Biological imaging is an indispensable tool in biological research. The contrast agents often limit image quality and utility. An optimal contrast agent would need great resolution, functional specificity, minimal sample preparation/ ability for use in-vivo versus pathological imaging, low background signal and low toxicity. Rare earth doped upconverting nanoparticles (UCNPs) are a promising alternative contrast agent that provide an equivalent resolution, tissue penetration, and low background as two-photon microscopy at the low pump power used in fluorescence imaging, while being of very low toxicity. Current UCNPs are dim, however, and current progress in increasing the efficiency of particles that can easily be taken up into tissue (diameter < 100 nm) has been slow since iterative systematic optimization is often slow, and not grounded in a central hypothesis. The PIs propose to drastically enhance upconversion brightness of UCNPs by coupling them to metal nanostructures that display electromagnetic resonance (plasmons). Because of the unique 'anti-Stokes' fluorescence that utilizes infrared excitation to yield visible (green and red) emission, the enhancement could considerably exceed the ones achieved using fluorescent (Stokes) surface enhanced emission.