K. Liu, M.M. Mckenna, K.H. Fansler, D. Pappas
NaMi Diagnostics,
United States
Keywords: nanoparticle, immunomagnetic separation, differential centrifugation, atomic emission spectroscopy, cellular-based disease diagnosis
Summary:
The goal is to develop a novel nanoparticle-enabled atomic emission spectroscopy (AES) approach to detect CD71+ expression for cancer diagnosis. As a proof-of-concept, iron-oxide nanoparticles were initially employed for both immune-magnetic cell separation and cell labeling. This is followed by a differential centrifugation step to remove unbound nanomaterials, enabling direct AES analysis of metallic signals from cell-nanoparticle duplexes. Using this design, we achieved a detection limit of 84 cells/mL., however, the interference from endogenous Fe2+/Fe3+ of the blood matrices could confound data interpretation. To overcome this signal-to-noise limitation and further maximize the sensitivity for identifying cancer specific biomarker cells, we modified the biosensor design by introducing gold (Au) nanoparticles conjugated with secondary anti-CD71 antibodies onto the isolated cell-magnetic nanoparticle structures. Because the inherent Au concentration in blood is extremely low and below the detection limit of our method, background interference will be significantly reduced. This work showcases an innovative biomedical application of traditional atomic spectroscopy for sensitive detection of cells of interest. With future improvements, such as selection of optimal particle size, use of internal standard, and optimization of sample prep process, we believe the described technology is feasible for cell-based disease diagnosis, including leukemia and sepsis.