Cancer diagnostic immunoassays are widely used for the detection of disease in vitro, but low antigen concentrations may not be detected in an early stage or confused for baseline noise, leading to false negative or positive diagnoses. Poly(carboxybetaine methacrylate) (PCB) is a zwitterionic polymer that strongly resists biofouling while allowing simple functionalization and effective bioconjugation to proteins. Coating this polymer on iron oxide nanoparticles via a DOPA attachment group allows for easy antibody immobilization, to realize low nonspecific binding and high signal-to-noise ratio in one platform. Methods for nanoparticle construction include synthesis of MNPs (magnetic nanoparticles) coated with PCB-DOPA and PCB-DOPA2. The coated particles are functionalized with FITC-BSA and FITC-streptavidin using EDC/NHS chemistry to optimize conjugation parameters. A model antibody (ALCAM antibody) is then conjugated to test the platform’s sensitivity for immunoassays. The functionalized nanoparticles are characterized with Dynamic Light Scattering (DLS), fluorescence spectroscopy, flow cytometry, and Surface Plasmon Resonance (SPR). Control groups with bare beads, functionalized beads with no polymer coating, or no functionalization are also processed in the experiment to compare with experimental groups. In preliminary tests, the functionalized magnetic nanoparticles have a high level of immobilization of each tested protein or antibody (FITC-BSA, FITC-streptavidin, and ALCAM antibody). In the plasma stability test, the PCB-coated and beads show low nonspecific binding even with high levels of functionalization. The experimental immunoassay can detect a low concentration of the ALCAM cancer biomarker in bovine serum, with less baseline noise than a commercial immunoassay (Luminex MagPlex®). The functionalized magnetic nanoparticles have a low detection limit to an early-stage cancer biomarker and a high signal-to-noise ratio due to reduced nonspecific binding. This platform could be extended to many clinical immunoassays in which either false negative or false positive diagnostic readings are problem.