i-SECTION: EDITORIAL

www.rsc.org/analyst | The Analyst

Nanometrologyis it the next big thing in measurement?

DOI: 10.1039/b609722g is a key part of modern detection science. These could be the measurement of distances up to 100 nm, such as features on a surface, or analysis of the interaction of two biological molecules. In terms of the analysis of events on a nano-scale this could be the interaction of two molecules or biomolecules leading to a significant outcome. In seeking to achieve these types of measurements new and highly innovative analytical approaches involving scientists from many different backgrounds are being created and developed to satisfy the different end users who will end up benefiting from these advances. The first use of the term nanometrology in a peer reviewed publication appears in April 1992, in the journal Metrologia (K. Nakayama, M. Tanaka, F. Shiota and K. Kuroda, Metrologia, 1992, 28(6), 483502). In that paper a Japanese group from the National Research Laboratory of Metrology used precision measurements to determine fundamental constants and test physical theory relating to silicon lattice spacing and magnetic flux quantum. Various other papers have followed from that original paper using the word nanometrology and a number of different techniques and approaches have been used. In the original paper scanning tunnelling microscopy (STM) was used to provide a physical measurement of distance. Various other techniques, such as near field optical microscopy, AFM and SEM/TEM, have been used to provide measurement on a nano-scale. In 2005 the Institute of Physics published a dedicated edition of the Journal of Measurement Science and Technology on nanometrology. In that particular edition there were 8 articles covering a number of topics critical to nanometrology. As an alternative to electron microscopy, fluorescence resonance energy transfer (FRET) has been used to provide measurement of distances between fluorophores between 1 and 10 nm. These fluorophores tend to be attached to biological molecules and can be used to give indications of distances between actives sites or interacting molecules, such as proteins and ligands or proteins to other proteins, or indeed DNA interactions using simple optical microscopy as opposed to some kind of force or electron microscopy. Obviously, biomolecules prefer to exist in an aqueous environment, which is not particularly suitable for the force or electron microscopies. Therefore, for nanometrology to move into the biological environment it was inevitable that new techniques would emerge to allow measurement on a nano-scale. FRET is the most obvious approach and has been well documented (R. F. Lakowicz, Principles of Fluorescence Spectroscopy, Plenum Publishing Corporation, 2nd edn, 1999). However, other new techniques are appearing which show considerable promise for the nanometrology of the future. Many of these are advances on FRET, such as using lifetimes instead of emission: however, one new approach that does not use fluorophores is plasmon resonance coupling to provide a plasmon ruler. The term plasmon ruler was originally published and coined by Paul Alivisatos from UC Berkeley when he published a seminal paper, in 2005, on the use of interacting gold and silver nanoparticles to provide measurement between DNA sequences by looking at the change in plasmon frequency of these nanoparticles when they were separated or coupled (C. Sonnichsen, B. M. Reinhard, J. Liphardt and P. Alivisatos, Nat. Biotechnol., 2005, 23(6), 741745). This paper reported that measurement of distances of between 1 and 70 nm should be possible using this approach, and due to the fact that they do not photo fade and are less susceptible to changing their properties in the environment, could make an excellent replacement for FRET. The FRET and plasmon coupling approaches are a significant change in the field in that it is the reagents that are providing the ability to
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Duncan Graham is Professor of Chemistry at the University of Strathclyde and a member of The Analyst Editorial Board. He is co-founder of the Strathclyde Centre for Molecular Nanometrology.

The term nanometrology appears alien to many people when they hear it mentioned or read it for the first time, so perhaps the first thing that I should do in this editorial is try to define the term nanometrology. As most people will be aware the word nano means one billionth and comes from the Greek nanos, meaning little old man, and the term metrology is defined as the science that deals with measurement or a system of measurement. Again the word has its origins from the Greek language and comes from the word metrologia meaning a theory of ratios. So put together we have nanometrology meaning the little old man and the theory of ratios or perhaps its small men measuring ratios, or perhaps it is the measurement of small old men. In a scientific context the term nanometrology can be interpreted quite broadly and has traditionally been used to describe approaches used in manufacturing technology, where very precise measurements are the foundations of the engineering industry. In recent years nanometrology has broadened its horizons and it now appears to encompass measurement of species or events on a nano-scale, which

This journal is The Royal Society of Chemistry 2007

achieve nano-scale measurements as opposed to sophisticated instrumentation. The choice of reagent and what data can be acquired is dependent on an understanding of the system under investigation and, as such, naturally leads to greater collaboration between those involved in the nanometrology techniques and those interested in the data. Very often this is the mix of expertise and expectation that leads to new approaches being created, and there is great scope for analytical chemists skilled in nanometrology to become central to many areas of research to produce significant world firsts with impact in other areas of science. As readers may have noticed, the significant advances in nanometrology have taken place outwith the UK, and in order to try and improve the UKs ability to compete in the sub-section of nanotechnology that is nanometrology, the engineering and physical sciences research council, EPSRC, has made nanometrology one of its priority areas

for science and innovation awards. This is designed to improve the capacity to conduct research into nanometrology and provide the new breakthroughs necessary to interface the physical measurement sciences with the end users, who will range from manufacturing industry to cell biologists and medics. As a result of this focusing of support, the London Institute of Nanotechnology, a joint centre between Imperial College London and University College London, have been awarded one of these science and innovation awards to provide new tools for nanometrology with appropriate spatial and temporal resolution. A second award was made to the University of Strathclyde, where we are combining our expertise in chemistry, physics and photonics with that of the interests of the medics at Guys Hospital, London, to attempt nanometrology with a focus on nanomedicine. In the USA the National Nanotechnology Initiative (NNI) was established in 2004 with the vision of a

future in which the ability to understand and control matter on the nano-scale leads to a revolution in technology and industry. There have been around 1 billion US dollars per annum available to support 7 different program areas, one of which is nanometrology, indicating the realisation that nanometrology has a role to play in the NNIs vision of the future. A lot of nano-words are being banded around and ultimately it all comes down to the same thing: good quality, precise analytical measurement that starts with a fundamental scientific drive and has the potential to provide significant impact on a number of areas outside science. For nanometrology to have a substantial impact innovative thinking and collaborative efforts are required where analysis is seen less of a service tool and more an enabling part of the overall effort in contributing to major scientific advances. Duncan Graham University of Strathclyde

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This journal is The Royal Society of Chemistry 2007