Multicolor single-molecule localization microscopy: review and prospect

Xi Chen; Xiangyu Wang; Fang Huang; Donghan Ma

doi:10.1186/s43074-024-00147-2

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Xi Chen, Xiangyu Wang, Fang Huang, Donghan Ma. Multicolor single-molecule localization microscopy: review and prospect[J]. PhotoniX. doi: 10.1186/s43074-024-00147-2

Citation:

Xi Chen, Xiangyu Wang, Fang Huang, Donghan Ma. Multicolor single-molecule localization microscopy: review and prospect[J]. PhotoniX. doi: 10.1186/s43074-024-00147-2

Xi Chen, Xiangyu Wang, Fang Huang, Donghan Ma. Multicolor single-molecule localization microscopy: review and prospect[J]. PhotoniX. doi: 10.1186/s43074-024-00147-2

Citation:

Xi Chen, Xiangyu Wang, Fang Huang, Donghan Ma. Multicolor single-molecule localization microscopy: review and prospect[J]. PhotoniX. doi: 10.1186/s43074-024-00147-2

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Multicolor single-molecule localization microscopy: review and prospect

doi: 10.1186/s43074-024-00147-2

1.
School of Optoelectronic Engineering and Instrumentation Science, Dalian University of Technology, Dalian, Liaoning, China
2.
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA
3.
Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, USA
4.
Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN, USA

Funds: This work was funded by the Natural Science Foundation of Liaoning Province (2023-MS-103), and the National Natural Science Foundation of China (62305041).

Received Date: 2024-08-13
Accepted Date: 2024-09-25
Rev Recd Date: 2024-09-19

Available Online: 2024-10-02

Abstract

Abstract

Single-molecule localization microscopy (SMLM) surpasses the diffraction limit by randomly switching fluorophores between fluorescent and dark states, precisely pinpointing the resulted isolated emission patterns, thereby reconstructing the super-resolution images based on the accumulated locations of thousands to millions of single molecules. This technique achieves a ten-fold improvement in resolution, unveiling the intricate details of molecular activities and structures in cells and tissues. Multicolor SMLM extends this capability by imaging distinct protein species labeled with various fluorescent probes, providing insights into structural intricacies and spatial relationships among different targets. This review explores recent advancements in multicolor SMLM, evaluates the strengths and limitations of each variant, and discusses the future prospects.
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- Super-resolution microscopy')">" data-track="click" data-track-action="view keyword" data-track-label="link">Super-resolution microscopy,
- Engineering",
- Singe-molecule localization microscopy')">" data-track="click" data-track-action="view keyword" data-track-label="link">Singe-molecule localization microscopy,
- Engineering",
- Multicolor imaging')">" data-track="click" data-track-action="view keyword" data-track-label="link">Multicolor imaging,
- Engineering",
- DNA-PAINT')">" data-track="click" data-track-action="view keyword" data-track-label="link">DNA-PAINT,
- Engineering",
- Ratiometric imaging')">" data-track="click" data-track-action="view keyword" data-track-label="link">Ratiometric imaging,
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- Spectroscopic imaging')">" data-track="click" data-track-action="view keyword" data-track-label="link">Spectroscopic imaging,
- Engineering",
- PSF engineering')">" data-track="click" data-track-action="view keyword" data-track-label="link">PSF engineering

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References(148)

References

[1]	Betzig E, Patterson GH, Sougrat R, Lindwasser OW, Olenych S, Bonifacino JS, et al. Imaging intracellular fluorescent proteins at nanometer resolution. Science. 2006;313:1642–5.
[2]	Hess ST, Girirajan TP, Mason MD. Ultra-high resolution imaging by fluorescence photoactivation localization microscopy. Biophys J. 2006;91:4258–72.
[3]	Rust MJ, Bates M, Zhuang X. Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nat Methods. 2006;3:793–5.
[4]	van de Linde S, Löschberger A, Klein T, Heidbreder M, Wolter S, Heilemann M, et al. Direct stochastic optical reconstruction microscopy with standard fluorescent probes. Nat Protoc. 2011;6:991–1009.
[5]	Endesfelder U, Heilemann M. Direct stochastic optical reconstruction microscopy (dSTORM). Methods Mol Biol. 2015;1251:263–76.
[6]	Jungmann R, Steinhauer C, Scheible M, Kuzyk A, Tinnefeld P, Simmel FC. Single-molecule kinetics and super-resolution microscopy by fluorescence imaging of transient binding on DNA origami. Nano Lett. 2010;10:4756–61.
[7]	Jungmann R, Avendaño MS, Woehrstein JB, Dai M, Shih WM, Yin P. Multiplexed 3D cellular super-resolution imaging with DNA-PAINT and Exchange-PAINT. Nat Methods. 2014;11:313–8.
[8]	Balzarotti F, Eilers Y, Gwosch KC, Gynnå AH, Westphal V, Stefani FD, et al. Nanometer resolution imaging and tracking of fluorescent molecules with minimal photon fluxes. Science. 2017;355:606–12.
[9]	Gwosch KC, Pape JK, Balzarotti F, Hoess P, Ellenberg J, Ries J, et al. MINFLUX nanoscopy delivers 3D multicolor nanometer resolution in cells. Nat Methods. 2020;17:217–24.
[10]	Schermelleh L, Ferrand A, Huser T, Eggeling C, Sauer M, Biehlmaier O, et al. Super-resolution microscopy demystified. Nat Cell Biol. 2019;21:72–84.
[11]	Möckl L, Moerner WE. Super-resolution microscopy with single molecules in biology and beyond–essentials, current trends, and future challenges. J Am Chem Soc. 2020;142:17828–44.
[12]	Lelek M, Gyparaki MT, Beliu G, Schueder F, Griffié J, Manley S, et al. Single-molecule localization microscopy. Nat Rev Methods Primers. 2021;1:39.
[13]	Jing Y, Chen J, Zhou L, Sun J, Cai M, Shi Y, et al. Super-resolution imaging of cancer-associated carbohydrates using aptamer probes. Nanoscale. 2019;11:14879–86.
[14]	Xu J, Ma H, Ma H, Jiang W, Mela CA, Duan M, et al. Super-resolution imaging reveals the evolution of higher-order chromatin folding in early carcinogenesis. Nat Commun. 2020;11:1899.
[15]	Das P, Pujals S, Ali LMA, Gary-Bobo M, Albertazzi L, Durand JO. Super-resolution imaging of antibody-conjugated biodegradable periodic mesoporous organosilica nanoparticles for targeted chemotherapy of prostate cancer. Nanoscale. 2023;15:12008–24.
[16]	Qiu L, Xu H, Sui B, Jiang P, Wang J, Xu D, et al. Elucidating the functional mechanism of PTK7 in cancer development through spatial assembly analysis using super resolution imaging. Anal Chem. 2024;96:7669–78.
[17]	Padmanabhan P, Kneynsberg A, Götz J. Super-resolution microscopy: a closer look at synaptic dysfunction in Alzheimer disease. Nat Rev Neurosci. 2021;22:723–40.
[18]	Dimou E, Katsinelos T, Meisl G, Tuck BJ, Keeling S, Smith AE, et al. Super-resolution imaging unveils the self-replication of tau aggregates upon seeding. Cell Rep. 2023;42:112725.
[19]	Böken D, Cox D, Burke M, Lam JYL, Katsinelos T, Danial JSH, et al. Single-molecule characterization and super-resolution imaging of Alzheimer’s disease-relevant tau aggregates in human samples. Angew Chem Int Ed Engl. 2024;63:e202317756.
[20]	Sang JC, Hidari E, Meisl G, Ranasinghe RT, Spillantini MG, Klenerman D. Super-resolution imaging reveals α-synuclein seeded aggregation in SH-SY5Y cells. Commun Biol. 2021;4:613.
[21]	Morten MJ, Sirvio L, Rupawala H, Mee Hayes E, Franco A, Radulescu C, et al. Quantitative super-resolution imaging of pathological aggregates reveals distinct toxicity profiles in different synucleinopathies. Proc Natl Acad Sci U S A. 2022;119:e2205591119.
[22]	Lobanova E, Whiten D, Ruggeri FS, Taylor CG, Kouli A, Xia Z, et al. Imaging protein aggregates in the serum and cerebrospinal fluid in Parkinson’s disease. Brain. 2022;145:632–43.
[23]	Pan L, Hu F, Zhang X, Xu J. Multicolor single-molecule localization super-resolution microscopy. Acta Optica Sinica. 2017;37:0318010.
[24]	Xiang L, Chen K, Xu K. Single molecules are your quanta: a bottom-up approach toward multidimensional super-resolution microscopy. ACS Nano. 2021;15:12483–96.
[25]	Power RM, Tschanz A, Zimmermann T, Ries J. Build and operation of a custom 3D, multicolor, single-molecule localization microscope. Nat Protoc. 2024;19:2467–525.
[26]	Bock H, Geisler C, Wurm CA, Middendorff CV, Jakobs S, Schönle A, et al. Two-color far-field fluorescence nanoscopy based on photoswitchable emitters. Appl Phys B. 2007;88:161–5.
[27]	Shroff H, Galbraith CG, Galbraith JA, White H, Gillette J, Olenych S, et al. Dual-color superresolution imaging of genetically expressed probes within individual adhesion complexes. Proc Natl Acad Sci U S A. 2007;104:20308–13.
[28]	Löschberger A, van de Linde S, Dabauvalle MC, Rieger B, Heilemann M, Krohne G, et al. Super-resolution imaging visualizes the eightfold symmetry of gp210 proteins around the nuclear pore complex and resolves the central channel with nanometer resolution. J Cell Sci. 2012;125:570–5.
[29]	Fei J, Singh D, Zhang Q, Park S, Balasubramanian D, Golding I, et al. Determination of in vivo target search kinetics of regulatory noncoding RNA. Science. 2015;347:1371–4.
[30]	Zhang Y, Lara-Tejero M, Bewersdorf J, Galán JE. Visualization and characterization of individual type III protein secretion machines in live bacteria. Proc Natl Acad Sci U S A. 2017;114:6098–103.
[31]	Zhang Y, Schroeder LK, Lessard MD, Kidd P, Chung J, Song Y, et al. Nanoscale subcellular architecture revealed by multicolor three-dimensional salvaged fluorescence imaging. Nat Methods. 2020;17:225–31.
[32]	Bates M, Huang B, Dempsey GT, Zhuang X. Multicolor super-resolution imaging with photo-switchable fluorescent probes. Science. 2007;317:1749–53.
[33]	Dani A, Huang B, Bergan J, Dulac C, Zhuang X. Superresolution imaging of chemical synapses in the brain. Neuron. 2010;68:843–56.
[34]	Bates M, Dempsey GT, Chen KH, Zhuang X. Multicolor super-resolution fluorescence imaging via multi-parameter fluorophore detection. ChemPhysChem. 2012;13:99–107.
[35]	Tam J, Cordier GA, Borbely JS, Sandoval Álvarez Á, Lakadamyali M. Cross-talk-free Multi-color STORM imaging using a single fluorophore. PLoS ONE. 2014;9:e101772.
[36]	Valley CC, Liu S, Lidke DS, Lidke KA. Sequential superresolution imaging of multiple targets using a single fluorophore. PLoS ONE. 2015;10:e0123941.
[37]	Tam J, Cordier GA, Bálint Š, Sandoval Álvarez Á, Borbely JS, Lakadamyali M. A microfluidic platform for correlative live-cell and super-resolution microscopy. PLoS ONE. 2014;9:e115512.
[38]	Klevanski M, Herrmannsdoerfer F, Sass S, Venkataramani V, Heilemann M, Kuner T. Automated highly multiplexed super-resolution imaging of protein nano-architecture in cells and tissues. Nat Commun. 2020;11:1552.
[39]	Auer A, Strauss MT, Schlichthaerle T, Jungmann R. Fast, background-free DNA-PAINT imaging using FRET-based probes. Nano Lett. 2017;17:6428–34.
[40]	Lee J, Park S, Kang W, Hohng S. Accelerated super-resolution imaging with FRET-PAINT. Mol Brain. 2017;10:63.
[41]	Jang S, Kim M, Shim SH. Reductively caged, photoactivatable DNA-PAINT for high-throughput super-resolution microscopy. Angew Chem Int Ed Engl. 2020;59:11758–62.
[42]	Geertsema HJ, Aimola G, Fabricius V, Fuerste JP, Kaufer BB, Ewers H. Left-handed DNA-PAINT for improved super-resolution imaging in the nucleus. Nat Biotechnol. 2021;39:551–4.
[43]	Chung KKH, Zhang Z, Kidd P, Zhang Y, Williams ND, Rollins B, et al. Fluorogenic DNA-PAINT for faster, low-background super-resolution imaging. Nat Methods. 2022;19:554–9.
[44]	Schueder F, Stein J, Stehr F, Auer A, Sperl B, Strauss MT, et al. An order of magnitude faster DNA-PAINT imaging by optimized sequence design and buffer conditions. Nat Methods. 2019;16:1101–4.
[45]	Strauss S, Jungmann R. Up to 100-fold speed-up and multiplexing in optimized DNA-PAINT. Nat Methods. 2020;17:789–91.
[46]	Civitci F, Shangguan J, Zheng T, Tao K, Rames M, Kenison J, et al. Fast and multiplexed superresolution imaging with DNA-PAINT-ERS. Nat Commun. 2020;11:4339.
[47]	Clowsley AH, Kaufhold WT, Lutz T, Meletiou A, Di Michele L, Soeller C. Repeat DNA-PAINT suppresses background and non-specific signals in optical nanoscopy. Nat Commun. 2021;12:501.
[48]	Unterauer EM, Shetab Boushehri S, Jevdokimenko K, Masullo LA, Ganji M, Sograte-Idrissi S, et al. Spatial proteomics in neurons at single-protein resolution. Cell. 2024;187:1785–800.
[49]	Schönle A, Hell SW. Fluorescence nanoscopy goes multicolor. Nat Biotechnol. 2007;25:1234–5.
[50]	Bossi M, Fölling J, Belov VN, Boyarskiy VP, Medda R, Egner A, et al. Multicolor far-field fluorescence nanoscopy through isolated detection of distinct molecular species. Nano Lett. 2008;8:2463–8.
[51]	Baddeley D, Crossman D, Rossberger S, Cheyne JE, Montgomery JM, Jayasinghe ID, et al. 4D super-resolution microscopy with conventional fluorophores and single wavelength excitation in optically thick cells and tissues. PLoS ONE. 2011;6:e20645.
[52]	Lampe A, Haucke V, Sigrist SJ, Heilemann M, Schmoranzer J. Multi-colour direct STORM with red emitting carbocyanines. Biol Cell. 2012;104:229–37.
[53]	Winterflood CM, Platonova E, Albrecht D, Ewers H. Dual-color 3D superresolution microscopy by combined spectral-demixing and biplane imaging. Biophys J. 2015;109:3–6.
[54]	Lampe A, Tadeus G, Schmoranzer J. Spectral demixing avoids registration errors and reduces noise in multicolor localization-based super-resolution microscopy. Methods Appl Fluoresc. 2015;3:034006.
[55]	Siemons ME, Jurriens D, Smith CS, Kapitein LC. https://www.biorxiv.org/content/10.1101/2022.01.14.476290v1.
[56]	Andronov L, Genthial R, Hentsch D, Klaholz BP. splitSMLM, a spectral demixing method for high-precision multi-color localization microscopy applied to nuclear pore complexes. Commun Biol. 2022;5:1100.
[57]	Li Y, Shi W, Liu S, Cavka I, Wu YL, Matti U, et al. Global fitting for high-accuracy multi-channel single-molecule localization. Nat Commun. 2022;13:3133.
[58]	Platonova E, Winterflood CM, Ewers H. A simple method for GFP- and RFP-based dual color single-molecule localization microscopy. ACS Chem Biol. 2015;10:1411–6.
[59]	Gimber N, Strauss S, Jungmann R, Schmoranzer J. Simultaneous multicolor DNA-PAINT without sequential fluid exchange using spectral demixing. Nano Lett. 2022;22:2682–90.
[60]	Friedl K, Mau A, Boroni-Rueda F, Caorsi V, Bourg N, Lévêque-Fort S, et al. Assessing crosstalk in simultaneous multicolor single-molecule localization microscopy. Cell Rep Methods. 2023;3:100571.
[61]	Huang B, Wang W, Bates M, Zhuang X. Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy. Science. 2008;319:810–3.
[62]	Vissa A, Giuliani M, Kim PK, Yip CM. Hyperspectral super-resolution imaging with far-red emitting fluorophores using a thin-film tunable filter. Rev Sci Instrum. 2020;91:123703.
[63]	Wang Y, Kuang W, Shang M, Huang ZL. Two-color super-resolution localization microscopy via joint encoding of emitter location and color. Opt Express. 2021;29:34797–809.
[64]	Shtengel G, Galbraith JA, Galbraith CG, Lippincott-Schwartz J, Gillette JM, Manley S, et al. Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure. Proc Natl Acad Sci U S A. 2009;106:3125–30.
[65]	Aquino D, Schönle A, Geisler C, Middendorff CV, Wurm CA, Okamura Y, et al. Two-color nanoscopy of three-dimensional volumes by 4Pi detection of stochastically switched fluorophores. Nat Methods. 2011;8:353–9.
[66]	Huang F, Sirinakis G, Allgeyer ES, Schroeder LK, Duim WC, Kromann EB, et al. Ultra-high resolution 3D imaging of whole cells. Cell. 2016;166:1028–40.
[67]	Chen J, Yao B, Yang Z, Shi W, Luo T, Xi P, et al. Ratiometric 4Pi single-molecule localization with optimal resolution and color assignment. Opt Lett. 2022;47:325–8.
[68]	Kim T, Moon S, Xu K. Information-rich localization microscopy through machine learning. Nat Commun. 2019;10:1996.
[69]	Li M, Shi W, Liu S, Fu S, Fei Y, Zhou L, et al. Fast and universal single molecule localization using multi-dimensional point spread functions. Opt Express. https://doi.org/10.1364/OE.531588.
[70]	Zhang Z, Kenny SJ, Hauser M, Li W, Xu K. Ultrahigh-throughput single-molecule spectroscopy and spectrally resolved super-resolution microscopy. Nat Methods. 2015;12:935–8.
[71]	Butler C, Saraceno GE, Kechkar A, Bénac N, Studer V, Dupuis JP, et al. Multi-dimensional spectral single molecule localization microscopy. Front Bioinform. 2022;2:813494.
[72]	Mlodzianoski MJ, Curthoys NM, Gunewardene MS, Carter S, Hess ST. Super-resolution imaging of molecular emission spectra and single molecule spectral fluctuations. PLoS ONE. 2016;11:e0147506.
[73]	Moon S, Yan R, Kenny SJ, Shyu Y, Xiang L, Li W, et al. Spectrally resolved, functional super-resolution microscopy reveals nanoscale compositional heterogeneity in live-cell membranes. J Am Chem Soc. 2017;139:10944–7.
[74]	Song KH, Brenner B, Yeo WH, Kweon J, Cai Z, Zhang Y, et al. Monolithic dual-wedge prism-based spectroscopic single-molecule localization microscopy. Nanophotonics. 2022;11:1527–35.
[75]	Jaqaman K, Loerke D, Mettlen M, Kuwata H, Grinstein S, Schmid SL, et al. Robust single-particle tracking in live-cell time-lapse sequences. Nat Methods. 2008;5:695–702.
[76]	Chang YP, Pinaud F, Antelman J, Weiss S. Tracking bio-molecules in live cells using quantum dots. J Biophotonics. 2008;1:287–98.
[77]	Huang T, Phelps C, Wang J, Lin LJ, Bittel A, Scott Z, et al. Simultaneous multicolor single-molecule tracking with single-laser excitation via spectral imaging. Biophys J. 2018;114:301–10.
[78]	Dong B, Almassalha L, Urban BE, Nguyen TQ, Khuon S, Chew TL, et al. Super-resolution spectroscopic microscopy via photon localization. Nat Commun. 2016;7:12290.
[79]	Bongiovanni MN, Godet J, Horrocks MH, Tosatto L, Carr AR, Wirthensohn DC, et al. Multi-dimensional super-resolution imaging enables surface hydrophobicity mapping. Nat Commun. 2016;7:13544.
[80]	Song KH, Zhang Y, Wang G, Sun C, Zhang HF. Three-dimensional biplane spectroscopic single-molecule localization microscopy. Optica. 2019;6:709–15.
[81]	Juette MF, Gould TJ, Lessard MD, Mlodzianoski MJ, Nagpure BS, Bennett BT, et al. Three-dimensional sub-100 nm resolution fluorescence microscopy of thick samples. Nat Methods. 2008;5:527–9.
[82]	Song KH, Zhang Y, Brenner B, Sun C, Zhang HF. Symmetrically dispersed spectroscopic single-molecule localization microscopy. Light Sci Appl. 2020;9:92.
[83]	Martens KJA, Gobes M, Archontakis E, Brillas RR, Zijlstra N, Albertazzi L, et al. Enabling spectrally resolved single-molecule localization microscopy at high emitter densities. Nano Lett. 2022;22:8618–25.
[84]	Zhang Z, Zhang Y, Ying L, Sun C, Zhang HF. Machine-learning based spectral classification for spectroscopic single-molecule localization microscopy. Opt Lett. 2019;44:5864–7.
[85]	Gaire SK, Zhang Y, Li H, Yu R, Zhang HF, Ying L. Accelerating multicolor spectroscopic single-molecule localization microscopy using deep learning. Biomed Opt Express. 2020;11:2705–21.
[86]	Manko H, Mély Y, Godet J. Advancing spectrally-resolved single molecule localization microscopy using deep learning. Small. 2023;19:e2300728.
[87]	Gaire SK, Daneshkhah A, Flowerday E, Gong R, Frederick J, Backman V. Deep learning-based spectroscopic single-molecule localization microscopy. J Biomed Opt. 2024;29:066501.
[88]	Baddeley D, Cannell MB, Soeller C. Three-dimensional sub-100 nm super-resolution imaging of biological samples using a phase ramp in the objective pupil. Nano Res. 2011;4:589–98.
[89]	Shechtman Y, Weiss LE, Backer AS, Sahl SJ, Moerner WE. Precise three-dimensional scan-free multiple-particle tracking over large axial ranges with tetrapod point spread functions. Nano Lett. 2015;15:4194–9.
[90]	Pavani SR, Thompson MA, Biteen JS, Lord SJ, Liu N, Twieg RJ, et al. Three-dimensional, single-molecule fluorescence imaging beyond the diffraction limit by using a double-helix point spread function. Proc Natl Acad Sci U S A. 2009;106:2995–9.
[91]	Lew MD, Lee SF, Badieirostami M, Moerner WE. Corkscrew point spread function for far-field three-dimensional nanoscale localization of pointlike objects. Opt Lett. 2011;36:202–4.
[92]	Shechtman Y, Sahl SJ, Backer AS, Moerner WE. Optimal point spread function design for 3D imaging. Phys Rev Lett. 2014;113:133902.
[93]	Jia S, Vaughan JC, Zhuang X. Isotropic three-dimensional super-resolution imaging with a self-bending point spread function. Nat Photonics. 2014;8:302–6.
[94]	Zhou Y, Carles G. Precise 3D particle localization over large axial ranges using secondary astigmatism. Opt Lett. 2020;45:2466–9.
[95]	Fu S, Li M, Zhou L, He Y, Liu X, Hao X, et al. Deformable mirror based optimal PSF engineering for 3D super-resolution imaging. Opt Lett. 2022;47:3031–4.
[96]	Broeken J, Rieger B, Stallinga S. Simultaneous measurement of position and color of single fluorescent emitters using diffractive optics. Opt Lett. 2014;39:3352–5.
[97]	Shechtman Y, Weiss LE, Backer AS, Lee MY, Moerner WE. Multicolour localization microscopy by point-spread-function engineering. Nat Photonics. 2016;10:590–4.
[98]	Opatovski N, Shalev Ezra Y, Weiss LE, Ferdman B, Orange-Kedem R, Shechtman Y. Multiplexed PSF engineering for three-dimensional multicolor particle tracking. Nano Lett. 2021;21:5888–95.
[99]	Hershko E, Weiss LE, Michaeli T, Shechtman Y. Multicolor localization microscopy and point-spread-function engineering by deep learning. Opt Express. 2019;27:6158–83.
[100]	Van den Eynde R, Hertel F, Abakumov S, Krajnik B, Hugelier S, Auer A, et al. Simultaneous multicolor fluorescence imaging using PSF splitting. Nat Methods. 2024. Epub ahead of print.https://doi.org/10.1038/s41592-024-02383-7.
[101]	Nehme E, Freedman D, Gordon R, Ferdman B, Weiss LE, Alalouf O, et al. DeepSTORM3D: dense 3D localization microscopy and PSF design by deep learning. Nat Methods. 2020;17:734–40.
[102]	Speiser A, Müller LR, Hoess P, Matti U, Obara CJ, Legant WR, et al. Deep learning enables fast and dense single-molecule localization with high accuracy. Nat Methods. 2021;18:1082–90.
[103]	Gómez-García PA, Garbacik ET, Otterstrom JJ, Garcia-Parajo MF, Lakadamyali M. Excitation-multiplexed multicolor superresolution imaging with fm-STORM and fm-DNA-PAINT. Proc Natl Acad Sci U S A. 2018;115:12991–6.
[104]	Wu W, Luo S, Fan C, Yang T, Zhang S, Meng W, et al. Tetra-Color superresolution microscopy based on excitation spectral demixing. Light Sci Appl. 2023;12:9.
[105]	Gu L, Li Y, Zhang S, Xue Y, Li W, Li D, et al. Molecular resolution imaging by repetitive optical selective exposure. Nat Methods. 2019;16:1114–8.
[106]	Gu L, Li Y, Zhang S, Zhou M, Xue Y, Li W, et al. Molecular-scale axial localization by repetitive optical selective exposure. Nat Methods. 2021;18:369–73.
[107]	Jones SA, Shim SH, He J, Zhuang X. Fast, three-dimensional super-resolution imaging of live cells. Nat Methods. 2011;8:499–508.
[108]	Adhikari S, Moscatelli J, Smith EM, Banerjee C, Puchner EM. Single-molecule localization microscopy and tracking with red-shifted states of conventional BODIPY conjugates in living cells. Nat Commun. 2019;10:3400.
[109]	König AI, Sorkin R, Alon A, Nachmias D, Dhara K, Brand G, et al. Live cell single molecule tracking and localization microscopy of bioorthogonally labeled plasma membrane proteins. Nanoscale. 2020;12:3236–48.
[110]	Huang B, Li J, Yao B, Yang Z, Lam EY, Zhang J, et al. Enhancing image resolution of confocal fluorescence microscopy with deep learning. PhotoniX. 2023;4:2.
[111]	Xu F, Zhang M, He W, Han R, Xue F, Liu Z, et al. Live cell single molecule-guided bayesian localization super resolution microscopy. Cell Res. 2017;27:713–6.
[112]	Li H, Xu F, Gao S, Zhang M, Xue F, Xu P, et al. Live-SIMBA: an ImageJ plug-in for the universal and accelerated single molecule-guided bayesian localization super resolution microscopy (SIMBA) method. Biomed Opt Express. 2020;11:5842–59.
[113]	Chen R, Tang X, Zhao Y, Shen Z, Zhang M, Shen Y, et al. Single-frame deep-learning super-resolution microscopy for intracellular dynamics imaging. Nat Commun. 2023;14:2854.
[114]	Zhao Z, Xin B, Li L, Huang ZL. High-power homogeneous illumination for super-resolution localization microscopy with large field-of-view. Opt Express. 2017;25:13382–95.
[115]	Archetti A, Glushkov E, Sieben C, Stroganov A, Radenovic A, Manley S. Waveguide-PAINT offers an open platform for large field-of-view super-resolution imaging. Nat Commun. 2019;10:1267.
[116]	Yan T, Richardson CJ, Zhang M, Gahlmann A. Computational correction of spatially variant optical aberrations in 3D single-molecule localization microscopy. Opt Express. 2019;27:12582–99.
[117]	Fu S, Shi W, Luo T, He Y, Zhou L, Yang J, et al. Field-dependent deep learning enables high-throughput whole-cell 3D super-resolution imaging. Nat Methods. 2023;20:459–68.
[118]	Xiao D, Kedem Orange R, Opatovski N, Parizat A, Nehme E, Alalouf O, et al. Large-FOV 3D localization microscopy by spatially variant point spread function generation. Sci Adv. 2024;10:eadj3656.
[119]	Mau A, Friedl K, Leterrier C, Bourg N, Lévêque-Fort S. Fast widefield scan provides tunable and uniform illumination optimizing super-resolution microscopy on large fields. Nat Commun. 2021;12:3077.
[120]	Du Y, Wang C, Zhang C, Guo L, Chen Y, Yan M, et al. Computational framework for generating large panoramic super-resolution images from localization microscopy. Biomed Opt Express. 2021;12:4759–78.
[121]	Tehrani KF, Xu J, Zhang Y, Shen P, Kner P. Adaptive optics stochastic optical reconstruction microscopy (AO-STORM) using a genetic algorithm. Opt Express. 2015;23:13677–92.
[122]	Tehrani KF, Zhang Y, Shen P, Kner P. Adaptive optics stochastic optical reconstruction microscopy (AO-STORM) by particle swarm optimization. Biomed Opt Express. 2017;8:5087–97.
[123]	Burke D, Patton B, Huang F, Bewersdorf J, Booth MJ. Adaptive optics correction of specimen-induced aberrations in single-molecule switching microscopy. Optica. 2015;2:177–85.
[124]	Mlodzianoski MJ, Cheng-Hathaway PJ, Bemiller SM, McCray TJ, Liu S, Miller DA, et al. Active PSF shaping and adaptive optics enable volumetric localization microscopy through brain sections. Nat Methods. 2018;15:583–6.
[125]	Siemons ME, Hanemaaijer NAK, Kole MHP, Kapitein LC. Robust adaptive optics for localization microscopy deep in complex tissue. Nat Commun. 2021;12:3407.
[126]	Zhou Z, Huang J, Li X, Gao X, Chen Z, Jiao Z, et al. Adaptive optical microscopy via virtual-imaging-assisted wavefront sensing for high-resolution tissue imaging. PhotoniX. 2022;3:13.
[127]	Zhang P, Ma D, Cheng X, Tsai AP, Tang Y, Gao HC, et al. Deep learning-driven adaptive optics for single-molecule localization microscopy. Nat Methods. 2023;20:1748–58.
[128]	Park S, Jo Y, Kang M, Hong JH, Ko S, Kim S, et al. Label-free adaptive optics single-molecule localization microscopy for whole zebrafish. Nat Commun. 2023;14:4185.
[129]	Zhang C, Yu B, Lin F, Samanta S, Yu H, Zhang W, et al. Deep tissue super-resolution imaging with adaptive optical two-photon multifocal structured illumination microscopy. PhotoniX. 2023;4:38.
[130]	Gradinaru V, Treweek J, Overton K, Deisseroth K. Hydrogel-tissue chemistry: principles and applications. Annu Rev Biophys. 2018;47:355–76.
[131]	Ueda HR, Ertürk A, Chung K, Gradinaru V, Chédotal A, Tomancak P, et al. Tissue clearing and its applications in neuroscience. Nat Rev Neurosci. 2020;21:61–79.
[132]	Mao C, Lee MY, Jhan JR, Halpern AR, Woodworth MA, Glaser AK, et al. Feature-rich covalent stains for super-resolution and cleared tissue fluorescence microscopy. Sci Adv. 2020;6:eaba4542.
[133]	Xu F, Ma D, MacPherson KP, Liu S, Bu Y, Wang Y, et al. Three-dimensional nanoscopy of whole cells and tissues with in situ point spread function retrieval. Nat Methods. 2020;17:531–40.
[134]	Liu S, Chen J, Hellgoth J, Müller LR, Ferdman B, Karras C, et al. Universal inverse modeling of point spread functions for SMLM localization and microscope characterization. Nat Methods. 2024;21:1082–93.
[135]	Dempsey GT, Vaughan JC, Chen KH, Bates M, Zhuang X. Evaluation of fluorophores for optimal performance in localization-based super-resolution imaging. Nat Methods. 2011;8:1027–36.
[136]	Zhang Y, Zhang Y, Song KH, Lin W, Sun C, Schatz GC, et al. Investigating single-molecule fluorescence spectral heterogeneity of rhodamines using high-throughput single-molecule spectroscopy. J Phys Chem Lett. 2021;12:3914–21.
[137]	Nehme E, Weiss LE, Michaeli T, Shechtman Y. Deep-STORM: super-resolution single-molecule localization microscopy by deep learning. Optica. 2018;5:458–64.
[138]	Boyd N, Jonas E, Babcock H, Recht B. https://www.biorxiv.org/content/10.1101/267096v1.
[139]	Ding T, Wu T, Mazidi H, Zhang O, Lew MD. Single-molecule orientation localization microscopy for resolving structural heterogeneities between amyloid fibrils. Optica. 2020;7:602–7.
[140]	Curcio V, Alemán-Castañeda LA, Brown TG, Brasselet S, Alonso MA. Birefringent Fourier filtering for single molecule coordinate and height super-resolution imaging with dithering and orientation. Nat Commun. 2020;11:5307.
[141]	Hulleman CN, Thorsen RØ, Kim E, Dekker C, Stallinga S, Rieger B. Simultaneous orientation and 3D localization microscopy with a Vortex point spread function. Nat Commun. 2021;12:5934.
[142]	Xiang L, Chen K, Yan R, Li W, Xu K. Single-molecule displacement mapping unveils nanoscale heterogeneities in intracellular diffusivity. Nat Methods. 2020;17:524–30.
[143]	Yan R, Chen K, Xu K. Probing nanoscale diffusional heterogeneities in cellular membranes through multidimensional single-molecule and super-resolution microscopy. J Am Chem Soc. 2020;142:18866–73.
[144]	Thiele JC, Helmerich DA, Oleksiievets N, Tsukanov R, Butkevich E, Sauer M, et al. Confocal fluorescence-lifetime single-molecule localization microscopy. ACS Nano. 2020;14:14190–200.
[145]	Oleksiievets N, Sargsyan Y, Thiele JC, Mougios N, Sograte-Idrissi S, Nevskyi O, et al. Fluorescence lifetime DNA-PAINT for multiplexed super-resolution imaging of cells. Commun Biol. 2022;5:38.
[146]	Cnossen J, Hinsdale T, Thorsen RØ, Siemons M, Schueder F, Jungmann R, et al. Localization microscopy at doubled precision with patterned illumination. Nat Methods. 2020;17:59–63.
[147]	Masullo LA, Lopez LF, Stefani FD. A common framework for single-molecule localization using sequential structured illumination. Biophys Rep (N Y). 2021;2:100036.
[148]	Jouchet P, Cabriel C, Bourg N, Bardou M, Poüs C, Fort E, et al. Nanometric axial localization of single fluorescent molecules with modulated excitation. Nat Photonics. 2021;15:297–304.