Laser-induced nucleation for crystallisation of high-value materials in continuous manufacturing processes

罐中分批处理是工业上生产高价值固体化学品（如农用化学品、染料和药物）的最佳方法。批量处理有许多缺点：每个阶段都有大量的材料;故障可能导致整个批次的损失;批次重复性可能存在很大的变化;由于热流的限制，很难扩大到更大的体积。管道中的连续流制造比批处理有显著改进：小批量的连续处理降低了过程故障的风险;它是更环保的技术，因为它产生的废物更少;产量可以增加;资本和运行成本更低;更高的表面积使加热和冷却过程更容易。实施连续流制造的巨大挑战是固体的处理，特别是细晶体的成核。固体的性质，如晶体的大小、形状和内部结构，对它们的适用性有很大的影响，例如，如药物、杀虫剂、化肥。这些属性可能难以控制。混合和剪切改变了流体生长晶体的准备程度。我们的研究计划旨在通过使用短而强的激光脉冲在连续流反应器的管道中的特定点和时间诱导成核来改进当前的连续流结晶方法。到目前为止，我们的激光诱导结晶方法已经在实验室中进行了研究，仅使用静态样品瓶和液滴。因此，我们需要在混合和流动条件下研究我们的技术。我们的目标是证明我们的方法可以在流体条件有利于某些晶体形状，尺寸和结构的不同位置生长晶体。这种技术目前还没有提供给工业界。即使通过这种方法的部分改进也可以在固体质量方面产生实质性的改进，并且可以鼓励工业转向连续流以用于更多的过程。当然，我们并不认为这将是解决高价值固体连续制造的所有挑战的灵丹妙药。然而，我们相信该技术可以在某些过程中实现显著的节省和改进，例如，为了使我们的计划与行业需求相关，我们的项目将与最近成立的连续制造和结晶（CMAC）财团合作。该集团已通过政府（EPSRC），七所大学，三家顶级全球规模制造商（葛兰素史克，阿斯利康，诺华）以及另外28家工业合作伙伴获得了大量投资。CMAC旨在加速采用连续生产工艺、系统和工厂，以更低的成本、更快的速度和更可持续的方式生产更高质量的药品和精细化学品。我们的合作将确保行业领导者能够快速直接地获得我们研究计划的成果。

Batch processing in tanks is the favoured method in industry for manufacture of high-value solid chemicals, such as agrochemicals, dyes and pharmaceuticals. There are a number of disadvantages to batch processing: large amounts of material are committed to each stage; failure can cause loss of the entire batch; there can be large variations in batch repeatability; and it is difficult to scale-up to larger volumes due to limitations on heat flow. Continuous flow manufacture in pipelines offers significant improvements over batch processing: continual processing of small volumes reduces risks in process failures; it is greener technology because it produces less waste; throughput can be increased; capital and running costs are lower; higher surface areas make it easier to heat and cool processes. A grand challenge in implementing continuous flow manufacture is handling of solids, in particular nucleation of fine crystals. Properties of the solid, such as size, shape and internal structure of crystals have enormous effects on their suitability, e.g., as drugs, pesticides, fertilizers. These properties can be difficult to control. Mixing and shear changes the fluid's readiness to grow crystals.Our research programme aims to improve on current methods for crystallisation in continuous flow by using short, intense pulses of laser light to induce nucleation at specific points and times in the tubes of a continuous flow reactor. So far our laser-induced crystallisation method has been studied in the laboratory using only static sample vials and droplets. We therefore need to study our technique under mixing and flow conditions. Our objective is to demonstrate that our method can grow crystals at different locations where the fluid conditions favour certain crystal shapes, sizes and structures. Such techniques are not already available to industry. Even fractional improvements through this method could yield substantial improvements in the quality of solids, and could encourage industry to switch to continuous flow for more processes. Of course we do not claim that this will be a magic bullet to solve all challenges for continuous manufacture of high-value solids. However, we believe that the technique could stand to make significant savings and improvements in some processes, e.g., in the pharmaceutical industry.To make our programme relevant to the needs of industry, our project will embark on collaboration with a recently formed consortium for Continuous Manufacture and Crystallisation (CMAC). This group have secured significant investment through government (EPSRC), seven universities, three top-tier global-scale manufacturers (GlaxoSmithKline, AstraZeneca, Novartis), and another 28 industrial partners. CMAC aims to accelerate the adoption of continuous manufacturing processes, systems and plants for the production of pharmaceuticals and fine-chemicals to higher levels of quality, with lower costs, more quickly, and in a more sustainable manner. Our collaboration will ensure that industry leaders have fast and direct access to the outcomes of our research programme.