High-resolution imaging and identification of biomolecules using Nano-DESI coupled to ion mobility spectrometry.
High-resolution imaging and identification of biomolecules using Nano-DESI coupled to ion mobility spectrometry.
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DOI：
10.1016/j.aca.2021.339085
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发表时间：
2021-11-22
影响因子：
6.2
通讯作者：
Laskin J
中科院分区：
文献类型：
--
作者：
Unsihuay D;Yin R;Sanchez DM;Yang M;Li Y;Sun X;Dey SK;Laskin J
复杂生物样品中分子的同时空间定位和结构表征是当前质谱学成像(MSI)技术面临的分析挑战。在这项研究中，我们描述了一个新的实验平台，它大大扩展了使用纳米螺旋解吸电喷雾电离(Nano-DESI)进行的高空间分辨率微束成像实验中获得的化学信息的能力和深度。具体地说，我们设计并构建了一个便携式纳米Desi MSI平台，并将其与漂移管离子迁移谱仪-质谱仪进行了耦合。我们使用怀孕第4天的小鼠子宫组织演示了漂移时间分离离子的成像，其高空间分辨率优于~25μm。碰撞截面测量提供了在Nano-DESI-IM-MSI中观察到的分子的唯一分子描述符，通过与数据库的比较，这些分子是明确识别分子所必需的。同时，异构体特异性成像显示了整个组织中异构体组成的变化。此外，离子迁移率分离有效地消除了来自溶剂峰、从组织中提取的内源分子的重叠同位素峰以及源内碎裂产物产生的等压和同分异构体干扰，这对于使用MSI获得准确的样品浓度梯度至关重要。IM分离提供的结构信息大大扩展了高分辨率MSI的分子特异性，这是解开生物系统复杂性所必需的。
Simultaneous spatial localization and structural characterization of molecules in complex biological samples currently represents an analytical challenge for mass spectrometry imaging (MSI) techniques. In this study, we describe a novel experimental platform, which substantially expands the capabilities and enhances the depth of chemical information obtained in high spatial resolution MSI experiments performed using nanospray desorption electrospray ionization (nano-DESI). Specifically, we designed and constructed a portable nano-DESI MSI platform and coupled it with a drift tube ion mobility spectrometer-mass spectrometer. We demonstrate imaging of drift time-separated ions with a high spatial resolution of better than ~25 μm using uterine tissues on day 4 of pregnancy in mice. Collision cross-section measurements provide unique molecular descriptors of molecules observed in nano-DESI-IM-MSI necessary for their unambiguous identification by comparison with databases. Meanwhile, isomer-specific imaging reveals variations in the isomeric composition across the tissue. Furthermore, ion mobility separation efficiently eliminates isobaric and isomeric interferences originating from solvent peaks, overlapping isotopic peaks of endogenous molecules extracted from the tissue, and products of in-source fragmentation, which is critical to obtaining accurate concentration gradients in the sample using MSI. The structural information provided by the IM separation substantially expands the molecular specificity of high-resolution MSI necessary for unraveling the complexity of biological systems.
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影响因子：
4.3
作者：
Kiss, Andras;Heeren, Ron M. A.
通讯作者：
Heeren, Ron M. A.
影响因子：
4.2
作者：
Bergman, Hilde-Marlene;Lundin, Erik;Lanekoff, Ingela
通讯作者：
Lanekoff, Ingela
DOI：
10.1007/s13361-019-02288-2
发表时间：
2019-11-01
影响因子：
3.2
作者：
Dodds, James N.;Baker, Erin S.
通讯作者：
Baker, Erin S.
影响因子：
7.4
作者：
Domingo-Almenara, Xavier;Montenegro-Burke, J. Rafael;Siuzdak, Gary
通讯作者：
Siuzdak, Gary
影响因子：
48
作者：
Cornett, Dale S.;Reyzer, Michelle L.;Caprioli, Richard M.
通讯作者：
Caprioli, Richard M.