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

项目总结-研发项目3 光声检测组织水平上的金属熔剂 现代光学显微镜提供以下光学对比：光学散射、自体荧光 (本征荧光)、分子探针(非本征荧光)和非线性光学效应。一键 对比度，即光学吸收，是现有的显微镜模式所无法达到的。因此，生物元素 在生物组织中的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量子产率低的问题，其中沉积到探针上的主要光能是 通过非辐射途径以热量而不是荧光发射的方式消散。 测量非辐射热产生或光吸收可以提供一种新的方法来研究生物元素 成像，绕过量子产额挑战。成像光学吸收法定量离子浓度 在摩尔消光系数已知的情况下具有很高的精度。成像光学吸收允许直接 某些高光学吸收离子(如血红蛋白中的铁)的定量，并将刺激发展 一种新的分子探测器，它只关注高消光系数，为此努力 实现高荧光量子产率变得不那么关键了。 在这个技术研发项目中，我们将开发一种新的光学吸收 显微镜模式，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检测到由 激光能量吸收，从而产生热和热弹性振动。与.相比 现有的光声显微镜，MRR-PAM提高了超声检测的带宽和轴向 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来使组织 在所有DBP主题中成像，如强散射脑片、厚组织切片或整个小鼠 肾脏、整个斑马鱼和斑马鱼幼体。这将为量化铁代谢提供一种新的工具。MRR-PAM 扩展了在其他研发项目中开发的成像功能，以量化生物元素分布和 固定组织切片和活组织切片中的通量。它提供了对整个器官进行成像的可能性，并有可能 动物。在这个研发项目中开发的独特的MRR可以广泛传播，并可能产生影响 生物元素研究之外的其他几个生物医学领域。

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.