Development of Multimodal Correlation Imaging Microscopy for Cell Biology

描述（由申请人提供）：我们提出开发一种多模态成像仪器，其特别适合于在非常低的强度水平下实时测量荧光或光散射。所提出的方法是基于受控的空间和时间调制的照明场的结合与出射光场的有效集成。这种灵活的照明的实现允许使用鲁棒且高效的低光检测方案，其可以在单光子水平下操作，使得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，并且可以应用于在透射或反射中操作的发射（荧光）或散射模式。照明的完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态，其中分辨率仅在视场内的感兴趣区域中增强。通过完全控制照明的能力实现的另一个有趣的结果是同时具有空间和光谱分辨率而不增加测量时间并且不使用色散光学元件和附加仪器的可能性。

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.