将金属及其化合物的纳米材料作为免疫和适体传感分析等的生物标记物，并采用阳极溶出伏安法（ASV）测定生物传感电极上标记物的金属含量，是一种重要的生物电分析方法（金属标记安培生物分析，MLAB）。然而，已有的MLAB法中，通常将标记物化学溶解并稀释转移到另一溶液中进行ASV分析，或在电极上进行无金属富集步骤的原位安培分析，使得很大部分的金属标记物难以转化为生物分析信号。本项目中，我们提出在生物传感电极上预先施加阴极富集电位，同时进行标记物的化学溶解和金属的阴极富集，再原位进行ASV分析，实现MLAB的信号放大；结合原电池置换反应和金标银染等技术，研究纳米金属标记物的选择性尺寸放大和信号增敏，可望实现单分子水平的生物分析，具有新意和意义。主要研究内容：（1）基于同步化学溶解/阴极富集的信号放大；（2）基于原电池置换反应等方式的信号放大；（3）MLAB新方法用于一些生物标志物的超敏分析检测。

It is a very important bioelectroanalysis method that metal and its compound nanomaterials are used as signaling biolabels for immunoassay and aptamer-based bioanalysis and then anodic stripping voltammetry (ASV) is used to quantify the metal species in these biolabels bio-tethered on the biosensing electrodes for indirect analysis of bioanalytes (metal-labeled amperometric bioanalysis, MLAB). However, in the existing MLAB protocols, either the signaling biolabels are chemically dissolved and then the lysate is diluted and transferred into another electrolyte solution for ASV analysis, or the signaling biolabels are in situ analyzed on the bioelectrodes by amperometry without the metal-preconcentration step, which make it difficult for most biolabels to output bioanalysis signals. In this project, we propose new signal amplification protocols for MLAB, by a beforehand exertion of a cathodic potential and then injection of a small-volume dissolving agent on the electrode surface for simultaneous chemical dissolution of metal biolabels and cathodic preconcentration of atomic metal, followed by in situ ASV analysis, and further by combination of galvanic replacement reaction (GRR) with gold labeling-silver staining technique to selectively enlarge the size of metal biolabels and thus enhance the bioanalysis sensitivity. These new signal-amplification protocols may enable single-molecule-level bioanalysis and are thus of considerable significance. The main investigation contents are (1) signal amplification based on simultaneous biolabel chemical dissolution/cathodic metal preconcentration; (2) signal amplification based on GRR protocol and so on; and (3) application of new MLAB methods for ultrasensitive analysis of some biomarkers.