Electrical detection method of oligomeric amyloid beta in blood plasma sample of Alzheimer's disease

摘要

Electrical detection of oligomeric amyloid beta (oAβ) in plasma samples in Alzheimer's disease (AD) using micro-machined inter-digital capacitors.A method is disclosed. The histopathological features of Alzheimer's disease (AD) show extracellular amyloid plaques and intracellular tangles. Neuropathological changes in AD include synaptic degeneration, nerve loss, and memory impairment. Recently, oligomeric amyloid beta (oAβ) may be an active virulence factor in very early stages of AD, and elevated oAβ levels are neurotoxic and result in cerebral neuropathy. Therefore, oAβ is a potential biomarker for diagnosing AD symptoms. Clinical studies suggest that abnormal levels of oAβ in blood, brain tissue and cerebrospinal fluid are involved in the progression of AD. The analysis and evaluation of oAβ is very important for the early diagnosis and treatment of AD, and so far no such kind of sensitive, selective, electrical and conventional method exists. Previously, oAβ antibody-based electrochemical immuno-sensing approaches have been attempted and have detected Aβ within 30-40 minutes compared to 6-8 hours of the ELISA test. In this study, an anti-oAβ antibody and ob5 aptamer were immobilized for label-free detection of oAβ by designing and processing on a Pt/Ti-interdigital capacitor chip of a biosensor. In the marker sandwich biosensor, real-time capacitive detection was monitored in 5 seconds even at very low concentrations of oAβ in plasma using an ob5 aptamer with extremely-high affinity. These results indicate that the ob5 aptamer chip system can determine within the femto-molar (fM) range of oAβ enrichment in plasma. Perhaps, the capacitance change sensing system of the biosensor showed excellent potential for easy and rapid monitoring of Alzheimer's disease (AD) in clinical samples with high selectivity and sensitivity.