Single-molecule orientation localization microscopy II: a performance comparison.

Various techniques have been developed to measure the 2D and 3D positions and 2D and 3D orientations of fluorescent molecules with improved precision over standard epifluorescence microscopes. Due to the challenging signal-to-background ratio in typical single-molecule experiments, it is essential to choose an imaging system optimized for the specific target sample. In this work, we compare the performance of multiple state-of-the-art and commonly used methods for orientation localization microscopy against the fundamental limits of measurement precision. Our analysis reveals optimal imaging methods for various experiment conditions and sample geometries. Interestingly, simple modifications to the standard fluorescence microscope exhibit superior performance in many imaging scenarios.

[1]  S. Stallinga.  Effect of rotational diffusion in an orientational potential well on the point spread function of electric dipole emitters. , 2015, Journal of the Optical Society of America. A, Optics, image science, and vision.

[2]  Biqin Dong,et al.  Super-resolution spectroscopic microscopy via photon localization , 2016, Nature Communications.

[3]  P. L. La Riviere,et al.  Spatio-angular fluorescence microscopy I. Basic theory. , 2018, Journal of The Optical Society of America A-optics Image Science and Vision.

[4]  T. Moon,et al.  Mathematical Methods and Algorithms for Signal Processing , 1999 .

[5]  D. Wales,et al.  Mapping Surface Hydrophobicity of α-Synuclein Oligomers at the Nanoscale , 2018, Nano letters.

[6]  Matthew D. Lew,et al.  Fundamental Limits on Measuring the Rotational Constraint of Single Molecules Using Fluorescence Microscopy. , 2018, Physical review letters.

[7]  Oleg Mirzov.  Single-­molecule spectroscopy of π-­conjugated polymers , 2008 .

[8]  Arye Nehorai,et al.  Dense Super-Resolution Imaging of Molecular Orientation Via Joint Sparse Basis Deconvolution and Spatial Pooling , 2019, 2019 IEEE 16th International Symposium on Biomedical Imaging (ISBI 2019).

[9]  D. Chemla,et al.  Hindered Rotational Diffusion and Rotational Jumps of Single Molecules , 1998 .

[10]  Y. Shechtman,et al.  Three-Dimensional Localization of Single Molecules for Super-Resolution Imaging and Single-Particle Tracking. , 2017, Chemical reviews.

[11]  Michael J Rust,et al.  Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM) , 2006, Nature Methods.

[12]  Adam S. Backer,et al.  Enhanced DNA imaging using super-resolution microscopy and simultaneous single-molecule orientation measurements , 2016, 2016 Conference on Lasers and Electro-Optics (CLEO).

[13]  N. Bertaux,et al.  Quantitative nanoscale imaging of orientational order in biological filaments by polarized superresolution microscopy , 2016, Proceedings of the National Academy of Sciences.

[14]  Stefano Pirandola,et al.  Ultimate Precision Bound of Quantum and Subwavelength Imaging. , 2016, Physical review letters.

[15]  Handler,et al.  Spatio-angular fluorescence microscopy II. Paraxial 4f imaging. , 2019, Journal of the Optical Society of America. A, Optics, image science, and vision.

[16]  Sean Quirin,et al.  Limits of 3D dipole localization and orientation estimation for single-molecule imaging: towards Green's tensor engineering. , 2012, Optics express.

[17]  Tomer Michaeli,et al.  Multicolor localization microscopy and point-spread-function engineering by deep learning. , 2019, Optics express.

[18]  Sophie Brasselet,et al.  Birefringent Fourier filtering for single molecule coordinate and height super-resolution imaging with dithering and orientation , 2019, Nature Communications.

[19]  W. E. Moerner,et al.  Azimuthal Polarization Filtering for Accurate, Precise, and Robust Single-Molecule Localization Microscopy , 2014, Nano letters.

[20]  Ruckstuhl,et al.  Forbidden light detection from single molecules , 2000, Analytical chemistry.

[21]  H. P. Kao,et al.  Tracking of single fluorescent particles in three dimensions: use of cylindrical optics to encode particle position. , 1994, Biophysical journal.

[22]  D. Chemla,et al.  Single Molecule Dynamics Studied by Polarization Modulation. , 1996, Physical review letters.

[23]  Adam S Backer,et al.  Single-molecule polarization microscopy of DNA intercalators sheds light on the structure of S-DNA , 2019, Science Advances.

[24]  H. Balci,et al.  Three-dimensional particle tracking via bifocal imaging. , 2007, Nano letters.

[25]  W E Moerner,et al.  A bisected pupil for studying single-molecule orientational dynamics and its application to three-dimensional super-resolution microscopy. , 2014, Applied physics letters.

[26]  W E Moerner,et al.  Determining the rotational mobility of a single molecule from a single image: a numerical study. , 2015, Optics express.

[27]  Matthew D. Lew,et al.  Single-molecule orientation localization microscopy I: fundamental limits. , 2020, Journal of the Optical Society of America. A, Optics, image science, and vision.

[28]  P. L. La Riviere,et al.  Spatio-angular fluorescence microscopy III. Constrained angular diffusion, polarized excitation, and high-NA imaging. , 2020, Journal of the Optical Society of America. A, Optics, image science, and vision.

[29]  Yoav Shechtman,et al.  Fundamental Precision Bounds for Three-Dimensional Optical Localization Microscopy with Poisson Statistics. , 2018, Physical review letters.

[30]  Michael D. Mason,et al.  Ultra-high resolution imaging by fluorescence photoactivation localization microscopy. , 2006, Biophysical journal.

[31]  Zhi Zhu,et al.  Hydrogel Droplet Microfluidics for High-Throughput Single Molecule/Cell Analysis. , 2017, Accounts of chemical research.

[32]  Klaus Schulten,et al.  Angular measurements of the dynein ring reveal a stepping mechanism dependent on a flexible stalk , 2017, Proceedings of the National Academy of Sciences.

[33]  Tianben Ding,et al.  Single-molecule orientation localization microscopy for resolving structural heterogeneities between amyloid fibrils , 2020, bioRxiv.

[34]  Yale E. Goldman,et al.  Three-dimensional structural dynamics of myosin V by single-molecule fluorescence polarization , 2003, Nature.

[35]  Single-molecule orientation localization microscopy for resolving structural heterogeneities between amyloid fibrils. , 2020, Optica.

[36]  Matthew D Lew,et al.  Simultaneous, accurate measurement of the 3D position and orientation of single molecules , 2012, Proceedings of the National Academy of Sciences.

[37]  Mankei Tsang,et al.  Quantum limit to subdiffraction incoherent optical imaging , 2018, Physical Review A.

[38]  D. Axelrod.  Fluorescence excitation and imaging of single molecules near dielectric‐coated and bare surfaces: a theoretical study , 2012, Journal of microscopy.

[39]  S W Hell,et al.  Confocal microscopy with an increased detection aperture: type-B 4Pi confocal microscopy. , 1994, Optics letters.

[40]  R. Hochstrasser,et al.  Wide-field subdiffraction imaging by accumulated binding of diffusing probes , 2006, Proceedings of the National Academy of Sciences.

[41]  S. Hell,et al.  Two-color nanoscopy of three-dimensional volumes by 4Pi detection of stochastically switched fluorophores , 2011, Nature Methods.

[42]  Lucien E. Weiss,et al.  DeepSTORM3D: dense 3D localization microscopy and PSF design by deep learning , 2020, Nature Methods.

[43]  Andrei Faraon,et al.  Removing Orientation-Induced Localization Biases in Single-Molecule Microscopy Using a Broadband Metasurface Mask , 2016, Nature Photonics.

[44]  J. Lippincott-Schwartz,et al.  Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure , 2009, Proceedings of the National Academy of Sciences.

[45]  Oumeng Zhang,et al.  Quantum limits for precisely estimating the orientation and wobble of dipole emitters , 2020, Physical review research.

[46]  Rafael Piestun,et al.  High-efficiency rotating point spread functions. , 2008, Optics express.

[47]  W. E. Moerner,et al.  ADP-induced rocking of the kinesin motor domain revealed by single-molecule fluorescence polarization microscopy , 2001, Nature Structural Biology.

[48]  Z Hradil,et al.  Optimal measurements for resolution beyond the Rayleigh limit. , 2017, Optics letters.

[49]  Adam S. Backer,et al.  Extending Single-Molecule Microscopy Using Optical Fourier Processing , 2014, The journal of physical chemistry. B.

[50]  Matthew D Lew,et al.  The role of molecular dipole orientation in single-molecule fluorescence microscopy and implications for super-resolution imaging. , 2014, Chemphyschem : a European journal of chemical physics and physical chemistry.

[51]  J. Lippincott-Schwartz,et al.  Imaging Intracellular Fluorescent Proteins at Nanometer Resolution , 2006, Science.

[52]  Jordan R. Myers,et al.  Ultra-High Resolution 3D Imaging of Whole Cells , 2016, Cell.

[53]  J. Beausang,et al.  Tilting and wobble of myosin V by high-speed single-molecule polarized fluorescence microscopy. , 2013, Biophysical journal.

[54]  Ke Xu,et al.  Spectrally Resolved, Functional Super-Resolution Microscopy Reveals Nanoscale Compositional Heterogeneity in Live-Cell Membranes. , 2017, Journal of the American Chemical Society.

[55]  Ashis Sen Gupta,et al.  Tests for Standardized Generalized Variances of Multivariate Normal Populations of Possibly Different Dimensions. , 1981 .

[56]  Petar N Petrov,et al.  3D single-molecule super-resolution microscopy with a tilted light sheet , 2017, Nature Communications.

[57]  S. Brasselet,et al.  Polarized super-resolution structural imaging inside amyloid fibrils using Thioflavine T , 2017, Scientific Reports.

[58]  Matthew D. Lew,et al.  Single-molecule 3D orientation imaging reveals nanoscale compositional heterogeneity in lipid membranes , 2020, bioRxiv.

[59]  H. Flyvbjerg,et al.  Optimized localization-analysis for single-molecule tracking and super-resolution microscopy , 2010, Nature Methods.

[60]  Sudhakar Prasad,et al.  Quantum-limited superlocalization and superresolution of a source pair in three dimensions , 2018, Physical Review A.