Journal
BIOSENSORS & BIOELECTRONICS
Volume 222, Issue -, Pages -Publisher
ELSEVIER ADVANCED TECHNOLOGY
DOI: 10.1016/j.bios.2022.114935
Keywords
Alzheimer?s disease; p-tau(396 404); Surface-enhanced Raman scattering; Phosphorylation-selective antibody; Magnetic nanoparticles
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In this research, a dual-mode magnetic immunosensor was developed for highly sensitive and specific detection of p-tau396,404 in blood samples. The immunosensor showed promising potential for rapid clinical diagnosis and large-scale screening of Alzheimer's disease.
Phosphorylation of tau at Ser 396, 404 (p-tau396,404) is the earliest phosphorylation event and a promising biomarker for the early diagnosis of Alzheimer's disease (AD). However, the detection of blood p-tau is challenging because of its low abundance, easy degradation, and complex formation with various blood proteins or cells, often leading to the underestimation of p-tau levels in conventional plasma-based assays. Herein, we developed a colorimetric and surface-enhanced Raman scattering (SERS) dual-mode magnetic immunosensor for highly sensitive, specific, and robust detection of p-tau396,404 in whole blood samples. The detection assay was based on an immunoreaction between p-tau396,404 proteins, wherein antibody-modified superparamagnetic iron oxide nanoparticles act as recognition elements to capture p-tau396,404 in blood, and then horseradish peroxidaseand Raman tags label the corresponding paired antibody as a reporter to provide high signal-to-noise ratios for the immunosensor. This dual-mode immunosensor achieved identified as low as 1.5 pg/mL of p-tau396,404 in the blood in SERS mode and 24 pg/mL in colorimetric mode by the naked eye. More importantly, this immunosensor rapidly and accurately distinguished AD patients from healthy individuals based on blood p-tau396,404 levels, and also had the potential to distinguish AD patients of different severities. Therefore, the dual-mode immunosensor is promising for rapid clinical diagnosis of AD, especially in large-scale AD screening.
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