摘要
脂质是生物体的重要组成成分,参与细胞膜流动、神经递质传递和运输以及能量供应等多个过程。研究表明,癌细胞为了适应不断变化的生物微环境和快速增殖的需求,其脂质代谢过程不同于正常细胞。因而,对脂质组分进行快速检测、识别及监测研究,对了解生命过程、监测诊疗过程变化、提升诊疗效率等具有重要意义。质谱是直接获取分子结构最有效的手段之一,在生物分子及脂质鉴定中具有独特优势。近年来,常压质谱技术(ambient mass spectrometry,AMS)不断涌现,该技术无需样品预处理,为直接快速脂质识别及监测提供了有效手段。软电离技术的不断发展也为复杂多样的脂质分子检测提供了广阔的发展空间。电喷雾离子化(ESI)作为主要的软电离技术之一,易于离子化中高极性的生物样品,能够满足生物体内大多数脂质的检测需求。因此,研究人员基于ESI技术,开展了广泛的癌症脂质代谢研究,实现了不同脂质的鉴定和相对定量研究。由于脂质存在丰富的异构体,人们又创新性地将各种化学衍生法和其他技术与AMS结合起来,实现了对复杂脂质结构异构体的准确识别和相对定量研究。基于此,本文综述了近5年用于脂质检测的主要常压质谱技术及应用进展,并汇总了质谱解析脂质精细结构的典型策略。
Lipids are indispensable components of living organisms and play pivotal roles in cell-membrane fluidity,energy provision,and neurotransmitter transmission and transport.Lipids can act as potential biomarkers of diseases given their abilities to indicate cell-growth status.For example,the lipid-metabolism processes of cancer cells are distinct from those of normal cells owing to their rapid proliferation and adaptation to ever-changing biological environments.As a result,the ability to rapidly detect,identify,and monitor lipid components is critical for tracking life-related processes and may enhance cancer diagnosis and treatment efficacy.Mass spectrometry(MS)is regarded to be among the most efficient methods for directly obtaining molecular-structural information,and is distinctly advantageous for identifying lipids.Recent years have witnessed the emergence of ambient mass spectrometry(AMS),which enables direct analyte sampling and ionization without the need for sample preprocessing.These characteristics endow AMS with special advantages for identifying and monitoring lipids.Furthermore,the ongoing development of soft ionization technologies has led to the widespread use of AMS for the detection of complex and diverse lipid molecules.Electrospray ionization(ESI)is a gentle ionization method that can be used to detect medium-to-high-polarity compounds and provide detailed chemical information for lipids by producing a fine mist of charged droplets from a liquid sample.Consequently,a series of ESI-based ionization methods have been developed for fabricating different AMS systems capable of rapidly detecting lipids in a simple manner.For example,desorption electrospray ionization(DESI)is among the most extensively employed ambient ionization techniques,and has been used to detect a wide range of samples,including solids,liquids,and gases.DESI involves spraying a charged solvent onto the surface of a sample,after which the solvent is desorbed,the analyte is ionized,and the generated ions are transferred to the detector of the mass spectrometer via a gas plume.DESI can easily and precisely regulate the sampling space,thereby offering a highly effective approach for the in-situ detection of lipids from tissue samples.Additionally,single-cell lipid analysis is limited by small cell volumes,complex cellular matrices,and minimal absolute amounts of analyte.Common detection methods for single cells include flow cytometry and fluorescence microscopy,both of which require fluorescent labeling to detect specific target molecules,which limits detection selectivity and reproducibility to some extent.ESI-based single-cell mass spectrometry has emerged as a more-effective method for detecting cellular lipids owing to advantages that include high sensitivity,low sample consumption,high throughput,and multiple-detection capabilities.Moreover,lipid chemical diversity poses a significant challenge for determining structural details.Therefore,AMS-based lipid detection has been augmented with a series of chemical-treatment methods that provide more-comprehensive structural information for lipids.For example,diverse gas-phase dissociation techniques have been used to discriminate between lipid C=C-bond isomers and their sn-positions.Strategies that involve chemically modifying specific target C=C bonds prior to MS detection have also been employed.For example,the Paternò-Büchi(P-B)photochemical reaction oxidizes C=C bonds in unsaturated lipids to form oxetane structures,C=C bonds can be epoxidized to form the corresponding oxaziridines,the N-H aziridination reaction converts C=C bonds into aziridines,and the 1ΔO 2 ene reaction adds an OOH group to a C=C bond.In this review,we discuss various environmental ionization techniques for lipid AMS developed over the past five years,with an emphasis on typical chemical strategies used to analyze lipid fine structures.Obtaining a high-coverage,high-sensitivity lipid-detection platform based on AMS remains challenging and requires further in-depth studies despite significant improvements in lipid MS-based detection techniques.
作者
王晓蓉
尹伊颜
欧阳津
那娜
WANG Xiaorong;YIN Yiyan;OUYANG Jin;NA Na(Key Laboratory of Radiopharmaceuticals,Ministry of Education,College of Chemistry,Beijing Normal University,Beijing 100875,China;Department of Chemistry,College of Arts and Sciences,Beijing Normal University,Zhuhai 519087,China)
出处
《色谱》
CAS
北大核心
2025年第1期22-32,共11页
Chinese Journal of Chromatography
基金
国家自然科学基金(22274012,22474010)
中央高校基本科研业务专项资金(2233300007)。
关键词
常压质谱
离子化技术
脂质
脂质精细结构
串联质谱
ambient mass spectrometry(AMS)
ionization techniques
lipid
lipid fine structure
tandem mass spectrometry(MS/MS)
作者简介
通讯联系人:那娜.E-mail:nana@bnu.edu.cn.
