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

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.