Enhanced Plasmonic Biosensor Utilizing Paired Antibody and Label-Free Fe3O4 Nanoparticles for Highly Sensitive and Selective Detection of Parkinson’s α-Synuclein in Serum

Abstract

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.

Broad-Spectrum Theranostics and Biomedical Application of Functionalized Nanomaterials

“…For DNA sensors, the detection limit was reported to be 25 ng/mL and 75 ng/mL [ 192 ]. Surface plasmonic resonance (SPR) biosensors were developed by directly depositing label-free iron oxide nanoparticles (Fe 3 O 4 NPs) together with paired antibodies to enhance the sensitivity and selectivity efficacy of biosensors in detecting α-synuclein in the serum of a sample of patients with Parkinson’s disease [ 193 ].Electrochemical glucose biosensorswere also developed with platinum nanoparticles (PtNPs) immobilized to the surface of glucose oxidase that was deposited on poly (Azure A). The sensor showed increased selectivity with a detection limit of 7.6 μMand high sensitivity towards glucose in patients’ samples, ultimately suggesting that it is a good alternative to glucose sensors when compared to existing sensors [ 194 ].…”

Deformation induced evolution of plasmonic responses in polymer grafted nanoparticle thin films

“…Recent studies indicate that the tunable optical properties of plasmonic nanoparticle assemblies make them attractive for applications in sensing, 28–31 energy conversion, 10,32 non-linear signal enhancement, 33,34 plasmon-enhanced catalysis, 35 opto-electronic devices 36,37 and theranostics. 10,38 The optical properties in such assemblies depends on the building blocks and their spatial organization. In particular, the arrangement of the plasmonic nanoparticles in a dielectric background can be used for tuning the coupled resonances of the nanoparticles and can also be used for coupling them to other photonic or plasmonic modes.…”

Non-invasive Monitoring of α-Synuclein in Saliva for Parkinson’s Disease Using Organic Electrolyte-Gated FET Aptasensor

“…Despite the promising LOD and linear ranges of these devices, the main challenges of laboratory prototypesvariations and susceptibility to small modificationsremain a significant barrier to large-scale production. Mandala et al observed the detection of αSyn in dilute serum samples with a LOD of 5.6 fg/mL, with a recovery rate of 84.5–104.3% with their plasmon resonance detector . Despite the promising LOD, the material costs and fabrication requirements are extreme with high intrinsic noise.…”

“…Mandala et al observed the detection of αSyn in dilute serum samples with a LOD of 5.6 fg/mL, with a recovery rate of 84.5−104.3% with their plasmon resonance detector. 19 Despite the promising LOD, the material costs and fabrication requirements are extreme with high intrinsic noise.…”