Affordable Low-volume Printed High-throughput Assays (Project ALPHA)

在面临重大的全球卫生挑战时，我们迫切需要发现新药，例如在应对抗菌素耐药性或推动癌症治疗新方法时。我们确定正确治疗方法的能力直接关系到有多少潜在药物可以针对不断增长的靶标进行测试。国家在应对这些挑战方面进行了大量投资，对能够使用高通量筛选技术测试大量潜在药物的设施进行了大量集中投资。通过这个项目，我们现在希望扩大测试能力，以达到前所未有的研究人员数量，通过大幅减少昂贵的试剂使用和设备占地面积的大小，为尽可能多的实验室提供研究工具，以快速测试想法，降低目前大多数实验室的过高成本。这些测试是在分析中进行的，因此小型化所需的样品或试剂体积对于最大限度地增加可能的测试数量至关重要。自20世纪90年代以来，小型化一直是一个焦点，使更多的并行分析成为可能。虽然在学术环境中很少见，但在最先进的工业平板上，有3456个反应区或井，每个反应区都进行一项分析，测试一种有目标的药物。这一提议正在推动一个戏剧性的转变，即在相同的板尺寸上进行超过1700万次测试，每个孔都提供一个3D的、生物相关的、细胞-药物相互作用的微环境，模仿它们的自然环境。独特的核心印刷技术是由工程系开发的，与化学工程和生物技术系以及英国癌症研究中心（剑桥中心）合作进行概念验证。PI和co-I研究员的前沿发现是，喷墨打印的液滴可以在流体表面捕获，每个液滴都被捕获为微尺度井。PI之前曾报道过控制和捕获类似的液滴阵列。每口井所需的材料减少了5万倍，而且液体处理的便捷性也只需要相对简单的机器人技术。对于每个检测阵列的“盘子”的创建有数字控制，将每个转换为用户定义的大小。这极大地减少了浪费，同时也通过最小的试剂和塑料材料的使用确保了对环境的最低影响。该团队旨在通过将试剂最小化与简单的现成自动化相结合，确保可负担性和快速的研究吸收。

There are major global health challenges where we need to discover new drugs urgently, such as when tackling antimicrobial resistance (AMR) or when driving new approaches to cancer treatment. Our ability to identify the right treatments is directly linked to how many potential drugs can be tested against the ever growing range of targets. National investments in responding to these challenges has been significant with large, centralised investments in facilities that can use high-throughput screening techniques to test large numbers of potential drugs. Through this project we want to now scale-out the testing capability to reach unprecedented numbers of researchers, giving as many labs as possible the research tools to test ideas rapidly by dramatically decreasing expensive reagent use and the size of equipment footprint, dropping the currently prohibitive costs for most labs.These tests are carried out in assays so miniaturising the required sample or reagent volumes is critical to maximising the number of possible tests. Miniaturisation has been a focus since the 1990s, enabling more parallel analyses. While rare in an academic environment, there are 3456 reaction zones, or wells, on the most advanced industrial plates, each carrying out one assay, testing a drug with a target. This proposal is pushing to drive a dramatic shift to over 17 million tests in the same plate size, with each well providing a 3D, biologically relevant, micro-environment for cell-drug interactions, mimicking their natural environment.The unique core printed technology is developed in Department of Engineering, working with Department of Chemical Engineering and Biotechnology and Cancer Research UK (Cambridge Centre) for this proof-of-concept. The cutting edge discovery by the PI and co-I Researcher is that inkjet printed drops can be captured at fluid surfaces, with each trapped as a microscale well. The PI has previously reported controlling and capturing similar arrays of liquid droplets. 50,000 times less material is needed per well and the surprising ease of liquid handling requires relatively simple robotics. There is digital control over the creation of the 'plate' for every array of assays, turning each to a user-defined size. This minimises waste dramatically while also ensuring the lowest possible environmental impact through minimal reagent and plastics material usage. The team aims to ensure affordability and rapid research uptake by coupling reagent minimisation with simple off-the-shelf automation.