Label-free cellphone microscopy with submicron resolution through high-index contact ball lens for in vivo melanoma diagnostics and other applications

Label-free cellphone microscopy with submicron resolution through high-index contact ball lens for in vivo melanoma diagnostics and other applications
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通过高折射率隐形球镜实现亚微米分辨率的无标记手机显微镜,用于体内黑色素瘤诊断和其他应用

DOI:
10.1117/12.2609911
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发表时间:
2022
期刊:
SPIE BiOS
影响因子:
--
通讯作者:
Boya Jin, Grant W.
Boya Jin, Grant W.
中科院分区:
--
文献类型:
--
作者:
Boya Jin, Grant W.

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2000 年代开发百万像素大面积 CCD 和 CMOS 传感器阵列激发了人们通过使用微光学方法与手机摄像头成像相结合来开发无需笨重显微镜支架和物镜即可运行的显微镜系统的想法。然而,由于放大倍率有限,此类系统的最佳分辨率目前受到约 1.5 μm 级别像素的有限尺寸的限制。我们提出了一种设计这种显微镜系统的新方法,该方法基于使用折射率接近 2 的接触球透镜,能够以极高的放大倍率和分辨率对生物医学和纳米等离子体物体进行成像。通过使用折射率 n = 2.02、λ = 600 nm 的玻璃制成的球透镜,我们构建了一个基于手机摄像头的显微镜系统,其放大倍率高达 50 倍,并且由于光衍射,分辨率基本上限制在 ~600 nm 水平。事实证明,这种系统的操作是玻璃中强烈色散效应的一个主题,导致放大率、分辨率和视场 (FOV) 接近临界指数 2 的复杂权衡。使用该系统,我们对黑色素瘤样本进行了成像,这表明使用球透镜辅助智能手机显微镜开发无活检体内皮肤组织学的潜力。
Developing megapixel large-area CCD and CMOS sensor arrays in the 2000-s stimulated ideas about developing microscope systems operating without heavy and bulky microscope stands and objectives by using microoptics approach in combination with imaging by cellphone cameras. Due to limited magnification, however, the best resolution of such systems is currently limited by the finite size of the pixels at ~1.5 μm level. We propose a novel approach to designing such microscope systems based on using contact ball lenses with index of refraction close to 2, which are capable of imaging biomedical and nanoplasmonic objects with extraordinarily high magnification and resolution. By using ball lenses made from glass with index n = 2.02 at λ = 600 nm we build a cellphone camera-based microscope system with up to x50 magnification and resolution fundamentally limited at ~600 nm level due to diffraction of light. It is demonstrated that the operation of such system is a subject for strong dispersive effects in glass leading to a complicated tradeoff of magnification, resolution, and field-of-view (FOV) in the proximity to critical index of 2. Using this system, we performed imaging of melanoma samples which shows a potential of developing biopsy-free in vivo histology of skin using ball lensassisted smartphone microscopy.
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