Differential Interference Contrast Optofluidic Microscopy

描述（由申请人提供）：本探索性/发展性研究（R21）申请提出了一种芯片上和低成本的相位成像显微镜的开发，可以显着简化广泛的现有生物医学分析程序。这种成像方法，称为微分干涉对比光流体显微镜（DIC-OFM），将建立在我们对光流体显微镜（OFM）的研究基础上-一种高分辨率，无透镜和紧凑的片上显微镜方法。我们的初步实验积极地表明，一种低成本，简单的相位成像方法基于使用图像化孔径簇，作为片上杨氏双缝干涉仪的功能，可以呈现微分干涉对比（DIC）显微镜类型的图像，而无需使用复杂的大块光学元件。这种片上和低成本的相显微镜方法意味着生物实体的高通量和大规模串行/并行成像的可能性。在其他用途中，它可以应用于基于微流体的细胞或微生物分析，以及任何其他类型的芯片上的实验室应用，其中需要一个紧凑和低成本的相位成像系统。我们的目标是展示一种能够高通量成像的工作装置，其空间分辨率至少为1.2微米（与10倍标准显微镜相当），定量空间差相灵敏度约为5度/微米。随着拟议研究的完成，我们期望该技术将得到充分完善，以应用于解决广泛的基础研究和生物医学挑战。提案的具体目的如下：构造一个中继图像几何DIC-OFM原型。2. 构建一个完全集成的DIC-OFM原型。3. 研究并评价模型对秀丽隐杆线虫相位图像的绘制效果。4. 检查其他DIC-OFM孔径配置。该研究将使我们能够探索构建片上、低成本和高分辨率差分干涉对比（DIC）显微镜的可能性。所提出的显微镜设计建立在我们成功的光流体显微镜工作的基础上。一种紧凑、低成本的DIC光流显微镜系统可以极大地简化相成像程序，并将相成像引入到更广泛的生物医学应用中，这目前受到传统DIC显微镜高成本的阻碍。

DESCRIPTION (provided by applicant): This Exploratory/Developmental Research (R21) application proposes the development of an on-chip and low cost phasing imaging microscope that can significantly simplify a broad range of existing biomedicine analysis procedures. This imaging approach, termed differential interference contrast optofluidic microscopy (DIC-OFM), will build upon our work on the optofluidic microscopy (OFM) - a high resolution, lensless and compact on-chip microscope method. Our preliminary experiments positively indicate that a low cost, simple phase imaging approach based on the use of patterned aperture clusters, that function as on-chip Young's double slit interferometers, can render differential interference contrast (DIC) microscopy type images without the use of elaborate bulk optical elements. Such an on-chip and low cost phase microscope method implies the possibility of high throughput and massively serial/parallel imaging of bio-entities. Among other uses, it can be applied in microfluidic based cell or microorganism analysis, and any other type of lab-on-a-chip applications where a compact and low cost phase imaging system is desired. We aim to demonstrate a working device that is capable of high throughput imaging with a spatial resolution of at least 1.2 micron (comparable to a 10x standard microscope) and quantitative spatial differential phase sensitivity of ~5 degree/micron. With the completion of the proposed research, we expect the technology will be sufficiently refined to be applied to tackle a wide range of basic research and biomedicine challenges. The specific aims of the proposal are as follows: 1. To construct a relay image geometry DIC-OFM prototype. 2. To construct a fully integrated DIC-OFM prototype. 3. To study and evaluate the prototypes' performance for rendering phase images of C. elegans. 4. To examine other DIC-OFM aperture configurations. The proposed research will allow us to investigate the possibility of constructing on-chip, low cost and high resolution differential interference contrast (DIC) microscopes. The propose microscope design builds upon our successful optofluidic microscope work. A compact and low cost DIC optofluidic microscope system can dramatically simplify phase imaging procedure and introduce phase imaging to a wider range of biomedical applications, which are presently hindered by the high cost of conventional DIC microscopes.