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The size, distribution, and specific shape of ordered nanophotonic structures are crucial for their biomedical applications. Bottom‐up approaches such as self‐assembly, emulsification, and precipitation are commonly fabricated nanophotonic structures, which often lack control of nanophotonic structures morphologies and monodispersed sizes. On the contrary, top‐down nanofabrication techniques offer the advantages of high fidelity and high controllability and are employed in the fabrication of nanophotonic structures. This review focuses on top‐down nanofabrication techniques to fabricate ordered nanophotonic structures and their biomedical applications. Several top‐down approaches used in the semiconductor industry and other fields requiring micro‐ and nanopatterns are used, including electron beam lithography/ion beam lithography, photolithography, interference lithography, nanoimprint lithography, nanosphere lithography, nanotransfer lithography, and nano‐electrodeposition. Various current and emerging biomedical applications of the ordered nanophotonic structures are also covered: i) surface‐enhanced Raman scattering, ii) plasmonics, including surface plasmon resonance and localized surface plasmon resonance, and iii) fluorescence enhancement. Finally, a future perspective of nanophotonic structures fabricated by top‐down techniques in biomedical applications is also summarized. [ABSTRACT FROM AUTHOR]

Nanophotonic metasurfaces are widely utilized in various domains, such as biomedical, healthcare, and environmental monitoring, benefiting from their unique advantages of label‐free, noninvasive, and real‐time response. However, nanophotonic metasurfaces usually rely on sophisticated instruments, and expensive and time‐consuming fabrication processes, which severely restricts their practical applications. Herein, a spatially gradient metasurface is integrated with an imaging‐based sensing scheme, waiving the requirement of spectrometers and achieving an ultrahigh imaging‐based sensitivity of 3321 pixels/refractive index unit superior to that characterized using conventional compact spectrometers. The metasurface is fabricated by nanoimprint lithography using a reusable cyclic olefin copolymer template featuring millions of unique nanostructures. Under the illumination of monochromatic light, the transmittance of different nanostructures on the metasurface differs, resulting in grayscale images with varied intensity distributions. Analyzing the intensity change of the metasurface's recorded image can obtain the covering medium's refractive index. Furthermore, through theory and experimentation, the high reliability of the proposed reusable and flexible template has been verified for nanophotonic metasurface fabrication which further reduces the fabrication cost of core sensing elements. Finally, with proper optimization of the metasurface structure and imaging system, this setup is expected to be applied to many emerging areas of point‐of‐care, real‐time, and on‐site biosensing. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is one of the most common ocular surface diseases, characterized by unstable tear film and ocular inflammation, affecting hundreds of millions of people worldwide. Currently, the clinical diagnosis of DED mainly relies on physical methods such as optical microscopy and ocular surface interferometric imaging, but classifying DED is still difficult. Here, we propose a compact and portable immune detection system based on the direct imaging of a nanophotonic metasurface with gradient geometry, for fast and ultra-sensitive detection of multiple biomarkers (i.e. Matrix metalloproteinase-9 (MMP-9), Lipocalin-1 (LCN-1), Lactoferrin (LTF)) in tears for the diagnosis and classification of DED. This centimeter-scale concentric nanophotonic metasurface, which consists of millions of unique metallic nanostructures, was fabricated through a cost-effective nanoimprint lithography (NIL) process. The immune detection system based on the antibody-modified metasurface shows favorable detection selectivity, an ultra-high sensitivity (3350 pixels/Refractive Index Unit (RIU)) and low limit of detection (LOD) (0.3 ng/mL for MMP-9, 1 ng/mL for LTF, and 0.5 ng/mL for LCN-1). Further clinical sampling and detection results demonstrated that this multi-biomarker detection system enabled accurate determination and symptom classification of DED, manifesting high correlation and consistency with clinical diagnosis results. The advantages such as low sample consumption, one-step detection, simple operation, and simultaneous detection of multiple biomarkers make the platform promising for screening and detecting a broader range of biomarker combinations in clinical practice. [ABSTRACT FROM AUTHOR]