Parkinson's disease (PD) is an acute and progressive neurodegenerative disorder, and diagnosis of the disease at its earliest stage is of paramount importance to improve the life expectancy of patients. α-Synuclein (α-syn) is a potential biomarker for the early diagnosis of PD, and there is a great need to develop a biosensing platform that precisely detects α-syn in human body fluids. Herein, we developed a surface plasmon resonance (SPR) biosensor based on the label-free iron oxide nanoparticles (Fe3O4 NPs) and paired antibody for the highly sensitive and selective detection of α-syn in serum samples. The sensitivity of the SPR platform is enhanced significantly by directly depositing Fe3O4 NPs on the Au surface at a high density to increase the decay length of the evanescent field on the Au film. Moreover, the utilization of rabbit-type monoclonal antibody (α-syn-RmAb) immobilized on Au films allows the SPR platform to have a high affinity-selectivity binding performance compared to mouse-type monoclonal antibodies as a common bioreceptor for capturing α-syn molecules. As a result, the current platform has a detection limit of 5.6 fg/mL, which is 20,000-fold lower than that of commercial ELISA. The improved sensor chip can also be easily regenerated to repeat the α-syn measurement with the same sensitivity. Furthermore, the SPR sensor was applied to the direct analysis of α-syn in serum samples. By using a format of paired α-syn-RmAb, the SPR sensor provides a recovery rate in the range from 94.5% to 104.3% to detect the α-syn in diluted serum samples precisely. This work demonstrates a highly sensitive and selective quantification approach to detect α-syn in human biofluids and paves the way for the future development in the early diagnosis of PD.
Keywords: Fe3O4 nanoparticles; Parkinson’s disease; human serum; paired antibody; surface plasmon resonance; α-synuclein.