Announcements - CNBC Expands Capacity for Research on Nanotechnologies, Soft and Biologically Relevant Materials

Small Angle Neutron Scattering

January 28, 2009 — Chalk River, Ontario

Many drugs produce unwanted side effects because they affect the entire body, that is, both healthy and diseased tissue. When drugs are designed to target diseased cells and leave healthy cells alone, treatments are more effective and reduce side effects. Recent research at the National Research Council Canadian Neutron Beam Centre (NRC-CNBC) in collaboration with the National Research Council Institute for Biological Sciences (NRC-IBS) involves the development of such targeted drugs using materials similar to what is found in our bodies naturally. For example, liposomes, which are microscopic balls, can be used to carry drugs and diagnostic contrast agents in their interior compartments. The outer walls of the spheres can be designed to carry molecules that cause the ball to stick to a specific tissue.

Diagram of a liposome

Drs. Mu-Ping Nieh and John Katsaras, researchers at the CNBC, have been working on developing liposomes that carry contrast agents, which will improve magnetic resonance imaging (MRI) for diagnosis of disease. Their liposomes are designed to be of uniform consistency, stable, and self-assembling – essential characteristics for effective use and industrial-scale production. While previous research focused on long-chain phospholipids that naturally form liposomes with multiple layers, their liposomes form a single layer resulting in a greater loading capacity, which is a significant improvement over multiple-layer liposomes.

One tool that is needed to study liposomes is Small Angle Neutron Scattering (SANS). SANS enables study of materials with nanometre-scale molecular structures and shapes. Thus, SANS is frequently used on nanotechnologies, soft materials, and biologically relevant materials. Using SANS, one can not only determine important features of these liposomes such as their size and their number of layers, but one can also resolve the shapes of aggregates in solutions, measure the molecular weights of polymers, learn about interactions between molecules and even parts of molecules, and detect patterns in the structure of materials less than 100 nanometres in scale.

SANS instruments are typically used with a source of cold neutrons, which exists at several foreign facilities, but the available beam time at these facilities falls short of meeting user demands. To help meet this need, CNBC has devised a way to compensate in part for the lack of a cold neutron source and adapt the N5 triple-axis spectrometer to perform Small Angle Neutron Scattering (SANS) measurements. The proof-of-principle occurred with the examination of polystyrene microsphere samples. The SANS data obtained at the CNBC practically matched the same measurements performed at a national facility employing cold neutrons south of the border. The details of the N5 spectrometer's adaptation for SANS was published in Review of Scientific Instruments [1] and is available online free of charge.

As a national user facility, CNBC assists external researchers to conduct their experiments using neutrons. Based on the successful demonstration of SANS using the N5 spectrometer, CNBC is accepting proposals to access beam time for SANS experiments. Those interested may submit a proposal for beam time. The CNBC has already been able to assist university and government researchers to use SANS to study polymers for applications in environmental management [2-3], and in fuel cells [4].

Further resources about SANS and recent CNBC publications

The theory of SANS is documented online by Stephen King, ISIS staff scientist. The details of the N5 spectrometer's adaptation for SANS are provided in [1]. SANS was used by CNBC staff to identify the structures of bio-surfactants doped with heavy metal ions [2] or organic compounds [3] and to resolve the structure of a di-block copolymer designed for proton exchange membranes used in fuel cells [4].

[1] Nieh, M.-P.; Yamani, Z.; Kučerka, N.; Katsaras, J.; Burgess, D.; and Breton, H. Adapting a Triple-Axis Spectrometer for Small Angle Neutron Scattering Measurements. Rev. Sci. Instrum. 2008, 79, 095102. doi:10.1063/1.2969254.

[2] Dahrazma, B.; Mulligan, C. N.; Nieh, M.-P. Effects of additives on the structure of rhamnolipid (biosurfactant): A small-angle neutron scattering (SANS) study J. Colloid Interf. Sci. 2008, 319, 590-593.

[3] Yuan, G.; Mulligan, C. N.; Nieh, M.-P. Small Angle Neutron Scattering (SANS) Study on Morphological Transformation of Rhamnolipid Aggregates Induced by Styrene. (Will be soon submitted to Langmuir).

[4] Nieh, M.-P.; Guiver, M. D.; Kim, D. S.; Ding, J.; Norsten, T. Morphology of Comb-Shaped Proton Exchange Membrane Copolymers Based on a Neutron Scattering Study. Macromolecules 2008, 41, 6176-6182.