Washington University in St Louis

The Preston M. Green Department of
Electrical & Systems Engineering

Journal covers

Anisotropic rotational diffusion of single molecules, represented here by magenta dipoles wobbling within cyan elliptical cones, can be measured using a fluorescence microscope. However, photon shot noise within these images (bottom) causes each measured cone to vary in shape. (Image credit: Matthew D. Lew)
J. Phys. Chem. A Vol. 128, Iss. 28 (2024). Image credit: Matthew D. Lew
Single-molecule orientation localization microscopy captures fluorescence from Nile red molecules as they transiently bind to self-assembled fibrils composed of engineered KFE8 peptides. We observe considerable polymorphism across the network of interconnected fibrils, revealed by the orientations and wobble of individual Nile red, with nanoscale resolution. (Image credit: Weiyan Zhou)
ACS Nano Vol. 18, Iss. 12 (2024). Image credit: Weiyan Zhou
Showcasing research from Professor Matthew D. Lew's laboratory, McKelvey School of Engineering, Washington University in St. Louis, MO, USA. Single-molecule electrochemical imaging resolves the midpoint potentials of individual fluorophores on nanoporous antimony-doped tin oxide.
Chem. Sci. Vol. 15, Iss. 6 (2024). Image credit: Jin Lu
W. E. Moerner Festschrift Virtual Special Issue
J. Phys. Chem. B Vol. 126, Iss. 6 (2022). Image credit: Matthew D. Lew
Single-Molecule Localization Microscopy of 3D Orientation and Anisotropic Wobble Using a Polarized Vortex Point Spread Function
J. Phys. Chem. B Vol. 125, Iss. 46 (2021). Image credit: Tianben Ding
Single‐Molecule 3D Orientation Imaging Reveals Nanoscale Compositional Heterogeneity in Lipid Membranes
Angew. Chem. Int. Ed. Vol. 59, Iss. 40 (2020). Image credit: Jin Lu
Super-resolution Imaging of Amyloid Structures over Extended Times by Using Transient Binding of Single Thioflavin T Molecules
ChemBioChem Vol. 19, Iss. 18 (2018) Image credit: Matthew D. Lew
Cellular Trafficking of Sn-2 Phosphatidylcholine Prodrugs Studied with Fluorescence Lifetime Imaging and Super-resolution Microscopy
Prec. Nanomed. Vol. 1, Iss. 2 (2018). Image credit: Dolon Maji

2026

  1. M. K. Shinn, D. T. Tomares, V. Liu, A. Pant, Y. Qiu, A. Vitalis, Y. J. Song, Y. Ayala, K. M. Ruff, G. W. Strout, M. D. Lew, K. V. Prasanth, R. V. Pappu, “Nuclear Speckle Proteins Form Intrinsic and MALAT1-dependent Microphases,” Cell 189, 832–852.e24 (2026). [Article]

2025

  1. S. Brasselet+ and M. D. Lew+. “Single-molecule orientation and localization microscopy,” Nat. Photon. 19, 925 (2025). [WashU Engineering News, WashU Scholarly Repository, Article]
  2. N. A. Erkamp*, M. Farag*, Y. Qiu*, D. Qian, T. Sneideris, T. Wu, T. J. Welsh, H. Ausserwöger, T. J. Krug, G. Chauhan, D. A. Weitz, M. D. Lew+, T. P. J. Knowles+, and R. V. Pappu+. “Differential interactions determine anisotropies at interfaces of RNA-based biomolecular condensates,” Nat. Commun. 16, 3463 (2025). [Article, Data]
  3. M. D. Lew. “Painting rich six-dimensional pictures using polarized fluorescence microscopy,” Proc. Natl. Acad. Sci. U.S.A. 122, e2501914122 (2025). [WashU Scholarly Repository, Commentary]
  4. T. Wu*, M. R. King*, Y. Qiu, M. Farag, R. V. Pappu+, and M. D. Lew+. “Single-fluorogen imaging reveals distinct environmental and structural features of biomolecular condensates,” Nat. Phys. 21, 778 (2025). [The Source - Washington University, EurekAlert!, Article, Data, Video abstract]
  5. Y. Chen, Y. Qiu, and M. D. Lew, “Resolving the Orientations of and Angular Separation Between a Pair of Dipole Emitters,” Phys. Rev. Lett. 134, 093805 (2025). [McKelvey Engineering News, Phys.org, arXiv, Article]

2024

  1. O. Zhang, and M. D. Lew, “Single-molecule orientation-localization microscopy: Applications and approaches,” Quarterly Reviews of Biophysics 57, e17 (2024). [Article]
  2. E. Bruggeman, O. Zhang, L.-M. Needham, M. Körbel, S. Daly, M. Cheetham, R. Peters, T. Wu, A. S. Klymchenko, S. J. Davis, E. K. Paluch, D. Klenerman, M. D. Lew, K. O’Holleran, and S. F. Lee, “POLCAM: Instant Molecular Orientation Microscopy for the Life Sciences,” Nat. Methods 21, 1873 (2024). [Article]
  3. W. Zhou, T. Wu, and M. D. Lew, “Fundamental Limits in Measuring the Anisotropic Rotational Diffusion of Single Molecules,” J. Phys. Chem. A 128, 5808 (2024). [Journal cover, The Source - Washington University, WashU Scholarly Repository, Article, Data]
  4. B. Sun, T. Ding, W. Zhou, T. S. Porter, and M. D. Lew, “Single-Molecule Orientation Imaging Reveals the Nano-Architecture of Amyloid Fibrils Undergoing Growth and Decay,” Nano Lett. 24, 7276 (2024). [The Source - Washington University, EurekAlert!, WashU Scholarly Repository, Article, Data]
    Correction: Nano Lett. 25, 13720 (2025). [Article]
  5. T. Wu and M. D. Lew, “Dipole-Spread Function Engineering for Six-Dimensional Super-Resolution Microscopy,” in Coded Optical Imaging (ed. J. Liang), 207 (Springer, 2024). [arXiv.org, Chapter]
  6. M. R. King, K. M. Ruff, A. Z. Lin, A. Pant, M. Farag, J. M. Lalmansingh, T. Wu, M. J. Fossat, W. Ouyang, M. D. Lew, E. Lundberg, M. D. Vahey, and R. V. Pappu, “Macromolecular condensation organizes nucleolar sub-phases to set up a pH gradient,” Cell 187, 1889 (2024). [The Source - Washington University, EurekAlert!, Article]
  7. W. Zhou, C. L. O’Neill, T. Ding, O. Zhang, J. S. Rudra, and M. D. Lew, “Resolving the Nanoscale Structure of β-Sheet Peptide Self-Assemblies Using Single-Molecule Orientation–Localization Microscopy,” ACS Nano 18, 8798 (2024). [Journal cover, The Source - Washington University, EurekAlert!, WashU Scholarly Repository, Article, Data]
  8. T. Wu, W. Zhou, J. S. Rudra, R. V. Pappu, and M. D. Lew, “6D single-fluorogen orientation-localization microscopy for elucidating the architecture of beta-sheet assemblies and biomolecular condensates,” Proc. SPIE 12853, 1285302 (2024). [Open Scholarship, Article]
  9. J. Lu and M. D. Lew, “Single-molecule electrochemical imaging resolves the midpoint potentials of individual fluorophores on nanoporous antimony-doped tin oxide,” Chem. Sci. 15, 2037 (2024). [Journal cover, Article, Data]

2023

  1. O. Zhang, Z. Guo, Y. He, T. Wu, M. D. Vahey, and M. D. Lew, “Six-dimensional single-molecule imaging with isotropic resolution using a multi-view reflector microscope,” Nat. Photon. 17, 179 (2023). [The Source - Washington University, WashU Scholarly Repository, Article, Data, Video abstract]

2022

‡editor's pick/hot paper

  1. ‡ J. M. Jusuf and M. D. Lew, “Towards optimal point spread function design for resolving closely spaced emitters in three dimensions,” Opt. Express 30, 37154 (2022). [Article, Data]
  2. T. Wu, P. Lu, M. A. Rahman, X. Li, and M. D. Lew, “Deep-SMOLM: deep learning resolves the 3D orientations and 2D positions of overlapping single molecules with optimal nanoscale resolution,” Opt. Express 30, 36761 (2022). [McKelvey Engineering News, Article, Code, Data, Video abstract]
  3. M. Shen, T. Ding, C. Tan, W. H. Rackers, D. Zhang, M. D. Lew, and B. Sadtler, “In Situ Imaging of Catalytic Reactions on Tungsten Oxide Nanowires Connects Surface–Ligand Redox Chemistry with Photocatalytic Activity,” Nano Lett. 22, 4694 (2022). [NSF-PAR, Article]
  4. T. Wu, J. Lu, and M. D. Lew, “Dipole-spread-function engineering for simultaneously measuring the 3D orientations and 3D positions of fluorescent molecules,” Optica 9, 505 (2022). [The Source - Washington University, Article, Data, Video abstract]
  5. O. Zhang, W. Zhou, J. Lu, T. Wu, and M. D. Lew, “Resolving the three-dimensional rotational and translational dynamics of single molecules using radially and azimuthally polarized fluorescence,” Nano Lett. 22, 1024 (2022). [The Source - Washington University, EurekAlert!, WashU Scholarly Repository, Article, Data, Summary PDF, Video abstract]

2021

‡editor's pick/hot paper

  1. T. Ding and M. D. Lew, “Single-molecule localization microscopy of 3D orientation and anisotropic wobble using a polarized vortex point spread function,” J. Phys. Chem. B 125, 12718 (2021). [Journal cover, The Source - Washington University, EurekAlert!, WashU Scholarly Repository, Article, Data, Summary PDF]
  2. T. Ding and M. D. Lew, “Elucidating the nanoscale architecture of amyloid aggregates using a polarized donut point spread function,” Microsc. Microanal. 27 (S1), 1428 (2021). [Article]
  3. T. Wu, J. Lu, and M. D. Lew, “pixOL: pixel-wise point spread function engineering for measuring the 3D orientation and 3D location of dipole-like emitters,” Microsc. Microanal. 27 (S1), 858 (2021). [Article]
  4. M. Shen, T. Ding, W. H. Rackers, C. Tan, K. Mahmood, M. D. Lew, and B. Sadtler, “Single-molecule colocalization of redox reactions on semiconductor photocatalysts connects surface heterogeneity and charge-carrier separation in bismuth oxybromide,” J. Am. Chem. Soc. 143, 11393 (2021). [NSF-PAR, Article]
  5. M. D. Lew, “Computational Modelling Enables Robust Multidimensional Nanoscopy,” in Computational Modeling: From Chemistry to Materials to Biology (eds. K. Wüthrich, B. Weckhuysen, L. Rongy, and A. De Wit), 189 (World Scientific, 2021). [WashU Scholarly Repository, Article]
  6. ‡ O. Zhang and M. D. Lew, “Single-molecule orientation localization microscopy II: a performance comparison,” J. Opt. Soc. Am. A 38, 288 (2021). [arXiv.org, Article]
  7. O. Zhang and M. D. Lew, “Single-molecule orientation localization microscopy I: fundamental limits,” J. Opt. Soc. Am. A 38, 277 (2021). [arXiv.org, Article]
    Correction: J. Opt. Soc. Am. A 42, 1880 (2025). [Article]

2020

‡editor's pick/hot paper

  1. H. Mazidi, T. Ding, A. Nehorai, and M. D. Lew, “Quantifying accuracy and heterogeneity in single-molecule super-resolution microscopy,” Nat. Commun. 11, 6353 (2020). [The Source - Washington University, EurekAlert!, Article, Data, Summary PDF]
  2. ‡ J. Lu, H. Mazidi, T. Ding, O. Zhang, and M. D. Lew, “Single-Molecule 3D Orientation Imaging Reveals Nanoscale Compositional Heterogeneity in Lipid Membranes,” Angew. Chem. Int. Ed. 59, 17572 (2020). [Journal cover, The Source - Washington University, The Analytical Scientist, EurekAlert!, WashU Scholarly Repository, Article, Data]
  3. O. Zhang and M. D. Lew, “Quantum limits for precisely estimating the orientation and wobble of dipole emitters,” Phys. Rev. Research 2, 033114 (2020). [Article, Summary PDF]
  4. M. Shen, T. Ding, J. Luo, C. Tan, K. Mahmood, Z. Wang, D. Zhang, R. Mishra, M. D. Lew, and B. Sadtler, “Competing Activation and Deactivation Mechanisms in Photodoped Bismuth Oxybromide Nanoplates Probed by Single-Molecule Fluorescence Imaging,” J. Phys. Chem. Lett. 11, 5219 (2020). [NSF-PAR, Article]
  5. T. Ding*, T. Wu*, H. Mazidi, O. Zhang, and M. D. Lew, “Single-molecule orientation localization microscopy for resolving structural heterogeneities between amyloid fibrils,” Optica 7, 602 (2020). [OSA news release, The Source - Washington University, EurekAlert!, Photonics Media, Article, Data, Summary PDF]
  6. T. Wu, T. Ding, H. Mazidi, O. Zhang, and M. D. Lew, “A computationally-efficient bound for the variance of measuring the orientation of single molecules,” Proc. SPIE 11246, 1124616 (2020). [WashU Scholarly Repository, Article]
  7. H. Mazidi, T. Ding, A. Nehorai, and M. D. Lew, “Measuring localization confidence for quantifying accuracy and heterogeneity in single-molecule super-resolution microscopy,” Proc. SPIE 11246, 1124611 (2020). [WashU Scholarly Repository, Article]
  8. M. Shen*, T. Ding*, S. T. Hartman, F. Wang, C. Krucylak, Z. Wang, C. Tan, B. Yin, R. Mishra, M. D. Lew+, and B. Sadtler+, “Nanoscale Colocalization of Fluorogenic Probes Reveals Role of Oxygen Vacancies in the Photocatalytic Activity of Tungsten Oxide Nanowires,” ACS Catal. 10, 2088 (2020). [WashU Scholarly Repository, Article]

2019

  1. H. Mazidi, E. S. King, O. Zhang, A. Nehorai, and M. D. Lew, “Dense Super-Resolution Imaging of Molecular Orientation via Joint Sparse Basis Deconvolution and Spatial Pooling,” 2019 IEEE 16th International Symposium on Biomedical Imaging (ISBI 2019), 325 (2019). [arXiv.org, Article]
  2. O. Zhang and M. D. Lew, “Fundamental Limits on Measuring the Rotational Constraint of Single Molecules using Fluorescence Microscopy,” Phys. Rev. Lett. 122, 198301 (2019). [The Source - Washington University, arXiv.org, Article, Summary PDF]
  3. O. Zhang and M. D. Lew, “Fundamental limits of measuring single-molecule rotational mobility,” Proc. SPIE 10884, 1088412 (2019). [WashU Scholarly Repository, Article]
  4. T. Ding, K. Spehar, J. Bieschke, and M. D. Lew, “Long-term, super-resolution imaging of amyloid structures using transient amyloid binding microscopy,” Proc. SPIE 10884, 108840J (2019). [Open Scholarship, Article]

2018

  1. H. Mazidi, J. Lu, A. Nehorai, and M. D. Lew, “Minimizing Structural Bias in Single-Molecule Super-Resolution Microscopy,” Sci. Rep. 8, 13133 (2018). [Article, Data, Summary PDF]
  2. D. Maji, J. Lu, P. Sarder, A. H. Schmieder, G. Cui, X. Yang, D. Pan, M. D. Lew, S. Achilefu, and G. M. Lanza “Cellular Trafficking of Sn-2 Phosphatidylcholine Prodrugs Studied with Fluorescence Lifetime Imaging and Super-resolution Microscopy,” Prec. Nanomed. 1, 128 (2018). [Journal cover, Article]
  3. K. Spehar*, T. Ding*, Y. Sun, N. Kedia, J. Lu, G. R. Nahass, M. D. Lew+, and J. Bieschke+, “Super-Resolution Imaging of Amyloid Structures over Extended Times Using Transient Binding of Single Thioflavin T Molecules,” ChemBioChem 19, 1944 (2018). [Journal cover, The Source - Washington University, NSF Science360, Futurity, EurekAlert!, OSA News Release, WashU Scholarly Repository, Article, Summary PDF]
  4. O. Zhang, J. Lu, T. Ding, and M. D. Lew, “Imaging the three-dimensional orientation and rotational mobility of fluorescent emitters using the Tri-spot point spread function,” Appl. Phys. Lett. 113, 031103 (2018). [WashU Scholarly Repository, Article, Summary PDF]
    Correction: Appl. Phys. Lett. 115, 069901 (2019). [Article]
  5. H. Mazidi, A. Nehorai, and M. D. Lew, “A robust statistical estimation (RoSE) algorithm jointly recovers the 3D location and intensity of single molecules accurately and precisely,” Proc. SPIE 10500, 105000E (2018). [WashU Scholarly Repository, Article]
  6. O. Zhang, T. Ding, J. Lu, H. Mazidi, and M. D. Lew, “Measuring 3D molecular orientation and rotational mobility using a Tri-spot point spread function,” Proc. SPIE 10500, 105000B (2018). [WashU Scholarly Repository, Article]