Quantum-enhanced biosensing for early detection of neurodegenerative disorders

Background: Early detection of neurodegenerative diseases is an important and unmet clinical need because traditional assays are not sensitive enough to detect low concentrations of biomarkers at the prodromal stages. Objective: This study presents a novel biosensing system based on quantum measurement principles and biomolecular recognition to achieve ultrasensitive detection of biomarkers for Alzheimer’s disease (AD) and Parkinson’s disease (PD) in patient samples. Methods: We developed a hybrid sensor that uses antibody-functionalized nanostructures for selective biomarker capture and nitrogen-vacancy centers in diamond for quantum spin-based readout. The performance was evaluated against standard fluorescence immunoassays of cerebrospinal fluid (CSF) and plasma collected from a clinical cohort (n = 120; 60 AD/PD, 60 controls) in endogenous amyloid-β42 (Aβ42), phosphorylated tau (p-tau181), and α-synuclein. Results: The quantum-enhanced platform detection limits of 12.6 fM for Aβ42, 15.8 fM for p-tau181, and 18.2 fM for α-synuclein are 150–300-fold better than enzyme-linked immunosorbent assay (ELISA). The signal-to-noise ratio increased by ~22 dB, within the quantum-limited scaling. Diagnostic accuracy was high, with an area under the receiver operating characteristic curve ranging from 0.94 to 0.96, superior to ELISA (0.72–0.81). In addition to sensitivity, analytical validation has excellent reproducibility (intra-assay coefficient of variation [CV] ≤ 7.5%, inter-assay CV ≤ 10.8%), high recovery in patients’ plasma and CSF (92–105%), low cross-reactivity (<3%), and a stable sensor performance of seven days of storage. Multiplexed detection reduced the sample volume by 60% and the assay turnaround time by more than threefold compared to ELISA. Conclusion: Quantum-enhanced biosensing is a powerful diagnostic method for detecting biomarkers at clinically relevant concentrations, providing a scalable, noninvasive approach to early diagnosis of neurodegenerative diseases in affected populations. Relevance for patients: Clinical implementation of quantum biosensing has the potential to enable pre-symptomatic disease detection, facilitating earlier therapeutic intervention and improved disease management.