A Nanoplasmonic Biosensor for Ultrasensitive Detection of Alzheimer's Disease Biomarker Using a Chaotropic Agent.

Abstract

Blood-based diagnosis (hemodiagnosis) of Alzheimer's disease (AD) is emerging as a promising alternative to cerebrospinal-fluid-based methods because blood contains various kinds of AD biomarkers, including amyloid beta 1-40, 1-42, and τ (tau) protein. However, with current technology, the accuracy of the blood-plasma-based methods is relatively low compared to the traditional methods because the concentration of AD biomarkers in blood plasma is incredibly low, and diverse interference is present in blood plasma, which hinders precise detection. Here, we suggest a nanoplasmonic biosensor using gold nanorods with a chaotropic agent for precise ultrasensitive detecting of Alzheimer's disease biomarkers in human plasma. This nanoplasmonic biosensor is based on the localized surface plasmon resonance (LSPR), which is extremely sensitive to the point where it can respond to an insignificant change of the refractive index around the gold nanoparticles. Also, using guanidine hydrochloride as a chaotropic agent, we can overcome the obstacles of blood-based AD diagnostics. In more detail, this agent interrupts the network between water molecules and weakens the hydrophobic interactions between proteins, remarkably improving detection capabilities to target τ protein. By reducing the overlapping ranges between protein levels in an age-matched control and AD patients' plasma, this system can accurately diagnose AD patients. This platform also can analyze disease from mild cognitive impairment using standardized blood biomarker tau protein, which is related to Alzheimer's disease. As a result, our platform can be applied to clinical trials, and thus it has excellent potential in the medical field.