Sensitive biodetection in flow using metasurface hosting quasi-bound state in the continuum resonances

Technical Summary: Sensitive Biodetection in Flow Using Metasurfaces Hosting Quasi-Bound State in the Continuum Resonances

Problem Statement
Optical biosensors require high sensitivity to detect biomolecules at low concentrations, often necessitating real-time monitoring without complex amplification steps. While plasmonic metasurfaces offer high sensitivity due to strong electric field localization, they suffer from low quality factors (Q-factors) due to intrinsic ohmic losses, which limits their practical detection limits. Conversely, dielectric metasurfaces utilizing Mie resonances offer negligible losses but typically localize the enhanced electric field within the high-refractive-index material itself, rather than in the surrounding sensing volume where the analyte resides. Furthermore, while quasi-bound states in the continuum (q-BIC) metasurfaces have demonstrated high Q-factors and sensitivity, their application for real-time, flow-based biosensing—particularly for point-of-care diagnostics—remains underexplored. Many existing q-BIC sensing demonstrations rely on incubation, multiplexing, or machine learning algorithms to enhance detection limits, rather than achieving high sensitivity through direct, real-time measurement.

Methodology
The authors designed and fabricated a dielectric metasurface composed of silicon nanoresonators arranged in a "2-bar" unit cell configuration. The design introduces structural asymmetry by varying the gap widths between the two bars within a unit cell ($G_1$) and the gaps between bars of neighboring unit cells ($G_2$). This asymmetry ($\Delta = |G_1 - G_2|$) breaks the symmetry of the structure, allowing far-field coupling to a q-BIC resonance that is specifically localized in the air gap between the nanoresonators.

• Fabrication: The metasurfaces were fabricated on amorphous silicon thin films using electron-beam lithography (EBL) followed by reactive ion etching (RIE). The final structures featured bars with widths of 242 nm, heights of 270 nm, and lengths of 405 nm and 373 nm, with a unit cell period of 770 nm.
• Experimental Setup: The sensors were integrated into a commercial microfluidic flow cell (Fluidic 864). Transmission spectra were measured in real-time using a custom optical setup with a white light source and an optical spectrum analyzer.
• Sensing Protocol:
  1. Bulk Sensitivity: The system was first characterized by flowing ethanol:water mixtures of varying refractive indices over the metasurface to determine bulk refractive index sensitivity.
  2. Functionalization: The metasurface was functionalized with biotin-PEG-silane receptors to enable specific binding with streptavidin.
  3. Biosensing: The platform was tested with streptavidin conjugated to quantum dots (strep-QD) to visually correlate resonance shifts with fluorescence. Subsequently, pure streptavidin solutions were flowed through the cell at concentrations ranging from $10^{-8}$ M to $10^{-4}$ M to determine the limit of detection (LOD) without amplification.

Key Contributions and Results

• Resonance Localization: The study successfully demonstrated that the q-BIC resonance is localized within the sensing volume (the gap between nanoresonators), combining the low-loss properties of dielectrics with the field enhancement required for high sensitivity.
• Bulk Refractive Index Sensitivity: The metasurface exhibited a bulk refractive index sensitivity of $315 \pm 22$ nm/RIU and a figure-of-merit (FOM) of $66 \pm 5$ RIU$^{-1}$. The experimental Q-factor was measured at 141 in air, increasing to 261 when immersed in Phosphate-Buffered Saline (PBS).
• Real-Time Kinetic Measurements: The flow-based setup allowed for real-time monitoring of resonance shifts. The system could detect refractive index changes corresponding to ethanol:water mixtures as low as 1% vol/vol, with full reversibility upon returning to pure water.
• Biosensing Performance:
  • Specific binding of streptavidin to the biotin-functionalized surface was confirmed, showing a distinct redshift in the q-BIC resonance.
  • The limit of detection (LOD), defined as 3$\sigma$ above the noise level, was determined to be $1.8 \times 10^{-8}$ M (1.1 µg/mL) for streptavidin.
  • The binding kinetics were successfully tracked in real-time, and the Hill equation was used to model the binding saturation, yielding a dynamic range of 3.9 nm.

Significance and Claims
The paper claims that this platform represents a compact optical approach suitable for point-of-care diagnostics with fast, real-time read-out. By localizing the q-BIC resonance in the gap between nanoresonators, the design overcomes the limitations of previous dielectric sensors where field enhancement occurs inside the material. The authors emphasize that high sensitivities were achieved for streptavidin detection without the need for additional amplification steps, incubation periods, or complex data processing algorithms, which are common requirements in other q-BIC sensing works. Additionally, the reversible nature of the streptavidin-biotin interaction at elevated temperatures suggests the potential for sensor reusability. The work highlights the viability of q-BIC metasurfaces for practical, flow-based biosensing applications.