MoNOS Huygens Laboratorium, Universiteit Leiden, 2300 RA Leiden, The Netherlands.
Nat Nanotechnol. 2012 Apr 15;7(6):379-82. doi: 10.1038/nnano.2012.51.
Existing methods for the optical detection of single molecules require the molecules to absorb light to produce fluorescence or direct absorption signals. This limits the range of species that can be detected, because most molecules are purely refractive. Metal nanoparticles or dielectric resonators can be used to detect non-absorbing molecules because local changes in the refractive index produce a resonance shift. However, current approaches only detect single molecules when the resonance shift is amplified by a highly polarizable label or by a localized precipitation reaction on the surface of a nanoparticle. Without such amplification, single-molecule events can only be identified in a statistical way. Here, we report the plasmonic detection of single molecules in real time without the need for labelling or amplification. Our sensor consists of a single gold nanorod coated with biotin receptors, and the binding of single proteins is detected by monitoring the plasmon resonance of the nanorod with a sensitive photothermal assay. The sensitivity of our device is ∼700 times higher than state-of-the-art plasmon sensors and is intrinsically limited by spectral diffusion of the surface plasmon resonance.
现有的单分子光学检测方法需要分子吸收光来产生荧光或直接吸收信号。这限制了可检测的物种范围，因为大多数分子都是纯折射的。金属纳米粒子或介电谐振器可用于检测非吸收分子，因为折射率的局部变化会产生共振位移。然而，目前的方法只有在共振位移通过高度极化的标签或纳米粒子表面的局部沉淀反应放大时才能检测到单个分子。没有这种放大，单分子事件只能通过统计方式来识别。在这里，我们报告了在不需要标记或放大的情况下实时等离子体检测单个分子。我们的传感器由单个涂有生物素受体的金纳米棒组成，通过用灵敏的光热法监测纳米棒的等离子体共振来检测单个蛋白质的结合。我们的设备的灵敏度比最先进的等离子体传感器高约 700 倍，并且固有地受到表面等离子体共振光谱扩散的限制。
