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芯片实验室内部结构的尺寸计量:光学相干断层扫描与共聚焦荧光显微镜的比较

Dimensional metrology of lab-on-a-chip internal structures: a comparison of optical coherence tomography with confocal fluorescence microscopy.

作者信息

Reyes D R, Halter M, Hwang J

机构信息

Physical Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, Maryland, U.S.A.

Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, Maryland, U.S.A.

出版信息

J Microsc. 2015 Jul;259(1):26-35. doi: 10.1111/jmi.12245. Epub 2015 Apr 8.

Abstract

The characterization of internal structures in a polymeric microfluidic device, especially of a final product, will require a different set of optical metrology tools than those traditionally used for microelectronic devices. We demonstrate that optical coherence tomography (OCT) imaging is a promising technique to characterize the internal structures of poly(methyl methacrylate) devices where the subsurface structures often cannot be imaged by conventional wide field optical microscopy. The structural details of channels in the devices were imaged with OCT and analyzed with an in-house written ImageJ macro in an effort to identify the structural details of the channel. The dimensional values obtained with OCT were compared with laser-scanning confocal microscopy images of channels filled with a fluorophore solution. Attempts were also made using confocal reflectance and interferometry microscopy to measure the channel dimensions, but artefacts present in the images precluded quantitative analysis. OCT provided the most accurate estimates for the channel height based on an analysis of optical micrographs obtained after destructively slicing the channel with a microtome. OCT may be a promising technique for the future of three-dimensional metrology of critical internal structures in lab-on-a-chip devices because scans can be performed rapidly and noninvasively prior to their use.

摘要

对聚合物微流控器件内部结构的表征,尤其是对最终产品的表征,将需要一套与传统用于微电子器件的不同的光学计量工具。我们证明,光学相干断层扫描(OCT)成像技术有望用于表征聚甲基丙烯酸甲酯器件的内部结构,而传统的宽视野光学显微镜往往无法对其亚表面结构进行成像。利用OCT对器件中通道的结构细节进行成像,并使用内部编写的ImageJ宏进行分析,以识别通道的结构细节。将OCT获得的尺寸值与充满荧光团溶液的通道的激光扫描共聚焦显微镜图像进行比较。还尝试使用共聚焦反射和干涉显微镜来测量通道尺寸,但图像中存在的伪像妨碍了定量分析。基于对用切片机对通道进行破坏性切片后获得的光学显微照片的分析,OCT对通道高度提供了最准确的估计。OCT可能是一种有前景的技术,可用于未来对芯片实验室器件关键内部结构进行三维计量,因为可以在使用前快速且无创地进行扫描。

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