Small-molecule , generally biomarkers

Intact-cell MALDI-TOF analysis offers several attractive features for rapid screening of bacterial collections. Analysis is performed directly on the cells after minimal sample preparation, and data acquisition is complete in only a matter of minutes. Intact biomarkers are introduced into the MALDI-TOF instrument under these conditions. Whether the observed biomarker molecules are desorbed directly from the surface of the cell wall or are extracted from the cells and co-crystallized with the matrix is currently unresolved, but MALDI spectra of intact bacteria generally contain a large number of peaks in the mass range 1-20 kDa [31]. For bacterial cells, proteins are the most often observed biomarkers. While this approach samples only a small percentage of the total proteins produced in the cells, these profiles have been reported by many groups to be suitable for taxonomic identification, down to at least the strain level. The wide availability of the MALDI-TOF instrumentation and its relative ease of use, coupled with relatively simple sample preparation procedures, have been key features in the rapid advancement of this approach. 

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