The preparation of colloidally stable, water-soluble, biocompatible, semiconductor nanocrystals with a small hydrodynamic diameter.

We report a simple, economical method for generating water-soluble, biocompatible nanocrystals that are colloidally robust and have a small hydrodynamic diameter. The nanocrystal phase transfer technique utilizes a low molecular weight amphiphilic polymer that is formed via maleic anhydride coupling of poly(styrene-co-maleic anhydride) with either ethanolamine or Jeffamine M-1000 polyetheramine. The polymer encapsulated water-soluble nanocrystals exhibit the same optical spectra as those formed initially in organic solvents, preserve photoluminescence intensities, are colloidally stable over a wide pH range (pH 3-13), have a small hydrodynamic diameter, and exhibit low levels of nonspecific binding to cells.

Experimental determination of quantum dot size distributions, ligand packing densities, and bioconjugation using analytical ultracentrifugation.

Analytical ultracentrifugation (AUC) was used to characterize the size distribution and surface chemistry of quantum dots (QDs). AUC was found to be highly sensitive to nanocrystal size, resolving nanocrystal sizes that differ by a single lattice plane. Sedimentation velocity data were used to calculate the ligand packing density at the crystal surface for different sized nanocrystals. Dihydrolipoic acid poly(ethylene glycol) was found to bind between 66 and 60% of the surface cadmium atoms for CdSe nanocrystals in the 1.54-2.59 nm radius size regime. The surface ligand chemistry was found to affect QD sedimentation, with larger ligands decreasing the sedimentation rate through an increase in particle volume and increase in frictional coefficient. Finally, AUC was used to detect and analyze protein association to QDs. Addition of bovine serum albumin (BSA) to the QD sample resulted in a reduced sedimentation rate, which may be attributed to an associated frictional drag. We calculated that one to two BSA molecules bind per QD with an associated frictional ratio of 1.2.