Matrix-assisted laser desorption/ionization time-of-flight (Maldi-Tof) mass spectrometry offers a robust tool for analysis of proteins and peptides. However, because the technique’s signal quality is concentration-dependent, high-quality signals may prove elusive if only a limited amount of sample is available.Researchers can improve the signal intensity by producing smaller Maldi spots that have the same concentrations of sample. Tingting Tu and Michael L. Gross of Washington University in St. Louis and Andrew D. Sauter of Nanoliter LLC in Henderson, Nev., have demonstrated a technique that makes spots as small as a few nanoliters. They reported the method at the 2007 meeting of the American Society for Mass Spectrometry (ASMS) in Indianapolis.The technique employs a nanoliter syringe and what the researchers call “induction-based fluidics” to ensure precise deposition of Maldi spots. This involves using electric fields to fly liquids to targets of all types from many devices — for example, syringes, pipettes or pumps — in a manner akin to how mass spectrometers fly gas phase ions, said Sauter, the inventor of the technology.He added that the induction-based technique offers extremely low per-channel cost without moving parts, in a manner similar to ink-jet technology. Unlike an ink jet, however, it can move vector liquids over both short and long distances, from microns to meters. Furthermore, in certain configurations, investigators can use the technique to deposit nanoliters of even viscous liquids such as glycerin and human serum.In recent work, the researchers demonstrated the technique by performing Maldi-Tof mass spectrometry with nanospots and 0.5-μl spots deposited by conventional means. For the nanoliter spots, they positioned a syringe containing the sample in the nanoliter wave’s inductor and energized the needle to charge a drop of known volume at the tip, thus depositing it on the Maldi plate. They obtained the spectra with a device made by Applied Biosystems of Foster City, Calif., operating in the positive-ion reflectron mode.The experiments confirmed the efficacy of the technique, and the nanoliter spots showed significant signal enhancement with respect to the normal-size spots. The researchers attributed the higher-quality signal to the increased spatial concentration of sample within the spot as well as to a large reduction in the matrix-caused noise. Additionally, they employed liquid ionic matrices, a technique championed by Gross to ensure sample homogeneity. The ASMS poster reported both a five times increase in analysis reproducibility and an approximately 103 times increase in sensitivity, approaching that of solid matrices.