Differential Interference Contrast Optofluidic Microscopy

描述(由申请人提供)：这项探索性/开发性研究(R21)申请建议开发一种芯片上低成本的相移成像显微镜，可以显著简化现有的广泛生物医学分析程序。这种成像方法被称为微分干涉对比光学流体显微镜(DIC-OFM)，它将建立在我们对光学流体显微镜(OFM)的工作的基础上--一种高分辨率、无透镜和紧凑的芯片上显微镜方法。我们的初步实验表明，一种低成本、简单的相位成像方法，基于使用图案化的孔系团，其功能相当于芯片上的Young双缝干涉仪，可以在不使用复杂的整体光学元件的情况下提供差分干涉对比(DIC)显微镜类型的图像。这种芯片上低成本的相位显微镜方法意味着高通量和大规模串联/并行生物实体成像的可能性。在其他用途中，它可以应用于基于微流控的细胞或微生物分析，以及任何其他类型的芯片上实验室应用，其中需要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(相当于10倍标准显微镜)和定量空间差分相位灵敏度~5度/微米。随着拟议研究的完成，我们预计这项技术将得到足够的改进，可以应用于应对广泛的基础研究和生物医学挑战。该方案的具体目标如下：1.构建了一个中继图像几何DIC-OFM原型系统。2.构建了一个完全集成的DIC-OFM原型。3.研究和评价了原型机绘制线虫阶段图像的性能。4.检查其他DIC-OFM孔径配置。这项拟议的研究将使我们能够探索构建芯片上、低成本和高分辨率差分干涉对比(DIC)显微镜的可能性。建议的显微镜设计建立在我们成功的光流控显微镜工作的基础上。体积小、成本低的DIC光流控显微镜系统可以大大简化相位成像过程，并将相位成像引入到更广泛的生物医学应用中，而这些应用目前受到传统DIC显微镜高昂成本的阻碍。

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.