CRYSTALGROWER - A NEW APPROACH TO UNDERSTANDING AND PREDICTING CRYSTAL GROWTH

阿斯利康资助的这一案例学生的研究计划将涉及将CrystalGrower方法应用于制药业特别是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，这是专门为在生长和溶解条件下观察微米级晶体而设计的；ii)应用CrystalGrower软件来模拟晶体习性和表面形貌，以提取基本生长过程中的自由能结晶；iii)开发CrystalGrower计算机软件，以解决特别感兴趣的问题。(Iii)部分将包括诸如处理相互竞争的多晶型成核的进展，但也将包括“理解和模拟为什么结晶有时不能去除杂质”，这是AZ职权范围中确定的目标之一。这是目前还没有包括的内容，但将是晶体生长器方法的扩展，该方法在我们的自然杂志上概述了生长调节剂的影响。学习计划将使学生在结晶科学方面有广泛的基础。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特征。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。学生将被鼓励参与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角，以及如何改变实验参数以影响：晶体习性、晶体尺寸、杂质的夹杂或其他；缺陷和相互生长的发展；多晶型之间的竞争。本课程的及时性与最近披露的这一新方法相关联。我们目前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方法方面开展合作，以了解晶体生长机制路径；俄罗斯萨马拉大学(弗拉迪斯拉夫·布拉托夫)为CrystalGrower输入生成数学晶体网络；STFC、Daresbury(Chris Morris)在超级计算设施和代码优化方面进行合作。这名学生将与所有这些世界级团体进行互动，这将为晶体生长模拟的各个方面奠定良好的基础。这项工作将发表在最高级别的期刊上，如《自然》、《科学》、《美国化学学会杂志》、《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.