Is redefining the kilogram useful for drug development and nanotechnology?

Question

With the redefinition of kilogram currently underway, I see recent online articles claiming that a precise definition of the kilogram is critical for drug development and nanotechnology. E.g. BBC.com

In a world where accurate measurement is now critical in many areas, such as in drug development, nanotechnology and precision engineering - those responsible for maintaining the international system had no option but to move beyond Le Grand K to a more robust definition.

Or joe.ie

Accurate measurement is critical in many areas of the world today, such as in drug development, nanotechnology and engineering and is among reasons the Le Grand K rule is being changed.

Is this claim justified? Can someone please exemplify by describing such a process where more accurate mass measurements make a difference?

Of course measuring weight is important, but I think the skeptical claim is whether any process actually requires the enhanced precision gained by redefining the reference kilogram. The actual difference is minuscule. — Ask About Monica, Nov 16 '18 at 19:48
The question is whether the expected variations in the current standards are significant enough to be a problem. It's hard to imagine a drug development project where measurements accurate to one part in a billion would be required. Yes, eventually the unit should be converted to some "absolute" measure, but that's more for convenience than for accuracy. — Daniel R Hicks, Nov 16 '18 at 21:25
@kbelder: I'd hope the difference should be close to zero - otherwise it should get a new name! — cbeleites unhappy with SX, Nov 17 '18 at 17:11
@Daniel Hold up second. You find it hard to imagine that high precision of molar weights is important in chemical engineering of drugs, where precisely controlling reaction rates impacts cost effectiveness and purity? — Konrad Rudolph, Nov 18 '18 at 09:07
@Konrad Rudolph: yes I find it hard to imagine that measuring mass to 7 decimal figures w.r.t. some easily available and stable absolute reference (as the new definition allows) matters to applied chemistry. Modern applied chemists tend to measure mass by way of weight, often without even thinking about it, and the ratio of weight to mass (known as g) varies significantly with the location (often in the 5th figure, or 6th figure after correction for altitude and latitude if I get [this](https://en.wikipedia.org/wiki/Gravimetry#How_gravity_is_measured) correctly), and this variation is ignored. — fgrieu, Nov 18 '18 at 09:53
@fgrieu Beyond $g,$ atomic masses given on a periodic table are [prevalence](https://en.wikipedia.org/wiki/Natural_abundance)-weighted averages of the isotopes found on Earth which can be misleading as actual sample compositions tend to vary. It's also pretty rare to have any chemical solution with a purity anywhere near 7-decimal places (with a few notable exceptions, e.g. silicon for modern microprocessors). In practice, chemists often make due with stuff that's [$\ge 95 \%$ pure](https://www.labmanager.com/business-management/2017/11/the-seven-most-common-grades-for-chemicals-and-reagents). — Nat, Nov 18 '18 at 10:58
Regarding this topic, I think that the best argument for the claim would likely follow from a cause-and-effect analysis from errors in the prior SI-standard to actual practice. Presumably variations in a standard may've led to errors in sub-standards, then to lab equipment, and then to actual measurements. A good analysis may be able to estimate the magnitude of the expected error - though I think it's fairly easy to guess that the expected error due to the alleged issues is probably going to be pretty trivial; it's probably there, but likely far too small to appreciate. — Nat, Nov 18 '18 at 11:15
The real conspiracy is this is a push to have less control from France, now if other countries can build a kibble balance of their own there is less influence from the nefarious french making things weigh ever so slightly less. — daniel, Nov 18 '18 at 19:29
.... trying to figure out a way to formulate an answer that make this somehow proof of supremacy of "US customary units" that won't get down-voted is epic fashion. 'Murika!! — PoloHoleSet, Nov 19 '18 at 18:37

cpcodes · Answer 1 · 2018-11-17T00:12:29.873

12

From the NPL (National Physical Laboratory) in the UK, there are three problems with the current system (using Le Grand K):

Its weight changes over time
These changes are unpredictable
The national copies cannot be monitored with the highest level of accuracy

Further, the system is expensive and prone to difficulties. The maintenance of Le Grand K is expensive and a logistical nightmare. The national copies exhibit varying drift from LGK - as much as 2 micrograms per year. Rectifying these drifts can leave the nations that depend on the copies without them for as much as 6 months.

Further, the kilogram is the only remaining SI unit still defined by a physical artifact.

According to NIST, even the US and UK pound measurement of mass is defined in relation to the kilogram. This makes the kilogram the standard for the most widely used units of mass in the world. Also from the article:

Moreover, this mass-comparison system is not easily scalable from large to small. The smaller the scale, the larger the uncertainty in measurement because a very long sequence of comparisons is necessary to get from a 1 kg standard down to tiny metal mass standards in the mg range, and each comparison introduces an added uncertainty. As a result, although a 1 kg artifact can be measured against a 1 kg standard to an uncertainty of a few parts in a billion, a milligram measured against the same 1 kg has relative uncertainties of a few parts in ten thousand.

However, the question isn't whether it is a good idea to change the definition to be based on a fundamental constant (it undeniably is), but whether medical and nano-technological processes are negatively affected by the small drift witnessed in the baselines.

To start, it's important to realize that the kilogram is a base for a number of other SI measurements based on mass - such as the volt or the ohm. It is likely that the correction of the small amounts of drift in the kilogram will benefit these things much more than straight mass measurements, but that is mere speculation on my part.

Additionally, NIST says this:

That uncertainty is not satisfactory for the ever-more-demanding needs of modern measurement science, device manufacture, material science, pharmaceutical research and testing, and environmental monitoring, to name only a few. Increasingly, those endeavors require accurate measurements on the order of micrograms (millionths of a gram) and smaller.

For nanotechnology, the benefit seems plain - at the scale of molecules, a micro-gram is an error magnitudes larger than those in use to measure the components. And electrical measurements are also likely critical in this space. As nanotechnology can involve the manipulation of a single atom, which weighs on the order of zeptograms.

For biochemistry (what drug development mostly boils down to, though the analysis of body processes - required for research/testing - could involve electrical measurements as well), measurements down to the microgram are considered common enough to be given as an example in a discussion of measures. As such, 2 micrograms/year of drift would constitute a significant fraction of the measurement.

So, yes, the accuracy of the definition of a kilogram is critical today for scientific endeavors, and will grow more critical in the future.

edited Nov 17 '18 at 00:12

answered Nov 16 '18 at 19:59

cpcodes

1,068
8
13

6

Why would a milligram measured against a 1 kg have relative uncertainties of a few parts in 10000 when the uncertainty of the kg itself is only a few parts in 1000000000? If I accidentally measure 3mm by using the 1/1000 part of a yardstick instead of a meter stick, I will end up with a relative error of less than 10%, the same error the full-length stick has. -- Likewise, if in nanotechnology I build a machine from, like, 50 atoms, their structural arrangement seems more relevant than whether together they have mass of 50 zeptograms or 50.00000001 zeptograms – Hagen von Eitzen Nov 16 '18 at 21:07
4

@HagenvonEitzen From the referenced NIST article, "Moreover, this mass-comparison system is not easily scalable from large to small. The smaller the scale, the larger the uncertainty in measurement because a very long sequence of comparisons is necessary to get from a 1 kg standard down to tiny metal mass standards in the mg range, and each comparison introduces an added uncertainty." – cpcodes Nov 16 '18 at 22:00
@HagenvonEitzen As for nanotechnology, suppose you wanted to measure the amount of atoms deposited upon a surface in order to characterize the results of an experiment. The surface in question is part of an object that weighs a micro-gram. You weighed the object before the experiment, then you weigh it afterwards, then use the difference to calculate the number of atoms deposited upon the surface. This is perhaps a poor example because an exact count is probably not needed, but when counting tens of thousands or millions of atoms, the error becomes relevant. – cpcodes Nov 16 '18 at 22:05
3

For small things wouldn't the lab coat guys use the number of atoms? https://en.wikipedia.org/wiki/Mole_(unit) – daniel Nov 16 '18 at 22:27
@Cpcodes The comment in response to HagenvotEitzen should be edited into your answer. – BobTheAverage Nov 16 '18 at 23:00
@BobTheAverage Done. – cpcodes Nov 17 '18 at 00:12
1

@daniel In some cases, I expect so, but a mole is a count by mass, and so is sensitive to an imprecise kilogram. As such, the change in the kilogram is probably going to interfere with Avogadro's number and the mole. Either AN will have to change, or the atomic number (which is based on the mass in grams of a mole of an element) will. Or there's a third option in that the new value of the kilogram will be selected to precisely match up with what particle physicists and chemist have been using. I'm not knowledgeable enough in these things to know. – cpcodes Nov 17 '18 at 00:18
8

The argument in the answer doesn't make any sense. It hasn't shown the error, in parts per billion, is amplified when dealing with microgram measurements. I am *wildly speculating* that the advantage is the new definition can be directly scaled mathematically (if I know the definition of kilogram, I know the definition of microgram) rather than having to physically scale down to a microgram. i.e. it isn't the initial part-per-billion errors that are causing problems at all. – Oddthinking Nov 17 '18 at 02:06
1

@daniel - The Mole was redefined at the same time as the kilogram, though we talk about it a lot less. Previously, a Mole was defined as the number of atoms in 12 grams of carbon-12. If the kilogram fluctuated, so did Avogadro's constant, which lead to a lot of incertitude at a molecular scale. Now that the kg has been fixed, Avogadro's constant is also fixed. Prior to this change, all the problems arising from the fluctuation of the kilogram also applied to the Mole unit. The new value is still based on the kg (still # of atoms in 12 grams of carbon-12), it just doesn't fluctuate anymore. – Dungarth Nov 18 '18 at 17:53
_the kilogram is still the only remaining SI unit still defined by a physical artifact_ - not any more - oh, and they agreed to redefine the kilogram, ampere, kelvin, and mole, not just the Kilogram. Now all seven base units are universal. – Baldrickk Nov 19 '18 at 13:53
@Dungarth - re *The new value is still based on the kg (still # of atoms in 12 grams of carbon-12), it just doesn't fluctuate anymore* That is not the case. The new definition explicitly separates the mole and mass. Future measurements will almost certainly will show that the mass of a mole of carbon 12 differs slightly from 12 grams. This was one of the key arguments against the new SI; that argument obviously failed to prevail. – David Hammen Nov 19 '18 at 14:46
@Baldrickk not yet. The change takes effect on 20 May 2019. – phoog Nov 24 '18 at 04:39

David Hammen · Accepted Answer · 2018-11-18T07:45:29.717

Is redefining the kilogram useful for drug development and nanotechnology?

Probably not, and almost certainly not with regard to drug development.

The redefinition of the kilogram achieved two key goals:

Getting rid of the very last physical prototype that underlies the International System of Units.
Breaking past the tenth of a part per million accuracy level with regard to mass.

Neither the pharmaceutical industry nor nanotechnology industry cares about the first goal, which is a rather academic concern. I don't know about the uncertainty or accuracy requirements of the nanotechnology industry, but for the pharmaceutical industry, those requirements are on the part of a part per thousand. To wit, from USP General Chapter 41, Balances:

Repeatability is satisfactory if two times the standard deviation of the weighed value, divided by the desired smallest net weight (i.e., smallest net weight that the users plan to use on that balance), does not exceed 0.10%.
The accuracy of a balance is satisfactory if its weighing value, when tested with a suitable weight(s), is within 0.10% of the test weight value.

Routinely attaining better than a part per thousand uncertainty and accuracy in assessing mass is rather nontrivial. Doing so requires very precise calibrated equipment and very careful attention to environmental details. This is the scale on which the pharmaceutical industry operates.

Attaining a tenth of a part per million uncertainty and accuracy is well beyond nontrivial. This is the scale at which the former prototype-based definition of the kilogram was problematic. That extreme of uncertainty and accuracy is the scale at which the very few laboratories of a national level research institutes operate, along with the level at which the very few academic laboratories funded by those national level research institutes operate. This extreme accuracy level is not the scale at which the pharmaceutical industry operates.

The number one unwritten rule in metrology: All changes shalt be backward compatible. The redefinition of the kilogram did not suddenly invalidate the huge number of weighing devices with certifiable traceability to the (former) IInternational Prototype Kilogram. — David Hammen, Nov 18 '18 at 08:06
Correction on the above comment: Soon to be former rather than former International Prototype Kilogram. The redefinition of the International System of Units voted on 16 November 2018 won't take effect until 20 May 2019. — David Hammen, Nov 18 '18 at 12:51

Is redefining the kilogram useful for drug development and nanotechnology?

2 Answers2