Time-of-flight secondary ion mass spectrometry chemical imaging analysis of micropatterns of streptavidin and cells without labeling

A bismuth cluster ion-beam-based time-of-flight secondary ion mass spectrometry (TOF-SIMS) has been successfully used to image micropatterns of streptavidin and Chinese hamster ovary (CHO-k1) cells, as received and without any labeling. Three different analysis ion beams (Bi+, Bi3+, and Bi3 2+) were compared to obtain label-free TOF-SIMS chemical images of micropatterns of streptavidin, which were subsequently used for generating biotinylated cell patterns. Unlike using a Bi+ ion beam, using a Bi3+ or Bi3 2+ primary analysis ion beam yielded well-contrasted-TOF-SIMS images of streptavidin characteristic secondary ions. A principal component analysis of TOF-SIMS data was performed to generate a chemical image of the streptavidin itself. A chemical specific TOF-SIMS image analysis gave us a better understanding of the localization of cells at the outer boundaries of the streptavidin-patterned circles. Our work suggests that using cluster-ion analysis beams together with multivariate data analysis for TOF-SIMS chemical imaging would be an effectual method for producing label-free chemical images of micropatterns of biomolecules, including proteins and cells.