Surface-functionalized SERS platform for deep learning-assisted diagnosis of Alzheimer's disease

Early diagnosis of Alzheimer's disease is crucial to stall the deterioration of brain function, but conventional diagnostic methods require complicated analytical procedures or inflict acute pain on the patient. Then, labelfree Surface-enhanced Raman spectroscopy (SERS) analysis of blood-based biomarkers is a convenient alternative to rapidly obtain spectral information from biofluids. However, despite the rapid acquisition of spectral information from biofluids, it is challenging to distinguish spectral features of biomarkers due to interference from biofluidic components. Here, we introduce a deep learning-assisted, SERS-based platform for separate analysis of blood-based amyloid beta (1-42) and metabolites, enabling the diagnosis of Alzheimer's disease. SERS substrates consisting of Au nanowire arrays are fabricated and functionalized in two characteristic ways to compare the validity of different Alzheimer's disease biomarkers measured on our SERS system. The 6E10 antibody is immobilized for the capture of amyloid beta (1-42) and analysis of its oligomerization process, while various self-assembled monolayers are attached for different dipole interactions with blood-based metabolites. Ultimately, SERS spectra of blood plasma of Alzheimer's disease patients and human controls are measured on the substrates and classified via advanced deep learning techniques that automatically extract informative features to learn generalizable representations. Accuracies up to 99.5% are achieved for metabolite-based analyses, which are verified with an explainable artificial intelligence technique that identifies key spectral features used for classification and for deducing significant biomarkers.