Calibration strategies for elemental analysis of biological samples by LA-ICP-MS and LIBS – A review

  • Mauro Martinez
  • Matthieu BaudeletEmail author
Part of the following topical collections:
  1. Young Investigators in (Bio-)Analytical Chemistry


Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and laser-induced breakdown spectroscopy (LIBS) are widely accepted techniques for direct sampling of biological materials for elemental analysis, with increasing applications being reported over the recent years. This review is focused on the calibration materials used to quantify trace elements in different biological samples such as soft tissues (for instance brain, liver, hair) and hard tissues (bones and teeth). The design of a correct calibration strategy relies on the choice of an adapted reference material that can be commercially available or prepared in-house, which will be reviewed here. A large variety of methods has been approached and considered promising over the years, and the development of matrix-matched reference biological materials seems now closer than ever and gives hope to even better quantitation using LIBS and LA-ICP-MS.


Matrix-matched standards Laser ablation LA-ICP-MS LIBS 


Compliance with ethical standards

This critical review did not involve human participants and/or animals.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Bauer OB, Hachmöller O, Borovinskaya O, Sperling M, Schurek H-J, Ciarimboli G, et al. LA-ICP-TOF-MS for rapid, all-elemental and quantitative bioimaging, isotopic analysis and the investigation of plasma processes. J Anal At Spectrom. 2019. Scholar
  2. 2.
    González de Vega R, Fernández-Sánchez ML, Pisonero J, Eiró N, Vizoso FJ, Sanz-Medel A. Quantitative bioimaging of Ca, Fe, Cu and Zn in breast cancer tissues by LA-ICP-MS. J Anal At Spectrom. 2017;32(3):671–7. Scholar
  3. 3.
    Busser B, Moncayo S, Trichard F, Bonneterre V, Pinel N, Pelascini F, et al. Characterization of foreign materials in paraffin-embedded pathological specimens using in situ multi-elemental imaging with laser spectroscopy. Modern Pathol: an official journal of the United States and Canadian Academy of Pathology, Inc. 2017. Scholar
  4. 4.
    Birka M, Wentker KS, Lusmoller E, Arheilger B, Wehe CA, Sperling M, et al. Diagnosis of nephrogenic systemic fibrosis by means of elemental bioimaging and speciation analysis. Anal Chem. 2015;87(6):3321–8. Scholar
  5. 5.
    Noel M, Spence J, Harris KA, Robbins CT, Fortin JK, Ross PS, et al. Grizzly bear hair reveals toxic exposure to mercury through salmon consumption. Environ Sci Technol. 2014;48(13):7560–7. Scholar
  6. 6.
    Pozebon D, Dressler VL, Mesko MF, Matusch A, Becker JS. Bioimaging of metals in thin mouse brain section by laser ablation inductively coupled plasma mass spectrometry: novel online quantification strategy using aqueous standards. J Anal At Spectrom. 2010;25(11):1739. Scholar
  7. 7.
    Romaris-Hortas V, Bianga J, Moreda-Pineiro A, Bermejo-Barrera P, Szpunar J. Speciation of iodine-containing proteins in Nori seaweed by gel electrophoresis laser ablation ICP-MS. Talanta. 2014;127:175–80. Scholar
  8. 8.
    Bianga J, Bouslimani A, Bec N, Quenet F, Mounicou S, Szpunar J, et al. Complementarity of MALDI and LA ICP mass spectrometry for platinum anticancer imaging in human tumor. Metallomics: integrated biometal science. 2014;6(8):1382–6. Scholar
  9. 9.
    Hare D, Austin C, Doble P, Arora M. Elemental bio-imaging of trace elements in teeth using laser ablation-inductively coupled plasma-mass spectrometry. J Dent. 2011;39(5):397–403. Scholar
  10. 10.
    Curtin P, Austin C, Curtin A, Gennings C, Arora M, Tammimies K, et al. Dynamical features in fetal and postnatal zinc-copper metabolic cycles predict the emergence of autism spectrum disorder. Sci Adv. 2018;4(5):eaat1293. Scholar
  11. 11.
    Feng L, Wang J, Li H, Luo X, Li J. A novel absolute quantitative imaging strategy of iron, copper and zinc in brain tissues by Isotope Dilution Laser Ablation ICP-MS. Anal Chim Acta. 2017;984:66–75. Scholar
  12. 12.
    Caceres JO, Pelascini F, Motto-Ros V, Moncayo S, Trichard F, Panczer G, et al. Megapixel multi-elemental imaging by laser-induced breakdown spectroscopy, a technology with considerable potential for paleoclimate studies. Sci Rep. 2017;7(1):5080. Scholar
  13. 13.
    Fingerhut S, Niehoff AC, Sperling M, Jeibmann A, Paulus W, Niederstadt T, et al. Spatially resolved quantification of gadolinium deposited in the brain of a patient treated with gadolinium-based contrast agents. J Trace Elements Med Biol: organ of the Society for Minerals and Trace Elements. 2018;45:125–30. Scholar
  14. 14.
    Reifschneider O, Wentker KS, Strobel K, Schmidt R, Masthoff M, Sperling M, et al. Elemental bioimaging of thulium in mouse tissues by laser ablation-ICPMS as a complementary method to heteronuclear proton magnetic resonance imaging for cell tracking experiments. Anal Chem. 2015;87(8):4225–30. Scholar
  15. 15.
    Koppen C, Reifschneider O, Castanheira I, Sperling M, Karst U, Ciarimboli G. Quantitative imaging of platinum based on laser ablation-inductively coupled plasma-mass spectrometry to investigate toxic side effects of cisplatin. Metallomics: integrated biometal science. 2015;7(12):1595–603. Scholar
  16. 16.
    Bartkus L, Amarasiriwardena D, Arriaza B, Bellis D, Yañez J. Exploring lead exposure in ancient Chilean mummies using a single strand of hair by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Microchem J. 2011;98(2):267–74. Scholar
  17. 17.
    Christensen JR, McBeth JM, Sylvain NJ, Spence J, Chan HM. Hartnell’s time machine: 170-year-old nails reveal severe zinc deficiency played a greater role than lead in the demise of the Franklin Expedition. J Archaeol Sci Rep. 2016. Scholar
  18. 18.
    Jimenez-Lamana J, Laborda F, Bolea E, Abad-Alvaro I, Castillo JR, Bianga J, et al. An insight into silver nanoparticles bioavailability in rats. Metallomics : integrated biometal science. 2014;6(12):2242–9. Scholar
  19. 19.
    Zheng L-N, Sang Y-B, Luo R-P, Wang B, Yi F-T, Wang M, et al. Determination of silver nanoparticles in single cells by microwell trapping and laser ablation ICP-MS determination. J Anal At Spectrom. 2019;34(5):915–21. Scholar
  20. 20.
    Costas-Rodríguez M, Van Acker T, Hastuti AAMB, Devisscher L, Van Campenhout S, Van Vlierberghe H, et al. Laser ablation-inductively coupled plasma-mass spectrometry for quantitative mapping of the copper distribution in liver tissue sections from mice with liver disease induced by common bile duct ligation. J Anal At Spectrom. 2017. Scholar
  21. 21.
    Samanta G, Sharma R, Roychowdhury T, Chakraborti D. Arsenic and other elements in hair, nails, and skin-scales of arsenic victims in West Bengal, India. Sci Total Environ. 2004;326(1-3):33–47. Scholar
  22. 22.
    Sussulini A, Becker JS. Application of laser microdissection ICP-MS for high resolution elemental mapping in mouse brain tissue: a comparative study with laser ablation ICP-MS. Talanta. 2015;132:579–82. Scholar
  23. 23.
    Grün R, Eggins S, Kinsley L, Moseley H, Sambridge M. Laser ablation U-series analysis of fossil bones and teeth. Palaeogeogr Palaeoclimatol Palaeoecol. 2014;416:150–67. Scholar
  24. 24.
    Stadlbauer C, Reiter C, Patzak B, Stingeder G, Prohaska T. History of individuals of the 18th/19th centuries stored in bones, teeth, and hair analyzed by LA-ICP-MS--a step in attempts to confirm the authenticity of Mozart’s skull. Anal Bioanal Chem. 2007;388(3):593–602. Scholar
  25. 25.
    Singh VK, Kumar V, Sharma J. Importance of laser-induced breakdown spectroscopy for hard tissues (bone, teeth) and other calcified tissue materials. Lasers Med Sci. 2015;30(6):1763–78. Scholar
  26. 26.
    Praamsma ML, Parsons PJ. Characterization of calcified reference materials for assessing the reliability of manganese determinations in teeth and bone. J Anal At Spectrom. 2014;29(7):1243–51. Scholar
  27. 27.
    Martinez M, Bayne C, Aiello D, Julian M, Gaume R, Baudelet M. Multi-elemental matrix-matched calcium hydroxyapatite reference materials for laser ablation: evaluation on teeth by laser-induced breakdown spectroscopy. Spectrochim Acta Part B: Atomic Spectroscopy. 2019;159:105650. Scholar
  28. 28.
    Praamsma ML, Parsons PJ. Calibration strategies for quantifying the Mn content of tooth and bone samples by LA-ICP-MS. Accred Qual Assur. 2016;21(6):385–93. Scholar
  29. 29.
    Horner NS, Beauchemin D. The use of sol-gels as solid calibration standards for the analysis of soil samples by laser ablation coupled to inductively coupled plasma mass spectrometry. J Anal At Spectrom. 2014;29(4):715–20. Scholar
  30. 30.
    Narukawa T, Willie S. Dried deposits of biological tissues solubilized using formic acid for LA ICP-TOF-MS. J Anal At Spectrom. 2010;25(7):1145. Scholar
  31. 31.
    Pořízka P, Klus J, Hrdlička A, Vrábel J, Škarková P, Prochazka D, et al. Impact of laser-induced breakdown spectroscopy data normalization on multivariate classification accuracy. J Anal At Spectrom. 2017;32(2):277–88. Scholar
  32. 32.
    Lee Y, Nam S-H, Ham K-S, Gonzalez J, Oropeza D, Quarles D, et al. Multivariate classification of edible salts: simultaneous laser-induced breakdown spectroscopy and laser-ablation inductively coupled plasma mass spectrometry analysis. Spectrochim Acta Part B: Atomic Spectroscopy. 2016;118:102–11. Scholar
  33. 33.
    Putnam RA, Mohaidat QI, Daabous A, Rehse SJ. A comparison of multivariate analysis techniques and variable selection strategies in a laser-induced breakdown spectroscopy bacterial classification. Spectrochim Acta Part B: Atomic Spectroscopy. 2013;87(0):161–7. Scholar
  34. 34.
    IUPAC (2014) Compendium of Chemical Terminology “Gold Book” 2nd Edition.Google Scholar
  35. 35.
    Monk SM, Lev SM. Toxicological applications of cryogenic laser ablation inductively coupled plasma time of flight mass spectrometry (CLA-ICP-TOF-MS). J Anal At Spectrom. 2013;28(2):274–9. Scholar
  36. 36.
    Wagner B, Syta O, Kępa L, Bulska E, Segal I, Halicz L (2018) Evaluation of the role of matrix matching for LA-ICP-MS calibration approaches in quantitative elemental analysis of tooth enamel. J Mex Chem Soc 62(2).
  37. 37.
    Kasem MA, Gonzalez JJ, Russo RE, Harith MA. Effect of the wavelength on laser induced breakdown spectrometric analysis of archaeological bone. Spectrochim Acta Part B: Atomic Spectroscopy. 2014;101:26–31. Scholar
  38. 38.
    Noel M, Christensen JR, Spence J, Robbins CT. Using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to characterize copper, zinc and mercury along grizzly bear hair providing estimate of diet. Sci Total Environ. 2015;529:1–9. Scholar
  39. 39.
    Gallagher CP, Howland KL, Sandstrom SJ, Halden NM. Migration tactics affect spawning frequency in an iteroparous salmonid (Salvelinus malma) from the Arctic. PLoS One. 2018;13(12):e0210202. Scholar
  40. 40.
    Warburton ML, Reid MR, Stirling CH, Closs G. Validation of depth-profiling LA-ICP-MS in otolith applications. Can J Fish Aquat Sci. 2017;74(4):572–81. Scholar
  41. 41.
    Grottoli AG, Matthews KA, Palardy JE, McDonough WF. High resolution coral Cd measurements using LA-ICP-MS and ID-ICP-MS: Calibration and interpretation. Chem Geol. 2013;356:151–9. Scholar
  42. 42.
    Ahmed I, Ahmed R, Yang J, Law AWL, Zhang Y, Lau C. Elemental analysis of the thyroid by laser induced breakdown spectroscopy. Biomed Opt Express. 2017;8(11):4865–71. Scholar
  43. 43.
    Bellis DJ, Santamaria-Fernandez R. Ink jet patterns as model samples for the development of LA-ICP-SFMS methodology for mapping of elemental distribution with reference to biological samples. J Anal At Spectrom. 2010;25(7):957. Scholar
  44. 44.
    Bonta M, Lohninger H, Marchetti-Deschmann M, Limbeck A. Application of gold thin-films for internal standardization in LA-ICP-MS imaging experiments. Analyst. 2014;139(6):1521–31. Scholar
  45. 45.
    Stark HJ, Wennrich R. A new approach for calibration of laser ablation inductively coupled plasma mass spectrometry using thin layers of spiked agarose gels as references. Anal Bioanal Chem. 2011;399(6):2211–7. Scholar
  46. 46.
    Turková S, Vašinová Galiová M, Štůlová K, Čadková Z, Száková J, Otruba V, et al. Study of metal accumulation in tapeworm section using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Microchem J. 2017;133:380–90. Scholar
  47. 47.
    Izmer A, Gholap D, De Houwer K, Cuyckens F, Vanhaecke F. A pilot study on the use of laser ablation-ICP-mass spectrometry for assessing/mapping the distribution of a drug and its metabolites across the body compartments of rats. J Anal At Spectrom. 2012;27(3):413. Scholar
  48. 48.
    Gholap D, Verhulst J, Ceelen W, Vanhaecke F. Use of pneumatic nebulization and laser ablation-inductively coupled plasma-mass spectrometry to study the distribution and bioavailability of an intraperitoneally administered Pt-containing chemotherapeutic drug. Anal Bioanal Chem. 2012;402(6):2121–9. Scholar
  49. 49.
    Niehaus R, Sperling M, Karst U. Study on aerosol characteristics and fractionation effects of organic standard materials for bioimaging by means of LA-ICP-MS. J Anal At Spectrom. 2015;30(10):2056–65. Scholar
  50. 50.
    Reifschneider O, Wehe CA, Diebold K, Becker C, Sperling M, Karst U. Elemental bioimaging of haematoxylin and eosin-stained tissues by laser ablation ICP-MS. J Anal At Spectrom. 2013;28(7):989. Scholar
  51. 51.
    Sancey L, Motto-Ros V, Busser B, Kotb S, Benoit JM, Piednoir A, et al. Laser spectrometry for multi-elemental imaging of biological tissues. Sci Rep. 2014;4:6065. Scholar
  52. 52.
    Cheajesadagul P, Wananukul W, Siripinyanond A, Shiowatana J. Metal doped keratin film standard for LA-ICP-MS determination of lead in hair samples. J Anal At Spectrom. 2011;26(3):493–8. Scholar
  53. 53.
    Ugarte A, Unceta N, Pécheyran C, Goicolea MA, Barrio RJ. Development of matrix-matching hydroxyapatite calibration standards for quantitative multi-element LA-ICP-MS analysis: application to the dorsal spine of fish. J Anal At Spectrom. 2011;26(7):1421. Scholar
  54. 54.
    Singh VK, Rai AK, Rai PK, Jindal PK. Cross-sectional study of kidney stones by laser-induced breakdown spectroscopy. Lasers Med Sci. 2009;24(5):749–59. Scholar
  55. 55.
    Bishop DP, Clases D, Fryer F, Williams E, Wilkins S, Hare DJ, et al. Elemental bio-imaging using laser ablation-triple quadrupole-ICP-MS. J Anal At Spectrom. 2016;31(1):197–202. Scholar
  56. 56.
    González-Iglesias H, Petrash C, Rodríguez-Menéndez S, García M, Álvarez L, Fernández-Vega Cueto L, et al. Quantitative distribution of Zn, Fe and Cu in the human lens and study of the Zn–metallothionein redox system in cultured lens epithelial cells by elemental MS. J Anal At Spectrom. 2017. Scholar
  57. 57.
    Ahmed I, Yang J, Law AWL, Manno FAM, Ahmed R, Zhang Y, et al. Rapid and in situ optical detection of trace lithium in tissues. Biomed Opt Express. 2018;9(9):4459–71. Scholar
  58. 58.
    Reifschneider O, Wehe CA, Raj I, Ehmcke J, Ciarimboli G, Sperling M, et al. Quantitative bioimaging of platinum in polymer embedded mouse organs using laser ablation ICP-MS. Metallomics : integrated biometal science. 2013;5(10):1440–7. Scholar
  59. 59.
    Eastman RR, Jursa TP, Benedetti C, Lucchini RG, Smith DR. Hair as a biomarker of environmental manganese exposure. Environ Sci Technol. 2013;47(3):1629–37. Scholar
  60. 60.
    Dressler VL, Pozebon D, Mesko MF, Matusch A, Kumtabtim U, Wu B, et al. Biomonitoring of essential and toxic metals in single hair using on-line solution-based calibration in laser ablation inductively coupled plasma mass spectrometry. Talanta. 2010;82(5):1770–7. Scholar
  61. 61.
    Pozebon D, Dressler VL, Matusch A, Becker JS. Monitoring of platinum in a single hair by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) after cisplatin treatment for cancer. Int J Mass Spectrom. 2008;272(1):57–62. Scholar
  62. 62.
    Byrne S, Amarasiriwardena D, Bandak B, Bartkus L, Kane J, Jones J, et al. Were Chinchorros exposed to arsenic? Arsenic determination in Chinchorro mummies' hair by laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS). Microchem J. 2010;94(1):28–35. Scholar
  63. 63.
    Steely S, Amarasiriwardena D, Jones J, Yañez J. A rapid approach for assessment of arsenic exposure by elemental analysis of single strand of hair using laser ablation-inductively coupled plasma-mass spectrometry. Microchem J. 2007;86(2):235–40. Scholar
  64. 64.
    Barats A, Pecheyran C, Amouroux D, Dubascoux S, Chauvaud L, Donard OF. Matrix-matched quantitative analysis of trace-elements in calcium carbonate shells by laser-ablation ICP-MS: application to the determination of daily scale profiles in scallop shell (Pecten maximus). Anal Bioanal Chem. 2007;387(3):1131–40. Scholar
  65. 65.
    Draxler J, Zitek A, Meischel M, Stranzl-Tschegg SE, Mingler B, Martinelli E, et al. Regionalized quantitative LA-ICP-MS imaging of the biodegradation of magnesium alloys in bone tissue. J Anal At Spectrom. 2015;30(12):2459–68. Scholar
  66. 66.
    Gruhl S, Witte F, Vogt J, Vogt C. Determination of concentration gradients in bone tissue generated by a biologically degradable magnesium implant. J Anal At Spectrom. 2009;24(2):181–8. Scholar
  67. 67.
    Balter V, Lécuyer C. Determination of Sr and Ba partition coefficients between apatite and water from 5°C to 60°C: a potential new thermometer for aquatic paleoenvironments 1 1Associate editor: A. Mucci Geochim Cosmochim Acta. 2004;68(3):423–32. Scholar
  68. 68.
    Tacail T, Télouk P, Balter V. Precise analysis of calcium stable isotope variations in biological apatites using laser ablation MC-ICPMS. J Anal At Spectrom. 2016;31(1):152–62. Scholar
  69. 69.
    Miliszkiewicz N, Walas S, Tobiasz A, Kołodziej M, Szostek K. Calibration for elemental dental tissue analysis by laser ablation inductively coupled plasma mass spectrometry. Anal Lett. 2016;50(8):1345–59. Scholar
  70. 70.
    Sutharsini U, Thanihaichelvan M, Singh R. Two-step sintering of ceramics. 2018. Scholar

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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.National Center of Forensic ScienceUniversity of Central FloridaOrlandoUSA
  2. 2.Chemistry DepartmentUniversity of Central FloridaOrlandoUSA
  3. 3.CREOL – The College of Optics and PhotonicsUniversity of Central FloridaOrlandoUSA

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