Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging
Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging
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DOI：
10.1073/pnas.0804612105
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发表时间：
2008-08-05
影响因子：
11.1
通讯作者：
Yang, Changhuei
中科院分区：
文献类型：
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作者：
Cui, Xiquan;Lee, Lap Man;Yang, Changhuei
低成本和高分辨率的片上显微镜对于降低现代生物医学和生物科学的成本和提高效率至关重要。尽管需要，传统的显微镜设计已被证明难以实现。在这里，我们报告的实施和应用的两个高分辨率（约为0.9 μ m的第一和约为0.8 μ m的第二），无透镜，完全芯片上的显微镜的基础上的光流体显微镜（OFM）的方法。这些系统放弃了传统的显微镜设计，这需要昂贵的镜头和大的空间来放大图像，而是利用微流体流来传递样品穿过在金属涂覆的CMOS传感器上限定的微米尺寸孔径的阵列，以生成直接投影图像。第一系统利用重力驱动的微流体流进行样品扫描，并适合于成像细长物体，如秀丽隐杆线虫;第二系统采用动电驱动进行流量控制，并适合于成像细胞和其他球形/椭圆形物体。作为生物科学研究的OFM示范，我们表明，原型可用于执行不同的秀丽隐杆线虫突变株的自动化表型表征，并成像孢子和单细胞实体。光流控显微镜的设计，很容易与现有的半导体和微流体技术制造，提供低成本和高度紧凑的成像解决方案。更多功能，例如片上相位和荧光成像，也可以很容易地适应OFM系统。我们预计，OFM可以显着解决一系列的生物医学和生物科学的需求，并产生新的显微镜应用。
Low-cost and high-resolution on-chip microscopes are vital for reducing cost and improving efficiency for modern biomedicine and bioscience. Despite the needs, the conventional microscope design has proven difficult to miniaturize. Here, we report the implementation and application of two high-resolution (approximate to 0.9 mu m for the first and approximate to 0.8 mu m for the second), lensless, and fully on-chip microscopes based on the optofluidic microscopy (OFM) method. These systems abandon the conventional microscope design, which requires expensive lenses and large space to magnify images, and instead utilizes microfluidic flow to deliver specimens across array(s) of micrometer-size apertures defined on a metal-coated CMOS sensor to generate direct projection images. The first system utilizes a gravity-driven microfluidic flow for sample scanning and is suited for imaging elongate objects, such as Caenorhabditis elegans; and the second system employs an electrokinetic drive for flow control and is suited for imaging cells and other spherical/ellipsoidal objects. As a demonstration of the OFM for bioscience research, we show that the prototypes can be used to perform automated phenotype characterization of different Caenorhabditis elegans mutant strains, and to image spores and single cellular entities. The optofluidic microscope design, readily fabricable with existing semiconductor and microfluidic technologies, offers low-cost and highly compact imaging solutions. More functionalities, such as on-chip phase and fluorescence imaging, can also be readily adapted into OFM systems. We anticipate that the OFM can significantly address a range of biomedical and bioscience needs, and engender new microscope applications.