Joint Synthetic Biology Initiative - Biological Amplification of Chemical Warfare Agent Sensors - Towards 'Deviceless Devices'

自第一次世界大战以来，化学战剂（CWA）的令人遗憾的使用导致了全球需要有效地检测，识别和净化这些剧毒剂。化学战剂现在被列为大规模毁灭性武器。主要关注的是G型和V型神经毒剂（如GB -沙林和VX）和芥子类起疱剂（如HD、芥子气）。由于化学武器可能被恐怖组织使用，最近对化学武器的关注有所增加。此外，还有许多剧毒工业化学品（TIC），如氰化氢和氟化氢，用于一系列不同的行业。如果有一个故意或意外释放这样的有毒化学品，准确地检测和识别CWA或TIC的存在的能力，将成为在确定最佳的行动方针，防止生命的损失是极其重要的。在拟议的工作中，我们希望开发一个系统，用于检测CWA的安全人员使用的操作培训很少。这里的中心主题是利用我们实验室以前进行的工作，这些工作导致了对主要类别CWA的高度选择性“测试”。这些系统在识别液态化学武器方面非常有效，我们希望将这项工作应用于有毒气体的检测。在化学武器区感兴趣的物剂中，沙林等物剂以蒸汽形式构成最大威胁。这种物质的高挥发性和极端毒性意味着，军事和民事当局必须有能力在气相中检测到这种物质。我们建议我们现有的G-代理化学传感器，通过使用生物“放大”机制的气相检测。因此，GB的存在将促进氟阴离子的释放，氟阴离子又将结合到合成传感器分子上。这一事件触发了生物化学物质的释放，随后由一系列天然存在的催化剂（酶）起作用。序列中的最终反应基于在萤火虫中引起生物发光的相同生物化学，因此系统的主要输出将是光。最后一个反应是一个循环的一部分，一个沙林分子会引发许多光子的释放。本质上，分析物GB触发级联反应，导致最初小事件的放大。人们希望这种方法可以推广到许多类型的目标化合物，并允许敏感的检测危险材料，而不需要使用复杂和昂贵的仪器。这在提供低成本传感器系统和减少对外部电源的需要方面将是巨大的益处。另一个好处是，安全人员将需要很少或不需要培训来使用所提出的“设备”。

Since WW1 the regrettable use of chemical warfare agents (CWAs) has resulted in a global need to efficiently detect, identify and decontaminate these supertoxic agents. Chemical warfare agents are now classified as weapons of mass destruction. Of prime concern are the G- and V-type nerve agents (e.g. GB - Sarin and VX) and the mustard vesicants (e.g. HD, mustard gas). Concerns over CWAs have recently increased due to their potential use by terrorist organisations. In addition, there are a number of highly toxic industrial chemicals (TIC) such as hydrogen cyanide and hydrogen fluoride which are used in a range of different industries. If there were to be a deliberate or accidental release of such toxic chemicals, the ability to accurately detect and identify the presence of CWA or TICs would become extremely important in determining the best course of action and preventing loss of life.In the proposed work we wish to develop a system for the detection of CWAs for use by security personnel with little operator training. The central theme here is to exploit previous work undertaken in our laboratories that has resulted in highly selective 'tests' for the main classes of CWA. These systems are very effective in identifying CWAs in liquid form and we wish to adapt this work to detection of toxic gases. Of the CWA agents of interest, it is agents such as Sarin that pose greatest threat as vapours. The high volatility, and extreme toxicity, of this agent means that the ability to detect it in the gas phase is essential for military and civilian authorities. We propose to adapt our existing G-agent chemical sensors to gas phase detection by using a biological 'amplification' mechanism. Hence the presence of GB will promote the release of fluoride anions which in turn will bind to a synthetic sensor molecule. This event triggers the release of biochemicals that are subsequently acted upon by series of naturally occurring catalysts (enzymes). The final reaction in the sequence is based upon the same biochemistry that causes bioluminescence in Fireflies, and thus the primary output of the system will be light. This last reaction is part of a cycle so that one molecule of Sarin triggers the release of many photons of light. In essence the analyte GB triggers a cascade of reactions that results in the amplification of an initially small event. It is hoped that approach can be generalised to many types of target compound and allow the sensitive detection of dangerous materials without the need to use complex and expensive instruments. This will be great benefit in providing low cost sensor systems and obviate the need for external power sources. A further benefit is that security personnel will require little or no training to use the proposed 'devices'.