the critical nucleus, the nucleus at the top of the free energy barrier to nucleation, is found to diverge as the isothermal compressibility. This divergence is due to a layer of the fluid phase of width equal to the fluid's correlation length which surrounds the core of the nucleus; the number of molecules in a crystalline environment in the nucleus does not diverge. The free energy barrier to nucleation remains finite but its derivative with respect to the chemical potential is equal to minus the number of molecules in the critical nucleus and so diverges.
RP Sear (1997)Theory for polymer coils with necklaces of micelles, In: Journal of Physics:Condensed Matter10(7)pp. 1677-1686 IOP
If many micelles adsorb onto the same polymer molecule then they are said to form a necklace. A minimal model of such a necklace is proposed and shown to be almost equivalent to a 1-dimensional fluid with nearest-neighbour interactions. The thermodynamic functions of this fluid are obtained and then used to predict the change in the critical micellar concentration of the surfactant in the presence of the polymer. If the amount of polymer is not too large there are two critical micellar concentrations, one for micelles in necklaces and one for free micelles.
RP Sear (2005)The cytoplasm of living cells: a functional mixture of thousands of components, In: JOURNAL OF PHYSICS-CONDENSED MATTER17(45)pp. S3587-S3595
RP Sear (2007)Nucleation at contact lines where fluid-fluid interfaces meet solid surfaces, In: JOURNAL OF PHYSICS-CONDENSED MATTER19(46)ARTN 46610 IOP PUBLISHING LTD
F N Braun, S Paulsen, RP Sear, P B Warren (2005)Miscibility Gap in the Microbial Fitness Landscape, In: Physical Review Letters94(17)
It is shown from molecular statistical considerations that a demixing instability exists in the moment space of a microbial protein expression profile. Although avoidance of demixing is generally requisite for biological function, a comparison with proteomic and genomic data suggests that many microbes lie close to the onset of this instability. Over evolutionary time scales, straying too close or into the immiscible domain may be associated with intracellular compartmentalization.
RP Sear (2007)Dishevelled: a protein that functions in living cells by phase separating, In: SOFT MATTER3(6)pp. 680-684 ROYAL SOC CHEMISTRY
Z Tavassoli, RP Sear (2001)Homogeneous nucleation near a second phase transition and Ostwald's step rule, In: J. Chemical Physics116pp. 5066-5072
Homogeneous nucleation of the new phase of one transition near a second phase transition is considered. The system has two phase transitions, we study the nucleation of the new phase of one of these transitions under conditions such that we are near or at the second phase transition. The second transition is an Ising-like transition and lies within the coexistence region of the first transition. It effects the formation of the new phase in two ways. The first is by reducing the nucleation barrier to direct nucleation. The second is by the system undergoing the second transition and transforming to a state in which the barrier to nucleation is greatly reduced. The second way occurs when the barrier to undergoing the second phase transition is less than that of the first phase transition, and is in accordance with Ostwald's rule.
Virginia Apostolopoulou, Niels Junius, Richard P. Sear, Monika Budayova-Spano (2020)Mixing salts and polyethylene glycol into protein solutions: The effects of diffusion across semipermeable membranes and of convection, In: Crystal Growth and Design American Chemical Society
Growing a protein crystal starts by mixing a solution of the protein, with a solution of a precipitant { such as a salt or polyethylene glycol (PEG). Mixing two solutions is a surprisingly complex process, but this complexity has not received much attention by those crystallising proteins, despite crystallisation being notoriously sensitive to solu- tion conditions. We combine experimental data with modelling to improve our ability to predict mixing timescales for conditions typical of protein crystallisation. We look at the effects of convection, and of diffusion through semipermeable membranes. Our experiments are with dialysis chambers, where the crystallisation chamber is separated from a precipitant reservoir by a semipermeable membrane. This membrane slows mixing down by factors that vary from ten for smaller PEG and salts, to a hundred, for dilute larger PEG. This agrees with our model prediction that for larger polymers diffusion through the membrane is sensitive to both molecular weight and concentra- tion. Both salt and PEG solutions are denser than dilute protein solutions, and this drives convection, which accelerates mixing. Convection is ow due to gravity acting on mass density differences. We show how to determine when convection occurs, and how to estimate its effect on mixing times.
RP Sear (2004)A model for the accidental catalysis of protein unfolding in vivo, In: EPL (Europhysics Letters)

Activated processes such as protein unfolding are highly sensitive to heterogeneity in the environment. We study a highly simplified model of a protein in a random heterogeneous environment, a model of the in vivo environment. It is found that if the heterogeneity is sufficiently large, the total rate of the process is essentially a random variable; this may be the cause of the species-to-species variability in the rate of prion protein conversion found by Deleault et al.

RP Sear, I Pagonabarraga, A Flaus (2015)Life at the mesoscale: the self-organised cytoplasm and nucleoplasm, In: BMC BIOPHYSICS8ARTN 4pp. ?-? BIOMED CENTRAL LTD
JP Mithen, RP Sear (2014)Epitaxial nucleation of a crystal on a crystalline surface, In: EPL105(1)
We consider the nucleation of a crystal phase, on a crystalline surface of a different substance. Sixty years ago, Turnbull and Vonnegut predicted that a crystalline surface is best at inducing nucleation of another crystal when there is a perfect epitaxial match between the two bulk lattices. We use computer simulation to show that this is not quite right. In fact, the crystal lattice of a finite nucleus is strained from that in the bulk, and nucleation is fastest when the surface matches this strained lattice. We also find that the approach of Hillier and Ward predicts when nucleation is epitaxial. © Copyright EPLA, 2014.
I Jurewicz, AAK King, P Worajittiphon, P Asanithi, EW Brunner, RP Sear, TJC Hosea, JL Keddie, AB Dalton (2010)Colloid-Assisted Self-Assembly of Robust, Three-Dimensional Networks of Carbon Nanotubes over Large Areas, In: MACROMOLECULAR RAPID COMMUNICATIONS31(7)pp. 609-615 WILEY-V C H VERLAG GMBH
RP Sear (1999)Adsorption of polydisperse polymer chains, In: Journal of Chemical Physics111(5)pp. 2255-2258 AIP
The adsorption of polydisperse ideal polymer chains is shown to be sensitive to the large N tail of the distribution of chains. If and only if the number of chains decays more slowly than exponentially then there is an adsorption transition like that of monodisperse infinite chains. If the number decays exponentially the adsorption density diverges continuously at a temperature which is a function of the mean chain length. At low coverages, chains with repulsive monomer--monomer interactions show the same qualitative behaviour
RP Sear (2004)A statistical theory of nucleation in the presence of uncharacterised impurities, In: Physical Review E v70, 021605 (2004)

First order phase transitions proceed via nucleation. The rate of nucleation varies exponentially with the free-energy barrier to nucleation, and so is highly sensitive to variations in this barrier. In practice, very few systems are absolutely pure, there are typically some impurities present which are rather poorly characterized. These interact with the nucleus, causing the barrier to vary, and so must be taken into account. Here the impurity-nucleus interactions are modelled by random variables. The rate then has the same form as the partition function of Derrida's random energy model, and as in this model there is a regime in which the behavior is non-self-averaging. Non-self-averaging nucleation is nucleation with a rate that varies significantly from one realization of the random variables to another. In experiment this corresponds to variation in the nucleation rate from one sample to another. General analytic expressions are obtained for the crossover from a self-averaging to a non-self-averaging rate of nucleation.

RP Sear, JA Cuesta (2000)What do emulsification failure and Bose-Einstein condensation have in common?, In: Europhys. Lett.55pp. 451-?
Ideal bosons and classical ring polymers formed via self-assembly, are known to have the same partition function, and so analogous phase transitions. In ring polymers, the analogue of Bose-Einstein condensation occurs when a ring polymer of macroscopic size appears. We show that a transition of the same general form occurs within a whole class of systems with self-assembly, and illustrate it with the emulsification failure of a microemulsion phase of water, oil and surfactant. As with Bose-Einstein condensation, the transition occurs even in the absence of interactions.
E Karakosta, PM Jenneson, RP Sear, PJ McDonald (2006)Observations of coarsening of air voids in a polymer-highly-soluble crystalline matrix during dissolution, In: PHYSICAL REVIEW E74(1)ARTN 0pp. ?-? AMERICAN PHYSICAL SOC
Starting from a protein solution which is metastable with respect to the crystalline phase, the effect of adding semidilute non-adsorbing polymer is considered. It is found to increase the chemical potential of the protein by a few tenths of kT, which may be enough to lower the barrier to nucleation of the crystalline phase by enough to allow crystallisation. It is also shown that assuming that the polymer induces a pairwise additive attraction leads to qualitatively incorrect results.

It is well known among molecular biologists that proteins with a common ancestor and that perform the same function in similar organisms, can have rather different amino-acid sequences. Mutations have altered the amino-acid sequences without affecting the function. A simple model of a protein in which the interactions are encoded by sequences of bits is introduced, and used to study how mutations can change these bits, and hence the interactions, while maintaining the stability of the protein solution. This stability is a simple minimal requirement on our model proteins which mimics part of the requirement on a real protein to be functional. The properties of our model protein, such as its second virial coefficient, are found to vary significantly from one model protein to another. It is suggested that this may also be the case for real proteins in vivo.

CA Che Abdullah, P Asanithi, EW Brunner, RP Sear, AB Dalton, C Lewis Azad, R Ovalle-Robles, MD Lima, X Lepro, S Collins, RH Baughman (2010)Cell patterning and alignment on nanostructured isotropic and anisotropic carbon nanotubes substrates, In: European Cells and Materials20(SUPPL.)pp. 39-39
RP Sear (2011)CRYSTAL NUCLEATION In a tight corner, In: NATURE MATERIALS10(11)pp. 809-810 NATURE PUBLISHING GROUP
NE Chayen, E Saridakis, RP Sear (2006)Experiment and theory for heterogeneous nucleation of protein crystals in a porous medium, In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA103(3)pp. 597-601 NATL ACAD SCIENCES
RPL Sear, JP Mithen (2016)A State Between Liquid and Crystal: Locally Crystalline but with the Structure Factor of a Liquid, In: Crystal Growth and Design16(6)pp. 3049-3053 ACS
Using computer simulations, we study a nonequilibrium state with a liquid-like S(k) but where over 95% of the molecules are in locally crystalline environments. Due to its liquid-like S(k) and slow dynamics, the state is apparently amorphous, although it contains nanocrystalline order. This nanocrystalline order can strongly bias the polymorph that forms when the state crystallizes.
RP Sear (2000)Molecular dynamics of a dense fluid of polydisperse hard spheres, In: Journal of Chemical Physics v113pp. p4732-4739
Slow dynamics in a fluid are studied in one of the most basic systems possible: polydisperse hard spheres. Monodisperse hard spheres cannot be studied as the slow down in dynamics as the density is increased is preempted by crystallisation. As the dynamics slow they become more heterogeneous, the spread in the distances traveled by different particles in the same time increases. However, the dynamics appears to be less heterogeneous than in hard-sphere-like colloids at the same volume fraction. The particles which move least far in a characteristic relaxation time and, particularly, the particles which move farthest in the same time are clustered, not randomly distributed throughout the sample. We study the dynamics at three different widths of the distribution of diameters of the hard spheres. For each width, the relaxation time is the same function of the compressibility factor, suggesting that this determines the relaxation time for hard spheres.
The more we learn about the cytoplasm of cells, the more we realise that the cytoplasm is not uniform but instead is highly inhomogeneous. In any inhomogeneous solution, there are concentration gradients, and particles move either up or down these gradients due to a mechanism called diffusiophoresis. I estimate that inside metabolically active cells, the dynamics of particles can be strongly accelerated by diffusiophoresis, provided that they are at least tens of nanometres across. The dynamics of smaller objects, such as single proteins are largely unaffected.
JA van Meel, AJ Page, RP Sear, D Frenkel (2008)Two-step vapor-crystal nucleation close below triple point, In: JOURNAL OF CHEMICAL PHYSICS129(20)ARTN 20450 AMER INST PHYSICS
RP Sear (2008)Nucleation in the presence of slow microscopic dynamics, In: JOURNAL OF CHEMICAL PHYSICS128(21)ARTN 2pp. ?-? AMER INST PHYSICS
RP Sear (2006)On the interpretation of quantitative experimental data on nucleation rates using classical nucleation theory, In: JOURNAL OF PHYSICAL CHEMISTRY B110(43)pp. 21944-21949 AMER CHEMICAL SOC
RP Sear (2006)Heterogeneous and homogeneous nucleation compared: Rapid nucleation on microscopic impurities, In: JOURNAL OF PHYSICAL CHEMISTRY B110(10)pp. 4985-4989 AMER CHEMICAL SOC
FC Meldrum, RP Sear (2008)MATERIALS SCIENCE Now You See Them, In: SCIENCE322(5909)pp. 1802-1803 AMER ASSOC ADVANCEMENT SCIENCE
Laurie Little, Alice A. K. King, Richard Sear, Joseph Keddie (2017)Controlling the crystal polymorph by exploiting the time dependence of nucleation rates, In: Journal of Chemical Physics147(14) AIP Publishing
Most substances can crystallise into two or more different crystal lattices, called polymorphs. Despite this, there are no systems in which we can quantitatively predict the probability of one competing polymorph forming, instead of the other. We address this problem using large scale (hundreds of events) studies of the competing nucleation of the alpha and gamma polymorphs of glycine. In situ Raman spectroscopy is used to identify the polymorph of each crystal. We find that the nucleation kinetics of the two polymorphs is very different. Nucleation of the alpha polymorph starts off slowly but accelerates, while nucleation of the gamma polymorph starts off fast but then slows. We exploit this difference to increase the purity with which we obtain the gamma polymorph by a factor of ten. The statistics of the nucleation of crystals is analogous to that human mortality, and using a result from medical statistics we show that conventional nucleation data can say nothing about what, if any, are the correlations between competing nucleation processes. Thus we can show that it is impossible to disentangle the competing nucleation processes. We also find that the growth rate and the shape of a crystal depends on when it nucleated. This is new evidence that nucleation and growth are linked.
BS Khatri, TCB McLeish, RP Sear (2009)Statistical mechanics of convergent evolution in spatial patterning, In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA106(24)pp. 9564-9569 NATL ACAD SCIENCES
RP Sear (2008)Continuity of the nucleation of bulk and surface phases, In: JOURNAL OF CHEMICAL PHYSICS129(16)ARTN 1pp. ?-? AMER INST PHYSICS
RP Sear (2008)Phase separation of equilibrium polymers of proteins in living cells, In: FARADAY DISCUSSIONS139pp. 21-34 ROYAL SOC CHEMISTRY
JP Mithen, AJ Callison, RP Sear (2015)Nucleation of crystals that are mixed composites of all three polymorphs in the Gaussian core model, In: JOURNAL OF CHEMICAL PHYSICS142(22)ARTN 2pp. ?-? AMER INST PHYSICS
RP Sear (1997)Scattering from small colloidal particles in a semidilute polymer solution, In: European Physical Journal B v1pp. 313-317
The correlations between the segments of a semidilute polymer solution are found to induce correlations in the positions of small particles added to the solution. Small means a diameter much less than the polymer's correlation length. In the presence of polymer the particles behave as if they attracted each other. It is shown how the polymer's correlation length may be determined from a scattering experiment performed on the spheres.
Silvia Nalesso, Madeleine J Bussemaker, Richard P Sear, Mark Hodnett, Judy Lee (2018)Development of sodium chloride crystal size during antisolvent crystallization under different sonication modes, In: Crystal Growth & Design19(1)pp. 141-149 American Chemical Society
This paper reports for the first time the development in the size and shape of sodium chloride crystals during the anti-solvent crystallization in ethanol under different sonication modes. Sonication using 98 kHz and calorimetric power of 6 W was applied either continuously for a range of crystallisation times (5 – 90 s) or intermittently (5 s pulse). Under silent conditions, crystallization time of 90 s generated crystals with an average size of 73.8 ± 6.9 μm, compared to 8.7 ± 2.8 μm under 90 s of continuous sonication. However, it was observed that within the first 5 s of sonication at the beginning of the crystallization, the average crystal size was already reduced to 7.0 ± 3.3 μm. If the system was left to crystallise further to 90 s without ultrasound, the crystal size grew only slightly to 8.2 ± 1.4 μm. When 5 s burst of ultrasound was applied during the crystallization process, a bimodal distribution of small (from sonication) and large crystals (from the silent period) was obtained. These results imply that the major influence of sonication is crystal nucleation rather than fragmentation, and equilibrium is reached with 5 s sonication by precipitating most of the crystals in solution.
AJ Page, RP Sear (2009)Crystallization Controlled by the Geometry of a Surface, In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY131(48)pp. 17550-17551 AMER CHEMICAL SOC
Ioatzin Rios de Anda, Francesco Turci, Richard Sear, Patrick Royall (2017)Long-Lived Non-Equilibrium Interstitial-Solid-Solutions in Binary Mixtures, In: Journal of Chemical Physics147 AIP Publishing
We perform particle resolved experimental studies on the heterogeneous crystallisation process of two component mixtures of hard spheres. The components have a size ratio of 0.39. We compared these with molecular dynamics simulations of homogenous nucleation. We find for both experiments and simulations that the final assemblies are interstitial solid solutions, where the large particles form crystalline close-packed lattices, whereas the small particles occupy random interstitial sites. This interstitial solution resembles that found at equilibrium when the size ratios are 0.3 [Filion et al., Phys. Rev. Lett. 107, 168302 (2011)] and 0.4 [Filion, PhD Thesis, Utrecht University (2011)]. However, unlike these previous studies, for our system simulations showed that the small particles are trapped in the octahedral holes of the ordered structure formed by the large particles, leading to long-lived non-equilibrium structures in the time scales studied and not the equilibrium interstitial solutions found earlier. Interestingly, the percentage of small particles in the crystal formed by the large ones rapidly reaches a maximum of 14% for most of the packing fractions tested, unlike previous predictions where the occupancy of the interstitial sites increases with the system concentration. Finally, no further hopping of the small particles was observed.
Classical nucleation theory is used to estimate the free-energy barrier to nucleation of the solid phase of particles interacting via a potential which has a short-ranged attraction. Due to the high interfacial tension between the fluid and solid phases, this barrier is very large, much larger than in hard spheres. It is divergent in the limit that the range of the attraction tends to zero. We predict an upper limit on nucleation in good agreement with the results of experiments on the crystallisation of proteins.
A Utgenannt, Ross Maspero, Andrea Fortini, R Turner, Marian Florescu, Christopher Jeynes, AG Kanaras, OL Muskens, Richard Sear, Joseph Keddie (2016)Fast Assembly of Gold Nanoparticles in Large-Area 2-D Nanogrids Using a One-Step, Near-Infrared Radiation-Assisted Evaporation Process, In: ACS Nano10(2)pp. 2232-2242 American Chemical Society
When fabricating photonic crystals from suspensions in volatile liquids using the horizontal deposition method, the conventional approach is to evaporate slowly to increase the time for particles to settle in an ordered, periodic close-packed structure. Here, we show that the greatest ordering of 10 nm aqueous gold nanoparticles (AuNPs) in a template of larger spherical polymer particles (mean diameter of 338 nm) is achieved with very fast water evaporation rates obtained with near-infrared radiative heating. Fabrication of arrays over areas of a few cm2 takes only seven minutes. The assembly process requires that the evaporation rate is fast relative to the particles’ Brownian diffusion. Then a two-dimensional colloidal crystal forms at the falling surface, which acts as a sieve through which the AuNPs pass, according to our Langevin dynamics computer simulations. With sufficiently fast evaporation rates, we create a hybrid structure consisting of a two-dimensional AuNP nanoarray (or “nanogrid”) on top of a three-dimensional polymer opal. The process is simple, fast and one-step. The interplay between the optical response of the plasmonic Au nanoarray and the microstructuring of the photonic opal results in unusual optical spectra with two extinction peaks, which are analyzed via finite-difference time-domain method simulations. Comparison between experimental and modelling results reveals a strong interplay of plasmonic modes and collective photonic effects, including the formation of a high-order stop band and slow-light enhanced plasmonic absorption. The structures, and hence their optical signatures, are tuned by adjusting the evaporation rate via the infrared power density.
Biominerals are typically composites of hard matter such as calcite, and soft matter such as proteins. There is currently considerable interest in how the soft matter component is incorporated into the hard matter component. This would typically be a protein that does not fold up into a single rigid domain but is closer to a simple polymer, being incorporated into a growing inorganic crystal in aqueous solution. Here I use computer simulation to study a very simple (2D lattice gas) model of a growing phase and a polymer. This allows me to study the microscopic dynamics of incorporation or rejection of a single polymer by the growing phase. It also allows me to look at how high concentrations of absorbing polymer can both arrest crystal growth, and change the shape of crystals. I find that the incorporation of a single polymer into the growing phase is due to slow dynamics of the polymer at the growth front. These slow dynamics are then unable to keep up with the advancing growth front. This is an intrinsically far-from-equilibrium process and so occurs even when incorporation is thermodynamically highly unfavourable. During the incorporation process, large polymers create large and deep, but transient, pits in the growth front. © The Royal Society of Chemistry 2012.
Véronique Dehan, Elodie Bourgeat-Lami, Franck D'Agosto, Brendan Duffy, Andrea Fortini, Sharon Hilton, Kalliopi Krassa, Joseph Keddie, Ming L. Koh, Muriel Lansalot, Michelle Lee, Jennifer Lesage de la Haye, Ignacio Martin-Fabiani, Christos Mantzaridis, Douglas P. Mazeffa, Richard Sear, Malin Schulz, Morgan Sibbald, Brian Skerry, Brett Thomas (2017)High-performance water-based barrier coatings for the corrosion protection of structural steel, In: Steel Construction10(3)pp. 254-259 Ernst und Sohn
This article provides an overview of the outcomes of a European-funded project called BarrierPlus. A new type of water-based barrier coating was developed for structural steel applications. The advantages of this coating include enhanced moisture resistance, low volatile organic compounds (VOCs) and one-component self-crosslinking free of isocyanates. To enable this performance, a latex polymer binder was uniquely designed without using soap-like molecules, known as surfactants, to form the dispersion. By minimizing surfactants in the coating, the barrier properties were significantly enhanced. The latex was successfully scaled up to 15 kg quantities by an SME, coating formulations were scaled to pilot quantities and a variety of characterization and coating performance tests were completed. A life cycle assessment found that the BarrierPlus coating has a better environmental profile than an industry benchmark solvent-borne coating and showed promising results relative to commercial waterborne benchmarks.
JP Mithen, RP Sear (2014)Computer simulation of epitaxial nucleation of a crystal on a crystalline surface, In: JOURNAL OF CHEMICAL PHYSICS140(8)ARTN 0pp. ?-? AMER INST PHYSICS
RP Sear (1999)Fluid-fluid transitions of hard spheres with a very short-range attraction, In: Physical Review E v61pp. p6019-6022
Hard spheres with an attraction of range a tenth to a hundredth of the sphere diameter are constrained to remain fluid even at densities when monodisperse particles at equilibrium would have crystallised, in order to compare with experimental systems which remain fluid. They are found to have a fluid-fluid transition at high density. As the range of the attraction tends to zero, the density at the critical point tends towards the random-close-packing density of hard spheres.
RP Sear (1999)Absence of the liquid phase when the attraction is not pairwise additive, In: Physical Review E61pp. p651-655
Recent work on charged colloidal suspensions with very low levels of added salt has suggested that although pairs of the colloidal particles repel, clusters of the particles attract. Motivated by this, we study simple model particles which have many-body attractions. These attractions are generic many-body attractions and are not calculated for any specific colloidal suspension. We find that many-body attractions can stabilise solid phases at low pressures but that the liquid phase is either completely absent from the equilibrium phase diagram or present only within a small region of parameter space
RP Sear (2009)Nucleation via an unstable intermediate phase, In: JOURNAL OF CHEMICAL PHYSICS131(7)ARTN 0pp. ?-? AMER INST PHYSICS
JA van Meel, RP Sear, D Frenkel (2010)Design Principles for Broad-Spectrum Protein-Crystal Nucleants with Nanoscale Pits, In: PHYSICAL REVIEW LETTERS105(20)ARTN 2pp. ?-? AMER PHYSICAL SOC
CA Abdullah, P Asanithi, EW Brunner, I Jurewicz, C Bo, CL Azad, R Ovalle-Robles, S Fang, MD Lima, X Lepro, S Collins, RH Baughman, RP Sear, AB Dalton (2011)Aligned, isotropic and patterned carbon nanotube substrates that control the growth and alignment of Chinese hamster ovary cells., In: Nanotechnology22(20)pp. 205102-? Institute of Physics
Here we culture Chinese hamster ovary cells on isotropic, aligned and patterned substrates based on multiwall carbon nanotubes. The nanotubes provide the substrate with nanoscale topography. The cells adhere to and grow on all substrates, and on the aligned substrate, the cells align strongly with the axis of the bundles of the multiwall nanotubes. This control over cell alignment is required for tissue engineering; almost all tissues consist of oriented cells. The aligned substrates are made using straightforward physical chemistry techniques from forests of multiwall nanotubes; no lithography is required to make inexpensive large-scale substrates with highly aligned nanoscale grooves. Interestingly, although the cells strongly align with the nanoscale grooves, only a few also elongate along this axis: alignment of the cells does not require a pronounced change in morphology of the cell. We also pattern the nanotube bundles over length scales comparable to the cell size and show that the cells follow this pattern.
Richard Sear (2014)Nucleation of a new phase on a surface that is changing irreversibly with time, In: Physical Review E: Statistical, Nonlinear, and Soft Matter Physics89 American Physical Society
Nucleation of a new phase almost always starts at a surface. This surface is almost always assumed not to change with time. However, surfaces can roughen, partially dissolve and change chemically with time. Each of these irreversible changes will change the nucleation rate at the surface, resulting in a time-dependent nucleation rate. Here we use a simple model to show that partial surface dissolution can qualitatively change the nucleation process, in a way that is testable in experiment. The changing surface means that the nucleation rate is increasing with time. There is an initial period during which no nucleation occurs, followed by relatively rapid nucleation.
F Bajanca, V Gonzalez-Perez, SJ Gillespie, C Beley, L Garcia, E Theveneau, RP Sear, SM Hughes (2015)In vivo dynamics of skeletal muscle Dystrophin in zebrafish embryos revealed by improved FRAP analysis, In: ELIFE4ARTN e ELIFE SCIENCES PUBLICATIONS LTD
Dystrophin forms an essential link between sarcolemma and cytoskeleton, perturbation of which causes muscular dystrophy. We analysed Dystrophin binding dynamics in vivo for the first time. Within maturing fibres of host zebrafish embryos, our analysis reveals a pool of diffusible Dystrophin and complexes bound at the fibre membrane. Combining modelling, an improved FRAP methodology and direct semi-quantitative analysis of bleaching suggests the existence of two membrane-bound Dystrophin populations with widely differing bound lifetimes: a stable, tightly bound pool, and a dynamic bound pool with high turnover rate that exchanges with the cytoplasmic pool. The three populations were found consistently in human and zebrafish Dystrophins overexpressed in wild-type or dmdta222a/ta222a zebrafish embryos, which lack Dystrophin, and in Gt (dmd-Citrine)ct90a that express endogenously-driven tagged zebrafish Dystrophin. These results lead to a new model for Dystrophin membrane association in developing muscle, and highlight our methodology as a valuable strategy for in vivo analysis of complex protein dynamics
AJ Page, RP Sear (2006)Heterogeneous nucleation in and out of pores, In: PHYSICAL REVIEW LETTERS97(6)ARTN 0pp. ?-? AMERICAN PHYSICAL SOC
A Fortini, Richard Sear (2017)Stratification and Size Segregation of Ternary and Polydisperse Colloidal Suspensions during Drying, In: LANGMUIR33(19)pp. 4796-4805 American Chemical Society
We investigate the drying process of three-component and polydisperse colloidal suspensions using Brownian dynamics simulations. We have previously reported (Phys. Rev. Lett. 2016, 116, 118301) on the drying of binary mixtures. For binary mixtures, we found that a gradient of colloidal osmotic pressure develops during drying and that this leads to the final film being stratified with a layer of smaller particles on top of a layer of larger particles. Here, we find that stratification by size is very general and also occurs in ternary and polydisperse mixtures. We name the segregation effect colloidal diffusiophoresis. In particular, we show that by changing the composition of a ternary mixture, different stratification morphologies can be achieved and hence the film properties can be tuned. In polydisperse spheres, colloidal diffusiophoresis leads to enrichment in the large particles at the bottom part of the film, whereas the top part is enriched with smaller particles. This segregation means that in the final film, the particle size distribution depends on height. Thus, the properties of the film will then depend on height. We propose a model that predicts a power-law dependence of the phoretic velocity on particle size. Results from the model and simulation show a good agreement
RP Sear (1999)Phase behaviour of a simple model of globular proteins, In: Journal of Chemical Physics v111pp. p4800-4806
A simple model of globular proteins which incorporates anisotropic attractions is proposed. It is closely related to models used to model simple hydrogen-bonding molecules such as water. Theories for both the fluid and solid phases are presented, and phase diagrams calculated. The model protein exhibits a fluid-fluid transition which is metastable with respect to the fluid-solid transition for most values of the model parameters. This is behaviour often observed for globular proteins. The model offers an explanation of the difficulty observed in crystallising some globular proteins and suggests that some proteins may not have a solid phase at all under all but extreme conditions.
RP Sear (2008)Nucleation of a liquid on aerosol nanoparticles, In: EPL-EUROPHYS LETT83(6)66002pp. 1-6 EDP SCIENCES
Nucleation of liquid water in the Earth’s atmosphere occurs via heterogeneous nucleation on aerosol particles. We consider nucleation on both water-insoluble and water-soluble aerosol particles. We find that, for particles of the same radius, nucleation on soluble particles dominates. Soluble particles dissolve in the liquid phase and form a droplet even at coexistence. The radius of this droplet essentially determines the supersaturation at which nucleation occurs: the larger the droplet the smaller the supersaturation required before it nucleates to form the bulk liquid. We find that the supersaturation is best measured by the Kelvin radius, which is the radius of a droplet of pure liquid that coexists with vapour of a given supersaturation. We show that nucleation occurs at a universal value of the ratio between the radius of the droplet at coexistence and the Kelvin radius.
Crystal polymorphism, where a molecule forms several different crystal lattices, is common, and often needs to be controlled. For example, crystalline drugs must be manufactured as one specified polymorph, so polymorph purity is essential to the pharmaceutical industry. This thesis is a quantitative study of the crystallization of glycine from aqueous solution, which focuses particularly on polymorphism. Crystallization is observed within a 96-well microplate, where each well is filled with 0.1 mL of supersaturated solution. We address the difficulty of obtaining reproducible nucleation data. This problem is difficult because induction times are extremely sensitive to factors such as how the crystallizing system is prepared, and small variations in the supersaturation. The appropriate statistical tests needed to show reproducibility are discussed. Glycine has two common polymorphs, alpha and gamma, the competition between these polymorphs is studied. We obtain data at multiple NaCl concentrations. Addition of NaCl is known to favour nucleation of the gamma polymorph. The polymorph of crystals are individually identified in-situ using Raman spectroscopy. At high salt concentrations, nucleation kinetics of the alpha and gamma polymorphs are qualitatively different. The gamma polymorph behaves like the hare in Aesop's story of the tortoise and the hare: Nucleation start off rapidly, but slows, while for the alpha polymorph, nucleation starts off slow but at later times almost overtakes that of the gamma polymorph. The opposite time dependencies of the nucleation of the competing polymorphs, allows optimisation of polymorph purity using time-dependent supersaturation. Growth of the two polymorphs is analysed. The alpha polymorph is observed to grow faster than the gamma polymorph. Growth rates were variable, so they were also analysed in relation to induction times and crystal habits. We show that crystals with long induction times tend to be needle-like, and needle-like morphologies tend to grow faster than non needle-like morphologies.