Fluorescence resonance energy transfer (FRET) is recognized as a sensitive and reliable analytical technique and has been widely used in biological assays.[1] To obtain improved FRET efficiency and analytical performance, it is of continuing interest to search for new energy donor-acceptor pairs. In the past few years, the use of anti-Stokes fluorophores including upconverting phosphors (UCP) and multiphotonexcited dyes as energy donors which can be excited in the near-infrared (NIR) region has successfully circumvented the problem of autofluorescence and scattering of light arising from biological substances. [2,3] This has made it possible to directly conduct FRET-based assays in biological samples. More recently, graphene, the newly emerging two-dimensional and zero-bandgap carbon nanomaterial, has attracted considerable attention in bioassays because of its unique electronic, mechanical, and thermal properties. In the pioneering work of Swathi et al., it was proposed through theoretical calculations that graphene could act as a superquencher of organic dyes, as a result of nonradiative transfer of electronic excitation energy from dye excited states to the p system of graphene.[4] The rate of this long-range resonance energy transfer was suggested to have a d À4 dependence on distance d, in sharp contrast to traditional FRET, for which the rate has a d À6 dependence. Inspired by this property, graphene and graphene oxide (GO) have been used as FRET acceptors with organic dyes and quantum dots as energy donors, [5][6][7][8][9][10][11] in which both graphene and GO exhibit high efficiency in quenching the donor emission and thus provide good sensitivity. Herein we reveal energy transfer from UCP to GO and thus construction of a new biosensing platform which could be used to detect glucose directly in serum samples and extended to detection of other biologically significant molecules.The previously reported FRET models based on graphene or graphene oxide all rely on the p-p stacking interaction between the carbon nanomaterial and nucleic acid chains, which bring the acceptor and donor (organic dyes or quantum dots) into close proximity. We hereby tried a different model in which donor and acceptor are brought into FRET proximity through specific molecular recognition (Figure 1).We used GO as energy acceptor because the abundance of carboxy, hydroxy, and epoxy groups on the surface of GO sheets [12] makes the material more water-soluble and also enables covalent conjugation with other molecules. Concanavalin A (conA) and chitosan (CS) were covalently attached to UCP and GO, respectively. The known tight binding of ConA with CS may bring UCP and GO into appropriate proximity and hence induce energy transfer. Thereafter, the FRET process is anticipated to be inhibited (in part) because of competition between glucose and CS for ConA, which could be the foundation of glucose sensing.To realize such design, we first synthesized water-soluble NaYF 4 :Yb,Er UCP nanocrystals modified with polyacrylic acid (PAA). Details ...