Full Text:   <6847>

Summary:  <1382>

CLC number: O439

On-line Access: 2024-08-27

Received: 2023-10-17

Revision Accepted: 2024-05-08

Crosschecked: 2020-12-24

Cited: 0

Clicked: 5867

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Ruheng Shi

https://orcid.org/0000-0001-7993-708X

Lingjie Kong

https://orcid.org/0000-0002-8250-7547

-   Go to

Article info.
Open peer comments

Frontiers of Information Technology & Electronic Engineering  2021 Vol.22 No.10 P.1289-1298

http://doi.org/10.1631/FITEE.2000410


Enhanced collection of scattered photons in nonlinear fluorescence microscopy by extended epi-detection with a silicon photomultiplier array


Author(s):  Ruheng Shi, Cheng Jin, Chi Liu, Lingjie Kong

Affiliation(s):  State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing 100084, China; more

Corresponding email(s):   konglj@tsinghua.edu.cn

Key Words:  Extended epi-detection, Enhanced collection, Nonlinear fluorescence microscopy, Silicon photomultiplier array


Ruheng Shi, Cheng Jin, Chi Liu, Lingjie Kong. Enhanced collection of scattered photons in nonlinear fluorescence microscopy by extended epi-detection with a silicon photomultiplier array[J]. Frontiers of Information Technology & Electronic Engineering, 2021, 22(10): 1289-1298.

@article{title="Enhanced collection of scattered photons in nonlinear fluorescence microscopy by extended epi-detection with a silicon photomultiplier array",
author="Ruheng Shi, Cheng Jin, Chi Liu, Lingjie Kong",
journal="Frontiers of Information Technology & Electronic Engineering",
volume="22",
number="10",
pages="1289-1298",
year="2021",
publisher="Zhejiang University Press & Springer",
doi="10.1631/FITEE.2000410"
}

%0 Journal Article
%T Enhanced collection of scattered photons in nonlinear fluorescence microscopy by extended epi-detection with a silicon photomultiplier array
%A Ruheng Shi
%A Cheng Jin
%A Chi Liu
%A Lingjie Kong
%J Frontiers of Information Technology & Electronic Engineering
%V 22
%N 10
%P 1289-1298
%@ 2095-9184
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/FITEE.2000410

TY - JOUR
T1 - Enhanced collection of scattered photons in nonlinear fluorescence microscopy by extended epi-detection with a silicon photomultiplier array
A1 - Ruheng Shi
A1 - Cheng Jin
A1 - Chi Liu
A1 - Lingjie Kong
J0 - Frontiers of Information Technology & Electronic Engineering
VL - 22
IS - 10
SP - 1289
EP - 1298
%@ 2095-9184
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/FITEE.2000410


Abstract: 
To maximize signal collection in nonlinear optical microscopy, non-descanned epi-detection is generally adopted for in vivo imaging. However, because of severe scattering in biological samples, most of the emitted fluorescence photons go beyond the collection angles of objectives and thus cannot be detected. Here, we propose an extended detection scheme to enhance the collection of scattered photons in nonlinear fluorescence microscopy using a silicon photomultiplier array ahead of the front apertures of objectives. We perform numerical simulations to demonstrate the enhanced fluorescence collection via extended epi-detection in the multi-photon fluorescence imaging of human skin and mouse brain through craniotomy windows and intact skulls. For example, with red fluorescence emission at a depth of 600 μm in human skin, the increased collection can be as much as about 150% with a 10×, 0.6-NA objective. We show that extended epi-detection is a generally applicable, feasible technique for use in nonlinear fluorescence microscopy to enhance signal detection.

采用硅光电倍增管阵列扩展探测实现非线性荧光显微技术中散射光子探测信号的增强

施汝恒1,靳程1,刘驰1,孔令杰1,2
1清华大学精密仪器系精密测试技术与仪器国家重点实验室,中国北京市,100084
2清华大学IDG/麦戈文脑科学研究院,中国北京市,100084
摘要:为提高非线性荧光显微技术在活体成像中的信号探测能力,人们常采用基于非退扫描的背向探测策略。然而,由于生物样本中存在严重散射,物镜前孔径处大部分荧光光子辐射角度超出物镜收集角范围,因而无法被探测。本文提出一种将硅光电倍增管阵列放置在物镜前孔径处以增强非线性显微镜对散射光子探测能力的扩展探测方案。通过数值仿真说明了扩展探测在对人体皮肤和小鼠大脑(透过颅窗及完整颅骨)进行多光子荧光成像的信号增强情况。例如,在人类皮肤60 µm成像深度处使用红色染料标记情况下,使用10×,0.6NA物镜进行成像,扩展探测方案引入的信号增强可达约150%。本文论证了扩展探测是一种灵活、广泛适用于非线性荧光显微镜增强探测信号的技术。

关键词:扩展背向探测;增强探测;非线性荧光显微镜;硅光电倍增管阵列

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Allen CH, Hansson B, Raiche-Tanner O, et al., 2020. Coherent anti-Stokes Raman scattering imaging using silicon photomultipliers. Opt Lett, 45(8):2299-2302.

[2]Binding J, Arous JB, Léger JF, et al., 2011. Brain refractive index measured in vivo with high-NA defocus-corrected full-field OCT and consequences for two-photon microscopy. Opt Expr, 19(6):4833-4847.

[3]Chen JL, Voigt FF, Javadzadeh M, et al., 2016. Long-range population dynamics of anatomically defined neocortical networks. eLife, 5:e14679.

[4]Cheong WF, Prahl SA, Welch AJ, 1990. A review of the optical properties of biological tissues. IEEE J Quant Electron, 26(12):2166-2185.

[5]Combs CA, Smirnov AV, Riley JD, et al., 2007. Optimization of multiphoton excitation microscopy by total emission detection using a parabolic light reflector. J Microsc, 228(3):330-337.

[6]Denk W, Strickler JH, Webb WW, 1990. Two-photon laser scanning fluorescence microscopy. Science, 248(4951):73-76.

[7]Dvornikov A, Gratton E, 2016. Imaging in turbid media: a transmission detector gives 2-3 order of magnitude enhanced sensitivity compared to epi-detection schemes. Biomed Opt Expr, 7(9):3747-3755.

[8]Engelbrecht CJ, Göbel W, Helmchen F, 2009. Enhanced fluorescence signal in nonlinear microscopy through supplementary fiber-optic light collection. Opt Expr, 17(8):6421-6435.

[9]Holtmaat A, Bonhoeffer T, Chow DK, et al., 2009. Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window. Nat Protoc, 4(8):1128-1144.

[10]Jacques SL, 2013. Optical properties of biological tissues: a review. Phys Med Biol, 58(11):R37-R61.

[11]Ji MB, Orringer DA, Freudiger CW, et al., 2013. Rapid, label-free detection of brain tumors with stimulated Raman scattering microscopy. Sci Trans Med, 5(201):201ra119.

[12]Jin C, Kong LJ, Dana H, et al., 2020. Advances in point spread function engineering for functional imaging of neural circuits in vivo. J Phys D Appl Phys, 53(38):383001.

[13]Kong LJ, Cui M, 2014. In vivo fluorescence microscopy via iterative multi-photon adaptive compensation technique. Opt Expr, 22(20):23786-23794.

[14]Kong LJ, Cui M, 2015a. In vivo deep tissue imaging via iterative multiphoton adaptive compensation technique. IEEE J Sel Top Quant Electron, 22(4):40-49.

[15]Kong LJ, Cui M, 2015b. In vivo neuroimaging through the highly scattering tissue via iterative multi-photon adaptive compensation technique. Opt Expr, 23(5):6145-6150.

[16]Lichtman JW, Conchello JA, 2005. Fluorescence microscopy. Nat Methods, 2(12):910-919.

[17]Lister T, Wright PA, Chappell PH, 2012. Optical properties of human skin. J Biomed Opt, 17(9):090901.

[18]Modi MN, Daie K, Turner GC, et al., 2019. Two-photon imaging with silicon photomultipliers. Opt Expr, 27(24):35830-35841.

[19]Oheim M, Beaurepaire E, Chaigneau E, et al., 2001. Two-photon microscopy in brain tissue: parameters influencing the imaging depth. J Neurosci Methods, 111(1):29-37.

[20]Saar BG, Freudiger CW, Reichman J, et al., 2010. Video-rate molecular imaging in vivo with stimulated Raman scattering. Science, 330(6009):1368-1370.

[21]Soleimanzad H, Gurden H, Pain F, 2017. Optical properties of mice skull bone in the 455- to 705-nm range. J Biomed Opt, 22(1):010503.

[22]Toublanc D, 1996. Henyey-Greenstein and Mie phase functions in Monte Carlo radiative transfer computations. Appl Opt, 35(18):3270-3274.

[23]Wang MR, Kim M, Xia F, et al., 2019. Impact of the emission wavelengths on in vivo multiphoton imaging of mouse brains. Biomed Opt Expr, 10(4):1905-1918.

[24]Wang TY, Ouzounov DG, Wu CY, et al., 2018. Three-photon imaging of mouse brain structure and function through the intact skull. Nat Methods, 15(10):789-792.

[25]Yang G, Pan F, Parkhurst CN, et al., 2010. Thinned-skull cranial window technique for long-term imaging of the cortex in live mice. Nat Protoc, 5(2):201-208.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE