This work presents the use of flickering nanoparticles for imaging biological samples. The method has high noise immunity, and it enables the detection of overlapping types of GNPs, at significantly sub-diffraction distances, making it attractive for super resolving localization microscopy techniques. The method utilizes a lock-in technique at which the imaging of the sample is done using a time-modulated laser beam that match the number of the types of gold nanoparticles (GNPs) that label a given sample, and resulting in the excitation of the temporal flickering of the scattered light at known temporal frequencies. The final image where the GNPs are spatially separated is obtained using post processing where the proper spectral components corresponding to the different modulation frequencies are extracted. This allows the simultaneous super resolved imaging of multiple types of GNPs that label targets of interest within biological samples. Additionally applying the post-processing algorithm of the K-factor image decomposition algorithm can further improve the performance of the proposed approach.
Tali Ilovitsh, Yossef Danan, Rinat Meir, Amihai Meiri, and Zeev Zalevsky, "Temporally flickering nanoparticles for compound cellular imaging and super resolution," Proc. SPIE 9721, Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications XIII, 97210V (Presented at SPIE BiOS: February 18, 2016; Published: 22 April 2016); https://doi.org/10.1117/12.2208864.
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