Ebook: New Frontiers for Metrology: From Biology and Chemistry to Quantum and Data Science

We are delighted to introduce the proceedings of the “Enrico Fermi” Summer School on “New Frontiers for Metrology: From Biology and Chemistry to Quantum and Data Science”. It was held in Varenna from 4th July to 13th July, 2019 and was organised by the Italian Physical Society (SIF), the Bureau International des Poids et Mesures (BIPM), and the Italian Istituto Nazionale di Ricerca Metrologica (INRIM).

The school was the seventh to have been held in the “Enrico Fermi” series that has been devoted to metrology. It followed the 26th meeting of the CGPM which adopted new definitions for the base units of the SI and was a milestone in the history of measurement. The scientific basis for this historic decision was thoroughly previewed in 2016 at the previous metrology summer school. The 2019 school reviewed the decision and discussed how this new foundation for metrology is opening new possibilities for physics. Several of the lecturers reflected on how it will allow for an easier exploration of the unification of quantum mechanics and gravity by, perhaps, showing the limitation of this new and improved foundation.

The programme for the 2019 school also looked to some of the new practical challenges for measurement science. These included the application of metrological principles to the management and interpretation of very large sets of scientific data and the application of metrology to biology.

The students at the summer school all had the opportunity to present their work at a poster session. The posters were reviewed by some of the lecturers and the best were given the opportunity to prepare a short abstract for publication in this volume.

The school had a modular structure. All students attended a 3-day Core Module on the “Fundamentals of Metrology” and choose one or both of the 3-day modules on either “Metrology for the Quality of Life” or “Physical Metrology and the Fundamental Constants”.

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   Physical Metrology and Fundamental Constants (12 lectures)

   Electricity and Magnetism, Mass and related quantities, Time, Length, Photometry and Radiometry.

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   Fundamentals of Metrology (15 lectures)

   Units, Temperature, Measurement uncertainty, The global quality infrastructure.

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   Metrology for Quality of Life (11 lectures)

   Chemistry and biology, Ionising radiation, Climate and environmental studies.

As always, the success of a school is due to the dedication and effort of many people and institutions. Our special thanks go to:

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   the lecturers who prepared their lessons and manuscripts and were available to spend time with the students, to visit their posters and to discuss ideas with them,

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   the 56 students and observers who were selected from 81 applications and who created a stimulating atmosphere throughout the period of the school, and to

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   the scientific secretary, Dr Michela Sega from INRIM, who devoted a lot of her time, energy, and creativity to the success of the school.

We particularly want to thank the sponsors: UFFC, METAS, SIM, and NIST. They supported the participation of students who did not have access to sufficient funding of their own and also the best poster award which stimulated students in the clear and efficient presentation of their work.

Finally, we wish to thank Prof. Luisa Cifarelli, former SIF President, for promoting the 7th edition of a school devoted to metrology, and to Mrs Barbara Alzani and to Mrs Ramona Brigatti of the SIF for their invaluable support in the management and organisation of the school.

M.J.T. Milton, D.S. Wiersma, C.J. Williams and M. Sega

On 20 May 2019, the definition of the SI unit of length, the metre, was changed to follow the explicit-constant format, i.e. with the emphasis on the fact that the speed of light is a constant of nature and that by regarding it as such (and making use of the SI unit of time, the second) the unit of length may be obtained. This paper regards the history of the SI metre before examining in more detail the revised definition and the methods of realising the metre in practice according to the Mise en Pratique document approved by the International Committee on Weights and Measures (CIPM).

Dimensional metrology —the measurement of dimensions, size, shape, form, texture, location— is a fundamental requirement for any manufacturing and trading economy. The SI unit of length, the metre, has recently been re-defined based on the speed of light, c. However the traceability route from c to practical measurements throughout all application fields is far from simple. This paper describes the traceability routes and solutions employed throughout the length scale, from nm to km, to deliver length metrology with traceability to the SI in a wide range of settings, from laboratory to factory.

In 2018, the General Conference on Weights and Measures reformed the International System of Units by adopting fixed values for some fundamental constant of physics. The kilogram, a unit previously defined by a material artefact, is now established and realised from the knowledge and the technology of the modern world.

Countless chemical measurements are performed worldwide each day and they rely not only on calibration standards and measurement methods but also on mathematical models. The choices analysts make about such models can have a significant effect on the reported measurement results. The challenge is therefore for analysts to explore the rich variety of modeling options, appreciate their effect on the results, and recognize that a larger statistical toolkit can raise the bar for more reliable results.

Atomic weights of the elements are the indicators for what is possible in chemical measurements. With very few exceptions, one cannot perform chemical measurements with more precision than the underlying atomic weights have. While determining the atomic weights and the corresponding isotopic compositions of the elements might seem like research topics from a bygone era, recent efforts in revising the International System of Units illustrate the continued relevance of this topic.

Ionizing radiation has benefits and risks for humankind: in cancer therapy, the cell-killing power of ionizing radiation can be used to destroy a tumour, but equally it can harm the patient through damage to healthy tissues or by causing cancer. Accurate measurement of the energy deposited in tissue —the radiation dose— is therefore needed to ensure cancer therapy is both effective and safe. Measurements of radiation dose are also required for the safety of the workforce and the general population and for other applications such as the sterilization of medical products. Harmonizing the measurement of radiation doses worldwide is therefore key to the use of ionizing radiation. There have been significant international efforts to establish and maintain a robust international measurement system, based on high-accuracy primary reference standards at metrology institutes underpinned by services at the Bureau International des Poids et Mesures (BIPM) to demonstrate the equivalence of these standards over the long term. International protocols published by the International Atomic Energy Agency (IAEA) support the clinical applications of the standards. This first article on ionizing radiation metrology explains how primary measurement standards for radiation dosimetry are realized and disseminated. A brief summary of the underpinning physics of the field is given and the main methods to construct and use primary standards for radiation dosimetry are explained.

The Metric System, now known as the International System of Units (SI), was adopted by the National assembly in France on 10 December 1799. The basic principles were decimalization, open access, and measurement units based on nature. The Treaty of the Metre that formally established the Metric System was signed on 20 May 1875 and ratified by United States in 1878. On 20 May 2019, the 144th anniversary of the signing of the 1875 Metre Convention, the world celebrated the biggest revolution in measurement units since the French Revolution. On that day, all of the base units of the SI became defined by fixed values of the fundamental constants or properties of nature. The redefinition effectively realized the original goals of the founders of the Treaty of the Metre. The following provides a brief history of human measurement systems from the ancient Egyptians to the development of the SI and on to the science and technology that gave birth to historical redefinition.

This lecture reviews the concepts of optical atomic clocks and their advantages in comparison to established atomic clocks in the microwave range. Several suitable transition frequencies in laser-cooled and trapped atoms and ions can now be realized with a relative uncertainty in the low 10^–18 range. Laser oscillators can be stabilized to the atomic transitions and are used to measure and to distribute the signals. This high accuracy and the opportunity to compare different atomic reference transitions enable experimental tests of fundamental principles and searches for “new physics” like violations of the Einstein equivalence principle. Some options and routes towards a redefinition of the SI second in terms of an optical frequency are discussed.

In this paper we use original texts written by those involved in the development of the metric system in the 18th and 19th centuries to show that many of them had the goal of establishing a system of units in cooperation with other nations and that could be implemented universally. The phrase “for all time, for all people” originates from 1799 and epitomises the international and universal ambitions of the founders of the metric system. We show how these ambitions were also the principal inspirations for those involved in the preparatory work for the Metre Convention. We include references to documents in the BIPM archives that have not been published before.

The measurement of appearance of objects seen by individuals is a necessity in order to answer industrial needs (quality control at the end of production lines) and societal needs (expectation projected on the objects of sensation of reliability, naturalness or aesthetic). This measurement need is getting more complex with the arrival of new effects like sparkle in automotive, iridescence in cosmetics, mat in silverware and ceramics. The measurement of appearance solicits several scientific fields: metrology, spectrophotometry, psychophysics and statistics. It is a proactive sector. Today, several measurement instruments exist but they usually characterize the visual appearance only partially. Other devices are currently being developed. At the highest level, National Metrological Institutes are working in order to develop new references, new transfer artefacts, new measurement protocols and even new quantities! This paper aims to give an overview of this specific metrological field. Metrology of appearance is a branch of photometry.

This second article on ionizing radiation covers the science of the measurement of radioactivity (radionuclide metrology). In common with radiation dosimetry, radionuclide metrology is an application-led science: the use of radionuclides in medical imaging and cancer therapy, the need to ensure safe disposal of radioactive wastes from the nuclear power industry and the requirement for worldwide monitoring systems to detect nuclear weapons tests all drive the development of primary standards and reference materials to ensure accurate measurement. After a short overview of the physics of radioactive decay, the methods used to realize primary standards are described, including the techniques that use recent developments in mathematical modelling and digital signal processing for radionuclides with complex decay schemes. The international measurement system for radionuclide metrology is summarized. The article concludes with a summary of the future challenges for the field, including how the skills of both dosimetrists and radionuclide metrologists are being called on to ensure safe and effective cancer treatment using a new class of drugs.

The principle of metrological traceability is foundational to the modern system of measurement. The concept of relating a measurement result to a reference through an unbroken chain of calibrations, each contributing to the measurement uncertainty allows us to achieve the quality of measurements that underpins our modern world. This paper describes metrological traceability and how it is recognized, how it fits into the wider metrological and quality infrastructure, and reflects on technological changes that may challenge the present paradigm.

A brief outline of the quantum physical basis of ¹H nuclear magnetic resonance (NMR) spectroscopy is provided. ¹H NMR is the pre-eminent method for the qualitative structural analysis of organic molecules. Its potential for quantitative analysis, although recognized soon after ¹H-NMR became commercially available, has recently become a focus for practical applications. Methods for the assignment of the purity of individual organic compounds based on NMR spectroscopy are now widely implemented for this purpose by National Metrology Institutes (NMIs) to underpin their in-house capabilities for the characterization of primary calibrator materials. Progress in a joint BIPM-NMIJ collaboration to develop and support the metrological basis of qNMR methods for purity assignment is described. This collaboration has investigated and validated experimental parameters for acquiring ¹H-qNMR spectra and identified a suite of seven Internal Standard Reference Materials (ISRMs) that provide a universal set of calibrators for use in internal standard qNMR. Examples are described of the application of qNMR to the assignment of the mass fraction content of mycotoxin and peptide materials that were required to support the BIPM Organic Analysis Work Program. These purity assignments would not be practicable by the traditional mass balance approach. There are inherent limitations in the resolution achievable by NMR when applied to structurally complex compounds. This meant that in order to assign the content of the specific analyte for these complex compounds the raw qNMR result, which provided an assignment of the “total” organic content in the material, required an additional correction for the related structure impurity content of the material determined by a high-resolution LC-MS/MS method. Finally recent developments reported in the general literature of the use of advanced multi-dimensional NMR techniques to investigate the higher-order structure of large, complex proteins are illustrated by an example of their application in the characterization of the higher-order structure of monoclonal antibodies.

Reference Materials (RMs) and Certified Reference Materials (CRMs) are widely used in all stages of measurement procedures and in interlaboratory comparisons. CRMs, in particular, play a key role in implementing the concept of metrological traceability of measurement results in chemistry, biology and physics among other sciences dealing with substances and materials and, in this context, laboratories use CRMs as readily accessible measurement standards. In the past decades, an extensive production of RMs and CRMs was carried out. Although some of them are intended for applications in physics, the great majority belongs to the amount of substance related fields. There are various normative references dealing with RMs and CRMs, and a broad scientific literature. This work aims at presenting a general overview on the production and characterization of RMs and CRMs, with particular focus on gaseous CRMs. An example of application of gaseous CRMs to support climate change studies is also given.

The analysis of a time series of measurements and the important instabilities that they may reveal is presented, describing some of the techniques that can find useful applications in the different fields of metrology.

Precise timekeeping and navigation systems have a lot in common. Both are based on ultraprecise atomic clocks, on the capacity to measure and synchronise clocks and on the formation of a common reference time traceable to international standard time. These similarities are described, showing how time and frequency metrology has found a major application in navigation systems, and how the pressing needs of navigation have promoted research in time metrology fields. The paper focuses on the clock and navigation equations, the necessary algorithms, and the definition of time scales used as a reference in navigation and in timekeeping.

In this paper I explore the very birth, due to Gauss, of today’s views on measurement uncertainty and its quantitative expression and propagation. I also try to understand and explain the influence of Bridgman’s operationalism on these views, and discuss the conflict between a certain misconception of his epistemology and the mathematical and probability tools necessary to treat measurement and measurement uncertainty quantitatively. I also give an overview of current trends in the field.

The redefinition of the International System of Units (SI) has resulted in a modern, robust SI that enables open-access, zero-length traceability chains, and the ability to democratize metrology. The SI units are now defined by fixed values of fundamental constants or properties of Nature and hence we have truly realized the original goals of the founders of the metric system and the Meter Convention. But continuing progress is leading to a new era. This lecture provides a preview of some coming advances in metrology and describes paths to making available world-class metrology on manufacturing floors and in consumer technology. The redefined SI, in the 21st Century and beyond, will also make possible improved tests of the Standard Model of Particle Physics (Standard Model).

Electrial metrology has undergone a series of profound changes during the last decades and strongly contributed to the 2019 revision of the SI based on a set of seven defining constants. The discovery of the Josephson and quantum Hall effect revolutionised the electrical standards by replacing reliance on material artefacts with constants of physics. This article presents an overview of both quantum effects and their implications on the electrical units and on metrology at large. Aspects of impedance metrology and some specificities of high-frequency metrology are presented along with a short consideration on how it differentiates from low-frequency metrology. Eventually, a few considerations on metrology in electrical power and energy are discussed.

Dimensional metrology is crucial for the accurate manufacture of parts. X-ray computed tomography (CT) promises to enhance measurements through its unique capability to image inner geometries non-destructively for dimensional analysis. Since establishing traceability is challenging, METAS launched a project with the objective of developing a high-resolution CT system and establishing the associated metrology. In this paper, scaling laws between the resolution and the CT measurement time are analysed. Due to the three-dimensional nature of the data, increasing the resolution scales up measurement times with higher powers, inflicting stringent requirements on the long-term stability of high-resolution CT systems. Solutions, using current and new technologies, are discussed.

Stable isotope ratio analysis has proven to be valuable for profiling illicit drugs, particularly for obtaining information regarding the drug’s synthetic origin. As part of its methylamphetamine profiling program (MPP) the National Measurement Institute of Australia has developed a capability to determine the stable isotope ratios of carbon, hydrogen and nitrogen of methylamphetamine. These ratios have proven valuable in determining the synthetic origin of methylamphetamine and information about its precursor. This capability has evolved over 10 years along with a quality system which allows for comparability of isotope ratio data obtained over time.

In the revised International System of Units (SI), the unit of electrical capacitance, the farad, is defined from the exact value of the von Klitzing constant, R_K = h/e² = 25812.8074593045 Ω, and from the unit of time. This opens the possibility of realizing the farad directly from the quantum Hall effect by means of suitable impedance bridges. We present here the design, the implementation and a preliminary validation against the Italian national capacitance scale of a four-terminal-pair fully-digital impedance bridge optimized for the direct comparison of an 8 nF standard capacitor with a quantum Hall resistance standard at a frequency of about 1541 Hz, where the impedance magnitude ratio is 1 : 1. The uncertainty of the 1 : 1 comparison, according to a preliminary evaluation, is at the level of 10^–7. We also present here a possible new traceability chain for the farad based on a fully-digital impedance bridge and on a graphene quantized Hall resistance in the AC regime.