Alzheimer’s disease (AD) is the leading cause of dementia, yet no simple blood test exists for its early, point-of-care detection. In this context, the quantification of blood-based biomarkers is critical for enabling timely treatment interventions, and the development of technologies capable of assessing small (a few kDa) peptides at extremely low (pg/mL) concentrations in blood is an urgent and global challenge. Here, we present a breakthrough biosensing technology that leverages major advances in photonics to transform blood-based biomarker detection. Using a handheld guided mode resonance biosensor, we combine refractive index sensing with nanoparticle-enhanced signal amplification to simultaneously detect biomarkers of AD with sensitivity in the clinically relevant range. Our resonator comprises a chirped sequence of precision-engineered nanopillars to translate spectral information into spatial outputs and offers exceptional Q-factor sensitivity and amplitude. Our platform mitigates against non-specific interactions, provides high specificity for isoforms of β-amyloid (Aβ) and phosphorylated tau (p-tau), which are key biomarkers of disease, and the amplification strategy, which takes advantage of gold and aluminium oxide nanoparticles, boosts the biosensor’s response by over an order of magnitude. We demonstrate the detection of biomarkers including Aβ(1-42), Aβ(1-40), and p-tau217 at pg/ml levels in vitro and in diluted serum, matching clinical thresholds for blood-based diagnosis. We also demonstrate the simultaneous detection of biomarkers on the same device, enabling quantification of their ratios, which represent hallmarks of AD progression. Constructed from amorphous silicon and compatible within a handheld readout, our platform is simple, robust, low-cost, scalable, and primed for translation into point-of-care diagnostics. Beyond Alzheimer’s disease, our strategy provides a generalizable framework for the ultrasensitive and multiplexed detection of biomarkers found in low-abundance in complex biofluids and exemplifies how emergent photonic innovations can address pressing challenges within the life sciences.
Arruda et al. (Sun,) studied this question.