Progress in cellular analysis using ToF-SIMS

The analysis of cellular biochemistry represents an exciting frontier for ToF-SIMS. The rewards of opening up the life sciences arena are extremely high and a number of groups are demonstrating significant progress towards this goal. However, there are many challenges to be overcome, including sample preparation, sensitivity of detection and data interpretation. In this paper we review some strategies for meeting these challenges.We report the preparation of microbial and mammalian cells using rapid freezing and freeze-fracture to preserve cellular chemistry in a ‘life-like’ state. ToF-SIMS images of both frozen-hydrated and freeze-dried samples reveal molecular information from single cells, including components of the cell wall, membrane and cytoplasm. The use of Auþ primary ions provides increased yields of molecular ions from cellular samples, compared to Gaþ bombardment. Polyatomic primary ions such as Aunþ and C60þ provide even higher yields, extending the mass range of detected biomolecules. The application of principal component analysis aids interpretation of the complex ToF-SIMS spectra from cellular samples. This ToF-SIMS/PCA approach allows the classification of yeast cells from different species and strains, and non-malignant and malignant cancer cells derived from different metastatic sites. # 2004 Elsevier B.V. All rights reserved. Keywords: ToF-SIMS; Cells; Polyatomic ions; Imaging