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Open Access Research article

Comparing the old and new generation SELDI-TOF MS: implications for serum protein profiling

Marie-Christine W Gast1*, Judith YMN Engwegen1, Jan HM Schellens23 and Jos H Beijnen13

Author Affiliations

1 Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands

2 Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

3 Faculty of Science, Department of Pharmaceutical Sciences, Division of Biomedical Analysis, Utrecht University, Utrecht, The Netherlands

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BMC Medical Genomics 2008, 1:4  doi:10.1186/1755-8794-1-4

Published: 31 January 2008

Abstract

Background

Although the PBS-IIc SELDI-TOF MS apparatus has been extensively used in the search for better biomarkers, issues have been raised concerning the semi-quantitative nature of the technique and its reproducibility. To overcome these limitations, a new SELDI-TOF MS instrument has been introduced: the PCS 4000 series. Changes in this apparatus compared to the older one are a.o. an increased dynamic range of the detector, an adjusted configuration of the detector sensitivity, a raster scan that ensures more complete desorption coverage and an improved detector attenuation mechanism. In the current study, we evaluated the performance of the old PBS-IIc and new PCS 4000 series generation SELDI-TOF MS apparatus.

Methods

To this end, two different sample sets were profiled after which the same ProteinChip arrays were analysed successively by both instruments. Generated spectra were analysed by the associated software packages. The performance of both instruments was evaluated by assessment of the number of peaks detected in the two sample sets, the biomarker potential and reproducibility of generated peak clusters, and the number of peaks detected following serum fractionation.

Results

We could not confirm the claimed improved performance of the new PCS 4000 instrument, as assessed by the number of peaks detected, the biomarker potential and the reproducibility. However, the PCS 4000 instrument did prove to be of superior performance in peak detection following profiling of serum fractions.

Conclusion

As serum fractionation facilitates detection of low abundant proteins through reduction of the dynamic range of serum proteins, it is now increasingly applied in the search for new potential biomarkers. Hence, although the new PCS 4000 instrument did not differ from the old PBS-IIc apparatus in the analysis of crude serum, its superior performance after serum fractionation does hold promise for improved biomarker detection and identification.