Proteins orchestrate nearly all cellular processes and serve as key biomarkers and therapeutic targets. Conventional detection bioassays are confined in centralized laboratories, dependent on bulky instruments or labeling workflows. Currently, they are limited to merely read out the concentration of proteins, leaving molecular details such as layer thickness and orientation inaccessible, which are critical for functional assessment. Here, we present a Mie-resonant nanosensor that transduces biomolecular binding events into vivid colorimetric changes through high-order quadrupole modes in the visible spectrum, unprecedently extending colorimetric sensing to the biomolecular scale. Coherent quadrupole interference enhances backward scattering enabling optical readout of protein layers as thin as 1.8 nm along with recognizing protein orientation, termed as the visualized Mie-resonance sensing (VIMS). Both quality control of antibody functionalization and quantitative detection of antigens can be achieved via VIMS, demonstrating a 0.4 pg/mL detection limit of cardiac troponin T (cTnT) within 20 minutes. Integrated with a smartphone-compatible point-of-care platform, the assay reliably diagnoses acute myocardial infarction (AUC > 0.95) from serum, saliva and urine (N=220), and identifies elevated baseline cTnT in high-stress populations. This work bridges nanophotonic field confinement with biomolecular structural resolution, enabling label-free, portable, and quantitative molecular-scale optical sensing for decentralized precision diagnostics.
Tan et al. (Fri,) studied this question.
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