Engineering Monovalent Quantum Dot-Antibody Bioconjugates with a Hybrid Gel System

Monovalent nanoparticles are of strong current interest in biological imaging and detection due to their potential for stoichiometric binding with target molecules. We report the preparation of monovalent quantum dot antibody bioconjugates using a high-resolution hybrid gel system specially designed for fractionation of nanoparticle bioconjugates. A key feature of this technology is that it is broadly applicable to many types of nanoparticle antibody complexes without the need of genetically engineered proteins. This is particularly important because antibodies are still the dominant molecular targeting probes, despite new discoveries made with other targeting probes such as aptamers and peptides. Furthermore, we show experimental evidence of improved quantification capability using the monovalent probes, whose advantages over their multivalent counterparts had largely been a theoretic prediction previously. This new class of nanoprobe should find broad application in quantitative biological detection and imaging in vitro and in vivo.