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 biomarker tests that can be readily used by practitioners. Although biomarker detection directly in patients' blood is now possible, low-cost point-of-care tests remain a challenge because relevant biomarkers, especially amyloid- $\beta$ ( $A\beta$ ) peptides, are small, they occur at very low concentrations, and detecting a single marker is insufficient. Here, we demonstrate a photonic resonant sensor able to detect 0.2 pg/ml of $A\beta 42$ and $A\beta 40$ 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, while also employing an immunoassay approach for high selectivity and specificity. The design combines high resonance Q-factor, amplitude, and sensitivity, ideally suited for sensing. We also show the detection of $A\beta 42$ and $A\beta 40$ peptides in the same channel, which is highly relevant for assessing disease progress and opens a route toward 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.