Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa , Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal.
Molecular Biosensing for Medical Diagnostics, Department of Applied Physics, Eindhoven University of Technology , Eindhoven, The Netherlands.
Langmuir. 2017 Jul 5;33(26):6503-6510. doi: 10.1021/acs.langmuir.7b00422. Epub 2017 Jun 20.
Gold nanorods are promising platforms for label-free biosensing. We have functionalized gold nanorods with biotin thiol linkers of increasing chain length and evaluated their ability in the molecular detection of streptavidin. We have found an unexpected effect of the increase in linker length, which resulted in a substantial improvement of the plasmon response at surface saturation. The plasmon peak shift increased from 5 to 14 nm, i.e., more than twice the response, between the short and long biotin linkers. This effect is observed only for site-selective tip functionalization, whereas for a full biotin coating there is no improvement observed with the linker length. The improved plasmon response for tip functionalization is attributed to low biotin coverage but is directed to the most sensitive regions, which, combined with a longer chain linker, reduces the steric hindrance for streptavidin binding on the rod's surface. The model sensors were further characterized by measuring their dose-response curves and binding kinetic assays. Simulations of the discrete dipole approximation give theoretical plasmon shifts that compare well with the experimental ones for the long linker but not with those of the short linker, thus suggesting that steric hindrance affects the latter. Our results highlight the importance of specifically functionalizing the plasmonic hot spots in nanoparticle sensors with the adequate density of receptors in order to maximize their response.
金纳米棒是用于无标记生物传感的有前途的平台。我们用生物素硫醇链接剂对金纳米棒进行了功能化，这些链接剂的链长逐渐增加，并评估了它们在链霉亲和素分子检测中的能力。我们发现了链接剂长度增加的意外影响，这导致在表面饱和时等离子体响应有了实质性的提高。等离子体峰位移从短生物素链接剂的 5nm 增加到 14nm，即响应提高了两倍多。这种效应仅在选择性尖端功能化时观察到，而对于完全的生物素涂层，链接剂长度没有观察到任何改善。尖端功能化的等离子体响应的改善归因于低生物素覆盖率，但指向最敏感的区域，这与较长链链接剂结合，减少了链霉亲和素在棒表面结合的空间位阻。通过测量剂量-响应曲线和结合动力学测定，进一步对模型传感器进行了表征。离散偶极近似的模拟给出了理论等离子体位移，与长链接的实验结果相比非常吻合，但与短链接的实验结果不符，这表明空间位阻会影响后者。我们的结果强调了在纳米粒子传感器中用适当密度的受体特异性功能化等离子体热点以最大化其响应的重要性。
