Abstract
A novel method for direct high-throughput analysis of multi-elements in cerebrospinal fluid (CSF) samples by laser ablation inductively coupled plasma mass spectrometry with an aerosol local extraction cryogenic ablation cell (ALEC-LA-ICP-MS) was developed. Microliter-level CSF samples were frozen by a designed cryogenic ablation cell and directly analyzed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) without time-consuming pretreatment. Compared with the precision obtained at room temperature (20℃), that obtained at low temperature (− 25℃) was significantly improved; the RSDs were reduced from 8.3% (Zn) to 32.6% (Mn) to 2.2% (Pb) to 6.5% (Mn) with six times parallel determination. To meet the analytical requirement of the micro-volume CSF samples, the laminar flow aerosol local extraction strategy was adopted to improve the transmission efficiency of aerosols, and the signal intensity was increased by four times compared with the standard commercial ablation cell. The standard solution with 0.4% bovine serum albumin (BSA) matrix was used as matrix-match external standard, and Rh was added into the samples as internal standard. The limits of detection (LODs) ranged from 0.17 μg·L−1 (Mn) to 8.67 μg·L−1 (Mg). Standard addition recovery experiments and the determination of CRM serum L-1 and L-2 were carried out to validate the accuracy of the method; all results indicated there were excellent accuracy and precision in the proposed method. The matrix-scanning function in the GeoLas software combined with the microwell plate realizes the high-throughput automatic analysis. Twenty-four CSF samples from different patients were determined; the results showed that there might be a correlation between the metal elements in CSF and the diseases, which means that the proposed method has potential in the diagnosis of neurological diseases.
Graphical Abstract
Similar content being viewed by others
References
Theiner S, Schoeberl A, Fischer L, Neumayer S, Hann S, Koellensperger G. FI-ICP-TOFMS for quantification of biologically essential trace elements in cerebrospinal fluid – high-throughput at low sample volume. Analyst. 2019;144:4653–60. https://doi.org/10.1039/C9AN00039A.
Yamada S, Kelly E. Cerebrospinal fluid dynamics and the pathophysiology of hydrocephalus: new concepts. Semin Ultrasound CT MRI. 2016;37:84–91. https://doi.org/10.1053/j.sult.2016.01.001.
Korvela M, Lind A-L, Wetterhall M, Gordh T, Andersson M, Pettersson J. Quantification of 10 elements in human cerebrospinal fluid from chronic pain patients with and without spinal cord stimulation. J Trace Elem Med Biol. 2016;37:1–7. https://doi.org/10.1016/j.jtemb.2016.06.003.
Gerhardsson L, Lundh T, Minthon L, Londos E. Metal concentrations in plasma and cerebrospinal fluid in patients with Alzheimer’s disease. Dement Geriatr Cogn Disord. 2008;25:508–15. https://doi.org/10.1159/000129365.
Melo TM, Larsen C, White LR, Aasly J, Sjobakk TE, Flaten TP, Sonnewald U, Syversen T. Manganese, copper, and zinc in cerebrospinal fluid from patients with multiple sclerosis. Biol Trace Elem Res. 2003;93:1–8. https://doi.org/10.1385/BTER:93:1-3:1.
Cañabate Á, García-Ruiz E, Resano M, Todolí J-L. Cerebrospinal fluid elemental analysis by using a total sample consumption system operated at high temperature adapted to inductively coupled plasma mass spectrometry. J Anal At Spectrom. 2017;32:1916–24. https://doi.org/10.1039/C7JA00210F.
Chen Z, Chen B, He M, Hu B. Negative magnetophoresis focusing microchips online-coupled with ICP–MS for high-throughput single-cell analysis. Anal Chem. 2022;94:6649–56. https://doi.org/10.1021/acs.analchem.1c04216.
Hu B, Li S, Xiang G, He M, Jiang Z. Recent progress in electrothermal vaporization–inductively coupled plasma atomic emission spectrometry and inductively coupled plasma mass spectrometry. Appl Spectrosc Rev. 2007;42:203–34. https://doi.org/10.1080/05704920601184317.
Cañabate Á, García-Ruiz E, Resano M, Todolí J-L. Analysis of whole blood by ICP-MS equipped with a high temperature total sample consumption system. J Anal At Spectrom. 2017;32:78–87. https://doi.org/10.1039/C6JA00374E.
Liao X, Luo T, Zhang S, Zhang W, Zong K, Liu Y, Hu Z. Direct and rapid multi-element analysis of wine samples in their natural liquid state by laser ablation ICPMS. J Anal At Spectrom. 2020;35:1071–9. https://doi.org/10.1039/C9JA00404A.
Liao X, Hu Z, Luo T, Zhang W, Liu Y, Zong K, Zhou L, Zhang J. Determination of major and trace elements in geological samples by laser ablation solution sampling-inductively coupled plasma mass spectrometry. J Anal At Spectrom. 2019;34:1126–34. https://doi.org/10.1039/C9JA00027E.
Becker JS, Matusch A, Wu B. Bioimaging mass spectrometry of trace elements – recent advance and applications of LA-ICP-MS: a review. Anal Chim Acta. 2014;835:1–18. https://doi.org/10.1016/j.aca.2014.04.048.
Deng H, Xu H, Zhou J, Tang D, Yang W, Hu M, Zhang Y, Ke Y. Multi-element imaging of urinary stones by LA-ICP-MS with a homogeneous co-precipitation CaC2O4-matrix calibration standard. Anal Bioanal Chem. 2023;415:1751–64. https://doi.org/10.1007/s00216-023-04576-z.
Tanvir EM, Whitfield KM, Ng JC, Shaw PN. Development and validation of an ICP-MS method and its application to determine multiple trace elements in small volumes of whole blood and plasma. J Anal Toxicol. 2021;44:1036–46. https://doi.org/10.1093/jat/bkaa033.
Hsieh H-F, Chang W-S, Hsieh Y-K, Wang C-F. Using dried-droplet laser ablation inductively coupled plasma mass spectrometry to quantify multiple elements in whole blood. Anal Chim Acta. 2011;699:6–10. https://doi.org/10.1016/j.aca.2011.05.002.
Keerthi K, George SD, Sebastian JG, Warrier AK, Chidangil S, Unnikrishnan VK. Optimization of different sampling approaches in liquid LIBS analysis for environmental applications. J Anal At Spectrom. 2022;37:2625–36. https://doi.org/10.1039/D2JA00202G.
Li F, Lei X, Li H, Cui H, Guo W, Jin L, Hu S. Direct multi-elemental analysis of whole blood samples by LA-ICP-MS employing a cryogenic ablation cell. J Anal At Spectrom. 2023;38:90–6. https://doi.org/10.1039/D2JA00282E.
Makino Y, Matsuo H, Masuda K, Onozawa S, Nakazato T. Rapid and sensitive determination of leached platinum group elements in organic reaction solution of metal-catalyzed reactions by laser ablation-ICP-MS with spot-drying on paper. J Anal At Spectrom. 2022;37:1787–92. https://doi.org/10.1039/D2JA00141A.
Cizdziel JV. Determination of lead in blood by laser ablation ICP-TOF-MS analysis of blood spotted and dried on filter paper: a feasibility study. Anal Bioanal Chem. 2007;388:603–11. https://doi.org/10.1007/s00216-007-1242-y.
Moreda-Piñeiro J, Cantarero-Roldán A, Moreda-Piñeiro A, Cocho JÁ, Bermejo Barrera P. Laser ablation inductively coupled plasma mass spectrometry for multi-elemental determination in dried blood spots. J Anal At Spectrom. 2017;32:1500–7. https://doi.org/10.1039/c7ja00168a.
Kumtabtim U, Siripinyanond A, Auray-Blais C, Ntwari A, Becker JS. Analysis of trace metals in single droplet of urine by laser ablation inductively coupled plasma mass spectrometry. Int J Mass Spectrom. 2011;307:174–81. https://doi.org/10.1016/j.ijms.2011.01.030.
Chantada-Vázquez MP, Moreda-Piñeiro J, Cantarero-Roldán A, Bermejo-Barrera P, Moreda-Piñeiro A. Development of dried serum spot sampling techniques for the assessment of trace elements in serum samples by LA-ICP-MS. Talanta. 2018;186:169–75. https://doi.org/10.1016/j.talanta.2018.04.049.
Velghe S, Delahaye L, Stove CP. Is the hematocrit still an issue in quantitative dried blood spot analysis? J Pharm Biomed Anal. 2019;163:188–96. https://doi.org/10.1016/j.jpba.2018.10.010.
Freeman JD, Rosman LM, Ratcliff JD, Strickland PT, Graham DR, Silbergeld EK. State of the science in dried blood spots. Clin Chem. 2018;64:656–79. https://doi.org/10.1373/clinchem.2017.275966.
Resano M, Belarra MA, García-Ruiz E, Aramendía M, Rello L. Dried matrix spots and clinical elemental analysis. Current status, difficulties, and opportunities. TrAC Trends Anal Chem. 2018;99:75–87. https://doi.org/10.1016/j.trac.2017.12.004.
Meesters RJ, Zhang J, van Huizen NA, Hooff GP, Gruters RA, Luider TM. Dried matrix on paper disks: the next generation DBS microsampling technique for managing the hematocrit effect in DBS analysis. Bioanalysis. 2012;4:2027–35. https://doi.org/10.4155/bio.12.175.
Feldmann J, Kindness A, Ek P. Laser ablation of soft tissue using a cryogenically cooled ablation cell. J Anal At Spectrom. 2002;17:813–8. https://doi.org/10.1039/b201960d.
Konz I, Fernández B, Fernández ML, Pereiro R, Sanz-Medel A. Design and evaluation of a new Peltier-cooled laser ablation cell with on-sample temperature control. Anal Chim Acta. 2014;809:88–96. https://doi.org/10.1016/j.aca.2013.11.040.
Konz I, Fernández B, Fernández ML, Pereiro R, González-Iglesias H, Coca-Prados M, Sanz-Medel A. Quantitative bioimaging of trace elements in the human lens by LA-ICP-MS. Anal Bioanal Chem. 2014;406:2343–8. https://doi.org/10.1007/s00216-014-7617-y.
Becker JS, Zoriy MV, Dehnhardt M, Pickhardt C, Zilles K. Copper, zinc, phosphorus and sulfur distribution in thin section of rat brain tissues measured by laser ablation inductively coupled plasma mass spectrometry: possibility for small-size tumor analysis. J Anal At Spectrom. 2005;20:912. https://doi.org/10.1039/b504978b.
Albrecht M, Derrey IT, Horn I, Schuth S, Weyer S. Quantification of trace element contents in frozen fluid inclusions by UV-fs-LA-ICP-MS analysis. J Anal Spectrom. 2014;29:1034–41. https://doi.org/10.1039/C4JA00015C.
Jian W, Albrecht M, Lehmann B, Mao J, Horn I, Li Y, Ye H, Li Z, Fang G, Xue Y. UV-fs-LA-ICP-MS analysis of CO 2-rich fluid inclusions in a frozen state: example from the Dahu Au-Mo deposit, Xiaoqinling Region, Central China. Geofluids. 2018;2018:1–17. https://doi.org/10.1155/2018/3692180.
Bleiner D, Bogaerts A. Computer simulations of sample chambers for laser ablation–inductively coupled plasma spectrometry. Spectrochim Acta Part B At Spectrosc. 2007;62:155–68. https://doi.org/10.1016/j.sab.2007.02.010.
Monticelli D, Gurevich EL, Hergenröder R. Design and performances of a cyclonic flux cell for laser ablation. J Anal At Spectrom. 2009;24:328. https://doi.org/10.1039/b807991a.
Hu Z, Liu Y, Gao S, Hu S, Dietiker R, Günther D. A local aerosol extraction strategy for the determination of the aerosol composition in laser ablation inductively coupled plasma mass spectrometry. J Anal At Spectrom. 2008;23:1192. https://doi.org/10.1039/b803934h.
Luo T, Wang Y, Hu Z, Günther D, Liu Y, Gao S, Li M, Hu S. Further investigation into ICP-induced elemental fractionation in LA-ICP-MS using a local aerosol extraction strategy. J Anal At Spectrom. 2015;30:941–9. https://doi.org/10.1039/C4JA00483C.
Bleiner D, Altorfer H. A novel gas inlet system for improved aerosol entrainment in laser ablation inductively coupled plasma mass spectrometry. J Anal At Spectrom. 2005;20:754. https://doi.org/10.1039/b505248c.
Liu Y, Hu Z, Gao S, Günther D, Xu J, Gao C, Chen H. In situ analysis of major and trace elements of anhydrous minerals by LA-ICP-MS without applying an internal standard. Chem Geol. 2008;257:34–43. https://doi.org/10.1016/j.chemgeo.2008.08.004.
Longerich HP, Jackson SE, Gunther D. Laser ablation inductively coupled plasma mass spectrometric transient signal data acquisition and analyte concentration calculation. J Anal At Spectrom. 1997;11:899–904. https://doi.org/10.1039/JA9961100899.
Acknowledgements
The editor and two anonymous reviewers are also thanked for their conscientious treatments and constructive suggestions on improving the manuscript.
Funding
This study was financially supported by the National Key R&D Program of China (No.2021YFC2903003) and the National Natural Science Foundation of China (No.41873072).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Source of biological material
Twenty-four CSF samples were taken from the Renmin Hospital of Wuhan University (Wuhan, China), after approval by the Renmin Hospital of Wuhan University (Wuhan, China).
Competing interests
The authors have no competing interests to declare that are relevant to the content of this article.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Li, F., Cui, H., Zhang, D. et al. Direct multi-elemental analysis of cerebrospinal fluid samples by LA-ICP-MS employing an aerosol local extraction cryogenic ablation cell. Anal Bioanal Chem 415, 6051–6061 (2023). https://doi.org/10.1007/s00216-023-04878-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-023-04878-2