NIR-emitting colloidal quantum dots having 26% luminescence quantum yield in buffer solution.

Efficient infrared lumophores are urgently needed in a host of biological sensing applications.1 Such applications demand light emitters that meet a number of requirements simultaneously. First, the light-emitting species must be stable and bright (quantum yield >10%) under biologically relevant conditions including buffered conditions. In addition, emission in the near-IR (NIR) and shortwavelength IR (SWIR) range of 800-1300 nm allows greatly reduced absorption of emitted light in biological samples: optical penetration depths as high as 1 cm have been reported in tissue.2 Finally, lumophores must have hydrodynamic diameters smaller than ∼10 nm to promote circulation transport in living organisms.3 To date, no single material displaying all of these attributes simultaneously has been reported. Instead, >10% quantum yield (QY) has been reported at tissue-penetrating SWIR emission wavelengths, but these materials were unstable in physiologically relevant buffer.4-6 IR-emitting quantum dots with hydrodynamic diameters <10 nm were reported following a III-V/II-VI coreshell colloidal synthesis; however, these particles exhibited sub10% QY in water.3 Efficient size-effect tunable >10% QY nanoparticle suspensions in water have been achieved using TOPOcopolymer-PEGylation of II-VI core-shell nanoparticles; however, this approach produced nanoparticles with 15-30 nm hydrodynamic diameters.8 Here we report high QY infrared lumophores that are stable under buffered conditions for greater than 5 days. The result was achieved through straightforward mercaptan-PEGylation ligand exchange which rendered organometallically synthesized lead sulfide (PbS) quantum dots stable in aqueous solution. The infrared lumophores described simultaneously meet requirements on brightness, stability, wavelength, and hydrodynamic diameter. The PbS quantum dots were synthesized using an organometallic route previously described.9 The particles exhibited hydrodynamic diameters less than 10 nm and, through quantum size effect tuning readily accessed in the organometallic route synthesis, have emission peaks tunable from 700 to 1600 nm. The material was transferred from organic solvent into aqueous solution by replacing oleate capping ligands with (1-mercaptoundec11-yl)tetra(ethylene glycol) (MTPEG). A solution of MTPEG in HEPES, Tris, or PBS buffer was mixed with oleic acid capped PbS nanocrystals (∼80 mg/mL) in toluene. An aqueous phase containing nanoparticles was separable from the toluene phase that previously solubilized the PbS. These results contrast with previous reports describing aqueous suspension of organometallic lead sulfide nanocrystals using carboxylic acid or amino mercaptan strategy. Experimentally, we found that thioglycerol, 6-mercapto-1-hexanol, and 2,3-dimercapto-1-propanol all produce high QY stable colloids in polar solvents following this strategy; however, only when we used MTPEG did we obtain high QY PbS nanocrystals stable in biologically relevant buffer. We selected the MTPEG ligand for three reasons. First, monodentate complexation of the thiol group is expected to achieve good passivation of PbS nanocrystals in view of thiol-Pb binding affinity (strong thiol-metal affinity has been widely exploited in, for example, Au nanoparticle functionalization).7 Second, its hydrophobic single-bonded carbon chain was expected to conserve QY. Third, its polar terminal group was expected to yield stable suspensions in aqueous solutions at physiological pH. Finally, these compact ligands enable hydrodynamically small nanoparticles that are comparable in size with a single antibody. Dynamic light scattering (DLS) was used to investigate nanoparticle hydrodynamic diameters before and after exchange, as shown in Figure 1. Prior to ligand exchange, oleate-capped nanoparticles in toluene constitute a monodispersed colloid with hydrodynamic diameter of ∼6 nm. Following exchange, 90% by mass of these particles have 10 ( 0.5 nm hydrodynamic diameter. The remaining 10% of these nanoparticles have formed small 4060 nm and larger aggregates. Ligand exchange is also supported by density phase segregation of MTPEG-exchanged nanocrystals in 20 mM HEPES buffer from fresh excess addition of organic solvent. Figure 2 reports the absorbance and photoluminescence spectra for the nanoparticles prior to and following exchange. The excitonic structure remains but is somewhat reduced in sharpness following exchange. There is a red shift of ∼70 meV in the photoluminescence and a ∼60 meV red shift in absorbance as a result of the exchange † Department of Electrical and Computer Engineering. ‡ Department of Biochemistry and Faculty of Pharmacy. Figure 1. Dynamic light scattering measurements of hydrodynamic radius, by % mass modeled as solid Rayleigh spheres, of unexchanged PbS nanocrystals with oleic acid ligands (solid bars) in toluene, and PbS nanocrystals exchanged to having MTPEG ligands (shaded bars) in water. Published on Web 05/16/2007