Time-delayed extraction, mass resolution

Fig. 3.5. Schematic representation of a time-of-flight mass analyser with reflectron and external ion storage for time-delay extraction. Ions that enter the field-free drift region migrate to the detector at a rate that is dependent on their m/z ratio. The reflectron lenses compensate for variations in kinetic energies of the injected ions these variations would otherwise produce broadened peaks and loss of spectral resolution.

Time-of-flight reflectron mass spectrometry with some form of time-delay extraction has become popular for large-molecule characterizations. Resolutions of up to 15,000 can be routinely achieved over very broad mass ranges, extending up to about 300,000 Da. As noted previously, time-of-flight analysers are particularly compatible with laser-based ionization techniques that produce very short bursts of ions. They are also very fast, with mass spectra often obtainable in about 25 p,s. Finally, time-of-flight analysers have been paired with a quadrupole to produce a hybrid two-dimensional mass spectrometry system that has found widespread use in protein analyses. This device will be discussed in more detail in the section on two-dimensional mass spectrometry. 

If delayed extraction increases the mass resolution without degradation of sensitivity compared with continuous extraction, it also has limitations. Indeed, delayed extraction complicates the mass calibration procedure. It can only be optimized for part of the mass range at a time and is less effective at high mass. Delayed extraction partially decouples ion production from the flight time analysis, thus improving the pulsed beam definition. However, calibration, resolution and mass accuracy are still affected by conditions in the source. For instance, in the usual axial MALDI-TOF experiments, optimum focusing conditions depend on laser pulse width and fluence, the type of sample matrix, the sample preparation method, and even the location of the laser spot on the sample. 

In the example of ions A, B, and C above, by delaying the extraction voltage relative to ion formation, the ions are allowed to expand, as a function of their inherent velocities, within the source under field-free conditions. Ion A therefore moves away from the extraction lens, ion C moves toward the extraction lens, and ion B remains stationary When the extraction voltage is applied, ions A and C will have moved to regions of higher and lower extraction potential respectively, relative to their initial positions within the source (see Fig. 20b). Because of this, the turnaround time for ion A will decrease, and the additional voltage push for ion C will be minimized. This ultimately improves mass resolution because the ion source residence time differentials between A, B, and C are minimized. 

LL Haney, DE Riederer. Delayed extraction for improved resolution of ion/surface collision products by time-of-flight mass spectrometry. Anal Chim Acta 397 225-233,1999. 

A significant improvement in mass resolution, respect to the above described "continuous extraction" procedure, was obtained by the introduction of "time lag focusing" or "delayed extraction" (DE). This principle can be used in both linear and reflection mode yielding an improvement in resolution by a factor of above ten in both cases. 

Vitalini, D., Mineo, R, and Scamjxjrrino, E., Effect of Combined Changes in Delayed Extraction and Potential Gradient on the Mass Resolution and Ion Discrimination in the Analysis of Polydisperse Poymers and Polymer Blends by Delayed Extraction Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry, Rapid Comm. Mass. Spectrom., 13, 2511,1999. 

Further performance improvements in analysing nucleic acids could be achieved by the introduction of 3-hydroxypicolinic add as matrix [8] and the introduction of delayed extraction in a linear time-of-flight mass spectrometer [9]. If, for MALDI Fourier transform mass spectrometry, the molecular weight range in analysing nucleic add fragments could be extended further this type of MALDI MS would become of significant value due to the extraordinary resolution possible [10, 11]. In order to reach the sensitivity level necessary for MALDI-TOF MS analysis an amplification step has to be incorporated into the sample preparation process for... 

Sulfur produces a series of intense peaks in both ionization modes. Peaks are more prolific in the negative mode, where signals are observed for the entire Sf to Si5 series. In contrast, in the positive mode, fewer peaks are observed from sulfur. Higher laser fiuences are required to observe peaks for very low mass ions such as mJz 32 and 64. Unfortunately, higher laser fluence results in the deterioration of peak resolution, shape, and intensity of the peaks for more abundant ions. However, with optimum adjustment of delayed extraction time and voltage, resolution of all isotopolog peaks can be achieved. Sulfur exists in nature as a mixture of four isotopes [94.93%], [0.76%],... 

The section was analyzed by MALDI TOE MS using an Autoflex 11 mass spectrometer operated in positive linear mode geometry under delayed extraction conditions time focused at w/z 15,000. In this case, signal resolutions M/A.M measured at lull width at half maximum) close to 1,000 were attainable for ions at or around m/z 15,000, whereas acceptable resolutions in the range of 600 were obtainable for m/z values in the range of 5,000-25,000. 

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