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

自第一次世界大战以来，令人遗憾的是，化学战剂的使用导致全球需要有效地探测、识别和净化这些超毒剂。化学战剂现在被列为大规模杀伤性武器。主要关注的是G型和v型神经毒剂（如GB -沙林和VX）和芥子气发泡剂（如HD、芥子气）。由于可能被恐怖组织利用，对化学武器的担忧最近有所增加。此外，还有一些剧毒工业化学品（TIC），如氰化氢和氟化氢，用于一系列不同的工业。如果出现蓄意或意外释放这种有毒化学品的情况，准确探测和确定化学武器或化学武器是否存在的能力在确定最佳行动方针和防止生命损失方面将变得极其重要。在建议的工作中，我们希望开发一种检测cwa的系统，供几乎没有操作员培训的安全人员使用。这里的中心主题是利用以前在我们实验室进行的工作，这些工作导致了对主要类别的CWA进行高度选择性的“测试”。这些系统在识别液态CWAs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。在我们感兴趣的化学武器制剂中，像沙林这样的蒸汽制剂构成了最大的威胁。该试剂的高挥发性和极高的毒性意味着在气相中检测它的能力对军事和民政当局至关重要。我们建议通过使用生物“放大”机制使现有的G-agent化学传感器适应气相检测。因此，GB的存在会促进氟化物阴离子的释放，而氟化物阴离子又会与合成的传感器分子结合。这一事件触发生物化学物质的释放，随后由一系列天然催化剂（酶）起作用。该序列中的最后一个反应是基于导致萤火虫生物发光的相同生物化学原理，因此该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，一个沙林分子触发了许多光子的释放。从本质上讲，分析物GB触发了一连串的反应，导致最初的小事件放大。希望该方法可以推广到许多类型的目标化合物，并允许在不需要使用复杂和昂贵的仪器的情况下对危险物质进行敏感检测。这将在提供低成本的传感器系统和避免需要外部电源方面有很大的好处。另一个好处是，安全人员只需很少或根本不需要培训就可以使用拟议的“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'.