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F Fluorescence-based detection techniques have been widely used in modern biochemical research and disease diagnosis. For the detection of trace levels of analytes, organic fluorophores are commonly exploited as signal transduction tools. Although these fluorophores are versatile and easy to use, their molecular nature determines their limitations. In most cases, only one or a few fluorophores can signal one biomolecule recognition event, and typically, only a limited number of fluorophores can be attached to a biomolecule without interfering with its binding specificity or causing it to precipitate. As a consequence, sample analysis can be particularly difficult when trace amounts of biological analytes are present, and the additional steps required for signal amplification can be time-consuming and impede analyte quantitation.When exposed to a continuous light source, organic fluorophores are not very photostable. In addition, the complex environment inside living cells can increase the vulnerability of organic fluorophores to degradation and photobleaching. These two factors can result in false-positive and false-negative signals and can affect prolonged cell monitoring and 3-D optical sectioning imaging. Moreover, although most organic fluorophores can be conjugated with biomolecules, such as DNA and proteins, a different conjugation chemistry must be used to attach the organic dye to a given biomolecule of interest; this chemistry can be too difficult, time-consuming, and/or expensive for routine applications. All of these limitations have greatly hindered the use of fluorophores for in vitro assays and in vivo cellular imaging.The rapidly evolving field of nanoscience and nanotechnology has opened up a promising era in new biomarker development, in which nanoparticles of various shapes, sizes, and compositions have been successfully used in bioimaging, labeling, and sensing because of their unique optical properties, high surface-to-volume ratio, and other size-dependent qualities (1-8). With manipulated composition and surface modification, these nanoparticle probes have enhanced the fluorescence signal, increased sensitivity, prolonged detection time, and generated better reproducibility.Quantum dots (QDs) and dye-doped nanoparticles are representative fluorescent nanoparticle probes of increasing research interest. QDs are ultrasmall (usually 1-10 nm in diameter), bright (20ϫ brighter than most organic fluorophores), and highly photostable nanocrystalline semiconductors. Their broad excitation spectra, along with narrow, symmetric, size-tunable fluorescence emission spanning the UV to NIR, make them ideal for multiplex analysis (simultaneous detection of multiple an-