Self-calibrating surface-enhanced Raman scattering-lateral flow immunoassay for determination of amyloid-β biomarker of Alzheimer's disease

Rapid early diagnosis of Alzheimer's disease (AD) is critical for its effective and prompt treatment since the clinically available treatments can only relieve the symptoms or slow the disease progression. However, it is still a grand challenge to accurately diagnose AD at its early stage because of the indiscernible early symptoms and the lack of sensitive detection tools. Here, we develop a self-calibrating surface-enhanced Raman scattering (SERS)-lateral flow immunoassay (LFIA) biosensor for quantitative analysis of amyloid-β1-42 (Aβ1-42) biomarker in biofluids, enabling accurate AD diagnosis. The designed SERS-LFIA biosensor makes full use of the unique aspects of the LFIA format and the SERS technique to quantify the Aβ1-42 level in complex biofluids with high sensitivity, excellent anti-interference capability, low-cost, and operation simplicity. The key aspect of the design of this biosensor is that internal standard (IS)-SERS nanoparticles are embedded in the test line of the test strip as a self-calibration unit for correction of fluctuations of SERS signals caused by various external factors such as test parameters and sample heterogeneity. We demonstrate significant improvement of the detection performance of the SERS-LFIA biosensor for ratiometric quantification of Aβ1-42 owing to the built-in IS in the test line. We expect that the present IS-based biosensing strategy provides a promising tool for accurate AD diagnosis and longitudinal monitoring of therapeutic response with great promises for clinical translation.