CRYSTALGROWER - A NEW APPROACH TO UNDERSTANDING AND PREDICTING CRYSTAL GROWTH

这个阿斯利康资助的案例研究项目将涉及将CrystalGrower方法应用于制药行业和阿斯利康特别感兴趣的问题。这将涉及：i）使用我们的原子力显微镜技术对晶体表面形貌进行实验测量，该技术专门用于观察生长和溶解条件下的微米级晶体; ii）应用CrystalGrower软件模拟晶体习性和表面形貌，以提取基本生长过程的自由能结晶iii）开发CrystalGrower计算机软件，以解决特定感兴趣的问题。第（iii）部分将包括发展，如处理竞争性多晶型物的成核，但也将包括“理解和建模为什么结晶有时不能去除杂质”，这是AZ职权范围内确定的目标之一。这不是目前包括的内容，而是我们在《自然》杂志上概述的生长调节剂效应的CrystalGrower方法的延伸。该学习计划将为学生提供结晶科学的广泛基础。这将包括晶体生产的实验方法，电子显微镜和X射线衍射的所有基本表征。学生将成为使用原位原子力显微镜研究晶体生长和溶解的专家。鼓励学生参与CrystalGrower软件的开发，培养编码技能。学生将利用CrystalGrower软件，从而获得晶体生长机制的详细纳米视图，以及如何改变实验参数以影响：晶体习性，晶体尺寸，杂质的夹杂物或其他;缺陷和共生体的发展;多晶型之间的竞争。这种学生奖学金的及时性不能与最近披露的这种新方法更相关的方法晶体生长目前，我们与澳大利亚科廷大学（Julian Gale）的合作伙伴在分子动力学和从头算路线上开展合作，以了解晶体生长机理途径;与俄罗斯萨马拉大学（Vladislav Blatov）合作，为CrystalGrower输入生成数学晶体网络;与STFC、达雷斯伯里（Chris Morris）合作，开发超级计算设施和代码优化。学生将与所有这些世界级的团体进行互动，这将为晶体生长模拟的各个方面提供良好的基础。工作将在最高级别的期刊上发表，如Nature，Science，Journal of the American Chemical Society，Angewande Chemie等。

The program of study for this AstraZeneca funded CASE studentship would involve applying the CrystalGrower methodology to problems of specific interest to the pharmaceuticals industry and AstraZeneca in particular. This will involve: i) experimental measurements of crystal surface topography using our Atomic Force Microscopy techniques which are specifically designed to observing micron-sized crystals under growth and dissolution conditions; ii) application of the CrystalGrower software to simulate crystal habit and surface topography to extract free energies crystallisation for fundamental growth processes iii) developments of the CrystalGrower computer software to address problems of specific interest. Part (iii) will include developments such as treating the nucleation of competing polymorphs but will also include "understanding and modelling why crystallisation sometimes fails to remove impurities" which is one of the targets identified in the AZ remit. This is not something that is included at present but would be an extension of the CrystalGrower approach to the effect of growth modifiers outlined in our Nature publication.The program of study will give the student a wide-ranging grounding in the science of crystallisation. This will include experimental methods of crystal production, all the basic characterisation of electron microscopy and x-ray diffraction. The student will become an expert in the use of in situ atomic force microscopy for the study of crystal growth and dissolution. The student will be encouraged to be involved in the development of the CrystalGrower software, developing coding skills. The student will utilise the CrystalGrower software, thereby obtaining a detailed nanoscopic view of the mechanism of crystal growth and how the experimental parameters may be altered to affect: crystal habit, crystal size, inclusion or otherwise of impurities; development of defects and intergrowths; competition between polymorphs.The timeliness of this studentship could not be more pertinent with the recent disclosure of this new methodology to approach crystal growth. We currently work together with partners in Curtin University, Australia (Julian Gale) on molecular dynamics and ab initio routes to understand crystal growth mechanistic pathways; Samara University, Russia (Vladislav Blatov) to produce mathematical crystal networks for the CrystalGrower input; STFC, Daresbury (Chris Morris) on super-computing facilities and code optimisation. The student would have interactions with all these world-class groups that will give an excellent grounding in all aspects of crystal growth simulation.The work will be publishable in the highest ranking journals such as Nature, Science, Journal of the American Chemical Society, Angewande Chemie etc.