Common-path interferometric label-free protein sensing with resonant dielectric nanostructures

Biosensors: Nanostructures team up to turn down the noise Portable devices that spot biomarkers in a patient's bloodstream stand to benefit from a photonic microchip that can achieve ultra-low detection limits. Isabel Barth from the University of York in the United Kingdom and colleagues designed a biosensor based on guided-mode resonances, a phenomenon that uses laser light to switch on strong resonant signals inside nanoscale gratings. The researchers improved this technology by simultaneously exciting two resonant modes with a low-cost laser diode. This approach enables sensing of protein-antibody binding induced refractive index changes using relative phase differences between the two modes, minimizing the impact of noise due to outside sources including mechanical vibrations. The team demonstrated label-free detection of procalcitonin, a key biomarker for bacterial infections, at picogram/milliliter scales, which could, for example, be relevant in the context of bacterial co-infections of COVID-19 patients. Research toward photonic biosensors for point-of-care applications and personalized medicine is driven by the need for high-sensitivity, low-cost, and reliable technology. Among the most sensitive modalities, interferometry offers particularly high performance, but typically lacks the required operational simplicity and robustness. Here, we introduce a common-path interferometric sensor based on guided-mode resonances to combine high performance with inherent stability. The sensor exploits the simultaneous excitation of two orthogonally polarized modes, and detects the relative phase change caused by biomolecular binding on the sensor surface. The wide dynamic range of the sensor, which is essential for fabrication and angle tolerance, as well as versatility, is controlled by integrating multiple, tuned structures in the field of view. This approach circumvents the trade-off between sensitivity and dynamic range, typical of other phase-sensitive modalities, without increasing complexity. Our sensor enables the challenging label-free detection of procalcitonin, a small protein (13 kDa) and biomarker for infection, at the clinically relevant concentration of 1 pg mL(-1), with a signal-to-noise ratio of 35. This result indicates the utility for an exemplary application in antibiotic guidance, and opens possibilities for detecting further clinically or environmentally relevant small molecules with an intrinsically simple and robust sensing modality.