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Categorizing Cells on the Basis of their Chemical Profiles: Progress in Single-Cell Mass Spectrometry Troy J. Comi, Thanh D. Do, Stanislav S. Rubakhin, and Jonathan V. Sweedler* Department of Chemistry and the Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States tions of cells emerge as unique, with individual characteristics and properties.3 Early successes of single-cell electrophoresis were reported from the 1950s to 1970s. In 1956, Edström8 successfully determined the relative composition of ribose nucleic acids within large, mammalian neuronal cells by microphoresis with a cellulose fiber. Separation of hemoglobin from individual erythrocytes using polyacrylamide fiber electrophoresis followed in 1965.9 Two-dimensional gel electrophroesis of proteins from single Aplysia californica neurons was reported in 1977,10 around the time single-cell mass spectrometry (MS) began to develop. In their pioneering work in the 1970s, Hillenkamp and co-workers11 used laser ablation mass analysis to generate mass spectra from tissue sections and cultured cells. They ablated several