On-Chip Optofluidic Laser Scanning Confocal Microscope for Early Cancer Detection

描述（由申请人提供） 翻译后摘要：激光扫描共聚焦显微镜（LSCM）有一个独特的能力，以解决在亚细胞水平下的表面组织结构。凭借这种能力，LSCM在早期癌症检测方面取得了令人瞩目的成果。传统上，LSCM是基于一个庞大的，昂贵的组件组件-电机控制的扫描镜，平移台，和高数值孔径（NA）透镜-的组件，以实现亚细胞分辨率和光学切片。因此，LSCM在癌症诊断中的应用，特别是对于人体难以到达的部位（如消化和呼吸系统）的癌症，受到限制。为了最大限度地发挥激光共聚焦显微镜在早期癌症诊断中的潜力，有必要开发微型激光共聚焦显微镜系统，该系统可以安装在内窥镜探头或导管针的尖端上，以促进高分辨率、微创、体内共聚焦显微镜成像。鉴于小型激光扫描共聚焦显微镜的巨大潜力和巨大挑战，本文提出了一种变革性的技术路线--光流控激光扫描共聚焦显微镜（O-LSCM）。具体来说，我将（1）解决光学和机械的挑战，在实施O-LSCM，（2）表征和优化预包装O-LSCM，（3）构建O-LSCM成像探针，并将其应用于组织成像的早期癌症检测。所提出的O-LSCM通过控制微流体腔室中的流体流动在单个实施例中实现了LSCM所需的所有光学和机械功能。O-LSCM没有移动部件，并且可以方便地用简单的微制造技术（即，微模注射）。因此，制造和组装过程可以显著简化，组装的系统可以小型化到适合于内窥镜应用的程度，并且系统的可靠性和光学对准精度可以显著提高。由于其强大的功能，简单，紧凑和鲁棒性，拟议的O-LSCM将有助于下一代内窥镜共焦显微镜系统的设计，并将有利于广泛的生物研究和临床应用。 公共卫生相关性：激光扫描共聚焦显微镜（LSCM）是一种用于获得各种生物样品的高分辨率三维（3D）显微图像的强大技术。这项资助的长期目标是发明一种范式转移技术路线，以LSCM-光流体激光扫描共聚焦显微镜（O-LSCM）。凭借其强大的功能，简单，紧凑和鲁棒性，拟议的O-LSCM将促进下一代高分辨率，微创内窥镜共聚焦显微镜系统的设计，并将有利于广泛的生物学研究和临床应用（如早期癌症检测）。

DESCRIPTION (Provided by the applicant) Abstract: The Laser Scanning Confocal Microscopy (LSCM) has a unique capability to resolve below- surface tissue structures at a sub-cellular level. With this capability, LSCM has contributed compelling results in early cancer detection. Conventionally, LSCM is based on an assembly of bulky, expensive components¿motor-controlled scanning mirrors, translation stages, and high numerical aperture (NA) lenses¿to achieve sub-cellular resolution and optical sectioning. Consequently, applications of LSCM in cancer diagnosis, especially for cancer in hard-to-reach parts of human bodies (such as digestive and respiratory systems), have been limited. In order to maximize the potential of LSCM in early cancer diagnosis, it is necessary to develop miniature LSCM systems that can be fitted on the tip of an endoscope probe or catheter needle to facilitate high-resolution, minimally-invasive, in vivo confocal microscopic imaging. In view of the tremendous potential and significant challenges in developing miniature LSCM, I propose a transformative technical route-Optofluidic Laser Scanning Confocal Microscope (O- LSCM). Specifically, I will (1) address optical and mechanical challenges in the implementation of O-LSCM, (2) characterize and optimize pre-packaged O-LSCM, and (3) construct O-LSCM imaging probe and apply it to tissue imaging for early cancer detection. The proposed O-LSCM realizes all optical and mechanical functions needed for an LSCM in a single embodiment via the control of fluid flows in a microfluidic chamber. O-LSCM has no moving components, and it can be conveniently realized with a simple micro-fabrication technique (i.e., micro mold injection). Therefore, fabrication and assembly process can be dramatically simplified, the assembled system can be miniaturized to such an extent that it is suitable for endoscopic applications, and reliability and optical alignment precision of the system can be significantly improved. With its strong functionalities, simplicity, compactness, and robustness, the proposed O-LSCM will facilitate the design of next-generation endoscopic confocal microscopy systems and will benefit a wide range of biological studies and clinical applications. Public Health Relevance: Laser scanning confocal microscopy (LSCM) is a powerful technique for obtaining high resolution three-dimensional (3D) microscopic images of various biological samples. The long-term objective of this grant is to invent a paradigm-shifting technical route to LSCM-Optofluidic Laser Scanning Confocal Microscope (O-LSCM). With its strong functionalities, simplicity, compactness, and robustness, the proposed O-LSCM will facilitate the design of next-generation high-resolution, minimum-invasive endoscopic confocal microscopy systems and will benefit a wide range of biological studies and clinical applications (such as early cancer detection).