Intelligent Continuous-flow Polymer Synthesis

该项目将开发用于制造复杂聚合物的新型人工智能（AI）连续流（CF）平台。其目的是为复杂药物开辟新的设计机会，同时确保商业生产具有成本效益，绿色和安全。聚合物是长链分子，它们以一种相互作用的方式产生各种各样的物理性质。聚合材料通常非常坚固、柔韧和绝缘。由于它们的多样性，聚合物比任何其他人造材料都要多。没有他们，我们将无法维持我们目前的生活质量。经常被忽视的是“特种”或“精密”聚合物，它们存在于许多高科技或高性能产品中，如电子产品、农药、润滑剂、涂料和药品。嵌段共聚物，其中两个不同的聚合物链系在一起，是特别感兴趣的；特别是当每个块具有相当不同的属性时。虽然这些产品的生产规模要小得多，但它们通常是产品功能的关键贡献者。也许最复杂的应用是在医疗保健领域（例如药物输送），在这个领域，“个性化医疗”的推动将受益于能够对当地条件（例如肿瘤中的温度或pH值）做出反应的聚合物。这些可用于针对患者的、有针对性的和可控的药物递送。除非开发出精确的、具有成本效益的和可重复的制造方法，否则这些产品永远不会成为现实。连续流是一种替代传统搅拌槽生产化学品的方法。它包括通过特殊设计的反应器不断泵送反应介质，这意味着在任何时候只有非常少量的物质处于反应条件下。这种技术的好处在推动可持续制造方面变得越来越重要。它通常被认为是最环保、最安全、最具成本效益的化学品制造方法。它也是一种多尺度技术，这是一个相当大的优势，因为对特种聚合物的需求可能会大幅波动。在这种情况下，只需长时间运行系统就可以制备更大批量的产品，从而消除了批量扩展所需的任何考虑。最有趣的方面之一是在线监测和反馈技术的便捷结合。这本质上是创造人工智能（AI）反应堆，它将能够立即改变条件，在没有人为干预的情况下实现所需的产品。这提供了额外的效率和潜在的成本节约。在本项目中，将设计、建造和评估一个适合于水基嵌段共聚物合成的连续流反应器。在此之后，将增加额外的监测设备，使远程编程成为可能。对生产条件和聚合物的实时监测将输入一个程序，该程序能够改变条件，以在规定的范围内获得具有组合物的产品。该系统随后将用于合成聚合物，这些聚合物可以通过在可溶性链和颗粒之间转换来响应局部温度或pH值。这些颗粒将能够封装活性成分，并在遇到特定条件（例如肿瘤内部）时将其释放到可溶性链。

This project will develop novel, artificially intelligent (AI) continuous-flow (CF) platforms for the manufacture of complex polymers. The aim is to open new design opportunities for sophisticated pharmaceuticals, while ensuring commercial manufacture is cost-effective, green and safe. Polymers are long chain molecules which interact with each other in a manner which results in a diverse range of physical properties. Polymeric materials are often extremely strong, flexible and insulating. Due to their diversity, more polymers are manufactured than any other man-made material. Without them we would not be able maintain our current quality of life. Often overlooked are 'speciality' or 'precision' polymers, which are present in many high-tech or performance products such as electronics, pesticides, lubricants, coatings and pharmaceuticals. Block copolymers, where two distinct polymer chains are tethered together, are of particular interest; especially when each block has considerably different properties. Although these are manufactured on a much smaller scale, they are often key contributors to a products functionality. Perhaps the most complex applications are within healthcare (e.g. drug delivery), where the drive toward 'personalised medicine' will benefit from polymers which are able to respond to local conditions (e.g. temperature or pH in a tumour). These can be used for patient specific, targeted and controlled delivery of drugs. These products will never become a reality unless precise, cost-effective and reproducible methods of manufacture are developed. Continuous-flow is an alternative method of manufacturing chemicals to traditional stirred tanks. It involves continuously pumping the reaction medium through specially designed reactors meaning only a very small amount of material is under reaction conditions at any one time. The benefits of this technique are becoming more relevant in the drive for a sustainable manufacturing. It is often regarded as the greenest, safest and most cost-effective method of chemical manufacture. It is also a multi-scale technique, which is a considerable advantage since the demand for speciality polymers is likely to fluctuate significantly. In this context, larger volumes of product can be prepared by simply running the system for longer, removing any considerations that would be required with batch scale-up.One of the most interesting aspects is the facile incorporation of online monitoring and feedback technology. This is essentially creating artificially intelligent (AI) reactors which will be able to immediately modify conditions to achieve the desired product without human intervention. This provides additional efficiency and potential cost savings.During this project, a suitable continuous-flow reactor will be designed, constructed and evaluated for synthesis of a water based block copolymer. Following this, additional monitoring equipment will be added which will enable remote programming. Real-time monitoring of the conditions and the polymer produced will feed into a program capable of changing the conditions to achieve a product with a composition within defined limits. The system will subsequently be used to synthesise polymers which can respond to local temperature or pH by transitioning between soluble chains and particles. These particles will be capable of encapsulating an active ingredient, and releasing it during the transition to soluble chains which occurs on encountering specific conditions (e.g. inside a tumour).