摘要
2,4,6‑三硝基甲苯(TNT)是军事活动中最重要的武器能源体,其不仅具有强大的毁伤作用,同时还具有化学毒性,即使是痕量的TNT,也会对自然环境、人类健康造成严重威胁。因此,发展具有高灵敏、高准确性、快响应的痕量炸药检测技术,对保护生态环境、维护人类健康具有深远研究意义。在众多痕量检测技术中,生物传感技术具有选择性好,合成简单,响应快,灵敏度高等优势,具有良好的应用前景。本文综述了近年来生物传感技术在痕量炸药检测中的研究进展,重点讨论了抗体免疫、肽、适配体、酶以及多参量加载5大类生物传感器的优势以及局限性。其中基于适配体制备的传感器对炸药分子具有良好的亲和力以及特异性,检出限相较于其他几类传感器低1000倍,且稳定性良好,易于改造修饰,结构拓展能力强。今后研究的重点为基于适配体等生物受体元件构筑的高通量痕量炸药传感系统,结合神经网络算法,机器学习技术,构筑具有多重检测以及仿生遥感性能的痕量炸药生物传感技术。
图文摘要
This paper reviews advances in biosensors for trace explosives detection, focusing on the advantages and limitations of five major classes of biosensors: antibody‑immune, peptide, aptamer, enzyme, and multiparametric loading. This paper points out the key directions for future research to provide technical support for early warning and identification of potential threats in the application of explosives.
炸药是战争和恐怖袭击中常见的能量源,其强大的毁伤能力将造成惨重的人员伤亡及财产损
痕量炸药检测的关键是利用分析物和传感元件间的化学键合、物理吸附或分子反应等相互作用,将生物信号转变为可通过仪器读取的光、电、磁等信号。目前,炸药传感元件主要有:有机小分子元
抗体是由浆细胞分泌、被免疫系统用来识别和中和病毒等外来物质的大型Y形蛋白质,主要分为单克隆抗体、多克隆抗体以及重组抗
一些硝基炸药在热裂解过程中会产生不同的反应性离子,如NO
图1 基于抗体生物传感元件的炸药检测机
Fig.1 Mechanism for explosive detection based on antibody‑based biosensing element
相较于其他传感器,生物传感器因其特异性而具有更高的准确度,但这也限制了其只对特定分析物进行响应。当同时检测多个待测物时,就需要携带不同的生物受体元件,这有悖于简单便携的基本理念。因此,在保证准确性的前提下,提高抗体等生物传感器多重检测的能力极具挑战性。Climent
利用生物传感器进行多重检测可以极大提高分析通量,增加单次测定中获得的信息量。但目前多重检测的目标物集中于蛋白质、DNA、病毒等生物体系,对于炸药等有害物质的研究较少,未来可进一步拓展至该领域。此外,随着微流控和纳米技术的发展,快速检测、高灵敏、小型化便携式的传感器件将成为多重检测生物传感器的主流。
肽是一种根据抗体结合位点而设计的氨基酸短链,具有更加稳定的结构,且更易于长期储存和在恶劣条件下使用。此外,氨基酸多样化的化学特性表明肽更适合作为目标分子的受
高特异性的生物传感器常常设计有荧光或电化学特性的信报单元,将生物信号转变为可分析的光/电信号,实现对分析物的检测。Li
图2 基于肽生物传感元件的炸药检测原
Fig.2 Mechanism for explosive detection based on peptide biosensing element
核酸适配体是一种单链寡核苷酸分子,能以高度特异性与靶目标结
目前,适配体作为抗体的替代品,以类似的方式用于各种小分子诊断。Kong
图3 基于适配体生物传感元件的炸药检测机
Fig.3 Explosive detection mechanism based on aptamer biosensing element
Hu
酶作为一类具有催化特性的核酸,可协同辅助因子裂解特定的底物。它一般通过体外选择来识别分析物,不需要使用动物或细胞试管培
Komarova
图4 基于酶生物传感元件的炸药检测机
Fig.4 Mechanism for explosive detection based on enzymatic biosensing element
除了利用酶的特异性对待测物进行识别,还可以通过其催化特性实现污染物的降解从而修复环境。Karthikeyan
Oluwasesan
由于大多数炸药受体的选择性不强,可以通过多参量加载的阵列形式来创建类似于人工触觉系统的响应模式,进而发展为电子类似物。电子类似物实现物质识别的机制与生物触觉信号传导的工作原理类
图5 电子类似物与生物嗅觉系统工作原理的比
Fig.5 Comparison of mechanism for electronic analogues and biological olfactory system
如图
图6 多参量加载生物传感元件的炸药检测机
Fig.6 Explosive detection mechanism for multiparametric loaded biosensing element
目前,地雷和简易爆炸装置的探测大多是通过操作人员现场搜寻,这种搜寻方式对现场作业人员的生命存在非常大的安全危险,加之探测非金属地雷的能力有限且极易出现假阳性识别,故而需要发展新检测方法准确安全地进行地雷探测。Belkin
本文综述了近年来基于生物传感痕量炸药检测的最新进展,重点讨论了抗体免疫、肽、适配体、酶以及多参量加载的炸药生物传感技术,生物传感具有较其他传感技术更好的特异性及准确性,使得其在炸药检测领域极具应用潜力:
(1)交通枢纽和边境管控要求传感器具有高灵敏、高选择性、快响应以及便携性。基于适配体等生物受体制成的传感器在满足上述要求的同时,与表面增强拉曼、质谱、荧光等技术联用,优势互补,弥补了传统检测方式中生物疲劳、工作时间有限的缺陷,可广泛应用于国土安全等领域。
(2)环境监测通常需要高灵敏度和高选择性的传感器来保证检测的准确性,对检测速度要求不高。而适配体等生物识别元件的高特异性可以减少复杂基底(如土壤、液体)中样品交叉反应的问题,从而提高检测的准确性。
尽管生物传感器表现出一定的优势,但在其技术开发方面仍需要进一步的改进,例如:
(1)多重检测生物传感器。生物传感器具有高度特异性的同时也限制了它只对特定的目标物响应,在同时检测多种分析物时,就需要携带和使用相应的生物受体元件,这有悖于简单便携的基本理念。因此,在保留便携性的同时结合高通量分析以实现多种待测物同时检测是该领域的研究重点之一。
(2)仿生遥感生物传感器。针对于某些特定的应用场所,例如战场或雷区的炸药检测,最重要的是能够在较远的距离进行安全探测。基于适配体等生物受体构筑高通量的痕量炸药传感系统,并结合神经网络算法,机器学习等人工智能技术制备出具有仿生遥感性能的生物传感器,为解决炸药产生的威胁提供技术支持。
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