Ultrasensitive Alzheimer’s Disease Biomarker Detection with Nanopillar Photonic Crystal Biosensors

The recent development of drugs able to mitigate neurodegenerative diseases has created an urgent need for tests that can be readily used by practitioners. Detection directly in patients’ blood has recently emerged as a possibility, however it remains a challenge, because relevant biomarkers, including amyloid-β (Aβ) peptides, are small, with low concentrations, and a single marker is insufficient. Despite advances in photonic technologies, low-cost tests compatible with these requirements remain elusive. Here, we demonstrate an immunoassay based photonic resonant sensor able to detect 0.2 pg/ml of Aβ42 and Aβ40 in 1% human blood serum, equivalent to 20 pg/ml in undiluted serum, which is the clinically required level. This high performance is achieved by combining gold nanoparticle amplification with a dielectric nanopillar photonic crystal structure in a dimer configuration. The design combines high resonance Q-factor, amplitude and sensitivity, ideally suited for sensing. We also show the detection of the Aβ42 and Aβ40 peptides in the same channel, which is highly relevant for assessing disease progress and opens a route towards multiplexing. Together with the handheld operation we have demonstrated previously, these photonic innovations make a major contribution to the ability to detect and monitor the progression of neurodegenerative diseases such as Alzheimer’s.