Abstract
We present a universal method to efficiently improve reproducibility and sensitivity of surface-assisted laser desorption/ionization time of flight mass spectrometry (SALDI-TOF MS). In this method, the Si pillar array with unique surface wettability is used as substrate for ionizing analyte. The Si pillar is fabricated based on the combination of photolithography and metal-assisted chemical etching, which is of hydrophilic top and hydrophobic bottom and side wall. Based on the surface wettability of the Si pillar, a droplet of an aqueous analyte solution can be confined on the top of the Si pillar. After evaporation of solvent, an analyte deposition spot is formed on the top of Si pillar. The visible size of the Si pillar allows the sample spot to be easily found. Meanwhile, the diameter of the Si pillar is smaller than that of the laser, allowing the observation of all analyte molecules under one laser shot. Therefore, the reproducibility and sensitivity are highly improved with this method, which allows for the quantitative analysis. Furthermore, this method is applicable for different analytes dissolved in water, including amino acids, dye molecules, polypeptides, and polymers. The application of this substrate is demonstrated by analyzing real samples at low concentration. It should be a promising method for sensitive and reproducible detection for SALDI-TOF MS.
Similar content being viewed by others
References
van Kampen JJA, Burgers PC, de Groot R, Gruters RA, Luider TM. Biomedical application of MALDI mass spectrometry for small-molecule analysis. Mass Spectrom Rev. 2011;30:101–20.
Cho YT, Su H, Huang TL, Chen HC, Wu WJ, Wu PC, et al. Matrix-assisted laser desorption ionization/time-of-flight mass spectrometry for clinical diagnosis. Clin Chim Acta. 2013;415:266–75.
Law KP, Larkin JR. Recent advances in SALDI-MS techniques and their chemical and bioanalytical applications. Anal Bioanal Chem. 2011;399:2597–622.
Abdelhamid HN, Lin YC, Wu HF. Thymine chitosan nanomagnets for specific preconcentration of mercury(II) prior to analysis using SELDI-MS. Microchim Acta. 2017;184:1517–27.
Guinan T, Ronci M, Vasani R, Kobus H, Voelcker NH. Comparison of the performance of different silicon-based SALDI substrates for illicit drug detection. Talanta. 2015;132:494–502.
Abdelhamid HN. Nanoparticle assisted laser desorption/ionization mass spectrometry for small molecule analytes. Microchim Acta. 2018;185:200.
Silina YE, Volmer DA. Nanostructured solid substrates for efficient laser desorption/ionization mass spectrometry (LDI-MS) of low molecular weight compounds. Analyst. 2013;138:7053–65.
Shi CY, Deng CH, Zhang XM, Yang PY. Synthesis of highly water-dispersible polydopamine-modified multiwalled carbon nanotubes for matrix-assisted laser desorption/ionization mass spectrometry analysis. ACS Appl Mater Interfaces. 2013;5:7770–6.
Xu SY, Li YF, Zou HF, Qiu JS, Guo Z, Guo BC. Carbon nanotubes as assisted matrix for laser desorption/ionization time-of-flight mass spectrometry. Anal Chem. 2003;75:6191–5.
Lai HZ, Wang SG, Wu CY, Chen YC. Detection of staphylococcus aureus by functional gold nanoparticle-based affinity surface-assisted laser desorption/ionization mass spectrometry. Anal Chem. 2015;87:2114–20.
Pilolli R, Ditaranto N, Di Franco C, Palmisano F, Cioffi N. Thermally annealed gold nanoparticles for surface-assisted laser desorption ionisation-mass spectrometry of low molecular weight analytes. Anal Bioanal Chem. 2012;404:1703–11.
Xu GJ, Liu SJ, Peng JX, Lv WP, Wu RA. Facile synthesis of gold@graphitized mesoporous silica nanocomposite and its surface-assisted laser desorption/ionization for time-of-flight mass spectroscopy. ACS Appl Mater Interfaces. 2015;7:2032–8.
Kim JI, Park JM, Hwang SJ, Kang MJ, Pyun JC. Top-down synthesized TiO2 nanowires as a solid matrix for surface-assisted laser desorption/ionization time-of-flight (SALDI-TOF) mass spectrometry. Anal Chim Acta. 2014;836:53–60.
Popovic IA, Nesic M, Vranjes M, Saponjic Z, Petkovic M. SALDI-TOF-MS analyses of small molecules (citric acid, dexasone, vitamins E and A) using TiO2 nanocrystals as substrates. Anal Bioanal Chem. 2016;408:7481–90.
Alhmoud HZ, Guinan TM, Elnathan R, Kobus H, Voelcker NH. Surface-assisted laser desorption/ionization mass spectrometry using ordered silicon nanopillar arrays. Analyst. 2014;139:5999–6009.
Tsao CW, Lin YJ, Chen PY, Yang YL, Tan SH. Nanoscale silicon surface-assisted laser desorption/ionization mass spectrometry: environment stability and activation by simple vacuum oven desiccation. Analyst. 2016;141:4973–81.
Wei J, Buriak JM, Siuzdak G. Desorption-ionization mass spectrometry on porous silicon. Nature. 1999;399:243–6.
Luo GH, Chen Y, Daniels H, Dubrow R, Vertes A. Internal energy transfer in laser desorption/ionization from silicon nanowires. J Phys Chem B. 2006;110:13381–6.
Tsao CW, Yang ZJ. High sensitivity and high detection specificity of gold-nanoparticle-grafted nanostructured silicon mass spectrometry for glucose analysis. ACS Appl Mater Interfaces. 2015;7:22630–7.
Kailasa SK, Wu HF. Surface-assisted laser desorption-ionization mass spectrometry of oligosaccharides using magnesium oxide nanoparticles as a matrix. Microchim Acta. 2013;180:405–13.
Wang JP, Wang Y, Guo XH, Wang P, Zhao T, Wang JY. Matrix assisted laser desorption/ionization time-of-flight mass spectrometric determination of benzo[a] pyrene using a MIL-101(Fe) matrix. Microchim Acta. 2018;185:175.
Abdelmaksoud HH, Guinan TM, Voelcker NH. Fabrication of nanostructured mesoporous germanium for application in laser desorption ionization mass spectrometry. ACS Appl Mater Interfaces. 2017;9:5092–9.
Yang M, Chen X, Jiang TJ, Guo Z, Liu JH, Huang XJ. Electrochemical detection of trace arsenic(III) by nanocomposite of nanorod-like alpha-MnO2 decorated with approximately 5 nm au nanoparticles: considering the change of arsenic speciation. Anal Chem. 2016;88:9720–8.
Li X, Xu GJ, Zhang HY, Liu SJ, Niu H, Peng JX, et al. A homogeneous carbon nanosphere film-spot: for highly efficient laser desorption/ionization of small biomolecules. Carbon. 2017;121:343–52.
Tu T, Gross ML. Miniaturizing sample spots for matrix-assisted laser desorption/ionization mass spectrometry. Trac-Trend Anal Chem. 2009;28:833–41.
Herzer N, Eckardt R, Hoeppener S, Schubert US. Sample target substrates with reduced spot size for MALDI-TOF mass spectrometry based on patterned self-assembled monolayers. Adv Funct Mater. 2009;19:2777–81.
Teng F, Zhu QY, Wang YL, Du J, Lu N. Enhancing reproducibility of SALDI MS detection by concentrating analytes within laser spot. Talanta. 2018;179:583–7.
Schuerenbeg M, Luebbert C, Eickhoff H, Kalkum M, Lehrach H, Nordhoff E. Prestructured MALDI-MS sample supports. Anal Chem. 2000;72:3436–42.
Xu YD, Watson JT, Bruening ML. Patterned monolayer/polymer films for analysis of dilute or salt-contaminated protein samples by MALDI-MS. Anal Chem. 2003;75:185–90.
Wallace RA, Charlton JJ, Kirchner TB, Lavrik NV, Datskos PG, Sepaniak MJ. Superhydrophobic analyte concentration utilizing colloid-pillar array SERS substrates. Anal Chem. 2014;86:11819–25.
Cheung M, Lee WWY, McCracken JN, Larmour IA, Brennan S, Bell SEJ. Raman analysis of dilute aqueous samples by localized evaporation of submicroliter droplets on the tips of superhydrophobic copper wires. Anal Chem. 2016;88:4541–7.
Song W, Psaltis D, Crozier KB. Superhydrophobic bull's-eye for surface-enhanced Raman scattering. Lab Chip. 2014;14:3907–11.
Cheung M, Lee WW, Cowcher DP, Goodacre R, Bell SE. SERS of meso-droplets supported on superhydrophobic wires allows exquisitely sensitive detection of dipicolinic acid, an anthrax biomarker, considerably below the infective dose. Chem Commun. 2016;52:9925–8.
Marinaro G, Accardo A, De Angelis F, Dane T, Weinhausen B, Burghammer M, et al. A superhydrophobic chip based on SU-8 photoresist pillars suspended on a silicon nitride membrane. Lab Chip. 2014;14:3705–9.
Coffinier Y, Kurylo I, Drobecq H, Szunerits S, Melnyk O, Zaitsev VN, et al. Decoration of silicon nanostructures with copper particles for simultaneous selective capture and mass spectrometry detection of His-tagged model peptide. Analyst. 2014;139:5155–63.
Kang MJ, Pyun JC, Lee JC, Choi YJ, Park JH, Park JG, et al. Nanowire-assisted laser desorption and ionization mass spectrometry for quantitative analysis of small molecules. Rapid Commun Mass Spectrom. 2005;19:3166–70.
Kim SM, Khang DY. Bulk micromachining of Si by metal-assisted chemical etching. Small. 2014;10:3761–6.
Alderman DJ. Malachite green: a review. J Fish Dis. 1985;8:289–98.
Hall Z, Hopley C, O'Connor G. High accuracy determination of malachite green and leucomalachite green in salmon tissue by exact matching isotope dilution mass spectrometry. J Chromatogr B. 2008;874:95–100.
Iores-Marçal LM, Viel TA, Buck HS, Nunes VA, Gozzo AJ, Cruz-Silva I, et al. Bradykinin release and inactivation in brain of rats submitted to an experimental model of Alzheimer's disease. Peptides. 2006;27:3363–9.
Funding
This work was supported by the National Natural Science Foundation of China (No. 21673096).
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(PDF 10182 kb)
Rights and permissions
About this article
Cite this article
Zhu, Q., Teng, F., Wang, Z. et al. Confining analyte droplets on visible Si pillars for improving reproducibility and sensitivity of SALDI-TOF MS. Anal Bioanal Chem 411, 1135–1142 (2019). https://doi.org/10.1007/s00216-018-01565-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-018-01565-5