Continuous ionization

ESI has become the most commonly used interface for LC/MS. It was recognized by John Fenn and co-workers as an important interface for LC/MS immediately after they developed it as an ionization technique for MS. ESI transforms ions in solution to ions in the gas phase and may be used to analyze any polar molecule that makes a preformed ion in solution. The technique has facilitated the ionization of heat-labile compounds and high-molecular-weight molecules such as proteins and peptides. ESI is a continuous ionization method that is particularly suitable for use as an interface with FiPLC. It is the most widely accepted soft-ionization technique for the determination of molecular weights of a wide variety of analytes and, has made a significant impact on drug discovery and development since the late 1980s. 

Because the situation in vivo is normally dynamic, continual removal of the nonionized form of the compound from the inside of the membrane causes continued ionization rather than the attainment of an equilibrium ... 

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. 

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. 

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. 

TOF analysers are directly compatible with pulsed ionization techniques such as plasma or laser desorption because they provide short, precisely defined ionization times and a small ionization region. However, to take advantage of TOF analysers, it is interesting to combine such powerful analysers with continuous ionization techniques. These ionization techniques can be compatible with TOF analysers but require some adaptations to pulse the source or to transform a continuous ion beam into a pulsed process. For instance, the coupling of an ESI (or any other API) source with a TOF mass spectrometer is difficult, because ESI yields a continuous ion beam, whereas the TOF system works on a pulsed process. 

The value of / should not exceed approximately 0.1 to prevent continuous ionization of the lamp. 

Pulsed-mode acceleration is needed since continuous ionization and acceleration would lead to a continuous stream of all ions with overlapping masses. The sequence of events for pulsed operation is to turn on the electron source for 10" s to form a packet of ions, and then the accelerating voltage for 10" s to draw the ions into the drift tube. Then the power is turned off for the remainder of the pulse interval as the ion packets drift down the tube to the detector. 

These states are formed inside the continuous spectra of the total Hamiltonian and are responsible for phenomena such as resonances in electron scattering from atoms or molecules, autoionization, predissociation, etc. Furthermore, in this work we also consider as unstable states those states that are constructs of the time-independent theory of the interaction of an atom (molecule) with an external field which is either static or periodic, in which case the effect of the interaction is obtained as an average over a cycle. In this framework, the "atom - - field" state is inside the continuous (ionization or dissociation) spectrum, and so certain features of the problem resemble those of the unstable states of the field-free Hamiltonian. The probability of decay of these field-induced unstable states corresponds either to tunneling or to ionization-dissociation by absorption of one or more photons. 

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. 

A therapeutic dose of a radiopharmaceutical is too active to count individual decays, but quite sufficient to produce robust continuous ionization current. It is important that amount of radioactive material be known quite accurately. O Figure 48.1 shows the geometry of an ionization chamber designed to measure the activities of, for example, batches of radioactive material packaged in a standard way. Although the detector can be stable over long periods of time, variations in absorption in the samples must be minimized. The system must be calibrated for each radionuclide and each geometry of container and contents. 

However, as it was difficult to control the laser energy absorbed, the mass spectra were less reproducible. In contrast, continuous ionization by primary ion bombardment provided more characteristic fragment peaks without losing molecular weight information and both the mass spectra and the chromatograms were more stable and reproducible. 

Chapter 7 Pulsed Extraction, Continuous Ionization, and Ion Storage Instruments... 

---