Skip to main content
SpringerLink
Log in

Assessment of strategies for the formation of stable suspensions of titanium dioxide nanoparticles in aqueous media suitable for the analysis of biological fluids

  • Communication
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Due to their omnipresence in consumer products, there is a growing concern about the potential effects of nanoparticles on human health. Toxicological assessment and NP end-product studies require proper quantification of these materials in biological fluids. However, their quantifications in these media require stable predispersed NP solutions in aqueous media to enable the fortification in the matrices of interest or the preparation of calibration standards. In this study, a sample preparation scheme was developed by studying various dispersion media (polyvinylpyrrolidone and polyethylene glycol) and sonication strategies (bath and ultrasonic probe) to ensure homogeneous dispersion of titanium dioxide nanoparticles. Optimization of the various parameters was performed using SRM NIST 1898 NP reference material, composed of rutile and anatase phases. Number-based size distribution for titanium dioxide NPs was determined by dynamic light scattering and single-particle inductively coupled plasma mass spectrometry to evaluate the procedure efficiency. Changes in mean size and most frequent size distribution were also studied to determine if the agglomeration of nanoparticles occurs at the various dispersion conditions tested. Among the different dispersion parameters tested herein, the use of polyvinylpyrrolidone combined with a sonication process generated by a probe leads to a significant improvement in terms of suspension efficiency and stability over 72 h. The dispersion efficiency of the proposed methodology was assessed by single-particle inductively coupled plasma mass spectrometry with spiked biological fluids such as urine and blood.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

References

  1. Recommendation 2011/696/EU. Journal officiel de l’Union européenne 2011.

  2. Contado C. Nanomaterials in consumer products: a challenging analytical problem. Front Chem. 2015;3. https://doi.org/10.3389/fchem.2015.00048.

  3. Shi H, Magaye R, Castranova V, Zhao J. Titanium dioxide nanoparticles: a review of current toxicological data. Part Fibre Toxicol. 2013;10:15. https://doi.org/10.1186/1743-8977-10-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dan Y, Shi H, Stephan C, Liang X. Rapid analysis of titanium dioxide nanoparticles in sunscreens using single particle inductively coupled plasma–mass spectrometry. Microchem J. 2015;122:119–26. https://doi.org/10.1016/j.microc.2015.04.018.

    Article  CAS  Google Scholar 

  5. Gondikas AP, von der Kammer F, Reed RB, Wagner S, Ranville JF, Hofmann T. Release of TiO2 nanoparticles from sunscreens into surface waters: a one-year survey at the Old Danube recreational Lake. Environ Sci Technol. 2014;48(10):5415–22. https://doi.org/10.1021/es405596y.

    Article  CAS  PubMed  Google Scholar 

  6. Peters RJB, van Bemmel G, Herrera-Rivera Z, Helsper HPFG, Marvin HJP, Weigel S, et al. Characterization of titanium dioxide nanoparticles in food products: analytical methods to define nanoparticles. J Agric Food Chem. 2014;62(27):6285–93. https://doi.org/10.1021/jf5011885.

    Article  CAS  PubMed  Google Scholar 

  7. de la Calle I, Menta M, Klein M, Séby F. Screening of TiO2 and au nanoparticles in cosmetics and determination of elemental impurities by multiple techniques (DLS, SP-ICP-MS, ICP-MS and ICP-OES). Talanta. 2017;171:291–306. https://doi.org/10.1016/j.talanta.2017.05.002.

    Article  CAS  PubMed  Google Scholar 

  8. López-Heras I, Madrid Y, Cámara C. Prospects and difficulties in TiO2 nanoparticles analysis in cosmetic and food products using asymmetrical flow field-flow fractionation hyphenated to inductively coupled plasma mass spectrometry. Talanta. 2014;124:71–8. https://doi.org/10.1016/j.talanta.2014.02.029.

    Article  CAS  PubMed  Google Scholar 

  9. Weir A, Westerhoff P, Fabricius L, Hristovski K, von Goetz N. Titanium dioxide nanoparticles in food and personal care products. Environ Sci Technol. 2012;46(4):2242–50. https://doi.org/10.1021/es204168d.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Raj S, Jose S, Sumod US, Sabitha M. Nanotechnology in cosmetics: opportunities and challenges. J Pharm Bioallied Sci. 2012:4. https://doi.org/10.4103/0975-7406.99016.

    Article  Google Scholar 

  11. Shakeel M, Jabeen F, Shabbir S, Asghar MS, Khan MS, Chaudhry AS. Toxicity of nano-titanium dioxide (TiO2-NP) through various routes of exposure: a review. Biol Trace Elem Res. 2016;172(1):1–36. https://doi.org/10.1007/s12011-015-0550-x.

    Article  CAS  PubMed  Google Scholar 

  12. Chang X, Zhang Y, Tang M, Wang B. Health effects of exposure to nano-TiO2: a meta-analysis of experimental studies. Nanoscale Res Lett. 2013;8(1):51. https://doi.org/10.1186/1556-276X-8-51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Vidmar J, Milačič R, Ščančar J. Sizing and simultaneous quantification of nanoscale titanium dioxide and a dissolved titanium form by single particle inductively coupled plasma mass spectrometry. Microchem J. 2017;132:391–400. https://doi.org/10.1016/j.microc.2017.02.030.

    Article  CAS  Google Scholar 

  14. Environmental and human health impacts of nanotechnology; Lead, J. R., Ed.; Wiley: Chichester, West Sussex, 2009.

  15. Stephan C, Hineman A. Analysis of NIST gold nanoparticles reference materials using the NexION 350 ICP-MS in single particle mode https://www.perkinelmer.com/lab-solutions/resources/docs/APP_NexION300Q-GoldNanoparticlesSP-ICPMS.pdf (accessed Oct 6, 2017).

  16. Loeschner K, Navratilova J, Købler C, Mølhave K, Wagner S, von der Kammer F, et al. Detection and characterization of silver nanoparticles in chicken meat by asymmetric flow field flow fractionation with detection by conventional or single particle ICP-MS. Anal Bioanal Chem. 2013;405(25):8185–95. https://doi.org/10.1007/s00216-013-7228-z.

    Article  CAS  PubMed  Google Scholar 

  17. Laborda F, Bolea E, Cepriá G, Gómez MT, Jiménez MS, Pérez-Arantegui J, et al. Detection, characterization and quantification of inorganic engineered nanomaterials: a review of techniques and methodological approaches for the analysis of complex samples. Anal Chim Acta. 2016;904:10–32. https://doi.org/10.1016/j.aca.2015.11.008.

    Article  CAS  PubMed  Google Scholar 

  18. Krystek P. A review on approaches to bio distribution studies about gold and silver engineered nanoparticles by inductively coupled plasma mass spectrometry. Microchem J. 2012;105:39–43. https://doi.org/10.1016/j.microc.2012.02.008.

    Article  CAS  Google Scholar 

  19. De la Calle I, Menta M, Séby F. Current trends and challenges in sample preparation for metallic nanoparticles analysis in daily products and environmental samples: a review. Spectrochim Acta B At Spectrosc. 2016;125:66–96. https://doi.org/10.1016/j.sab.2016.09.007.

    Article  CAS  Google Scholar 

  20. Krystek P, Braakhuis H, Park M, de Jong WH. Inductively coupled plasma-mass spectrometry in biodistribution studies of (engineered) nanoparticles. In: Meyers RA, editor. Encyclopedia of analytical chemistry. Chichester: John Wiley & Sons, Ltd; 2013. https://doi.org/10.1002/9780470027318.a9337.

    Chapter  Google Scholar 

  21. Roman M, Rigo C, Castillo-Michel H, Munivrana I, Vindigni V, Mičetić I, et al. Hydrodynamic chromatography coupled to single-particle ICP-MS for the simultaneous characterization of Ag NPs and determination of dissolved Ag in plasma and blood of burn patients. Anal Bioanal Chem. 2016;408(19):5109–24. https://doi.org/10.1007/s00216-015-9014-6.

    Article  CAS  PubMed  Google Scholar 

  22. Pergantis SA, Jones-Lepp TL, Heithmar EM. Hydrodynamic chromatography online with single particle-inductively coupled plasma mass spectrometry for ultratrace detection of metal-containing nanoparticles. Anal Chem. 2012;84(15):6454–62. https://doi.org/10.1021/ac300302j.

    Article  CAS  PubMed  Google Scholar 

  23. Montaño MD, Olesik JW, Barber AG, Challis K, Ranville JF. Single particle ICP-MS: advances toward routine analysis of nanomaterials. Anal Bioanal Chem. 2016;408(19):5053–74. https://doi.org/10.1007/s00216-016-9676-8.

    Article  CAS  PubMed  Google Scholar 

  24. Schwertfeger D, Velicogna J, Jesmer A, McShane H, Scroggins R, Princz J. Ion exchange technique (IET) to characterise Ag+ exposure in soil extracts contaminated with engineered silver nanoparticles. Environ Chem. 2017;14(2):123. https://doi.org/10.1071/EN16136.

    Article  CAS  Google Scholar 

  25. Kim ST, Kim HK, Han SH, Jung EC, Lee S. Determination of size distribution of colloidal TiO2 nanoparticles using sedimentation field-flow fractionation combined with single particle mode of inductively coupled plasma-mass spectrometry. Microchem J. 2013;110:636–42. https://doi.org/10.1016/j.microc.2013.07.015.

    Article  CAS  Google Scholar 

  26. Cirtiu, C.-M.; Fleury, N.; Stephan, C. Assessing the fate of nanoparticles in biological fluids using SP-ICP-MS http://www.perkinelmer.de/CMSResources/Images/44-171044APP_012008_01-NexION-350S-Fate-of- NPs-in-Bio-Fluids.pdf (accessed Jun 29, 2016).

  27. Cirtiu C-M, Stephan C. Tracking metal-based nanoparticles in biological fluids using single particle-ICP-MS. In 4th Edition of the CRC Press Encyclopedia of Nanoscience and Nanotechnology; 2016.

  28. Ariel RD, Shi H, Adams C, Stephan C. Rapid analysis of silver, gold, and titanium dioxide nanoparticles in drinking water by single particle ICP-MS. https://www.perkinelmer.com/de/lab-solutions/resources/docs/APP_NexION-350-NPs-in-Drinking-Water-App-Note.pdf (accessed Oct 6, 2017).

  29. Taurozzi JS, Hackley VA, Wiesner MR. A standardised approach for the dispersion of titanium dioxide nanoparticles in biological media. Nanotoxicology. 2013;7(4):389–401. https://doi.org/10.3109/17435390.2012.665506.

    Article  CAS  PubMed  Google Scholar 

  30. Vidmar J, Milačič R, Golja V, Novak S, Ščančar J. Optimization of the procedure for efficient dispersion of titanium dioxide nanoparticles in aqueous samples. Anal Methods. 2016;8(5):1194–201. https://doi.org/10.1039/C5AY03305E.

    Article  CAS  Google Scholar 

  31. French RA, Jacobson AR, Kim B, Isley SL, Penn RL, Baveye PC. Influence of ionic strength, PH, and cation valence on aggregation kinetics of titanium dioxide nanoparticles. Environ Sci Technol. 2009;43(5):1354–9. https://doi.org/10.1021/es802628n.

    Article  CAS  PubMed  Google Scholar 

  32. Othman SH, Abdul Rashid S, Mohd Ghazi TI, Abdullah N. Dispersion and stabilization of photocatalytic TiO2 nanoparticles in aqueous suspension for coatings applications. J Nanomater. 2012;2012:1–10. https://doi.org/10.1155/2012/718214.

    Article  CAS  Google Scholar 

  33. Kania K, Byrnes EA, Beilby JP, Webb SAR, Strong KJ. Urinary proteases degrade albumin: implications for measurement of albuminuria in stored samples. Ann Clin Biochem. 2010;47(2):151–7. https://doi.org/10.1258/acb.2009.009247.

    Article  CAS  PubMed  Google Scholar 

  34. D10, D50, D90 - for DLS? Yes not just diffraction - with caution.

  35. Particle size distribution - D10, D50 & D90 - sieve analysis https://www.innopharmalabs.com/tech/applications-and-processes/particle-size-monitoring (accessed Jun 14, 2019).

  36. Hineman A, Stephan C. Effect of dwell time on single particle inductively coupled plasma mass spectrometry data acquisition quality. J Anal At Spectrom. 2014;29(7):1252. https://doi.org/10.1039/c4ja00097h.

    Article  CAS  Google Scholar 

  37. Stephan C, Neubauer K. White Paper: Single particle inductively coupled plasma mass spectrometry: understanding how and why; 2014. https://www.perkinelmer.com/Lab-Solutions/Resources/Docs/NanoSingleParticleICPMSTheory.Pdf.

  38. Pace HE, Rogers NJ, Jarolimek C, Coleman VA, Higgins CP, Ranville JF. Determining transport efficiency for the purpose of counting and sizing nanoparticles via single particle inductively coupled plasma mass spectrometry. Anal Chem. 2011;83(24):9361–9. https://doi.org/10.1021/ac201952t.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Laborda F, Bolea E, Jiménez-Lamana J. Single particle inductively coupled plasma mass spectrometry for the analysis of inorganic engineered nanoparticles in environmental samples. Trends Environ Anal Chem. 2016;9:15–23. https://doi.org/10.1016/j.teac.2016.02.001.

    Article  CAS  Google Scholar 

  40. Moore LT, Rodriguez-Lorenzo L, Hirsch V, Balog S, Urban D, Jud C, et al. Nanoparticle colloidal stability in cell culture media and impact on cellular interactions. Chem Soc Rev. 2015;44(17):6287–305. https://doi.org/10.1039/C4CS00487F.

    Article  CAS  PubMed  Google Scholar 

  41. Hasanzadeh H. Stabilizing and dispersing methods of TiO2 nanoparticles in biological studies. J Paramed Sci. 2015;6:96–105.

    Google Scholar 

  42. Safaei-Naeini Y, Aminzare M, Golestani-Fard F, Khorasanizadeh F, Salahi E. Suspension stability of titania nanoparticles studied by UV-Vis spectroscopy method. Iran J Mater Sci Eng. 2012;9(1).

  43. Hirai H, Yakura N. Protecting polymers in suspension of metal nanoparticles. Polym Adv Technol. 2001;12(11–12):724–33. https://doi.org/10.1002/pat.95.

    Article  CAS  Google Scholar 

  44. de Moraes Porto ICC. Polymer biocompatibility. In Polymerization; De Souza Gomes, A., Ed.; InTech, 2012. https://doi.org/10.5772/47786.

    Google Scholar 

  45. TiO2 Nanoparticles / TiO2 Nanopowder (TiO2, anatase, 99.9%, 100nm) http://www.us-nano.com/inc/sdetail/47163.

  46. Soltani N, Saion E, Erfani M, Rezaee K, Bahmanrokh G, Drummen GPC, et al. Influence of the polyvinyl pyrrolidone concentration on particle size and dispersion of ZnS nanoparticles synthesized by microwave irradiation. Int J Mol Sci. 2012;13(10):12412–27. https://doi.org/10.3390/ijms131012412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Aznar R, Barahona F, Geiss O, Ponti J, José Luis T, Barrero-Moreno J. Quantification and size characterisation of silver nanoparticles in environmental aqueous samples and consumer products by single particle-ICPMS. Talanta. 2017;175:200–8. https://doi.org/10.1016/j.talanta.2017.07.048.

    Article  CAS  PubMed  Google Scholar 

  48. Badalova K, Herbello-Hermelo P, Bermejo-Barrera P, Moreda-Piñeiro A. Possibilities of single particle—ICP-MS for determining/characterizing titanium dioxide and silver nanoparticles in human urine. J Trace Elem Med Biol. 2019;54:55–61. https://doi.org/10.1016/j.jtem.2019.04.003.

    Article  CAS  PubMed  Google Scholar 

  49. Donovan AR, Adams CD, Ma Y, Stephan C, Eichholz T, Shi H. Detection of zinc oxide and cerium dioxide nanoparticles during drinking water treatment by rapid single particle ICP-MS methods. Anal Bioanal Chem. 2016;408:5137–45. https://doi.org/10.1007/s00216-016-9432-0.

    Article  CAS  PubMed  Google Scholar 

  50. National Institue of Standard & Technology. Certificate of Analysis Standard Reference Material® 1898 Titanium Dioxide Nanomaterial https://www-s.nist.gov/srmors/certificates/1898.pdf (accessed Apr 25, 2018).

  51. Taurozzi, J. S.; Hackley, V. A.; Wiesner, M. R. Preparation of nanoscale TiO2 dispersions in an environmental matrix for eco-toxicological assessment - Version 1.1; National Institute of Standards and Technology, 2012. https://doi.org/10.6028/NIST.SP.1200-5.

  52. Li J, Inukai K, Takahashi Y, Tsuruta A, Shin W. Effect of PVP on the synthesis of high-dispersion core–shell barium-titanate–polyvinylpyrrolidone nanoparticles. J Asian Ceram Soc. 2017;5(2):216–25. https://doi.org/10.1016/j.jascer.2017.05.001.

    Article  Google Scholar 

  53. Brar SK, Verma M. Measurement of nanoparticles by light-scattering techniques. TrAC Trends Anal Chem. 2011;30(1):4–17. https://doi.org/10.1016/j.trac.2010.08.008.

    Article  CAS  Google Scholar 

  54. Hughes JM, Budd PM, Grieve A, Dutta P, Tiede K, Lewis J. Highly monodisperse, lanthanide-containing polystyrene nanoparticles as potential standard reference materials for environmental “nano” fate analysis. J Appl Polym Sci. 2015;132(24). https://doi.org/10.1002/app.42061.

    Article  Google Scholar 

  55. Clayton KN, Salameh JW, Wereley ST, Kinzer-Ursem TL. Physical characterization of nanoparticle size and surface modification using particle scattering diffusometry. Biomicrofluidics. 2016;10(5):054107. https://doi.org/10.1063/1.4962992.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Dispersity or polydispdersity is a key parameter for GPC SEC.

  57. Titanium Oxide TiO2 Nanoparticles / Nanopowder (TiO2 Anatase HighPurity 99.98% 30nm) https://www.us-nano.com/inc/sdetail/7709 (accessed Sep 27, 2019).

  58. Union, P. O. of the E. Titanium dioxide, NM-100, NM-101, NM-102, NM-103, NM-104, NM-105 : characterisation and physico-chemical properties. https://publications.europa.eu/en/publication-detail/-/publication/0ca3a430-cd22-4eea-9d29-e2953b290b71/language-en (accessed Jun 14, 2019).

  59. Buy TiO2- Anatase, 100 nm, Ultra Pure | TiO2- Anatase, 100 nm, Ultra Pure Online : MKNano.com https://www.mknano.com/Nanoparticles/Single-Element-Oxides/Titanium-Oxide-Nanopowder/TiO2-Anatase-100-nm-Ultra-Pure (accessed Jun 14, 2019).

  60. Titanium Oxide Nanoparticles in Water Dispersion (TiO2, Rutile-Anatase Mixed, 40wt%, 30nm) https://www.us-nano.com/inc/sdetail/29897 (accessed Jun 14, 2019).

  61. Ho YT, Azman N‘A, Loh FWY, Ong GKT, Engudar G, Kriz SA, et al. Protein corona formed from different blood plasma proteins affects the colloidal stability of nanoparticles differently. Bioconjug Chem. 2018;29(11):3923–34. https://doi.org/10.1021/acs.bioconjchem.8b00743.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The author (S. Salou) wishes to thank Rodica Neagu Plesu for providing access to the DLS instrumentation and training, Richard Janvier for the TEM training and support, and Girish Shah and Mihaela Robu for the sonication device to optimize the sample preparation procedure. The author thanks Dr. Chady Stephan and Andrew Rams from PerkinElmer for the fruitful discussion regarding this study and C. Bedwin for her editorial comments. We thank the European Commission for providing the NM10200a TiO2 NP nanomaterials for free.

Author information

Authors and Affiliations

  1. Chemistry Department, Université Laval, 1045 Ave de la médecine, Quebec, QC, G1V 0A6, Canada

    Samantha Salou & Dominic Larivière

  2. Institut National de Santé Publique du Québec, Centre de Toxicologie du Québec, 945 Avenue Wolfe, Quebec, QC, G1V 5B3, Canada

    Samantha Salou, Ciprian-Mihai Cirtiu & Normand Fleury

Authors
  1. Samantha Salou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ciprian-Mihai Cirtiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dominic Larivière
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Normand Fleury
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ciprian-Mihai Cirtiu or Dominic Larivière.

Ethics declarations

The authors declare that they have no conflicts of interest. The authors alone are responsible for the content and writing of this paper.

The samples were provided from another CTQ division as a reference matrix for analytical purposes only.

All volunteers provided written informed consent to Centre de Toxicologie du Québec (CTQ) before any study-specific procedures or assessments were performed.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Salou, S., Cirtiu, CM., Larivière, D. et al. Assessment of strategies for the formation of stable suspensions of titanium dioxide nanoparticles in aqueous media suitable for the analysis of biological fluids. Anal Bioanal Chem 412, 1469–1481 (2020). https://doi.org/10.1007/s00216-020-02412-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-020-02412-2

Keywords

Search

Navigation