Copyright 2004 by Marcel Dekker, Inc. All Rights Reserved.

n-doped GaAs substrates. The GaAs substrates were either bare or pretreatedwith dithiol self-assembled monolayers (SAMs). In the absence of the 1,6-hexanedithiol layer, the NQDs were only physically absorbed to the substrateand did not withstand a thorough toluene wash. In contrast, NQDs selfassembledonto the dithiol SAMs were very robust due to covalent linkagesbetween the NQDs and the exposed thiols [99]. Soluble, covalently linkedNQD clusters have also been prepared. Dimers and larger-order NQD‘‘molecules’’ were prepared from dilute solutions in which bifunctional linkersprovided covalent attachment between two or several CdSe NQDs[100,101]. Improving yields and enhancing control over ‘‘molecule’’ size(dimer versus trimer, etc.) remain as future challenges.Both electrostatic and covalent linkage strategies have been applied tobiological labeling applications where fluorescent NQDs provide specific tagsfor cellular constituents [102]. The NQDs are negatively charged using, forexample, either dihydrolipoic acid (DHLA) [103] or octylamine-modifiedpolyacrylic acid [104] as a surface-capping agent (Fig. 37). In the former case,positively charged proteins are coupled electrostatically directly to thenegatively charged NQD or indirectly through a positively charged leucinezipper peptide bridge [103]. In the latter case, coupling to antibodies,streptavidin, or other proteins is covalent to the polyacrylate cap via traditionalcarbodiimide chemistry [104]. Both the DHLA and the polyacrylatemethods provide relatively simple NQD surface-modification procedures forFigure 37 Three strategies for bioconjugation to NQDs as reviewed in Ref. 102.Highly luminescent (CdSe)ZnS (core)shell NQDs comprise the fluorescent probe.The NQD surfaces are negatively charged using the carboxylate groups of eitherdihydrolipoic acid (DHLA) (a,b) or an amphiphilic polymer (40% octylaminemodified polyacrylic acid) (c). In (a,b), proteins are conjugated electrostatically to theDHLA–NQDs either (a) directly or (b) indirectly via a bridge comprising a positivelycharged leucine zipper peptide, zb, fused to a recombinant protein, PG, that binds toa primary antibody, Ab, with target specificity. In (c), covalent binding by way oftraditional carbodiimide chemistry is used to couple antibodies, streptavidin, orother proteins to the polyacrylate cap. (From Ref. 102 reprinted with permission.)Copyright 2004 by Marcel Dekker, Inc. All Rights Reserved.