SELF BAR-CODED COLLOIDAL METAL NANOPARTICLES

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A common thread in life science research today is the need to organize and access the vast array of potential information inherent in complex molecular systems. In drug discovery, the beads in combinatorial libraries are tagged with series of organic molecules to facilitate their identification. Genomics projects rely on spatially-defined planar arrays to monitor reactions of hundreds or thousands of different oligonucleotides. In the macroscopic world, complex systems are often simplified by bar coding, a technology that tremendously streamlines data collection and identification. This proposal relates to nanometer-scale metallic bar codes. Its foundation rests on very recently-developed chemistry to produce free-standing, cylindrically-shaped colloidal metal nanoparticles (30 - 200 nm in width, 0.4 - 4 mum length) in which the metal composition can be alternated (e.g. Pt-Au-Pt-Au-Pt) along the length, and in which the metal segments can be both length-tuned and selectively chemically functionalized. The proposal further exploits the finding that intrinsic differences in reflectivity, permit metal segments in individual rods to be visualized by conventional optical microscopy. These innovations have brought the notion of the bar code (and the bar code reader) to biologically-relevant length scales. If properly developed, these novel materials could have an enormous impact in life science, in areas as diverse as combinatorial organic synthesis, analysis of gene expression, detection of single nucleotide polymorphisms and genotyping, high throughput screening, simultaneous (multipexed) bioassays, and even flow cytometry: in short, in any activity in which identifying and tracking a large number of molecules or molecular assemblies is necessary or desirable. Accordingly, this proposal aims to develop and/or improve bar code synthesis, bar code readout, bioassay readout, and bar code surface chemistry, so as to maximize their potential utility. To that end, specific research milestones for the proposed work include the following: (i) fabrication of metallic bar codes with up to twelve distinguishable segments, using up to six different metals; (ii) demonstration of programmable, automated synthesis of nanoscale bar codes; (iii) adaptation of high-resolution bar code identification (ID) to both narrow, time-varying and wide, static fields of view; (iv) development of instrumentation capable of simultaneous bar code ID and fluorescence bioassay readout; (v) demonstration of a novel and highly general detection mechanism that allows in a mixture of many different barcodes, each with different chemistry, only those undergoing a chemical reaction to be visualized; and (vi) simultaneous quantitation of three different analytes on a single bar code.