Programmable 'Digital' Synthesis for Discovery & Scale-up of Molecules, Clusters & Nanomaterials

在过去的三百年里，化学合成已经走过了漫长的道路，从炼金术时代到像紫杉醇这样复杂的天然产物的完全合成，再到复杂纳米分子粒子的组装和染料敏化太阳能电池的装置。今天，快速计算机、无处不在的传感器、成像技术和算法的可用性正在将科学从电子工程转变为合成生物学，但化学家们还没有接受这场革命，因为整合化学、传感器、软件和材料处理的困难。最近，我们开始探索可配置化学机器人平台的开发，用于使用一系列方法（包括流动系统、3D打印和混合机器人平台）来发现、优化、放大和控制合成。虽然国际上和英国的一些领先团体正致力于开发优化化学合成的新方法，我们希望将这一想法进一步发展，开发一个用于发现分子实体的集成平台（最初专注于无机物），然后根据用户需求评估它们的“适应性”，构建一个新的可编程化学构建模块库，从而形成可以在一系列应用领域快速制造和测试的新系统。分子发现平台的发展是前所未有的；这一变化将使英国成为世界领先者，使我们能够将基础发现与更快、更智能、更清洁地制造具有用户驱动特性和功能的新化学实体联系起来。因此，我们的目标是开发一个新的合成化学和工程平台，用于发现分子，簇和纳米材料，使用集成的混合化学机器人系统，集成湿软件（化学试剂），硬件（反应器和传感器）和软件（智能算法）。通过“数字”编程，将有可能优化/改变湿软件的过程，作为使用使用软件系统控制的算法测量属性的功能，该软件系统利用化学家，电气工程师和物理学家团队的专业知识，他们共享集成和先进软件控制物质的愿景。化学输入将基于具有明确物理性质的分子金属氧化物（多金属氧酸盐）的组装，使用计算机控制的反应系统，首次实现闭环化学合成和发现。整个系统将通过从通用构建块库（UBBL）方法中选择的化学平台，将构建块的性质与生成的簇和材料的紧急性质联系起来，以具有全新性质的新型催化和电子活性材料为目标。硬件将由可负担得起的定制液体处理机器人、3D打印反应器、可编程微流体以及线性、网络化和阵列流动系统组成，这些系统具有一系列定制（基于CMOS的氧化还原相机/离子敏感阵列）和现成的传感器系统（pH、UV、拉曼、质谱）。目标特性包括光化学、电化学和催化活性分子和最终用户定义的材料，这将使我们能够开发算法，用于发现和扩大新集群等。该项目得到了一些合作伙伴的支持，其中包括190万英镑的现金支持，90万英镑的实物支持，包括葛兰素史克、联合利华、FTDICHIP、ACAL能源、CMAC、格拉斯哥大学将投资50万英镑的设备资金和4名博士生，这表明了他们对EPSRC投资增值的坚定承诺。

During the last three hundred years chemical synthesis has come a long way, from the time of Alchemy to the complete synthesis of complex natural products like Taxol, to the assembly of complex nanomolecular particles and devices for dye sensitised solar cells. Today, the availability of fast computers, ubiquitous sensors, imaging techniques, and algorithms are transforming science from electrical engineering to synthetic biology but chemists are yet to embrace the revolution due to the difficulties of integrating chemistry, sensors, software, and material handling. Very recently we have started to explore the development of configurable chemical-robotic platforms for the discovery, optimisation, scale-up and control of syntheses using a range of approaches including flow systems, 3D printing and hybrid robotic platforms. While a number of leading groups internationally and in the UK are aiming to develop new approaches to the optimisation of chemical synthesis, we wish to take the idea a stage further and develop an integrated platform for the discovery of molecular entities (initially focussing on inorganics) and then assess their 'fitness' according to user needs to construct a new library of programmable chemical building blocks leading to new systems that can be rapidly manufactured and tested in a range of application areas. The development of a platform for molecular discovery is unprecedented; this step-change will place the UK as the world leader allowing us to link fundamental discovery with faster, smarter and cleaner manufacturing of new chemical entities with user-driven properties and functions.Therefore we aim to develop a new synthetic chemistry and engineering platform for the discovery of molecules, clusters and nanomaterials using an integrated hybrid chemo-robotic system integrating wetware (chemical reagents), hardware (reactors and sensors) and software (intelligent algorithms). By 'digital' programming it will be possible to optimise / change the course of the wetware as a function of the properties measured using algorithms controlled using a software system utilising the expertise of a team of chemists, electrical engineers and physicists, who share the vision of integration and advanced software control of matter. The chemical inputs will be based upon the assembly of molecular metal oxides (polyoxometalates) with well-defined physical properties using a computer controlled reaction system enabling closed loop chemical synthesis and discovery for the first time. The overall system will target new types of catalytically and electronically active materials with radically new properties via the chemical platform choosing from a Universal Building Block Library (UBBL) approach that links properties of the building blocks with emergent properties of the resulting clusters and materials. The hardware will be built from affordable customisable liquid handling robots, 3D printed reactionware, programmable milli-fluidics as well as linear, networked, and arrayed flow systems with a range of bespoke (CMOS based redox camera / ion sensitive arrays) and off the shelf sensor systems (pH, UV, Raman, mass spectrometry). Targeted properties include photochemical, electrochemical, and catalytically active molecules and materials defined by end-users that will allow us to develop algorithms for the discovery and scale-up of new clusters etc.This programme is supported by a number of partners with support of around £1.9 M in cash, £0.9 M in kind with support from GSK, Unilever, FTDICHIP, ACAL Energy, CMAC, and also with support from the University of Glasgow who will invest ca. £0.5 M equipment funds and 4 PhD students demonstrating a very strong commitment adding value to the EPSRC investment.