Continuous ionization sources

A 30-lb field-portable quadrupole ion trap TOF (QitTof) mass spectrometer with an atmospheric photoionization source was constructed [17]. The photoionization source has the ability to choose a narrow-band ionization energy that is sufficiently high to ionize and detect most compounds of interest but low enough to avoid ionization of most common air constituents, such as N2, 02, H20, C02, CO, Ar, etc. Fragmentation is minimal because ionization occurs just above the ionization thresholds, with very little excess energy. The ion trap stores ions from a continuous ionization source followed by pulsed extraction into the TOF mass analyzer. 

Another significant challenge remains in further increasing the efficiency with which sample species are utilized through increased ion throughput and duty factor. Currently many of the ions generated by continuous ionization sources are lost because of the pulsed nature of the instrument. Realization of higher duty factor and the unit transmission efficiency of which TOF-MS is capable could propel the TOF-MS into a sensitivity realm well beyond that of current mass analyzers. 

While this level of mass measurement accuracy is rarely necessary in quantitative analyses, the fast spectral acquisition rates of TOFs have been used to advantage in methods employing extremely fast GC separations. Standalone TOF analyzers cannot readily mass select ions, thus precluding the use of SIM mode. As such, quantitative assays performed on TOFs must currently make use of full scan MS mode. Moreover, TOFs have a low duty cycle when operated with continuous ionization sources since the slowest (highest m/z) ions in one ion packet accelerated into the flight tube must be allowed to reach the detector before the next packet is selected. At the other extreme, TOF analyzers have an essentially 100% duty cycle when directly interfaced to pulsed ionization sources like MALDI if the ionization pulse is synchronized with the TOF acceleration. 

The first time-of-flight mass spectrometers used electron impact (El) ionization, so that the need for accomodating continuous ionization sources was recognized from the beginning. Many of these early instruments utilized beam-deflection techniques " to admit a narrow initial ion packet into the flight tube. Later, Pinkston et al. " utilized beam deflection in an E-TOF (where E is an electrostatic energy... 

One of the challenges has been to develop TOF mass spectrometers, which are basically pulsed instruments that can be used with continuous ionization sources. Since the major interest here is electrospray, then the requirement is also compatibility with ionization at atmospheric or intermediate pressure. 

A further important property of the two instruments concerns the nature of any ion sources used with them. Magnetic-sector instruments work best with a continuous ion beam produced with an electron ionization or chemical ionization source. Sources that produce pulses of ions, such as with laser desorption or radioactive (Californium) sources, are not compatible with the need for a continuous beam. However, these pulsed sources are ideal for the TOF analyzer because, in such a system, ions of all m/z values must begin their flight to the ion detector at the same instant in... 

A major advantage of the TOF mass spectrometer is its fast response time and its applicability to ionization methods that produce ions in pulses. As discussed earlier, because all ions follow the same path, all ions need to leave the ion source at the same time if there is to be no overlap between m/z values at the detector. In turn, if ions are produced continuously as in a typical electron ionization source, then samples of these ions must be utihzed in pulses by switching the ion extraction field on and off very quickly (Figure 26.4). 

The compatibility is excellent with continuous ion sources such as ESI, dynamic SIMS, CF-FAB, ICP, El, Cl, etc. Sector instalments are not well-suited for pulsed ionization methods, although there are examples where MALDI sources have been utilized [225-229]. Sector instruments are usually larger and more expensive than other mass analyzers, such as TOFs, quadrupole filters, and traps. 

Like sector analyzers, quadrupole analyzers are well suited for continuous ion sources such as ESI, but are not well-suited for pulsed ionization methods. Quadmpole mass spectrometers are generally substantially cheaper and smaller than sector instruments and Qq-TOFs. They are very often used in combination with GC and LC, and single or triple quadmpole mass filters are very common benchtop instruments for routine measurements. 

Many interfaces have been developed to meet these demanding challenges. Some of these coupling methods, such as the moving belt or the particle beam interface, are based on the concomitant elimination of the solvent before it enters the mass spectrometer. Other methods such as direct liquid introduction (DLI) or continuous flow FAB rely on splitting the flow of the liquid that is introduced into the interface in order to obtain a flow that can be directly infused into the ionization source. However, these types of interfaces can only handle a fraction of the liquid flow from the LC. 

As explained above, the continuous radioactive source used in our IMS also produces small, and sometimes troublesome, amounts of impurities within the ion source. In an effort to eliminate this problem, we are presently exploring the use of other source designs by which less radiation damage is done to the source gas. One of these alternative ionization methods is based on the photoemission of electrons from the back side of a gold foil. This ion source offers an attractive advantage for the study of negative IM reactions in that it can be shut off during most of the IMS duty cycle. 

Mass Spectrometry of Carotenoids NOTE For LC/MS or flow injection using continuous-flow FAB, the mass spectrometer must be equipped with a continuous-flow ionization source. 

Mass spectrometer or tandem mass spectrometer (JEOL, Micromass, MAT from ThermoFinnigan) equipped with direct insertion probe and fast atom bombardment (FAB) or liquid secondary ion mass spectrometry (LSIMS) for LC/MS or flow injection using continuous-flow FAB, mass spectrometer must be equipped with continuous-flow ionization source... 

Since FAB (or LSIMS) requires that the analyte be dissolved in a liquid matrix, this ionization technique was easily adapted for infusion of solution-phase samples into the FAB ionization source, in an approach known as continuous-flow FAB. Continuous-flow FAB was connected to microbore HPLC columns for LC/MS applications (Ito et al., 1985). Since this method is limited to microbore HPLC applications at flow rates of <10 pl/min... 

The obvious benefit of the quadrupole ion trap is that it is an ion storage device. Therefore, ions can be both accumulated and stored for extended periods. Accumulation can occur over a continuous ionization event or over multiple pulsed ionization periods. When used with pulsed ionization sources, duty cycle, defined in terms of sample utilization, can be as high as 100%. Because a broad range of atomic ions can be stored simultaneously, the quadrupole ion trap is a promising analyzer for transient peak analysis. 

Much of the work in the early development of the preceding techniques incorporated pulsed electron-impact ionization sources or any of several types of laser ionization techniques. In almost all of these cases the ions were created in a pulsed fashion in vacuum and formed in or sent into the acceleration region of the mass spectrometer, where a static acceleration field present there injected them into the mass spectrometer. Such ion sources use the TOF-MS very efficiently because the repetition rate of the spectrometer is limited by the frequency of the ionization event itself. This arrangement allows the TOF-MS to mass analyze of all of the ions formed completely. However, many of the most popular ionization techniques being used in inorganic analysis today are continuous in nature. 

MALDI differs from ESI in two major aspects (a) the MALDI ionization process is not continuous, but is a pulsed event, and (b) while the analytes for ESI are dissolved in the appropriate solvent and introduced into the ionization source, the MALDI analytes are dissolved and mixed with a solution of the appropriate matrix and then are cocrystallized with the matrix. Sensitivity for both techniques enables analyses at the low femtomole range (and even below), although most analyses are conducted at the low picomole range because of the greater convenience of sample handling at this level. Mass measurement accuracy, as indicated elsewhere in this discussion, depends on the choice of analyzer. These techniques are complementary and neither has exhibited dominance in the analysis of biological molecules. 

Contrary to most other ionization sources that yield a continuous ion beam, MALDI is a pulsed ionization technique that produces ions in bundles by an intermittent process. The pulsed nature of the MALDI source is well suited for the time-of-flight (TOF) analyser. In addition, the TOF analyser has the ability to analyse ions over a wide mass range and thus... 

---