Microfluidic Microdroplet Reactors

我们计划为实验科学产生一种新的平台技术，并通过将其应用于识别化学反应的新型生物催化剂来证明其实用性。该技术的主要特点将是其速度，规模和通用性。各个反应将在微流体通道内的氟碳化合物连续相中携带的水的微滴内发生。这些微反应器将装载用于反应的组分。然后可以通过将液滴与第二液滴融合来添加另外的化合物。一旦在液滴中发生反应，将通过光谱法或质谱法确定产物的存在。质谱法的优点在于它可以提供高分辨率的结构信息。然而，将其与微滴连接是该提案中未探索且非常具有挑战性的部分。通过这种方式，新的催化剂将被识别，然后可以通过几轮选择来改进它们。一个模块化设备将被组装，装载，融合，孵育，分选和分裂液滴，然后呈现给光谱或质谱屏幕。该装置的制造，特别是各种组件的集成是一个重大的挑战，将是该项目的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。这些酶要么是具有新功能的酶，要么是来自不寻常生物的酶。这是一个重要项目的例子，使用我们开发的系统比使用现有方法更容易访问。我们希望获得超过104的效率提升。该项目是多学科的，处于几个领域的前沿：微滴的使用，微流体在芯片实验室应用中的使用，质谱的使用以及酶的定向进化。我们可以定制我们生产的设备，以解决生物，化学和材料科学中的广泛问题。

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.