Traceable characterization of hollow organosilica beads as potential reference materials for extracellular vesicle measurements with optical techniques

Jérôme Deumer; Robin Schürmann; Anikó Gaál; Zoltán Varga; Britta Bettin; Edwin van der Pol; Rienk Nieuwland; David Ojeda; Aneta Sikora; Dorota Bartczak; Heidi Goenaga-Infante; Johanna Noireaux; Mahrad Khakpour; Virpi Korpelainen; Christian Gollwitzer

doi:10.1186/s11671-024-03956-3

Traceable characterization of hollow organosilica beads as potential reference materials for extracellular vesicle measurements with optical techniques

Jérôme Deumer^*, Robin Schürmann, Anikó Gaál, Zoltán Varga, Britta Bettin, Edwin van der Pol, Rienk Nieuwland, David Ojeda, Aneta Sikora, Dorota Bartczak, Heidi Goenaga-Infante, Johanna Noireaux, Mahrad Khakpour, Virpi Korpelainen, Christian Gollwitzer^*

^*Corresponding author for this work

SU1201 Length metrology

Research output: Contribution to journal › Article › Scientific › peer-review

3 Citations (Scopus)

Abstract

The concentration of cell-type specific extracellular vesicles (EVs) is a promising biomarker for various diseases. However, concentrations of EVs measured by optical techniques such as flow cytometry (FCM) or particle tracking analysis (PTA) in clinical practice are incomparable. To allow reliable and comparable concentration measurements suitable reference materials (RMs) and SI-traceable (SI—International system of units) methods are required. Hollow organosilica beads (HOBs) are promising RM candidates for concentration measurements of EVs based on light scattering, as the shape, low refractive index, and number concentration of HOBs are comparable to EVs of the respective size range that can be detected with current optical instrumentation. Here, we present traceable methods for measuring the particle size distribution of four HOB types in the size range between 200 and 500 nm by small-angle X-ray scattering (SAXS) and atomic force microscopy (AFM), as well as the number concentration by single-particle inductively coupled plasma mass spectrometry (spICP-MS). Based on the size and shape results, traceable reference values were obtained to additionally determine the refractive index of the shell of the HOB samples by FCM. Furthermore, the estimated refractive indexes of the HOBs plausibly agree with the refractive indexes of EVs of corresponding size. Due to their narrow size distribution and their similar shape, and low refractive index, all HOB samples studied are suitable RM candidates for calibration of the measured sample volume by optical methods within the photon wavelength range used, and thus for calibration of number concentration measurements of EVs in the size range indicated. This was confirmed as the number concentration values obtained by PTA and two independent flow cytometric measurements agreed with the concentration reference values obtained by two independent spICP-MS measurements within the calculated uncertainty limits.

Original language	English
Article number	14
Pages (from-to)	14
Journal	Discover Nano
Volume	19
Issue number	1
DOIs	https://doi.org/10.1186/s11671-024-03956-3
Publication status	Published - 22 Jan 2024
MoE publication type	A1 Journal article-refereed

Funding

Open Access funding enabled and organized by Projekt DEAL. This work was partially funded by the (18HLT01) METVES II project, which received funding from the EMPIR program, co-funded by the participating states, and from the European Union’s Horizon 2020 research and innovation program. Edwin van der Pol acknowledges funding from the Dutch Research Council (NWO), VIDI 19724. Zoltán Varga acknowledges the support of the János Bolyai Research Fellowship of the Hungarian Academy of Sciences and the funding from the National Research, Development and Innovation Office, Hungary (NKFIH), TKP2021-EGA-31 and 20201.1.2-PIACI-KFI-2020-00021. Special thanks go to Levent Cibik and Dieter Skroblin from Physikalisch-Technische Bundesanstalt for their technical support at the beamline and to Dr. Michael Krumrey for his scientific advice. We would also like to thank Dr. Armin Hoell from Helmholtz-Zentrum Berlin for his support at the SAXS facility.

Keywords

Extracellular vesicles
Flow cytometry
Hollow organosilica beads
Nanometrology
Particle tracking analysis
Reference materials

Access to Document

10.1186/s11671-024-03956-3Licence: CC BY

Cite this

Deumer, J., Schürmann, R., Gaál, A., Varga, Z., Bettin, B., van der Pol, E., Nieuwland, R., Ojeda, D., Sikora, A., Bartczak, D., Goenaga-Infante, H., Noireaux, J., Khakpour, M., Korpelainen, V., & Gollwitzer, C. (2024). Traceable characterization of hollow organosilica beads as potential reference materials for extracellular vesicle measurements with optical techniques. Discover Nano, 19(1), 14. Article 14. https://doi.org/10.1186/s11671-024-03956-3

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title = "Traceable characterization of hollow organosilica beads as potential reference materials for extracellular vesicle measurements with optical techniques",

abstract = "The concentration of cell-type specific extracellular vesicles (EVs) is a promising biomarker for various diseases. However, concentrations of EVs measured by optical techniques such as flow cytometry (FCM) or particle tracking analysis (PTA) in clinical practice are incomparable. To allow reliable and comparable concentration measurements suitable reference materials (RMs) and SI-traceable (SI—International system of units) methods are required. Hollow organosilica beads (HOBs) are promising RM candidates for concentration measurements of EVs based on light scattering, as the shape, low refractive index, and number concentration of HOBs are comparable to EVs of the respective size range that can be detected with current optical instrumentation. Here, we present traceable methods for measuring the particle size distribution of four HOB types in the size range between 200 and 500 nm by small-angle X-ray scattering (SAXS) and atomic force microscopy (AFM), as well as the number concentration by single-particle inductively coupled plasma mass spectrometry (spICP-MS). Based on the size and shape results, traceable reference values were obtained to additionally determine the refractive index of the shell of the HOB samples by FCM. Furthermore, the estimated refractive indexes of the HOBs plausibly agree with the refractive indexes of EVs of corresponding size. Due to their narrow size distribution and their similar shape, and low refractive index, all HOB samples studied are suitable RM candidates for calibration of the measured sample volume by optical methods within the photon wavelength range used, and thus for calibration of number concentration measurements of EVs in the size range indicated. This was confirmed as the number concentration values obtained by PTA and two independent flow cytometric measurements agreed with the concentration reference values obtained by two independent spICP-MS measurements within the calculated uncertainty limits.",

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Deumer, J, Schürmann, R, Gaál, A, Varga, Z, Bettin, B, van der Pol, E, Nieuwland, R, Ojeda, D, Sikora, A, Bartczak, D, Goenaga-Infante, H, Noireaux, J, Khakpour, M, Korpelainen, V & Gollwitzer, C 2024, 'Traceable characterization of hollow organosilica beads as potential reference materials for extracellular vesicle measurements with optical techniques', Discover Nano, vol. 19, no. 1, 14, pp. 14. https://doi.org/10.1186/s11671-024-03956-3

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T1 - Traceable characterization of hollow organosilica beads as potential reference materials for extracellular vesicle measurements with optical techniques

AU - Deumer, Jérôme

AU - Schürmann, Robin

AU - Gaál, Anikó

AU - Varga, Zoltán

AU - Bettin, Britta

AU - van der Pol, Edwin

AU - Nieuwland, Rienk

AU - Ojeda, David

AU - Sikora, Aneta

AU - Bartczak, Dorota

AU - Goenaga-Infante, Heidi

AU - Noireaux, Johanna

AU - Khakpour, Mahrad

AU - Korpelainen, Virpi

AU - Gollwitzer, Christian

PY - 2024/1/22

Y1 - 2024/1/22

N2 - The concentration of cell-type specific extracellular vesicles (EVs) is a promising biomarker for various diseases. However, concentrations of EVs measured by optical techniques such as flow cytometry (FCM) or particle tracking analysis (PTA) in clinical practice are incomparable. To allow reliable and comparable concentration measurements suitable reference materials (RMs) and SI-traceable (SI—International system of units) methods are required. Hollow organosilica beads (HOBs) are promising RM candidates for concentration measurements of EVs based on light scattering, as the shape, low refractive index, and number concentration of HOBs are comparable to EVs of the respective size range that can be detected with current optical instrumentation. Here, we present traceable methods for measuring the particle size distribution of four HOB types in the size range between 200 and 500 nm by small-angle X-ray scattering (SAXS) and atomic force microscopy (AFM), as well as the number concentration by single-particle inductively coupled plasma mass spectrometry (spICP-MS). Based on the size and shape results, traceable reference values were obtained to additionally determine the refractive index of the shell of the HOB samples by FCM. Furthermore, the estimated refractive indexes of the HOBs plausibly agree with the refractive indexes of EVs of corresponding size. Due to their narrow size distribution and their similar shape, and low refractive index, all HOB samples studied are suitable RM candidates for calibration of the measured sample volume by optical methods within the photon wavelength range used, and thus for calibration of number concentration measurements of EVs in the size range indicated. This was confirmed as the number concentration values obtained by PTA and two independent flow cytometric measurements agreed with the concentration reference values obtained by two independent spICP-MS measurements within the calculated uncertainty limits.

AB - The concentration of cell-type specific extracellular vesicles (EVs) is a promising biomarker for various diseases. However, concentrations of EVs measured by optical techniques such as flow cytometry (FCM) or particle tracking analysis (PTA) in clinical practice are incomparable. To allow reliable and comparable concentration measurements suitable reference materials (RMs) and SI-traceable (SI—International system of units) methods are required. Hollow organosilica beads (HOBs) are promising RM candidates for concentration measurements of EVs based on light scattering, as the shape, low refractive index, and number concentration of HOBs are comparable to EVs of the respective size range that can be detected with current optical instrumentation. Here, we present traceable methods for measuring the particle size distribution of four HOB types in the size range between 200 and 500 nm by small-angle X-ray scattering (SAXS) and atomic force microscopy (AFM), as well as the number concentration by single-particle inductively coupled plasma mass spectrometry (spICP-MS). Based on the size and shape results, traceable reference values were obtained to additionally determine the refractive index of the shell of the HOB samples by FCM. Furthermore, the estimated refractive indexes of the HOBs plausibly agree with the refractive indexes of EVs of corresponding size. Due to their narrow size distribution and their similar shape, and low refractive index, all HOB samples studied are suitable RM candidates for calibration of the measured sample volume by optical methods within the photon wavelength range used, and thus for calibration of number concentration measurements of EVs in the size range indicated. This was confirmed as the number concentration values obtained by PTA and two independent flow cytometric measurements agreed with the concentration reference values obtained by two independent spICP-MS measurements within the calculated uncertainty limits.

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KW - Flow cytometry

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Traceable characterization of hollow organosilica beads as potential reference materials for extracellular vesicle measurements with optical techniques

Abstract

Funding

Keywords

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METVES II: Standardisation of concentration measurements of extracellular vesicles for medical diagnoses

Cite this

Traceable characterization of hollow organosilica beads as potential reference materials for extracellular vesicle measurements with optical techniques

Abstract

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Projects

METVES II: Standardisation of concentration measurements of extracellular vesicles for medical diagnoses

Cite this