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开发一种能够分析兆道尔顿 MALDI 离子的线性离子阱质谱仪。

Development of a linear ion trap mass spectrometer capable of analyzing megadalton MALDI ions.

机构信息

Department of Physics, National Dong Hwa University, Shoufeng, Hualien, 97401, Taiwan.

AcroMass Technologies Inc., Hukou, Hsinchu, 30352, Taiwan.

出版信息

Talanta. 2023 Jul 1;259:124555. doi: 10.1016/j.talanta.2023.124555. Epub 2023 Apr 15.

DOI:10.1016/j.talanta.2023.124555
PMID:37088041
Abstract

Detecting megadalton matrix-assisted laser desorption/ionization (MALDI) ions in an ion trap mass spectrometer is a technical challenge. In this study, megadalton protein and polymer ions were successfully measured by MALDI linear ion trap mass spectrometer (LIT-MS) for the first time. The LIT-MS is comprised of a Thermo linear ion trap mass analyzer and a highly sensitive charge-sensing particle detector (CSPD). A newly designed radio frequency (rf) scan mode with dipolar resonance ejection techniques is proposed to extend the mass range of LIT-MS up to one million Thomson (Th). We analyze high mass ions with mass-to charge (m/z) ratios ranging from 100 kTh to 1 MTh, including thyroglobulin, alpha-2-macroglobulin, immunoglobulins (e.g., IgG and IgM), and polymer (∼ 940 kTh) ions. Besides, it is also very challenging for ion trap mass spectrometry to detect megadalton ions at low concentrations. By adopting high affinity carboxylated/oxidized detonation nanodiamonds (oxDNDs) to enrich IgM molecules and form antibody-nanodiamond conjugates, we have successfully reached ∼ 5 nM (5 μg/mL) concentration which is better than that by the other techniques.

摘要

在离子阱质谱仪中检测兆道尔顿基质辅助激光解吸/电离(MALDI)离子是一项技术挑战。在这项研究中,兆道尔顿蛋白质和聚合物离子首次成功地通过 MALDI 线性离子阱质谱仪(LIT-MS)进行了测量。LIT-MS 由 Thermo 线性离子阱质谱分析仪和高灵敏度的电荷感应颗粒探测器(CSPD)组成。提出了一种新设计的射频(rf)扫描模式,具有偶极共振喷射技术,将 LIT-MS 的质量范围扩展到一百万汤姆逊(Th)。我们分析了质量荷比(m/z)比值从 100 kTh 到 1 MTh 的高质量离子,包括甲状腺球蛋白、α-2-巨球蛋白、免疫球蛋白(如 IgG 和 IgM)和聚合物(约 940 kTh)离子。此外,离子阱质谱仪在低浓度下检测兆道尔顿离子也极具挑战性。通过采用高亲和力的羧基化/氧化爆轰纳米金刚石(oxDND)来富集 IgM 分子并形成抗体-纳米金刚石缀合物,我们已经成功地达到了约 5 nM(5 μg/mL)的浓度,优于其他技术。

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