Detection of Alzheimer’s Disease Through Fluorescent Nanodiamonds-Based Spin-Enhanced Lateral Flow Immunoassay

Fluorescent nanodiamond (FND) has recently been regarded as a superior alternative reporter for lateral flow immunoassays (LFIA). The negatively charged nitrogen-vacancy (NV^–) center in FND is a point defect with unique magneto-optical properties, giving outstanding characteristics to detect biomarkers of diseases. Alzheimer’s disease (AD) is the most common form of dementia, characterized by decreased memory, thinking, cognition, behavior, personality, and ability to conduct everyday duties, which might result in complete brain failure and, eventually, death. The two most commonly used detection techniques to detect changes in the brain caused by AD are brain imaging (CT, MRI, PET) and lumbar puncture. However, while brain imaging is costly and time-consuming, lumbar puncture is controversial since 30% of patients get severe headaches followed by nausea and vomiting lasting more than a week. To this end, we have developed a Spin-Enhanced Lateral Flow Immuno-Assay (SELFIA) for non-invasive AD diagnostics utilizing the spin properties of the NV^– centers in FND to achieve background-free ultrasensitive detection. In addition, to enhance sensitivity and specificity, we employed a sandwich assay of SELFIA to further noncovalently conjugate FND to anti-pTau antibodies toward detecting pTau protein (a critical AD biomarker involved in AD pathology), while the capture antibody immobilized on the membrane. Note that we have a comparable result with Enzyme-Linked Immunosorbent Assay (ELISA), as our FND-based SELFIA only requires approximately 30 minutes to reach a detection limit of 7 pg/mL for pTau (the sensitivity/specificity threshold is 15 pg/mL in plasma). Hopefully, this study will contribute to developing a safe, simple, and accurate AD detection platform that can identify this illness in its earliest stages and might also be applied to other diseases in precision health.