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Nanomaterial Characterization Methods: Leaping Towards Validation

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A special issue of Materials (ISSN 1996-1944). This special issue belongs to the section "Advanced Materials Characterization".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 28278

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Special Issue Editors

Prof. Dr. Keld Alstrup Jensen

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Guest Editor

National Research Centre for the Working Environment (NRCWE), Copenhagen, Denmark
Interests: nanomaterials; characterization; reactivity; dustiness; risk assessment

Dr. Wendel Wohlleben

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Guest Editor

BASF SE, Ludwigshafen, Germany
Interests: nano-enabled products; characterization; nanosafety; spectroscopy

Special Issue Information

Dear Colleagues,

SCOPE: In this special volume, we openly invite papers on characterization methods that support the identification, registration, characterization of nanomaterials and that have been demonstrated via in-house, intra-, and/or inter-laboratory comparison. Exemplary elements of a method standard operational procedure include: methods description, sample preparation, instructions, data reduction and evaluation, benchmarking or validation of results. In this context, contributions that report on different (nano)forms of the same substance or other systematic variations of nanomaterials are welcome.

BACKGROUND: Over the last approximately 15 years, there has been extensive research and development focus on manufactured 1D, 2D and 3D nanomaterials and their use as for example catalysts, conductors, magnetics, colorants, optical sources, flame-retardants, biocides with application in electronics, ceramics, construction materials, coatings, food, feed, medicinal and medical devices, environmental remediation etc. The list of both nanomaterials and applications is very long and reflects the growing success of manufactured nanomaterials as a key-enabling technology.

In parallel with the technological developments, the small sizes, and in some cases high chemical and structural complexity of manufactured nanomaterials, have challenged many established physicochemical characterization and test methods. High-quality characterization and measurement of intrinsic and extrinsic properties is essential to establish good and reliable data and to transfer knowledge from research to industry, as well as transferring data from material producers to regulators and downstream users.

While research laboratories can simply adapt to new characterization requirements, any change of methods for regulatory use is a long process before data is mutually accepted. However, it has been identified that several international standard methods accepted for regulatory characterization and testing are not or only partially adequate for characterization and testing of manufactured nanomaterials. Moreover, a need for new characteristics have emerged to improve material and hazard grouping, read-across and quantitative structural activity relationships(QSAR), and fate modelling in human and environmental compartments. In consequence, there is an urgent need to revise regulatory guidance on how to characterize, test, and even assess the risk of manufactured nanomaterials.

At this stage, the characterization community must find a balance between data reliability (repeatability, accuracy, precision) with cost and practical implementation. Several regulatory bodies have already made their decisions on which methods must be improved and which new characteristics that must be reported, or are in the process of doing so. This generates high pressure on the developers of regulatory characterization methods to identify and validate suitable methods to meet the regulatory needs.

REGULATORY RELEVANCE: There is particular interest in contributions that can support, by robust scientific data, the further selection and guidance and standardization at OECD and ISO level. In this regard, there is high interest in methods documentation on materials where eco- and toxicological assessments have already been published elsewhere to allow future testing and calibration of grouping and predictive risk assessment methods. Lower priority will be given to novel and yet not validated methods.

Yours sincerely,

Prof. Dr. Keld Alstrup Jensen
Dr. Wendel Wohlleben
Guest Editors

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Keywords

nanomaterials
characterization methods
validation
material grouping
regulation

Published Papers (9 papers)

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Research

20 pages, 1744 KiB

Open AccessEditor’s ChoiceArticle

Development and Validation of Optical Methods for Zeta Potential Determination of Silica and Polystyrene Particles in Aqueous Suspensions

by Yannic Ramaye, Marta Dabrio, Gert Roebben and Vikram Kestens

Materials 2021, 14(2), 290; https://doi.org/10.3390/ma14020290 - 08 Jan 2021

Cited by 11 | Viewed by 2436

Abstract

Zeta potential is frequently used to examine the colloidal stability of particles and macromolecules in liquids. Recently, it has been suggested that zeta potential can also play an important role for grouping and read-across of nanoforms in a regulatory context. Although the measurement of zeta potential is well established, only little information is reported on key metrological principles such as validation and measurement uncertainties. This contribution presents the results of an in-house validation of the commonly used electrophoretic light scattering (ELS) and the relatively new particle tracking analysis (PTA) methods. The performance characteristics were assessed by analyzing silica and polystyrene reference materials. The ELS and PTA methods are robust and have particle mass working ranges of 0.003 mg/kg to 30 g/kg and 0.03 mg/kg to 1.5 mg/kg, respectively. Despite different measurement principles, both methods exhibit similar uncertainties for repeatability (2%), intermediate precision (3%) and trueness (4%). These results confirm that the developed methods can accurately measure the zeta potential of silica and polystyrene particles and can be transferred to other laboratories that analyze similar types of samples. If direct implementation is impossible, the elaborated methodologies may serve as a guide to help laboratories validating their own methods. Full article

(This article belongs to the Special Issue Nanomaterial Characterization Methods: Leaping Towards Validation)

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12 pages, 1569 KiB

Open AccessCommunication

A Method to Assess the Relevance of Nanomaterial Dissolution during Reactivity Testing

by Willie J. G. M. Peijnenburg, Emmanuel Ruggiero, Matthew Boyles, Fiona Murphy, Vicki Stone, Derek A. Elam, Kai Werle and Wendel Wohlleben

Materials 2020, 13(10), 2235; https://doi.org/10.3390/ma13102235 - 13 May 2020

Cited by 20 | Viewed by 2372

Abstract

The reactivity of particle surfaces can be used as a criterion to group nanoforms (NFs) based on similar potential hazard. Since NFs may partially or completely dissolve over the duration of the assays, with the ions themselves inducing a response, reactivity assays commonly measure the additive reactivity of the particles and ions combined. Here, we determine the concentration of ions released over the course of particle testing, and determine the relative contributions of the released ions to the total reactivity measured. We differentiate three classes of reactivity, defined as being (A) dominated by particles, (B) additive of particles and ions, or (C) dominated by ions. We provide examples for each class by analyzing the NF reactivity of Fe₂O₃, ZnO, CuO, Ag using the ferric reduction ability of serum (FRAS) assay. Furthermore, another two reactivity tests were performed: Dichlorodihydrofluorescin diacetate (DCFH₂-DA) assay and electron paramagnetic resonance (EPR) spectroscopy. We compare assays and demonstrate that the dose-response may be almost entirely assigned to ions in one assay (CuO in DCFH₂-DA), but to particles in others (CuO in EPR and FRAS). When considering this data, we conclude that one cannot specify the contribution of ions to NF toxicity for a certain NF, but only for a certain NF in a specific assay, medium and dose. The extent of dissolution depends on the buffer used, particle concentration applied, and duration of exposure. This culminates in the DCFH₂-DA, EPR, FRAS assays being performed under different ion-to-particle ratios, and differing in their sensitivity towards reactions induced by either ions or particles. If applied for grouping, read-across, or other concepts based on the similarity of partially soluble NFs, results on reactivity should only be compared if measured by the same assay, incubation time, and dose range. Full article

(This article belongs to the Special Issue Nanomaterial Characterization Methods: Leaping Towards Validation)

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14 pages, 1369 KiB

Open AccessArticle

Tackling Complex Analytical Tasks: An ISO/TS-Based Validation Approach for Hydrodynamic Chromatography Single Particle Inductively Coupled Plasma Mass Spectrometry

by Yves U. Hachenberger, Daniel Rosenkranz, Fabian L. Kriegel, Benjamin Krause, René Matschaß, Philipp Reichardt, Jutta Tentschert, Peter Laux, Norbert Jakubowski, Ulrich Panne and Andreas Luch

Materials 2020, 13(6), 1447; https://doi.org/10.3390/ma13061447 - 22 Mar 2020

Cited by 8 | Viewed by 2672

Abstract

Nano-carrier systems such as liposomes have promising biomedical applications. Nevertheless, characterization of these complex samples is a challenging analytical task. In this study a coupled hydrodynamic chromatography-single particle-inductively coupled plasma mass spectrometry (HDC-spICP-MS) approach was validated based on the technical specification (TS) 19590:2017 of the international organization for standardization (ISO). The TS has been adapted to the hyphenated setup. The quality criteria (QC), e.g., linearity of the calibration, transport efficiency, were investigated. Furthermore, a cross calibration of the particle size was performed with values from dynamic light scattering (DLS) and transmission electron microscopy (TEM). Due to an additional Y-piece, an online-calibration routine was implemented. This approach allows the calibration of the ICP-MS during the dead time of the chromatography run, to reduce the required time and enhance the robustness of the results. The optimized method was tested with different gold nanoparticle (Au-NP) mixtures to investigate the characterization properties of HDC separations for samples with increasing complexity. Additionally, the technique was successfully applied to simultaneously determine both the hydrodynamic radius and the Au-NP content in liposomes. With the established hyphenated setup, it was possible to distinguish between different subpopulations with various NP loads and different hydrodynamic diameters inside the liposome carriers. Full article

(This article belongs to the Special Issue Nanomaterial Characterization Methods: Leaping Towards Validation)

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19 pages, 6553 KiB

Open AccessArticle

Applicability and Limitations in the Characterization of Poly-Dispersed Engineered Nanomaterials in Cell Media by Dynamic Light Scattering (DLS)

by Arianna Marucco, Elisabetta Aldieri, Riccardo Leinardi, Enrico Bergamaschi, Chiara Riganti and Ivana Fenoglio

Materials 2019, 12(23), 3833; https://doi.org/10.3390/ma12233833 - 21 Nov 2019

Cited by 16 | Viewed by 2792

Abstract

The dispersion protocol used to administer nanomaterials (NMs) in in vitro cellular tests might affect their toxicity. For this reason, several dispersion procedures have been proposed to harmonize the toxicological methods, allowing for the comparison of the data that were obtained by different laboratories. At the same time, several techniques and methods are available to monitor the identity of the NMs in the cell media. However, while the characterization of suspensions of engineered NMs having narrow size distribution may be easily performed, the description of aggregated NMs forming polydispersions is still challenging. In the present study, sub-micrometric/nanometric TiO₂, SiO₂, and CeO₂ were dispersed in cell media by using two different dispersion protocols, with and without albumin (0.5%) and with different sonication procedures. Dynamic Light Scattering (DLS) was used to characterize NMs in stock solutions and culture media. Pitfalls that affect DLS measurements were identified and, guidance on a critical analysis of the results provided. The NMs were then tested for their cytotoxicity (LDH leakage) toward murine macrophages (RAW 264.7) and PMA-activated human monocytes (THP-1). As markers of pro-inflammatory response, nitric oxide (NO) and cytokine IL-1β production were measured on RAW 264.7 and THP-1 cells, respectively. The pre-treatment with albumin added to a strong sonication treatment increases the stability and homogeneity of the suspensions of nanometric samples, but not of the submicrometric-samples. Nevertheless, while TiO₂ and CeO₂ were non-cytotoxic in any conditions, differences in cytotoxicity, NO, and IL-1β releases were found for the SiO₂, depending upon the protocol. Overall, the results suggest that there is no one-fits-all method valid for all NMs, since each class of NMs respond differently. The definition of validated procedures and parameters for the selection of the most appropriate method of dispersion for each class of NM appears to be a more efficacious strategy for the harmonization of the dispersion protocols. Full article

(This article belongs to the Special Issue Nanomaterial Characterization Methods: Leaping Towards Validation)

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21 pages, 1153 KiB

Open AccessFeature PaperArticle

Thermogravimetry and Mass Spectrometry of Extractable Organics from Manufactured Nanomaterials for Identification of Potential Coating Components

by Per Axel Clausen, Vivi Kofoed-Sørensen, Asger W. Nørgaard, Nicklas Mønster Sahlgren and Keld Alstrup Jensen

Materials 2019, 12(22), 3657; https://doi.org/10.3390/ma12223657 - 06 Nov 2019

Cited by 20 | Viewed by 3410

Abstract

Manufactured nanomaterials (MNMs) often have a surface-chemical modification in order to tailor their physicochemical properties, including also powder properties and miscibility. Surface-chemical modifications may influence the toxicological properties of the MNM, but the specific chemistry and extent are rarely described in detail in suppliers’ technical data sheets. Chemical and quantitative information on any surface-chemical treatment, coating and functionalization are required for chemicals registration in Europe. Currently there is no globally accepted and documented approach to generate such data. Consequently, there is a continued research need to establish a structured approach to identify and quantify surface-chemical modifications. Here we present a tiered approach starting with screening for mass-loss during heating in a furnace or thermogravimetric analysis (TGA) followed by solvent extraction, and analysis by several mass spectrometry (MS) techniques depending on the target analytes. Thermal treatment was assumed to be able to quantify the amount of organic coating and MS was used to identify the extractable organic coatings after pressurized liquid extraction (PLE) using methanol at 200 °C. Volatile organic compounds in extracts were identified with gas chromatography and MS (GC-MS), non-volatile organic compounds with liquid chromatography MS (LC-MS), and polymeric compounds with matrix-assisted laser desorption ionization time-of-flight MS (MALDI-TOF-MS). The approach was demonstrated by analysis of 24 MNM, comprising titanium dioxide, synthetic amorphous silica, graphite, zinc oxide, silver, calcium carbonate, iron oxide, nickel-zinc-iron oxide, and organoclay. In extracts of 14 MNMs a range of organic compounds were identified and the main groups were silanes/siloxanes, fatty acids, fatty acid esters, quaternary ammonium compounds and polymeric compounds. In the remaining 10 MNMs no organic compounds were detected by MS, despite the fact an organic coating was indicated by TGA. Full article

(This article belongs to the Special Issue Nanomaterial Characterization Methods: Leaping Towards Validation)

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23 pages, 3095 KiB

Open AccessArticle

NanoDefiner e-Tool: An Implemented Decision Support Framework for Nanomaterial Identification

by Raphael Brüngel, Johannes Rückert, Wendel Wohlleben, Frank Babick, Antoine Ghanem, Claire Gaillard, Agnieszka Mech, Hubert Rauscher, Vasile-Dan Hodoroaba, Stefan Weigel and Christoph M. Friedrich

Materials 2019, 12(19), 3247; https://doi.org/10.3390/ma12193247 - 04 Oct 2019

Cited by 7 | Viewed by 4128

Abstract

The European Commission’s recommendation on the definition of nanomaterial (2011/696/EU) established an applicable standard for material categorization. However, manufacturers face regulatory challenges during registration of their products. Reliable categorization is difficult and requires considerable expertise in existing measurement techniques (MTs). Additionally, organizational complexity is increased as different authorities’ registration processes require distinct reporting. The NanoDefine project tackled these obstacles by providing the NanoDefiner e-tool: A decision support expert system for nanomaterial identification in a regulatory context. It provides MT recommendations for categorization of specific materials using a tiered approach (screening/confirmatory), and was constructed with experts from academia and industry to be extensible, interoperable, and adaptable for forthcoming revisions of the nanomaterial definition. An implemented MT-driven material categorization scheme allows detailed description. Its guided workflow is suitable for a variety of user groups. Direct feedback and explanation enable transparent decisions. Expert knowledge is held in a knowledge base for representation of MT performance criteria and physicochemical particle type properties. Continuous revision ensured data quality and validity. Recommendations were validated by independent case studies on industry-relevant particulate materials. Besides supporting material identification and registration, the free and open-source e-tool may serve as template for other expert systems within the nanoscience domain. Full article

(This article belongs to the Special Issue Nanomaterial Characterization Methods: Leaping Towards Validation)

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17 pages, 1088 KiB

Open AccessArticle

Estimation of the Uncertainties Related to the Measurement of the Size and Quantities of Individual Silver Nanoparticles in Confectionery

by Nadia Waegeneers, Sandra De Vos, Eveline Verleysen, Ann Ruttens and Jan Mast

Materials 2019, 12(17), 2677; https://doi.org/10.3390/ma12172677 - 22 Aug 2019

Cited by 21 | Viewed by 3055

Abstract

E174 (silver) is a food additive that may contain silver nanoparticles (AgNP). Validated methods are needed to size and quantify these particles in a regulatory context. However, no validations have yet been performed with food additives or real samples containing food additives requiring a sample preparation step prior to analysis. A single-particle inductively coupled plasma mass spectrometry (spICP-MS) method was developed and validated for sizing and quantifying the fraction of AgNP in E174 and in products containing E174, and associated uncertainties related to sample preparation, analysis and data interpretation were unraveled. The expanded measurement uncertainty for AgNP sizing was calculated to be 16% in E174-containing food products and increased up to 23% in E174 itself. The E174 food additives showed a large silver background concentration combined with a relatively low number of nanoparticles, making data interpretation more challenging than in the products. The standard uncertainties related to sample preparation, analysis, and challenging data interpretation were respectively 4.7%, 6.5%, and 6.0% for triplicate performances. For a single replicate sample, the uncertainty related to sample preparation increased to 6.8%. The expanded measurement uncertainty related to the concentration determination was 25–45% in these complex samples, without a clear distinction between additives and products. Overall, the validation parameters obtained for spICP-MS seem to be fit for the purpose of characterizing AgNP in E174 or E174-containing products. Full article

(This article belongs to the Special Issue Nanomaterial Characterization Methods: Leaping Towards Validation)

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8 pages, 997 KiB

Open AccessArticle

Monitoring the Environmental Aging of Nanomaterials: An Opportunity for Mesocosm Testing?

by Armand Masion, Mélanie Auffan and Jérôme Rose

Materials 2019, 12(15), 2447; https://doi.org/10.3390/ma12152447 - 31 Jul 2019

Cited by 10 | Viewed by 1996

Abstract

Traditional aging protocols typically examine only the effects of a limited number of stresses, and relatively harsh conditions may trigger degradation mechanisms that are not observed in actual situations. Environmental aging is, in essence, the complex interaction of multiple mechanical, physicochemical and biological stresses. As yet, there is no (pre)standardized procedure that addresses this issue in a satisfactory manner. Mesocosm experiments can be designed to specifically cover the aging of nanomaterials while characterizing the associated exposure and hazard. The scenario of exposure and the life time of the nanomaterial appear as the predominant factors in the design of the experiment, and appropriate precautions need to be taken. This should the subject of guidance that may be divided into product/application categories. Full article

(This article belongs to the Special Issue Nanomaterial Characterization Methods: Leaping Towards Validation)

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20 pages, 2263 KiB

Open AccessArticle

Evaluation of a TEM based Approach for Size Measurement of Particulate (Nano)materials

by Eveline Verleysen, Thorsten Wagner, Hans-Gerd Lipinski, Ralf Kägi, Robert Koeber, Ana Boix-Sanfeliu, Pieter-Jan De Temmerman and Jan Mast

Materials 2019, 12(14), 2274; https://doi.org/10.3390/ma12142274 - 15 Jul 2019

Cited by 36 | Viewed by 4591

Abstract

An approach for the size measurement of particulate (nano)materials by transmission electron microscopy was evaluated. The approach combines standard operating procedures for specimen preparation, imaging, and image analysis, and it was evaluated on a series of certified reference materials and representative test materials with varying physical properties, including particle size, shape, and agglomeration state. The measurement of the median value of the minimal external particle diameter distribution was intra-laboratory validated. The validation study included an assessment of the limit of detection, working range, selectivity, precision, trueness, robustness, and ruggedness. An uncertainty that was associated to intermediate precision in the range of 1–7% and an expanded measurement uncertainty in the range of 7–20% were obtained, depending on the material and image analysis mode. No bias was observed when assessing the trueness of the approach on the certified reference materials ERM-FD100 and ERM-FD304. The image analysis method was validated in an inter-laboratory study by 19 laboratories, which resulted in a within-laboratory precision in the range of 2–8% and a between-laboratory precision of between 2% and 14%. The automation and standardization of the proposed approach significantly improves labour and cost efficiency for the accurate and precise size measurement of the particulate materials. The approach is shown to be implementable in many other electron microscopy laboratories. Full article

(This article belongs to the Special Issue Nanomaterial Characterization Methods: Leaping Towards Validation)

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