Surface modification of Quantum dots

In traditional methods, QDs could be prepared in the various media, from atomic deposition on solid-phases to colloidal synthesis in aqueous solution. However, the highly homogeneous and crystalline QDs are most important in the synthesis. Previous authors reported the highest quality QDs are typically prepared at elevated temperatures in organic solvents, such as tri-n-octylphosphine oxide (TOPO) and hexadecylamine, all of them are high boiling point bases containing long alkyl chains. These hydrophobic organic molecules serve as the capping agents that coordinate with unsaturated metal atoms on the QDs surface to prevent the formation of bulk semiconductor. Therefore, the organic ligands capped on the QDs surface and are only soluble in hydrophobic solvents, such as chloroform and hexane. For biological application, these hydrophobic QDs must first be made form water-soluble. As a result, different QDs solubilization strategies have been devised over the past few years, including (i) ligand exchange with simple thio-containing molecules [20-21] or more sophisticated ones, such as oligomeric phosphines [22], dendrons[23], and peptides[24]; (ii) encapsulation by a layer of amphiphilic diblock [25] or triblock copolymers[26] or in silica shells [4,27], phospholipid micelles [28], polymer beads [29], polymer shells [30], or amphiphilic polysaccharides [31]; and (iii) combinations of layers of different molecules conferring the required colloidal stability to QDs [3, 32] (as

shown in Figure 1.7 ).

Figure 1.7 Qdot solubilization and functionalization. (A) Surface chemistries. TOPO (trioctylphosphine oxide)– passivated qdots can be solubilized in aqueous buffer by addition of a layer of amphiphilic molecules containing hydrophilic (wt) and hydrophobic (w–) moieties, or by exchange of TOPO with molecules that have a Zncoordinating end (usually a thiol group, SH) and a hydrophilic end. Examples of addition include (a) formation of a cross-linked polymer shell (30), (b) coating with a layer of amphiphilic triblock copolymer (25), and (c) encapsulation in phospholipid micelles (28). Examples of exchange include (d) mercaptoacetic acid (MAA) (20), (e) dithiothreitol (DTT) (21), (f) dihydrolipoic acid (DHLA) (32), (g) oligomeric phosphines (22), (h) cross-linked dendrons (22), and (i) peptides (24). The curved arrow indicates sites available for further functionalization [3].

For describing the above methods, we take some example and reported to depict them. In perceiving of QDs surface modification methods, as elaborated in the previous sections, it is clearly that the water-soluble QDs was prepared mostly by capping with a mercaptocarboxylic acid layer, such as mercaptoacetic acid (MAA), mercaptopropionic acid (MPA), and dihydroxylipoic acid (DHLA) etc.

The main reason is that the thio group derivatives as a linkage has higher affinity binding than other functional groups on the QDs. For example, Chan and Nie (1998) [20] reported a method by using mercap toacetic acid for solubilization and covalent protein attachment. Sun (2001) used MSA to replace mercaptoacetic acid because one MSA molecule provides two carboxyl groups that may increase binding number of IgG on each QD [33]. In addition, the MSA layer is expected to reduce passive protein adsorption on QDs. In addition to this general method, the encapsulation on the hydrophobic QDs surface by polymer has recently been developed. Pellegrino (2004) have developed a simple and general strategy for decorating hydrophobic nanocrystals of various materials, such as CoPt, Au, CdSe/ZnS, and Fe2O3 with a hydrophilic polymer shell by exploiting the nonspecific hydrophobic interactions between the alkyl chains of poly(maleic anhydride alt-1-tetradecene) and the nanocrystal surfactant molecules . Then, addition of bis(6-aminohexyl)amine results in the cross-linking of the polymer chains around each nanoparticle (Figure 1.8 ). Therefore, the nanocrystal become soluble into water upon hydrolyzation of the unreacted anhydride groups [30].

Figure 1.8 Scheme of the polymer coating procedure. The following plausible configuration is then assumed for the polymer coating process:

The hydrophobic alkyl chains of the polymer intercalate with the surfactant coating. The anhydride rings are located on the surface of the polymer-coated nanocrystal. The amino end groups of the cross-linker molecule open the rings and link the individual polymer chains. The surface of the polymer shell becomes negatively charged, stabilizing the particles in water by electrostatic repulsion. A structural analysis aimed at determining the detailed conformation of the cross-linked polymer shell is in progress [30].

Petruska (2004) have successfully employed hydrophobically modified polymers to solubilize nanoparticle [34]. Using low-molecular weight polyacrylates modified with octyl chains were developed to stabilize and encapsulate QDs, rendering them soluble in polar media, e.g. water or alcohol. The amphiphilic polymer encases the nanoparticle, creating a micellar shell around QDs. Then, the hydrophobic groups are cross-linked to stabilize the QDs-polymer conjugate for preparing shell cross-linked knedels (SCKs) (as shown in Figure 1.9).

Figure 1.9 Formation of the polymer-QD complex showing an idealized micellar polymer shell (40% octylamine-modified PAA) encapsulating the QDs [34].

Mattoussi (2000) reported the strategy of combining the use of alkyl-COOH capped CdSe/ZnS (Figure 1.10) and two-domain recombinant proteins cloned with a highly charged leucine zipper tail offers several advantages. (1) The alkyl-COOH teriminated capping groups, which permit dispersion of the QDs into water solutions, also provide a surface charge distribution that can promote direct self-assembly with other molecules that have a net positive charge. (2)

The fusion protein approach provides a general and consistent way to prepare a wide selection of biological macromolecules amenable to alterations of the interaction domain, such as charge, size, stability to pH, and temperature [32].

Figure 1.10 (a) Schematic of the CdSe-ZnS core-shell nanoparticle with dihydrolipoic acid surface capping groups; (b) cartoon of the S-S linked MBP-zb homodimer and detail showing nucleotide and primary amino acid sequences of the C-terminal basic leucine zipper interaction domain. Poly-Asn flexible linker is boxed with dashed lines, unique engineered cysteine is double boxed, and lysine residues contributing to net positive charge of leucine zipper are single boxed [32].

Comparing the ligand exchange and polymer encapsulation method, the ligand exchange are wide used into modification QDs surface, because of the surfactant (contain thio group) are cheaper than other polymers and have high binding affinity on the metal atoms.

Furthermore, the encapsulation polymer on the hydrophobic surface is easily form the emulsification in the environment. Consequently, most research all like to use the thio derived molecules capping on the QDs surface.