Unveiling simultaneous detection and identification of different forms of amyloid-β peptides in Alzheimer's disease via multi-channel TFBG-SPR biosensor

Early diagnosis and related treatments of Alzheimer's disease (AD) are still a big challenge in medicine. Current clinical examinations for AD pathophysiology combine the quantification of protein biomarkers (i.e., Amyloid-β (Aβ) peptides, total and hyperphosphorylated Tau protein) in cerebrospinal fluid (CSF) with neuroimaging techniques and patient cognitive and psychological assessments. Our work proposes the use of a new label-free biophotonic platform that leverages the unique features of surface plasmon resonance (SPR)-assisted tilted fiber Bragg gratings (TFBGs) and multichannel microfluidics for an accurate and simultaneous analysis of AD markers. We firstly demonstrated that the developed in-operando platform remarkably enables not only an ultra-sensitive detection of Aβ peptides, but also their discrimination between different forms (i.e., monomers and oligomers). The system attains limits of detection (LOD) in the range from 30 to 170 pg mL^-1 below the clinical cut-off level, providing high detection sensitivity for monitoring of AD pathological conditions at early stage. The performance validation and clinical significance are assessed using CSF from animal samples. Key innovations encompass the ability to carry out parallel measurements empowered by multi-channel microfluidics that works with small volume samples, and the capability via binding kinetic analysis to differentiate between the monomeric and oligomeric forms of Aβ peptides, a distinction that is critical since the transition from monomer to oligomer initiates the aggregation and pathogenic transformation in AD. Further advantages include a low consumption of reagents, precision and reproducibility of measurements and improved performances compared to traditional methods, thus providing promising features for clinical diagnostics.