Misbah Ibrahim, Ohannesian Nareg, Qiao Yawei, Lin Steven H, Shih Wei-Chuan
University of Houston, Houston, TX 77204 USA.
University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA.
IEEE Sens J. 2021;21(21):23971-23978. doi: 10.1109/jsen.2021.3111125. Epub 2021 Sep 7.
We report radiatively coupled arrayed gold nanodisks on invisible substrate (AGNIS) as a cost-effective, high-performance platform for nanoplasmonic biosensing. By substrate undercut, the electric field distribution around the nanodisks has been restored to as if the nanodisks were surrounded by a single medium, thereby provides analyte accessibility to otherwise buried enhanced electric field. The AGNIS substrate has been fabricated by wafer-scale nanosphere lithography without the need for costly lithography. The LSPR blue-shifting behavior synergistically contributed by radiative coupling and substrate undercut have been investigated for the first time, which culminates in a remarkable refractive index sensitivity increase from 207 nm/RIU to 578 nm/RIU. The synergy also improves surface sensitivity to monolayer neutravidin-biotin binding from 7.4 nm to 20.3 nm with the limit of detection (LOD) of neutravidin at 50 fM, which is among the best label-free results reported to date on this specific surface binding reaction. As a potential cancer diagnostic application, extracellular vesicles such as exosomes excreted by cancer and normal cells were measured with a LOD within 112-600 (exosomes/L), which would be sufficient in many clinical applications. Using CD9, CD63, and CD81 antibodies, label-free profiling has shown increased expression of all three surface antigens in cancer-derived exosomes. This work demonstrates, for the first time, strong synergy of arrayed radiative coupling and substrate undercut can enable economical, ultrasensitive biosensing in the visible light spectrum where high-quality, low-cost silicon detectors are readily available for point-of-care applications.
我们报道了一种基于隐形衬底的辐射耦合阵列金纳米盘（AGNIS），它是一种用于纳米等离子体生物传感的经济高效、高性能平台。通过对衬底进行底切，纳米盘周围的电场分布已恢复到如同纳米盘被单一介质包围的状态，从而使分析物能够接触到原本被掩埋的增强电场。AGNIS衬底是通过晶圆级纳米球光刻技术制造的，无需昂贵的光刻工艺。首次研究了辐射耦合和衬底底切协同作用导致的局域表面等离子体共振（LSPR）蓝移行为，其最终使得折射率灵敏度从207 nm/RIU显著提高到578 nm/RIU。这种协同作用还将表面对单层中性抗生物素蛋白-生物素结合的灵敏度从7.4 nm提高到20.3 nm，中性抗生物素蛋白的检测限为50 fM，这是迄今为止报道的关于这种特定表面结合反应的最佳无标记结果之一。作为一种潜在的癌症诊断应用，对癌症和正常细胞分泌的细胞外囊泡（如外泌体）进行了测量，检测限在112 - 600（外泌体/升）范围内，这在许多临床应用中已足够。使用CD9、CD63和CD81抗体进行的无标记分析表明，癌症来源外泌体中所有三种表面抗原的表达均有所增加。这项工作首次证明，阵列辐射耦合和衬底底切的强大协同作用能够在可见光谱中实现经济、超灵敏的生物传感，在该光谱范围内，高质量、低成本的硅探测器可方便地用于即时检测应用。
