<p>Sensitive, label-free detection of biomarkers is critical for clinical diagnostics. However, conventional nanophotonic biosensors typically remain confined to either the real or imaginary components of the refractive index. This isolation results in weak signal responses, limited operational stability and high instrumental complexity. Here we introduce a <i>Q</i>-modulated refractometric sensing mechanism that operates in the complex-variable domain. This mechanism transduces subtle variations in refractive index into a pronounced modulation of the radiative quality factor, yielding an amplified intensity response in the strong-coupling regime. We implement this mechanism using a non-local three-dimensional bound state in the continuum metasurface fabricated via aluminium-based lithography on 8-inch wafers. The system achieves a photoelectronic sensitivity of 3.3 × 10⁴ mV per refractive index unit with a limit of detection as small as 10⁻⁶ refractive index units. Our sensor enables the detection of small extracellular vesicles at concentrations as low as 24 aM within 15 min, corresponding to an approximately four orders of magnitude increase in sensitivity compared with standard immunoassays. Clinical validation in a cohort of 171 human serum samples demonstrates excellent diagnostic performance, with an area under the receiver operating characteristic curve of up to 94.9% for early lung cancer detection and 92.1% for postoperative monitoring. This work establishes a scalable and robust nanophotonic biosensing paradigm for miniaturized, high-performance diagnostics in clinical, remote and at-home settings.</p>