Our Gold Nanoparticle Labels

Although colloidal gold is effective for many applications, it is not ideal. The attached antibodies are not permanently chemically bound and can dissociate from the gold. The probes can aggregate, and because of their negative charge they can bind non-specifically to other proteins in the system under study, which gives rise to background signal or false positive results. For many applications, especially in high-resolution immunoelectron microscopy, labeling nucleic acids and other non-protein species, or where the target antigen is in a hard-to-reach region of the cell such as a nuclear organelle, probes with better penetration and less "stickiness" are desirable.

Undecagold structure, showing maleimide-functionalized ligand for cross-linking to thiols.

Metal cluster complexes, such as the undecagold shown above, are in many ways inherently better. Many are uncharged; they are ligated, so that the metal is not exposed; and they can be attached by a specific chemical reaction to anchor the label to a region of the antibody which does not interfere with binding. The problem: most clusters are relatively small. This was addressed by the development of Nanogold®, a larger gold cluster 1.4 nm in diameter which can be visualized directly in the transmission electron microscope. Nanogold® can also be used to label other molecules, such as peptides, nucleic acids or drugs, in much the same mannner as fluorophores like FITC: this opens up whole new classes of electron microscopy probes, based on molecules which cannot be labeled with colloidal gold.

The central goal of our research, however, is to develop much larger clusters or covalently linkable nanoparticles as alternatives to the larger sized colloidal gold. This research will produce improved research reagents for microscopy; but more importantly, it will yield an improved type of immunodiagnostic reagent which will give higher sensitivity, fewer false positives and more consistent results. Such a label could be used in every diagnostic test which now uses colloidal gold. Furthermore, covalent linking opens the way to making test kits from a much wider range of targeted probes, perhaps letting us detect conditions which are inaccessible to today's technology.

Bound colloidal gold, especially the smaller sizes, may not produce sufficiently visible color to be optically detected at low antigen concentrations. However, this is not the end of the story. Silver enhancement can then be used to boost up the signal. See how this works next...