Despite recent advances in analytical and computational chemistry, lipid identification remains a significant challenge in lipidomics. Ion-mobility spectrometry provides an accurate measure of the molecules’ rotationally averaged collision cross-section (CCS) in the gas phase and is thus related to ionic shape. Here, we investigate the use of CCS as a highly specific molecular descriptor for identifying lipids in biological samples. Using traveling wave ion mobility mass spectrometry (MS), we measured the CCS values of over 200 lipids within multiple chemical classes. CCS values derived from ion mobility were not affected by instrument settings or chromatographic conditions, and they were highly reproducible on instruments located in independent laboratories (interlaboratory RSD < 3% for 98% of molecules). CCS values were used as additional molecular descriptors to identify brain lipids using a variety of traditional lipidomic approaches. The addition of CCS improved the reproducibility of analysis in a liquid chromatography-MS workflow and maximized the separation of isobaric species and the signal-to-noise ratio in direct-MS analyses (e.g., “shotgun” lipidomics and MS imaging). These results indicate that adding CCS to databases and lipidomics workflows increases the specificity and selectivity of analysis, thus improving the confidence in lipid identification compared to traditional analytical approaches. The CCS/accurate-mass database described here is made publicly available.

The isolation of ligands for large numbers of proteins is an important goal in proteomics. Whereas peptide libraries are rich sources of protein-binding molecules, native peptides have certain undesirable properties, such as sensitivity to proteases that make them less than ideal for some applications. We report here the construction and characterization of large, chemically diverse combinatorial libraries of peptoids (N-substituted oligoglycines). A protocol for the isolation of specific protein-binding molecules from these libraries is described. These data suggest that peptoid libraries will prove to be inexpensive and convenient sources of protein ligands.

Microwave irradiation reduces the reaction time for the solid-phase synthesis of peptoids. Under these conditions, coupling of each residue requires only 1 min. The purity and yields of peptoids synthesized in this way are as good as or better than those achieved using standard methods. [reaction: see text]

Seeing red: A new methodology for the on‐bead screening of proteins has been developed with the aid of red‐emitting quantum dots. Use of this nanomaterial allowed a dual‐color fluorescence assay to be developed that overcomes the limitation of the autofluorescence of TentaGel beads. The figure shows a positive control (red fluorescence) and a negative control (background green fluorescence).

Fluorocarbons are lipophobic and non-polar molecules that exhibit remarkable bio-compatibility, with applications in liquid ventilation and synthetic blood. The unique properties of these compounds have also enabled mass spectrometry imaging of tissues where the fluorocarbons act as a Teflon-like coating for nanostructured surfaces to assist in desorption/ionization. Here we report fluorinated gold nanoparticles (f-AuNPs) designed to facilitate nanostructure imaging mass spectrometry. Irradiation of f-AuNPs results in the release of the fluorocarbon ligands providing a driving force for analyte desorption. The f-AuNPs allow for the mass spectrometry analysis of both lipophilic and polar (central carbon) metabolites. An important property of AuNPs is that they also act as contrast agents for X-ray microtomography and electron microscopy, a feature we have exploited by infusing f-AuNPs into tissue via fluorocarbon liquids to facilitate multi-modal (molecular and anatomical) imaging.