A SERS nanocellulose-paper-based analytical device for ultrasensitive detection of Alzheimer's disease

Alzheimer's disease (AD), the most prevalent neurodegenerative ailment worldwide, results in severe cognitive decline and irreversible memory loss. Early identification of AD is significant to patients for personalized intervention since effective cure and treatment methods for AD are lacking. Despite the severity of the disease, existing highly sensitive AD detection methods, including neuroimaging and brain deposit-positive lesion tests, are challenging due to their high cost and complicated operation. Therefore, these methods are unsuitable for early detection, especially in low-resource settings. Although regular paper-based microfluidics are cost-efficient, they are restricted by a high limit of detection (LOD) and susceptibility to contamination. To address the above limitations, for the first time, we report the ultrasensitive and low-cost nanocellulose paper (nanopaper)-based analytical microfluidic devices (NanoPADs) for AD detection using Surface-enhanced Raman scattering (SERS) immunoassay method. Nanopaper offers advantages as SERS substrates, such as an ultrasmooth surface, high optical transparency, and tunable chemical properties. Therefore, our NanoPADs are distinguished by their cost-efficiency and ease of implementation, presenting an avenue for effective early detection of AD with ultra sensitivity. More importantly, our work provides the foundation for SERS-based immunoassay detection of multiple biomarkers on NanoPADs for various diseases in the future.