Microfluidic Microdroplet Reactors

我们计划建立一种新的实验科学平台技术，并将其应用于化学反应新型生物催化剂的鉴定。这项技术的关键特征将是其速度、规模和通用性。单独的反应将在微流体通道内的氟碳连续相中携带的微滴水滴中进行。这些微反应器将装满反应所需的成分。然后，可以通过将一个液滴与第二个液滴融合来添加额外的化合物。一旦在液滴中发生反应，产物的存在将通过光谱或质谱学来确定。质谱学具有提供高分辨率结构信息的优势。然而，将其与微滴相结合是该提案中一个未经探索和极具挑战性的部分。通过这种方式，将识别出新的催化剂，然后通过几轮选择来改进它们。将组装一个模块设备，该设备将加载、引信、孵化、分类和分解液滴，然后呈现在光谱或质谱学屏幕上。这种装置的制造，特别是各种部件的集成是一个巨大的挑战，也将是该项目第一部分的主要重点。我们计划使用这种模块化装置来发现新型生物催化剂。它们要么是结合了新功能的酶，要么是来自不寻常生物体的酶。这是一个重要项目的例子，与使用现有方法相比，使用我们开发的系统将变得更容易获得。我们预计效率将提高104以上。该项目是多学科的，走在几个领域的前沿：微滴的使用，芯片实验室应用的微流体的使用，质谱学的使用，以及酶的定向进化。我们将有可能定制我们生产的设备，以解决生物、化学和材料科学中的一系列问题。

We plan to generate a novel platform technology for experimental science, and demonstrate its utility by applying it to the identification of novel biological catalysts for chemical reactions. The key features of the technology will be its speed, scale and general utility. Individual reactions will take place inside microdroplets of water carried in a fluorocarbon continuous phase within microfluidic channels. These microreactors will be load up with the components for a reaction. Additional compounds can then be added by fusing a droplet with a second droplet. Once a reaction has occurred in a droplet the presence of product will be determined either spectroscopically or by mass spectrometry. Mass spectrometry has the advantage that it can provide high resolution structural information. However interfacing it with microdroplets is an unexplored and very challenging part of the proposal. In this way new catalysts will be identified which can then be improved by taking them through several rounds of selection.A modular device will be assembled that load, fuse, incubate sort and split droplets and present then to either a spectroscopic or mass spectrometric screen. The fabrication of this device, and especially the integration of the various components is a significant challenge, and will be the main focus of the first part of the project.We plan to use this modular device for the discovery of novel biological catalysts. These will either be enzymes that incorporate new functionality, or enzymes from unusual organisms. This is an example of an important project that will become more accessible using the system we develop than using than with existing approaches. We expect to get an efficiency enhancement of over 104. The project is multidisciplinary and at the forefront of several areas: the use of microdroplets, the use of microfluidics for lab-on-a-chip applications, the use of mass spectrometry, and the directed evolution of enzymes. It will be possible to customise the devices we generate to tackle a broad range of problems in biological, chemical and materials science.