For the love of a metre, if not 3 feet will do.

By Jason Major

TechNyou

The world of measurement is more than a kilogram or metre, it involves validating highly sensitive ways of diagnosing cancer, measuring and determining the fate and toxicity of nanoparticles, defining mathematically the precise red for a red traffic light and making sure we don’t lose a second of valuable time, fleeting as it is. It is also where you go to find out the precise metrics for the standard metre, or kilogram.

At the end of February I was in Sydney for the Australian Science Communicators conference. As part of that trip I visited the Australian Government’s National Measurement Institute (NMI). Yes we have one of those and it far more than a bunch of anal, obsessive-compulsive scientists fretting over the precise nature of a kilogram or nanometre, or debating the prospect of a leap second. Yes they provide the primary standards for all these measures and they can do it precisely, so heaven forbid the next butcher who tries to rig his scales and overcharge you for that rump steak. This latter role, referred to as trade measurement, is actually a responsibility NMI only took on in 2010. These are standards that have been set and these guys are there to ensure those standards can be measured accurately and to enforce those standards out there in the real world.

OK, maybe there are a small handful of scientists who are a tiny bit obsessive, but who isn’t. The majority are involved in stuff that is, to me, simply profound. It is mind boggling the scale and accuracy that we can measure things. We are talking detecting and measuring the presence of atoms and molecules in detail and in concentrations hard to imagine.

Cancer

Worldwide researchers have made huge advances in understanding the biological mechanisms behind many cancers and from this discovered molecules and genetic markers associated with these cancers that could be useful for diagnostic purposes. The problem is there are few suitable standards anywhere in the world to gauge the accuracy of these diagnostic tests. This makes proving the usefulness of cancer markers difficult.

(Standards are just a reference from which to compare something so you know what it is you actually have. For instance we have a set standard to test the acidity of stuff. It is called the PH scale. I measured the PH of my rain water on the weekend which was 4 on the standard PH scale – 7 is neutral – so I know my rain water is quite acidic, but within the normal range for rain water. Without this, the level of acidity in my rainwater would have been meaningless.)

The job the NMI guys set themselves was to develop some standards for the genetic cancer markers, specifically to develop novel genetic measurement technologies for the accurate measurement of DNA methylation.

Messing with methylation

Associated with cancers is the methylation of DNA, which involves a methyl group (one carbon and three hydrogen atoms) that stick to one of the DNA nucleotides (cytosine). When this happens, the expression of the gene it is attached to alters – eg, is silenced or switches off. Methylation is part of normal cell functioning and fine unless the methylation occurs on, in this case, a tumour suppressor gene. Methlyation in this case switches the gene off eventually causing cancer. If you could detect the occurrence and frequency of methylation you would have an early warning signal for the cancer. However, inaccuracies in the measurement of DNA methylation can occur at many stages in the process. Comparing results and drawing meaningful conclusions then becomes difficult. If DNA methylation is to be used as a diagnostic tool for cancer, the accuracy and comparability of measurements must be known and certified reference materials will be needed to validate prospective methodologies.

NMI scientists have devised techniques that effectively detect the difference in weight between the gene fragments that have been methylated and those that haven’t. Given that a methyl group is just one carbon and three hydrogen atoms that difference is very small relative to the scale of DNA. For those with some science nous they can detect a difference of 14 in 140,000 atomic mass units (or 1 on 10,000). For others the inaccurate analogy is their ability to measure the weight of two identical haystacks and detecting the presence (or weight) of the needle in one of them. It is an inaccurate analogy because haystacks can be a few hundred or a few thousand bales, but I just had to use the needle-in-a-haystack analogy.

Super athletes

Gene doping is a growing fear in the sporting world. The technology to insert into us copies of genes that could boost muscle growth, or some other performance enhancing trait is more than possible in the near future. The problem is detecting when someone has done it as the protein will be a natural one. Short of a muscle biopsy which will obviously impede performance it is difficult to detect. A method to detect gene doping is a priority for NMI and they have published scientific papers on an approach that could be suitable to detect gene doping by analysis of small volumes of blood.  I doubt that pleading ignorance and blaming your mum or your coach will get you far in this situation.

Other stuff they do

• Provide the tools for measuring the presence of transgenes in genetically modified crops
• Provide the standards and analytical tools to measure light (irradiance, watts, flux.. and so on) For example, if your traffic light isn’t the precise red then these dudes can coordinate the chromaticity to within two points, which I am told is way too precise for any human eye to detect the difference.
• Detect pollutants, and greenhouse gases, test water quality
• Collaborate with all the other international metrology institutes to develop accurate methods and instruments for measuring dimensions of nanoparticles.

On this last task NMI is part of an OECD project examining the full life cycle of nanoparticles – their fate and toxicity from manufacture to what happens once they are disposed of and enter the environment. And they have a cool laser machine to help them – see image below

Measuring the nanometre

Ultimate reference machine for nanoparticles. This is Australia’s primary reference tool for the measurement of the nanometre, which is then cross referenced against their primary reference for the metre. Every measurement in the nanometre scale will be able to be traced back to this tool. Once built the room it is now sitting in will be temperature controlled so that temperature will remain within 0.01 degree celcius (100 mili Kelvin) over a 24 hour period. It will be vibration controlled so that even the minor vibrations of the trains a couple of kilometres down the road won’t upset its stability.

Micro chip

Able to perform 9000 pcr reactions at once. Its neighbouring machine can take 20 millilitres and turn that into 30,000 ultra-fine droplets and analyse each droplet for specific molecules, a process that is done in the time it takes to drink  a cup of coffee – about 15 minutes.

The time lords

One of the atomic clocks used to keep precise time. If you are wondering why we need to keep precise time, see this story from UNSW