In every scientific discipline, from physics to chemistry to biology and environmental science, measurement plays a pivotal role. It allows us to observe patterns, detect changes and evaluate the effects of various variables on a system. Accurate measurement acts as a foundation for developing and testing scientific theories, ultimately leading to technological advancements, and understanding of natural phenomena.
Accurate and precise measurement is an essential foundation for progress in the fields of biotechnology and health. The ability to measure and quantify various biological parameters is critical for understanding disease mechanism, developing effective therapies and evaluating the safety and efficacy of new treatments. From genetic sequencing to diagnostic tests, accurate measurements are key to scientific research, clinical practice and the development of innovative solutions that improve human health.
The National Measurement Institute is part of the Department of Industry, Science and Resources. NMI develops and maintains Australia’s physical, chemical and biological measurement standards. It is responsible for developing measurement systems and delivering measurement products and client services to a wide cross-section of stakeholders, including government, industry, and science and technology partners.
Within the health sector, NMI works to give medical practitioners and consumers confidence in measurement results so they can make informed decisions.
Calibrating infectious disease measurements
Quantitative polymerase chain reaction (qPCR) is a very popular method for identifying and quantifying genetic sequences of interest. It can detect even a single copy of a specific DNA molecule, making it an invaluable tool for diagnosing infectious diseases. For instance, in the wake of the COVID-19 pandemic, qPCR has been instrumental in identifying the SARS-CoV-2 virus in patient samples, guiding public health measures and clinical management of patients. During the COVID-19 pandemic, the National Measurement Institute (NMI) prepared an inactivated whole-virus SARS-CoV-2 reference material, which was certified by a combination of digital PCR (dPCR), the more advanced version of qPCR, and mass spectrometry. This higher-order reference material was provided to stakeholders nationally and internationally. These materials are currently being used as calibrators, and for accuracy, precision and limits of detection verification of qPCR-based measurements.
To underpin wastewater epidemiology during the COVID-19 pandemic, NMI ran an inter-laboratory study for Australian and New Zealand laboratories performing critical wastewater surveillance; participants were provided with NMI whole-virus SARS-CoV-2 as a reference material.
DNA methylation technology
NMI has developed unique expertise in quantitative measurement of methylated DNA sequences. The measuring systems are based on a combination of dPCR, isotope dilution mass spectrometry, ultraviolet spectroscopy and liquid chromatography–mass spectrometry that enables preparation, qualitative characterisation and quantitative measurement of gene-specific methylation reference materials.
The technology was developed in response to the challenges experienced by a number of medical research institutes. It could have a significant impact on detection and management of cancer and will also help to contain pathology costs, especially if efficient measuring systems can be introduced early in the clinical validation process. Early detection of many cancer types may also be possible using methylation markers.
Gene and cell molecular therapies promise to be effective treatments for many genetic diseases and for cancer, using modified T-cells (chimeric antigen receptor modified, or CAR T-cells). Accurate, standardised quantification is needed to evaluate the therapeutic and safe dose for this new kind of biological therapeutic agent.
NMI has partnered with the Children’s Medical Research Institute and their Viral Vector Manufacturing Facility to produce and validate genetic standards and to develop accurate quantification methods for clinical manufacturing of several gene therapy ‘drugs’. NMI’s reference materials will contribute to improved production of gene therapy ‘drugs’ and their approval by regulators, and facilitate bringing effective gene therapies to patients in Australia and globally.
Virus testing – hepatitis A and norovirus in foods
Development and the continued delivery of this service has been driven by repeated outbreaks of hepatitis A in berries (particularly) and other commodities. It is a challenging method (probably why few, if any other, labs in Australia offer these tests routinely) due to a complex multi-step extraction process. Detection is by reverse transcriptase PCR with virus-specific genetic sequences. The common matrices are also challenging, including those with polyphenols, pH extremes and other method-interfering components or characteristics.
Food allergen analysis
NMI food allergen capabilities currently cover at least 23 different allergens and are based on protein or DNA targets, detectable at sub ppm (mg kg–1) levels. This analysis supports accurate food labelling and aids the safe consumption of packaged food by allergic individuals. The development of PCR methods also supports the new plain English allergen labelling food regulations, which include the distinction between the gluten-containing cereals (wheat, rye and barley), which is only possible by a genetic approach.
Genetic services related to food, water and the environment
Food authentication and provenance has become critical for ensuring food safety and maintaining supply chains. NMI has developed a capability to measure the relative proportion of the species present in processed meat products and rendered pet foods.
In agricultural testing, we are developing the capacity to produce reference materials for agricultural pathogens and participating in an international study comparing capabilities across metrology institutes for measuring these organisms. We have provided DNA reference materials designed for PCR analysis of multiple environmental pathogens of interest in drinking water.
Bioassays for honey
NMI methods are based on bioassays or inhibition screens. Total activity and non-peroxide activity measurements support the labelling and marketing of high-end honeys, such as manuka, jarrah and marri. These honeys are in high demand in Australia and beyond, with the product value directly linked to the level of antimicrobial activity. Method selection in this area can be challenging as new method developments may give marketing-friendly high(er) numbers while concerns remain about comparability to historical data and other honey parameters such as methylglyoxal content.
The bacterial filtration efficiency test is one of three tests in Standard AS4381 for surgical face masks, the other two being physical tests. Modelling a biological system, bacterial filtration efficiency testing effectively measures the capability of a face mask to capture the small aerosol particles likely to transfer respiratory viruses such as COVID-19. Developed by NMI’s Analytical Services Branch, and NATA accredited, this method was developed in response to a lack of test availability and limited stocks of face masks during the pandemic. Another complex, multidisciplinary technique, this method requires microbiological culturing, aerosol/air flow physics, a six-stage Anderson impactor (that mimics the different levels of the human lungs) and colony-counting techniques and interpretations.
In addition to a range of traditional biochemical and serological bacterial identification approaches currently performed, NMI is investigating and expanding into bacterial characterisation via mass spectrometry (MALDI-TOF) and genetic approaches. These newer developments and applications open a range of future opportunities including antimicrobial resistance information and very rapid identifications.
This article is a collaborative effort of the Analytical Services Branch and the Chemical and Biological Branch of the National Measurement Institute (firstname.lastname@example.org).