Next-Generation Optical Contrasts for Characterization of Biological Tissue, Hard Matter, and Cultural Heritage Objects

在化学系化学测量与成像(CMI)项目的支持下，杜克大学的Martin Fischer博士和Warren Warren博士将开发光学显微镜技术，以研究各种材料的三维结构和功能，包括历史艺术品中使用的生物组织和颜料。传统上，这些复杂的材料对光学成像构成了严峻的挑战，通常需要切开样品来研究表面以下的层。新开发的成像方法允许在不破坏样本的情况下进行三维成像，研究人员正在开发技术来扩大化学对比的范围、成像的深度和解释结果的能力。这一进展有可能检测到恶化开始期间皮肤和艺术品的微观变化，这可能有助于早期诊断和更好地选择治疗方案。该项目开发的方法有利于学术研究，并可能导致生物医学研究人员和自然资源保护者同样感兴趣的设备。多个超快激光脉冲可以通过广泛的非线性过程与物质相互作用。研究人员开创了一种成像方法-泵浦-探测显微镜，将这种相互作用转化为可检测的对比度，以便在高速下以低平均功率成像，他们已经展示了在生物组织、历史艺术品和工程材料中的应用。用这种显微镜方法获得的信号取决于许多参数，如激光脉冲波长、脉冲间延迟、相对偏振和检测方向。由于响应的复杂性，参数的范围是一个挑战，但也提供了使用多个参数记录图像的机会，以提供不同的对比度类型和多样化和全面的样本视图。研究人员正在开发一种泵浦-探针式显微镜平台，该平台可以高效、安全和快速地获取多模式、多参数的数据集，为生物和文化遗产提供具有分子特异性的图像。具体地说，研究人员和他们的团队将追求以下研究目标：(I)系统地研究成像和样本参数(即波长、偏振、散射角)的依赖关系，以分离复杂的非线性光学相互作用并将图像分解为基本分量；以及(Ii)开发一种相干飞秒脉冲整形和检测方法，用于高效的多模式和多参数采集。这项研究旨在开发一种能够非侵入性地提取生物组织和历史艺术品中的全面分子和结构信息的显微镜。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Measurement and Imaging (CMI) Program in the Division of Chemistry, Drs. Martin Fischer and Warren Warren at Duke University will develop optical microscopy techniques to investigate the three-dimensional structure and function of a wide range of materials, including biological tissue and pigments used in historical artwork. Traditionally, these complex materials pose severe challenges for optical imaging and often the samples need to be cut open to investigate layers below the surface. Newly developed imaging methods allow for three-dimensional imaging without sample destruction and the investigators are developing techniques to extend the range of chemical contrast, the depth of imaging, and the ability to interpret the results. This development has the potential to detect microscopic changes in skin and artwork during the onset of deterioration, which could aid in early diagnosis and better choice of treatment options. The methods developed by this program benefit academic research and could lead to a device of great interest to biomedical researchers and conservators alike.Multiple ultrafast laser pulses can interact with matter via a wide range of nonlinear processes. The investigators have pioneered an imaging method, pump-probe microscopy, that turns such interactions into detectable contrast for imaging with low average power at high speeds and they have demonstrated applications in biological tissue, historical artworks, and engineered materials. The signals acquired with this microscopy method depend on many parameters, such as the laser pulse wavelengths, inter-pulse delay, relative polarization, and detection direction. The range of parameters presents a challenge due to the complexity of the response, but also an opportunity for recording images using multiple parameters to provide different contrast types and a diverse and comprehensive view of the sample. The investigators are developing a pump-probe microscopy platform that can efficiently, safely, and rapidly acquire multi-modal, multi-parameter data sets that provide images with molecular specificity for biology and cultural heritage. Specifically, the investigators and their team will pursue the following research goals: (i) systematically investigate and model the dependence on imaging and sample parameters (i.e., wavelength, polarization, scattering angle) to separate the complex set of nonlinear optical interactions and decompose the images into fundamental components; and (ii) develop a coherent femtosecond pulse shaping and detection approach for efficient multi-modal and multi-parameter acquisition. The research seeks to develop a microscope that will be able to non-invasively extract comprehensive molecular and structural information in biological tissue and historical artwork.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.