Cluster Impact Desolvation: A New Method of Mass Spectrometry of Biological Molecules

There is a significant demand for methods to detect and determine the masses of very large biomoleculessuch as proteins, nucleic acids and carbohydrates, using mass spectrometry. The major barrier to such measurements is the difficulty of generating intact gas-phase ions of these large and often fragile molecules. The earliest techniques to achieve success used the impact of energetic atomic projectiles to desorb intact ions from surfaces, but this approach was limited by the extensive radiation damage caused by such projectiles. A variant of these methods, massive cluster impact (MCI), uses massive, highly charged cluster projectiles which have been shown to desorb analyte ions without causing extensive radiation damage, but this approach has not been widely investigated. The primary methods in use today are Matrix Assisted Laser Desorption/Ionization (MALDI) and ElectroSpray Ionization (ESI).In the MALDI technique, a solid target is prepared and irradiated by a pulsed laser resulting in explosive evaporation of a shallow layer of the matrix, carrying the biomolecular analyte into the gas phase. The major disadvantage of MALDI involves the difficulty of readily interfacing with liquid chromatography techniques and the fact that a substantial amount of chemistry can occur in the irradiated volume, leading to either fragmentation of the analyte or extensive formation of clusters, which degrade mass resolution. In ESI, a liquid solution of the biomolecular analyte is electrosprayed in air or an inert gas. The electrospray process produces a divergent spray of charged droplets, which contain analyte molecules. A fraction of these droplets is drawn through a fine heated capillary where the solvent evaporates leaving highly-charged gas-phase ions of the analyte molecules. The major disadvantage of ESI is that ions are produced with a wide range of charges. The method is thus very poorly suited to analyzing mixtures.Researchers at Arizona State University have devised a new method, termed "Cluster Impact Desolvation (CID)." This new method combines the advantages of electrospray ionization with a novel new desolvation procedure which produces ions with high efficiency and are formed with a low initial energy at a surface from which they can be collected with high efficiency using standard ion optical designs. Typical cluster sizes are estimated to be in the range 10 6 - 107 Da with positive (negative) charges corresponding to ~ 50 - 100 excess (deficient) protons. With an accelerating voltage ~ 5 - 10 kV, these clusters achieve kinetic energies as high as 1 MeV, sufficient to cause shock heating when they impact a surface.