TR&D Project 3: Photoacoustic Detection of Metal Fluxes at the Tissue Level

项目概要- TR&D项目3 组织水平金属通量的光声检测 现代光学显微镜模式提供以下光学对比：光学散射、自发荧光 （内在荧光）、分子探针（外在荧光）和非线性光学效应。一个关键 对比度、光学吸收是现有的显微镜形态无法达到的。因此，生物元素 生物组织中研究主要依赖于各种荧光探针。设计中的持久挑战 荧光探针是为了克服低量子产率，其中沉积到探针的主要光能是 通过非辐射途径作为热量而不是作为荧光发射消散。 测量非辐射热产生或光吸收可以提供一种新的方法来进行生物元素 成像并绕过量子产量挑战。成像光学吸收定量离子浓度 当摩尔消光系数已知时具有高精度。成像光学吸收允许直接 定量某些高光学吸收离子（即血红蛋白中的铁），并将刺激发展 一类新的分子探针，只关注高消光系数， 实现高荧光量子产率变得不那么重要。 在这个技术研究和开发（TR&D）项目中，我们将开发一种新的光吸收 显微镜模态，被称为基于光学微环谐振器的光声显微镜或MRR。 PAM，它使用超声波测量光吸收。MRR-PAM检测由以下物质引起的超声波： 激光能量吸收，并因此产生热量和热弹性振动。较 现有的光声显微镜，MRR-PAM提高了超声检测带宽和轴向 分辨率提高10倍，检测灵敏度提高100倍。MRR-PAM提供了一种独特的工具， 在所有DBP主题中成像，例如强散射脑切片、厚组织切片或整个小鼠 肾脏、整条斑马鱼和斑马鱼幼体。它将为定量铁代谢提供一种新的工具。MRR-PAM 扩展了在其他TR&D项目中开发的成像能力，以量化生物元素分布， 固定和活组织切片中的通量。它提供了对整个器官成像的可能性， 动物本技术研究与发展项目中制定的独特的减少残留风险报告可以广泛传播， 生物元素研究之外的其他生物医学领域。

PROJECT SUMMARY – TR&D PROJECT 3 Photoacoustic Detection of Metal Fluxes at the Tissue Level Modern optical microscopic modalities offer the following optical contrasts: optical scattering, autofluorescence (intrinsic fluorescence), molecular probes (extrinsic fluorescence), and nonlinear optical effects. One key contrast, optical absorption, is inaccessible by established microscopic modalities. As a result, bioelement investigation in biological tissue mainly rely on various fluorescence probes. A lasting challenge in designing fluorescence probes is to overcome low quantum yield, where major optical energy deposited to the probes is dissipated via a non-radiative pathway as heat instead of as fluorescent emissions. Measuring nonradiative thermal generation or optical absorption could offer a new way to conduct bioelement imaging and bypass the quantum yield challenge. Imaging optical absorption quantifies ionic concentrations with high accuracy when the molar extinction coefficient is known. Imaging optical absorption permits direct quantitation of certain highly-optically absorbing ions (i.e. Fe in hemoglobin) and will stimulate the development of a new class of molecular probes that focus on high extinction coefficients only, for which the struggle to achieve high fluorescent quantum yield becomes much less critical. In this Technology Research and Development (TR&D) project we will develop a new optical absorption microscopy modality, referred to as optical Micro-Ring Resonator-Based Photoacoustic Microscopy or MRR- PAM, which measures optical absorption using ultrasound. MRR-PAM detects ultrasound waves induced by laser energy absorption and, consequently, heat generation and thermoelastic vibration. Compared with existing photoacoustic microscopy, MRR-PAM improves the ultrasound detection bandwidth and axial resolution by 10-fold and detection sensitivity by 100-fold. MRR-PAM provides a unique tool to enable tissue imaging in all the DBP themes, such as the strongly scattering brain slices, thick tissue slice or whole mouse kidney, whole zebrafish and zebrafish larvae. It will provide a new tool to quantify iron metabolism. MRR-PAM extends the imaging capabilities developed in other TR&D projects to quantify bioelement distributions and fluxes in both fixed and living tissue slices. It offers the possibility to image whole organs and, potentially, living animals. The unique MRR developed in this TR&D project can be broadly disseminated and will likely impact several other biomedical fields beyond bioelement research.