Quantum dots are a class of light-emiting nanocrystal used for high-sensitivity multi-color imaging of molecules and cells. A major ongoing challenge is to coat these particles with a ligand shell that is compact in size, stable, and resistant to nonspecific binding to biological structures. Here we report a new series of multidentate molecular and polymeric ligands that fulfill these needs, which we have designed by optimizing the nanocrystal binding domains and hydrophilic domains for colloidal dispersion. The binding domains have a tunable number of thiols or imidazoles and the hydrophilic domains incorporate sulfobetaine and ethylene glycol oligomers that resist nonspecific interactions with proteins, cells, and tissues. Using these materials we have generated stable quantum dots with just a 1-nanometer radial increase in hydrodynamic size arising from the coating. We have further developed a universal technology for phase transfer to aqueous solvents compatible with a diverse range of molecular and polymeric ligand coatings to reproducibly yield homogeneous nanocrystals with high stability and high quantum yield. We expect that these materials and techniques will be broadly applicable for generating quantum dot probes with substantially reduced size and increased target specificity for molecular imaging applications in complex cells and tissues.

Compact coatings for quantum dots that resist nonspecific binding to proteins, cells, and tissues

249th National Meeting (2015)

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