蛋白质是重要的生物分子，参与生命活动中的信号调控和转导等诸多功能。某些蛋白质的表达水平与生物体/细胞中特定的功能相关，而一些蛋白质的表达异常则与疾病密切相关。质谱技术具有可提供丰富的结构信息、检测灵敏度高、分析速度快、分析通量高、可实现绝对定量等优势，近年来在生命分析领域的应用越来越广泛。然而，由于样品基质复杂、离子化效率低及仪器分辨率等因素的限制，蛋白质类大分子的直接质谱分析中能够获得的检测灵敏度仍十分有限。本论文中，针对蛋白质直接检测灵敏度不足的问题，我们结合课题组的前期工作，采用质谱信标标记蛋白分子的质谱增敏策略，基于实验室搭建的常压敞开环境下的解吸电喷雾质谱（desorption electrospray ionization mass spectrometry，DESI-MS）平台，实现蛋白质的快速和高灵敏检测。我们以血小板衍生生长因子BB（platelet-derived growth factor-BB ，PDGF-BB）为检测模型，经过实验条件和实验参数的系统优化，本方法检测PDGF-BB的线性范围为0.094-94 amol，检测限低至0.0286 amol。血清基质中的加标实验回收率为96.3%-97.9%（RSD = 0.728-6.81%，n=3）。该方法表现出检测灵敏度高、特异性好、基质耐受性强、简便快速等优势，有望进一步应用于蛋白质快速筛查和疾病早期诊断等领域。

Proteins, essential biomolecules in living organisms, are involved in a wide range of signal modulation and transduction in life activities and many other biological functions. The expression level of a particular protein is related to specific function in the organism or cell, while abnormal expression of proteins is often associated with diseases. Mass spectrometry (MS) has many advantages, such as providing abundant structure information, high detection sensitivity, fast analysis speed, high analytical throughput, and absolute quantification etc. In recent years, MS has been used more and more widely in life science. However, owing to the complexity of the sample matrix, the low ionization efficiency, and the limitation of the instrument resolution, the detection sensitivity of intact proteins is still limited and remains challenging. In this work, aiming at the problem of insufficient sensitivity of direct protein detection, we utilized small molecule mass tags to label target proteins for signal amplification on the basis of signal amplification of MS. A platform based on desorption electrospray ionization mass spectrometry (DESI-MS) was established which enabled the fast and highly sensitive detection of proteins. We used platelet-derived growth factor BB (PDGF-BB) as the model protein. After optimization of DESI-MS setup parameters and immunoassay conditions, PDGF-BB in the range of 0.094-94 amol with a limit of detection (LOD) as 0.0286 amol was achieved. In the spiked serum experiments, a spike recovery of 96.3%-97.9% was obtained (RSD =0.728-6.81%, n=3). The method can realize the simple and rapid detection of proteins with high sensitivity, good specificity, and strong matrix tolerance, which is promising in the further application in rapid protein screening and early disease diagnosis etc.