Cai Y. Ma

Multi-dimensional population balance modeling of the growth of rod-like L-glutamic acid crystals using growth rates estimated from in-process imaging

Abstract —Traditionally, population balance (PB) modeling of crystal growthin crystallizers has been based on a single scalar parameter for particle size, typically the volume equivalent diameter. This misses important information about particle shape, especially for crystals of high aspect ratios. In recent years attempts have been made to extend PB to two or more size dimensions by taking into consideration of the crystal shape. A key step in multi-dimensional PB (M-PB) modeling is the estimation of the growth rates of individual faces as a function of temporal operating conditions, e.g. the supersaturation. In this paper, we propose to carry out M-PB modeling based on real-time experimentally derived growth rates for different faces using in-process imaging and image analysis. Results are presented for the seeded cooling crystallisation of rod-like β-form L-glutamic acid in a 0.5-l batch reactor.

Nano(Q)SAR: Challenges, pitfalls and perspectives

Abstract Regulation for nanomaterials is urgently needed, and the drive to adopt an intelligent testing strategy is evident. Such a strategy will not only provide economic benefits but will also reduce moral and ethical concerns arising from animal testing. For regulatory purposes, such an approach is promoted by REACH, particularly the use of quantitative structure–activity relationships [(Q)SAR] as a tool for the categorisation of compounds according to their physicochemical and toxicological properties. In addition to compounds, (Q)SAR has also been applied to nanomaterials in the form of nano(Q)SAR. Although (Q)SAR in chemicals is well established, nano(Q)SAR is still in early stages of development and its successful uptake is far from reality. This article aims to identify some of the pitfalls and challenges associated with nano-(Q)SARs in relation to the categorisation of nanomaterials. Our findings show clear gaps in the research framework that must be addressed if we are to have reliable predictions from such models. Three major barriers were identified: the need to improve quality of experimental data in which the models are developed from, the need to have practical guidelines for the development of the nano(Q)SAR models and the need to standardise and harmonise activities for the purpose of regulation. Of these three, the first, i.e. the need to improve data quality requires immediate attention, as it underpins activities associated with the latter two. It should be noted that the usefulness of data in the context of nano-(Q)SAR modelling is not only about the quantity of data but also about the quality, consistency and accessibility of those data.

Effect of seed loading and cooling rate on crystal size and shape distributions in protein crystallization—A study using morphological population balance simulation

Abstract A morphological population balance model is applied to crystallization of hen-egg white lysozyme for investigation of the effect of seed loading and cooling rate on supersaturation, and crystal size and shape distributions. Growth rates of individual faces and final crystal size and shape distributions were examined under varied seeding and cooling conditions. It was found that for growth only crystallization, desired crystal size and shape can be obtained by coordinative manipulation of the seed loading and cooling rate: low seed loading and high cooling rate lead to large crystals of low aspect ratio, but care has to be taken to avoid nucleation and major shape change such as width becoming larger than the length. The interesting results not only demonstrate the effectiveness of morphological population balance simulation for protein crystallization but also provide useful knowledge for process optimization and control.

Prediction of lifted, non-premixed turbulent flames using a mixedness-reactedness flamelet model with radiation heat loss

The laminar flamelet approach is frequently applied to model turbulent non-premixed flames based on the assumption of adiabatic combustion. This generally results in the significant overprediction of temperatures for flames where thermal radiation is important. In the present study, an adiabatic, mixedness-reactedness flamelet combustion model has been extended to incorporate the effect of radiation heat transfer using the concept of enthalpy defect. This requires the generation of flamelet data sets using a detailed chemical kinetic mechanism and introduction of enthalpy defect as an additional flamelet parameter. The methodology developed has been applied to simulate lifted, free, turbulent non-premixed natural gas flames for which measurements are reported in the literature. A non-adiabatic flamelet data library for methane-air flames has been generated with the GRI reaction mechanism using the modified CHEMKIN code for the modeling of turbulent radiating flames. The turbulent flame computational results, with and without radiation heat transfer, are compared with experimental data for mean gas temperatures, species concentrations and flame lift-off heights for a number of laboratory- and large-scale lifted turbulent jet flames. Predictions obtained using the non-adiabatic flamelet model are found to be in good agreement with temperature measurements, whereas the original adiabatic model significantly overestimates temperatures in the downstream regions of flames where significant heat loss occurs. Species concentration and lift-off height results show small differences between predictions with and without radiation losses in regions close to the base of the flame, although both methodologies provide satisfactory agreement with the available data.

On-line measurement of the real size and shape of crystals in stirred tank crystalliser using non-invasive stereo vision imaging

Non-invasive stereo vision imaging technique was applied to monitoring a cooling crystallisation process in a stirred tank for real-time characterisation of the size and shape of needle-like l-glutamic acid (L-GA) β polymorphic crystals grown from solution. The instrument consists of two cameras arranged in an optimum angle that take 2D images simultaneously and are synchronised with the lighting system. Each 2D image pair is processed and analysed and then used to reconstruct the 3D shape of the crystal. The needle shaped L-GA β form crystal length thus obtained is found to be in good agreement with the result obtained from off-line analysis of crystal samples, and is about three times larger than that estimated using 2D imaging technique. The result demonstrates the advantage of 3D imaging over 2D in measurement of crystal real size and shape.

Population Balance Modelling and Experimental Validation for Synthesis of TiO2 Nanoparticles Using Continuous Hydrothermal Process

Population balance (PB) modelling is investigated as a tool to study hydrothermal synthesis (CHS) technique for nanomaterial formulation. In particular, the effects of solution concentration and reactor residence time on the particle size distribution were examined. For the purpose of model validation, the simulated results were compared with data obtained from experiments conducted using a continuous stirred tank reactor for production of nanosize TiO2 particles. Product composition was analysed using Fourier transform infrared spectroscopy, and particle size was characterised scanning electron microscopy, zetasizer and image analysis. Good agreement between experimental and simulation results was achieved.

Morphological Population Balance Models for the Dynamic Evolution of Particle Shape and Size Distribution in Protein Crystallization

Abstract Protein crystallization is known to be affected by many factors and inherently difficult to control. Being able to model the crystal growth, especially at process scale for the population of particles in a reactor rather than for a single particle, will no doubt greatly help the formulation and manufacture of protein crystals. In this paper, a morphological population balance model is presented which has incorporated the crystal shape information into the population balance process model therefore is able to simultaneously simulate the dynamic evolution of shape as well as size for crystals of tetragonal Hen-Egg-White (HEW) lysozyme within a crystallizer. Morphological population balance models require growth kinetics data for each facet, which was obtained from published data in literature for the two identified independent crystallographic faces, {101} and {110}, of HEW lysozyme.

Mathematical modelling of nitric oxide formation in turbulent diffusion flames doped with a nitrogen compound

A numerical study has been effected to investigate nitric oxide (NO) formation in large-scale gas-oil spray flames doped with a nitrogen compound to simulate fuel-nitrogen. The mathematical model for aerodynamic/combustion incorporates a Reynolds-stress model for turbulence and an eddy-dissipalion model (Magnussen and Hjertager, 1978) for combustion. NO predictions are obtained using the Zeldovich mechanism for thermal-NO with two variants for the calculation of oxygen-atom concentration, and the kinetic rate expressions of De Soete (1975) for the formation of prompt- and fuel-NO. The effect of turbulence/chemistry interactions on NO formation rates is represented by a single variable beta probability density function. Predictions are compared with detailed in-flame and flue-gas data obtained in previous studies for different levels of doping with quinoline while maintaining the same flame conditions. These data allowed contributions of thermal- and fuel-NO to the total NO emissions to be estimated with a reasonable degree of accuracy. The predicted and measured gas temperature and major species concentrations are generally in good agreement though discrepancies exist in the shear layers near the burner. Validation of the NO post-processor against experimental data for different fuel-nitrogen doping levels has revealed good qualitative predictions and, in most cases, good quantitative agreements. The contributions of individual NO formation mechanisms to the total NO emissions are well simulated by the NO model.

Development of a stereo imaging system for three-dimensional shape measurement of crystals

Despite the availability of various Process Analytical Technologies (PAT) for measuring other particle properties, their inherit limitations for the measurement of crystal shape have been restricted. This has impacted, in turn, on the development and implementation of optimisation, monitoring and control of crystal shape and size distributions within particle formulation and processing systems In recent years, imaging systems have shown to be a very promising PAT technique for the measurement of crystal growth, but still essentially limited as a technique only to provide two-dimensional information. The idea of using two synchronized cameras to obtain 3D crystal shape was mentioned previously (Chem Eng Sci 63(5) 1171-1184, 2008) but no quantitative results were reported. In this paper, a methodology which can directly image the full three-dimensional shape of crystals has been developed. It is based on the mathematical principle that if the two-dimensional images of an object are obtained from two different angles, the full three-dimensional crystal shape can be reconstructed. A proof of concept study has been carried out to demonstrate the potentials in using the system for the three-dimensional measurement of crystals.

Modelling and Simulation of Counter-Current and Confined Jet Reactors for Continuous Hydrothermal Flow Synthesis of Nano-Materials

Abstract Computational fluid dynamics is applied to a comparative study of a counter-current reactor and a confined jet reactor for continuous hydrothermal flow synthesis of nanomaterials under supercritical water conditions. The fluid flow and heat transfer variables including velocity and temperature profiles in both reactor configurations are simulated using ANSYS Fluent package. The tracer concentration profiles are also modelled via solving species equations from which the mixing behaviour in the reactors is investigated. The predicted temperatures are found to be in good agreement with experimental data. The simulation also provides suggestions to improving the reactor designs and process control.