小型化无透镜微流控片上生物成像检测

doi:10.11959/j.issn.2096-3750.2019.00111

物联网学报 ›› 2019, Vol. 3 ›› Issue (2): 9-19.doi: 10.11959/j.issn.2096-3750.2019.00111

小型化无透镜微流控片上生物成像检测

陈津,黄汐威(),李阳波,刘季璇,孙玲玲

杭州电子科技大学射频电路与系统教育部重点实验室，浙江杭州310018

修回日期:2019-06-02 出版日期:2019-06-30 发布日期:2019-07-17
作者简介:陈津（1992- ），男，福建三明人，杭州电子科技大学硕士生，主要研究方向为微流控片上成像电路与系统设计和声表面波传感检测。|黄汐威（1987- ），男，江西上饶人，博士，杭州电子科技大学副教授，主要研究方向为CMOS集成传感器和微流控分析系统。|李阳波（1994- ），男，山西朔州人，杭州电子科技大学硕士生，主要研究方向为CMOS图像传感检测和无透镜全息成像。|刘季璇（1996- ），女，黑龙江齐齐哈尔人，杭州电子科技大学硕士生，主要研究方向为基于深度学习的片上细胞成像智能处理。|孙玲玲（1956- ），女，山东泗水人，杭州电子科技大学射频电路与系统教育部重点实验室主任、教授，主要研究方向为微波毫米波集成电路与智能系统设计。
基金资助:
国家自然科学基金资助项目(61827806);国家自然科学基金资助项目(61501156);浙江省钱江人才计划D类项目(QJD1802021);浙江省公益性技术应用研究计划项目(2017C31064)

Miniaturized lensless microfluidic on-chip bio-imaging detection

Jin CHEN,Xiwei HUANG(),Yangbo LI,Jixuan LIU,Lingling SUN

Ministry of Education Key Lab of RF Circuits and Systems,Hangzhou Dianzi University,Hangzhou 310018,China

Revised:2019-06-02 Online:2019-06-30 Published:2019-07-17
Supported by:
The National Natural Science Foundation of China(61827806);The National Natural Science Foundation of China(61501156);Qianjiang Talent Project Type-D of Zhejiang(QJD1802021);Public Welfare Technology Application Research Project of Zhejiang(2017C31064)

摘要/Abstract

摘要：

用于生物医疗成像的传统高分辨率光学显微镜由于复杂的光学透镜系统导致高成本、不便携。为了实现小型化成像检测，基于CMOS图像传感芯片与微流控集成的无透镜微流控片上成像系统近年来发展迅速，是解决小型化显微成像检测的重要方法。综述了无透镜微流控片上成像系统的结构、成像原理、存在的问题与改进的方法，主要包括阴影成像系统、全息成像系统、荧光成像系统以及彩色成像系统等，分析了无透镜微流控片上成像系统的不足和可能的发展方向。

关键词: 片上成像, 无透镜, 微流控, CMOS图像传感器, 小型化

Abstract:

The conventional high-resolution optical microscopy for biomedical imaging has high cost and low portability due to bulky optical lenses system.To realize miniaturized imaging,the recent advance of lensless microfluidic on-chip imaging technique based on the integration of CMOS image sensor and microfluidics has provided one promising solution.Therefore,the architecture,principle,problems and improvement solutions for different miniaturized lensless microfluidic on-chip bio-imaging,including shadow imaging,holographic imaging,fluorescent imaging and color imaging were reviewed.And the deficiencies and possible development directions were discussed.

Key words: on-chip imaging, lensless, microfluidic, CMOS image sensor, miniaturization

中图分类号:

TP391

陈津,黄汐威,李阳波,刘季璇,孙玲玲. 小型化无透镜微流控片上生物成像检测[J]. 物联网学报, 2019, 3(2): 9-19.

Jin CHEN,Xiwei HUANG,Yangbo LI,Jixuan LIU,Lingling SUN. Miniaturized lensless microfluidic on-chip bio-imaging detection[J]. Chinese Journal on Internet of Things, 2019, 3(2): 9-19.

图/表 13

图1

图2

图3

图4

图5

图6

图7

图8

图9

图10

图11

图12

表1

参考文献 70

[1]	GABOR D . A new microscopic principle[J]. Nature, 1948,161(4098):777.
[2]	MUDANYALI O , OZTOPRAK C , TSENG D ,et al. Detection of waterborne parasites using field-portable and cost-effective lensfree microscopy[J]. Lab on a Chip, 2010,10(18): 2419-2423.
[3]	WU Y C , SHILEDAR A , LI Y C ,et al. Air quality monitoring using mobile microscopy and machine learning[J]. Light-Science ＆ Applications, 2017,6:12.
[4]	BALAKRISHNAN P , DUNNE M , KUMARASAMY N ,et al. An inexpensive,simple,and manual method of CD4 T-cell quantitation in HIV-infected individuals for use in developing countries[J]. JAIDS—Journal of Acquired Immune Deficiency Syndromes, 2004,36(5): 1006-1010.
[5]	DITTRICH P S , MANZ A . Lab-on-a-chip:microfluidics in drug discovery[J]. Nature Reviews Drug Discovery, 2006,5(3): 210-218.
[6]	LEE S , ONCESCU V , MANCUSO M ,et al. A smartphone platform for the quantification of vitamin D levels[J]. Lab on a Chip, 2014,14(8): 1437-1442.
[7]	STARKUVIENE V , PEPPERKOK R . The potential of high-content high-throughput microscopy in drug discovery[J]. British Journal of Pharmacology, 2007,152(1): 62-71.
[8]	GREENBAUM A , LUO W , SU T W ,et al. Imaging without lenses:achievements and remaining challenges of wide-field on-chip microscopy[J]. Nature Methods, 2012,9(9): 889-895.
[9]	GOROCS Z , OZCAN A . On-chip biomedical imaging[J]. IEEE Reviews in Biomedical Engineering, 2013,6: 29-46.
[10]	ISIKMAN S O , BISHARA W , MUDANYALI O ,et al. Lensfree on-chip microscopy and tomography for biomedical applications[J]. IEEE Journal of Selected Topics in Quantum Electronics, 2012,18(3): 1059-1072.
[11]	YUAN X , PU Y C . Parallel lensless compressive imaging via deep convolutional neural networks[J]. Optics Express, 2018,26(2): 1962-1977.
[12]	LUO W , GREENBAUM A , ZHANG Y B ,et al. Synthetic aperture-based on-chip microscopy[J]. Light-Science ＆ Applications, 2015,4:9.
[13]	ALEXANDROV S A , HILLMAN T R , GUTZLER T ,et al. Synthetic aperture fourier holographic optical microscopy[J]. Physical Review Letters, 2006,97(16):4.
[14]	WEI Q S , MCLEOD E , QI H F ,et al. Lensfree holographic cytometry using plasmonic nanoparticles[C]// 2013 IEEE Photonics Conference. IEEE, 2013: 3-4.
[15]	HUANG X W , GUO J H , WANG X L ,et al. A contact-imaging based microfluidic cytometer with machine-learning for single-frame super-resolution processing[J]. Plos One, 2014,9(8):10.
[16]	DELACROIX R , MOREL S N A , HERVE L ,et al. Cerebrospinal fluid lens-free microscopy:a new tool for the laboratory diagnosis of meningitis[J]. Scientific Reports, 2017,7:8.
[17]	OZCAN A , MCLEOD E . Lensless imaging and sensing[J]. Annual Review of Biomedical Engineering, 2016,18: 77-102.
[18]	SU T W , SEO S , ERLINGER A ,et al. High-throughput lensfree imaging and characterization of a heterogeneous cell solution on a chip[J]. Biotechnology and Bioengineering, 2009,102(3): 856-868.
[19]	SU T W , SEO S , EDINGER A ,et al. High-throughput cellimaging,counting and characterization on a chip[M]. New York: Amer Soc Mechanical EngineersPress, 2009.
[20]	HUANG X , FAROOQ U , CHEN J ,et al. A surface acoustic wave pumped lensless microfluidic imaging system for flowing cell detection and counting[J]. IEEE Transactions on Biomedical Circuits and Systems, 2017,11(6): 1478-1487.
[21]	黄汐威, 程涛, 丁诚翔 ,等. 无透镜微流控成像流动细胞检测与计数系统[J]. 传感器与微系统, 2017,36(5): 94-98.
	HUANG X W , CHENG T , DING C X ,et al. Lensless microfluidic imaging flow cell detection and counting system[J]. Transducer and Microsystem Technologies, 2017,36(5): 94-98.
[22]	ZHENG G A , LEE S A , ANTEBI Y ,et al. The ePetri dish,an on-chip cell imaging platform based on subpixel perspective sweeping microscopy(SPSM)[J]. Proceedings of the National Academy of Sciences of the United States of America, 2011,108(41): 16889-16894.
[23]	HENG X , ERICKSON D , BAUGH L R ,et al. Optofluidic microscopy—a method for implementing a high resolution optical microscope on a chip[J]. Lab on a Chip, 2006,6(10): 1274-1276.
[24]	LEE L M , CUI X Q , YANG C H . The application of on-chip optofluidic microscopy for imaging Giardia lamblia trophozoites and cysts[J]. Biomedical Microdevices, 2009,11(5): 951-958.
[25]	ROY M , SEO D , OH S ,et al. A review of recent progress in lens-free imaging and sensing[J]. Biosensors ＆ Bioelectronics, 2017,88: 130-143.
[26]	BISHARA W , SIKORA U , MUDANYALI O ,et al. Holographic pixel super-resolution in portable lensless on-chip microscopy using a fiber-optic array[J]. Lab on a Chip, 2011,11(7): 1276-1279.
[27]	CHO C , CHOI B , KANG H ,et al. Numerical twin image suppression by nonlinear segmentation mask in digital holography[J]. Optics Express, 2012,20(20): 22454-22464.
[28]	SEO D , OH S , LEE M ,et al. A field-portable cell analyzer without a microscope and reagents[J]. Sensors, 2018,18(1):14.
[29]	XU W , JERICHO M H , MEINERTZHAGEN I A ,et al. Digital in-line holography for biological applications[J]. Proceedings of the National Academy of Sciences of the United States of America, 2001,98(20): 11301-11305.
[30]	XU W , JERICHO M H , MEINERTZHAGEN I A ,et al. Digital in-line holography of microspheres[J]. Applied Optics, 2002,41(25): 5367-5375.
[31]	GARCIA-SUCERQUIA J , XU W B , JERICHO S K ,et al. Digital in-line holographic microscopy[J]. Applied Optics, 2006,45(5): 836-850.
[32]	NOOM D W E , EIKEMA K S E , WITTE S . Lensless phase contrast microscopy based on multiwavelength Fresnel diffraction[J]. Optics Letters, 2014,39(2): 193-196.
[33]	BANYASZ I , KORNIS J . High-resolution lensless Fourier-transform digital holography[J]. International Society for Optical Engineering, 2005,5856: 71-79.
[34]	FIENUP J R . Phase retrieval algorithms:a comparison[J]. Applied Optics, 1982,21(15): 2758-2769.
[35]	FAULKNER H M L , RODENBURG J M . Movable aperture lensless transmission microscopy:a novel phase retrieval algorithm[J]. Physical Review Letters, 2004,93(2):4.
[36]	GARCIA-SUCERQUIA J , XU W B , JERICHO M H ,et al. Immersion digital in-line holographic microscopy[J]. Optics Letters, 2006,31(9): 1211-1213.
[37]	SEO S , SU T W , TSENG D K ,et al. Lensfree holographic imaging for on-chip cytometry and diagnostics[J]. Lab on a Chip, 2009,9(6): 777-787.
[38]	GARCIA-SUCERQUIA J . Color digital lensless holographic microscopy:laser versus LED illumination[J]. Applied Optics, 2016,55(24): 6649-6655.
[39]	LUO W , GREENBAUM A , ZHANG Y B ,et al. High-resolution on-chip imaging using synthetic aperture[C]// 2015 Conference on Lasers and Electro-Optics. IEEE, 2015.
[40]	ISIKMAN S O , BISHARA W , SIKORA U ,et al. Field-portable lensfree tomographic microscope[J]. Lab on a Chip, 2011,11(13): 2222-2230.
[41]	GREENBAUM A , SIKORA U , OZCAN A . Field-portable wide-field microscopy of dense samples using multi-height pixel super-resolution based lensfree imaging[J]. Lab on a Chip, 2012,12(7): 1242-1245.
[42]	GRANERO L , FERREIRA C , ZALEVSKY Z ,et al. Single-exposure super-resolved interferometric microscopy by RGB multiplexing in lensless configuration[J]. Optics and Lasers in Engineering, 2016,82: 104-112.
[43]	FEIZI A , ZHANG Y B , GREENBAUM A ,et al. Yeast viability and concentration analysis using lens-free computational microscopy and machine learning[C]// Optics and Biophotonics in Low-Resource Settings III Spie-Int Soc Optical Engineering, 2017.
[44]	DALOGLU M U , OZCAN A . Computational imaging of sperm locomotion[J]. Biology of Reproduction, 2017,97(2): 182-188.
[45]	DI CAPRIO G , GIOFFRE M A , SAFFIOTI N ,et al. Quantitative label-free animal sperm imaging by means of digital holographic microscopy[J]. IEEE Journal of Selected Topics in Quantum Electronics, 2010,16(4): 833-840.
[46]	SOLER C , PICAZO-BUENO J A , MICO V ,et al. Effect of counting chamber depth on the accuracy of lensless microscopy for the assessment of boar sperm motility[J]. Reproduction,Fertility,and Development, 2018,30(6): 924-934.
[47]	LI G X , ZHANG R B , YANG N ,et al. An approach for cell viability online detection based on the characteristics of lensfree cell diffraction fingerprint[J]. Biosensors ＆ Bioelectronics, 2018,107: 163-169.
[48]	SANZ M , PICAZO-BUENO J A , GARCIA J ,et al. Dual-mode holographic microscopy imaging platform[J]. Lab on a Chip, 2018,18(7): 1105-1112.
[49]	AXELROD D . Total internal reflection fluorescence microscopy in cell biology[J]. Traffic (Copenhagen,Denmark), 2001,2(11): 764-774.
[50]	COSKUN A F , SENCAN I , SU T W ,et al. Lensfree fluorescent on-chip imaging of transgenic caenorhabditis elegans over an ultra-wide field-of-view[J]. Plos One, 2011,6(1):9.
[51]	GREENBAUM A , ZHANG Y B , FEIZI A ,et al. Wide-field computational imaging of pathology slides using lens-free on-chip microscopy[J]. Science Translational Medicine, 2014,6(267):10.
[52]	SASAGAWA K , KIM S H , MIYAZAWA K ,et al. Dual-mode lensless imaging device for digital enzyme linked immunosorbent assay[C]// Frontiers in Biological Detection:From Nanosensors to Systems Vi Spie-Int Soc Optical Engineering, 2014.
[53]	IMAI K , NISHIGAKI M , ONOZUKA Y ,et al. A lens-freesingle-shot fluorescent imaging system using CMOS image sensors with dielectric multilayer filter[M]. Piscataway: IEEE PressPress, 2017.
[54]	LEE S A , OU X Z , LEE J E ,et al. Chip-scale fluorescence microscope based on a silo-filter complementary metal-oxide semiconductor image sensor[J]. Optics Letters, 2013,38(11): 1817-1819.
[55]	MUDRABOYINA A K , BLOCKSTEIN L , LUK C C ,et al. A novel lensless miniature contact imaging system for monitoring calcium changes in live neurons[J]. IEEE Photonics Journal, 2014,6(1):15.
[56]	BIGGS D S , ANDREWS M . Acceleration of iterative image restoration algorithms[J]. Applied Optics, 1997,36(8): 1766-1775.
[57]	COSKUN A F , SU T W , OZCAN A . Wide field-of-view lens-free fluorescent imaging on a chip[J]. Lab on a Chip, 2010,10(7): 824-827.
[58]	HAN C , PANG S , BOWER D V ,et al. Wide field-of-view on-chip talbot fluorescence microscopy for longitudinal cell culture monitoring from within the incubator[J]. Analytical Chemistry, 2013,85(4): 2356-2360.
[59]	TAKEHARA H , NAGASAKI M , SASAGAWA K ,et al. Micro-light-pipe array with an excitation attenuation filter for lensless digital enzyme-linked immunosorbent assay[J]. Japanese Journal of Applied Physics, 2016,55(3):9.
[60]	AMOLINS K , ZHANG Y , DARE P . Wavelet based image fusion techniques-an introduction,review and comparison[J]. ISPRS Journal of Photogrammetry and Remote Sensing, 2007,62(4): 249-263.
[61]	LEE S A , ERATH J , ZHENG G A ,et al. Imaging and identification of waterborne parasites using a chip-scale microscope[J]. Plos One, 2014,9(2):5.
[62]	PANG S , CUI X Q , DEMODENA J ,et al. Implementation of a color-capable optofluidic microscope on a RGB CMOS color sensor chip substrate[J]. Lab on a Chip, 2010,10(4): 411-414.
[63]	GREENBAUM A , FEIZI A , AKBARI N ,et al. Wide-field computational color imaging using pixel super-resolved on-chip microscopy[J]. Optics Express, 2013,21(10): 12469-12483.
[64]	GREENBAUM A , AKBARI N , FEIZI A ,et al. Field-portable pixel super-resolution colour microscope[J]. Plos One, 2013,8(9):9.
[65]	WU Y C , ZHANG Y B , LUO W ,et al. Demosaiced pixel super-resolution for multiplexed holographic color imaging[J]. Scientific Reports, 2016,6:9.
[66]	ZHANG Y B , WU Y C , ZHANG Y ,et al. Fusion of lens-free microscopy and mobile-phone microscopy images for high-color-accuracy and high-resolution pathology imaging[C]// Optics and Biophotonics in Low-Resource Settings III Spie-Int Soc Optical Engineering, 2017.
[67]	MCLEOD E , NGUYEN C , HUANG P ,et al. Tunable vapor-condensed nanolenses[J]. ACS Nano, 2014,8(7): 7340-7349.
[68]	FEIZI A , ZHANG Y B , GREENBAUM A ,et al. Rapid,portable and cost-effective yeast cell viability and concentration analysis using lensfree on-chip microscopy and machine learning[J]. Lab on a Chip, 2016,16(22): 4350-4358.
[69]	HUANG X W , WANG X L , YAN M ,et al. A robust recognition error recovery for micro-flow cytometer by machine-learning enhanced single-frame super-resolution processing[J]. Integration—The VLSI Journal, 2015,51: 208-218.
[70]	COSTA F F . Big data in biomedicine[J]. Drug Discovery Today, 2014,19(4): 433-440.

系统	阴影	全息	荧光
光源	单色光或白光	相干或部分相干	特定波长
结构特征	样本靠近像素平面	LED+小孔	滤光片
样本属性	不透光或部分透光	不透光或部分透光	荧光标记
计算量	中等	极大	中等
恢复彩色细节	可以	可以	不能

小型化无透镜微流控片上生物成像检测

Miniaturized lensless microfluidic on-chip bio-imaging detection

在线阅读

PDF下载

可视化

摘要/Abstract

引用本文

使用本文

图/表 13

参考文献 70

相关文章 15

Metrics

推荐阅读 0

[1]	王柱, 张化磊, 胡千红, 於志文. 基于可见光的环境自适应手势识别系统[J]. 物联网学报, 2023, 7(2): 15-25.
[2]	刘文昌, 魏赟, 袁浩轩, 高跃. 基于SMOTE和gcForest的医疗小样本数据分类研究[J]. 物联网学报, 2023, 7(2): 76-87.
[3]	曾钰婷, 毕宿志, 郑莉莉, 林晓辉, 王晖. 基于CSI小样本学习的场景鲁棒性跌倒检测系统[J]. 物联网学报, 2023, 7(2): 118-132.
[4]	江恺, 曹越, 周欢, 任学锋, 朱永东, 林海. 车联网边缘智能：概念、架构、问题、实施和展望[J]. 物联网学报, 2023, 7(1): 37-48.
[5]	袁培燕, 邵赛珂, 魏然, 张俊娜, 赵晓焱. 基于时延和能耗约束的感知数据协作卸载策略研究[J]. 物联网学报, 2023, 7(1): 109-117.
[6]	苏麟, 党小超, 郝占军, 汝春瑞, 尚旭. 基于WPT-MEC的动态自适应卸载方法[J]. 物联网学报, 2022, 6(4): 128-138.
[7]	郭佳慧, 陈卓越, 高玮, 王玺钧, 孙兴华, 高林. 基于背包模型的联邦学习客户端选择方法[J]. 物联网学报, 2022, 6(4): 158-168.
[8]	李养群, 张登银. 物品万维网资源管理框架研究与应用[J]. 物联网学报, 2022, 6(2): 50-64.
[9]	罗丹, 徐茹枝, 关志涛. 物联网环境中基于深度学习的差分隐私预算优化方法[J]. 物联网学报, 2022, 6(2): 65-76.
[10]	李芬芳, 党小超, 郝占军. 基于三维Voronoi图划分的加权混合回归定位算法[J]. 物联网学报, 2022, 6(2): 106-116.
[11]	方娟, 叶志远, 张梦媛, 史佳眉, 滕自怡. 边云协同场景下基于强化学习的精英分层任务卸载策略研究[J]. 物联网学报, 2022, 6(1): 91-100.
[12]	周毅, 胡姝婷, 李伟, 承楠, 路宁, 沈学民. 图神经网络驱动的交通预测技术：探索与挑战[J]. 物联网学报, 2021, 5(4): 1-16.
[13]	马嘉华, 孙兴华, 夏文超, 王玺钧, 谭洪舟, 朱洪波. 基于标签量信息的联邦学习节点选择算法[J]. 物联网学报, 2021, 5(4): 46-53.
[14]	茅敏敏, 居家奇, 欧阳玉玲, 金妍. 基于NB-IoT技术的环境温湿度监测系统的研制[J]. 物联网学报, 2021, 5(4): 99-106.
[15]	赵甘霖, 余畅, 张建富, 杨建新, 冯平法, 沈群. 基于AR虚实图像注意力机制的电缆装配质量检测方法[J]. 物联网学报, 2021, 5(3): 27-38.