Further Improvement of Resolution

Improved vacuum conditions effect an elongated mean free path for the ions and thus a lower risk of collision on their transit through the TOF analyzer. The background pressure in the analyzer is directly reflected by the resolution. [40] Despite improvements of resolving power in the order of a factor of two can be realized (Fig. 4.9), enhanced pumping systems alone are not able to effect a breakthrough in resolving power. 

Note With the exception of the quadrupole ion trap, which uses buffer gas to damp ion trajectories, a reduced background pressure, i.e., better vacuum, is also beneficial for all other types of mass analyzers. 

43] (The concept of using a time delay to separate charged species in space is also employed in ZEKE-PES and MATI, Chap. 2.10.3.) 

Note Unfortunately, establishing patents and trademarks has caused redundant names for almost the same thing Time Lag Focusing (TLF, Micromass) Delayed Extraction (DE, Applied Biosystems) Pulsed Ion Extraction (PIE, Bru-ker Daltonik). 

Example Regardless of the manufacturer of the hardware, the effect of a time lag on resolution is quite dramatic. The resolving power of linear instruments is improved by a factor of 3-4 and reflector instruments become better by a factor of about 2-3. [36] The advantages are obvious by comparison of the molecular ion signal of Ceo as obtained from a ReTOF instrument with continuous extraction (Fig. 4.7) and from the same instrument after upgrading with PIE (Fig. 4.12), or by examination of MALDI-TOF spectra of substance P, a low mass peptide, as obtained in continuous extraction mode and after PIE upgrade of the same instrument (Eig. 4.11). 

---

The resolution as adjusted by the U/V ratio cannot arbitrarily be increased, but is ultimately limited by the mechanical accuracy with which the rods are constructed and supported ( 10pm). [Ill] Above an m/z value characteristic of each quadrupole assembly, any further improvement of resolution can only be achieved at the cost of significantly reduced transmission. High-performance quadrupoles allowing for about 10-fold unit resolution have only recently been developed. [112]... 

A further improvement of resolution can be found in deep UV or X-ray lithography. This development requires special resist formulations that are sensitive (and sufficiently transparent) to these kinds of radiation. Although much research is going on in this field at present, this effort will probably increase if deep UV or X-ray projection tools become more readily available. 

Hence, application of the MAS technique for the investigation of quadrupole nuclei leads to a decrease of the linewidth of the CT by a factor of about 3.6. A further improvement of the resolution of the NMR spectra of quadrupole nuclei requires the application of more sophisticated techniques, such as the DOR (27) or the more recently developed MQMAS NMR spectroscopy (26,28). Until now, however, neither of these techniques has been applied for investigations of working solid catalysts, and they are therefore not considered in this review. 

Tire MALDI method is especially useful for complex mixtures of peptides and can be utilized in peptide sequencing. The technique is also appropriate for studying mixtures of glycoproteins. Negative-ion MALDI can be applied to oligonucleotide mixtures. Further improvements in resolution in both MALDI... 

Significant further improvement of this process resulted from solvent screening. It was found that acylations proceed faster and with even higher selectivity in tert-amyl alcohol [20]. Scheme 12.8 illustrates the impressive performance of this easy-to-handle kinetic resolution which works almost perfectly even at catalyst loadings as low as 0.5 mol% [20]. 

Several groups at ISOLDE are planning further improvements of their techniques. For each element the most appropriate experimental scheme has to be found. Today, collinear laser spectroscopy is the most general high-resolution and sensitive method for optical spectroscopy on radioactive beams delivered by on-line mass separators. Its sensitivity ranges from 10 - 10 atoms/s depending on the strength and multiplicity of the optical transitions. 

Other examples of application of this concept are presented in Table 7.2. It should be mentioned that the resolutions described in Table 7.2 intentionally are performed in nonoptimized conditions. Therefore, further improvement of the resolution efficiency should be possible when nucleation inhibitors are applied. The procedure clearly offers the opportunity to improve the outcome of a classical resolution without the need for stoichiometric mixtures of resolving agents. The original DR procedure as well as molecular modeling calculations32 can help in identifying efficient nucleation inhibitors. 

Direct analysis with the on-line ORD detector linked to the HPLC was hampered by peak broadening, which led to incomplete resolution of the two peptides. Diffusion in the large flow cell may be a major factor in this difficulty. Because detector response can be either positive or negative, it is important to have an excellent signal-to-noise ratio and baseline HPLC resolution of the peptide isomers to be able to quantitate the degree of racemization by this technique. While the on-line ORD detector is promising, further improvements in resolution as well as sensitivity are required for it to be useful for routine peptide analysis. 

This chapter has presented a review of the parameters involved in Mossbauer spectroscopy within the context of phase transformations. Although the Mossbauer effect can be considered a mature technique, now more than forty years old, technical developments continue to expand the experimental possibilities. Spatial resolution has improved within the last decade. The development of the Mossbauer milliprobe, for example, has enabled spatial resolution to be increased by more than two orders of magnitude (McCammon et al. 1991, McCammon 1994). Further improvement of spatial resolution may be anticipated with advances in nuclear forward scattering. Other possibilities on the horizon include development of a Mossbauer electron microscope which would focus conversion electrons using conventional electron optics (Rancourt and Klingelhofer 1994). 

A number of developments to further improve the resolution and specificity of the method have been reported [78,79], namely cross-over electrophoresis, rocket electrophoresis, two-dimensional Immunoelectrophoresis, and radioimmunoassay. 

If the dimensions of stationary phase coating thickness and diffusion distance to the film from the gas phase have been optimized, for further improvement of GC resolution, it becomes necessary to increase the length of the column. This is seen from the simple relation of Eq. (11.7), which indicates that for an optimal minimized value of H (the height equivalent to a theoretical plate) the number of plates, N, is proportional to the length of the column. From Eqs. (11.8) and (11.9) we note that the resolution is proportional to the square root of N. For columns packed with particles of optimal size, and operated at the optimal linear flow rate at the minimum of the Van Deempter curve (Fig. 11.3), the typical maximum pressure of 100 psi achievable from a regulated gas cylinder requires that most packed columns be less than 4-7 m long. More typically they are only 1 -2 m in length. These considerations hmit the resolution achievable in packed column GC. 

Although the mass resolution of commercial instruments is poor (unit mass resolution), substantial improvements can be realized on research instruments by reducing the scan speed and the frequency and amplitude of the resonance ejection signal [44,45]. For example, a resolution of 1.13 x 10 was achieved for a cluster of Csl ions at 3510 u with a 2000-fold decrease in the scan speed [44]. The reduction of the scan rate to 0.1 miq unit/s has led to a further improvement in resolution to 1.2 x 10 for mIq 614 [45]. A zoom scan, in which a narrow window of masses is scanned, is another alternative to enhance resolution. 

---