Novel Matrixes for Mass Spectrometry Imaging and Research Progress of It in Analyzing Biological Samples

doi:10.13560/j.cnki.biotech.bull.1985.2022-0158

Abstract

Abstract:

As a new molecular imaging technology，mass spectrometry imaging（MSI）can not only retain the spatial structure information of biological tissues，but also detect the expressions of biomolecules in tissues without labeling in situ，including proteins，peptides，amino acids，lipids，drugs and their metabolites，thus in situ detection of biological samples can be achieved. With the continuous development and optimization of ionization technology，matrix materials，analytical instruments and software，MSI technology has been increasingly applied to biological research，medical research，drug research and many other fields in recent years. In this review，a variety of novel matrixes developed by matrix-assisted laser desorption（MALDI）imaging technology for biological samples are summarized. The latest application and progress of new MSI technology and new data processing methods are summarized. Finally，the development direction of MSI technology，single cell horizontal，absolute quantification，and portable instrument，is prospected.

Key words: mass spectrometry imaging, MALDI, matrix, ionization, secondary ion mass spectroscopy, desorption electrospray ionization, quantitative MSI

MIAO Yu-jiao, ZHU Long-jiao, XU Wen-tao. Novel Matrixes for Mass Spectrometry Imaging and Research Progress of It in Analyzing Biological Samples[J]. Biotechnology Bulletin, 2022, 38(12): 156-167.

Figures/Tables 3

References 69

[1]	Caprioli RM, Farmer TB, Gile J. Molecular imaging of biological samples:localization of peptides and proteins using MALDI-TOF MS[J]. Anal Chem, 1997, 69(23):4751-4760. pmid: 9406525
[2]	Fernández-Vega A, Chicano-Gálvez E, Prentice BM, et al. Optimization of a MALDI-Imaging protocol for studying adipose tissue-associated disorders[J]. Talanta, 2020, 219:121184. doi: 10.1016/j.talanta.2020.121184 URL
[3]	Zhang YX, Zhao XB, Ha W, et al. Spatial distribution analysis of phospholipids in rice by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging[J]. J Chromatogr A, 2021, 1651:462302. doi: 10.1016/j.chroma.2021.462302 URL
[4]	Yang JH, Caprioli RM. Matrix sublimation/recrystallization for imaging proteins by mass spectrometry at high spatial resolution[J]. Anal Chem, 2011, 83(14):5728-5734. doi: 10.1021/ac200998a pmid: 21639088
[5]	Shikano H, Miyama Y, Ikeda R, et al. Localization analysis of multiple vitamins in dried persimmon(Diospyros kaki)using matrix-assisted laser desorption/ionization mass spectrometry imaging[J]. J Oleo Sci, 2020, 69(8):959-964. doi: 10.5650/jos.ess20143 pmid: 32641617
[6]	Jaskolla TW, Lehmann WD, Karas M. 4-Chloro-alpha-cyanocinnamic acid is an advanced, rationally designed MALDI matrix[J]. Proc Natl Acad Sci USA, 2008, 105(34):12200-12205. doi: 10.1073/pnas.0803056105 URL
[7]	Liu HH, Zhou YM, Wang JY, et al. N-phenyl-2-naphthylamine as a novel MALDI matrix for analysis and in situ imaging of small molecules[J]. Anal Chem, 2018, 90(1):729-736. doi: 10.1021/acs.analchem.7b02710 pmid: 29172460
[8]	Barré FPY, Claes BSR, Dewez F, et al. Specific lipid and metabolic profiles of R-CHOP-resistant diffuse large B-cell lymphoma elucidated by matrix-assisted laser desorption ionization mass spectrometry imaging and in vivo imaging[J]. Anal Chem, 2018, 90(24):14198-14206. doi: 10.1021/acs.analchem.8b02910 pmid: 30422637
[9]	Li W, Ren LW, Zheng XJ, et al. 3-O-Acetyl-11-keto-β-boswellic acid ameliorated aberrant metabolic landscape and inhibited autophagy in glioblastoma[J]. Acta Pharm Sin B, 2020, 10(2):301-312. doi: 10.1016/j.apsb.2019.12.012 URL
[10]	Li B, Sun RY, Gordon A, et al. 3-aminophthalhydrazide(luminol)as a matrix for dual-polarity MALDI MS imaging[J]. Anal Chem, 2019, 91(13):8221-8228. doi: 10.1021/acs.analchem.9b00803 URL
[11]	Li N, Wang P, Liu XL, et al. Developing IR-780 as a novel matrix for enhanced MALDI MS imaging of endogenous high-molecular-weight lipids in brain tissues[J]. Anal Chem, 2019, 91(24):15873-15882. doi: 10.1021/acs.analchem.9b04315 pmid: 31718156
[12]	Ibrahim H, Jurcic K, Wang JSH, et al. 1, 6-diphenyl-1, 3, 5-hexatriene(DPH)as a novel matrix for MALDI MS imaging of fatty acids, phospholipids, and sulfatides in brain tissues[J]. Anal Chem, 2017, 89(23):12828-12836. doi: 10.1021/acs.analchem.7b03284 pmid: 29095596
[13]	Sun CL, Liu W, Ma SS, et al. Development of a high-coverage matrix-assisted laser desorption/ionization mass spectrometry imaging method for visualizing the spatial dynamics of functional metabolites in Salvia miltiorrhiza Bge[J]. J Chromatogr A, 2020, 1614:460704. doi: 10.1016/j.chroma.2019.460704 URL
[14]	Sun CL, Liu W, Mu Y, et al. 1, 1'-binaphthyl-2, 2'-diamine as a novel MALDI matrix to enhance the in situ imaging of metabolic heterogeneity in lung cancer[J]. Talanta, 2020, 209:120557. doi: 10.1016/j.talanta.2019.120557 URL
[15]	Liu YQ, Chen LL, Qin L, et al. Enhanced in situ detection and imaging of lipids in biological tissues by using 2, 3-dicyanohydroquinone as a novel matrix for positive-ion MALDI-MS imaging[J]. Chem Commun(Camb), 2019, 55(83):12559-12562.
[16]	Rzagalinski I, Kovačević B, Hainz N, et al. Toward higher sensitivity in quantitative MALDI imaging mass spectrometry of CNS drugs using a nonpolar matrix[J]. Anal Chem, 2018, 90(21):12592-12600. doi: 10.1021/acs.analchem.8b02740 pmid: 30260620
[17]	He HX, Qin L, Zhang YW, et al. 3, 4-dimethoxycinnamic acid as a novel matrix for enhanced in situ detection and imaging of low-molecular-weight compounds in biological tissues by MALDI-MSI[J]. Anal Chem, 2019, 91(4):2634-2643. doi: 10.1021/acs.analchem.8b03522 URL
[18]	Enomoto H, Takahashi S, Takeda S, et al. Distribution of flavan-3-ol species in ripe strawberry fruit revealed by matrix-assisted laser desorption/ionization-mass spectrometry imaging[J]. Molecules, 2019, 25(1):103. doi: 10.3390/molecules25010103 URL
[19]	Kaya I, Jennische E, Lange S, et al. Multimodal chemical imaging of a single brain tissue section using ToF-SIMS, MALDI-ToF and immuno/histochemical staining[J]. Analyst, 2021, 146(4):1169-1177. doi: 10.1039/d0an02172e pmid: 33393562
[20]	Yerra NV, Dyaga B, Dadinaboyina SB, et al. 2-cyano-3-(2-thienyl)acrylic acid as a new MALDI matrix for the analysis of a broad spectrum of analytes[J]. J Am Soc Mass Spectrom, 2021, 32(1):387-393. doi: 10.1021/jasms.0c00398 URL
[21]	Liu HQ, Han MM, Li JM, et al. A caffeic acid matrix improves in situ detection and imaging of proteins with high molecular weight close to 200, 000 Da in tissues by matrix-assisted laser desorption/ionization mass spectrometry imaging[J]. Anal Chem, 2021, 93(35):11920-11928. doi: 10.1021/acs.analchem.0c05480 URL
[22]	McLaughlin N, Bielinski TM, Tressler CM, et al. Pneumatically sprayed gold nanoparticles for mass spectrometry imaging of neurotransmitters[J]. J Am Soc Mass Spectrom, 2020, 31(12):2452-2461. doi: 10.1021/jasms.0c00156 URL
[23]	Qin R, Li P, Du MY, et al. Spatiotemporal visualization of insecticides and fungicides within fruits and vegetables using gold nanoparticle-immersed paper imprinting mass spectrometry imaging[J]. Nanomaterials(Basel), 2021, 11(5):1327.
[24]	Guan M, Zhang Z, Li SL, et al. Silver nanoparticles as matrix for MALDI FTICR MS profiling and imaging of diverse lipids in brain[J]. Talanta, 2018, 179:624-631. doi: S0039-9140(17)31197-9 pmid: 29310285
[25]	Wang T, Lee HK, Yue GGL, et al. A novel binary matrix consisting of graphene oxide and caffeic acid for the analysis of scutellarin and its metabolites in mouse kidney by MALDI imaging[J]. Analyst, 2021, 146(1):289-295. doi: 10.1039/d0an01539c pmid: 33140762
[26]	Chen CC, Laviolette SR, Whitehead SN, et al. Imaging of neurotransmitters and small molecules in brain tissues using laser desorption/ionization mass spectrometry assisted with zinc oxide nanoparticles[J]. J Am Soc Mass Spectrom, 2021, 32(4):1065-1079. doi: 10.1021/jasms.1c00021 URL
[27]	Dutkiewicz EP, Su CH, Lee HJ, et al. Visualizing vinca alkaloids in the petal of Catharanthus roseus using functionalized titanium oxide nanowire substrate for surface-assisted laser desorption/ionization imaging mass spectrometry[J]. Plant J, 2021, 105(4):1123-1133. doi: 10.1111/tpj.15092 URL
[28]	Fincher JA, Korte AR, Yadavilli S, et al. Multimodal imaging of biological tissues using combined MALDI and NAPA-LDI mass spectrometry for enhanced molecular coverage[J]. Analyst, 2020, 145(21):6910-6918. doi: 10.1039/D0AN00836B URL
[29]	Samarah LZ, Tran TH, Stacey G, et al. Mass spectrometry imaging of bio-oligomer polydispersity in plant tissues by laser desorption ionization from silicon nanopost arrays[J]. Angew Chem Int Ed Engl, 2021, 60(16):9071-9077. doi: 10.1002/anie.202015251 URL
[30]	Fincher JA, Jones DR, Korte AR, et al. Mass spectrometry imaging of lipids in human skin disease model hidradenitis suppurativa by laser desorption ionization from silicon nanopost arrays[J]. Sci Rep, 2019, 9(1):17508. doi: 10.1038/s41598-019-53938-0 pmid: 31767918
[31]	Fincher JA, Korte AR, Dyer JE, et al. Mass spectrometry imaging of triglycerides in biological tissues by laser desorption ionization from silicon nanopost arrays[J]. J Mass Spectrom, 2020, 55(4):e4443. doi: 10.1002/jms.4443
[32]	Xu Q, Tian R, Lu C. Mass spectrometry imaging of low-molecular-weight phenols liberated from plastics[J]. Anal Chem, 2021, 93(40):13703-13710. doi: 10.1021/acs.analchem.1c03397 URL
[33]	Calvano CD, Monopoli A, Cataldi TRI, et al. MALDI matrices for low molecular weight compounds:an endless story?[J]. Anal Bioanal Chem, 2018, 410(17):4015-4038. doi: 10.1007/s00216-018-1014-x URL
[34]	Baker TC, Han J, Borchers CH. Recent advancements in matrix-assisted laser desorption/ionization mass spectrometry imaging[J]. Curr Opin Biotechnol, 2017, 43:62-69. doi: 10.1016/j.copbio.2016.09.003 URL
[35]	Zhou QQ, Fülöp A, Hopf C. Recent developments of novel matrices and on-tissue chemical derivatization reagents for MALDI-MSI[J]. Anal Bioanal Chem, 2021, 413(10):2599-2617. doi: 10.1007/s00216-020-03023-7 pmid: 33215311
[36]	Misiorek M, Sekuła J, Ruman T. Mass spectrometry imaging of low molecular weight compounds in garlic(Allium sativum L.)with gold nanoparticle enhanced target[J]. Phytochem Anal, 2017, 28(6):479-486. doi: 10.1002/pca.2696 URL
[37]	Zhu ZP, Shen JJ, Xu YF, et al. The improved performance of MALDI-TOF MS on the analysis of herbal saponins by using DHB-GO composite matrix[J]. J Mass Spectrom, 2019, 54(8):684-692. doi: 10.1002/jms.4385 pmid: 31271243
[38]	马雯, 白玉, 刘虎威. 新型表面辅助激光解吸附/离子化质谱基质及其在生物检测中的应用[J]. 分析测试学报, 2020, 39(1):1-9.
	Ma W, Bai Y, Liu HW. Novel matrixes for surface-assisted laser desorption/ionization mass spectrometry and their applications in biological detection[J]. J Instrum Anal, 2020, 39(1):1-9.
[39]	Lin ZA, Wu J, Dong YQ, et al. Nitrogen and sulfur co-doped carbon-dot-assisted laser desorption/ionization time-of-flight mass spectrometry imaging for profiling bisphenol S distribution in mouse tissues[J]. Anal Chem, 2018, 90(18):10872-10880. doi: 10.1021/acs.analchem.8b02362 pmid: 30139256
[40]	Fincher JA, Dyer JE, Korte AR, et al. Matrix-free mass spectrometry imaging of mouse brain tissue sections on silicon nanopost arrays[J]. J Comp Neurol, 2019, 527(13):2101-2121. doi: 10.1002/cne.24566 pmid: 30358893
[41]	Agüi-Gonzalez P, Jähne S, Phan NTN. SIMS imaging in neurobiology and cell biology[J]. J Anal At Spectrom, 2019, 34(7):1355-1368. doi: 10.1039/C9JA00118B URL
[42]	蔡乐斯, 夏梦婵, 李展平, 等. 二次离子质谱生物成像[J]. 化学进展, 2021(1):97-110. doi: 10.7536/PC200458
	Cai I, Xia MC, Li ZP, et al. Bioimaging by secondary ion mass spectrometry[J]. Prog Chem, 2021(1):97-110. doi: 10.7536/PC200458
[43]	Passarelli MK, Pirkl A, Moellers R, et al. The 3D OrbiSIMS-label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power[J]. Nat Methods, 2017, 14(12):1175-1183. doi: 10.1038/nmeth.4504 pmid: 29131162
[44]	Ogrinc Poto\u010dnik N, Fisher GL, Prop A, et al. Sequencing and identification of endogenous neuropeptides with matrix-enhanced secondary ion mass spectrometry tandem mass spectrometry[J]. Anal Chem, 2017, 89(16):8223-8227. doi: 10.1021/acs.analchem.7b02573 pmid: 28753276
[45]	Takáts Z, Wiseman JM, Gologan B, et al. Mass spectrometry sampling under ambient conditions with desorption electrospray ionization[J]. Science, 2004, 306(5695):471-473. doi: 10.1126/science.1104404 pmid: 15486296
[46]	Javanshad R, Venter AR. Ambient ionization mass spectrometry:real-time, proximal sample processing and ionization[J]. Anal Methods, 2017, 9(34):4896-4907. doi: 10.1039/C7AY00948H URL
[47]	Soudah T, Zoabi A, Margulis K. Desorption electrospray ionization mass spectrometry imaging in discovery and development of novel therapies[J]. Mass Spectrom Rev, 2021, doi:10.1002/mas.21736. doi: 10.1002/mas.21736 URL
[48]	Vijayalakshmi K, Shankar V, Bain RM, et al. Identification of diagnostic metabolic signatures in clear cell renal cell carcinoma using mass spectrometry imaging[J]. Int J Cancer, 2020, 147(1):256-265. doi: 10.1002/ijc.32843 pmid: 31863456
[49]	Yang XH, Song XW, Zhang XX, et al. In situ DESI-MSI lipidomic profiles of mucosal margin of oral squamous cell carcinoma[J]. EBioMedicine, 2021, 70:103529. doi: 10.1016/j.ebiom.2021.103529 URL
[50]	Rivera ES, Djambazova KV, Neumann EK, et al. Integrating ion mobility and imaging mass spectrometry for comprehensive analysis of biological tissues:a brief review and perspective[J]. J Mass Spectrom, 2020, 55(12):e4614.
[51]	Levy AJ, Oranzi NR, Ahmadireskety A, et al. Recent progress in metabolomics using ion mobility-mass spectrometry[J]. Trac Trends Anal Chem, 2019, 116:274-281. doi: 10.1016/j.trac.2019.05.001 URL
[52]	Fu TT, Oetjen J, Chapelle M, et al. In situ isobaric lipid mapping by MALDI-ion mobility separation-mass spectrometry imaging[J]. J Mass Spectrom, 2020, 55(9):e4531. doi: 10.1002/jms.4531 URL
[53]	Towers MW, Karancsi T, Jones EA, et al. Optimised desorption electrospray ionisation mass spectrometry imaging(DESI-MSI)for the analysis of proteins/peptides directly from tissue sections on a travelling wave ion mobility Q-ToF[J]. J Am Soc Mass Spectrom, 2018, 29(12):2456-2466. doi: 10.1007/s13361-018-2049-0 URL
[54]	Stopka SA, Vertes A. Metabolomic profiling of adherent mammalian cells in situ by LAESI-MS with ion mobility separation[M]// Paglia G, Astarita G. Methods in Molecular Biology. New York, NY: Springer US, 2019:235-244.
[55]	Schramm T, Hester Z, Klinkert I, et al. imzML—a common data format for the flexible exchange and processing of mass spectrometry imaging data[J]. J Proteomics, 2012, 75(16):5106-5110. doi: 10.1016/j.jprot.2012.07.026 URL
[56]	Robichaud G, Garrard KP, Barry JA, et al. MSiReader:an open-source interface to view and analyze high resolving power MS imaging files on Matlab platform[J]. J Am Soc Mass Spectrom, 2013, 24(5):718-721. doi: 10.1007/s13361-013-0607-z URL
[57]	Parry RM, Galhena AS, Gamage CM, et al. omniSpect:an open MATLAB-based tool for visualization and analysis of matrix-assisted laser desorption/ionization and desorption electrospray ionization mass spectrometry images[J]. J Am Soc Mass Spectrom, 2013, 24(4):646-649. doi: 10.1007/s13361-012-0572-y URL
[58]	Bodzon-Kulakowska A, Marszalek-Grabska M, Antolak A, et al. Comparison of two freely available software packages for mass spectrometry imaging data analysis using brains from morphine addicted rats[J]. Eur J Mass Spectrom, 2016, 22(5):229-233. pmid: 27882888
[59]	He JM, Huang LJ, Tian RT, et al. MassImager:a software for interactive and in-depth analysis of mass spectrometry imaging data[J]. Anal Chim Acta, 2018, 1015:50-57. doi: 10.1016/j.aca.2018.02.030 URL
[60]	Cordes J, Enzlein T, Marsching C, et al. M2aia-Interactive, fast, and memory-efficient analysis of 2D and 3D multi-modal mass spectrometry imaging data[J]. GigaScience, 2021, 10(7):giab049. doi: 10.1093/gigascience/giab049 URL
[61]	Veselkov K, Sleeman J, Claude E, et al. BASIS:High-performance bioinformatics platform for processing of large-scale mass spectrometry imaging data in chemically augmented histology[J]. Sci Rep, 2018, 8(1):4053. doi: 10.1038/s41598-018-22499-z pmid: 29511258
[62]	Zhang WQ, Claesen M, Moerman T, et al. Spatially aware clustering of ion images in mass spectrometry imaging data using deep learning[J]. Anal Bioanal Chem, 2021, 413(10):2803-2819. doi: 10.1007/s00216-021-03179-w pmid: 33646352
[63]	Tian H, Sparvero LJ, Blenkinsopp P, et al. Secondary-ion mass spectrometry images cardiolipins and phosphatidylethanolamines at the subcellular level[J]. Angew Chem Int Ed Engl, 2019, 58(10):3156-3161. doi: 10.1002/anie.201814256 URL
[64]	Niehaus M, Soltwisch J, Belov ME, et al. Transmission-mode MALDI-2 mass spectrometry imaging of cells and tissues at subcellular resolution[J]. Nat Methods, 2019, 16(9):925-931. doi: 10.1038/s41592-019-0536-2 pmid: 31451764
[65]	Sparvero LJ, Tian H, Amoscato AA, et al. Direct mapping of phospholipid ferroptotic death signals in cells and tissues by gas cluster ion beam secondary ion mass spectrometry(GCIB-SIMS)[J]. Angew Chem Int Ed Engl, 2021, 60(21):11784-11788. doi: 10.1002/anie.202102001 URL
[66]	Zhao C, Cai ZW. Three-dimensional quantitative mass spectrometry imaging in complex system:from subcellular to whole organism[J]. Mass Spectrom Rev, 2022, 41(3):469-487. doi: 10.1002/mas.21674 URL
[67]	Unsihuay D, Mesa Sanchez D, Laskin J. Quantitative mass spectrometry imaging of biological systems[J]. Annu Rev Phys Chem, 2021, 72:307-329. doi: 10.1146/annurev-physchem-061020-053416 pmid: 33441032
[68]	Huang L, Wan JJ, Wei X, et al. Plasmonic silver nanoshells for drug and metabolite detection[J]. Nat Commun, 2017, 8(1):220. doi: 10.1038/s41467-017-00220-4 pmid: 28790311
[69]	Gan JR, Wei X, Li YX, et al. Designer SiO₂@Au nanoshells towards sensitive and selective detection of small molecules in laser desorption ionization mass spectrometry[J]. Nanomedicine, 2015, 11(7):1715-1723. doi: 10.2217/nnm-2016-0109 URL

	基质名称 Name of matrix	目标分析物类别 Target analyte class	离子模式 Ion mode	特点Characteristic	沉积方法 Deposition method	参考文献 Reference
有机小分子新型基质 Novel organic small molecule matrix	N-苯基-2-萘胺（PNA） N-Phenyl-2-naphthylamine	脂质、氨基酸、抗氧化剂、	/	强紫外线吸收、低基质背景信号、强耐盐能力	喷涂 Spray	[7]
	N-（1-萘基）乙二胺二盐酸盐（NEDC）N-（1-Naphthyl）ethylenediamine dihydrochloride	葡萄糖、Na⁺、K⁺、氨基酸、核苷酸、抗氧化剂、甘油磷脂	/	强耐盐能力，基质背景信号低，提高了对分析物类别的灵敏度	喷涂 Spray	[8-9]
	3-氨基邻苯二甲酰肼（3-APH） 3-Aminophthalhydrazide	核苷酸、脂质	+，-	双极性、高灵敏度、分子覆盖范围广、低基质背景信号、真空稳定性好	喷涂 Spray	[10]
	IR-780	高分子量脂质	/	强紫外吸收、强光热能力、强耐盐能力、共结晶均匀、低背景信号、高真空稳定性	喷涂 Spray	[11]
	1,6-二苯基-1,3,5-己三烯（DPH）1,6-Diphenyl-1,3,5-hexatriene	脂肪酸、多烯结构的脂类	/	高真空稳定性、高空间分辨率	升华 Sublimation	[12]
	1,1'-联萘-2,2'-二胺（BNDM） 1,1'-Binaphthyl-2,2'-diamine	氨基酸、有机酸、核苷、核苷酸、含氮碱基、胆固醇、多肽、脂肪酸、胆碱、肉碱、多胺、肌酸、磷脂等	+，-	双极性、低基质背景信号、高灵敏度、广泛的分子覆盖范围	喷涂 Spray	[13-14]
	2,3-二氰基氢醌（DCH） 2,3-Dicyanohydroquinone	脂质	+	高真空稳定性、高空间分辨率、高化学稳定性、高灵敏度	喷涂 Spray	[15]
	DCTB（2-[（2E）-3-（4-tert-butylphenyl）-2-methylprop-2-enylidene]malononitrile）	中枢神经系统药物	+	高灵敏度，低信号抑制	喷涂 Spray	[16]
	3,4-二甲氧基肉桂酸（DMCA） 3,4-Dimethoxycinnamic acid	小分子	+	低基质背景信号、高灵敏度、分子覆盖范围广	喷涂 Spray	[17]
	1,5-二氨基萘（DAN） 1,5-Diaminonaphthalene	脂质、酚类物质如原花色素及其单体等小分子	-	低激光能量、最小化发射次数、数据采集速度快、基质沉积均匀、在细胞水平保存特定组织学信息	升华 Sublimation	[18-19]
	2-氰基-3-（2-噻吩基）丙烯酸（CTA）2-Cyano-3-（2-thienyl）acrylic acid	脂质、蛋白质、多肽、正离子模式下的糖类、天然产物（即环烯醚萜）、聚乙二醇、有机金属	+，-	高信噪比和分辨率、可以用作分析大多数类别分析物的通用基质、提供组织表面的完整轮廓	升华 Sublimation	[20]
	咖啡酸（CA）Caffeic acid	高分子量蛋白质	/	强紫外线吸收、接近20 kDa的超宽检测范围、高电离效率	升华 Sublimation	[21]
无机纳米材料新型基质 Novel inorganic nano material matrix	金纳米粒子（AuNPs） Gold nanoparticles	神经递质（单胺类或乙酰胆碱类物质）、氯虫苯甲酰胺、嘧菌酯	/	高电离效率、增强了丰度低小分子类物质的成像信号、高空间分辨率，横向分辨率达到 5 μm（单细胞水平）	喷涂 Spray	[22-23]
	银纳米粒子（AgNPs） Silver nanoparticles	脂质如脂肪酸、甘油磷脂、鞘脂、甾醇以及一些小代谢物分子	﹢	通过银的选择性阳离子化来提高含有 π 键的分析物的电离效率	喷涂 Spray	[24]
	氧化石墨烯（GO） Graphene oxide	脂质等小分子、黄芩苷-灯盏花乙素	﹢，-	高电离效率、增强丰度低小分子类物质的成像信号、低基质背景信号	喷涂 Spray	[25]
	氧化锌纳米粒子（ZnO NPs） Zinc oxide nanoparticles	低分子量分子	﹢	在酸性pH值中溶解，定期酸洗可有效减少喷雾器喷嘴堵塞、结果高重现性	喷涂 Spray	[26]
	改性二氧化钛纳米线（TiO₂） Modified titanium dioxide nanowire	低分子量代谢物（长春花生物碱）	﹢	高选择性、高检测限、修改程序简单且具有成本效益、适用于复杂的天然生物样品	/	[27]
	硅纳米柱阵列（NAPA） Silicon nanopost array	中性脂质如甘油三酯、胆固醇酯、己糖神经酰胺和一些小代谢物；聚羟基丁酸、聚谷氨酸和多糖寡聚物	+，-	允许分离异构体、信号强度增加、均匀性好、和传统基质MALDI-MSI 平台之间实现脂质覆盖的互补性	/	[28-31]
	层状双氢氧化物（LDH） Layered double hydroxide	低分子量酚类物质	-	高稳定性、氢键促进分析物电离、优先检测以羟基为主的分析物	喷涂 Spray	[32]

	基质名称 Name of matrix	目标分析物类别 Target analyte class	离子模式 Ion mode	特点Characteristic	沉积方法 Deposition method	参考文献 Reference
有机小分子新型基质 Novel organic small molecule matrix	N-苯基-2-萘胺（PNA） N-Phenyl-2-naphthylamine	脂质、氨基酸、抗氧化剂、	/	强紫外线吸收、低基质背景信号、强耐盐能力	喷涂 Spray	[7]
	N-（1-萘基）乙二胺二盐酸盐（NEDC）N-（1-Naphthyl）ethylenediamine dihydrochloride	葡萄糖、Na⁺、K⁺、氨基酸、核苷酸、抗氧化剂、甘油磷脂	/	强耐盐能力，基质背景信号低，提高了对分析物类别的灵敏度	喷涂 Spray	[8-9]
	3-氨基邻苯二甲酰肼（3-APH） 3-Aminophthalhydrazide	核苷酸、脂质	+，-	双极性、高灵敏度、分子覆盖范围广、低基质背景信号、真空稳定性好	喷涂 Spray	[10]
	IR-780	高分子量脂质	/	强紫外吸收、强光热能力、强耐盐能力、共结晶均匀、低背景信号、高真空稳定性	喷涂 Spray	[11]
	1,6-二苯基-1,3,5-己三烯（DPH）1,6-Diphenyl-1,3,5-hexatriene	脂肪酸、多烯结构的脂类	/	高真空稳定性、高空间分辨率	升华 Sublimation	[12]
	1,1'-联萘-2,2'-二胺（BNDM） 1,1'-Binaphthyl-2,2'-diamine	氨基酸、有机酸、核苷、核苷酸、含氮碱基、胆固醇、多肽、脂肪酸、胆碱、肉碱、多胺、肌酸、磷脂等	+，-	双极性、低基质背景信号、高灵敏度、广泛的分子覆盖范围	喷涂 Spray	[13-14]
	2,3-二氰基氢醌（DCH） 2,3-Dicyanohydroquinone	脂质	+	高真空稳定性、高空间分辨率、高化学稳定性、高灵敏度	喷涂 Spray	[15]
	DCTB（2-[（2E）-3-（4-tert-butylphenyl）-2-methylprop-2-enylidene]malononitrile）	中枢神经系统药物	+	高灵敏度，低信号抑制	喷涂 Spray	[16]
	3,4-二甲氧基肉桂酸（DMCA） 3,4-Dimethoxycinnamic acid	小分子	+	低基质背景信号、高灵敏度、分子覆盖范围广	喷涂 Spray	[17]
	1,5-二氨基萘（DAN） 1,5-Diaminonaphthalene	脂质、酚类物质如原花色素及其单体等小分子	-	低激光能量、最小化发射次数、数据采集速度快、基质沉积均匀、在细胞水平保存特定组织学信息	升华 Sublimation	[18-19]
	2-氰基-3-（2-噻吩基）丙烯酸（CTA）2-Cyano-3-（2-thienyl）acrylic acid	脂质、蛋白质、多肽、正离子模式下的糖类、天然产物（即环烯醚萜）、聚乙二醇、有机金属	+，-	高信噪比和分辨率、可以用作分析大多数类别分析物的通用基质、提供组织表面的完整轮廓	升华 Sublimation	[20]
	咖啡酸（CA）Caffeic acid	高分子量蛋白质	/	强紫外线吸收、接近20 kDa的超宽检测范围、高电离效率	升华 Sublimation	[21]
无机纳米材料新型基质 Novel inorganic nano material matrix	金纳米粒子（AuNPs） Gold nanoparticles	神经递质（单胺类或乙酰胆碱类物质）、氯虫苯甲酰胺、嘧菌酯	/	高电离效率、增强了丰度低小分子类物质的成像信号、高空间分辨率，横向分辨率达到 5 μm（单细胞水平）	喷涂 Spray	[22-23]
	银纳米粒子（AgNPs） Silver nanoparticles	脂质如脂肪酸、甘油磷脂、鞘脂、甾醇以及一些小代谢物分子	﹢	通过银的选择性阳离子化来提高含有 π 键的分析物的电离效率	喷涂 Spray	[24]
	氧化石墨烯（GO） Graphene oxide	脂质等小分子、黄芩苷-灯盏花乙素	﹢，-	高电离效率、增强丰度低小分子类物质的成像信号、低基质背景信号	喷涂 Spray	[25]
	氧化锌纳米粒子（ZnO NPs） Zinc oxide nanoparticles	低分子量分子	﹢	在酸性pH值中溶解，定期酸洗可有效减少喷雾器喷嘴堵塞、结果高重现性	喷涂 Spray	[26]
	改性二氧化钛纳米线（TiO₂） Modified titanium dioxide nanowire	低分子量代谢物（长春花生物碱）	﹢	高选择性、高检测限、修改程序简单且具有成本效益、适用于复杂的天然生物样品	/	[27]
	硅纳米柱阵列（NAPA） Silicon nanopost array	中性脂质如甘油三酯、胆固醇酯、己糖神经酰胺和一些小代谢物；聚羟基丁酸、聚谷氨酸和多糖寡聚物	+，-	允许分离异构体、信号强度增加、均匀性好、和传统基质MALDI-MSI 平台之间实现脂质覆盖的互补性	/	[28-31]
	层状双氢氧化物（LDH） Layered double hydroxide	低分子量酚类物质	-	高稳定性、氢键促进分析物电离、优先检测以羟基为主的分析物	喷涂 Spray	[32]

离子源 Ion source	基质辅助激光解吸电离质谱成像 MALDI MSI	二次离子质谱成像 SIMS MSI	解吸电喷雾电离质谱成像 DESI MSI
电离类型Ionization type	软	硬	软
是否需要基质Need matrix or not	是	否	否
可检测物质类型 The type of substance that can be detected	小分子代谢物和药物、生物大分子如多肽、蛋白质、核酸、聚糖等	元素、小分子代谢物和药物、脂类	小分子代谢物和药物、脂类、多肽
质量范围Mass range/Da	300-100 000	<2 000	100-2 000
空间分辨率Spatial resolution/μm	5-100	0.1-1	40-200
扫描深度Depth of the scanning/μm	0.1-20	0.5-10	1-50

离子源 Ion source	基质辅助激光解吸电离质谱成像 MALDI MSI	二次离子质谱成像 SIMS MSI	解吸电喷雾电离质谱成像 DESI MSI
电离类型Ionization type	软	硬	软
是否需要基质Need matrix or not	是	否	否
可检测物质类型 The type of substance that can be detected	小分子代谢物和药物、生物大分子如多肽、蛋白质、核酸、聚糖等	元素、小分子代谢物和药物、脂类	小分子代谢物和药物、脂类、多肽
质量范围Mass range/Da	300-100 000	<2 000	100-2 000
空间分辨率Spatial resolution/μm	5-100	0.1-1	40-200
扫描深度Depth of the scanning/μm	0.1-20	0.5-10	1-50