Imaging mass spectrometry has emerged as a powerful technique based on time-of-flight secondary-ion mass spectrometry (TOF-SIMS) [1] and matrix-assisted laser desorption/ ionization (MALDI). [2,3] However, until now, the massspectrometric analysis of biological tissues has been limited to techniques that require sample preparation after which the sample is confined to the high-vacuum region of the instrument, thus making this approach inaccessible to further physical or chemical manipulations. Herein, direct chemical profiling of biological tissues is achieved under ambient conditions at atmospheric pressure by desorption electrospray ionization mass spectrometry (DESI-MS), [4] which is a new and versatile method for the creation of ions from surfaces outside of the mass spectrometer. The profiling of lipids in biological tissues by using DESI-MS provides highly sensitive and chemically specific information almost instantaneously. This capability is illustrated by examples in which phospholipid profiles of mouse pancreas, rat brain, and metastatic human-liver adenocarcinoma tissues are obtained without any sample pretreatment.
Biological membranes serve as crucial mediators in cellular differentiation and proliferation; the former being important in tumor formation, the latter in tumor progression. Phospholipids play important roles in maintaining the structural integrity of the cell by forming of the characteristic bilayer of the membrane and by serving as key mediators in important cellular events, for example, cell signaling and protein sorting on so-called lipid rafts. As such, the chemical and physical properties of the cell membrane are determined by the phospholipid composition. Alterations in the phospholipid composition of tissues have been reported for certain diseases, including cancer and Alzheimers disease. [5] Importantly, the abundance of certain phospholipids and their enzymatic by-products has been associated with malignant transformations in some tissues. [6] These findings emphasize the importance of the determination of the composition of phospholipids in biological tissues, information which may serve as prognostic variables in diseased and nondiseased tissues.
Mass spectrometry has been used extensively to investigate lipids (e.g., phospholipids), [7] although not under ambient conditions. MALDI-TOF has been used for the analysis of lipids in lens tissue [8] and has emerged as a particularly powerful technique for profiling the spatial distributions of peptides and proteins in biological tissues. [3,9] An alternative molecular imaging method, TOF-SIMS, has been applied to the investigation of the phosphocholine distribution in Tetrahymena mating junction by monitoring the phosphocholine head group at m/z 184. [10] In another report, TOF-SIMS imaging of lipids in mouse-brain sections was performed and various sulfatides, as well as phosphatidylinositol, phosphatidylcholine, and cholesterol, were identified and their spatial distributions determined. [11] DESI belongs to the family of spray ionization methods, such as electrospray ionization (ESI), [12] as well as to the family of desorption ionization methods. [13] DESI allows direct and rapid analysis of surfaces without sample preparation or the need to introduce the sample into a vacuum system. [4] The methodology has been applied to the analysis of trace levels of many classes of compounds, including peptides, proteins, nucleotides, nitroaromatic compounds, and others.