Hyperlens Imaging of Synaptic Vesicle Dynamics

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We are undertaking an imaging initiative to build a hyperlens nanoscope, using newly advanced meta-material hyperlens technology, to achieve superior temporal and spatial resolution and to investigate membrane dynamics during brain synaptic transmission and cellular endocytosis/exocytosis in general. The hyperlens consists of specially designed and micro-fabricated structure elements that can magnify near-field images at sub-diffraction-limited spatial resolution and project the high resolution image at far-field in real time (Yao, et al, 2008, Science, 321:930; Liu, et. al, 2007, Science, 315:1686; Fang, et. al, 2005, Science, 308:534-7). This form of optical nanoscope possesses a unique advantage of both near real time optical imaging (at video rate) and nanometric spatial resolution, in compare with other invasive and slow scanning, structured-illumination, or single-probe localization based imaging techniques such as EM, STED (Hell, 2007, Science, 316: 1153-8), and STORM/PALM (Huang, et al., 2008, Science, 319:810-813; Bates, et. al, 2007, Science 317, 1749-53; Hess, et al, 2007, PNAS 104, 17370-5; Betzig, et. al, 2006, Science 313:1642). Hyperlens-related technology is under rapid development led by the groups of Prof. X. Zhang (UC Berkeley) and Prof. Cheng Sun (the extramural collaborator now at Northwestern University). We believe that hyperlens imaging should be applied to investigate important molecular and cellular events where both imaging resolution and imaging speed are essential. This collaboration team has won an equipment grant from the trans-NIH imaging initiative and is now developing the necessary imaging setup at NIH. We are working to extend the technique and to investigate membrane dynamics during exocytoses and endocytosis where vesicle fusion and fission underpin both fundamental biology and medicine.