A vibratome instrument for serial histology of fresh tissue using multiple microscopy techniques to study the bio-distribution of optical molecular markers

连续的组织学和获得大组织切片数据集的自动工具的开发正变得至关重要，以帮助在微米尺度的成像细胞组成和形态与显微镜和活体从毫米到厘米尺度的整体器官成像之间架起空间尺度的桥梁。我们将开发一个成像平台，用于快速表征新鲜组织样本和整个器官，其基础是制造高精度的定制振动刀，该振动刀将与显微镜无缝同步并集成在一起，允许使用光学相干断层扫描(OCT)和双光子显微镜(2PH)进行体积组织表征。这里需要资金购买飞秒迈泰激光器，它将允许将2PH显微镜集成到系统中。预计这项技术将在申请者之间以及与对各种健康和疾病问题感兴趣的当地研究人员网络成员之间产生极富成效的合作。这一应用将支持的研究项目包括(但不限于)：(I)用于脑研究的神经髓鞘纤维追踪；(Ii)开发通过检测荧光生物标记物指导大脑以及口腔和喉部肿瘤切除的新方法；(Iii)开发用于软骨和半月板修复的生物材料。建议的仪器将对我们的研究计划产生立竿见影的影响，使我们能够与生物学家和临床医生同事合作，使用广泛的生物标志物以前所未有的精度解决紧迫的问题。

Serial histology and the development of automatic tools to obtain large tissue section datasets is becoming essential to help bridge spatial scales between imaging cellular composition and morphology at the micrometer scale with microscopy and whole organ imaging performed in vivo from millimeter to centimeter scales. We will develop an imaging platform for rapid characterization of fresh tissue samples and whole organs based on the fabrication of a high-precision custom vibratome that will be seamlessly synchronized and integrated with a microscope allowing volumetric tissue characterization using optical coherence tomography (OCT) and two-photon microscopy (2Ph). Funds are requested here to purchase a femtosecond Mai Tai laser that will allow the integration of 2Ph microscopy to the system. This technology is expected to generate tremendously productive collaborations amongst the applicants and with members of the local network of researchers interested in various questions of health and disease. The research projects that will be supported by this application include (but are not limited to): (i) neural myelin fiber tracking for brain studies, (ii) the development of new methods to guide the resection of brain as well as mouth & throat tumors through the detection of fluorescent biological markers, (iii) the development of biomaterials for cartilage and meniscus repair. The proposed instruments will have an immediate impact on our research programs allowing us, in collaboration with our biologist and clinician colleagues, to address pressing questions with an unprecedented level of precision using a wide array of biomarkers.