Chemically patterned microspheres for controlled nanoparticle assembly in the construction of SERS hot spots

An important challenge in developing ultra-sensitive surface enhanced Raman spectroscopy (SERS) platforms lies in the creation of nanoscale hot spots, locations where the electromagnetic field is greatly concentrated. Even when this is successful, finding these hot spots is a difficult task. We describe a novel chemical microsphere patterning technique utilizing contact masking during silanization for bonding silver nanoparticles preferentially to geometrically restricted sites. Small bifunctional linkers (i.e., < 2 nm) are used to bind silver particles on different microspheres drawing the two together, thereby forming small nanoparticle aggregates containing one or more hot spots with the dimensions of the linker at the junction. The microspheres limit the extent of nanoparticle aggregation and are large enough to be visible by optical microscopy leading in most cases directly to the location of the hot spots and hence the most intense SERS signals.