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Protein analysis provides abundant information crucial to understanding mechanisms and giving insight into life on the molecular level. Because of its unparalleled sensitivity and specificity, mass spectrometry [1–4] is the premier method for protein analysis. The native protein conformation, key to understanding the structure and function of proteins,[2, 5–7] is difficult to determine by conventional electrospray ionization mass spectrometry (ESI-MS)[1–4] owing to multiple steps required for matrix cleanup.[8–10] The charge state distribution (CSD) of protein ions recorded using ESI-MS provides a highly sensitive tool to probe the overall compactness of a protein in solution,[11] and thus it is being used increasingly to gauge protein conformations.[11–13] Real-world protein samples such as cell materials contain intrinsically complex mixtures including liquids, salts, and almost every type of species involved in biological processes. Prior to protein analysis, specific sample pretreatments (separation, preconcentration, digestion, etc.) are usually required for most analytical techniques.[2–4] High-throughput protein analysis has been demonstrated using ambient ionization techniques such as desorption electrospray ionization (DESI),[14, 15] electrospray laser desorption/ionization (ELDI),[16] and ambient matrix-assisted laser desorption/ionization (MALDI).[17] These techniques are suitable for the characterization of proteins on solid surfaces with minimal sample pretreatment. However, conformational changes occur rapidly (10À12–102 s)[9] when the molecular environment of the native proteins is changed dramatically.[2, 11, 18] The use of drying …