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{/* Authors */}Early detection of amyloid-β (Aβ) aggregation remains a central obstacle in pre-symptomatic Alzheimer diagnostics. Existing modalities — positron emission tomography, cerebrospinal fluid biomarkers — are either invasive, expensive, or insensitive to the rapid oligomeric phase preceding fibril formation. Here we report a cell-free microfluidic assay capable of resolving Aβ aggregation kinetics within 42 minutes, enabling longitudinal monitoring without tissue sampling. In a pilot cohort of 42 pre-symptomatic participants…
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"The lag-phase shortening preceded detectable amyloid-PET positivity by a median of 2.8 years — a window wide enough for intervention trials to matter."
§3 · Resolving aggregation in 42 minutes
Real-time fluorescence readout enabled kinetic fitting to a modified Finke–Watzky two-step model, capturing both nucleation and elongation rate constants. Across three biological replicates, the assay resolved the lag phase with a coefficient of variation below 8%.
The 42-minute completion time represents a >60-fold speed improvement over standard thioflavin-T plate assays. Throughput of 96 samples per device-hour compares favorably with PET imaging — and without the attendant radioligand exposure.