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。其目的是为尖端药物打开新的设计机会，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，它们彼此相互作用，从而导致各种物理性质。聚合物材料通常是非常坚固、柔韧和绝缘的。由于它们的多样性，制造的聚合物比任何其他人造材料都多。没有他们，我们就不能保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被拴在一起，特别是当每个嵌段具有相当不同的性质时，特别令人感兴趣。尽管这些产品的制造规模要小得多，但它们往往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)，在这一领域，“个性化药物”的发展将受益于能够对局部条件(例如，肿瘤的温度或PH值)做出反应的聚合物。这些药物可用于针对患者的、有针对性的和受控的药物输送。除非开发出精确、成本效益高和可重复使用的制造方法，否则这些产品永远不会成为现实。连续流是生产化学品的一种替代传统搅拌槽的方法。它包括通过专门设计的反应器连续泵送反应介质，这意味着在任何时候都只有非常少量的材料处于反应条件下。这项技术的好处在推动可持续制造方面正变得更加相关。它通常被认为是最绿色、最安全和最具成本效益的化学制造方法。这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有很大的波动。在这种情况下，只需运行系统更长时间，消除批量扩大所需的任何考虑因素，就可以制备更大数量的产品。最有趣的方面之一是在线监控和反馈技术的轻松整合。这本质上是创造了人工智能(AI)反应堆，它将能够立即改变条件，在没有人工干预的情况下获得所需的产品。这提供了额外的效率和潜在的成本节约。在这个项目中，将设计、建造和评估一个合适的连续流动反应器来合成水基嵌段共聚物。在此之后，将增加额外的监控设备，以实现远程编程。对生产的条件和聚合物的实时监控将输入到一个能够改变条件的程序中，以实现成分在规定限度内的产品。该系统随后将被用于合成能够通过在可溶链和颗粒之间过渡而对局部温度或pH作出响应的聚合物。这些颗粒将能够包裹活性成分，并在遇到特定条件时(例如在肿瘤内)转变为可溶性链的过程中释放它。

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).