Continuous Flow for Materials Synthesis, Assembly & Crystallisation at Diamond: Discovery & Delivery of High Value Materials

该项目的第一阶段将包括开发和安装一个缩小版的动态调节自动输入结晶器设备。最初的实验工作将针对Diamond的I11光束线上多晶分子材料的流动结晶，而作为KRAIC设计开发的一部分，适应替代光束线的即时需求也将被考虑在内。分段流，在KRAIC装置中实现，本质上是在稳定状态下运行，确保所有反应物在整个反应器中经历相同的条件。这意味着对于反应器长度的任何一点，每个经过的段塞都处于相同的反应/结晶阶段，从而可以深入研究瞬态事件，如多态转变。为了开发最初的KRAIC设备概念，双方与利兹大学的Kapur和Meldrum团队合作，他们率先使用具有ESRF和Diamond经验的微流控设备进行原位功率x射线衍射分析。在分段流动环境中，结晶溶液的每个液滴都很小，流速也很小，这意味着不可能用人工衍射仪在现场观察结晶；这将通过使用金刚石光束线上可用的高通量来克服。由该大学与利兹大学合作建造的KRAIC设备中尺度分段流结晶器将安装在Diamond的I11光束线上，其中包含可通过垂直对齐移动舞台进入的观察窗口。目标多晶共晶系统尿素：巴比妥酸的冷却结晶将使用加热的进料容器和绝缘线圈支架进行。甲醇溶液的分割是通过添加惰性载液（PFPE）和空气来实现的，并使用十字形混合器确保堵塞流动，从而稳定运行。然后，溶液通过氟化乙烯丙烯管线圈，由带有PTFE衬里卡普顿窗口的3D打印观看部分连接。观察段被放置在两个交替上升的管盘管之间，这样溶液的流动就会以一定的间隔通过它。这将使我们能够通过在Diamond的I11光束线（EH2）的第二个舱中的大型测角仪阶段（+5 cm zaxis）的垂直定位远程引导光束通过结晶器长度的各个点。由于通过的浆料不断被新的浆料所取代，x射线对每个晶体的损伤被最小化，如果有必要，可以延长采集时间。在建议的采集时间内，沿结晶器长度的设定点将获得汞化粉末的x射线衍射图。在设定值处重复实验将确认分段流优化的稳态运行。随着时间的推移/结晶剂长度的增加，特别是在低流速下，预计UBA III会向UBA I过渡。流动结晶过程的在线x射线监测是一个令人兴奋的新领域，使用中尺度结晶器检测晶体结构演变迄今为止是前所未有的。该技术的发展不仅可以为结晶过程的阐明提供机会，还可以为高通量材料的发现提供机会。通过使用具有多种进料的流动结晶器，可以使用最少的材料快速评估高范围的排列，如反应物比，pH和浓度。为了这个目标已经做了一些工作，但是在线x射线分析还没有实现。从这个开始，KRAIC器件概念及其在可切换功能材料和目标多晶系统中的应用将被探索。随着项目的发展，还将对替代连续结晶和材料组装平台的适应性进行研究和评估。

The first stage of the Project will involve the development and installation of a descoped version of the Kinetically Regulated Automated Input Crystalliser device. The initial experimental work will target flow crystallisation of polymorphic molecular materials on Diamond's I11 beamline, while as part of the KRAIC devise development, immediate needs for adaptation to alternative beamlines will also be taken into account. Segmented flow, as implemented in the KRAIC devices, by nature operates at steady state ensuring all reactants experience the same conditions throughout the reactor. This means that for any point of the reactor length each passing slug is at the same stage of reaction/crystallisation enabling in-depth investigations into transient events such a polymorphic transitions. To develop the initial KRAIC device concept, the Parties have partnered with the Kapur and Meldrum groups at the University of Leeds who have pioneered in-situ power X-Ray Diffraction analysis using microfluidic devices with experience at both ESRF and Diamond. In a segmented flow environment each droplet of crystallisation solution is small and the flow rate means it is not possible to observe crystallisation in-situ with labsource diffractometers; this will be overcome by the use of the high flux available on Diamond beamlines. The KRAIC device mesoscale segmented flow crystalliser constructed at the University in collaboration with the University of Leeds, will be installed at Diamond's I11 beamline, incorporating viewing windows that can be accessed by vertical alignment of the mobile stage.A cooling crystallisation of the target polymorphic cocrystal system urea: barbituric acid will be performed using heated feed vessels and insulating coil holders. Segmentation of the methanol solution is achieved by addition of both inert carrier fluid (PFPE) and air with a crosspiece mixer ensuring plug flow and thus steady state operation. The slugs of solution then pass through coils of Fluorinated Ethylene Propylene tubing joined by a 3D printed viewing section with PTFE lined Kapton windows. The viewing section is placed in between two alternately ascending tubing coils such that the flow of solution passes it at regular intervals. This will enable us to direct the beam through various points of the crystalliser length remotely by vertical positioning of the large goniometer stage (+5 cm zaxis) in the second hutch of Diamond's I11 beamline (EH2). As the passing slurries are continually being replaced by new slurries, the X-ray Damage to each crystallite is minimised and long acquisition times can be possible if necessary.With the proposed acquisition time an amalgamated powder X-ray Diffraction pattern will be obtained for set points along the crystalliser length. Repeat experiments at set points will confirm steady state operation of segmented flow optimisation. A transition of UBA III to UBA I is expected over time/crysatalliser length especially at low flow rates. Online X-Ray monitoring of flow crystallisation processes is an exciting new area and use of mesoscale crystalliser in examining crystal structure evolution is hitherto unprecedented. The development of this technique could offer opportunities not just for the elucidation of crystallisation processes but also high throughput materials discovery. By using a flow crystalliser with multiple feeds a high range of permutations such as reactant ratio, pH and concentration can be very quickly evaluated using minimal material. There has been some work towards this goal but online X-Ray analysis of assays has yet to be realised.From this beginning the KRAIC device concept and its application across switchable function materials and target polymorphic systems will be explored. As the project evolves, the adaptation of alternative continuous crystallisation and materials assembly platforms will also be persued and assessed for deployment.