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2022

2 CITAC News // May 2022

TABLE OF CONTENTS

FOREWORD BY THE CHAIR ...................................................................4


ADDRESS OF THE VICE-CHAIR ..............................................................6
MESSAGE FROM THE CITAC SECRETARY ..............................................8
EDITORIAL ..........................................................................................11
NEW GUIDES, EVENTS, AND WORSHOPS ...........................................13
FIRST EDITION OF THE EURACHEM/CITAC GUIDE ON ASSESSMENT
OF PERFORMANCE AND UNCERTAINTY IN QUALITATIVE CHEMICAL
ANALYSIS .........................................................................................14
CITAC/EURACHEM ONLINE WORKSHOP ON ASSESSMENT OF
PERFORMANCE AND UNCERTAINTY IN QUALITATIVE CHEMICAL
ANALYSIS .........................................................................................16
VTH INTERNATIONAL SCIENTIFIC AND TECHNICAL CONFERENCE
"METROLOGY OF PHYSICAL AND CHEMICAL MEASUREMENTS"
VNIIFTRI, RUSSIA, 14-16 SEPTEMBER 2021......................................19
LIAISON REPORTS 2021 OF THE SISTER INTERNATIONAL
ORGANIZATIONS ................................................................................22
AFRIMETS REPORT ...........................................................................23
APMP REPORT .................................................................................28
EURAMET ACTIVIES IN 2021 ............................................................30
ILAC REPORT ....................................................................................33
IMEKO REPORT ................................................................................38
3 CITAC News // May 2022

ISO/TC 334 REPORT .........................................................................40


IUPAC REPORT .................................................................................43
CITAC BEST PAPER AWARD 2021 .......................................................47
SUMMARY OF “COMBINING ISOTOPE DILUTION AND STANDARD
ADDITION – ELEMENTAL ANALYSIS IN COMPLEX SAMPLES” ...........48
SUMMARY OF ’METROLOGICAL FRAMEWORK TO SUPPORT
ACCURATE, RELIABLE, AND REPRODUCIBLE NUCLEIC ACIDS
MEASUREMENTS’’ ...........................................................................53
SUMMARY OF “LABEL-FREE DETECTION OF SARS-COV-2 SPIKE S1
ANTIGEN TRIGGERED BY ELECTROACTIVE GOLD NANOPARTICLES
ON ANTIBODY COATED FLUORINE-DOPED TIN OXIDE (FTO)
ELECTRODE” ....................................................................................60

CITAC NEWS published by:


Cooperation on International Traceability in Analytical Chemistry (CITAC)

Chair: Prof. Dr. Bernd Güttler


Physikalisch-Technische Bundesanstalt (PTB), Bundesallee 100, 38116, Braunschgweig, Germany
E-mail: bernd.guttler@ptb.de

CITAC News Editor: Prof. Dr. Felipe Rebello Lourenço


Faculty of Pharmaceutical Sciences, University of São Paulo, Brazil
E-mail: feliperl@usp.br
4 CITAC News // May 2022

FOREWORD BY THE CHAIR

CITAC ACTIVITY IN 2021


Bernd Güttler // PTB, Germany

With the current pandemic crisis already lasting seminars organized by the CCQM and BIPM. This
for over two years, the need for correct testing initiated a detailed discussion about metrological
and internationally comparable measurement issues and priorities in the pandemic to identify
results for COVID-19 is now obvious, although the the most critical points of interaction.
benefits of vaccinations reduce the burden of the
Several seminars were conduct between July
disease. The metrology community is now active
2020 and March 2021, each with different
in the field of pandemics and related publications
themes and time frames. It started with the
touching the subject field are now even amongst
exchange of Information between pandemic
the winners of our Best Paper Award. It's worth
expert laboratories and scientists to inform the
having a brief look into the evolution of the
metrological community on the on-going
metrological activities in the field up to today.
activities to ensure the robustness of testing in
Correct measurements for pandemic needs
support of COVID-19 management and response.
became the center of a range of activities in the
This was followed by a workshop in October 2020
National Metrology institutes and the related
that included reports on activities from NMIs with
bodies in the CCQM. Previously, fighting a global
an active work program addressing Covid-19. The
pandemic was not a prominent point on the
workshop in April 2021 addressed the technical
agenda of metrological activities – the legal
issues on standardization challenges and
requirements related to measurements in the
progress for measurements in response to the
case of a pandemic are simply scarce, or
Covid-19. All this led to a workshop on developing
completely absent. Further to this, the
"A roadmap for metrology of infectious disease
understanding and availability of technical tools
and future pandemic readiness" in October 2021
for primary metrological measurements in this
aiming for future concerted collaborative
domain were scarcely available.
activities at the NMIs and the expert laboratories
So, institutions responsible for tackling infectious for future pandemics.
diseases were not always in close cooperation
Information about the activities is available in the
with their national metrology institutes (NMIs)
newsletter of the Joint Committee for
and the NMIs were not ready for the necessary
Traceability in Laboratory Medicine (JCTLM-
extremely fast responses required. Since Covid-
Newsletter), special issue: Member and
19 it is clear to everybody that this gap has to be
Stakeholder Activities on COVID-19 at:
closed. At this point identifying and
understanding the most important measurement https://www.bipm.org/documents/20126/42834
challenges was of foremost interest for both 057/JCTLM-Newsletter-2020-COVID-
communities which resulted in a series of
5 CITAC News // May 2022

19.pdf/a025477a-dbd6-40ed-e142- measurement capabilities for this larger protein


81a3382272b3 within the National Metrology Institute
community, using a recombinant humanized IgG
Further to this exchange of information, CCQM
monoclonal antibody against spike glycoprotein
started comparison activities already in March
of SARS-CoV-2 (Anti-SIgG mAb) in solution. The
2020 with a comparison on SARS-CoV-2 PCR
consistency of the results was comparable to
quantification.
earlier results on much smaller analytes and
A fast-tracked inter-laboratory study for SARS- enabled NMIs to extend their capabilities into this
CoV-2 RNA genome measurement (CCQM- important field. A final report of the study is
P199.b), focussed on measuring key genes that available at:
are targeted by diagnostic tests for SARS-CoV-2.
https://iopscience.iop.org/article/10.1088/0026-
National Metrology Institutes were participating
1394/59/1A/08001
in the study along with guest laboratories who are
experts in virus detection and quantification. The EURAMET's European Metrology Network on
aim was a high accuracy quantification of Traceability in Laboratory Medicine (EMN
biological reference standards to ensure TraceLabMed) launched a "Workshop on
improved testing quality and defined test measurement challenges: SARS-COV2 and future
performance criteria such as limits of detection Pandemics" in November 2021 in order to initiate
and better comparability of diagnostic test collaborations among European NMIs for
results. First results showed a good agreement research projects tackling COVID-19 within the
between results from molecular reverse framework of the European Partnership on
transcription-digital PCR (RT-dPCR) based Metrology. Ideas related to "quality assurance of
methods and between those and other, SI- tests for infectious diseases and pandemics" (R.
traceable methods based on ID-mass Macdonald, PTB), "Metrology to support vaccine
spectrometry and flow cytometry. development and manufacturing” (E. De Santis,
Reproducibility of RT-dPCR was found to be much NPL) or on "Certified reference materials for
superior compared to conventional molecular SARSCoV2 serology assays" (G. Auclair, JRC) and
diagnostic methods commonly used for COVID-19 more were discussed. Information on the
testing. workshop and presentations are available at:

Further information about the pilot study can be https://www.euramet.org/publications-media-


found at: centre/events/detail/event/open-workshop-on-
measurement-challenges-sars-cov-2-and-
https://www.bipm.org/en/-/2020-nmi-covid
future-pandemics
A comparison on the "Quantification of SARS-
The European Partnership on Metrology launched
CoV-2 monoclonal antibodies" was launched in
a call for their target program on Health in
September 2020. The SARS-CoV-2 monoclonal
February 2022. Project proposals will be
antibody was used here as a model system for
evaluated later this year and project funding will
capacity building for antibody quantification.
start mid 2023.
Antibodies are immune system proteins that are
All this shows that metrology in biochemistry for
essential for diagnostics, therapeutics and
pandemics has taken off and can significantly
targeted drug delivery systems. The
contribute to the quality of diagnostic testing in
comprehensive analysis of monoclonal antibodies
the pandemic and will hopefully further
is, however, difficult. But the potential
contribute more metrology to solutions for
applications of these complex molecules require
pandemics in the future.
the standardization of suitable analytical
methods. The study allowed the development of
6 CITAC News // May 2022

ADDRESS OF THE VICE-CHAIR

MESSAGE FROM THE VICE


CHAIR
Zoltan Mester // National Research Council (NRC), Canada

This past year, the second year of COVID19, has measurement related information such as
seen an unprecedented global vaccination effort, quantities, units, values uncertainties in the
reopening of societies and overall a slow coming years instruction manuals, “digital SI
consolidation and a start of return to normalcy. Brochure” for computers will be developed how to
2021 has given us a new appreciation of the read and interpret measurement information.
importance of rules based multilateral CITAC will likely be key conduit in this work brining
arrangements as effective tools to deal with truly the unique requirements and challenges of
global issues from vaccine distribution to supply analytical chemical practitioners such as digitally
chain management. representation of chemical entities in quantity
definitions.
In the metrology world 2021 has been of
particular significance heralding the launch of In 2021 in my role as the coordinator of the CITAC
many digital metrology efforts. In particular the Best Paper in Metrology Award I had the pleasure
“SI digital frame work” of the BIPM is working of facilitating the award process and announce
toward creating international consensus on how three papers were voted by the CITAC
measurement related information to be constituency to be awarded:
represented digitally, including measurement
data, uncertainty, models, software etc. In
chemistry, one can envision a world where the F. R. Pennecchi, A. Di Rocco, I. Kuselman, D. B.
certificates of the CRM we are using for Hibbert, M. Sega, Correlation of test results and
calibration are directly accessed / “read” by our influence of a mass balance constraint on risks in
measuring instrument, creating error free data conformity assessment of a substance or
transfers from the producer of the CRM to the end material, Measurement 163 (2020) 107947 (Link)
user, facilitating traceability definitions,
automatically checking for updates of the
certificates. Clearly, these are highly desirable B. Toman, M. A. Nelson, Y. Ma, Optimizing
attributes for analytical chemists and also for the experiment design for chemical measurement,
users of our data. Just as the current SI and its Metrologia 57 (2020) 064003 (Link)
“human readable” instruction manual the SI
Brochure is enabling humans to read and parse
7 CITAC News // May 2022

H.-B. Yoo, C. Lee, K.-S. Hong, S.-R. Park, I. Yang, would like to thank all the CITAC members for
Quantification of single-strand DNA by sequence- supporting the nomination and selections
specific counting in capillary flow cytometry, process.
Metrologia 57 (2020) 065019 (Link)
I hope to see all of you, in person, in 2023!

First time ever, the CITAC Award ceremony and


Zoltan Mester
the lectures given by the authors of the awarded
papers were live casted and are now available CITAC vice chair
online (Link). Congratulations to the winners and I
8 CITAC News // May 2022

MESSAGE FROM THE CITAC SECRETARY

WHEN DID MEASUREMENT


UNCERTAINTY BECOME
USEFUL?
Ricardo Bettencourt da Silva // University of Lisbon, Portugal

The first records of measurements in chemistry, facilitate trading between partners that do not
i.e., measurements of a chemical species, date know how trustful each one is.
about 3000 years ago in documents from Ancient
In 1993, the international community produced
Egypt. At that time, neighbour civilisations
the ISO guide to the expression of uncertainty in
determined the gold content of gold alloys using a
measurements [1] that proposed a harmonised
gravimetric method to define the price or assess
way of dealing with the many challenges of
alloys' conformity with minimum gold content. In
evaluating the measurement uncertainty to allow
Ancient Egypt times, conformity assessment was
using this parameter in interpreting and assessing
based both on chemical analysis and on previous
measurement results. Six years later, the
records of the conformity of gold alloys from the
International Accreditation of Test Laboratories
few available gold producers. All these
introduced the evaluation of the uncertainty of
assessments, several Millenia before the known
measurements performed by accredited
father of Chemistry, Lavoisier, have applied the
laboratories [2]. For accredited tests, in the
scientific method to study chemical processes.
subsequent two decades, the laboratories and
The chemical principles of the analysis were
their assessors have been adapting to this
unknown but internal checks were used to assess
requirement by getting training and being more
laboratories' and analysts' performance
demanding and rigorous in accessing how
adequately.
laboratories evaluated and manage the
However, in the XX century, the outstanding uncertainty of their measurements. In some of
development of transport and communication the more regulated analytical fields, a maximum
methods that made globalisation invented in admissible uncertainty was established, and
Iberian discoveries much more effective, forced guidelines on evaluating the measurement
relevant development of trading rules. New tools uncertainty and using it in conformity
for a more objective assessment of traded assessment were defined. However, in many
product's conformity needed to be developed to more analytical fields, laboratories had to find
their own way of calculating this parameter.
9 CITAC News // May 2022

In 2020, after a rather long transition period of However, the new test accreditation
the third edition of the ISO 17025 standard from requirements on measurement uncertainty make
2017 [3], the measurement uncertainty concept us very optimistic about how international
became a daily concern for laboratories due to the recognition of competencies will evolve. The
need to define how it is considered in conformity community is paying attention to the need for
assessment. The standard even indicates the improving tests while being realistic about how
need for quantifying the risk of false conformity much time laboratories need to implement new
decisions based on the measurement uncertainty. practices. The requirements have become more
However, frequently, laboratories agree with the strict and ambitious as laboratories become able
customer about using the shared risk approach [4] to handle them.
that does not take the measurement uncertainty
It is time to look for new challenges laboratories
in conformity assessment into account. This rule
have to face, such as the validation and evaluation
is often agreed with the customer without
of the uncertainty in qualitative analysis [5] and
informing them that shared risk can be associated
how to characterise large populations, such as the
with a risk of up to 50% of false decisions.
contamination of a large river area [6]. Tools in
To summarise, 27 years after the publication of these areas have been developed but must be
the GUM, the measurement uncertainty concept disseminated and probably improved to make
is being used in conformity assessments of many them useful for the community. Let's hope these
products, although, in many cases, not with the will take less than a quarter of a century to
rigour that they could. This delay is justified by become useful for all.
the difficulty of introducing new concepts in an
already established industry of test laboratories
and the lack of laboratory customer organisations Ricardo Bettencourt da Silva
with the technical knowledge and the energy to
encourage the evolution of analytical practices.
10 CITAC News // May 2022

1. ISO/IEC, Guide to the expression of uncertainty 4. ILAC, Guidelines on Decision Rules and
in measurement (GUM) (SO/IEC GUIDE 98), ISO, Statements of Conformity (ILAC G8:09), ILAC,
1993. 2019.

2. ISO/IEC 17025, General requirements for the 5. Eurachem/CITAC, Assessment of performance


competence of testing and calibration and uncertainty in qualitative chemical analysis.
laboratories, ISO, 1999. First Edition, Eurachem, 2021.

3. ISO/IEC 17025, General requirements for the 6. C. Borges, C. Palma, R. B. Silva, Optimisation of
competence of testing and calibration river sampling: application to nutrients
laboratories, ISO, 2017. distribution in Tagus river estuary, Anal. Chem. 91
(2019) 5698-5705.
11 CITAC News // May 2022

EDITORIAL

METROLOGY IN MEDICINE
ANALYSIS
Felipe Rebello Lourenço

In May 2022, the new USP chapter <1220> The ATP is based on the intended use for the
“Analytical Procedure Life Cycle” became official. procedure and should include upper limits on the
The analytical procedure life cycle approach precision and trues of the measured value. The
proposed in <1220> is consistent with the ATP focuses the design goals for a new analytical
analytical quality by design (AQbD) concepts procedure, serves as a basis for procedure
described in International Council for qualification criteria, and provides a guide for
Harmonisation (ICH) guidelines. AQbD emphasizes monitoring of the procedure during its life cycle.
the importance of sound scientific approaches Ideally, the ATP should be specified in way that is
and quality risk management for the independent of the measurement technology;
development, control, establishment, and use of however, in some cases it may be necessary to
analytical procedures. link it directly to a measurement technology. The
ATP can be defined in many ways, but the overall
A fundamental component of the AQbD is the
focus of having a procedure with acceptable bias
definition of the analytical target profile (ATP) for
and precision should be part of the ATP. An
the analytical measurement. The ATP defines the
example of ATPs is shown below.
criteria for the procedure performance
characteristics that are linked to the intended
analytical application, aligned with the quality
“The procedure must be able to quantify
target product profile (QTPP). In other words, the
the active pharmaceutical ingredient (API)
ATP describes the required quality of the
in a range from 80 to 120% of the labeled
measured value since the measured value
content in the pharmaceutical dosage
obtained using the analytical procedure will
form in the presence of its impurities and
provide the basis for key decisions regarding the
degradation products with a target
conformity (non-conformity) assessment of a test
expanded measurement uncertainty of
item or batch with regulatory, compendial, and
2.5%.”
manufacturing limits. The measurement
uncertainty is widely used to assess the quality of
a measured value.
12 CITAC News // May 2022

The acceptable level of risk of false conformity specification acceptance range provides
(non-conformity) decision can also be considered adequate protection.
when establishing ATP criteria.
However, the closer the acceptance range is to
In my opinion, one of the most relevant issues the safe and efficacious range, the larger the
that is presented in the new chapter <1220> is the impact the measurement uncertainty can have on
use of measurement uncertainty information and decision rule risks. In this situation, guard bands
decision rules in the conformity (non-conformity) can be applied to the specification range to
assessment of medicines. determine the acceptance range. The guard band
is usually obtained by multiplying the standard
Deciding if an item or batch conforms to
measurement uncertainty by an appropriate
specification relies on the use of a decision rule. A
coverage factor. In situations where additional
decision rule provides the acceptable level of the
risk reduction is desired, a multistage testing
probability of a false conformity (non-conformity)
approach could be used with an indecision zone
decision, which can be used to define the target
for the initial stage of testing. When the
expanded measurement uncertainty (e.g.
measured value is within the indecision zone, a
maximum admissible expanded uncertainty). The
predetermined supplementary sampling and
most common type of decision rule is the simple
testing plan and decision rule are used to assess
acceptance (also called shared risk decision rule).
conformity (or non-conformity).
ATP determination must consider the impact that
The concepts presented in the new USP chapter
measurement uncertainty has on the risk of a
<1220> “Analytical Procedure Life Cycle” are
false conformity (non-conformity) decision. In
aligned with the subjects of several
other words, the risk that the item or batch is
Eurachem/CITAC guides, such as “Quantifying
considered to conform (or not conform) to
Uncertainty in Analytical Measurement, 3rd
specification limits when in fact the opposite is
edition” (2012), “Setting target measurement
true. This risk may be strongly impacted by the
uncertainty” (2015), “Measurement uncertainty
procedure variability. If the specification
arising from sampling, 2nd edition” (2019), and
acceptance criteria are well within a safe and
“Use of uncertainty information in compliance
efficacious range, using the simple acceptance
assessment, 2nd edition” (2021).
rule that the measured value must be within the
NEW GUIDES, EVENTS,
AND WORSHOPS
FIRST EDITION OF THE EURACHEM/CITAC
GUIDE ON ASSESSMENT OF PERFORMANCE
AND UNCERTAINTY IN QUALITATIVE
CHEMICAL ANALYSIS
Ricardo Bettencourt da Silva // University of Lisbon, Portugal

CITAC/EURACHEM ONLINE WORKSHOP ON


ASSESSMENT OF PERFORMANCE AND
UNCERTAINTY IN QUALITATIVE CHEMICAL
ANALYSIS
Tang Lin Teo // Health Sciences Authority, Singapore
Ricardo Bettencourt da Silva // University of Lisbon, Portugal

VTH INTERNATIONAL SCIENTIFIC AND


TECHNICAL CONFERENCE "METROLOGY OF
PHYSICAL AND CHEMICAL MEASUREMENTS"
N.G. Oganyan // VNIIFTRI, Russia
14 CITAC News // May 2022

NEW GUIDES, EVENTS, AND WORKSHOPS


FIRST EDITION OF THE EURACHEM/CITAC
GUIDE ON ASSESSMENT OF
PERFORMANCE AND UNCERTAINTY IN
QUALITATIVE CHEMICAL ANALYSIS
Ricardo Bettencourt da Silva // University of Lisbon, Portugal

The Eurachem/CITAC Qualitative Analysis including the signal comparison algorithm. An


Working Group has published a guide on how to alternative for determining false results rates to
quantify and express the performance of a either experimentation or database search,
qualitative analysis. This guide aims at applicable to instrumental methods of analysis, is
highlighting the need for an adequate validation simulating signals from items with and without
of qualitative analysis methods performed prior the studied property to determine the chance of
to or not integrated into the measurement of a false results. However, signals simulation
chemical property. In this guide, qualitative requires the development of adequate signal
analysis is defined as “classification according to models. The guide also discusses how to quantify
specified criteria”, where this criterion should be and report analysis performance where metrics
as objective as possible for easier control of driven from the Bayes Theorem such as posterior
analysis performance. Since qualitative analysis probability and likelihood ratio are presented
involves reporting a not quantifiable property, i.e. together with their limitations. The guide
a nominal property, the way performance is presents some examples of how performance can
assessed, compared and reported differs from be reported and closes with some application
measurement cases. The document describes the
type of false results that can occur in qualitative
analysis and how the rate of true and false results
can be quantified. When the qualitative analysis
method is very selective, time-consuming and/or
expensive, analysis performance cannot be
adequately quantified by analysing items known
to have or have not the studied property. If
qualitative analysis involves the assessment of
the match between reference and sample signal,
for instance, identification by comparing infrared
or mass spectra with a library of reference
spectra, the false results rate can be quantified by
the number of wrong reference signals matching
some sample signals. However, reference
databases are frequently not representative of
the population of studied items making this
evaluation method only adequate for an initial
assessment of the identification method,
15 CITAC News // May 2022

examples of identifications by GC-MS/MS, online workshop organised by the Health


infrared spectroscopy, immunoassay and qPCR. Sciences Authority of Singapore in January 2022
The guide was presented in a CITAC/Eurachem (See other CITAC News).
16 CITAC News // May 2022

NEW GUIDES, EVENTS, AND WORKSHOPS


CITAC/EURACHEM ONLINE WORKSHOP ON
ASSESSMENT OF PERFORMANCE AND
UNCERTAINTY IN QUALITATIVE CHEMICAL
ANALYSIS
Tang Lin Teo // Health Sciences Authority, Singapore
Ricardo Bettencourt da Silva // University of Lisbon, Portugal

Eurachem and CITAC jointly published the Guide which perform qualitative analysis by large, was
titled “Assessment of Performance and thus conceived in August 2021.
Uncertainty in Qualitative Chemical Analysis”
The workshop was organised by CITAC, Eurachem
after several years of hard work to detail key
and Health Sciences Authority (HSA, Singapore)
concepts and practical examples for users to
and additionally sponsored by IUPAC. The
implement the Guide for their professional work
workshop congregated like-minded experts (see
or research. The success of any Guide, which is
Figure 1) in the areas of qualitative analyses or
often painstakingly prepared lies in its degree of
examinations, metrology, analytical chemistry,
adoption or implementation. The key element in
forensics and laboratory medicine to organise
achieving this is to explain the Guide to its users
and present 16 talks. Due to the breadth in which
through active engagements. The idea of holding
the topic impacts multiple fields of chemical or
an online workshop, covering foundational
biochemical analyses, the online workshop was
materials such as terminologies and concepts,
held over four 3-hour sessions on 19th, 20th, 24th &
followed by examples targeted at specific fields
27th January 2022.

Table 1. Links to access the recording of the online workshop

Session 1: Terminology and content https://www.youtube.com/watch?v=VbguwpD6diQ


of the EURACHEM/CITAC Guide

Session 2: Qualitative chemical https://www.youtube.com/watch?v=q4V1KWXc_0I


analysis

Session 3: Qualitative forensic https://www.youtube.com/watch?v=ZiDODjkXGq8


analysis

Session 4: Qualitative analysis in https://www.youtube.com/watch?v=GJzU2UOPvnU


laboratory medicine
17 CITAC News // May 2022

Figure 1. Scientific Committee members and invited speakers for the workshop

Since the workshop was meant to benefit as many issue a Certificate of Completion to these
people as possible, the Scientific Committee individuals. The recordings will remain in YouTube
introduced the elements of easy to access online for a long period for individuals to re-view them
platform and made sure that its stakeholders as many times as they wish.
received news and open access recordings of the
The workshop garnered over 500 individuals from
workshop via YouTube (see Table 1) through
about 75 economies. Their affiliations covered
various professional networks and websites of
the following:
CITAC (https://www.citac.cc), Eurachem
(https://www.eurachem.org), HSA • Academia
(https://www.hsa.gov.sg) and IUPAC • Accreditation bodies
(https://iupac.org). In recognition of the workshop • Chemical/Clinical/Forensic testing
participants’ time and effort, the Scientific laboratories
Committee issued a digital certificate to any • Consulting firms
individual who has attended majority of the • Hospitals
duration for each session. • Intergovernmental organisations
To cater to individuals who were unable to attend • Metrology institutes
the session live for reasons, such as difficulty in • Ministries
adjusting to the time difference, but wished to • National laboratories
access the recordings and be recognised for their • Professional associations
effort in post-workshop self-learning, the ANSI • Regulatory & enforcement agencies
National Accreditation Board in United States • Research & development institutes
kindly hosted the videos in their learning
platform. This allowed the Scientific Committee
to track the completion of the viewings and to
18 CITAC News // May 2022

The Speakers were kept thoroughly engaged window of the online platform. A summary of
throughout the workshop as the audience the feedback is provided below.
posted several questions through the Chat

Figure 2. Summary of feedback on the workshop


19 CITAC News // May 2022

NEW GUIDES, EVENTS, AND WORKSHOPS


VTH INTERNATIONAL SCIENTIFIC AND
TECHNICAL CONFERENCE "METROLOGY
OF PHYSICAL AND CHEMICAL
MEASUREMENTS"
VNIIFTRI, RUSSIA, 14-16 SEPTEMBER 2021
N.G. Oganyan // VNIIFTRI, Russia

Since 2015 the All-Russian Scientific Research The Organizing Committee tries to expand the
Institute of Physicotechnical and Radio geography of participants, involving well known
Engineering Measurements (VNIIFTRI) organizes international experts in the field of metrology in
now biannual International Scientific and chemistry and biology to the work of the Program
Technical Conference "Metrology of Physical and Committee. As a result, the members of the
Chemical Measurements", contributing to the Consultative Committee for Amount of
CCQM Strategy and worldwide traceability. Substance: Metrology in Chemistry and Biology
(CCQM), of the International Bureau of Weights
On September 14-16, 2021, VNIIFTRI (Russia)
and Measures (BIPM), and of the Cooperation on
hosted the fifth Conference.
International Traceability in Analytical Chemistry
(CITAC) took part in the fifth Conference.

Despite of the travel restrictions caused by


COVID-19, the conference was organized in a
combined format (offline and online participants)
gathered more than 120 participants from 14
countries: Belarus, Great Britain, Germany, Israel,
Italy, Portugal, Uzbekistan, Ukraine, Uruguay,
France, Switzerland, South Africa, Japan and
Russia. The main sponsor and scientific organizer
of the conference was VNIIFTRI. Technical support
and organization were traditionally performed by
NTC "NAVITEST". Producers of measuring
equipment, such as Analitic Yena and CityAir,
participated in the conference as sponsors.
20 CITAC News // May 2022

It’s a pleasure to notes that five members of and CCQM members at the next such
CITAC took part as speakers at this conference: conferences.
Dr. Mickela Sega (Ex-chair of CITAC, InRIM, Italy),
A total of 50 reports were presented in person,
Dr. Ilya Kuselman (Ex-Editor of the CITAC News,
and 13 lectures were delivered by participants
independent consultant on metrology, Israel),
online.
Dr. Angelique Botha (NMISA, South Africa), Dr.
Samuel Wunderli (independent consultant on
metrology, Switzerland ) with an online
performane and Dr. Ricardo Da Silva (Secretary
of CITAC, Portugal) was able to come to Russia
to take part in the conference in person.

In addition to the lectures, poster presentations


were organized. In particular, representatives
of the Metrological Institute of Belarus (BelGIM)
informed the participants about the new
laboratory for characterization of particles. As
All participants highly appreciated the a result, an agreement was reached between
contribution of CITAC and CCQM members to VNIIFTRI and BelGIM specialists to organize a
the work of the conference and expressed their pilot study within the framework of the
gratitude for organizing their participation. As technical committee TC1.8 “Physical Chemistry”
well as, expressed their hopeful to see CITAC of COOMET (Euro-Asian Cooperation of
21 CITAC News // May 2022

National Metrological Institutions) to confirm conferences you can get on the conference
the equivalence of measurement results. Some website:
representatives of Russian metrological http://conference.vniiftri.ru/index.php/en/.
institutes reported their work on traceability in
ACKNOWLEDGEMENTS
the relevant areas of measurements in Russia
at the poster presentations. I am truly grateful to the Reviewers, among
which were CITAC members too, the voluntary
Sponsors and participants (VNIIFTRI, Analitic
work and high professional knowledge of which
Yena, CityAir, LabTest, Sortorius, etc.) were able
helped prepare and published the Conference
to demonstrate their products in a small
Proceedings. Also, I would like to thank the
exhibition, organized within the framework of
Members of the Program and Organizing
the Conference.
Committees, the Sponsors and the Editor teams
Following the conference, about 40 papers for their contributions to the Conference.
discussed at the conference were published as
the Conference Proceedings. The English
versions of the papers were included in a
volume of “Journal of Physics. Conference
series” and published on the IOPScience
publisher website with open access. The
Russian version was printed in the issue of
“Almanaс of Modern Metrology” (journal of
VNIIFTRI) and published on the website:
https://www.elibrary.ru, with open access.

The next conference will be organized in


September, 2023. Please add this event to your
calendar. More information about these
CITAC News // May 2022 22

LIAISON REPORTS 2021 OF THE


SISTER INTERNATIONAL
ORGANIZATIONS
AFRIMETS REPORT
Angelique Botha // NMISA, South Africa

APMP REPORT
Hongmei Li // NIM, China

EURAMET ACTIVITIES IN 2021


Michela Sega // INRIM, Italy

ILAC REPORT
Maire Walsh // LC liaison, Ireland

IMEKO REPORT
Michela Sega // INRIM, Italy, IMEKO TC8 Chair

ISO/TC 334 REPORT


Angelique Botha // NMISA, South Africa, ISO/REMCO Chair

IUPAC REPORT
Zoltan Mester // NRC, Canada, President of the IUPAC ACD
23 CITAC News // May 2022

LIAISON REPORTS

AFRIMETS REPORT
Angelique Botha // NMISA, South Africa

SUMMARY OF GENERAL ISSUES Trade Area (AfCFTA). PHASE 2: Capacity building


and harmonisation of standards and conformity
With the restrictions on travel imposed by the
assessment systems of the PTB sponsored PAQI
pandemic, the 14th Intra Africa Metrology
project “Harnessing quality infrastructure in the
System (AFRIMETS) General Assembly (GA) was
cassava value chain to improve quality of cassava
not held in 2020 but was held as an on-line
and cassava products and boost intra-African and
General Assembly in July 2021. ECOMET
global trade”, is currently being implemented. The
consisting of the Economic Community of West
projects under PHASE 2 include brochures to
African states has been formed as the 7th sub
create awareness about the importance and value
regional metrology organisation (RMO) of
of conformity assessment for all stakeholders
AFRIMETS.
from the farmers to the processors and
consumers of cassava products. Other projects
include the harmonisation of conformity
assessment standards for the cassava value
chain, the organisation of proficiency testing
schemes for different measurands in different
cassava products, etc.

The AFRIMETS TC-QS continued with its activities


and reviewed and approved the quality systems
of NMISA (South Africa) and KEBS (Kenya) as part
of the 5-year renewal cycle. The chemical
metrology activities at these institutes are
included in the scope of the quality systems (QS).
The review of the NIS (Egypt) quality system was
Figure 1: Schematic diagram of the countries and completed and approved by TC-QS in May 2021.
geographical location of ECOWAS (the Economic
CURRENT TC AND WORKING GROUP CHAIRS AND
Community of West African States).
CONTACT DETAILS
AFRIMETS continues to focus on the activities of
the Pan African Quality Infrastructure (PAQI) that The AFRIMETS structure includes working groups
is currently developing proposals for how the to mirror the international consultative
quality infrastructure (QI) can assist the committee working groups (CC-WGs) and are
implementation of the African Continental Free identified as TC-(parameter).
24 CITAC News // May 2022

The contact details of the TC-Chairs important to Chemistry are listed below:

Function Name Details

TC-QM Dr Angelique Botha National Metrology Institute of South


Africa (NMISA), Private Bag X34, Lynnwood
Vice-Chair Mrs Désirée Prevoo- Ridge, 0040, RSA
Franszen
(Bio analysis) Tel: +27 12 947 2705

e-mail: abotha@nmisa.org

Tel: +27 12 947 2738

e-mail: dprevoo@nmisa.org

TC-Mass and Related Mr Thomas Mautjana National Metrology Institute of South


Quantities Africa, Private Bag X34, Lynnwood Ridge,
0040, RSA

Tel: +27 12 947 2880

e-mail: tmautjana@nmisa.org

TC-QS Dr Noha Emad Khaled National Institute for Standards (NIS),

Vice-Chair (CMCs) Dr Wynand Louw Tersa Street, El Haram, Giza, 12211 Egypt

Tel: ++(202)33862322

e-mail: nemadnis@yahoo.co.uk or
nemadnis@netscape.net

National Metrology Institute of South


Africa (NMISA), Private Bag X34, Lynnwood
Ridge, 0040, RSA

Tel: +27 12 947 2895

e-mail: wlouw@nmisa.org
25 CITAC News // May 2022

AFRIMETS CMCs Validation were also presented during November


and December 2021.
As of 6 April 2022, there were a total of 708
AFRIMETS CMCs accepted in Appendix C of the The comprehensive training included evaluation
KCDB. of the implementation of the theoretical concepts
learned through 2 practical external quality
The CMCs originate from: assurance exercises with test sample analysis. A
feedback workshop was held after the first round
South Africa (NMISA) = 532
of the external quality assurance exercise to
(123 CMCs in Chemistry and Biology)
provide constructive feedback for improvements
Egypt (NIS) = 83 in the second round. The test samples were
(2 CMCs in Chemistry) prepared and distributed by NMISA according to
ISO/IEC 17043 requirements.
Zimbabwe (SIRDC) = 19
On behalf of AFRIMETS, supported by the PTB,
Kenya (KEBS) = 27 NMISA is conducting a Pan African Survey of Food
(2 CMCs in Chemistry) Safety Testing Laboratories within the Africa
Continental Free Trade Area (AfCFTA) during
Tunisia (DEFNAT) = 21
March to April 2022. The outcomes of the survey
Zambia (ZMA) = 11 will inform the technical infrastructure
institutions (metrology, standards, accreditation,
Namibia (NSI) = 7 conformity assessment) on how best to support
food safety testing within the AfCFTA.
Morocco (LPEE) = 5
NMISA hosted the Virtual Africa Food Safety
Botswana (BOBS) = 3 workshop (AFSW) on 4 August 2021, in
collaboration with the Africa Food Safety
DEVELOPMENT WORK IN CHEMISTRY AND
Network, and the FAO/IAEA Joint technical centre
BIOLOGY
for nuclear techniques in Food and Agriculture.
NMISA delivered a training programme on behalf There were over 600 attendees from across
of SADCMet (the Southern African sub RMO), Africa. The workshop resulted in an improved
supported by the PTB, from October 2021 to understanding of the needs and gaps related to
March 2022. The training programme was aimed food testing capabilities on the African continent
at “Strengthening Chemical Metrology for Food by all role players in the AfCFTA, including
Safety testing in the SADC Region”. The metrology institutes. The AFSW also included
programme consisted of: presentations by the African Union Commission
Minister of agriculture on the implementation of
An Introductory Chemical Metrology training sanitary and phytosanitary standards in the
course, region and discussion panels composed of food
A Comprehensive training suite for NMIs/DIs with monitoring laboratory representatives.
chemical testing capabilities. NMISA’s 11 new organic CMCs for mycotoxin
The Introductory Chemical Metrology training Certified Reference Materials (CRMs), matrix
course was conducted virtually over two half days CRMs as well as broad-scope CMCs for polar and
from 7 to 8 October and was attended by 22 non-polar organic substance purity assignment,
representatives from Eswatini, Zambia, Lesotho, was published on the Key Comparison Database
the Democratic Republic of the Congo (DRC), (KCDB) 2.0 in July 2021.
Botswana, Malawi, Madagascar, Mozambique, Due to COVID-19, the implementation of the
Mauritius, Seychelles, Tanzania, Namibia, and planned AFRIMETS supplementary comparison
Zimbabwe. After the introductory course, three for pesticides in fruit was delayed to 2022/23. The
other courses covering Metrological Traceability, comparison would enable AFRIMETS NMIs, such
Uncertainty of Measurement and Method as INRAP in Tunisia, who has an advanced
26 CITAC News // May 2022

capability in this area, to claim new CMCs. Much production of solution reference materials, INRAP
interest has also been shown by developing NMIs is currently participating in the on-line BIPM CBKT
from the SIM region, such as Columbia, Bolivia, activities. The activities offer theoretical and
and Argentina as well as from other NMIs active in practical knowledge of the use of techniques
the Organic Analysis Working Group (OAWG) of including Karl Fischer titration,
the CCQM. thermogravimetric analysis (TGA), sorption
analysis, elemental analysis and techniques
INRAP, who is the designated institute for
based on GC- and NMR-methods to obtain an
metrology in chemistry in Tunisia, is currently in
accurate, traceable quantification of the non-
the process of implementing a national strategy
structure related impurity content present in a
in Metrology in Chemistry to achieve
high purity organic material.
comparability of measurement results to meet
the national needs in terms of production of INRAP is also participating in the knowledge
certified reference materials (CRMs) and transfer study on Tetracycline.HCl purity
organisation of proficiency testing (PT) schemes. evaluation. The study offers institutes developing
INRAP has developed a roadmap for the capabilities in organic pure material
implementation of the national strategy in characterisation an opportunity to participate on
metrology in chemistry with the support of BIPM a “learn-as-you-measure” basis for capacity
and AFRIMETS experts. building purposes while also being able to
compare their results against laboratories with
INRAP is currently preparing for the
established capabilities in the field.
commissioning of the Gravimetric Unit for CRM
production with the support of the PTB under a FUTURE ACTIVITIES
bilateral project. This unit is estimated to be fully
NMISA will be hosting the second Africa Food
operational by the end of 2022. As a first step
Safety Workshop (AFSW) in collaboration with the
INRAP will be focusing on calibration solution
FAO-IAEA Joint Technical Centre and the Africa
production, such as aflatoxin B1 in acetonitrile,
Food Safety Network, to promote standards,
patulin in acetonitrile and copper in dilute nitric
reliable methods of analysis and inter-
acid. In conjunction with the commissioning of the
institutional cooperation for better public health
gravimetric unit INRAP is also receiving training in
and trade. The theme for the workshop is “Joining
ISO 17034:2016 and ISO Guide 35 for the
Hands to enable Food Safety in Africa” and will be
competent production of reference materials
held in Johannesburg, South Africa from 27 June
supported by the PTB.
to 1 July 2022.
To enhance the laboratory’s competence in the
application of gravimetric methods for the

Figure 2: Internet banner for the promotion of the 2nd Africa Food Safety Workshop (click on the link to go to the
webpage).
27 CITAC News // May 2022

The purpose of the event is to enhance • Risk Analysis: Assessment, management,


networking among food safety stakeholders in and communication
Africa; to facilitate the sharing of analytical • Sanitary and Phytosanitary requirements
knowledge and transfer of developed within the AfCFTA
technologies related to a range of food hazards. • Food monitoring and surveillance
Also, to encourage continent-wide discussions on programmes; Maximum Residue Limits
how to best improve national/regional food (MRLs)/Maximum levels (MLs)
safety control systems to safeguard consumers • Food Borne illnesses/outbreaks:
and facilitate trade. This event will utilise diverse Notification, responses, and epidemiology
discussion panels to explore how to: best align • Food safety education, the private sector
laboratories to address the challenges associated and stakeholder awareness
with setting food safety standards for both trade
The AFRIMETS TCQM meeting is planned to take
and public health; fit food safety control systems
place in conjunction with the Africa Food Safety
into the African Continental Free Trade
Workshop on the Friday, 1 July 2022.
Agreement arrangements; and reduce trade
rejections.

The workshop will take place in the form of


lecturers, posters and interactive panel
discussions covering the following topics: For any further information on the activities in
AFRIMETS or the activities of the TC-QM for
• Scientific capacity building and recognition Chemistry, please contact:
of capabilities
• Measurement standards; proficiency AFRIMETS Chair: Prof. Dr Mohamed Amer (NIS,
testing and accreditation; sustainable Egypt): amer_nis@yahoo.com
skilling
Head of the Secretariat: Dr Wynand Louw (NMISA,
• Advances in screening and confirmatory
South Africa): wlouw@nmisa.org
analysis applied to food safety testing for:
pesticides, mycotoxins, veterinary drug TC-QM Chair; Dr Angelique Botha (NMISA, South
residues, heavy metals, marine biotoxins, Africa): abotha@nmisa.org
phycotoxins, persistent organic pollutants,
microplastics and radionuclides TC-QM Vice-Chair; Ms Désirée Prevoo-Franszen
• Foodborne microbial hazards: zoonoses, (NMISA, South Africa): dprevoo@nmisa.org
One Health and antimicrobial resistance
• Food fraud
28 CITAC News // May 2022

LIAISON REPORTS

APMP REPORT
Hongmei Li // NIM, China

ASIA PACIFIC METROLOGY PROGRAMME (APMP) food (22.33%), and gas areas (28.14%) are majors
ACTIVITIES in APMP. Main trend include CMCs for food
analysis has increased, especially for PT
The 37th APMP General Assembly & Related
providing; Adopting broad claim approach: most
Meetings
of CMCs in cat. high purity chemicals & organic
The 37th APMP General Assembly & Related solutions, would be merged into broad claims; the
Meetings was held on-line on 1 – 26 November total CMCs will slowly reduce year by year.
2021, with over 230 delegates from 9
Comparisons: From 1999 APMP TCQM organized:
international/regional organizations and over 20
14 key comparisons (13 completed, 1 on-going),
economies in Asia. Highlights of the meeting
categories: gases (10) and pH (4). 23
include:
supplementary comparisons (19 completed, 4 on-
1) The APMP Metrology Digital Transformation going), categories: gases (14) and food (9). 38 pilot
Focus Group (DXFG) was established to studies (31 completed, 7 on-going), categories:
promote regional cooperation and external food and biological materials (27), pH (5), water(2),
liaison on APMP's metrology digital cosmetics (2), inorganic solutions (1) and surface
transformation. (1).
2) The APMP Response Program against COVID-
Meetings & Activities: The 21th Meeting of APMP
19 initiated in June 2021 goes smoothly,
bringing benefits to a dozen of developing TCQM was held on 4/8 November 2021 online.
economies. Topics in this programme include Food Safety Focus Group (FSFG)
respirator testing and calibration, RM
development for nucleic acid of COVID-19 FSFG Annual Meeting: On 4 November, 2021, the
virus , testing for personal protective APMP Food Safety Focus Group (FSFG) annual
equipment, etc. meeting was held on-line. 55 participants from 13
3) Election of next APMP Chair: Hyun-Min Park, economies attend the meeting. Prof. Li Hongmei,
President of Korea Research Institute of Chair of FSFG gave a report on the FSFG activities
Standards and Science (KRISS) was elected as over the past year. Representatives from GLHK
next APMP Chair, with his term to start from Hong Kong, KRISS Korea, NIM China, NIMT
the end of 2022 APMP General Assembly. Thailand, NMIJ Japan, NMISA South Africa and
NPL India were invited to introduce food safety
TCQM
activities in their economies. Besides, Dr.
TCQM has 26 economies (46 NMIs/DIs) as full Sutthinun Taebunpakul introduced the FGI
members and 11 economies as associated project on behalf of overseers from NIMT, GLHK
members. and HSA.
Total number of CMCs from APMP TCQM is 2,512 FSFG FGI: The topic of this year’s FGI is “Toxic
(by 5 Nov 2021). High purity chemicals (16.16 %), Inorganic Elements in Seafood”, which is jointly
29 CITAC News // May 2022

organized by NIMT, GLHK, and HSA. Under this by NIM, with 17 participating laboratories. A
topic, an on-line workshop was held from May 31 parallel APMP-APAC PT is about to be carried out.
to June 4, 2021, with a total participants of 230
THE 4TH TD-MSQS WORKSHOP IN PLAN
person-times. Besides, a post-training activity
was organized, with participating institutes from In 2022, under the theme of “Measurements,
ITDI Philippines, MASM Mongolia, NIS Egypt, Standards, Quality and Safety”, the 4th
NMISA South Africa, NPL India, SNSU-BSN Therapeutics and Diagnostics: Measurements,
Indonesia, TISTR Thailand. Standards, Quality and Safety (TD-MSQS)
BCEIA CHEMICAL METROLOGY AND REFERENCE workshop will be co-organized by NIM China and
MATERIAL SESSION the BIPM on July 11-13, 2022. The on-site
conference will be set in Chengdu, China, with on-
The 19th Beijing Conference and Exhibition on line access for international participants. Three
Instrumental Analysis (BCEIA 2021) was held on sub-sessions will include:
September 27-29, 2021 at China International
Exhibition Center (Tianzhu New Hall), Beijing. The A: Drug characterization and quality assurance
‘Chemical Metrology & Reference Materials sub- B: Research and quality control for in vitro
session’ was organized by NIM, with Prof. Li diagnostics
Hongmei being the Chair, over 100 participants
attended. It invited a total of 28 presentations C: Reference standards, regulation and metrology
covering the following four topics:new
Product efficacy and quality control for
techniques for chemical metrology and reference
therapeutics and diagnostic reagents and devices
materials, metrology in clinical and
are of great interest to biopharmaceutical and
pharmaceutical chemistry; metrology in food
diagnostics industries, and is a focus of R&D and
safety; metrology in environmental analysis.
standardization activities. To present state-of-
INTERNATIONAL COOPERATION PROJECT ON art researches and bridge stakeholders, an
MYCOTOXIN METROLOGY international workshop themed TD-MSQS was
jointly initiated by the BIPM and NIM China, and is
The acceptance meeting for the international held every two years. The 1st and 2nd TD-MSQS
cooperation project ‘Demonstration Research and workshops were held in Chengdu, China in 2016
Mutual Recognition of Measurement Standards and 2018, bringing together over 450
and Technological System for Agro-product representatives and delegates within
Safety’ was held on 23 February 2022. The project international organizations, National Metrology
was coordinated by NIM, with an implementation Institutes/Designated Institutes (NMIs/DIs),
period from 2017 to 2021. Participating members academic institutions and industries. Due to
include BIPM, NMISA, VMI, HSA, DSS, NPSL, STD- global travel restrictions caused by COVID-19, the
ITDI, NMC, etc. Under this project:1) High- 3rd workshop in 2020 run both on-site (Nanjing,
accuracy measurement technology for China) and on-line, with a live broadcast in
mycotoxins and relevant reference materials parallel. The workshop attracted over 300 on-site
developed; 2) An Inter-regional PT and 30,000 on-line audiences home and abroad.
‘Zearalenone in Maize’ was coordinated by NIM, Highlights of the 2022 Workshop will include
with 75 laboratories from 9 countries returned cutting-edge researches and techniques in
results; 3) CCQM-K168: ‘Non-polar analytes in measurement methods and standards for
high carbohydrate food matrix: trans- therapeutics characterization as well as advances
Zearalenone in Maize Powder’ was coordinated in IVD measurements and standardization.
30 CITAC News // May 2022

LIAISON REPORTS

EURAMET ACTIVIES IN 2021


Michela Sega // INRIM, Italy

EURAMET is the Regional Metrology In 2021 the first call within the potential
Organization (RMO) of Europe. It coordinates European Partnership on Metrology framework
the cooperation of National Metrology was launched, via the same EMPIR’s two stage
Institutes (NMI) in Europe in different fields of process, on the major topics of green deal,
metrology, such as traceability of normative, research potential, and an
measurements to the SI units, international additional call on capacity building for
recognition of national measurement researcher mobility grants. More information
standards and related Calibration and on the 2021 call can be found at
Measurement Capabilities (CMC), research https://www.metpart.eu/previous-calls.
projects, etc. Through the knowledge transfer
In 2022 a new call in the European Partnership
and cooperation among its members, EURAMET
on Metrology framework will be launched, via
facilitates the development of the national
the same two stage process, on the following
metrology infrastructures.
major topics, addressing specific challenges:
EURAMET is currently chaired by Jörn Stenger digital transformation, health, integrated
(PTB, Germany) who succeeded to Hans Arne European metrology, normative, research
Frøystein (JV, Norway); the two Vice- potential. Stage 1, opening on the 12th January,
Chairpersons Maria Luisa Rastello (INRIM, Italy) aims at offering stakeholders from any country
for the General Assembly (GA) and Maguelonne the opportunity to influence the projects
Chambon (LNE, France) who replaced Erkki undertaken by the European Community by
Ikonen (VTT, Finland) for the European identifying potential research topics. The
Metrology Programme for Innovation and highest priority topics received at Stage 1 will
Research (EMPIR) related matters. Due to provide the basis for Stage 2 which will open
Covid-19 pandemic, the EURAMET 15th GA took later in 2022. Major information on the calls,
place as an online meeting on 7th-10th June including the draft call scopes, can be found at
2021. The EURAMET 16th GA will take place from https://www.metpart.eu/.
30th May to 2nd June 2022, hosted by BEV, the
One of the most important initiatives
Austrian NMI.
undertaken by EURAMET for the promotion of
The cooperation among metrology institutes, cooperation conceived in a broader scope
academia, stakeholders, was implemented in towards better partnership, communication,
the last years through the European Metrology and harmonization is the European Metrology
Research Programme (EMRP) and EMPIR with Networks (EMNs). These are collaborative
more than 100 joint research projects. More structures which go beyond joint research to
information on the EMPIR calls can be found at increase the coordination of measurement
the webpage https://msu.euramet.org. science across Europe, addressing scientific and
societal challenges, infrastructure and services
in response to European and global metrology
31 CITAC News // May 2022

needs. Currently there are nine EMNs: The technical activities are carried out within
Advanced Manufacturing, Climate and Ocean the four technical Sub-committees dealing with
Observation, Energy Gases, Mathematics and gas analysis (SC-GA), inorganic analysis (SC-IA),
Statistics, Quantum Technologies, Radiation electrochemical analysis (SC-EA), bio and
Protection, Smart Electricity Grids, Smart organic analysis (SC-BOA). The convenors of the
Specialisation in Northern Europe, and subcommittees are: Janneke van Wjik (VSL, NL)
Traceability in Laboratory Medicine. Each EMN, for SC-GA, Rainer Stosch (PTB, DE) for SC-IA,
by providing a single point of contact, aims at Daniel Stoica (LNE, FR) for SC-EA, Mine Bilsel
underpinning regulation and standardization (UME, TR) for SC-BOA. In addition, a strategy
by establishing a comprehensive and longer- working group, chaired by the TC-Chair, is also
term infrastructure, promoting best practice active on the following tasks: advice to TC-Chair
and disseminating knowledge in its respective and subcommittee convenors, strategic
fields. Further EMNs are in preparation or under planning of comparisons, support actions,
consideration. More information on EMNs can coordination, organization of workshops.
be found at https://www.euramet.org/
The TC-MC members are actively participating
european-metrology-networks/.
in the European Programmes on Metrology,
Technical collaboration in EURAMET is being involved in all the targeted programmes;
organized within ten Technical Committees in addition they cooperate within various EMN,
(TCs), focusing on specific areas which among which Climate and Ocean Observation,
represent the forum for scientific and technical Energy Gases and Traceability in Laboratory
cooperation in the respective fields. In addition, Medicine, thus indicating the cross-disciplinary
two Committees deal with the overall topics nature of the TC itself.
Quality and Interdisciplinary Metrology. The
TC-MC MEETING IN 2021
TCs are responsible for the execution of the
activities required by EURAMET as RMO for the The annual meeting of the TC-MC was held
fulfilment of the Mutual Recognition online from 1st to 3rd February 2021, due to
Arrangement of the International Committee of Covid-19 pandemic. The first day was reserved
Weights and Measures (CIPM-MRA). The types for the Strategy WG meeting.
of technical cooperation carried out within the
TCs are: cooperation in research, comparison of The four technical subcommittees reconvened,
measurement standards, metrological as usual, ahead of the annual TC-MC plenary
traceability, and consultation on facilities. meeting on 2nd February 2021. A review of new
claims were carried out under cycle XXII of the
One of the ten TCs is devoted to Metrology in CMC claim period. Running and new projects
Chemistry (Technical Committee for Metrology and comparisons in the framework of EURAMET
in Chemistry, TC-MC), which is concerned with and EMPIR and also proposals for the call within
primary methods and reference materials for the potential European Partnership on
chemical measurements and research in Metrology (EMP) were discussed in detail in all
metrology to support different sectors in the sub-committees.
amount of substance fields.
A brainstorming joint session in preparation for
NEWS FROM EURAMET TECHNICAL the EMP programme followed the SCs
COMMITTEE IN METROLOGY IN CHEMISTRY (TC- meetings. Eight speakers presented ideas for
MC) Potential Research Topics mainly related to the
Green Deal Call.
TC-MC is chaired by Sophie Vaslin-Reimann
(LNE, France). 28 EURAMET member countries The plenary meeting took place on the 3rd
are represented in TC-MC plus the European February 2021. Some highlights on EURAMET,
Commission. BIPM and SASO, the NMI of Saudi BIPM and on CCQM strategy and activities
Arabia, have the status of observers. within its main working groups were given. The
convenors of the TC-MC subcommittees gave
32 CITAC News // May 2022

an overview of the activities of each with a particular focus on health, due also to the
subcommittee and of the main outcomes of the activities carried out within the various NMIs
meetings carried out in the previous day. The and DIs.
topic of metrology for digitalization was also
The plenary meeting took place on the 2nd
discussed.
February 2022. Some highlights on EURAMET,
TC-MC MEETING IN 2022 BIPM/CIPM, CCQM strategy and activities
within its main working groups were given. The
The annual meeting of the TC-MC was held
convenors of the subcommittees gave an
online from 31st January to 2nd February 2022,
overview of the activities of each
due to the persistence of the emergency related
subcommittee and of the main outcomes of the
to Covid-19 pandemic. The first day was
meetings carried out in the previous day. A
reserved for the Strategy WG meeting. Sophie
section of the meeting was devoted to EMNs
Vaslin – Reimann (LNE) will end her second
dealing with topics related to the amount of
chairperson mandate in June 2022; Teemu
substance field dealing with topics related to
Näykki (FMI – SYKE, FI) will officially take over
the amount of substance field. An overview was
during the next EURAMET GA.
given on the EMN for Climate and Ocean
The four technical subcommittees reconvened, Observation (coordinated by NPL), EMN for
as usual, ahead of the annual TC-MC plenary Energy Gases (coordinated by VSL), EMN for
meeting on 1st February 2022. A review of new Laboratory Medicine (coordinated by PTB). The
claims as well as the obligatory re-review of a following potential future EMNs were also
range of existing claims were carried out. presented: EMN for Environment (LNE) and
Running and new projects and comparisons in EMN for Safe and Sustainable Food (INRIM).
the framework of EURAMET and EMPIR and also
The next TC-MC meeting will be held at the
proposals for the upcoming EMP call were
beginning of February 2023. RISE, the Swedish
discussed in detail in all sub-committees. ).
NMI, had already offered the availability to host
Janneke Van Wijk (SC-GA) and Rainer Stosch
the 2022 meeting; also VSL offered the
(SC-IA) will end their mandate by the end of the
availability to host the meeting. The way in
year; the TC chair asked for their availability to
which the meeting will be held, either in face-
remain in office for an additional mandate. The
to-face mode, or hybrid or online, will be
voting will be carried out within each SC.
evaluated according to the evolution of the
On 1st February a specific workshop in Covid-19 pandemic. In case the pandemic
preparation for the 2022 EMP call was held, situation prevent a face-to-face meeting, the
with the presence of about 75 participants. The possibility of having an additional TC-MC
proposals addressed all the different targeted meeting in summer time will be evaluated to
programmes, i.e. digital transformation, health, give TC-MC members the opportunity to meet
integrated European metrology, normative, in person.
33 CITAC News // May 2022

LIAISON REPORTS

ILAC REPORT
Maire Walsh // LC liaison, Ireland

ILAC MEETINGS COVID-19 UPDATE

All ILAC Committees, including the Executive Information on the ILAC response to the COVID-
Committee and the Joint IAF MLA and ILAC MRA 19 pandemic continues to be published on the
Management (JMC), Joint Marketing and ILAC website as required via Latest ILAC News.
Communications and Joint Development Support
IAF, ILAC and ISO, under the coordination of the
Committees held virtual meetings during 2021.
IAF/ILAC/ISO Joint Strategic Group (JSG), worked
The 25th ILAC General Assembly was held together in late 2021 to produce a survey to
virtually for the second year running on 2 better understand the views of the conformity
November 2021. The Adopted Resolutions are assessment community and those that rely on the
available to download from the ILAC website. results of conformity assessment, on the use of
remote techniques for audit/ assessment/
The IAF/ILAC mid-term meetings were again held
evaluation activities.
virtually in April this year and included meetings
of the ILAC AIC and Inspection Committees and This follows the rapid take-up of remote
the Joint ILAC/IAF Development Support techniques for audit, assessment and evaluation
Committee. The online platform, registration that has occurred since the commencement of
process and management of these meetings was the pandemic.
provided by Say Something Communications.
Participants were asked to complete the survey
The annual meetings in 2022 are scheduled to be for their own organisation and/or as an individual
held in person at Le Westin, Montreal, Canada carrying out a remote activity, and to also share
from 2 - 11 November 2022. At this time it is the the survey link with their customers,
intention to hold the meetings in person, with the stakeholders and any others they felt may wish to
option for on-line access also where possible. contribute information for the survey.
Planning for these meetings is currently
There was an excellent response to the survey
underway and further information will be
with more than 4000 participants contributing.
available as the details are finalised.
The report on the outcome of the survey was
In addition to the meetings noted above all ILAC released in October 2021 and can be accessed
Committees, Working Groups and Task Forces are from the ILAC website: Full Article and Survey
continuing to progress the items on their work Report.
plans via a combination of email and remote
DECISION TO ESTABLISH A SINGLE
meetings.
INTERNATIONAL ORGANISATION FOR
Information on future meetings and events, ACCREDITATION
including major regional meetings, can also be
The contract for the IAF-ILAC Single Organization
found in the ILAC Calendar.
Project has been signed and work commenced on
34 CITAC News // May 2022

1 March 2021 to establish a Single International signatories/recognised-regional-cooperation-


Accreditation Organisation in accordance with bodies/.
the 2019 JGA Frankfurt Resolutions. The
There are currently 104 signatories to the ILAC
successful contractor is Dr.-Ing. Thomas Facklam
MRA representing 105 economies. The ILAC MRA
Unternehmensberatung.
covers recognition for accreditation in the areas
JGA Frankfurt Resolution 1 – Recommendation to of calibration (ISO/IEC 17025), testing (ISO/IEC
Establish a Single International Accreditation 17025), medical testing (ISO 15189), inspection
Organisation (1): The Joint General Assembly (ISO/IEC 17020), proficiency testing providers
endorses the recommendation of the Joint (ISO/IEC 17043) and reference material producers
Executive Committee to establish a single (ISO 17034). The list of signatories to the ILAC MRA
international organisation for accreditation on is available from the ILAC MRA Signatory Search.
the basis of the results of the “Survey In Support
The ILAC MRA Annual Report 2020 was been
of the IAF 2020 – 2025 and ILAC 2021 – 2025
published in June 2021 and is available from
Strategic Plans”
https://ilac.org/publications-and-resources/ilac-
JGA Frankfurt Resolution 2 –Recommendation to promotional-brochures/. The 2021 version of this
Establish a Single International Accreditation report has been prepared and reviewed by the
Organisation (2): The Joint General Assembly AMC and will be published in May 2022.
endorses the recommendation of the Joint
The regions provided reports on the final
Executive Committee to create a Steering
transition data to ISO/IEC 17025:2017 (deadline
Committee, reporting to the Joint Executive
for transition was 1 June 2021). These reports
Committee, to lead the process to establish a
were subsequently reviewed by the members of
single international organisation for
the ILAC AMC in July 2021. ARAC, EA and IAAC
accreditation. In this regard, a contractor will be
confirmed all signatory ABs achieved 100% of
engaged and the costs for the project will be
laboratories transitioned by the revised 1 June
shared equally by IAF and ILAC.
2021 deadline. APAC, AFRAC and SADCA provided
The contractor is currently working closely with supporting information of actions taken (e.g.
the Joint Steering Committee on various tasks suspension) by ABs for accredited laboratories
associated with this project and gave a that had not transitioned by 1 June 2021.
presentation to the ILAC General Assembly on 2
The ILAC AMC Chair, Jennifer Evans, in particular
November 2021. In addition, a webinar was held
thanked the regional MRA/MLA Committees for
for all IAF and ILAC members on 13 December
their extensive commitment and work in
following the distribution of the draft of the
achieving these transition deadlines.
partial bylaws for the new organisation in late
November 2021 for review. The comment period Work to extend the ILAC MRA to include
closed in mid-January 2022 and the comments accreditation of biobanking continues following
received and contractor’s observations were the adoption of the following resolution during
distributed for information to all members in the 25th ILAC General Assembly in 2022: ILAC
March. Meetings of the Steering Committee and Resolution GA 25.09 The General Assembly
the JEC have since been held to discuss the endorses the recommendation of the ARC to
outcomes and next steps. extend the ILAC Mutual Recognition Arrangement
(MRA) to include accreditation of biobanking as a
THE ILAC MRA
Level 2 activity, to the criteria specified in the
The recognition of the IAAC MLA to the ILAC MRA Level 3 normative document, ISO 20387. ILAC will
was extended to include the accreditation of RMP therefore accept applications for recognition as
using ISO 17034 in June 2021. soon as the documents within ILAC applicable to
the MRA are updated to cover this new scope.
The scope of recognition of the recognised
regions to the ILAC MRA is available from The relevant documents have been updated, the
https://ilac.org/ilac-mra-and- member comment period completed and the
35 CITAC News // May 2022

voting referendum is currently underway. laboratories, inspection bodies, PTPs and RMPs
Accordingly, the process for finalising the revision are available from the ILAC Facts & Figures page.
of the documents applicable to the ILAC MRA to
ILAC EXECUTIVE
cover the new scope of biobanking is now well
advanced. In 2021, ILAC Executive meetings were held
virtually on 24 February, 1 June and 21 October.
Case studies and research on the recognition of
An extraordinary meeting of the Executive was
the ILAC MRA by governments and regulators are
also held on 19 May.
available from the Public Sector Assurance
website. The website is a collaborative initiative In 2022 the Executive has continued to meeting
of the INetQI members and there are over 330 virtually with the first meeting being on 28 March
case studies, 90 research papers and 60 and another currently being scheduled for June. A
supporting materials available to view. virtual meeting of the Joint ILAC and IAF
Executive Committees (JEC) was held on the 5th
The Business Benefits website a reference
April 2022. Key topics included the progress on
website designed to demonstrate the monetary
the Single Organisation Project and future joint
value of standards, conformity assessment and
meetings.
accreditation for businesses. The website
represents another successful collaboration of ILAC LIAISONS AND OTHER INTERNATIONAL
the INetQI partners with over 95 case studies ACTIVITIES
categorised into 6 areas of value. All of the case
studies identify a clear financial benefit. The site The current list of ILAC liaison activities includes:
also includes more than 75 research papers. ILAC Liaisons with ISO and ISO/CASCO Policy
Both the Public Sector Assurance and the Committees
Business Benefits websites had upgrades during • ISO-IAF-ILAC JSG (Joint Strategic Group)
2021 to improve the search capabilities including • ISO/CASCO Plenary
the addition of a dedicated search function for • ISO/CASCO CPC (Chairman’s Policy Committee)
each of the 17 Sustainable Development Goals • ISO/CASCO STAR (Strategic Alliance and
(SDGs). The case studies on these sites are now all Regulatory Group)
linked to applicable goals. • ISO/CASCO TIG (Technical Interface Group)
ILAC MEMBERSHIP • ISO TC 69/ SC6 (Application of statistical
methods)
The ILAC membership as at 2 May 2022 is: • ISO TC 176 (Quality Management & Quality
• 104 Full Members (signatories to the ILAC Assurance)
MRA) representing 105 economies; • ISO TC 212 Plenary (Clinical Laboratory
• 19 Associates representing 24 economies; Testing and In-Vitro Diagnostic Systems) and
• 22 Stakeholders; WG1 (ISO 15189 revision)
• 6 Regional Cooperation Bodies (includes 5 • ISO TC 272 WGs 1-5 (Forensic Sciences)
Recognised Regional Cooperation Bodies) • ISO TC 276 WG2 (Biobanking)
• ISO TC 334 (Reference Materials - formerly
As per the 2019 revised ILAC Articles of
ISO/REMCO)
Association, the ILAC Affiliate category of
membership ceased to exist on 1 January 2022. ILAC Liaisons with ISO/CASCO Working
Groups/Task Forces
The ILAC membership consists of 151
organisations from 126 different economies • ISO/CASCO CPC TG Future of CASCO Toolbox
worldwide. Over 85,000 laboratories, 13,000 • ISO/CASCO WG 56 Revision of Guide 60 - Code
inspection bodies, 600 PTP and 250 RMP are of Practice
accredited by the ILAC Full Members (signatories • ISO/CASCO WG 57 Revision of ISO/IEC 17043
to the ILAC MRA).The latest statistics and graphs ILAC Liaisons with Other Organisations
on the number of accreditation bodies, accredited
• BIPM-ILAC WG Bipartite
36 CITAC News // May 2022

• BIPM-ILAC-ISO-OIML Quadripartite releases and MoUs, is available from the ILAC


• OIML-CS Management Committee (MC) Partnerships page.
• CITAC (Cooperation on International
ILAC thanks all of the ILAC liaison officers, and
Traceability in Analytical Chemistry)
their organisations, who volunteer their time to
• EUROLAB Conference
assist ILAC in carrying out these activities for the
• IEC/IECEE International Electro-technical
benefit of all ILAC members.
Commission (ILAC-IAF-IEC Steering
Committee) The Liaison information page, located in the
• INetQI International Network on Quality member’s area of the ILAC website, continues to
Infrastructure serve as the main repository for the reports and
• JCGM Joint Committee for Guides in documents produced as part of ILAC’s liaison
Metrology Plenary and WGs 1 (GUM) and 2 activities. ILAC members can also find copies of all
(VIM) ILAC comments submitted during ISO/CASCO
• JCTLM Joint Committee on Traceability in ballots on international standards pertinent to
Laboratory Medicine the work of ILAC. The ILAC Liaison Procedure,
• ITU International Telecommunication Union which provides information relating to ILAC’s
• OECD Organisation for Economic Cooperation liaison activities, can also be downloaded from
and Development this page.
• WADA World Anti-Doping Agency ILAC SECRETARIAT

Stephanie Sun, the ILAC Project Officer


The Third ILAC-WADA Communiqué issued with commenced maternity leave in July 2021 for 12
respect to the ILAC-WADA cooperation regarding months.
the WADA anti-doping laboratories was
Vanessa Oconer Muhi, ILAC Quality Officer, left
published on 1 April 2021. The Communique is for
the Secretariat to take up a permanent position at
the attention of all accreditation bodies involved
the beginning of July 2021.
in the accreditation of WADA anti-doping
laboratories in accordance with ISO/IEC 17025 The ILAC Secretariat staff currently includes:
and is available from https://ilac.org/about- Annette Dever, Sharon Kelly, Stephanie Sun
ilac/partnerships/international-partners/wada/ (maternity leave July 2021- August 2022),
under Communiqués. Rebecca Sheehan, Rose De Rota (0.7 FTE), Hannah
Yeoh (increased from 0.6 to 1.0 FTE to provide
A joint WADA/ILAC Webinar on the topic: Raw data
some maternity leave coverage) and Joelle
integrity – considerations for the future was held
Nicolas (0.8 FTE).
on 27 April 2021. This webinar was a collaboration
between ILAC and WADA and included the WORLD ACCREDITATION DAY (WAD)
presentation of a case study by WADA and
Forensic Experts from the Criminal School of World Accreditation Day was celebrated on 9
Lausanne University demonstrating the June with the theme for WAD 2021:
manipulation and subsequent tracing of raw data “Accreditation: Supporting the Implementation of
in a laboratory setting. In particular it highlighted the Sustainable Development Goals (SDGs).”
lessons learnt from this case study and how these The theme for WAD 2022 is: “Accreditation:
may be applied in assessing and confirming the Sustainability in Economic Growth and the
integrity of raw data in the future across many Environment”
areas of laboratory and inspection activities
where raw data is generated. A contest was held again this year to develop the
official poster for World Accreditation Day 2022.
The WADA-ILAC MoU was re-signed on 25 The promotional materials are now being finalised
November 2021. and will be available from the ILAC website in the
Information on ILAC’s partnerships, including near future: https://ilac.org/news-and-events/
copies of communiqués, joint procedures, press
37 CITAC News // May 2022

DOCUMENTS AND BROCHURES ILAC G7:04/2021 Accreditation Requirements and


Operating Criteria for Horseracing Laboratories
Publications finalised and released since March ILAC-R1:12/2021 Management of ILAC
2021 include: Documents
ILAC-G18:12/2022 Guideline for describing
ILAC B15:03/2021 Specifying accreditation for
Scopes of Accreditation
COVID-19 (SARS-CoV-2)
Statement 03/2021 Replacement of Assessments
During the COVID-19 Pandemic
38 CITAC News // May 2022

LIAISON REPORTS

IMEKO REPORT
Michela Sega // INRIM, Italy, IMEKO TC8 Chair

IMEKO, the International Measurement (Germany) as the new President of IMEKO, Prof.
Confederation, founded in 1958, is a non- Paolo Carbone (Italy) as new President Elect and
governmental federation of 42 Member Chair of the Technical Board, Prof. Masatoshi
Organizations individually concerned with the Ishikawa (Japan), past President, as the Advisory
advancement of measurement technology. It has President and Chair of the Advisory Board. The
a consultative status with UNESCO and UNIDO. Its General Council took place on the 28th and 29th of
fundamental objectives are the promotion of August. New IMEKO Officers and Chairs of IMEKO
international interchange of scientific and Committees were elected or re-elected for the
technical information in the field of measurement next three-year mandate (2021-2024). Two new
and instrumentation and the enhancement of TCs were founded: TC6 “Digitalization” chaired by
international co-operation among scientists and Sascha Eichstädt (Germany) and TC25 “Quantum
engineers from research and industry. measurement and quantum information” chaired
by Barbara Goldstein (US). Two new members
IMEKO Secretariat is located in Budapest
joined IMEKO: INMETRO of Brazil and ETS-UPN
(Hungary). More information about IMEKO and its
(School of Telecommunications and Space
structure can be found on the IMEKO website
Remote Sensing, National Pedagogical University)
(www.imeko.org).
of the Democratic Republic of Congo. IN
In 2021, due to the Covid-19 pandemic, the Decembre 2021 also IMBiH, the Metrology
greatest part of IMEKO events were organized Institute of Bosnia and Herzegovina, joined
virtually, including the Presidential Board and the IMEKO as new member organization; it will keep
General Council meetings, with the fundamental the Observer status until the next GC session.
and excellent support of IMEKO Secretariat.
A workshop for TC officers was organized in May
For the first time since IMEKO foundation in 1958, 2021 leading to the establishment of four
also the IMEKO World Congress, organised by the working groups, i.e. “TC functioning”, “TC events”,
Science Council of Japan, had to be held virtually “IMEKO publishing activity”, “TB functioning”,
from August 30th to September 3rd 2021. The aiming at revising the existing IMEKO documents.
organisers, within a very short time, had to cancel
As a consequence of the pandemic and due to the
the face–to-face meeting planned in Yokohama,
number of online events that were organized,
and arranged an online conference, with keynote
IMEKO is investigating suitable formats for
speakers, scientific and technical sessions for the
online or hybrid events in addition to face-to-
various Technical Committes (TCs), giving also the
face events.
opportunities to the TCs to hold their meetings.
The Congress had 463 registered participants; The TCs can select best contributions to IMEKO
306 papers were submitted from 36 countries. events to be published, as enhanced versions of
During the World Congress the change in the the corresponding papers, in Measurement, the
Presidential Board was ratified: Prof. Frank Härtig official journal of IMEKO, after the events.
39 CITAC News // May 2022

Additional contributions to IMEKO events can be The preparation for the XXIV IMEKO World
also published in the IMEKO Online Journal ACTA Congress is ongoing. It will take place at the new
IMEKO, which published its 4 issues in 2020 Congress Center of Hamburg (Germany) on 26th-
(https://acta.imeko.org/index.php/acta-imeko). In 29th August 2024, hosted by PTB, the German
addition, two more specific journals are also Member Organization of IMEKO. More
available: Measurement: Sensors, in line with the information and updates can be found on the
increasing demand for sensor-related dedicated website (https://www.imeko2024.org/).
publications and for open-access publishing The meetings of the IMEKO Annual Advisory
model, and Measurement: Food, in line with the Board Meeting, the General Council Session and
rapid growth of studies on food and nutrition the Technical Board and the Measurement
measurements. Editorial Board will be held on August 24th and
25th.
40 CITAC News // May 2022

LIAISON REPORTS

ISO/TC 334 REPORT


Angelique Botha // NMISA, South Africa, ISO/REMCO Chair

CREATION OF THE NEW ISO TECHNICAL are written to support the work of standards
COMMITTEE FOR REFERENCE MATERIALS writers. Contrary to this definition, the
(ISO/TC 334) ISO/REMCO Guides, were developed as general
technical guidance documents in the specific field
ISO/REMCO was the Committee for Reference
of the production and use of reference materials
Materials of the International Organisation for
to be used by producers and users of reference
Standardisation (ISO) that carried out and
materials.
encouraged a broad international effort for the
harmonisation and promotion of the production ISO TMB then decided in February 2020, that it
and use of reference materials. It aimed to be the will be more appropriate for ISO/REMCO to
global centre of excellence with respect to issues become an ISO technical committee. As a
relating to reference materials. Since the 1970s, technical committee, ISO/REMCO could review the
ISO/REMCO has developed internationally scope and purpose of the ISO/REMCO Guides and
harmonised guidance for the production and use decide to transform the Guides into other ISO
of reference materials and published a suite of deliverables, including international standards.
five ISO/REMCO Guides (ISO Guide 30 to 35, and On 14 December 2020, ISO TMB approved the
more recently ISO Guide 80 for the in-house creation of the new technical committee, ISO/TC
preparation of quality control materials (QCMs)). 334, Reference materials. ISO TMB approved the
disbandment of ISO/REMCO on 15 February 2021
In February 2019, the ISO Committee on
and allocated REMCO’s published documents and
Consumer Policy (COPOLCO) raised concerns with
current projects to ISO/TC 334.
the ISO Technical Management Board (TMB) about
the purpose and intended use of ISO Guides. ISO This change is a very beneficial change for the
TMB then instructed ISO/Central Secretariat (CS) committee in all aspects of the activities of the
to review all the existing ISO Guides and propose committee. ISO/TC 334 will be able to develop
a course of action for the future of each Guide. international standards, which has been on the
The course of action could either include a specific wish list of the committee since 2002. The
plan to promote the Guide to the ISO technical committee will now be able to decide to
committee community or to transform the Guide transform some, or all, of the guidance
into other ISO deliverables, such as an documents that it has developed over the years
international standard or technical report. During into international standards and will also be able
the review performed by ISO/CS, it was found that to develop new guidance documents as
the Guides developed by ISO/REMCO did not meet international standards. As international
the criteria of a Guide. The definition of a Guide as standards the guidance documents developed for
published in the ISO/IEC Directives Part 2 state the production and use of reference materials will
that Guides should function as guidance now have the standing of internationally
documents to assist the development of ISO harmonised documents that can be adopted as
documents, principally standards, i.e., ISO Guides part of regulations, as it is the requirement for the
41 CITAC News // May 2022

European Union (EU) and other countries, such as FIRST MEETING OF ISO/TC 334
Japan.
The first meeting of ISO/TC 334 was held on 8 and
On this point, it is important to note that 9 September 2021. The most important decisions
international standards as per the definition of that were taken during the first meeting included
the ISO/IEC Directives Part 2 are not required to the approval of the title of the committee to be
only consist of requirements, which is the usual ISO/TC 334 – Reference materials with the scope
perception of a ‘standard’. There are a number of to develop standards in the competent
published international standards that consist of production and use of reference materials,
only recommendations, e.g., ISO 26000:2010 (this including the concepts, terms and definitions
example is also mentioned in clause 11.5.2 of the related to reference materials. Discussions on the
ISO/IEC Directives, Part 2) and ISO 24156-1:2014. way forward to meet the mandate from the ISO
ISO/TC 334 will therefore be able to continue to TMB to transform the ISO/REMCO Guides into
develop its documents either as a mixture of other ISO deliverables lead to the extension of the
requirements and recommendations or solely as meeting to 16 November 2021 for the finalisation
recommendations. and approval of the resolutions.

Figure 1: Schematic diagram of the planned ISO 33400 series standards for the transformation of the ISO/REMCO
Guides 30 to 35 to international standards as well as the other projects of ISO/TC 334
42 CITAC News // May 2022

It was decided to transform the ISO/REMCO between the different documents previously
Guides into international ISO standards without developed and currently being developed by
technical change through a draft international ISO/TC 334.
standard (DIS) enquiry stage. The structure of
• ISO/WD 33400 (previously ISO Guide 30) –
ISO/TC 334 was expanded with the establishment
Reference materials – Selected terms and
of new working groups to facilitate the new work
definitions
item proposals for the transformation of the
existing ISO/REMCO Guides. • ISO/CD 33401 (previously ISO Guide 31) –
Reference materials – Contents of
The liaison relationships that ISO/REMCO certificates, labels and accompanying
previously had with other ISO/TCs, and several documentation
external organisations have been re-established • ISO/CD 33402 (previously ISO Guide 80) –
in the new committee. This strong horizontal Guidance for the in-house preparation of
function of ISO/REMCO to advise other technical quality control materials (QCMs)
committees on issues related to reference • ISO/CD 33403 (previously ISO Guide 33) –
materials will continue as part of the work of the Reference materials – Good practice in using
new committee. It is hoped that the recognition reference materials
that the ISO/REMCO Guides will gain when they • ISO/CD 33405 (previously ISO Guide 35) –
become international standards will also highlight Reference materials – Guidance for the
the importance of reference materials in the field characterization and assessment of
of the establishment of metrological traceability homogeneity and stability
for chemical as well as biological measurements
• ISO/CD 33406 (previously WD/ISO Guide 85) –
and other fields of testing.
Guidance for the production of reference
PROGRAM OF WORK OF ISO/TC 334 materials having one or more assigned
qualitative property values
The program of work of ISO/TC 334 have now • ISO/CD 33407 (previously WD/ISO Guide 86) –
been updated based on the decisions taken at the Guidance for the production of pure organic
first and second meetings and are listed below. certified reference materials
The program includes the transformation of the
• ISO/AWI 33408 (previously AWI/ISO Guide 87)
existing ISO/REMCO Guides as well as the new
– Guidance for ‘pure’ reference materials for
work items of the committee that will also be
metals and metalloids
transformed into international standards.
Figure 1 below also depicts the relationships
43 CITAC News // May 2022

LIAISON REPORTS

IUPAC REPORT
Zoltan Mester // NRC, Canada, President of the IUPAC ACD

EVENTS OF INTEREST IN 2022-2023 2021-015-2-500 - GREENNESS OF OFFICIAL


STANDARD METHODS
1, 2022 as the International Year of Basic Sciences
for Sustainable Development (IYBSSD2022) 1. Evaluate the current status of greenness of the
https://www.iybssd2022.org sample preparation methods used in official
standard methods;
2, IUPAC General Assembly and World Chemistry
Congress, 2023 - IUPAC | CHAINS 2023 – Chains 2. Provide metric tools to assess the greenness of
beyond the molecular frontier (iupac2023.org) sample preparation methods;

3, IUPAC Analytical Chemistry Award(s) 3. Proposing events and publications for up-to-
nomination deadline – January 2022 date discussion related to the official standard
methods based on their greenness degree;

4. Develop a roadmap for greener alternative


PROJECTS OF INTEREST analytical methods, emphasizing in sample
Top Ten Emerging Technologies in Chemistry preparation;

The goal of this Top Ten Emerging Technologies in 5. Contribute to the permanent establishment of
Chemistry project is to showcase the value of a network of specialists as well as interested
Chemistry and to inform the general public as to representatives and institutions involved in this
how the chemical sciences contribute to the well- topic to promote a common understanding of
being of society and the sustainability of Planet greenness degree;
Earth. Since 2019, the Jury selects emerging
6. Linking universities, industries, and
technologies on the basis of those in between a
governmental/non-governmental sectors to
new scientific discovery and a fully-
better approach relevant themes and contents in
commercialized technology, and those with the
the topic.
greatest capacity to open new opportunities in
chemistry and beyond. 2021-017-2-500 - HARMONIZATION OF
APPROACHES TO INTERLABORATORY
The search for the 2022 Top Ten Emerging
COMPARISON OF QUALITATIVE AND RELATED
Technologies in Chemistry is on-going
PROPERTY VALUES OF A SUBSTANCE OR
Make a nomination by 31 March 2022 MATERIAL

Top Ten Emerging Technologies in Chemistry - Qualitative property values of a substance or


IUPAC | International Union of Pure and Applied material are nominal values. A nominal property
Chemistry value is a word or alphanumerical code given for
identification reasons, where the property
(variable) has no magnitude (JCGM 200:2012 –
44 CITAC News // May 2022

VIM clause 1.30). Nominal variables are coded by 2017 Recommendations


exhaustive and disjoint classes or categories with (https://doi.org/10.1515/pac-2011-0613), and as
no natural ordering. For example, imperfections a member organization of JCGM developing the
of welds are coded by the following five forthcoming International Vocabulary of
classes/categories: cracks, cavities, inclusions, Metrology (VIM4).
lack of fusion/penetration, and geometrical shape
Harmonization of approaches to interlaboratory
errors.
comparisons of nominal and ordinal values, alone
If a quantity has a clear ordering, then it is an and together with quantitative values, will be
‘ordinal quantity’ (VIM clause 1.26). For example, helpful for characterization of examination
the ordinal Mohs scale of mineral hardness is methods and reference materials with qualitative
based on the ability of one mineral natural sample and related properties, for proficiency testing of
to scratch another: corundum (Al2O3) is harder chemical laboratories involved in qualitative
than topaz (Al2SiO4(OH−,F−)2), but diamond (C) is analysis, and will contribute to world-wide
harder than corundum, etc. Such ordinal property conformity assessment.
values are categorical, as nominal data, but are
2019-039-3-500 - A REVIEW OF CURRENT
not entirely qualitative. They are not quantitative
STATUS OF ANALYTICAL CHEMISTRY EDUCATION.
also and could be named as semi-quantitative
values. Moreover, some products are There is plenty of anecdotal evidence for the
characterized by combined quantitative and erosion of analytical chemistry as a discipline. This
qualitative property values. For example, the is impacted by faculty appointments, funding
property values of dry sausages include mass structures and perception of the field as being a
fractions of fat, protein, moisture and salt service function. Additionally, as instruments
(quantitative values), as well as color of the become easier to use there is a mistaken belief in
sausage cross section, smell and taste (qualitative some industrial organisations that there is a
values). A comprehensive (universal) scale of reduced need for highly trained analytical
property values is necessary for comparison of specialists. There have been warning signs that
complete test results of the sausage in different the current, university chemistry curriculum,
laboratories. often with a does not address the needs of
chemistry graduates and future employers and
The problem of analysis of qualitative data is
does not enable analytical practitioners to
recognized by international groups, such as ISO TC
maximise the value of their work. The project will
334 (former ISO/REMCO), ISO TC69 SC6 and
reflect on the interdisciplinary curriculum
Eurachem/CITAC WG, working on development of
development efforts which has been the trend in
guidelines for different applications of
many universities worldwide. This is a significant
metrological concepts to qualitative data. There
economic cost, considering that in many
are also publications on intensive development of
economies the most used practical skills of
statistical methods CATANOVA for nominal values
graduates is actually related to chemical analysis.
and ORDANOVA for ordinal values, e.g., papers of
A deep and fundamental understanding of
Tamar Gadrich et al.
analytical chemistry is required to foster the next
https://doi.org/10.1007/s42452-020-03907-4
generation of analytical scientists who have the
and https://doi.org/10.1016/j.jspi.2021.04.005,
insight and capacity to contribute to fundamental
respectively. These methods are analogous to
new developments in this field as well as the
ANOVA (analysis of variance) for quantitative
generation of new disruptive technologies. The
values.
project will document the status quo in various
IUPAC has contributed terminology efforts in this regions of the world regarding the health of the
field, starting from Rene Dybkaer’s “Ontology on discipline, proportion of professorships, funding
Property” (https://ontology.iupac.org/ or and quality of analytical chemistry education. It
https://doi.org/10.1351/978-87-990010-1-9), will examine current attempts to address these
the IUPAC Silver Book (https://iupac.org/what- shortcomings and offer some ways forward. The
we-do/books/silverbook/) and Nominal Properties findings will be published in the form of white
45 CITAC News // May 2022

paper to support future curriculum development, and food samples, and others. The project intends
funding and hiring decision. to produce a guidance document on best
analytical chemistry practices for the
2017-031-1-050 IUPAC100 - PERIODIC TABLE
characterization of such materials. 2016-007-1-
CHALLENGE.
500 Risks of conformity assessment of a
Following the phenomenal success of periodic multicomponent material or object in relation to
table challenge during the 100 year celebration of measurement uncertainty of its test results. To
IUPAC and the 150 years of the Periodic Table the develop an approach for evaluation of the
project was extended as an ongoing outreach probability of false decisions in conformity
effort. This activity is about educating people assessment of a multicomponent material or
about the work of IUPAC. In this context, we also object in relation to measurement uncertainty of
note that: The UN General Assembly has test (chemical analytical) results of a sample of the
proclaimed 2019 as the “International Year of the material or object. This probability, combining
Periodic Table of Chemical Elements” (see more in probabilities of false decisions concerning
IUPAC news 20th December 2017). different components of the material or object,
will characterize the sample conformity as a
2012-005-1-500 Vocabulary of Concepts and
whole. The solution to this problem is important
Terms in Analytical Chemistry - the revised
for understanding conformity assessment risks in
Orange Book project. The Orange Book (present
customs control, clinical analysis, pharmaceutical
title “Compendium of Analytical Nomenclature”
industry, environmental control, and other fields.
3rd Edition) was published in 1998, and now is in
2019.
the process of revision. The new Orange Book will
be in a consistent glossary style format with ANALYTICAL CHEMISTRY DIVISION
definitions of concepts in different fields of
Division Details - IUPAC | International Union of
analytical chemistry. The nineteen chapters of
Pure and Applied Chemistry
the 3rd edition will become eleven in the present
revision. We have taken the decision to ANALYTICAL CHEMISTRY AWARDS
concentrate on methods and not attempt to
The Analytical Chemistry Division of IUPAC has
venture into the ocean of applications. The first
established two awards, including:
chapter will set the metrological scene with
definitions from the Green Book, the – The Emerging Innovator Award in Analytical
International Vocabulary of Concepts and Chemistry – an award to recognize outstanding
Associated Terms in Metrology (VIM) and selected work undertaken by an emerging analytical
chemometrics and statistical terms. The project is scientist that corresponds to the aims of the
nearing completing, publication is expected in Analytical Chemistry Division.
2020. 2017-005-3-500 - ANALYTICAL – The IUPAC Analytical Chemistry Medal – an
CHEMISTRY OF NANOMATERIALS. award to recognize significant lifetime
The impact of materials structured at the contribution to the aims of the Analytical
nanometer scale becomes enormous and Chemistry Division.
continues to increase. Analytical chemistry of The awards are open worldwide to researchers
nanomaterials belongs to emerging issues in this working in the field of analytical chemistry. The
field. Together with physical and physicochemical Emerging Innovator Award is for researchers who
characterization of shape, size, and structure are at an early stage of their independent career,
nanoparticles, analytical chemistry research as measured by the completion of a PhD within
considers isolation/purification and detection- the last ten years. Appropriate consideration will
CITAC News // April 2020 39 identification/ be given to those who have taken a career break
quantification/ spatial composition or followed a different study path. Nominations
characterization of nanomaterials in bulk must be based on published works in the field of
materials, special nanotechnology products, analytical chemistry. The Analytical Chemistry
complex matrices of environmental, biological Medal is for researchers who have a substantial
46 CITAC News // May 2022

record of achievements demonstrated by the IUPAC ANALYTICAL CHEMISTRY PUBLICATIONS IN


number and quality of their publications, by being 2021
actively involved in international partnerships as
Goenaga Infante, Heidi, Warren, John, Chalmers,
well as by their commitment in the training of the
John, Dent, Geoffrey, Todoli, Jose Luis,
next generation of analytical chemists.
Collingwood, Joanna, Telling, Neil, Resano,
The Award will be presented every two years Martin, Limbeck, Andreas, Schoenberger,
during the IUPAC General Assembly/World Torsten, Hibbert, D. Brynn, LeGresley, Adam,
Chemistry Congress. The awardees will be invited Adams, Kristie and Craston, Derek. "Glossary of
to the meeting of the Analytical Chemistry methods and terms used in analytical
Division to receive their award and to present a spectroscopy (IUPAC Recommendations 2019)"
lecture. Pure and Applied Chemistry, vol. 93, no. 6, 2021,
pp. 647-776. https://doi.org/10.1515/pac-2019-
Nomination package must include a letter of 0203
nomination and a curriculum vitae of the
nominee. See specific details in the application Radtke, Valentin, Stoica, Daniela, Leito, Ivo,
forms. Camões, Filomena, Krossing, Ingo, Anes, Bárbara,
Roziková, Matilda, Deleebeeck, Lisa, Veltzé, Sune,
ORGANIZATION Näykki, Teemu, Bastkowski, Frank, Heering,
As results of the 2021 election of Analytical Agnes, Dániel, Nagy, Quendera, Raquel, Liv,
Chemistry division membership the composition Lokman, Uysal, Emrah and Lawrence, Nathan. "A
of the division for the 2022-2023 biennium is as unified pH scale for all solvents: part I – intention
follows: and reasoning (IUPAC Technical Report)" Pure and
Applied Chemistry, vol. 93, no. 9, 2021, pp. 1049-
Division President - David Shaw; 1060. https://doi.org/10.1515/pac-2019-0504
Division Past President - Zoltán Mester, Stoica, Daniela, Anes, Bárbara Velasco, Fisicaro,
Division Secretary – Luisa Torsi Paola and Camões, Maria Filomena. "Feasibility of
multifunction calibration of H+-responsive glass
Division Vice President - Derek Craston, electrodes in seawater (IUPAC Technical Report)"
Pure and Applied Chemistry, vol. 93, no. 12, 2021,
Titular Members – Resat Apak; Vasilisa B.
pp. 1487-1497. https://doi.org/10.1515/pac-
Baranovskaia; Jiri Barek; Ilya Kuselman; Takae
2020-0202
Takeuchi; Susanne Kristina Wiedmer
Hibbert, David Brynn, Korte, Ernst-Heiner and
Associate Members – Franziska Emmerling; Erico
Örnemark, Ulf. "Metrological and quality concepts
Marlon de Moraes Flores; Ivo Leito; Hongmei Li;
in analytical chemistry (IUPAC Recommendations
Aura Tintaru ; Winfield Earle Waghorne
2021)" Pure and Applied Chemistry, vol. 93, no. 9,
National Representatives - Maria Filomena 2021, pp. 997-1048. https://doi.org/10.1515/pac-
Camoes, Orawon Chailapakul, Attila Felinger, D. 2019-0819
Brynn Hibbert, Serigne Amadou Ndiaye, Mariela
Apak, Reşat, Calokerinos, Antony, Gorinstein,
Pistón, Rufus H. Sha’Ato, Luisa Torsi, Frank
Shela, Segundo, Marcela Alves, Hibbert, David
Vanhaecke.
Brynn, Gülçin, İlhami, Demirci Çekiç, Sema, Güçlü,
COUNCIL Kubilay, Özyürek, Mustafa, Çelik, Saliha Esin,
Magalhães, Luís M. and Arancibia-Avila, Patricia.
The IUPAC Council will has met virtually as part of
"Methods to evaluate the scavenging activity of
virtual World Chemistry Congress in August 2021.
antioxidants toward reactive oxygen and
Next Council Meeting will take place, face to face
nitrogen species (IUPAC Technical Report)" Pure
in The Hague. Technical details and program is
and Applied Chemistry, vol. 94, no. 1, 2022, pp. 87-
currently being developed to account for the
144. https://doi.org/10.1515/pac-2020-0902
virtual meeting. It is expected that large part of
the IUPAC meetings will be publically accessible
capitalizing on the remote conferencing features.
CITAC News // May 2022 47

CITAC BEST
PAPER AWARD
2021

SUMMARY OF “COMBINING ISOTOPE DILUTION AND STANDARD


ADDITION – ELEMENTAL ANALYSIS IN COMPLEX SAMPLES”
Christine Brauckmann, Axel Pramann, Olaf Rienitz, Alexander Schulze, Pranee
Phukphatthanachai, and Jochen Vogl

SUMMARY OF ’METROLOGICAL FRAMEWORK TO SUPPORT ACCURATE,


RELIABLE, AND REPRODUCIBLE NUCLEIC ACIDS MEASUREMENTS’’
Mojca Milavec, Megan H. Cleveland, Young-Kyung Bae, Robert I. Wielgosz,
Maxim Vonsky, Jim F. Huggett

SUMMARY OF “LABEL-FREE DETECTION OF SARS-COV-2 SPIKE S1


ANTIGEN TRIGGERED BY ELECTROACTIVE GOLD NANOPARTICLES ON
ANTIBODY COATED FLUORINE-DOPED TIN OXIDE (FTO) ELECTRODE”
Akanksha Roberts, Subhasis Mahari, Deepshikha Shahdeo, Sonu Gandhi
48 CITAC News // May 2022

CITAC BEST PAPER AWARD 2021


SUMMARY OF “COMBINING ISOTOPE DILUTION AND
STANDARD ADDITION – ELEMENTAL ANALYSIS IN
COMPLEX SAMPLES”
Molecules, 2021, 26, 2649

Christine Brauckmann1, Axel Pramann1*, Olaf Rienitz1, Alexander Schulze1,


Pranee Phukphatthanachai2,3, and Jochen Vogl2

1Physikalisch-Technische Bundesanstalt (PTB), Bundesallee 100, 38116 Braunschweig,


Germany
2Bundesanstalt für Materialforschung und -prüfung (BAM), Richard-Willstätter-Str.11, 12489

Berlin, Germany
3National Institute of Metrology (Thailand) (NIMT), 3/4-5 Moo 3, Klong 5, Klong Luang,

Pathumthani 12120, Thailand

INTRODUCTION previous theoretical work by Pagliano and Meija,


isotope dilution and standard addition methods
Several calibration strategies for the
were merged with the intention to reduce or
determination of the element content are
avoid matrix effects as a consequence of a
established in inductively coupled plasma mass
matched matrix in all analysed solutions [9]. In our
spectrometry (ICP-MS) techniques which is
work, a different approach, which combines
progressively used in metrology in chemistry –
isotope dilution and standard addition, is
analytical chemistry in general – and other related
presented. The new method has been applied and
fields [1-4]. In case of an analyte element with at
validated independently for the first time by
least two stable isotopes, isotope dilution mass
three laboratories using ICP-MS. Each lab focuses
spectrometry (IDMS) strategies are currently the
on a different matrix and analyte system: In the
method of choice yielding smallest measurement
first application trace amounts of natural silicon
uncertainties according to the Guide to the
in aqueous tetramethylammonium hydroxide
Expression of Uncertainty in Measurement (GUM)
(TMAH) blank solutions were measured. This
[5-7]. Several variations of the IDMS principle
quantification was and is of strong relevance in
have been developed (single, double, triple, and
the context of the realization and dissemination
higher order IDMS). If an analyte element is
of the SI base units mole and kilogram in the
monoisotopic, an internal calibration method like
“Avogadro-Project” [10]. The second example was
standard addition is used, being more sensitive
the measurement of sulphur in a biodiesel fuel
and accurate as an external calibration method
(BDF) matrix. This sample was previously
[8]. It is the method of choice when the matrix is
measured using a usual IDMS technique in the
complex and/or the analyte content is low.
context of an international interlaboratory
Standard addition is based on a linear regression
comparison [11]. The BDF matrix was challenging
analysis of the analyte signal in few aliquots
due to its volatility and impurities and the
versus the mass ratio of the standard and sample
appearance of sulphur in different compounds.
aliquot yielding in the x-axis intercept the desired
The third application was the quantification of
mass fraction w of the analyte element. In a
transferrin (TRF) in human serum – a complex
49 CITAC News // May 2022

matrix as well. Usually, high performance liquid isotopic composition), and a reference material z
chromatography (HPLC) coupled to ICP-MS is used (same as the analyte element with the same or
to quantify the protein TRF via its iron content. close isotopic composition as in x) with increasing
The sample – a certified serum material – provides mass per blend (Figure 1).
target values, with which the results of the new
approach were compared [12]. The new
combination of standard addition and IDMS aims
at establishing SI-traceability with lowest
measurement uncertainties especially when y
y
dealing with complex matrices. An additional
y
benefit is the reduction of workload in sample y z
z x
preparation, because of avoiding the separation z x z x
y x b5
of the analyte from the matrix. x b3
b4
b2
b1
MATHEMATICAL BACKGROUND AND
EXPERIMENTAL Figure 1. Schematic of blends b1…b5 having nearly the
same masses mx,i of the sample x, nearly the same
The new combination of IDMS and standard
masses my,i of a spike solutions y, and increasing
addition yields directly the mass fraction wx of an masses mz,i of the reference solution z.
element in a sample x. Only one isotope ratio
needs to be measured in blends which have to be
prepared gravimetrically. Each blend consists of
The evaluation is based on a linear regression
three components: the sample x, a spike solution
according to eqs. (1) and (2)
y (same element as x with preferably inverse

my,i

Ry − Rb,i
=
1 My R y
 wz 
mz,i
+
1 My R y
 wx
mx,i Rb,i − Rx wy M x R x mx,i wy M x R x
= yi = a1 = xi = a0
(1)

a0
wx =  wz
a1 (2)

Ry, Rx, and Rb,i denote the isotope ratios measured A brief overview of the three different
in the respective sample x, spike y, and ith blend investigated sample/matrix systems (preparation
solution bi. The molar masses Mx and My need not and measurement) and respective
necessarily be known. Only the knowledge of the instrumentation is given in table 1. All three
mass fraction wz of the element of interest in the systems were measured with ICP-MS.
reference material z is required (available from a RESULTS AND DISCUSSION
certificate or a separate measurement). The slope
a1 and y-intercept a0 yield the mass fraction wx of Here, only the first system (Si in TMAH aq) is
the analyte element in the original sample ( x). highlighted as an example. Table 2 shows an
Mass bias correction – as usually required in ICP- example of an experimental run (regression plot in
MS – is not necessary, the correction factors Figure 2).
cancel from eq. (1). The detailed mathematical
derivations as well as the relation to ref. [9] are
given in [13].
50 CITAC News // May 2022

Table 1. Instrumentation and sample preparation applied for the three sample/matrix systems.

1
System Silicon/TMAH Sulphur/Biodiesel Fuel TRF/Human Serum
Laboratory PTB BAM PTB
Analyte natural silicon sulphur iron
Sample x w(TMAH) = 0.0006 g/g biodiesel fuel BDF human serum
(matrix) in purified H2O (18 M (SeronormTM
cm) Immunoprotein Lyo L-
1, Invicon GmbH,
Germany)
Spike y Si crystals dissolved in
30
BAM S-34 TRF spike solution
w(TMAH) = 0.0006 g/g (human apo-TRF,
wy = 2 µg/g Sigma-Aldrich) and 54Fe
(Trace Science)
Reference z Si crystal (WASO04) NIST SRM3154 ERM®-DA470k/IFCC
dissolved in w(TMAH) = “Human Serum” (Merck
0.0006 g/g KGaA, Germany)
wz = 4 µg/g
Instrument Thermo Fisher Scientific Thermo Fisher Scientific Agilent
MC-ICP-MS Neptune MC-ICP-MS Neptune Plus 8900 ICP-QQQ-MS
Sample PFA nebulizer 100 Aridus II desolvating PFA MicroFlow
Introduction µL/min system nebulizer 700 µL/min,
PEEK/PFA cyclonic PFA nebulizer 100 µL/min Scott chamber at 3 °C
+ Scott chamber Aridus PFA spray chamber torch with 1mm
sapphire torch + standard torch and injector injector
injector
Machine high resolution (M/M = high resolution (M/M = MS/MS mode
Parameters 8000) 8000)

The regression analysis of this example wx(Si) = using double IDMS yielding wx = 7.394(46) µg/g
0.13(11) µg/g with k = 1. Although the relative [11]. This excellent agreement between the
uncertainty is rather large in this case, one has primary approach (double IDMS) and the new
to consider that the absolute amount is in the isotope dilution/standard addition method
ultra-trace range of 130 ng/g. reported here, serves as a validation of the new
approach. The third system (TRF in human
The determination of sulphur in BDF yields an
serum) yields as an representative value wx(TRF)
average mass fraction wx(S) = 7.36(11) µg/g with
= 2.128(45) mg/g (for k = 1, consistent with the
k = 2. In the interlaboratory comparison CCQM-
certified target value).
K123, the sulphur determination has been done
51 CITAC News // May 2022

Table 2. Representative experimental run with quantities and regression parameters for the determination of Si
in TMAHaq; wz = 4.0069 µg/g.

x z y
bi TMAHaq WASO04 “Si30” Rb,i Rx,i Ry,i
i mx,i mz,i my,i I(30Si)/I(28Si) xi yi I(30Si)/I(28Si) I(30Si)/I(28Si)
g g g V/V g/g g/g V/V mol/mol
1 10.0863 0.0000 22.8557 113.77732 0.0000 1.80 0.03353 204.19578
2 9.7836 7.8858 22.7577 1.59655 0.8060 301.51 0.03353 204.19578
3 9.6700 10.5255 22.3198 1.18847 1.0885 405.71 0.03353 204.19578
4 11.3192 15.3000 22.4864 0.83531 1.3517 503.86 0.03353 204.19578
5 10.0440 22.4061 22.7651 0.61405 2.2308 794.84 0.03353 204.19578

a1 a0 wx
(g/g)/(g/g) (g/g) µg/g
356.10062 11.474 0.13

900 the described new method of this work,


800 sample: TMAHaq demonstrating its better robustness in practical
use.
700

600 CONCLUSION
yi / (g/g)

500
The new combination of isotope dilution and
400
standard addition is best suited for the
300 determination of mass fractions wx of trace
200 amounts (ng/g) of elements in complex matrices.
100
The new method based on linear regression was
compared to the closed-form analytical approach
0
0.0 0.5 1.0 1.5 2.0 2.5 reported in [9] yielding the mathematical
xi / (g/g) agreement of both methods. When applied to real
measurement data, our new method provides
more accurate results with lower associated
Figure 2. Regression curve based on table 1 using 5
blends. uncertainties in comparison to [9]. The new
method uses a simpler evaluation and helps to
As stated in the beginning, our new method yields avoid laborious sample preparation in comparison
a convenient mathematical solution compared to with IDMS methods. The new method has been
the theoretical method given in [9]. For a practical successfully applied to three completely different
comparison of both methods, a dataset of the sample/matrix combinations showing the general
silicon determination in the TMAH matrix (with applicability of the isotope dilution/standard
five available blends) has been used. The addition combination. The validation was
associated uncertainties of the results additionally performed with the determination of
determined in this work are significantly smaller sulphur in biodiesel fuel applying the double IDMS
than the respective uncertainties of the results technique in an international key comparison
determined using the approach of ref. [9]. Both (CCQM-K123) yielding matching results within the
approaches (this work and that of ref. [9]) have limits of uncertainty.
been checked for consistency using simulated
ideal data yielding exactly the same result. REFERENCES
However, it was found that both the results as [1] F. Vanhaecke, P. Degryse, MC-ICPMS in Isotopic
well as the associated uncertainty of [9] depend Analysis: Fundamentals and Applications Using
strongly on the input data, which is not the case in ICP-MS (Wiley-VCH, Weinheim, 2012).
52 CITAC News // May 2022

[2] J. Vogl, Calibration strategies and quality Guide to the expression of uncertainty in
assurance. In: Inductively Coupled Plasma Mass measurement, JCGM 100:2008.
Spectrometry Handbook; ed. S. M. Nelms; [8] A.-L. Hauswaldt, O. Rienitz, R. Jährling, N.
Blackwell Publishing Ltd; Oxford, 2005; pp.147- Fischer, D. Schiel, G. Labarraque, B. Magnusson,
181. Accred. Qual. Assur. 2012, 17, 129-138.
[3] M. Sargent, H. Goenaga-Infante, K. Inagaki, L. [9] E. Pagliano, J. Meija, Metrologia 2016, 53, 829-
Ma, J. Meija, A. Pramann, O. Rienitz, R. Sturgeon, 834.
J. Vogl, J. Wang, and L. Yang, Metrologia 2019, [10] K. Fujii, H. Bettin, P. Becker, E. Massa, O. Rienitz,
56, 1-32. A. Pramann, A. Nicolaus, N. Kuramoto, I. Busch,
[4] L. Yang, S. Tong, Z. Zhou, Z. Hu, Z. Mester, J. M. Borys, Metrologia 2016, 53, A19-A45.
Meija, J. Anal. At. Spectrom. 2018, 33, 1849- [11] T. Kuroiwa, et al. Metrologia 2017, 54, 08008.
1861. [12] L. Feng, D. Zhang, J. Wang, H. Li, Anal. Methods
[5] K. G. Heumann, Fresenius Z. Anal. Chem. 1986, 2014, 6, 7655.
325, 661-666. [13] C. Brauckmann, A. Pramann, O. Rienitz, A.
[6] P. De Bièvre, Fresenius Z. Anal. Chem. 1990, 327, Schulze, P. Phukphatthanachai, and J. Vogl,
766-771. Molecules 2021, 26, 2649.
[7] JCGM (BIPM, IEC, IFCC, ILAC, ISO, IUPAC, IUPAP
and OIML) Evaluation of measurement data -
53 CITAC News // May 2022

CITAC BEST PAPER AWARD 2021


SUMMARY OF ’METROLOGICAL FRAMEWORK TO
SUPPORT ACCURATE, RELIABLE, AND REPRODUCIBLE
NUCLEIC ACIDS MEASUREMENTS’’
Analytical and Bioanalytical Chemistry, https://doi.org/10.1007/s00216-021-03712-x

Mojca Milavec1, Megan H. Cleveland2, Young-Kyung Bae3, Robert I. Wielgosz4,


Maxim Vonsky5, Jim F. Huggett6,7

1Department of Biotechnology and Systems Biology, National Institute of biology, Večna pot 111,
1000 Ljubljana, Slovenia
2National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, Maryland

20899, United States


3Korea Research Institute of Standards and Science (KRISS), Daejeon, Republic of Korea
4Bureau International des Poids et Mesures (BIPM), Pavillon de Breteuil , 92312 Sèvres Cedex,

France
5D.I. Mendeleev Institute for Metrology, Moskovsky pr., 19, Saint-Petersburg, 190005, Russian

Federation
6National Measurement Laboratory (NML), LGC, Queens Road, Teddington, Middlesex, TW11

0LY, United Kingdom


7School of Biosciences & Medicine, Faculty of Health & Medical Science, University of Surrey,

Guildford, United Kingdom

INTRODUCTION sequencing in 1970s, and the invention of


polymerase chain reaction (PCR) in 1960s, all these
Nucleic acid (NA) analysis is fundamental for life
analytical approaches faced extremely intensive
science research spanning areas including
developments. Currently RNA sequencing,
biotechnology, cell biology, genetics,
typically by complementary DNA intermediates
microbiology, and molecular biology. Applied NA
but increasingly as direct sequencing of RNA, is an
analysis is increasingly required in fields such as
indispensable tool for transcriptome-wide
medicine, pharmacy, veterinary medicine, food
analysis and is contributing to a fuller
safety, and environmental monitoring. NA
understanding of RNA biology [1]; the third
analysis encompasses the detection,
generation DNA sequencing has revolutionized
identification and quantification of NA from
sequencing by increasing the length of reads and
different organisms, often from diverse matrices.
reducing the time and costs of analysis [2,3]; and
Accurate and metrologically traceable
digital PCR (dPCR) has enabled absolute
measurements of NA enable reliable results to
quantification of specific nuvcleic acid targets [4].
support decision makers like healthcare workers,
sanitary inspectors and competent authorities. Despite broad use of nucleic analysis, the
comparability of nucleic acid quantification
In the last few decades NA analysis has rapidly
results is unsatisfactory among laboratories in
developed supported by an increasingly diverse
many areas. This is especially evident where
array of technologies. After the understandably
quantitative analysis of nucleic acids is required.
slow beginnings of RNA sequencing in 1960s, DNA
54 CITAC News // May 2022

For example, in the food and feed safety area or developing programs related to the measurement
health. This overview outlines the benefits of of quantities important in biotechnology and that
metrological support for nucleic acid analysis in national laboratories collaborate with
the life science sectors that are more international scientific unions and organizations
metrologically established, while also to establish an adequate international
championing advancements in the other sectors. measurement infrastructure to ensure
traceability to the SI in measurements in
NAWG AT CCQM
biotechnology.
Many international organizations and societies
An Ad hoc Biometrology Task Group was
are making efforts to improve the consistency of
established and in 2000 it presented a report on
results among laboratories in general and in
new measurement challenges. In 2001, this Task
specific fields like healthcare, or food safety and
Group became the BioAnalysis Working Group
security in the field of detection, identification
(BAWG) of the CCQM [11]. In 2014 the BAWG was
and quantification of genetically modified
split into three new CCQM Working Groups
organisms, or in plant health. One of the
according to major analytes: the Nucleic Acid
international groups dedicated to improving the
Analysis WG – NAWG [5], the Protein Analysis WG
comparability of nucleic acid measurements
– PAWG [12], and the Cell Analysis WG – CAWG [13]
independent of the field is the Working Group on
due to the growing number of separated activities
Nucleic Acid Analysis (NAWG) [5] of the
and increased membership. In the same year, the
Consultative Committee for Amount of
name and the scope of the CCQM were broadened
Substance: Metrology in Chemistry and Biology
from CCQM - Metrology in Chemistry to CCQM -
(CCQM) [6]. CCQM is one of the consultative
Metrology in Chemistry and Biology [6].
committees (CCs) of the International Committee
for Weights and Measures (CIPM) [7] with a The focus of the NAWG is to support global
mission to advance global comparability of comparability and metrological traceability of
chemical and biological measurement standards measurement results in the area of the analysis of
and capabilities, enabling Member States and nucleic acid polymer sequences, their
Associates to make measurements with modifications and their abundance. Members of
confidence, and with a published strategy for the NAWG are NMIs and DIs that provide nucleic
2021-2030 [8] to do so. CCQM is responsibile for acid measurement services developed in
developing, improving and documenting the response to the needs of their national and
equivalence of National Metrological Institutions international stakeholders. The ubiquity of the
(NMIs) and Designated Institutions (DIs) nucleic acid analysis methods, the molecules they
calibration and measurement capabilities and target and the associated challenges are agnostic
national standards (certified reference materials to sectors in most cases. Consequently, as an
and reference methods) for chemical and international working group that focuses on
biological measurements, following the nucleic acid analysis regardless of sector, the
processes set out in the CIPM Mutual Recognition NAWG is uniquely placed to advance the
Arrangement (CIPM MRA) [9]. measurements in one sector using knowledge
from another [14]. This constitutes a firm basis for
Activities related to nucleic acid analysis within
NAWG’s ability to respond to challenges in the
CCQM began in 1999, the year that the XXI
nucleic acid analysis field despite the field’s rapid
General Conference for Weights and Measures
technological development and implementation.
(CGPM) [10] discussed the growing importance of
This was exemplified by the response of the
biotechnology in human health, food production,
NAWG to the COVID-19 pandemic through the
forensic medicine and the protection of the
SARS-CoV-2 pilot study (CCQM-P199.b) with the
environment. CCQM recognized the need for
participation of 18 NMI/DIs, many of whom had
accurate, SI-traceable measurements in these
not previously measured viral genomic material
fields and the lack of an adequate metrological
[15]. The NAWG will need to explore how this pan
infrastructure to ensure such traceability. It
sector characteristic can be capitalized on to
recommended that national laboratories consider
55 CITAC News // May 2022

support different groups of stakeholders in the in which it has been presented, as nucleic acids are
future. almost exclusively measured in solution.
Consequently, considerations associated with
STANDARDIZATION, TRACEABILITY AND
sources of uncertainty and routes to traceability
SCIENTIFIC CHALLENGES
frequently include volume measurements as an
The primary focus of NAWG is to support the additional factor. Nucleic acid analyses typically
development and maintenance of measurement require multistep processes with prior
capabilities and dissemination of measurement manipulation of the sample to isolate and purify
services from NMIs/DIs. This is supported via the nucleic acids for further analysis (‘pre-
interlaboratory comparisons to evaluate the analytical’ steps). When conducting nucleic acid
competencies of NMIs and DIs and provide analysis, a key distinction is whether the analyte
evidence of the validity and international is a part of a larger molecule (typically the case
equivalence of measurement services for with genes associated with genetic modification
customers and stakeholders worldwide. In or pathogen genome) or whether it is contained
parallel with recognizing current and future within the sequence being measured (such as
needs in standardization and traceability, NAWG when measuring actionable cancer genetic
is also addressing some of the fundamental variants or genetic polymorphism). From an
scientific challenges associated with nucleic acid analytical point of view, these two categories can
analysis. present distinct challenges when considering
sources of uncertainty. Furthermore, the
Scientific challenges associated with the analytical sources of error can differ when the
measurement of a given nucleic acid vary same nucleic acid sequence is measured in
depending on the complexity of the nucleic acid in different matrices (pure nucleic acids in aqueous
question (e.g. sequence, size, secondary solution, synthetic matrices or biological samples)
structure, etc.) as well as the complexity of matrix (Figure 1a).

Figure 1. Type of sample (a) and Type of analysis (b); Nucleic acid measurements/examinations vary in the
complexity of the analysis and the type of sample. The simplest type of measurements would be the detection of
the presence or absence of a plasmid in a buffered solution. A much more complex measurement would be the
identification of all nucleic acid species in a processed food matrix, along with the abundance of each.
56 CITAC News // May 2022

When discussing a particular NAWG-supported CMCs for NMIs exist in food


measurement/examination, and associated analysis sector. To date (as of September 2021),
challenges, the type of sample (including the all completed NAWG Key Comparisons have been
properties of the nucleic acid and its matrix) must in the area of food analysis and related to the
also be considered (Figure 1a). At the simplest needs of NMIs and DIs to provide services for
level of complexity, nucleic acids can vary from detection, identification, and quantification of
less than 100 to billions of bases (the term is used genetically modified organisms (GMOs) and food
to describe a nucleotide monomer that is about adulterations.
300 g/mol, consequently large DNA molecules can
NAWG is working to support members in
be >108 g/mol). Additionally, samples can consist
developing nucleic acid reference materials and
of mixtures of different genomes, which further
calibration services for relative GMO quantity and
complicates measurement/examination. Further
food adulteration. This process involves DNA
potential sources of error are added when
extraction from a complex biological matrix,
additional steps are required to prepare nucleic
followed by measurement of specific genomic
acids for analysis, such as purification, nucleic
DNA fragments - the GMO-specific sequence and
acid digestion (e.g. restriction enzyme treatment),
the endogenous (species-specific) gene specific
adaptation (e.g. adapter ligation), modification
sequence. The measurements are performed
(bisulfite conversion), or reverse transcription
either by qPCR using an independent reference
(generation of complementary nucleic acids) .
material as a calibrant, or by dPCR [16–18].
Extraction is often required when performing
nucleic acid analysis, because the matrix is A series of four Key Comparisons enabled NMIs
typically unsuitable for the final molecular and DIs to demonstrate and document their
analysis steps. All these steps contribute to the capabilities in measurements of the number of
uncertainty associated with the final analysis. copies of specified intact sequence fragments
extracted from different matrices and to
When considering a given analyte, the type of
determine their relative quantity. In the first two
nucleic acid analysis (Figure 1b) can be
studies, matrices were rich in polymeric
categorized into ‘targeted’ methods (such as PCR
carbohydrate (amylose and amylopectin) and
or hybridization) or ‘non targeted’ methods (such
poor in fat; maize (Zea maize L.) seed powder in
as sequencing). Targeted methods identify
CCQM-K86 study [19], and rice (Oryza sativa L.)
defined sequence(s) (and potentially their
seed powder in CCQM-K86.b study [20]. In the
quantities and/or modifications); while with non-
third study, CCQM-K86.c, high fat/oil matrix was
targeted methods the nucleic acid sequence(s)
selected, represented by rapeseed/canola
(and potentially their quantities and/or
(Brassica napus L.) seed powder [21]. Currently, a
modifications) is often unknown and the analysis
study on measuring DNA in high protein matrix
intends to determine this. The type of analysis can
(meat) is in progress. All three studies on plant
also be broadly categorized into
seed matrices had good agreement in the
presence/absence ‘nominal property’
reported results, despite low relative quantities
examination (e.g. sequence is present or not),
measured (ranging between 0.1% and 4% of GM
measurements of relative quantity/fractional
content). While in the first study the majority of
abundance (e.g. percentage of sequence) or
laboratories used the qPCR approach and
absolute quantification (e.g. copy number of
calibrators for measurements, in the third study
sequence per unit volume).
all laboratories used the dPCR approach without
METROLOGY FOR FOOD SAFETY AND calibrators.
AUTHENTICATION
These results confirmed consistency of
Nucleic acid analysis for food authentication is measurements at NMIs and DIs worldwide, which
most metrologically advanced (in terms of resulted in the establishment of Calibration and
traceability and understanding sources of Measurement Capabilities (CMCs) in 7 NMIs/DIs at
uncertainty), relative to other routinely applied present.
nucleic acid measurements. Therefore, most of
57 CITAC News // May 2022

METROLOGY FOR HEALTH good concordance. In addition, the study


highlighted the lack of a standardized approach
While molecular testing is used in clinical
for uncertainty calculations, especially when
diagnostics, reference methods are not as
performing fractional abundance quantifications.
prevalent in this sector as they are in clinical
Based on these results, a multiple cancer cell
chemistry; however, due to the desire of
biomarker measurement pilot study (CCQM-P155)
stakeholders to apply increasingly advanced
was organized, which used whole cell materials
high-throughput and quantitative
for analysis, to enable participant laboratories to
measurements, this is changing and NAWG
develop and compare their nucleic acid extraction
activities in the health sector are increasing.
capabilities (Table S3). Another study dedicated to
Currently, molecular diagnostic tools are used to
supporting the DNA based diagnostics of cancer
genotype patients, to quantify pathogenic
(CCQM-P184) is ongoing. The aim of this study is
burden, to quantify transcriptional surrogate
to measure the copy number concentrations of
biomarkers of disease, or to measure disease
a single nucleotide variant (SNV) and small
predictors using subtle changes at the epigenetic
insertions and deletions (INDEL) present in a
level. To support NMI measurement capacity in
background of wild-type (wt) DNA. To expand the
these areas, a series of pilot studies focused on
measurement capabilities from small variants to
the identification and quantification of nucleic
large (structural) variants, a new study (CCQM-
acid sequences were conducted. In accordance
K176) on copy number variation of a breast cancer
with the BIPM guidelines Measurement
biomarker (HER2), is being conducted; this is the
comparisons in CIPM MRA (CIPM MRA-G-11) [22],
first key study in cancer diagnostics.
pilot studies are a third category of comparisons
typically conducted to establish measurement Following the progress in the field and to further
parameters for a "new" field or instrument or as a explore the potential for using higher accuracy SI
training exercise. traceable methods for nucleic acid quantification,
a study on absolute quantification of HIV-1 RNA
To date, health related NAWG pilot studies have
copy number (CCQM-P199) was proposed
mainly focused on the relative or absolute
followed by a similar study on SARS-CoV-2 copy
quantification of specific targets in simple
number quantification (CCQM-P199.b) which was
matrices (aqueous buffer or cell suspension). The
NAWG’s response to the COVID-19 pandemic.
studies used a variety of sample types including
Both studies demonstrated that NAWG members
pure synthetic and natural RNA and DNA, as well
are capable of high accuracy measurement of
as whole cells.
RNA molecules in buffered solutions. The CCQM-
The initial health studies aimed to investigate the P199.b study demonstrated SARS-CoV-2
capabilities to support measurements of mRNA quantification was possible with most
biomarkers. Two studies were organized using laboratories submitting values with +/- 40% of
exogenous synthetic targets from the External the mean [15]. Reports of these studies are in
RNA Controls Consortium (ERCC) [23] as preparation. These five RNA pilot studies open the
measurands. For the CCQM-P103 study, ERCC possibility of future key comparisons, which are
number 81 was selected as the measurand, while selected by the corresponding CCs to test the
in the subsequent CCQM-P103.1 study, six ERCC principal techniques and methods in the field [22].
standards were measured along with three
FUTURE PERSPECTIVES
endogenous gene transcripts present in the
human cell line RNA background [24]. In the latter As we progress into the next decade, NAWG
study, the majority of participants used RT-qPCR activities will likely continue to support food
to measure the transcripts, while two associated testing with Key Comparisons
participants used RT-dPCR and one used RNA- reflecting additional unmet needs, such as
Seq. The results of these studies showed that the different matrices (e.g. protein rich), species (e.g.
participating laboratories were able to measure food adulterations) and molecular challenges (e.g.
target RNA quantities and fractional abundance fragment size, strandedness, modifications like
(ratios) in a complex (total RNA) background with methylation). It is anticipated that food
58 CITAC News // May 2022

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60 CITAC News // May 2022

CITAC BEST PAPER AWARD 2021


SUMMARY OF “LABEL-FREE DETECTION OF SARS-COV-2
SPIKE S1 ANTIGEN TRIGGERED BY ELECTROACTIVE
GOLD NANOPARTICLES ON ANTIBODY COATED
FLUORINE-DOPED TIN OXIDE (FTO) ELECTRODE”
Anal. Chim. Acta, Vol. 1188, 2021, Article 339207

Akanksha Roberts1, Subhasis Mahari1, Deepshikha Shahdeo1, Sonu Gandhi1

1DBT-National Institute of Animal Biotechnology (NIAB), Hyderabad-500032, Telangana, India

INTRODUCTION AND SUMMARY diagnostics as they do not get affected by sample


absorbance or turbidity8 and the sensitivity can
The pneumonia outbreak in Wuhan, China in be enhanced by nanomaterial as signal amplifiers.
December 2019, caused by the pathogen 2019 Since gold nanoparticles (AuNPs) show excellent
novel coronavirus (2019‐nCoV) or Severe acute conductive properties, are easy to synthesise and
respiratory syndrome coronavirus 2 (SARS-CoV- biocompatible, we have selected it as the signal
2) and its subsequent variants has brought the amplifier in this research work.
entire world to its knees.1 This positive single
stranded RNA virus, made up of four structural In this study, we have developed a AuNPs/SARS-
proteins i.e. spike, envelope, matrix and CoV-2Ab modified fluorine-doped tin oxide (FTO)
nucleocapsid protein, is responsible for based electrode SARS-CoV-2 Spike S1 antigen (Ag)
respiratory tract disease2 which has led to a fatal detection a shown in Figure 1. FTO electrodes are
pandemic scenario. Conventional techniques such known to show high electrical conductivity,
as chest computed tomography (CT)3 and real- chemical stability, high tolerance towards
time reverse-transcriptase polymerase chain physical abrasions and cost effectiveness. SARS-
reaction (RT-PCR)4 continue to remain the gold CoV-2 Spike S1 polyclonal immunoglobulin G (IgG)
standard for etiologic diagnosis of this antibody (Ab) were produced in-house and its
Coronavirus Disease 2019 (COVID-19) but are purity, and affinity against SARS-CoV-2 Spike S1
laborious and time consuming, and sometimes Ag were analysed. AuNPs were drop casted onto
provide false negative results as a result of low the conductive FTO electrode surface and the Ab
viral load. Hence, rapid mass screening assays are was immobilized onto the AuNPs. All fabrication
imperative to manage the pandemic, especially stages and optimisation of response time, Ab
transmission from asymptomatic patients. concentration, temperature, and pH were
Different serological assay and biosensor are thoroughly characterised. The LOD of the
being developed as supplemental tools for rapid immunosensor was calculated as 0.63 fM within
diagnosis,5–7 however, intensive research is still the linear range of 1 fM to 1 μM. The sensor also
required as these sensors need to be highly showed high specificity towards SARS-CoV-2
specific and sensitive for SARS-CoV-2 detection. Spike S1 Ag spiked in saliva samples when
Biosensors are sensitive, portable, easy to use, checked for cross-reactivity against other viral Ag
rapid and moreover can be designed specifically (Middle East Respiratory Syndrome (MERS) Ag,
for a particular target analyte biomarker of Avian Influenza Virus (AIV) Ag, and Human
viruses, bacteria, cancer, etc. Electrochemical Immunodeficiency Virus (HIV) Ag), a rapid
biosensors are preferred for infectious disease response within 10 s and stability up to 4 weeks
61 CITAC News // May 2022

at 4˚C. This immunosensor provides a promising peak due to an increase in the size and
base for the development of a rapid, non- aggregation upon AuNPs-Ab conjugation in UV-
invasive, specific, and sensitive screening Vis Spectroscopy. Similarly, three additional
diagnostic method for SARS-CoV-2 Spike S1 Ag peaks were observed in the Fourier Transform
directly from a patient’s saliva sample. Infra-red (FT-IR) spectra (Figure 3 B) after
conjugation of Ab and AuNPs at 1290 cm-1 (C-O
stretching) and 2564 cm-1 (S-H bond) and a new
peak at 2328 cm-1 (C-N bond) which further
confirmed immobilisation of Ab onto AuNPs. The
increase in size due to formation of the AuNPs-Ab
conjugate was also observed in the increase in the
hydrodynamic diameter from 21 nm (bare AuNPs)
to 30±5 nm (AuNPs-Ab) when analysed via
Dynamic Light Scattering (DLS) (Figure 3 C) and a
single peak confirmed monodispersed particles in
a colloidal solution. Furthermore, Figure 3 D
Figure 1. Electrochemical immunosensor modified with shows zeta potential shifted from -42 mV (bare
AuNPs/SARS-CoV-2Ab for detection of SARS-CoV-2
AuNPs) to -39 mV (AuNPs-Ab) due to increase in
Spike S1 antigen.
instability of the complex tending towards
EXPERIMENTAL RESULTS AND CONCLUSION aggregation.

The in-house generated SARS-CoV-2 Spike S1 Ab


by immunising New Zealand white rabbits with
SARS-CoV-2 Spike S1 Ag was purified and
characterised via SDS-PAGE, Western Blot and
ELISA. The binding affinity of the Ab with the Ag
was determined as 7.5 ng/mL via competitive
ELISA as shown in Figure 2.

Figure 3. Confirmation of AuNPs-Ab conjugation: A. UV-


Vis spectra; B. FT-IR spectra; C. DLS-Hydrodynamic
diameter graph; D. DLS-Zeta potential graph.

As depicted in Figure 4, the FTO electrode was


then fabricated by drop casting AuNPs followed
Figure 2. Electrochemical immunosensor modified with by immobilisation of SARS-CoV-2 Spike Ab. SARS-
AuNPs/SARS-CoV-2Ab for detection of SARS-CoV-2 CoV-2 Spike Ag was added to the sensorand
Spike S1 antigen. changes in current were detected using a
potentiostat.
The Ab was then used as a bioreceptor by
immobilizing it on AuNPs surface on the
electrode. To confirm the physisorption of Ab
onto AuNPs, Figure 3 A demonstrates a red shift
from 520 nm to 529 nm in the AuNPs
characteristic surface plasmon resonance (SPR)
62 CITAC News // May 2022

A linear range from 1 µM to 1 fM of SARS-CoV-2


Spike S1 Ag was tested on the FTO/AuNPs/SARS-
CoV-2Ab sensor and a decrease in current was
observed in the DPV spectra with increasing Ag
concentration (Figure 6 A). The limit of detection
was calculated as 0.63 fM from the linear
calibration curve (Figure 6 B) using the formula
3(Sy/S), where signal/noise ratio is 3, Sy
corresponds to the standard deviation of the
response and S corresponds to the slope of the
Figure 4. Schematic of working of fabricated electrode calibration curve.

Each fabrication step was analysed using cyclic


voltammetry (CV) (Figure 5 A). The conductive
properties of AuNPs led to increase in the current
upon deposition on the electrode whereas Ab
immobilisation led to a decrease due to protein
masking effect. On further binding of Ag on the
FTO/AuNPs/Ab electrode, the current reduced due
to the same protein masking effect and this Figure 6. Analytical performance of the developed
principal was applied for detection of JEV NS1 Ag sensor: A. DPV spectra of testing 1 µM to 1 fM of SARS-
by the fabricated sensor. The sensor was also CoV-2 Spike S1 Ag; B. Linear calibration curve of DPV
spectra.
optimised for maximum current output using
both CV and Differential Pulse Voltammetry (DPV) Furthermore, the senor also showed minimal
for and the optimised parameters were as cross reactivity with other viral Ag such as MERS,
follows: 1 µg Ab immobilisation (Figure 5 B), 0.1 V/s AIV and HIV as a drop in current was only observed
scan rate (Figure 5 C and D), response time of 10 s in the spiked saliva samples containing SARS-
(Figure 5 E), pH 7.5 (Figure 5 F) and room CoV-2 Ag (Figure 7 A). This experiment also proved
temperature 25 ˚C (Figure 5 G). that the sensor was able to successfully detect
SARS-CoV-2 Spike Ag specifically in saliva
samples and could be further developed for mass
screening of clinical saliva samples. A single
electrode could also be reused upto 4 times
(Figure 7 B) as well as stored at 4 ˚C for upto 3
weeks (Figure 7 C) without any substantial effect
to the current output i.e. electrode performance.

Figure 5. Fabrication and optimisation of FTO electrode:


A. Layering steps of sensor CV; B. Ab concentration DPV; Figure 7. A. Cross-reactivity studies in spiked saliva
C. Scan rate CV; D. Scan rate calibration curve; E. samples; B. Repeatability tested upto 5 times; C.
Response time DPV; F. pH CV; G. Temperature DPV. Storage stability tested for a month.
63 CITAC News // May 2022

The developed immunosensor shows great future R.; Meijer, A.; Chu, D. K.; Bleicker, T.; Brünink, S.;
research potential for miniaturisation as well as Schneider, J.; Schmidt, M. L.; Mulders, D. G.;
detection of various other diseases since the Haagmans, B. L.; van der Veer, B.; van den Brink,
S.; Wijsman, L.; Goderski, G.; Romette, J. L.; Ellis,
electrode may easily be customised by
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64 CITAC News // May 2022

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