Probing nanoparticles and nanoparticle-conjugated biomolecules using time-of-flight secondary ion mass spectrometry

Bio‐conjugated nanoparticles have emerged as novel molecular probes in nano‐biotechnology and nanomedicine and chemical analyses of their surfaces have become challenges. The time‐of‐flight (TOF) secondary ion mass spectrometry (SIMS) has been one of the most powerful surface characterization techniques for both nanoparticles and biomolecules. When combined with various nanoparticle‐based signal enhancing strategies, TOF‐SIMS can probe the functionalization of nanoparticles as well as their locations and interactions in biological systems. Especially, nanoparticle‐based SIMS is an attractive approach for label‐free drug screening because signal‐enhancing nanoparticles can be designed to directly measure the enzyme activity. The chemical‐specific imaging analysis using SIMS is also well suited to screen nanoparticles and nanoparticle–biomolecule conjugates in complex environments. This review presents some recent applications of nanoparticle‐based TOF‐SIMS to the chemical analysis of complex biological systems. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 34: 237–247, 2015.