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In the past decade, fluorescence lifetime imaging microscopy (FLIM) has been widely used in biomedical research and other fields. As the fluorescence lifetime is unaffected by probe concentration, excitation intensity and photobleaching, the FLIM has the advantages of high specificity, high sensitivity and capability of quantitative measurement in monitoring microenvironment changes and reflecting the intermolecular interactions. Despite decades of technical development, the FLIM technology still faces some challenges in practical applications. For example, its resolution is still difficult to overcome the diffraction limit and the trade-off among imaging speed, image quality and lifetime accuracy needs to be considered. In recent years, a great advance in FLIM and its application has been made due to the rapid development of hardware and software and their integration with other optical technologies. In this review, we first introduce the principle and characteristics of FLIM technology based on time domain and frequency domain. We then summarize the latest progress of FLIM technology:1) imaging speed enhancement based on hardware improvement such as optimized time-correlated single photon counting module, single photon avalanche diode array detector, and acousto-optic deflector scanner; 2) lifetime measurement accuracy improvement by the proposed algorithms such as maximum likelihood estimate, Bayesian analysis and compressed sensing; 3) imaging quality enhancement and spatial resolution improvement by integrating FLIM with other optical technologies such as adaptive optics for correcting the aberration generated in the optical path, special illumination for equipping wide-field FLIM with optical sectioning ability, and super-resolution techniques for exceeding the resolution limit. We then highlight some recent applications in biomedical studies such as signal transduction or plant cell growth, disease diagnosis and treatment in cancers, Alzheimer's disease and skin diseases, assessment for toxicity and treatment efficiency of nanomaterials developed in the past few years. Finally, we present a short discussion on the current challenges and provide an outlook of the future development of enhanced imaging performance for FLIM technology. We hope that our summary on the state-of-the-art FLIM, our commentary on future challenges, and some proposed avenues for further advances will contribute to the development of FLIM technology and its applications in relevant fields.
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Keywords:
- fluorescence lifetime imaging microscopy /
- fast imaging /
- super-resolution imaging /
- biomedical application
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[1] Lin D Y, Ma W Y 2007 Physics 36 783 (in Chinese)[林丹樱, 马万云 2007 物理 36 783]
[2] Huang R, Zhou X M 2013 Acta Laser Biol. Sin. 22 289 (in Chinese)[黄茹, 周小明 2013 激光生物学报 22 289]
[3] Meyer-Almes F J 2017 Methods Appl. Fluores. 5 042002
[4] Liu C, Zhou Y, Wang X W, Liu Y L 2011 Las. Optoelect. Prog. 48 46 (in Chinese)[刘超, 周燕, 王新伟, 刘育梁 2011 激光与光电子学进展 48 46]
[5] Becker W 2012 J. Microsc. Oxford 247 119
[6] Qu J L, Niu H B, Guo B P 1997 Appl. Laser 17 100 (in Chinese)[屈军乐, 牛憨笨, 郭宝平 1997 应用激光 17 100]
[7] Liu L X, Qu J L, Lin Z Y, Chen D N, Guo B P, Niu H B 2005 J. Shenzhen Univ. Sci. Eng. 22 133 (in Chinese)[刘立新, 屈军乐, 林子扬, 陈丹妮, 郭宝平, 牛憨笨 2005 深圳大学学报(理工版) 22 133]
[8] Li J 2016 M. S. Thesis (Kaifeng:Henan University) (in Chinese)[李珺 2016 硕士学位论文 (开封:河南大学)]
[9] Wu Q Q 2017 M. S. Thesis (Shenzhen:Shenzhen University) (in Chinese)[吴茜茜 2017 硕士学位论文 (深圳:深圳大学)]
[10] Wang X, Uchida T, Minami S 1989 Appl. Spectrosc. 43 840
[11] Marois A L, Suhling K 2017 Quantitative Live Cell FLIM Imaging in Three Dimensions (Cham, Switzerland:Springer International Publishing) pp31-48
[12] Alexiev U, Volz P, Boreham A, Brodwolf R 2017 Eur. J. Pharm. Biopharm. 116 111
[13] Krishnan R V, Saitoh H, Terada H, Centonze V E, Herman B 2003 Rev. Sci. Instrum. 74 2714
[14] Koenig M, Orthaus-Mueller S, Dowler R, Kraemer B, Tannert A, Schulz O, Roehlicke T, Wahl M, Rahn H J, Patting M, Koberling F, Erdmann R 2017 Biophys. J. 112 298a
[15] O'Connor D V 2012 Time-Correlated Single Photon Counting (London:Academic Press) pp36-54
[16] Karami M A, Ansarian M 2017 Basic Clin. Neurosci. 8 19
[17] Field R M, Realov S, Shepard K L 2014 IEEE J. Solid-St. Circ. 49 867
[18] Hirvonen L M, Suhling K 2017 Meas. Sci. Technol. 28 012003
[19] Suhling K, Hirvonen L M, Becker W, Smietana S, Netz H, Milnes J, Conneely T, Marois A L, Jagutzki O 2016 Proc. SPIE 9858 98580I
[20] Nie K M, Wang X L, Qiao J, Xu J T 2016 Sensors 16 160
[21] Poland S P, Krstajić N, Monypenny J, Coelho S, Tyndall D, Walker R J, Devauges V, Richardson J, Dutton N, Barber P, Li D D U, Suhling K, Ng T, Henderson R K, Ameer-Beg S M 2015 Biomed. Opt. Express 6 277
[22] Liu L X, Li Y H, Sun L G, Li H, Peng X, Qu J L 2014 Proc. SPIE 8948 89482L
[23] Qi J, Shao Y H, Liu L X, Wang K G, Chen T S, Qu J L, Niu H B 2013 Opt. Lett. 38 1697
[24] Wu Q Q, Qi J, Lin D Y, Yan W, Hu R, Peng X, Qu J L 2017 Proc. SPIE 10069 1006922
[25] Maus M, Cotlet M, Gensch T, Hofkens J, Schryver F C D 2001 Anal. Chem. 73 2078
[26] Chessel A, Waharte F, Salamero J, Kervrann C 2013 21st European Signal Processing Conference Marrakech, Morocco, September 9-13, 2013 pp1-5
[27] Day R N 2014 Methods 66 200
[28] Digman M A, Caiolfa V R, Zamai M, Gratton E 2008 Biophys. J. 94 L14
[29] Lakner P H, Monaghan M G, Mller Y, Olayioye M A, Schenke-Layland K 2017 Sci. Rep-UK. 7 42730
[30] Marois A L, Labouesse S, Suhling K, Heintzmann R 2017 J. Biophotonics 10 1124
[31] Xu L L 2013 Ph. D. Dissertation (Wuhan:Huazhong University of Science and Technology) (in Chinese)[徐玲玲 2013 博士学位论文 (武汉:华中科技大学)]
[32] Shao Y X 2015 M. S. Thesis (Tianjin:Tianjin University of Technology) (in Chinese)[邵永鑫 2015 硕士学位论文 (天津:天津理工大学)]
[33] Liu C 2013 M. S. Thesis (Beijing:University of Chinese Academy of Sciences) (in Chinese)[刘超 2013 硕士学位论文 (北京:中国科学院大学)]
[34] Liu Y, Zhou Y, Liu Y L 2015 Las. Optoelect. Prog. 52 101102 (in Chinese)[刘洋, 周燕, 刘育梁 2015 激光与光电子学进展 52 101102]
[35] Rowley M I, Coolen A C C, Vojnovic B, Barber P R 2016 PLoS One 11 e0158404
[36] Yang S, Lee J, Lee Y, Lee M, Lee B U 2015 J. Biomed. Opt. 20 096003
[37] Zhang Y L, Li D D U 2017 Phys. Med. Biol. 62 1632
[38] Wan W B, Hua D X, Yue J, Liu M X, Cao N 2013 Acta Phys. Sin. 62 190601 (in Chinese)[万文博, 华灯鑫, 乐静, 刘美霞, 曹宁 2013 62 190601]
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[42] Hinsdale T, Olsovsky C, Rico-Jimenez J J, Brodwolf R, Maitland K C, Jo J A, Malik B H 2017 Biomed. Opt. Express 8 1455
[43] Greger K, Neetz M J, Reynaud E G, Stelzer E H K 2011 Opt. Express 19 20743
[44] Lenz M O, Brown A C N, Auksorius E, Davis D M, Dunsby C, Neil M A A, French P M W 2011 Proc. SPIE 7903 79032D
[45] Auksorius E, Boruah B R, Dunsby C, Lanigan P M P, Kennedy G, Neil M A A, French P M W 2008 Opt. Lett. 33 113
[46] Auksorius E 2017 Ph. D. Dissertation (London:Imperial College London)
[47] Gu Z T, Kuang C F, Li S, Xue Y, Zheng Z R, Liu X 2012 Asia Communications and Photonics Conference Guangzhou, China, November 7-10, 2012 pp1-3
[48] Lin D Y, Qu J L 2017 Acta Phys. Sin. 66 148703 (in Chinese)[林丹樱, 屈军乐 2017 66 148703]
[49] Yan W, Yang Y L, Tan Y, Chen X, Li Y, Qu J L, Ye T 2017 Photonics Res. 5 176
[50] Grlitz F, Corcoran D, Castano E G, Leitinger B, Mark Neil M, Dunsby C, French P 2017 Photonics 4 40
[51] Walsh A J, Sedelnikova A, Tolstykh G P, Ibey B L, Beier H T 2017 Proc. SPIE 10069 100691B
[52] Margineanu A, Chan J J, Kelly D J, Warren S C, Flatters D, Kumar S, Katan M, Christopher W, Dunsby C W, French P W M 2016 Sci. Rep.-UK 6 28186
[53] Frederik G F, Kelly D J, Warren S C, Alibhai D, West L, Kumar S, Alexandrov Y, Munro L, Garcia E, McGinty J, Talbot C, Serwa R A, Thinon E, Paola V D, Murray E J, Stuhmeier F, Neil M A A, Tate E W, Dunsby C, French P W M 2017 Jove-J. Vis. Express 119 e55119
[54] Tian W M, Chen J, Deng L Z, Yang H P, Zheng Y, Fei L P, Cui R R, Sha G H, Zhang C H 2013 The 13th National Conference on Chemical Dynamics Wuhan, August 23-28, 2013 pp5-158 (in Chinese)[田文明, 陈钧, 邓列征, 杨何平, 郑阳, 费丽萍, 崔荣荣, 沙国河, 张存浩 2013 第13届全国化学动力学会议 武汉, 2013年8月2328日, 第5158页]
[55] Long Y C, Stahl Y, Weidtkamp-Peters S, Postma M, Zhou W K, Goedhart J, Snchez-Prez M I, Gadella J T W J, Simon R, Scheres B, Blilou I 2017 Nature 548 97
[56] Kodama Y 2016 PLoS One 11 e0152484
[57] Camborde L, Jauneau A, Brire C, Deslandes L, Dumas B, Gaulin E 2017 Nat. Protoc. 12 1933
[58] Pastore M N, Studier H, Bonder C S, Roberts M S 2017 Exp. Dermatol. 26 607
[59] Alam S R, Wallrabe H, Svindrych Z, Wallrabe H 2017 Proc. SPIE-OSA 10414 1041402
[60] Alam S R, Wallrabe H, Svindrych Z, Christopher K G, Chandra D, Periasamy A 2017 Proc. SPIE 10069 100691L
[61] Shirmanova M V, Lukina M M, Lyubov'E S, Kuimova M K, Dudenkova V V, Shcheslavskiy V I, Zagaynova E V 2017 Proc. SPIE-OSA 10411 1041102
[62] Chen W Y, Young L J, Lu M, Zaccone A, Strohl F, Yu N, Schierle G S K, Kaminski C F 2016 Nano Lett. 17 143
[63] Li W Y, Fang B Q, Jin M, Tian Y 2017 Anal. Chem. 89 2553
[64] Chen M H, Li H, Chen R, Song C L 2014 Acta Laser Biol. Sin. 23 207 (in Chinese)[陈明惠, 李昊, 陈荣, 宋成利 2014 激光生物学报 23 207]
[65] Jin L 2013 M. S. Thesis (Nanjing:Nanjing University of Chinese Medicine) (in Chinese)[金路 2013 硕士学位论文 (南京:南京中医药大学)]
[66] Luo T, Lu Y, Liu S X, Lin D Y, Qu J L 2017 Anal. Chem. 89 8104
[67] Ruedas-Rama M J, Walters J D, Orte A, Hall E A H 2012 Anal. Chim. Acta 751 1
[68] Giraud G, Schulze H, Bachmann T T, Campbell C J, Mount A R, Ghazal P, Khondoker M R, Ross A J, Ember S W J, Ciani I, Tlili C, Walton A J, Terry J G, Crain J 2009 Int. J. Mol. Sci. 10 1930
[69] Lin L L, Grice J E, Butler M K, Zvyagin A V, Becker W, Robertson T A, Soyer H P, Roberts M S, Prow T W 2011 Pharm. Res. -Dordr. 28 2920
[70] Chen K, Preu A, Hackbarth S, Wacker M, Langer K, Roder B 2009 J. Photoch. Photobio. B 96 66
[71] Zhou T, Luo T, Song J, Qu J L 2018 Anal. Chem. 90 2170
[72] Zhang Y N, Chen Y, Yu J, Birch D J S 2017 Proc. IASTED Int. Conf. Biomed. Eng. Innsbruck, Austria, February 20-21, 2017 pp26-31
[73] Zhang Y N, Chen Y, Yu J, Birch D J 2017 Med. Devices Diagn. Eng. 2 78
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