Single cell analysis at the nanoscale.

The fundamental life processes such as signal transduction, intracellular trafficking, protein degradation, and DNA repair often occur in nanometric subcellular compartments. It is essential to conduct single cell analysis specifically at the nanoscale to fully understand the critical cellular processes while providing important medical applications. However, there are great challenges in achieving high spatial resolution in single cells for uncovering spatial heterogeneity, high sensitivity for biomolecule detections and high specificity in complicated cellular environment. In this tutorial review, we survey recent progress toward single cell analysis at the nanoscale by emphasizing how the advancement in nanotechnology has brought a plethora of nanotools to interrogate single cells with high spatiotemporal resolutions. In particular, analysis principle, nanoscale probe fabrication, high resolution cellular analysis, data collection and processing are introduced. New cell biochemistry and biology insights revealed by the unique single cell analysis methods are highlighted. The perspectives on future opportunities and unsolved challenges are also discussed.