The lateral organization of binary, phase-separated supported lipid bilayers has been probed on the length scales of tens to hundreds of nanometers using a high-resolution imaging secondary ion mass spectrometry technique called a NanoSIMS. [228], [238], [244], [263]  Since phosphocholine lipids are composed of the same basic elements (H, C, N, O, and P), the synthesis of isotopically-labeled lipids was necessary to differentiate these species.  When supported bilayers are formed with different isotopic mixtures of lipids and the samples are flash-frozen and freeze-dried, very high spatial resolution images of membrane domains can be obtained with the NanoSIMS.  The ultimate spatial resolution is on the order of 50 nm with extremely high sensitivity.  Because of the specific use of isotopic labels, this is a genuine analytical method permitting the semi-quantitative analysis of biological membranes and model systems.  These measurements are currently performed on an instrument at the Livermore National Laboratory; we will have a NanoSIMs instrument at Stanford within the next year. Current work focuses on more complex phases where cholesterol, other lipids, and proteins are imaged.

"Advances in Imaging Secondary Ion Mass Spectrometry for Biological Samples", Steven G. Boxer, Mary L. Kraft and Peter K. Weber, Annual Rev. Biophys., 38, 53-74, (2009). [pdf]

"Phase Separation of Lipid Membranes Analyzed with High-Resolution Secondary Ion Mass Spectrometry", Mary L. Kraft, Peter K. Weber, Marjorie L. Longo, Ian D. Hutcheon, and Steven G. Boxer, Science, 313, 1948-1951 (2006). [pdf] [Supplement] See also: [Jay Groves' Perspectives in Science]

"Quantitative Analysis of Supported Membrane Composition Using the NanoSIMS", Mary L. Kraft, Simon Foster Fishel, Carine Galli Marxer, Peter K. Weber, Ian D. Hutcheon, and Steven G. Boxer, Applied Surface Science, 252, 6950-6956 (2006). [pdf]