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

连续组织学和自动工具的发展，以获得大的组织切片数据集，是必不可少的，以帮助连接成像细胞组成和形态之间的空间尺度在微米尺度显微镜和全器官成像从毫米到厘米尺度在体内进行。我们将开发一个成像平台，用于快速表征新鲜组织样品和整个器官，基于高精度定制振动体的制造，该振动体将与显微镜无缝同步并集成，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。现申请资金用于购买飞秒迈泰激光器，该激光器可将2Ph显微镜集成到系统中。这项技术有望在申请人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巨大的富有成效的合作。该申请将支持的研究项目包括（但不限于）：(i)用于大脑研究的神经髓鞘纤维跟踪，（ii）通过荧光生物标记物检测指导脑和口腔及咽喉肿瘤切除的新方法的开发，（iii）用于软骨和半月板修复的生物材料的开发。拟议的仪器将对我们的研究项目产生直接影响，使我们能够与生物学家和临床医生同事合作，利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.