Abstract
A generalized label-free platform for surface-selective molecular sensing in living cells can transform the ability to examine complex events in the cell membrane. While vertically aligned semiconductor and metal-semiconductor hybrid nanopillars have rapidly surfaced for stimulating and probing the intracellular environment, the potential of such constructs for selectively interrogating the cell membrane is surprisingly underappreciated. In this work, a new platform, entitled nano-PROD (nano-pillar based Raman optical detection), enables molecular recording by probing fundamental vibrational modes of membrane constituents of cells adherent on a large-area silver-coated silicon nanopillar substrate fabricated using a precursor solution-based nanomanufacturing process. It is shown that the nano-PROD platform sustains live cells in near-physiological conditions, which can be directly profiled using surface-enhanced Raman spectroscopy due to the confined electromagnetic field enhancement. The experimental results highlight the utility of the platform in probing specific cell surface markers for accurately recognizing the phenotypically identical prostate cancer cells, differing only in prostate-specific membrane antigen expression. Due to its tunability, nano-PROD has the promise to be readily extendable to other applications that can leverage its unique combination of nanoscale topographic features and molecular sensing capabilities, from stain-free cytopathology inspection to understanding spatio-mechanical regulation in membrane receptor function.