Optofluidic Microscope

描述（由申请人提供）：本探索性/发展性研究（R21）申请提出了一种新型成像显微镜，可以大大增加光学显微镜的应用范围，简化现有的生物医学分析程序。这种方法被称为光流显微镜（OFM），其工作原理是将样品流过微流控通道内的一组特殊设计的孔，并用均匀的光场照射该通道。然后可以通过通过孔的传输来监测物体与照明场的相互作用；生物实体的形状和折射率变化可以用受孔尺寸限制的分辨率来解决。此外，这种新型显微镜采用的成像方法意味着生物实体的高通量和大规模串行/并行成像是可能的。该设备将非常紧凑（大约火柴盒大小），完全不需要大量光学器件，能够进行高通量处理，而且价格低廉。它的制造可以用现有的半导体芯片技术完成。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成像系统。考虑到目前在芯片实验室系统上的成像通常是用笨重的显微镜进行的，OFM将使真正紧凑的芯片实验室系统的创建成为可能。我们已经展示了一种能够以0.6微米的分辨率进行高通量成像的工作装置。我们初步研究中采用的制造技术很容易扩展，我们相信，有了合适的资源，我们可以充分展示OFM的实用性，大规模生产的低成本以及相关优势。为了评估OFM在生物医学应用中的效用，我们将应用OFM来解决一个特定的生物医学应用——秀丽隐杆线虫表型。随着拟议研究的完成，我们预计该技术将得到充分完善，以应对广泛的基础研究和生物医学挑战。

DESCRIPTION (provided by applicant): This Exploratory/Developmental Research (R21) application proposes a new type of imaging microscope that can dramatically increase the application range of optical microscopy and simplify existing biomedicine analysis procedures. This method, termed Optofluidic Microscopy (OFM), operates by flowing the sample over a specially designed array of holes within a microfluidic channel that is illuminated with a uniform light field. The interaction of the object with the illumination field can then by monitored via the transmission through the holes; the shape and refractive index variation of the bioentity can be resolved with a resolution that is limited by the hole size. In addition, the imaging approach employed in this new microscope type implies that high throughput and massively serial/parallel imaging of bioentities is possible. The device will be very compact (about the size of a matchbox), completely free of bulk optics, capable of high throughput processing, and inexpensive. Its fabrication can be done with existing semiconductor chip technology. 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 imaging system is desired. Given that imaging on a lab-on-a-chip system is generally performed with a bulky microscope at present, the OFM will enable the creation of truly compact lab-on-a-chip systems. We have already demonstrated a working device that is capable of high throughput imaging with resolution of 0.6 microns. The fabrication technology employed in our preliminary studies is readily scalable and we are confident that, with the right resources, we can fully demonstrate the utility, low cost to mass produce, and associated advantages of the OFM. To evaluate OFM's utility for biomedical applications, we will apply the OFM to address a specific biomedical application - C. elegans phenotyping. With the completion of the proposed research, we expect the technology will be sufficiently refined to tackle a wide range of basic research and biomedicine challenges.