The proposed research embodies two primary innovations: 1) a dendrimer-based heterogeneous cross-linking chemistry for the preparation of immobilized enzymes and antibodies with enhanced stability, activity, and mass transfer characteristics; and 2) sequestration of zero valent ferromagnetic metals such as Fe, Ni, and Co within the hydrophobic inner pores of the dendrimer as the basis for magnetic separations using these materials. If successful, the research will result in significantly improved methods for binding and separation of a wide variety of analytes of clinical significance, including those assayed by RIA and ELISA methodologies. Anticipated benefits include: the ability to detect clinically significant analytes in lower concentrations, reduction in unit cost, compatibility with microchemical assay methods, improved chemical and thermal stability, and simplification of the requirements for automation. Using the proposed dendrimer-based chemistry, immobilization of antibodies and enzymes on solid supports to facilitate detection becomes unnecessary, and is replaced by immobilization on dissolved or colloidal dendrimers. This will then facilitate antigen-antibody binding by minimizing the mean free diffusion path required for reaction. The material can then be separated from solution or colloidal suspension in bulk serum (or other matrix) using magnetic forces, resulting rapid, accurate, and sensitive assays. Also, a new class of materials may be prepared in which the cross-linked dendrimer antibody conjugate is self-supporting.
The most promising application of a magnetic dendrimer based immunologic assay will be in microminiaturized analytical systems. The multifunctional surface of a spherical magnetic dendrimers should result in improved reaction rates between the antibody and antigen, while the small size and spherical shape will enhance micro-channel flow of the antigen - magnetic dendrimer complex to the detector. Determination of the very small magnetic signal originating from the superparamagnetic cobalt particles within the dendrimer at a detector surface will require a very sensitive detector such as the giant magnetoresistive materials utilized by the high density magnetic storage media.
| Atwater, James E; Akse, James R; Holtsnider, John T (2008) Cobalt - poly(amido amine) superparamagnetic nanocomposites. Mater Lett 62:3131-3134 |
