AbstractThis paper focuses on development of time‐of‐flight (TOF) mass spectrometry in response to the invention of matrix‐assisted laser desorption/ionization (MALDI). Before this breakthrough ionization technique for nonvolatile molecules, TOF was generally considered as a useful tool for exotic studies of ion properties but was not widely applied to analytical problems. Improved TOF instruments and software that allow the full potential power of MALDI to be applied to difficult biological applications are described. A theoretical approach to the design and optimization of MALDI‐TOF instruments for particular applications is presented. Experimental data are provided that are in excellent agreement with theoretical predictions of resolving power and mass accuracy. Data on sensitivity and dynamic range using kilohertz laser rates are also summarized. These results indicate that combinations of high‐performance MALDI‐TOF and TOF‐TOF with off‐line high‐capacity separations may ultimately provide throughput and dynamic range several orders of magnitude greater than those currently available with electrospray LC‐MS and MS‐MS. Copyright © 2009 John Wiley & Sons, Ltd.

Advances in laser desorption time-of-flight mass spectrometry for biological applications

作者: Vestal, Marvin L.

Several new instruments have been designed using a recently developed theor. approach for optimizing the performance of each of the major elements of a time-of-flight (TOF) mass spectrometer.The major emphasis in the design and construction of these instrument is on biol. applications employing Matrix Assisted Laser Desorption/Ionization (MALDI).The optimized elements include one and two-stage MALDI ion sources, two-stage ion mirrors, both gridded and gridless, timed-ion selectors, ion focusing and deflecting elements, pulsed and static ion accelerators, ion fragmentors, and ion detectors.Prototype instruments were constructed to allow performance of each of these elements to be evaluated and compared with theor. predictions.Recent results demonstrating the performance of these instruments for selected biol. applications are summarized.

Sensitivity of MALDI-TOF and TOF-TOF: Current status and prospects for improvement

作者: Vestal, Marvin L.

Recent work has substantially improved the sensitivity particularly in reflector MS and MS-MS modes by increasing the efficiency of the overall processes involved in ion production, transmission, and detection.But if sensitivity is defined in an operational sense as the min. amount of sample required to produce a desired result with high confidence, then the improvements in sensitivity are more modest.The two main reasons for this are interference from chem. noise associated with impurities in matrixes and solvents and poor sample utilization.A method is described for routine determination of overall efficiency.Using higher laser rates and smaller sample spots, it is relatively easy to desorb all of the sample.The detector response can be calibrated in terms of the average peak area per ion by recording the single-ion signals under very low laser intensity.This gives a calibration factor of area/ion in arbitrary height units multiplied by width in nanoseconds (or channels) for a single ion.Integrated total intensity over a peak or any region of the spectrum multiplied by the number of laser shots averaged and divided by this calibration factor gives the total number of ions in the peak or region.The integrated number of ions detected divided by the number of mols. consumed in complete desorption of a known sample amount provides an accurate measurement of overall efficiency.Application of this method may identify some areas where efficiency can be improved further, but at present it appears that chem. noise is the major limit on useful sensitivity.This may be addressed by improving the resolving power in both MS and MS-MS to better sep. samples from interferences and by software improvements that allow more confident, automated extraction and interpretation of the spectra of samples even in the presence of chem. noise.

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