Mass spectrometry imaging sample preparation

Bouschen, W. and Spengler, B., Artifacts of MALDI sample preparation investigated by high-resolution scanning microprobe matrix-assisted laser desorption/ionization (SMALDI) imaging mass spectrometry, Int. J. Mass Spectrom., 266(1-3), 129, 2007. 

The preparation of samples for mass spectrometric analysis almost always requires recovery of the analyte from a matrix, often followed by further preparative steps prior to introduction of the sample into the ion source. Such destructive processes are unacceptable when the objective is to determine the specific location of a particular compound within a biological sample, e.g., the location of a certain lipid in a tissue, and led to the development of imaging mass spectrometry with MALDI as the ionization method, although DESI is also applicable. 

Key words Cisplatin, renal injury, calcium stores, freeze-fracture, cellular potassium and sodium, SIMS, imaging mass spectrometry, cryogenic sample preparation for SIMS. 

Nevertheless, the introduction of time-of-flight (ToF) analysers for SIMS analyses at the beginning of the 1980s, as well as the recent development of liquid ion sources delivering cluster projectiles now permit the analysis of organic materials with high sensitivity and selectivity. Moreover, thanks to its excellent lateral resolution (in the order of micrometres), and its minimal sample preparation, ToF-SIMS has become the reference technique for chemical imaging by mass spectrometry. 

In addition to some early applications in bioanalysis, ambient ionization mass spectrometry has been used as an imaging tool to study drug distribution in tissue sections. Most of the work reported so far involved the use of DESI as the ambient ionization method. Compared to other mass spectrometry-based tissue imaging techniques such as MALDI and SIMS, DESI allows tissue samples to be analyzed under ambient conditions without sample preparation, which simplifies the procedure and prevents the redistribution of analytes during matrix deposition. A major drawback of DESI as an imaging tool is its relatively low spatial resolution (typically 250 pm) and therefore cannot be used for cellular or subcellular imaging. 

Two new independently developed techniques called Dart ° (direct analysis in real time) and Desi (desorption electrospray ionisation) are making a huge impact on mass spectrometry. Together they remove the need for sample preparation and vacuum, speed up analysis time and can work in the open air. The sample is held in a gas or liquid stream at room temperature and the impact induces the surface desorption of ions. The ions then continue into the vacuum interface of the MS for analysis. Samples can be hard, soft or even liquid in nature. Ifa et al. have used Desi to image biological samples in two dimensions, recording images of tissue sections and the relative concentrations of molecules therein. Jeol have launched a commercial Dart ion source for non-contact analysis of materials in open air under ambient conditions. 

The laser-based optical and chemical imager (LOCI) is a unique instrument that combines accurate isotope ratio analyses obtained both by laser desorption Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and by LIBS without any sample preparation (Scott and Mcjunkin 2009). A single photon ionization (SPI) process is implemented allowing near 100% ionization efficiency for elements and compounds with ionization energies less than 10.5 eV. The FTICR-MS and LIBS isotope capability coupled with LOCI s wide mass range, mapping capability, high resolution, and automated data collection as well as data interpretation offers an alternative to the labor-intensive bulk analysis of traditional methods. 

BruneUe, A., Laprevote, O. (2007) Recent advances in biological tissue imaging with time-of-flight secondary ion mass spectrometry polyatomic ion sources, sample preparation, and appUcations. Curr Pharm Des, 13, 3335-3343. 

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