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微型头戴式单光子荧光显微成像技术研究进展

付强 张智淼 赵尚男 刘洋 董洋

付强, 张智淼, 赵尚男, 刘洋, 董洋. 微型头戴式单光子荧光显微成像技术研究进展[J]. 中国光学(中英文), 2023, 16(5): 1010-1021. doi: 10.37188/CO.2023-0007
引用本文: 付强, 张智淼, 赵尚男, 刘洋, 董洋. 微型头戴式单光子荧光显微成像技术研究进展[J]. 中国光学(中英文), 2023, 16(5): 1010-1021. doi: 10.37188/CO.2023-0007
FU Qiang, ZHANG Zhi-miao, ZHAO Shang-nan, LIU Yang, DONG Yang. Research progress of miniature head-mounted single photon fluorescence microscopic imaging technique[J]. Chinese Optics, 2023, 16(5): 1010-1021. doi: 10.37188/CO.2023-0007
Citation: FU Qiang, ZHANG Zhi-miao, ZHAO Shang-nan, LIU Yang, DONG Yang. Research progress of miniature head-mounted single photon fluorescence microscopic imaging technique[J]. Chinese Optics, 2023, 16(5): 1010-1021. doi: 10.37188/CO.2023-0007

微型头戴式单光子荧光显微成像技术研究进展

doi: 10.37188/CO.2023-0007
基金项目: 国家自然科学基金资助项目(No. 62005271);中国科学院青年创新促进会资助(No. 2021221);吉林省科技发展计划青年成长科技计划项目(No. 20210508054RQ)
详细信息
    作者简介:

    付 强(1985—),男,黑龙江佳木斯人,博士,副研究员,2008 年、2010 年于哈尔滨工业大学分别获得学士、硕士学位,2020 年于中国科学院大学获得博士学位,主要从事光学系统设计、红外探测设备总体论证等方面的研究。E-mail:fuqianghit@163.com

    张智淼(1999—),男,吉林长春人,硕士研究生,2021年于长春理工大学获得学士学位,主要从事光学系统设计方面的研究。E-mail:zhimiaozhang@qq.com

    赵尚男(1993—),女,吉林长春人,博士研究生,助理研究员,2015年、2018年于北京理工大学分别获得学士、硕士学位,主要从事计算成像、机器视觉、光学设计方面的研究。E-mail:1109949193@qq.com

    刘 洋(1989—),男,吉林长春人,硕士,助理研究员,2012年、2015年于北京航空航天大学分别获得学士、硕士学位,主要从事光学系统设计、杂散光抑制设计等方面的研究。E-mail:liu9527aaa@163.com

    董 洋(1987—),男,吉林长春人,硕士,助理研究员,2012年、2013年于白俄罗斯国立大学分别获得学士、硕士学位,主要从事光学系统设计方面的研究。E-mail:283841835@qq.com

  • 中图分类号: TH742;R318.51

Research progress of miniature head-mounted single photon fluorescence microscopic imaging technique

Funds: Supported by National Natural Science Foundation of China (No. 62005271); Youth Innovation Promotion Association, CAS (No. 2021221); Youth growth technology program of Jilin province science and technology development plan (No. 20210508054RQ).
More Information
  • 摘要:

    微型头戴式单光子荧光显微成像技术是近些年出现的用于神经科学研究的一种突破性方法,可以对自由移动活体动物的神经活动进行实时成像,提供了一种前所未有的方式来访问神经信号,增强了对大脑如何工作的理解。在脑科学研究需求的推动下,目前已经出现了许多种类型的微型头戴式单光子荧光显微镜,如高分辨率成像、无线记录、三维成像、双区域成像和双色成像等。为了更加全面地了解和认识这种新兴的光学神经成像技术,本文按成像视场进行分类,对目前报道的不同类型微型头戴式单光子荧光显微镜所具有的特点进行了介绍,重点讨论了其所采用的光学系统方案和光学性能参数,分析对比了不同方案的优缺点,以及未来的改进方向,以便为脑科学研究人员的实际应用提供参考。

     

  • 图 1  具有基本成像功能的系统。(a)Ghosh等人的集成显微镜的横截面图[10];(b)MiniScope V3的分解图; (c)戴着微型显微镜的小鼠示意图[14];(d)小鼠大脑中神经元活动的荧光图像[14]

    Figure 1.  A system with a basic imaging function. (a) Cross sectional view of integrated microscope proposed by Ghosh et al; (b) exploded view of the MiniScope V3; (c) a schematic of a mouse wearing a miniature microscope; (d) fluorescent images of neural activity in a mouse brain

    图 2  具有无线功能的系统。(a)FinchScope的横截面图[19];(b)无线miniscope的内部光学元件布局图[22]

    Figure 2.  A system with wiress function. (a) Cross sectional view of FinchScope; (b) internal optics element layout of wireless miniscope

    图 3  具有三维成像功能的系统。(a)MiniLFM的横截面图[24];(b)Miniscope3D的横截面图[27];(c)Bagramyan等人的显微镜横截面图[28];(d)SIMscope3D的横截面图[29]

    Figure 3.  A system with 3D imaging functionality. (a) Cross sectional view of MiniLFM; (b) cross sectional view of Miniscope3D; (c) microscope cross section by Bagramyan et al; (d) cross sectional view of SIMscope3D

    图 4  具有双区域成像功能的系统。(a) NINscope的主体和内部光学元件布局图[31];(b)一只安装了两个NINscope的小鼠[31]

    Figure 4.  A system with dual region imaging functionality. (a) NINscope body and internal optics element layout; (b) a mouse with two NINscopes mounted

    图 5  具有双色成像功能的系统。(a)MiniScope V4的横截面图;(b)DCFIMM-SBI的横截面图[35];(c)DCFIMM-DBI的横截面图[35]

    Figure 5.  A system with two-color imaging functionality. (a) Cross sectional view of MiniScope V4; (b) cross sectional view of DCFIMM-SBI; (c) cross sectional view of DCFIMM-DBI

    图 6  现有的大视场系统。(a)cScope的成像路径光路图[36];(b)CM2的成像路径光路图[37];(c)完全组装的mScope[46]

    Figure 6.  Existing large filed of view system. (a) Imaging optical path of cScope; (b) imaging optical path of CM2; (c) fully assembled mScope

    表  1  具有基本成像功能的微型荧光显微镜的光学系统和光学性能参数

    Table  1.   Optical system and optical performance parameters of the miniature fluorescence microscope with basic imaging functionality

    系统参数Ghosh 等人MiniScope V3miniscopeCHEndoscopeBagramyan 等人
    物镜梯度折射率透镜梯度折射率透镜非球面透镜梯度折射率透镜梯度折射率透镜
    管镜双胶合透镜双胶合透镜双胶合透镜双胶合透镜平凸透镜
    视场600 μm×800 μm750 μm×450 μm1100 μm×1100 μm~500 μm~105 μm
    分辨率2.5 μm1.0 μm/pix单细胞分辨率单细胞分辨率1.0 μm
    图像传感器MT9V021
    (5.6 μm/pix)
    MT9V032
    (6.0 μm/pix)
    MT9V022
    (6.0 μm/pix)
    MT9P031
    (2.2 μm/pix)
    OV7251
    (3.0 μm/pix)
    成像速度36 Hz60 Hz10 Hz20 Hz50 Hz
    下载: 导出CSV

    表  2  具有无线功能的微型荧光显微镜的光学系统和光学性能参数

    Table  2.   Optical system and optical performance parameters of a miniature fluorescence microscope with wireless function

    系统参数FinchScopeWire-free MiniScopeminiscopewScope
    物镜梯度折射率透镜梯度折射率透镜非球面透镜梯度折射率透镜
    管镜双胶合透镜双胶合透镜双胶合透镜双胶合透镜
    视场800 μm×600 μm500 μm×500 μm700 μm×450 μm
    分辨率单细胞分辨率1 μm/pix单细胞分辨率1.8 μm
    图像传感器OV7960(6.00 μm/pix)EV76C454(5.80 μm/pix)MT9V022(6.00 μm/pix)OV7690 (1.75 μm/pix)
    成像速度30 Hz10 Hz10 Hz25 Hz
    下载: 导出CSV

    表  3  具有三维成像功能的微型荧光显微镜的光学系统和光学性能参数

    Table  3.   Optical system and optical performance parameters of the miniature fluorescence microscope with 3D imaging functionality

    系统参数MiniLFMMiniscope3DBagramyan等人OMKAR 等人
    物镜梯度折射率透镜梯度折射率透镜梯度折射率透镜两片双胶合透镜
    管镜双胶合透镜相位掩模板平凸透镜双胶合透镜
    视场700 μm×600 μm×360 μm900 μm×700 μm×390 μm横向 150 μm
    轴向 98 μm
    横向207 μm
    轴向220 μm
    三维成像元件微透镜阵列相位掩模板可调谐液晶透镜电湿润透镜
    横向分辨率6.0 μm2.8 μm1.4 μm1.0 μm/pix
    轴向分辨率30.0 μm15.0 μm15.0 μm18.0 μm
    图像传感器MT9V032 (6.0 μm/pix)MT9V032 (6.0 μm/pix)OV7251 (3.0 μm/pix)MT9P031 (2.2 μm/pix)
    成像速度16 Hz40 Hz50 Hz
    下载: 导出CSV

    表  4  具有双区域成像功能的微型荧光显微镜的光学系统和光学性能参数

    Table  4.   Optical system and optical performance parameters of a miniature fluorescence microscope with dual region imaging functionality

    系统参数Gonzalez 等人NINscope
    物镜梯度折射率透镜梯度折射率透镜
    管镜双胶合透镜平凸透镜
    视场600 μm×479 μm786 μm×502 μm
    分辨率0.83 μm/pix单细胞分辨率
    图像传感器OV7690 (6 μm/pix)PYTHON480 (4.8 μm/pix)
    成像速度30 Hz
    下载: 导出CSV

    表  5  具有双色成像功能的微型荧光显微镜的光学系统和光学性能参数

    Table  5.   Optical system and optical performance parameters of a miniature fluorescence microscope with two-color imaging functionality

    系统参数MiniScope V4DCFIMM-SBIDCFIMM-DBI
    物镜两片双胶合透镜两片双胶合透镜双胶合透镜
    管镜双胶合透镜双胶合透镜双胶合透镜
    视场~1.00 mm21.10 mm×1.10 mm0.77 mm×0.77 mm
    分辨率单细胞分辨率3.47 μm3.47 μm
    图像传感器PYTHON480
    (4.8 μm/pix)
    EV76C454
    (5.8 μm/pix)
    EV76C454
    (5.8 μm/pix)
    成像速度120 Hz20 Hz20 Hz
    下载: 导出CSV

    表  6  小视场微型单光子荧光显微镜的光学系统组成和光学性能参数

    Table  6.   Optical system composition and optical performance parameters of miniature single photon fluorescence microscope with a small field

    系统参数小视场系统 (FOV<1mm)
    物镜梯度折射率透镜[9-10,15-17,21,23-24,27-28,30-31]
    双胶合透镜[29,32,35] 、非球面透镜 [12,22]
    管镜双胶合透镜[9-10,12,15,17,21-24,29-30,32,35]
    平凸透镜[16,28,31] 、相位掩模板 [27]
    分辨率范围最小:1 μm [16] , 最大:6 μm [24]
    重量范围最小:1.3 g[16] , 最大:6.7 g[29]
    下载: 导出CSV

    表  7  大视场微型荧光显微镜的光学系统和光学性能参数

    Table  7.   Optical system and optical performance parameters of a large field miniature fluorescence microscope

    cScopeCM2mScope
    物镜多片球面透镜微透镜阵列双凸透镜
    管镜多片球面透镜
    视场7.8 mm×4.0 mm7.3 mm×8.1 mm×
    2.5 mm
    8.0 mm×10.0 mm
    横向分辨率14.0 μm7 μm39.4~55.7 μm
    图像传感器MT9V032
    (6 µm/pix)
    MT9P031
    (2.2 µm/pix)
    MT9V032
    (6 µm/pix)
    成像速度60Hz
    下载: 导出CSV
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出版历程
  • 收稿日期:  2023-01-10
  • 修回日期:  2023-02-05
  • 录用日期:  2023-03-24
  • 网络出版日期:  2023-05-05

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