Ultrasensitive detection of nanometer sized metal particles in living cells.

以高空间和时间分辨率直接在活细胞内可视化，跟踪和量化分子和事件的能力对于理解生物系统至关重要。金纳米颗粒作为光学标记物非常有吸引力，因为它们提供无限的观察时间，并且可以通过完善的程序轻松连接到（生物）分子。该项目面临的挑战是在环境条件下直接在活细胞内用光学方法检测和跟踪小于5 nm的金属纳米颗粒。检测单个小纳米颗粒的挑战在于，只有一小部分入射光会照射到颗粒上，导致信号非常弱。我们的目标是通过与强光学参考干涉来放大来自纳米颗粒的信号来检测这些弱信号。我们将比较依赖于颗粒环境的局部折射率的光致变化的方法与依赖于纳米颗粒的本征散射性质的方法。将这些用于检测小金属纳米颗粒的方法与共聚焦显微镜的三维成像能力相结合，将产生强大的检测系统，以在快速时间尺度上在生物相关条件下监测活细胞内的生化过程。

The ability to visualize, track and quantify molecules and events directly inside living cells with high spatial and temporal resolution is essential for understanding biological systems. Gold nano-particles are very attractive as optical labels because they offer unlimited observation time and can be easily linked to (bio-)molecules via well-established procedures. The challenge undertaken in this project is to detect and follow metal nanoparticles smaller than 5 nm at ambient conditions directly inside a living cell with optical methods. The challenge in detecting small single nanoparticles lies in the fact that only a small fraction of the incident light will impinge on the particle leading to very weaks signals. We aim to detect these weak signals by amplifying the signal from the nanoparticle by interference with a strong optical reference. We will compare a method relying on photo-induced changes of the local refractive index of the environment of the particle to a method relying on the intrinsic scattering properties of the nano-particle. Combining these methods for detecting small metal nanoparticles in combination with the three-dimensional imaging ability of a confocal microscopy would result in a powerful detection system to monitor biochemical process inside living cells under biological relevant conditions on fast time-scales.