MRI: Development of a hybrid quantitative phase microscope for live cell imaging

这项研究的目标是开发一种新型的定量相差显微镜，用于研究和分析由于环境影响和疾病引起的病理导致的细胞结构和功能的变化。为了实现这一目标，提出了一种混合光学干涉成像和传感系统，将能够可视化快速细胞动力学的低相干广域数字干涉(WFDI)和利用等离子体纳米粒子(NPs)的光热加热来实现分子成像的新型光学相干层析(OCT)方法相结合。低相干WFDI系统的作用是可视化细胞动力学，以评估由于外部影响对细胞功能的调节。这种传输模式系统将定量记录已通过样品的光的光路延迟，从而将创建局部折射率变化的定量相位图像。这种信息可以用来描述动态的细胞现象，也可以用来解释细胞内物质的运输，这可以描述各种类型的疾病。OCT系统将用于检测细胞表面受体和细胞内蛋白质的位置和密度等分子物种。将功能化的金纳米颗粒与特定分子结合，将使用光热方法选择性加热，激发调谐到NP等离子激元共振波长，以实现OCT的分子选择性传感。该混合系统预计将允许对细胞动力学进行广泛的研究，而两个子系统(WFDI和OCT)的结合将使研究由于疾病的发生和发展而导致的动态行为的调节成为可能。

1039562WaxThe goal of this research is to develop a novel quantitative phase microscope for investigating and analyzing changes in cellular structure and function due to environmental influences and pathology due to disease. To achieve this goal, a hybrid optical interferometric imaging and sensing system is proposed, combining low-coherence wide-field digital interferometry (WFDI), capable of visualizing fast cellular dynamics, with a novel optical coherence tomography (OCT) approach that uses photothermal heating of plasmonic nanoparticles (NPs) to achieve molecular imaging. The role of the low-coherence WFDI system is to visualize cell dynamics in order to assess modulation of cell function due to external influences. This transmission-mode system will quantitatively record optical path delays of light that has been transmitted through the sample, and thus will create quantitative phase images of local refractive index changes. This information can be used to characterize dynamic cell phenomena, as well as to account for transport of intracellular materials, which can characterize various types of disease. The OCT system will be used to detect molecular species such as cell surface receptors and the location and density of intracellular proteins. Gold NPs, functionalized to bind to specific molecules, will be heated selectively using the photothermal method, with excitation tuned to the NP plasmon resonance wavelength, to enable molecularly selective sensing by OCT. The hybrid system is expected to allow a wide range of studies of cellular dynamics, while the combination of the two sub-systems (WFDI and OCT) will enable investigation of modulation of dynamic behaviors due to onset and progression of disease.