Large-Scale Nanophotonic Structures for Long-Term Monitoring of Cell Proliferation

Innovative sensing materials have enabled the discovery of cell biology principles at the nanoscale. In order to evaluate cell behavior and responses, it is necessary to accurately monitor cell proliferation. However, it remains challenging to develop nanomaterials possessing pertinent properties for sensing, while ensuring long-term cell survival and unaltered cellular responses. This work develops highly sensitive, large-scale, and biocompatible nanoplasmonic biosensors for long-term monitoring of cell proliferation, reported for the first time. The nanoplasmonic sensor consists of mushroom-like structures, with stems of silicon dioxide and caps of gold covering a total surface area of 18.75 cm ² . The localized surface plasmons on the nanomushroom caps are exploited to monitor proliferating fibroblast cells. Changes in nanoplasmonic resonances of the nanomushrooms are directly proportional to the number of cells that bind to them. Fibroblast proliferation is successfully monitored for 7 d, demonstrating remarkable biocompatibility of the nanomushroom substrates. These nanomushroom substrates preserve cell viability and serve as a label-free platform for long-term monitoring of cell proliferation. These results also open new opportunities in developing standard cell assays without chemical labels to detect cellular responses at the nanoscale.