World Metrology Day: Setting the standard for measurement

This Sunday, 20th May, is World Metrology Day, the birthday of the signing of the Metre Convention on 20 May 1875 (and pretty much the best day of the year for measurement scientists like us). This convention set the framework for global collaboration in the science of measurement (metrology). Its aim- to ensure we use uniform measurements across the globe- remains as important for industry, commerce and society today as it was over 140 years ago.

Measurement is present in everything: from food and drink safety to the efficacy of pharmaceuticals, from diagnosis and detection of disease to navigation, from air and water quality to forensics. Mobile phones and computers run on accurate measurement, and if you’ve ever had to consistently reset a clock, it was inaccurate measurement that was annoying you.

As the National Measurement Laboratory (designated for chemical and bio-measurement), LGC forms part of the UK National Measurement System (NMS) that provides the core measurement infrastructure for the UK. The measurements we make support manufacture and trade, protect consumers and enhance quality of life.

Did you know that, for all of human history, measurements have been based on actual physical weights and measures, called artefacts? Humans have been working on measurement standardisation for a long time. The ancient Egyptians used what is widely regarded as the first measurement standard, the cubit, a wooden rod that was used to determine standard lengths and heights, like for measuring flood levels of the Nile River. In ancient Babylon, the mina was created and used to measure weight, and the early Chinese civilisation used the chi. Even these standards had much variation within their societies, making wider trade and exchanges difficult. The Magna Carta in 1215 required that the same set of standards be used throughout the realm.  Finally, the International System of Units (SI) was agreed to during the Metre Convention on 20 May 1875, when representatives from seventeen countries set out to close gaps and reach uniformity of measurement around the world.

Even now, the Kilogram is a cylinder made from platinum and iridium alloy that sits in a vault near Paris. The vault is a necessary precaution to ensure the kilogram isn’t damaged, but the last time it was taken out and weighed against a copy, it actually lost weight. Think about that. Mass is always calibrated against another officially confirmed mass, but what happens when the official artefact is no longer reliable? Is the artefact the correct weight or is the copy? Does this mean all of the weights in the world are incorrect?

This could have huge consequences, especially when you consider how integral accurate measurement is to our society, which is why scientists have long been looking for a way to redefine standards, developing an independent system that means we don’t have to rely on a physical artefact which could be damaged or degraded. And the most logical way to revolutionise metrology is with math.

Scientists have been searching for a natural constant, an unchanging number present in nature that would represent each unit and would therefore make accurate measurement reproducible without physical weights. The theme for this year’s World Metrology Day is ‘Constant evolution of the International System of Units (SI)’, chosen because this year sees the culmination of that change: the four base units not defined in terms of natural constants – the kilogram, the mole, the ampere and the kelvin – are expected to be revised.

The world will come together at the General Conference on Weights and Measures in November 2018 and is expected to agree to this change. If approved, this will be the most radical change to the SI since its inception and it will hopefully improve measurement forever, providing a springboard for future innovation.

So feel free to celebrate this Metrology Day in style!

Alzheimer’s disease diagnosis: the end of the guessing game?

There are currently around 850,000 people living with dementia in the UK, and the number of people affected is expected to reach 2 million by 2051. The costs associated with dementia, estimated now at £26 billion a year, are likely to treble.

Alzheimer’s disease is the most common type of dementia, affecting between 60 and 80 percent of those diagnosed. There is no known cure, with treatments limited to preserving cognitive function. Currently, there is no non-invasive method for diagnosing Alzheimer’s disease with GP’s relying on in depth cognitive tests, with clinical confidence in diagnosis typically at 70-80%.

Doctor Helping Elderly

If confident early diagnosis could be achieved through noninvasive techniques, treatment could be introduced earlier delaying the onset of memory impairment.

The solution

The development of plaques or tangles of certain proteins (β-amyloid and tau proteins) in the brain is a known feature in Alzheimer’s disease. It is also known that abnormal accumulation of metals underlies several neurodegenerative diseases. Iron, in particular, is associated with the formation of neurofibrillary tangles in the β-amyloid plaques. The recent advances in the use of Magnetic Resonance Imaging (MRI) for the earlier detection of neurological diseases require validation to ensure the integrity of the images obtained is adequate for diagnostic purposes.

Researchers at LGC, in collaboration with partners, have been working to establish a link between novel MRI scans and quantitative elemental mapping of soft tissues. A method of mapping the levels of iron in sections of the brain using laser ablation (LA) coupled to Inductively Coupled Plasma Mass Spectrometry (ICP-MS) has been developed, along with a novel calibration strategy and standard to support quantitative tissue imaging. Correlation of the metal content associated with β-amyloid protein and MRI images will help diagnosis of AD at an early stage, where preventative therapy will have greater impact.

LGC has developed a novel calibration strategy for LA-ICP-MS that produced quantitative images for iron in whole mouse brain sections (provided through collaboration with Kings College London and the University of Warwick) and compared them with results from micro x-ray fluorescence (μ-XRF) (provided through collaboration with Ghent University and the University of Warwick). The data showed good agreement in total iron concentrations for a selection of areas within the mouse brain sections. This finding supports the proposed method as a quantitative approach; the calibration strategy has been published in the Journal of Analytical Atomic Spectrometry¹.

Impact

The development of this method for quantitative imaging of iron in the brain has the potential to lead to techniques for earlier diagnosis of Alzheimer’s disease, enabling earlier intervention, therapies and treatment aimed at delaying the onset of symptoms.

Delaying the onset of neurodegenerative disorders, such as Alzheimer’s disease, by five years could halve the number of deaths from the condition, saving 30,000 lives a year and billions of pounds in treatment costs. Reducing severe cognitive impairment in the elderly by 1% pa would cancel all estimated increases in long-term care costs due to our ageing population.

The methodology will also provide deeper understanding of the early development of Alzheimer’s disease leading the way for new treatments aimed at preventing the disease.

Heidi Goenaga-Infante, Principal Scientist for inorganic analysis at LGC, commented: “This cutting-edge research is already proving to be of significant benefit to the validation of non-invasive diagnostic tools for Alzheimer’s disease. The potential for metal imaging mass spectrometry of other biological tissues to probe the reported links between metals and disease states is now a step closer.”

If you’d like to learn more about our work and read other case studies, visit our website.

¹ J O’Reilly, D Douglas, J Braybrook, P.-W. So, E Vergucht, J Garrevoet, B Vekemans, L Vinczec and H Goenaga-Infante, “A novel calibration strategy for the quantitative imaging of iron in biological tissues by LA-ICP-MS using matrix-matched standards and internal standardisation”, J Anal. At. Spectrom., 2014, 29, 1378-1384

Delivering impact to support AIDS research

LGC is helping to ensure that research into a cure for HIV is based on sound fundamental measurements.

Over 36 million people currently live with HIV, with approximately 2 million becoming infected each year (WHO 2015). Although HIV can be successfully managed with combination antiretroviral therapy (cART), the therapy must be continued indefinitely as no cure presently exists. This can be challenging in regions with high HIV prevalence and long-term use can potentially have toxic side effects.

One barrier to curing HIV is the presence of infected host cells that are not targeted by current therapies but lay dormant (so-called ‘viral reservoir’). These cells have the potential to become re-activated so novel strategies to cure HIV aim to target this reservoir. To determine whether these new approaches are successful, accurate and robust, methods for measuring HIV DNA are required.

The Molecular and Cell Biology team at LGC perform research to support accurate and reliable measurement as part of our National Measurement Laboratory (NML) role. Recent work by NML scientists comparing different molecular methods (qPCR, digital PCR) for quantification of HIV DNA has raised some concerns around the current popular choice of calibrator used to compare results between HIV clinical studies (8E5, ATCC® CRL-8993). It appears to lose HIV DNA copies during cell growth, potentially producing misleading estimates of how much HIV DNA is present and affecting whether novel strategies towards curing HIV are deemed successful or not.

Based in part on our work, the NIH AIDS Reagent Program, which provides critical reagents and resources to support research in the areas of AIDS therapeutics and vaccine development, has recently highlighted the potential instability of the standard on its reagent database to support the research community and enable the best chances of success.

 

 

Citation:

Busby E et al. Instability of 8E5 calibration standard revealed by digital PCR risks inaccurate quantification of HIV DNA in clinical samples by qPCR (2017) Sci Rep 7(1):1209. doi:10.1038/s41598-017-01221-5

The importance of iodine – are you drinking enough milk?

Ensuring the safety of the food we eat is of paramount importance. Iodine is an essential element naturally found in some foods. Insufficient amounts of iodine in the diet results in low levels of thyroid hormones, which are responsible for regulation of metabolism.

In pregnant women and infants iodine is of particular importance as it plays a critical role in brain development. The primary sources of iodine for most people are milk and dairy products but due to increases in dairy intolerance and changes in diet, milk-products are being increasingly substituted for non-milk alternatives.

To identify the impact that such dietary changes might have on iodine levels across the population, an understanding of the levels of iodine naturally present in milk is necessary. This includes the effects of seasonal variations or fat content and any processing effects of pasteurisation which might reduce the iodine content. These variations have been investigated by the Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, with milk samples collected over a 12-month period. However, these differences needed to be measured accurately in order to properly determine the influence different conditions have on iodine content.

As part of the UK’s National Measurement Laboratory (NML) role, scientists at LGC have developed a high accuracy quantitative method (inductively-coupled plasma mass spectrometry) for the analysis of iodine in milk and milk-products to support the regulation on iodine levels in infant formulas. Using this expertise, we were able to support the work being done at Ulster University, providing the analytical capability required to determine the levels of iodine in milk under a variety of conditions.

Of the collaboration, Maria O’Kane, lead author on the paper, said: “LGC facilitated my visit to the laboratory in Teddington and enabled me to undertake analysis of the milk samples collected using high accuracy ICP-MS. The expert staff at LGC supported my learning and enabled me to develop a greater knowledge and understanding of ICP-MS analysis.”

The findings were recently published in the Journal of Nutrition, where Maria concluded that consuming additional cow milk can significantly increase the amount of iodine observed in the urine of women of childbearing age.

This work will help our understanding of current iodine intake and support future research in this area and clearly demonstrates the impact the UK’s National Measurement Laboratory (NML) can have on real-world problems, protecting human health and ensuring the safety of our food.

Finding harmony in newborn blood spot screening

Every forty seconds, a baby is born in the UK. That’s nearly 775,000 births across the United Kingdom in 2016 alone. It’s important that each of these children is given their best chance at a healthy future from the moment they are born.

Currently, all parents of newborns in the UK are offered newborn blood spot screening, a test which detects nine conditions and inherited diseases, including cystic fibrosis, congenital hypothyroidism, and sickle cell disease. The level of hormones or amino acids in the blood at the time the sample is taken leads to early detection. The goal is to detect and treat conditions before they cause severe developmental problems or unnecessary suffering so children can lead as normal lives as possible.

With the number of infants tested each year and the use of nationally agreed protocols with specified cut-off values, harmonisation of methods across the 14 laboratories performing these tests is extremely vital.  Each time a sample is analysed, it should produce the same results. The cost and time of retesting samples can be great and can cause unnecessary stress to the families at an already challenging time.  Additionally, the network of newborn screening laboratories in the UK should have access to the newest, most accurate methods and data.

This is why we have partnered with Dr Rachel Carling, one of the country’s foremost authorities on newborn screening, and the NHS England as part of the CSO’s Knowledge Transfer Partnership (KTP), a programme that teams up leaders in healthcare with the UK National Measurement System’s lab, including the National Measurement Laboratory (NML) at LGC, to solve measurement challenges in their fields.

Through the partnership, we plan to help create methods and materials that will lead to greater harmonisation and provide a framework within which more analytes can be added to the UK’s screening programme to be able to test for new diseases at birth.

As part of the KTP, LGC’s Chris Hopley and Simon Cowen will be discussing best practice in newborn screening with the network of labs at a workshop in London this week. Together, we hope to help deliver greater efficiency and certainty for these children and their families.

Analysis for Innovators: How we can solve your measurement problem

LGC, in our role as the UK National Measurement Laboratory and Designated Institute for chemical and bio-measurement, partnered with Innovate UK to launch a new funding programme ‘Analysis for Innovators’ (A4I) last year.

The aim of A4I was simple: to solve real problems affecting productivity or performance of UK companies of all sizes using the world-leading measurement facilities available at LGC and other national laboratories (NPL, NEL, STFC).

After the success of the first round, Analysis for Innovators is opening a new round of applications in March to UK companies who wish to take advantage of our expertise, research and development to help solve a measurement problem. And this year’s round has £4 million reserved to fund 12-month projects, with up to £250,000 for each project.

Companies are asked to submit a two-minute video outlining an existing measurement problem, without providing any solutions. This gives us insight in to what the obstacle looks like, the approaches the companies have already tried, and how solving it might change their business going forward.

After watching the videos from last year’s competition, LGC scientists sat down with the competition winners and discussed the problems in more detail. This approach encouraged creative thinking from our scientists and provided companies with access to our experts even if they did not progress to the next competition stage. In fact, feedback from the first round indicated that this stage was itself incredibly useful, and as a result the initial successful outcome of the current A4I programme will be a longer consultancy session with our measurement experts before progressing on to potential projects.

Previous collaborations included developing an assay to continuously monitor cortisol for a wearable device to improve diagnosis and treatment of disease, improving the sensitivity of a novel assay developed to ensure the safety of cell therapy products, and optimising an innovative non-chemical disinfection process to provide a cost-effective system for cleaning water and other fluids.

This programme benefits companies who otherwise would not be able to consult with our scientists, but it also benefits LGC by giving us the opportunity to see the outcomes of the vital measurement work we do every day. Our scientists are at the forefront of measurement technology, so it’s exciting to see how our science can affect and change lives for the better. These applications of our expertise remind us why what we do is important and inspire us to continue.

If you’re planning on applying for the next round of funding, or if you’d just like to learn more about the programme, register to join us at one of the remaining roadshows in February and March. We’ll be there to help share the work of our collaborations and illustrate how our analysis can help solve your problem.