Abstract

Fluorescence microscopy, which enables the direct observation and detection of biologic materials, has become a powerful tool in biologic research. Concise evaluation, accurate quantification, and precise localization with ultimate sensitivity in the analysis of biomolecules can be achieved when single molecule microscopy is used. Classically, studies of biomolecules at the single molecule level often involve large teams of specialized biophysicists, sophisticated and finely tuned equipment, and long periods of time to record and analyze relatively few events. In the meantime, these studies also suffer from the limitations of certain organic dyes, such as photobleaching, instability, and low quantum efficiency. It is very desirable now to have fast, robust assays with single molecule sensitivity using photo-stable components readily available for routine diagnostics in clinical or scientific applications. For the sake of speed and simplicity, such assays would ideally be separation free and capable of multiplexing. The combination of nanotechnology with biology and medicine is expected to lead to major advances in molecular diagnostics, molecular biology, and therapeutics [1,2]. Nanoparticles have been recently used for the detection of specific nucleic acid sequences [3-5]. The study described by Yeh et al [6] in the current issue of the Journal represents a step toward single particle bioassays in a simple, robust, and rapid format; combining advances in several scientific fields into this one assay is a novel and promising approach. The authors took advantage of the unique optical properties of core shell semiconductor nanoparticles [quantum dots (QD)] (Figure 1, A and B), which are pioneering achievements in nanotechnology [1]. Quantum dots are nanocrystals; the term

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