ISO/TS 4966:2026

Technical
Specification
ISO/TS 4966
First edition
Nanotechnologies — Silica
2026-06
nanomaterials — Specification of
characteristics and measurement
methods for nanoporous silica
microparticles applied in liquid
chromatography
Nanotechnologies — Nanomatériaux de silice — Spécification des
caractéristiques et des méthodes de mesure des microparticules
de silice nanoporeuse utilisées en chromatographie liquide
Reference number
© ISO 2026
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ii
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms, definitions and abbreviated terms . 1
3.1 Terms and definitions .1
3.2 Abbreviated terms .3
4 Characteristics and their measurement methods . 3
4.1 General .3
4.2 Critical characteristics .3
4.3 Additional characteristics .4
5 Descriptions of characteristics and measurement methods. 4
5.1 General .4
5.2 Sample preparation .4
5.3 Particle size .4
5.3.1 Particle size .4
5.3.2 Particle size distribution.5
5.4 Specific surface area .5
5.5 Pore size .5
5.6 Specific pore volume .5
5.7 Metal impurity content .5
5.8 Tap density .5
5.9 Loss on drying .6
5.10 Surface silanol acidity .6
5.11 Carbon content .6
6 Test report . 6
Bibliography . 7

iii
Foreword
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iv
Introduction
Owing to their excellent physicochemical properties, silica-based materials have been used in various
[1]
fields, such as electronics, optics, and materials. Silica materials with nanopores (1-100 nm) have widely
been applied in separation due to their chemical inertness, naturally porous structure, large surface area,
[2]
and reversible adsorption-desorption ability under certain circumstances. These features also make it
an ideal candidate as liquid chromatography packing materials since liquid chromatography is essentially
based on selective adsorption and desorption of molecules in nanopores of stationary phases to achieve
[3]
desired separation of target molecules.
Originally, nanoporous silica materials as liquid chromatography media were mainly produced by sol-gel
[4]
methodology. The particles produced by this method had an irregular shape and broad size distribution,
from nanometres to millimetres. Typically, those particles needed to be further separated by passing through
a series of sieves with different meshes; thus irregular nanoporous silica particles, when used as liquid
chromatography media, were usually labelled with mesh size to indicate their particle size distribution.
[5]
Nowadays, more advanced synthetic techniques enable the production of spherical silica particles for a
new generation of liquid chromatography media. Compared to the irregular silica particles, spherical silica
particles exhibit narrower size distribution, leading to more even column packing and better separation
[6]
efficiency. Also, the packing of spherical silica particles minimizes voids and variability inside the column
bed, which can endure higher column pressure and flow rates and, consequently, are welcomed by engineers
who desire higher throughput of products when using liquid chromatography for preparative purposes.
Despite these advancements in particle morphology and packing performance, pure silica faces limitations
in chemical stability under extreme pH conditions. Ongoing research has led to the development of spherical
hybrid silica-based phases integrating organic moieties within the silica framework, offering enhanced
chemical stability, reduced silanol interactions, and greater mechanical robustness. This represents an
active technological direction aimed at expanding the operational range of silica materials. Currently,
major chromatography suppliers offer hybrid silica products as part of their portfolio. Nevertheless, pure
silica materials continue to be extensively utilized across diverse separation scenarios due to their well-
established manufacturing processes, consistent performance profiles, and cost efficiency.
The particle size of nanoporous silica microparticles determine the separation efficiency when the particles
are packed in liquid chromatography columns. Smaller particles provide better efficiency. Nevertheless,
the column back pressure is inversely proportional to the size of the particles. So, when high resolution for
complex samples or high-speed separation is desired, smaller particles packed in high-pressure columns
are the best candidates. When loading capacity is of high importance, e.g. in preparative chromatography,
larger particles are used to pack columns with larger volume and slower flow speed. The nanopores in silica
microparticles play a key role in separation processes. Most of the surface area of silica particles used as
liquid chromatography media is provided by the internal nanopores of the particles. Spherical particles will
have larger surface area when the pore size decreases, which is more suitable for the separation of smaller
molecules. Other factors influencing the chromatographic performance of nanoporous silica microparticles
[7]
include bulk density, water content, surface silanol group density, etc.
In common with other nanostructured materials, the manufacturing and material specification of
nanoporous silica microparticles are complex. Small variations in the synthesis conditions during
manufacturing and functionalization can lead to dramatic shifts in chromatographic properties. Moreover,
characterization methods can vary between different manufacturers and are typically not mentioned in the
document provided along with commercial products. Standardization of nanoporous silica microparticles
for liquid chromatography is therefore critical to harmonize test methodologies and specifications across
both pure and hybrid silica materials. Such standardization will enable users to compare or select the most
suitable and qualified silica microparticles for their applications.

v
Technical Specification ISO/TS 4966:2026(en)
Nanotechnologies — Silica nanomaterials — Specification of
characteristics and measurement methods for nanoporous
silica microparticles applied in liquid chromatography
1 Scope
This document specifies characteristics to be measured and applicable measurement methods of nanoporous
silica microparticles in powder form used as stationary phases in liquid chromatography.
This document does not cover materials with surface treatments after manufacturing, and characteristics
specific for health, the environment and safety issues.
NOTE 1 Silica and hybrid silica are both covered.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content constitutes
requirements of this document. For dated references, only the edition cited applies. For undated references,
the latest edition of the referenced document (including any amendments) applies.
ISO 80004-1, Nanotechnologies – Vocabulary — Part 1: Core vocabulary
ISO/TS 80004-6, Nanotechnologies — Vocabulary — Part 6: Nano-object characterization
3 Terms, definitions and abbreviated terms
3.1 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 80004-1, ISO/TS 80004-6 and the
following apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1.1
particle
minute piece of matter with defined physical boundaries
[SOURCE: ISO 26824:2022, 3.1.1]
3.1.2
particle size
linear dimension of a particle determined by a specified measur
...