Every DNA counts – and we would know

The National Measurement Laboratory at LGC turned 30 years old this year, and to celebrate we’ve been looking back at notable accomplishments, and looking at where we are now. Clinical measurement is one field where our scientists have excelled and innovated throughout our time.

biology-clinic-doctor-4154Clinical measurement “is the development, use, on-going support, and maintenance of technology for diagnosing, aiding or treating patients.” Modern medicine wouldn’t be possible if we couldn’t rely on the accuracy of clinical tests and diagnosis. Poor measurement can lead to misdiagnosis, incorrect prescription and dosage of medicine, or false interpretation of data. Therefore, reliable certified reference materials are absolutely necessary to ensure the quality and accuracy of clinical measurement.

Throughout the last 30 years, the National Measurement Laboratory (NML) at LGC has worked in this area to ensure that testing methods and reference materials are of the highest quality.

In one case study from 2006¹, scientists in the NML developed isotope dilution liquid chromatography-mass spectrometry (IDMS) methodologies that were then used to generate reference values for clinical reference materials (CRM), some of which led to the analysis of creatine in frozen serum and testosterone in frozen serum CRMs.

In another blog post, we outlined the work we’ve done to improve Alzheimer’s diagnosis, which could lead to techniques for earlier diagnosis of the disease, and in another, we illustrate the importance of harmonising newborn blood sport screening tests to ensure infants are diagnosed and treated early so that they can live as normal lives as possible.

An important part of working in the field of clinical medicine and measurement is communicating our knowledge with other scientists and medical professionals to ensure that good measurement is being performed consistently across the board. We have worked with the NHS and England’s Chief Scientific Officer Sue Hill on doing just that as part of the Knowledge Transfer Partnership Programme, which aims to improve patient care through new approaches to measurement.

And now, our scientists can even count DNA and measure changes to that DNA over time. Identification and targeting of specific genetic sequences forms the basis of many promising advanced healthcare solutions such as: precision (personalised) medicine in cancer, gene therapies to end genetic disorders in children and the detection of pathogenic and non-pathogenic bacteria in a wide spectrum of infectious and autoimmune diseases.

However, the new methods and technologies currently being developed will only achieve their full potential if we can ensure they are safe and can be reproduced. High accuracy reference methods are one of the key factors in supporting their development into routine application.

Using tests for guiding treatment of colorectal cancer as a model, our scienists outlined in a paper published in Clinical Chemistry how a range of dPCR assays and platforms compared and how precisely they measured the cancer mutation. An inter-laboratory study of clinical and National Measurement Institute laboratories demonstrated reproducibility of the selected method. Together these results reveal the unprecedented accuracy of dPCR for copy number concentration of a frequently occurring gene mutation used to decide on drug treatment.

This study has shown that using high-accuracy dPCR measurements can support the traceable standardisation, translation and implementation of molecular diagnostic procedures that will advance precision medicine.

All of this just goes to show you how far we’ve come in 30 years!

¹VAM Bulletin, Issue 35, Autumn 2006, pp 13. ‘Case Study 3: IDMS certification of clinical reference materials using LC-MS/MS”

Nanotechnology: The big challenge behind the characterization of the small

Nanomaterials and nanotechnology developments are having an increasingly significant impact on human life, from enabling more targeted cancer treatments to improving the efficacy of vaccines or the delivery of agrochemicals. However, their small size can lead to potentially toxic effects.

To protect human health and the environment, it is crucial that we are able to characterise nanomaterials effectively and understand their behaviour within biological systems. What do we really know about the potential effects when they come into contact with complex matrices and how do we ensure that nanoproducts are safe?

The global market for nanomaterials are estimated by Allied Market Research to have a market value of $14.7 billion in 2015, and some reports forecast that to grow to as much as $55 billion by 2022.

We know that the properties of nanomaterials can change significantly when used in complex matrices, such as biological systems, potentially affecting functionality and behaviour. Nanobiotechnology or nanomedical applications exploit these changes. For example, in some therapeutic applications, protein coated nanoparticles (apolipoprotein E coatings) can target specific locations, such as the brain.

However, there may be other currently unknown biological interactions which could pose a potential risk to human health. These risks are compounded by a lack of robust methods to characterise nanomaterials in complex biological matrices.

AB Still 0003As the NML we have been instrumental in developing new international documentary standards (ISO) to support this field. For example, we provided expert input into a newly released Technical Specification (ISO TS 19590:2017) that outlines a novel method (single particle inductively coupled plasma-mass spectrometry, spICP-MS) for determining the size distribution and concentration of nanoparticles in aqueous samples. We’ve been invited to provide the UK expert view for a new standard on the analysis of nano-objects using a gentle separation technique (field flow fractionation, ISO TS 21362).

These standards have been produced as a response to the worldwide demand for suitable methods for the detection and characterization of nanoparticles in food and consumer products. In addition, we provided the particle size reference measurements for a new silica reference material (ERM-FD101b) released this year by the European Commission (EC JRC Directorate F (Health, Consumers and Reference Materials). This material will support the implementation of the EC definition of ‘nanomaterial’.

The NML is co-ordinating the first international measurement comparison study between National Measurement Institutes (under the auspices of the CCQM) on the determination of number concentration of nanoparticles (colloidal gold). An interlaboratory comparison using the same material that is open to industrial and academic laboratories with an interest in nanoparticle analysis will be run in parallel through VAMAS (Versailles Project on Advanced Materials and Standards) in collaboration with NPL. This will allow a comparative evaluation across users and measurement institutes and may lead to the development of new international written standards to support regulation around nanoparticles.

LGC’s involvement supporting the development of nanotechnology regulation, and the underpinning standardisation efforts required at both a national and international level, recognises both the individual expertise of our scientists and our reputation in this field.

Our input will help ensure current and future consumer safety and ultimately protect human health and the environment whilst supporting the growth and development of this enabling technology.

You can read more about the work we do in our Annual Review, and have a look through our case studies to learn about our impact.

A4I is back for another round!

Analysis for Innovators is back! The latest round of the A4I programme from Innovate UK and its partners (LGC, NPL, NEL, & STFC) has now opened, with up to £3M available in total for Round 3.

In our role as the National Measurement Laboratory, we have worked with Innovate UK since the very start of A4I, back in January 2017, and the programme has proved such a success that we are already moving on to the third round!

But be quick to take advantage of this opportunity as the first stage of the application closes at noon on 6th September.  A4I is a very unique programme from Innovate UK – it helps UK businesses address difficult problems that restrict their potential productivity and competitiveness.  The scope is very wide (chemical, physical, biological and computing) but the problems must be of a measurement or analysis nature.

A4I targets real industry problems that haven’t been solved with existing products or services. As such, it is of interest to companies that have not traditionally considered applying for funding. Any size of business, with any type of measurement or analysis problem, are eligible to apply. If your company makes it past the first stage, you will be matched with us, NPL, NEL or STFC for a consultation. After this stage, some companies will continue to work with us in our own world-class measurement labs.

The first two rounds of the A4I programme have seen us help several companies overcome measurement problems. In Round 1, we worked with the Coconut Collaborative, a manufacturer of coconut yoghurt, and STFC to develop a rapid and robust screening method to detect rancid coconut cream before its use. The use of rancid cream led to lost sales and waste for the company. We helped develop a novel screening approach with multi-spectral imaging, which will help the Coconut Collective avoid annual costs of £500k.

We also worked with Sistemic to help ensure the safety of cell therapy products, by increasing the sensitivity of their novel technology, which detects contamination in cell therapy products. Cell therapies are seen as the future of treatment in a number of areas including diabetes and cardiovascular disease. However, one type of cell being used to generate cell therapy products (pluripotent stem cells, or PSCs) has the potential to form tumours. The NML enhanced the sensitivity and specificity of the Sistemic novel prototype miRNA-assay to the levels required for market (<10 cells per million). This assay will ensure producers can accurately assess PSC contamination in their cell therapy products.

Other examples of the companies that were funded under A4I Round 1 can be found at Analysis for Innovators winning projects, and for more information about the work and case studies of the NML at LGC, have a look here at our latest annual review.

And don’t forget to apply now– there’s £3 million up for grabs!

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.