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通过近场盲叠层摄影调制实现的宽视场、高分辨率无透镜片上显微镜技术。

Wide-field, high-resolution lensless on-chip microscopy via near-field blind ptychographic modulation.

作者信息

Jiang Shaowei, Zhu Jiakai, Song Pengming, Guo Chengfei, Bian Zichao, Wang Ruihai, Huang Yikun, Wang Shiyao, Zhang He, Zheng Guoan

机构信息

Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA.

Department of Electrical and Computer Engineering, University of Connecticut, Storrs, CT 06269, USA.

出版信息

Lab Chip. 2020 Mar 17;20(6):1058-1065. doi: 10.1039/c9lc01027k.

DOI:10.1039/c9lc01027k
PMID:32073018
Abstract

We report a novel lensless on-chip microscopy platform based on near-field blind ptychographic modulation. In this platform, we place a thin diffuser in between the object and the image sensor for light wave modulation. By blindly scanning the unknown diffuser to different x-y positions, we acquire a sequence of modulated intensity images for quantitative object recovery. Different from previous ptychographic implementations, we employ a unit magnification configuration with a Fresnel number of ∼50 000, which is orders of magnitude higher than those of previous ptychographic setups. The unit magnification configuration allows us to have the entire sensor area, 6.4 mm by 4.6 mm, as the imaging field of view. The ultra-high Fresnel number enables us to directly recover the positional shift of the diffuser in the phase retrieval process, addressing the positioning accuracy issue plaguing regular ptychographic experiments. In our implementation, we use a low-cost, DIY scanning stage to perform blind diffuser modulation. Precise mechanical scanning that is critical in conventional ptychography experiments is no longer needed in our setup. We further employ an up-sampling phase retrieval scheme to bypass the resolution limit set by the imager pixel size and demonstrate a half-pitch resolution of 0.78 μm. We validate the imaging performance via in vitro cell cultures, transparent and stained tissue sections, and a thick biological sample. We show that the recovered quantitative phase map can be used to perform effective cell segmentation of a dense yeast culture. We also demonstrate 3D digital refocusing of the thick biological sample based on the recovered wavefront. The reported platform provides a cost-effective and turnkey solution for large field-of-view, high-resolution, and quantitative on-chip microscopy. It is adaptable for a wide range of point-of-care-, global-health-, and telemedicine-related applications.

摘要

我们报道了一种基于近场盲叠层摄影调制的新型无透镜片上显微镜平台。在该平台中,我们在物体和图像传感器之间放置一个薄漫射器用于光波调制。通过将未知漫射器盲目扫描到不同的x-y位置,我们获取一系列调制强度图像以进行定量的物体恢复。与以前的叠层摄影实现方式不同,我们采用单位放大配置,菲涅耳数约为50000,这比以前的叠层摄影装置的菲涅耳数高几个数量级。单位放大配置使我们能够将整个6.4毫米×4.6毫米的传感器区域作为成像视野。超高的菲涅耳数使我们能够在相位恢复过程中直接恢复漫射器的位置偏移,解决了困扰常规叠层摄影实验的定位精度问题。在我们的实现中,我们使用低成本的自制扫描台来执行盲漫射器调制。在我们的设置中不再需要传统叠层摄影实验中至关重要的精确机械扫描。我们进一步采用上采样相位恢复方案来绕过成像器像素大小设置的分辨率限制,并展示了0.78μm的半间距分辨率。我们通过体外细胞培养、透明和染色组织切片以及厚生物样本验证了成像性能。我们表明,恢复的定量相位图可用于对密集酵母培养物进行有效的细胞分割。我们还基于恢复的波前展示了厚生物样本的3D数字重聚焦。所报道的平台为大视野、高分辨率和定量片上显微镜提供了一种经济高效的交钥匙解决方案。它适用于广泛的即时医疗、全球健康和远程医疗相关应用。

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