The field of lipidomics has been significantly advanced by mass spectrometric analysis, but the distinction and quantitation of the unsaturated lipid isomers, however, remain a long-standing challenge.
A new analytical tool for medical applications might be used to diagnose cancer more rapidly than conventional methods and has implications for the field of lipidomics, which involves the identification and quantification of cellular lipid molecules, how they interact with other components in cells and their role in biological systems.
Scientists at Purdue University (West Lafayette, IN, USA) and their colleagues developed a new approach to easily pinpoint the location of double bonds between carbon atoms in lipid molecules, allowing the identification of “isomers,” a capability that could lead to the early diagnosis of cancer. Lipids are important components of living cells and include fats, oils and waxes. They may exist as isomers, which have identical mass but possess subtle structural differences not easily detected by conventional analytical technologies. The new tool uses techniques called tandem mass spectrometry and the Paternò-Büchi reaction.
In tandem mass spectrometry, charged molecules are fragmented into pieces, which are then measured and identified by their mass. A so-called “shotgun lipidomics” analysis enhanced by the Paternò-Büchi photochemical reaction, which modifies double bonds into rings that can then be easily cleaved into two parts. This allows the bonds to be measured and identified using mass spectrometry. The method can be completed within hours, starting with small amounts of tissue, tens of milligrams, compared to weeks and hundreds of milligrams using conventional analytical techniques.
Although the study was conducted using a conventional laboratory mass spectrometer, the same operation could be carried out with a new miniature mass spectrometer. Whereas conventional mass spectrometers are relatively heavy, bulky instruments, Purdue scientists have recently developed miniature mass spectrometers, including the Mini 12, (PURSPEC Technologies Inc.; West Lafayette, IN, USA) which weighs 18 kg, is 31.8 cm wide and 40.6 cm high. The system was used to identify 96 unsaturated fatty acids and glycerophospholipids in the brain tissue of rats, revealing that 50% of the lipids were mixtures of isomers characterized by the location of their carbon-carbon double bonds.
Zheng Ouyang, PhD, a professor and coauthor of the study, said, “Direct analysis using ambient sampling methods will further speed up the analysis process from hours to a minute. We want to apply this to imaging to study tissue, and we currently are integrating this method into miniature mass spectrometry systems. Eventually we hope to have biologists and medical professionals using it.” The study was published on February 22, 2016, in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).