Small-Angle Neutron Scattering

At the Institut Laue Langevin (ILL) researchers from a range of fields are utilising the world’s most powerful instruments for small angle neutron scattering (SANS) to investigate the structures of many materials across sizes ranging from 1-100 nanometres. These include polymers, alloys, and biological macromolecules. SANS offers significant advantages compared to other probes. In particular, neutrons are less destructive than other forms of radiation, such as X-rays – they do not damage sensitive biological samples – and they can be used to detect magnetic properties thanks to their magnetic moment.

SANS has proven to be a powerful technique addressing a number of societal challenges, such as discovering better drugs and understanding superconductors. Three recent publications have emerged from ILL that demonstrate the success and importance of SANS for scientific progress across a range of research fields. They highlight the power of SANS in increasing our understanding of how molecules behave in different solvents, how currents and magnetic fields behave in superconductors, and what processes we might be able to analyse in the future using this technique.

Conformation of drugs in the body

Scientists from Kyoto University, Tohoku University, The University of Tokyo and ILL were the first to apply SANS to the conformational analysis of synthetic helical macromolecules. As published in the Journal of the American Chemical Society, scientists used the D22 instrument as well as the super-computer at the Institute for Chemical Research, Kyoto University. The helix is a very important shape in biology – systems built using helices show great structural strength – and is found in critical macromolecules including polypeptides and polysaccharides, which make up proteins and carbohydrates, and DNA, the molecule of life.
This study looked at inherently ‘racemic’ polymer main chains, which are in an equilibrium between right and left-handed helical structures in solution at ambient temperature. The researchers set out to explore the phenomenon whereby the side chains of the helix, which are ‘chiral’ in contrast, transfer this characteristic to the main chain of the helix and cause it to appear to twist or contract. A change in this conformation is often observed when external conditions, such as the solvent, are changed. However, how the solvent plays a part in the transfer of this structural characteristic is yet to be explored at a molecular level. It could have significant practical applications, such as predicting how drugs behave in the body, but understanding the process is critical to exploiting it. Though SANS techniques have recently been used to examine bio-macromolecule structures in solution, the group was the first to use SANS to explore the puzzle of solvent-dependent switching, and the first to outline the characteristics of this behaviour.

Our D22 instrument was key in this research – the world-leading SANS instrument is especially suited to probing a variety of samples as the setup is very flexible, accommodating different experimental environments. This technique allowed the helix to be studied in high-resolution and produced detailed structural information. Features such as side chains could be visualised according to the pattern produced by neutrons. SANS with selectively deuterated samples is the only technique capable of distinguishing the side chains from the main backbone of the helix – X-ray scattering simply would not produce a scattering pattern with enough detail to differentiate between these distinct features. By examining the polymers using this technique, the researchers discovered that a subtle difference in how strongly the side-chains of the helix were bound to the solvent – i.e. the degree of solvation – was a main factor that induced the difference in conformation.

Using this data, the researchers could confirm the preferred confirmation of the side-chains in the two different solvents. In the first solvent one side chain extended towards the solvent, while the other was tight against the main chain. This was a stronger degree of solvation, and resulted in a right-handed helical structure. In the second solvent, the solvation was weaker, as the side-chains were folded in towards the main helical backbone due to their preference to interact with each other or the main backbone. This caused the macromolecule to form a shrunken, contracted helix. The novel use of SANS to explore and explain solvent-dependent switching demonstrates what a powerful tool this technique may be for increasing our understanding of this switching process. This knowledge may impact the pharmaceutical industry and drug development, as the left or right-handed, helical, macromolecular catalysts will selectively generate enantiopure drugs, with a specific form that allows any side effects in our bodies to be minimised.

Expanding the use of superconductors

Another study published inNature Communications from researchers at the Technical University of Denmark, University of Fribourg, University of Birmingham, and ILL, explores the use of SANS to probe the vortex order of superconductors - materials that allow electrical currents to flow through them with zero resistance when the temperature is lowered below a critical point. Most superconductors are Type-II, which means they exhibit a ‘vortex state’ and often have high critical magnetic fields, above which the superconductor loses its superconductivity.

This study also used the D22 instrument at ILL to probe a Type-II superconductor, vanadium, using SANS. Researchers examined the vortex order in a vanadium crystal and provided experimental evidence for the Bragg glass phenomenon, where vortex diffraction peaks are reshaped due to disorder within the superconductor. Without SANS, the transition point between the Bragg glass state and a disordered ‘vortex glass’ could not be identified – most previous studies characterising the states observed in this research did not involve directly probing the vortex order, and numerous assumptions were made in an attempt to understand macroscopic phenomena, which are yet to be fully understood.

This is important research as superconductors are widely used in magnets, for example in Magnetic Resonance Imaging (MRI). By improving our understanding of how superconducting wires function under different conditions, and what occurs at these intriguing vortex states, we can in turn improve their capabilities when used in applications. Further research into the Bragg glass phenomenon could bring us closer to superconductors that function more effectively at elevated magnetic fields in applications such as MRI, thus impacting the healthcare landscape.

Optimising SANS for the future of neutron research

Given the potential of SANS to help a range of potential scientific fields, including biology and medicine, and improve our understanding of materials, other researchers at ILL are focusing on optimising the experimental technique, in a way that may particularly benefit specific fields.

Recently, researchers from the Technical University of Berlin, using the D11 instrument at ILL, successfully developed a new sample environment for SANS, publishing their work in Scientific Reports. This new development will allow ongoing chemical reactions to be observed in-situ via SANS.

The significance of this progress is quite clear when compared to previous work. The standard use of a SANS instrument is to measure samples in a “static” manner. In this case, the samples are prepared beforehand and the structures that are measured are those of the final or equilibrium state. In many cases this is sufficient, however, there are also cases where researchers would like more detail about how these structures form and how they react to changing chemical environments. The continuous-flow method allows these structural transitions to be observed as they occur, and, together with a combination of complementary chemical characterisation techniques, provides a more complete picture of how samples change during rapid or sensitive chemical processes. Such experiments are especially useful for establishing the relationship between the function or properties of materials and their structure at the nanoscale, particularly in the case of polymeric or biological systems.

The researchers successfully demonstrated their new sample environment using the D11 instrument at ILL. They investigated an aqueous surfactant solution (the primary ingredient of household and personal cleaning products), which undergoes significant structural changes in response to a change in pH, in order to demonstrate the benefits of the continuous-flow method. The sample was observed and characterised over the course of a potentiometric titration. This process is similar to a classical titration experiment using indicators that respond to pH and result in colour changes, but the progress of the reaction is instead tracked through electrodes that measure the effective concentration of hydrogen ions. They found that their method was efficient in enabling the collection of a great deal of structural detail on the sample as it changed in response to differences in pH.

The paper indicates that the understanding of reactions in biological samples and soft-matter structures will be significantly enhanced by this new SANS sample environment. Although similar techniques have previously been used on SAXS instruments (the X-ray analogue of SANS), they may not be as well suited for biological and soft-matter samples. Not only can high intensity X-rays damage or destroy sensitive samples, the lack of contrast between organic materials can also make it difficult to get precise information on more complex, multicomponent structures. Expanding the range of experiments that can be performed on SANS instruments will provide scientists with more tools to investigate complex soft-matter systems undergoing chemical change. This may be of particular benefit to the fields of molecular biology and biochemistry where the interplay between the chemistry, structure and function of macromolecules is often complex and not well understood.

With our world-leading SANS instruments at their fingertips, the researchers from the Technical University of Berlin have opened doors for future researchers across biological and soft-matter communities wishing to utilise the impressive power and flexibility of SANS instruments for their studies.

As these three stories show, whether probing deep into unexplored states of matter, or examining the structures which are core to our biological make-up, SANS is allowing scientists to examine the world around us with more detail than ever before. Research across all scientific fields can benefit from a fundamental understanding of the molecular mechanisms and structures at play in their research, and the continued upgrading and refinement of the SANS technique, such as the development of new sample environments as we have discussed, will make SANS an even more accessible and useful tool for science.

The D11 and D22 instruments at ILL were used for small angle neutron scattering experiments (SANS) in these studies.

 References:

• A small-angle neutron scattering environment for in-situ observation of chemical processes. D. Hayward et al. Scientific Reports (2018). doi: 10.1038/s41598-018-24718-z
• Elucidating the Solvent Effect on the Switch of the Helicity of Poly(quinoxaline-2,3-diyl)s: A Conformational Analysis by Small-Angle Neutron Scattering. Y. Nagata et al. Journal of the American Chemical Society (2018). doi: 10.1021/jacs.7b11626. 
• Decomposing the Bragg glass and the Peak Effect in a Type-II superconductor. R. Toft-Petersen et al. Nature Communications (2018). doi: 10.1038/s41467-018-03267-