Table 2.
MALDI-MSI approaches with on-tissue chemical derivatization of analytes in tissue sections
| Target analytes in tissue sections | OTCD reagent | Solution | Application and incubation | Tissue | Ref. |
|---|---|---|---|---|---|
| Amine as targeted functional groups | |||||
| Isoniazid | CA | 50% in MeOH | High velocity spin coating, 30 min at RT | Lung tissue sections of rabbit infected with M. tuberculosis and dosed with isoniazid | [59] |
| Dopamine, norepinephrine, epinephrine, γ-aminobutyric acid | CA | 23 mg/mL CA and 8.5 mg/mL trans-ferulic acid in MeOH | Automatic spraying | Adrenal gland tissue sections of pig, brain tissue sections of rat | [60] |
| Glycine, alanine, serine, proline, valine, threonine, isoleucine/leucine, aspartate, glutamine, lysine, glutamate, tryptophan, dopamine, γ-aminobutyric acid, taurine, 3-methoxytyramine, serotonin, L-dihydroxyphenylalanine | CA | 4 mg/mL in 50% MeOH | Automatic spraying, overnight at RT | Brain tissue sections from female C57BL/6J mice | [61] |
| Glycine, alanine, aminobutenoic acid, serine, γ-aminobutyric acid and more other metabolites | CA | 20 mg/mL in MeOH | Electrospraying | Leaf and root tissue sections of two different maize genotypes (B73 and Mo17) | [62] |
| 67 small-molecule metabolites including amino acids, neurotransmitters, dipeptides and others | CA | 5 mg/mL in 50% MeOH | Electrospraying, overnight at 37 °C | Brain tissue sections of rats | [63] |
| Neuropeptides | NBA + hv | 5 mg/mL in ACN/EtOH/FA/H2O | Automatic spraying, nanosecond with hv | Brain tissue sections from mouse brain | [64] |
| Amino acids excluding lysine, serine, histidine, threonine, aspartate and arginine | TAHS | 5 mg/mL in ACN | Airbrush, overnight at 55 °C | Liver tissue sections from xenograft mouse models of human colon cancer | [65] |
| Glycine, alanine, serine, proline, valine, threonine, isoleucine/leucine, aspartate, glutamine, lysine, glutamate, tryptophan, dopamine, γ-aminobutyric acid, taurine, 3-methoxytyramine, serotonin, L-dihydroxyphenylalanine | TAHS | 5 mg/mL in 50% ACN | Automatic spraying, overnight at RT | Brain tissue sections from female C57BL/6 J mice | [61] |
| Phenylalanine, tyrosine | TAHS | 5 mg/mL in ACN | Automatic spraying, 24 h at 55 °C | Liver tissue sections from a H460 human NSCLC xenograft mouse model | [66] |
| Noradrenaline | TAHS | 5 mg/mL in ACN | Airbrush, 15 min at 55 °C | Adrenal gland tissue sections from tumor patients | [67] |
| Glutamine | TAHS | 5 mg/mL in ACN | Automatic spraying, 24 h at 55 °C | Tumor and benign tissue sections from tumor patients | [68] |
| Dopamine, tyrosine, tryptamine, tyramine, phenethylamine, 3-methoxytyramine, serotonin, γ-aminobutyric acid, glutamate | DPP-TFB**, TMP-TFB | 0.09 mg/mL in 50% MeOH with 0.06% TEA | Automatic spraying, 30 min at RT | Brain tissue sections from treated and control male Sprague-Dawley rats and C57BL/6J male mice, brain tissue sections from primate | [69] |
| Dopamine and amphetamine, β-N-methylamino-L-alanine | DPP*, TMP, PBDPP* | 1.11 mg/mL in 75% MeOH with 0.05% TEA, 1 mg/mL in 83% MeOH with 0.05% TEA, 0.2 mg/mL in 80% MeOH with 0.07% TEA | Automatic spraying, 15 min at RT | Brain tissue sections from the treated and untreated C57BL/6J male mice, male Wistar rat pups or adult Sprague-Dawley rats | [70] |
| Glycine, alanine, serine, proline, valine, threonine, isoleucine/leucine, aspartate, glutamine, lysine, glutamate, tryptophan, dopamine, γ-aminobutyric acid, taurine, 3-methoxytyramine, serotonin, L-dihydroxyphenylalanine | DPP-TFB | 5 mg/mL in MeOH | Automatic spraying, overnight at RT | Brain tissue sections from female C57BL/6J mice | [61] |
| Glutamate, γ-aminobutyric acid | DPP-TFB | 1.33 mg/mL in MeOH | Manual spraying, direct spraying of matrix | Brain tissue sections from SCR-KO and WT mice | [71] |
| Dopamine, serotonin, norepinephrine | DPP-TFB | 1.3 mg/mL in MeOH | Airbrush, direct spraying of matrix | Whole brain of the C57BL/6J mouse | [72] |
| Dopamine, 3-methoxytyramine | DPP-TFB | 1.3 mg/mL in MeOH | Airbrush, direct spraying of matrix | Brain tissue sections from male C57BL/6J mice and WT mice | [73] |
| Dopamine, glycine, alanine, γ-aminobutyric acid, proline, valine, threonine, taurine, leucine, aspartate, tyramine, glutamine, lysine, glutamate, tryptamine, 3-methoxytyramine, tyrosine, L-dihydroxyphenylalanine | DPP-TFB | 5 mg/mL in MeOH | Automatic spraying, overnight | Brain tissue sections from glioblastoma multiforme mice and WT mice | [74] |
| Dopamine, serotonin, γ-aminobutyric acid, histamine, threonine, phenethylamine, methylhistamine, agmatine, adenine, tyramine, lysine, tryptamine, L-dihydroxyphenylalanine | DPP-TFB | 1.33 mg/mL in 75% MeOH with 0.05% TEA | Automatic spraying, 24 h at RT | Brain tissue sections from rock crabs Cancer irroratus | [75] |
| Dopaminergic and serotonergic neurotransmitters and their associated metabolites containing primary and secondary amine groups | FMP-8*, FMP-9*, FMP-10* | 4.4 mM in 70% ACN | Automatic spraying, no incubation | Brain tissue sections from treated and untreated rat and primate models of Parkinsonism, brain tissue sections from a patient with Parkinson’s disease | [76] |
| Dopamine, γ-aminobutyric acid | FMP-10* | 1.8 mg/mL in 70% ACN | Automatic spraying, no incubation | Brain tissue sections from GPR37 KO mice and WT mice | [77] |
| Phenolic hydroxyl as targeted functional groups | |||||
| Cannabinoids and their metabolites | FMPTS | 10 mg/mL in ACN | Airbrush | Human hair | [78] |
| Catecholamines (dopamine, epinephrine, norepinephrine) | (N-Me)Py+B(OH)2* | 12 mg/mL in 60% ACN | Automatic spraying | Adrenal gland tissue sections from pig | [79] |
| Dopaminergic and serotonergic neurotransmitters and their associated metabolites containing phenolic hydroxyl groups | FMP-8*, FMP-9*, FMP-10* | 4.4 mM in 70% ACN | Automatic spraying, no incubation | Brain tissue sections from treated and untreated rats and primate models of Parkinsonism, brain tissue sections from a patient with Parkinson’s disease | [76] |
| Carbonyl as targeted functional groups | |||||
| Fluticasone propionate | DMNTH*, DNPH* | 5 mg/mL in 50% ACN with 0.1% TFA, 4 mg/mL in 50% ACN | Spotting, 48 h at 37 °C | Rat lung tissue sections | [80] |
| 11-Dehydrocorticosterone and corticosterone | GirT | 0.15 mg/cm2, addition spraying of MeOH with 0.2% TFA | Precoated, 60 min at 40 °C | Adrenal gland tissue sections of Sprague-Dawley rat and brain tissue sections of C57BL/6 mice | [81] |
| Triamcinolone acetonide | GirT | 5 mg/mL in MeOH with 0.2% TFA | Automatic spraying, 150 min at 40 °C | Human incubated cartilage | [82] |
| Testosterone | GirT | 5 mg/mL in 2.5% acetic acid | Airbrush, 90 min at RT | Testis tissue sections of C57BL/6 mice after human chorionic gonadotrophin treatment | [83] |
| Testosterone and 5α-dihydrotestosterone | GirT | 5 mg/mL in 80% MeOH with 0.1% TFA | Automatic spraying, 60 min at 40 °C | Testis tissue sections of C57BL/6 mice and prostate tissue sections of Sprague-Dawley rats after human chorionic gonadotrophin treatment | [84] |
| Cortisone, aldosterone, 18-oxocortisol and progesterone | GirT | 10 mg/mL in 20% acetic acid | Airbrush, 90 min at RT | Adrenal gland tissue sections of human patients and Sprague Dawley rats | [85] |
| Abscisic acid and 12-oxo-phytodienoic acid | GirT | 5 mg/mL in 80% MeOH with 2% TFA | Airbrush, 30 min at RT | Immature P. vulgaris L. seed sections | [86] |
| Pyruvic acid, glycolaldehyde, 2-pentenal, dithylacetone, 1-hexanal, 1-heptanal, jasmonic acid, dotriacontanal and more other metabolites | GirT | 10 mg/mL in MeOH with 2% TFA | Electrospraying | Leaf and root tissue sections of two different maize genotypes (B73 and Mo17) | [62] |
| 11-Dehydrocorticosterone, corticosterone | GirT | 5 mg/mL in 80% MeOH with 0.2% TFA | Electrospraying, 1 h at 40 °C | Brain tissue sections of Sprague-Dawley rats | [63] |
| Aldosterone, cortisol, cortisone, 18-OH-corticosterone | GirT | 10 mg/mL in 20% acetic acid | Airbrush, 60 min at RT | Tissue sections of human adrenal glands | [67] |
| Carboxylic acid as targeted functional groups | |||||
| Docosahexaenoic acid, arachidonic acid, oleic acid, palmitoleic acid, eicosapentaenoic acid, linoleic acid | PA | 2 mM with 10 mM of activation reagents in ACN | Electrospraying or airbrush | Brain tissue sections from rats | [87] |
| 3-Maleylpyruvate, N-acetyl-L-glutamate, palmitic acid, oleic acid, stearic acid and more other metabolites | PA | 6 mM PA and 30 mM activation reagents in ACN | Electrospraying | Leaf and root tissue sections of two different maize genotypes (B73 and Mo17) | [62] |
| Fatty acids (C16:1, C16:0, C18:2, C18:1, C18:0, C18:3, C20:4, C20:0, C22:6, C22:4) | DMPI | 3 mM with 1 mM HATU in 80% ACN | Electrospraying | Tumor and normal tissue sections of patients with thyroid carcinoma, brain tissue sections of rat | [88] |
| Thiol as targeted functional groups | |||||
| α-Chain and ß-chain of reduced insulin, glutathione, cysteine, cysteinylglycine | CHC-MAL*** | 10 mg/mL in 50% ACN | Automatic spraying | Liver and pancreas tissue sections of pig, tumor tissue sections of mouse xenograft | [89] |
| Double bond groups | |||||
| PC 36:1, PS 36:2 isomers | Benzaldehyde | Vapor of benzaldehyde | Custom-made reaction chamber, triggered by 254 nm | Brain tissue sections of C57BL6/N mice | [90] |
| PC 34:1, PC 36:1 isomers | BPh* | 20 mg/mL in solution (ACN: isopropanol: H2O, 6:3:1 with 0.5% TFA) | 3 min with UV-light | Brain tissue sections of C57BL6/N mice and tegument of S. mansoni | [91] |
| PC 34:1, PC 36:1 isomers | Ozone | Gas | High-pressure linear ion trap with ozone | Brain tissue sections of ND2:SmoA1 transgenic mice containing tumors | [92] |
| PC 34:1 isomers | Ozone | Ozone from an ozone generator | Glass flask flushed with the flow of ozone, up to 30 min | Brain tissue sections of BALB/c mice, human colon tissue sections | [93] |
CA, 4-hydroxy-3-methoxycinnamaldehyde; NBA, 2-nitrobenzaldehyde; TAHS, p-N,N,N-trimethylammonioanilyl N-hydroxysuccinimidyl carbamate iodide; DPP-TFB, 2,4-diphenyl-pyranylium tetrafluoroborate; DPP, 2,4-diphenyl-pyranylium; PBDPP, 1,4-phenylene-4,4′-bis (2,6-diphenyl-4-pyrylium); TMP, 2,4,6-trimethylpyrylium; FMP-8: 4-(10-bromoanthracen-9-yl)-2-fluoro-1-methylpyridin-1-ium iodide; FMP-9, 4-(anthracen-9-yl)-2-fluoro-1-ethylpyridin-1-ium iodide; FMP-10, 4-(anthracen-9-yl)-2-fluoro-1-methylpyridin-1-ium iodide; FMPTS, 2-fluoro-1-methylpyridinium p-toluenesulfonate; (N-Me)Py+B(OH)2, 4-(N-methyl)pyridinium boronic acid; DNPH, 2,4-dinitrophenylhydrazine; DMNTH, 4-dimethylamino-6-(4-methoxy-1-naphthyl)-1,3,5-triazine-2-hydrazine; GirT, Girard’s reagent T; PA, 2-picolylamine (PA); DMPI, N,N-dimethylpiperazine iodide; CHC-Mal, (E)-2-cyano-N-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)-3-(4-hydroxyphenyl)-acrylamide (CHC-Mal); BPh, benzophenone; ACN, acetonitrile; TFA, trifluoroacetic acid; EtOH, ethanol; FA, formic acid; TEA, triethylamine; RT, room temperature; HATU, 2-(7-azabenzotriazol-1-yl)-N,N,N´,N´-tetramethyluronium hexafluorophosphate; MeOH, methanol
*Reactive matrix; **Reactive matrix in high concentration; ***Reactive matrix for small thiol-containing molecules