On-chip integrated lensless microscopy module for optical monitoring of adherent growing mammalian cells
On-chip integrated lensless microscopy module for optical monitoring of adherent growing mammalian cells
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DOI：
10.1109/iembs.2010.5627771
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发表时间：
2010-11
期刊：
影响因子：
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通讯作者：
Wei Li;T. Knoll;H. Thielecke
中科院分区：
文献类型：
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作者：
Wei Li;T. Knoll;H. Thielecke
芯片实验室系统越来越多地应用于基于细胞的毒理学和药物测试分析。在本文中，提出了一种片上集成无透镜显微镜模块，使用直接投影方法对贴壁生长的哺乳动物细胞的阴影图像进行光学监测。生物细胞通过带有 1 µm 厚氮化硅 (Si3N4) 基板的微加工腔芯片保存并连接到像素尺寸为 2.2 µm 的 5 兆像素 CMOS 图像传感器的表面上。组件的光学分辨率通过光学光刻的接触/邻近印刷理论来估计。通过对带有 Si3N4 膜的芯片中的微珠以及带有由干膜抗蚀剂（DFR，厚度 20、40 和 60 µm）制成的膜的空腔芯片中的微珠进行成像来进行进一步表征。该模块代表用于细胞形态成像的 3 倍光学显微镜。该功能通过对在 Si3N4 基质的空腔芯片中培养 2 天的 L929 细胞的生长监测以及通过检查膜受损的细胞的比色染色来证明。
Lab-on-a-chip systems are increasingly applied in cell-based assays for toxicology and drug testing. In this paper, an on-chip integrated lensless microscopy module using a direct projection method for optical monitoring of the shadow images of adherent growing mammalian cells is presented. The biological cells are conserved and interfaced by a microfabricated cavity chip with a 1 µm thick silicon nitride (Si3N4) substrate onto the surface of a 5 megapixel CMOS image sensor with 2.2 µm pixel size. The optical resolution of the assembly is estimated by the contact/proximate printing theory from optical lithography. Further characterization is made by imaging microbeads in chips with the Si3N4-membrane as well as in cavity chips with membranes made from dry film resist (DFR, thickness 20, 40 and 60 µm). The module represents a 3 × optical microscope for cell morphology imaging. The function is demonstrated by the growth monitoring of L929 cells cultured in cavity chips with Si3N4 substrate for 2 days and by checking the colorimetric staining of cells with a compromised membrane.