AP-MALDI

Moyor, S. C. Marzilli, L. A. Woods, A. S. Laiko, V. V. Doroshenko, V. M. Cotter, R. J. Atmospheric pressure matrix-assisted laser desorption/ionization (AP MALDI) on a quadrupole ion trap mass spectrometer. Int. I. Mass Spectrom. 2003, 226,133-150. 

In contrast to the other ion sources, the MALDI source may operate under high vacuum or under atmospheric pressure. In the latter case the acronym AP-MALDI (atmospheric pressure matrix assisted laser desorption ionization) is used. 

DGE a AC AMS APCI API AP-MALDI APPI ASAP BIRD c CAD CE CF CF-FAB Cl CID cw CZE Da DAPCI DART DC DE DESI DIOS DTIMS EC ECD El ELDI EM ESI ETD eV f FAB FAIMS FD FI FT FTICR two-dimensional gel electrophoresis atto, 10 18 alternating current accelerator mass spectrometry atmospheric pressure chemical ionization atmospheric pressure ionization atmospheric pressure matrix-assisted laser desorption/ionization atmospheric pressure photoionization atmospheric-pressure solids analysis probe blackbody infrared radiative dissociation centi, 10-2 collision-activated dissociation capillary electrophoresis continuous flow continuous flow fast atom bombardment chemical ionization collision-induced dissociation continuous wave capillary zone electrophoresis dalton desorption atmospheric pressure chemical ionization direct analysis in real time direct current delayed extraction desorption electrospray ionization desorption/ionization on silicon drift tube ion mobility spectrometry electrochromatography electron capture dissociation electron ionization electrospray-assisted laser desorption/ionization electron multiplier electrospray ionization electron transfer dissociation electron volt femto, 1CT15 fast atom bombardment field asymmetric waveform ion mobility spectrometry field desorption field ionization Fourier transform Fourier transform ion cyclotron resonance... 

Atmospheric pressure matrix-assisted laser desorption/ ionization AP- MALDI Photon induced desorption/ ionization Nonvolatile molecular ions Soft method Large molecules... 

Atmospheric pressure MALDI (AP-MALDI) was introduced in 1998 by Laiko et al. [198, 199]. The advantage with the AP version of MALDI is the possibility of coupling... 

There is a recent hybrid between AP-MALDI and ESI, matrix-assisted laser desorption electrospray ionization (MALDESI) [202], where species desorbed from a MALDI target are subjected to an electrospray before entering the mass spectrometer. The method is similar to ELDI except that the analyte is embedded in a matrix as in MALDI. 

Fig. 10.18. AP-MALDI ion source with extended transfer capillary. Insets (a) the target holder can be equipped with a 64-spot MALDI target or (b) a 10 x 10-spot DIOS chip. Adapted fromRef. [142] by permission. John Wiley Sons, 2002.

API offers unique opportunities for the implementation of new sources or to develop new applications. Atmospheric pressure matrix assisted laser desorption (AP-MALDI) [21] can be mounted on instruments such as ion traps which were originally designed only for electrospray and LC-MS. New API desorption techniques such as desorption electrospray (DESI) [22] or direct analysis in real time (DART) [23] have been described and offer unique opportunities for the analysis of surfaces or of solid samples. 

In 2000, various developments in the field of MALDI led to the advent of new methods such as the atmospheric pressure MALDI (AP-MALDI) source. This method combines the atmospheric pressure (AP) source and MALDI [45-47]. Indeed, this source produces ions of analytes under normal atmospheric pressure conditions from analyte-doped matrix microcrystals by irradiating these crystals with laser pulses. 

Diagram of an AP-MALDI source. Ions are transferred into the mass analyser using the atmospheric pressure interface. 

The AP-MALDI source is illustrated in Figure 1.17. It works in a similar manner to the conventional MALDI source. The same sample preparation techniques and the same matrices used for conventional vacuum MALDI can be used successfully for AP-MALDI. The main difference is the pressure conditions where ions are produced. Conventional MALDI is a vacuum ionization source where analyte ionization takes place inside the vacuum of the mass spectrometer whereas AP-MALDI is an atmospheric ionization source where ionization occurs under atmospheric pressure conditions outside of the instrument vacuum. 

The advantages of AP-MALDI include those advantages typically associated with a MALDI source but without some of the drawbacks. Indeed, AP-MALDI does not require a vacuum region and is decoupled from the mass analyser, allowing it to be coupled with any mass spectrometer equipped with API. It is also easily interchangeable with other... 

Besides AP-MALDI, already described earlier, electrospray (ESI), atmospheric pressure chemical ionization (APCI), atmospheric pressure photoionization ionization (APPI), DESI and DART are other examples of atmospheric pressure ionization (API) sources. 

The Cl source operates at low pressure. Ion-molecule reactions occur and are needed for sample ionization. The MALDI source is under vacuum, but during the ionization process the pressure increases in the plume close to the target and ion-molecule reactions occur. The various sources operating at atmospheric pressure include ESI, APCI, APPI and AP-MALDI. All these sources operate at sufficient pressure to have numerous collisions between ions and molecules, and reactions between these species are observed. 

Atmospheric-pressure MALDI (AP-MALDI) is conceptually similar to normal MALDI except that it is performed ontside the source vacuum at atmospheric pressure [63,64]. Similar to other AP ion sources (e.g., ESI), orthogonal acceleration TOP, quadrupole ion trap, Unear ion trap (LIT), and FT-ICR instruments are ideal MS systems for conpUng with AP-MALDI. Ion gnides made of... 

Figure 13.7. AP-MALDI mass spectrum of two 21-mer oligonucleotides, QZl and QZ2. (Reproduced from ref. 35 by permission of Elsevier Science, copyright C> 2005 American...

MALDI has also been used to quantify small molecules. This aspect has been demonstrated by the analysis of lysergic acid diethyl amide (LSD) with atmospheric pressure (AP) MALDI [20]. LSD is a hallucinogen. Its quantification is highly important from forensic and clinical point of views. In this method, LSD was extracted and precleaned from urine samples by SPE and quantified by recording the ion current due to m/z 327 226 and 324 223 transitions. The standard curves were plotted by analyzing several LSD standard solutions, each of which was spiked with LSD-iis as an IS. A linear calibration curve was obtained over the concentration range 1 to 100 ng mL with = 0.9917. The results were comparable with those of an existing HPLC/ESI-MS method. 

Atmospheric pressure matrix-assisted laser desorpt-ion/ionization (ap-MALDI) A variant of the conventional MALDI technique is ap-MALDI in which the sample is ionized outside the vacuum system and ions are captured through a small orifice, usually into an ion trap mass spectrometer. Its advantage appears to be a considerable amount of rapid collisional cooling of the ions by the high atmospheric pressure, leading to stabilization of sensitive compounds. On the other hand, some compounds, such as carbohydrates, appear to suffer increased fragmentation under these conditions. 

Because of the large installed base of API instruments there is an opportunity to try and use the source and mass analyzer for new techniques and applications. One such technique is MALDI, which is normally combined with TOE mass separation under vacuum. AP-MALDI can be combined with ion traps and quadrupoles to give a low-cost expansion of the capabilities of those instruments, in particular in laboratories that cannot justify the purchase of several instruments dedicated to a specific task. AP-MALDI on an ion trap is a cost-effective way of obtaining fragmentation in combination with MALDI. 

The vibrational cooling effect has been extended to the analysis of ions desorbed at atmospheric pressure [15-20]. This arrangement is extremely simple, and involves merely placing the MALDI sample directly in front of an electrospray ionization source orifice. This proved to be effective, and Cotter et al. shortly thereafter duplicated the ganghoside investigations of O Connor et al., thus proving that the AP-MALDI source was also a coUisionaUy cooled ion source design [21,... 

However, compared to operation at a few millibars, ionization at atmospheric pressure requires that the ions be extracted down a small tube and through a molecular beam skimmer in order to move them into the vacuum where they can be analyzed. Considering the losses expected on the capillary walls and on the skimmer, it is unlikely that the AP-MALDI method will become as sensitive as the vacuum or low-pressure MALDI experiments. 

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