Department of Chemical Sciences, University of Padova, Via Marzolo 1, 35131 Padova, Italy.
Chem Soc Rev. 2011 Sep;40(9):4488-505. doi: 10.1039/c1cs15024c. Epub 2011 May 17.
The naked eye detection of single molecules in a complex mixture is the ultimate detection limit. Since a single molecule is unable to generate a strong enough signal, sensing methodologies able to reach that limit by necessity need to rely on signal amplification. This tutorial review describes various molecular approaches towards signal amplification in which a single analyte molecule affects the properties of a multitude of reporter molecules. Sensing by advanced instrumentation or changes in the physical properties of materials are excluded. The review is divided into four parts (catalysts, macromolecules, metal surfaces and supramolecular aggregates) depending on the species responsible for generating reporter molecules. Although on first sight apparently very diverse in nature, the majority of approaches rely on two key concepts: catalysis and multivalency. The ability of a catalyst to convert a multitude of substrate molecules into product (defined by the turn over number) makes a catalyst an intrinsic signal amplifier in case the chemical conversion of the substrate is accompanied by a measurable change in physical properties. For sensing purposes, catalytic activity must depend on the interaction between the analyte and the catalyst. Sensing using multivalent structures such as polymers and functionalized nanoparticles relies on the ability of a single analyte molecule to affect the properties of a multitude of reporter molecules collected in the multivalent structure. Chemical sensing systems will be discussed with detection limits that indeed go down to a few molecules and can rival the best biological assays. It will be shown that the most sensitive methods rely on a cascade of amplification mechanisms.
在复杂混合物中对单个分子进行肉眼检测是最终的检测极限。由于单个分子无法产生足够强的信号，因此达到该极限的传感方法必然需要依赖信号放大。本教程综述描述了各种分子方法的信号放大，其中单个分析物分子影响大量报告分子的性质。不包括先进仪器的传感或材料物理性质的变化。该综述分为四个部分（催化剂、大分子、金属表面和超分子聚集体），这取决于负责产生报告分子的物种。尽管乍一看在性质上显然非常多样化，但大多数方法都依赖于两个关键概念：催化和多价性。催化剂将大量底物分子转化为产物的能力（由周转率定义）使其成为内在信号放大器，前提是底物的化学转化伴随着可测量的物理性质变化。对于传感目的，催化活性必须取决于分析物与催化剂之间的相互作用。使用多价结构（如聚合物和功能化纳米粒子）进行传感依赖于单个分析物分子影响收集在多价结构中的大量报告分子的性质的能力。将讨论化学传感系统，其检测限确实降至几个分子，并且可以与最佳的生物测定相媲美。将表明，最灵敏的方法依赖于级联的放大机制。
