Development of Multimodal Correlation Imaging Microscopy for Cell Biology

描述（由申请人提供）：我们建议开发一种多模态成像仪器，特别适合于在非常低强度水平下实时测量荧光或光散射。该方法基于照明场的可控时空调制，并结合出射光场的有效集成。这种灵活照明的实现允许使用健壮且高效的低光检测方案，该方案可以在单光子水平上运行，使整个系统与高速活细胞成像要求兼容。所提出的成像概念是通用的，可以应用于发射（荧光）或散射模式在传输或反射操作。照明的全时间和控制提供了独特的好处，例如分辨率和速度之间的可调节权衡，但最重要的是，它允许自适应成像模式，其中分辨率仅在视野内感兴趣的区域增强。完全控制照明的能力带来的另一个有趣的结果是，在不增加测量时间和不使用色散光学元件和额外仪器的情况下，同时具有空间和光谱分辨率的可能性。

DESCRIPTION (provided by applicant): We propose to develop a multimodal imaging instrument that is particularly suitable for real-time measurement of either fluorescence or light scattering at very low intensity levels. The proposed approach is based on controlled spatial and temporal modulation of the illumination field in conjuncture with an efficient integration of the outgoing optical field. The implementation of such a flexible illumination permits using robust and efficient low-light detection schemes that can operate at single photon levels making the entire system compatible with high speed, live-cell imaging requirements. The proposed imaging concept is general and can be applied to both emission (fluorescence) or scattering mode operated in either transmission or reflection. The full temporal and control of the illumination offers exclusive benefits such as adjustable tradeoff between resolution and speed but, most importantly, it allows for an adaptive imaging modality where the resolution is enhanced only in areas of interest within the field of view. Another interesting outcome enabled by the ability to fully control the illumination is the possibility to simultaneously have spatial nd spectral resolution without increasing the measurement time and without using dispersive optical elements and additional instrumentation.