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付强; 张智淼; 赵尚男; 刘洋; 董洋

doi:10.37188/CO.2023-0007

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doi: 10.37188/CO.2023-0007

付强 ^1,,,
张智淼 ^{1, 2,},
赵尚男 ^{1, 2,},
刘洋 ^{1, 2,},
董洋 ^1,

1.
中国科学院长春光学精密机械与物理研究所, 吉林长春 130033
2.
中国科学院大学, 北京 100049

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：[email protected]

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：[email protected]

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：[email protected]

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：[email protected]

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：[email protected]

中图分类号:TH742;R318.51
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365彩票官网网页版
- 收稿日期: 2023-01-10
- 录用日期: 2023-03-24
- 修回日期: 2023-02-05
- 网络出版日期: 2023-05-05

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FU Qiang ^{1
,,},
ZHANG Zhi-miao ^{1, 2
,},
ZHAO Shang-nan ^{1, 2
,},
LIU Yang ^{1, 2
,},
DONG Yang ^{1
,}

1.
Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences , Changchun 130033, China
2.
University of Chinese Academy of Sciences, Beijing 100049, China

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

Corresponding author: [email protected]

摘要

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。
- 微型单光子荧光显微镜 /
- 神经信号 /
- 脑科学 /
- 光学系统
Abstract:
Miniature head-mounted single-photon fluorescence microscopy is a breakthrough approach for neuroscience research that has emerged in recent years. It can image the neural activity of freely moving vivo animals in real time, providing an unprecedented way to access neural signals and rapidly enhancing the understanding of how the brain works. Driven by the needs of brain science research, there have been many types of miniature head-mounted single-photon fluorescence microscopes, such as high-resolution imaging, wireless recording, 3D imaging, two-region imaging and two-color imaging. In order to have a more comprehensive understanding of this new optical neuroimaging technology, we classify its technologies according to the imaging field of view, introduce the characteristics of different types of micro-head-mounted single-photon fluorescence microscopes reported so far, and focus on the optical system scheme and optical performance parameters used. The advantages and disadvantages of different schemes are analyzed and compared and the future direction of development is described to provide reference for the practical application of brain science researchers.
- miniature single-photon fluorescence microscope /
- neural signals /
- brain science /
- optical system

HTML全文

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

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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

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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

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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

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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

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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

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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 V3	miniscope	CHEndoscope	Bagramyan 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 μm	750 μm×450 μm	1100 μm×1100 μm	~500 μm	~105 μm
分辨率	2.5 μm	1.0 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 Hz	60 Hz	10 Hz	20 Hz	50 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	FinchScope	Wire-free MiniScope	miniscope	wScope
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 μm	—	500 μm×500 μm	700 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 Hz	10 Hz	10 Hz	25 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	MiniLFM	Miniscope3D	Bagramyan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 μm	900 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 μm	2.8 μm	1.4 μm	1.0 μm/pix
轴向分辨率	30.0 μm	15.0 μm	15.0 μm	18.0 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 Hz	40 Hz	50 Hz	—

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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 μm	786 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 V4	DCFIMM-SBI	DCFIMM-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 mm²	1.10 mm×1.10 mm	0.77 mm×0.77 mm
分辨率	单细胞分辨率	3.47 μm	3.47 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 Hz	20 Hz	20 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 ]}

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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

	cScope	CM²	mScope
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	微透镜阵列	双凸透镜
视场	7.8 mm×4.0 mm	7.3 mm×8.1 mm× 2.5 mm	8.0 mm×10.0 mm
横向分辨率	14.0 μm	7 μm	39.4~55.7 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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