Abstract
State-of-the-art methods in high-resolution three-dimensional optical microscopy require that the focus be scanned through the entire region of interest. However, an analysis of the physics of the light–sample interaction reveals that the Fourier-space coverage is independent of depth. Here we show that, by solving the inverse scattering problem for interference microscopy, computed reconstruction yields volumes with a resolution in all planes that is equivalent to the resolution achieved only at the focal plane for conventional high-resolution microscopy. In short, the entire illuminated volume has spatially invariant resolution, thus eliminating the compromise between resolution and depth of field. We describe and demonstrate a novel computational image-formation technique called interferometric synthetic aperture microscopy (ISAM). ISAM has the potential to broadly impact real-time three-dimensional microscopy and analysis in the fields of cell and tumour biology, as well as in clinical diagnosis where in vivo imaging is preferable to biopsy.
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Acknowledgements
We thank K. Rowland, P. Johnson, J. Kotynek and F. Bellafiore from Carle Foundation Hospital and Clinic Association, and F. Nguyen and E. Chaney from the Beckman Institute, for their assistance in obtaining and sectioning human tissue specimens. We thank A. Oldenburg for helping to design and fabricate tissue phantoms and the Beckman Institute Visualization Laboratory for assistance in figure design. This work was supported in part by the National Institutes of Health (NIBIB, 1 R01 EB005221 and 1 R21 EB005321, to S.A.B.), the National Science Foundation (CAREER Award, 0239265, to P.S.C.) and the Beckman Institute Graduate Fellowship Program (to T.S.R.).
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Ralston, T., Marks, D., Scott Carney, P. et al. Interferometric synthetic aperture microscopy. Nature Phys 3, 129–134 (2007). https://doi.org/10.1038/nphys514
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DOI: https://doi.org/10.1038/nphys514
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