Zeptomolar detection of analytes via nanoplasmonic biochips based on optimized L-shaped gold nanogratings

Label-free, chip-scale biosensors that exploit periodic nanophotonic and nanoplasmonic structures convert binding-induced refractive-index changes into sharp spectral signatures, enabling compact biochemical and hormone testing. Advances in metasurface and nanograting architectures have improved spectral quality factors and bulk sensitivity; however, for small molecules, pushing label-free limits of detection into the zeptomolar regime in fiber-compatible, low-cost formats remains difficult because of the intrinsically weak mass load and the trade-off between near-field confinement and resonance linewidth. Here, we show an electron-beam–patterned metasurface of L-shaped gold nanogratings on PMMA, engineered to support a Fano-shaped localized surface plasmon resonance, interrogated in transmission through polymer optical fibers and a 3D-printed liquid cell. Finite-element modeling guided the geometry, and the fabricated device exhibits a bulk sensitivity of 1001 ± 61 nm RIU − 1 over n = 1 . 332 –1.352. After immobilizing estrogen receptor α , the platform quantifies β -estradiol from 0.05 to 100 aM ; Langmuir analysis yields a low-dose slope of 9 . 18 ± 2 . 9 nm ( aM ) − 1 and an instrumental limit of detection of 63 ± 20 zM ( 3 σ / S low ), while dihydrotestosterone and bovine serum albumin controls induce negligible shifts. These results indicate that deterministic metasurface design coupled to fiber-based interrogation can deliver ultrasensitive, chip-scale steroid assays without labels and provide a general route to portable photonic biosensing. These features are directly relevant to ultra trace hormone monitoring in clinical endocrinology and fertility medicine, as well as on site surveillance of endocrine disrupting compounds in natural/industrial waters, where the fiber coupled readout and 3D printed liquid cell facilitate portable, low footprint deployment outside laboratory environments. • L-shaped gold nanogratings patterned on PMMA form a compact, label-free nanoplasmonic biochip. • Finite-element optimization of the metasurface geometry yields a bulk refractive index sensitivity of 1001 ± 61 nm/RIU . • A polymer optical fiber and a 3D-printed liquid cell enable a simple, robust, and portable interrogation scheme. • The sensor detects β - estradiol from 0.05 to 100 aM , achieving a limit of detection of 63 ± 20 zM . • Accurate β -estradiol quantification is demonstrated in simulated seawater and artificial saliva , confirming the potential for environmental and clinical applications.