Plasmonic microcarriers for sensing and cell expansion

Microcarriers (MCs, typically 50–200 µm) are promising growth supports for high-throughput cell expansion, with capability to overcome the limitations of surface area availability and nutrient access encountered by cell culture in 2D well plate configurations. Equipping MCs with in-built capability to sense molecular biomarkers is a key step forward to meet the emerging demands of personalized cell-based therapies. However, integrating sensing functionality into MCs is non-trivial due to fabrication limitations imposed by their large size, curved surfaces, and their suspension in fluid. If achieved, the sensor-integrated MCs should face further concerns of reduced stability and cytocompatibility during cell-culture. Here we demonstrate plasmonic microcarriers (PMCs) that integrate spectroscopic sensing and cell expansion functions through the deposition of gold nanoparticle (AuNP) assemblies on dextran-based MCs. Hydrogel characteristics of the dextran microcarriers was found to profoundly enhance the binding density and kinetics of AuNPs, as seen by attainment of saturated densities in few seconds, and at nanoparticle concentrations only twice that of the surface sites. The approaches to prepare PMCs are distinguished by simple, scalable routes, without need for sophisticated lab infrastructure. The capability of PMCs to act as spectroscopic transducers was demonstrated by surface-enhanced spectroscopic (SERS) detection of a model molecular probe.  The growth, proliferation and migration of human mesenchymal stem cells on the PMCs was found to be comparable to that of the uncoated MCs. The results pave the way to smart, multifunctional cell growth supports to interrogate, control and report cell behavior during culture.