Embodiments of the present disclosure generally relate to wide field-of-view, high-resolution digital imaging techniques. More specifically, certain embodiments relate to Fourier ptychographic imaging (FPI) devices, systems and methods for wide-field, high-resolution imaging.
The throughput of a conventional imaging platform (e.g., microscope) is generally limited by the space-bandwidth product defined by its optical system. The space-bandwidth product refers to the number of degrees of freedom (e.g., number of resolvable pixels) that the optical system can extract from an optical signal, as discussed in Lohmann, A. W., Dorsch, R. G., Mendlovic, D., Zalevsky, Z. & Ferreira, C., “Space-bandwidth product of optical signals and systems,” J. Opt. Soc. Am. A 13, pages 470-473 (1996), which is hereby incorporated by reference in its entirety. A conventional microscope typically operates with a space-bandwidth product on the order of 10 megapixels, regardless of the magnification factor or numerical aperture (NA) of its objective lens. For example, a conventional microscope with a ×20, 0.40 NA objective lens has a resolution of 0.8 mm and a field-of-view of 1.1 mm in diameter, which corresponds to a space-bandwidth product of about 7 megapixels. Prior attempts to increase space-bandwidth product of conventional microscopes have been confounded by the scale-dependent geometric aberrations of their objective lenses, which results in a compromise between image resolution and field-of-view. Increasing the space-bandwidth product of conventional imaging platforms may be limited by: 1) scale-dependent geometric aberrations of its optical system, 2) constraints of the fixed mechanical length of the relay optics and the fixed objective parfocal length, and/or 3) availability of gigapixel digital recording devices.
Some attempts to increase the spatial-bandwidth product using interferometric synthetic aperture techniques are described in Di, J. et al., “High resolution digital holographic microscopy with a wide field of view based on a synthetic aperture technique and use of linear CCD scanning,” Appl. Opt. 47, pp. 5654-5659 (2008); Hillman, T. R., Gutzler, T., Alexandrov, S. A., and Sampson, D. D., “High-resolution, wide-field object reconstruction with synthetic aperture Fourier holographic optical microscopy,” Opt. Express 17, pp. 7873-7892 (2009); Granero, L., Micó, V., Zalevsky, Z., and García, J., “Synthetic aperture superresolved microscopy in digital lensless Fourier holography by time and angular multiplexing of the object information,” Appl. Opt. 49, pp. 845-857 (2010); Kim, M. et al., “High-speed synthetic aperture microscopy for live cell imaging,” Opt. Lett. 36, pp. 148-150 (2011); Turpin, T., Gesell, L., Lapides, J., and Price, C., “Theory of the synthetic aperture microscope,” pp. 230-240; Schwarz, C. J., Kuznetsova, Y., and Brueck, S., “Imaging interferometric microscopy,” Optics letters 28, pp. 1424-1426 (2003); Feng, P., Wen, X., and Lu, R., “Long-working-distance synthetic aperture Fresnel off-axis digital holography,” Optics Express 17, pp. 5473-5480 (2009); Mico, V., Zalevsky, Z., García-Martínez, P., and García, J., “Synthetic aperture superresolution with multiple off-axis holograms,” JOSA A 23, pp. 3162-3170 (2006); Yuan, C., Zhai, H., and Liu, H., “Angular multiplexing in pulsed digital holography for aperture synthesis,” Optics Letters 33, pp. 2356-2358 (2008); Mico, V., Zalevsky, Z., and García, J., “Synthetic aperture microscopy using off-axis illumination and polarization coding,” Optics Communications, pp. 276, 209-217 (2007); Alexandrov, S., and Sampson, D., “Spatial information transmission beyond a system's diffraction limit using optical spectral encoding of the spatial frequency,” Journal of Optics A: Pure and Applied Optics 10, 025304 (2008); Tippie, A. E., Kumar, A., and Fienup, J. R., “High-resolution synthetic-aperture digital holography with digital phase and pupil correction,” Opt. Express 19, pp. 12027-12038 (2011); Gutzler, T., Hillman, T. R., Alexandrov, S. A., and Sampson, D. D., “Coherent aperture-synthesis, wide-field, high-resolution holographic microscopy of biological tissue,” Opt. Lett. 35, pp. 1136-1138 (2010); and Alexandrov, S. A., Hillman, T. R., Gutzler, T., and Sampson, D. D., “Synthetic aperture Fourier holographic optical microscopy,” Phil. Trans. R. Soc. Lond. A 339, pp. 521-553 (1992), which are hereby incorporated by reference in their entirety. Most of these attempts use setups that record both intensity and phase information using interferometric holography approaches, such as off-line holography and phase-shifting holography. The recorded data is then synthesized in the Fourier domain in a deterministic manner.
These previous attempts to increase spatial-bandwidth product using interferometric synthetic aperture techniques have limitations. For example, interferometric holography recordings typically used in these techniques require highly-coherent light sources. As such, the reconstructed images tend to suffer from various coherent noise sources, such as speckle noise, fixed pattern noise (induced by diffraction from dust particles and other optical imperfections in the beam path), and multiple interferences between different optical interfaces. The image quality is, therefore, not comparable to that of a conventional microscope. On the other hand, the use of an off-axis holography approach sacrifices useful spatial-bandwidth product (i.e., the total pixel number) of the image sensor, as can be found in Schnars, U. and Jüptner, W. P. O., “Digital recording and numerical reconstruction of holograms,” Measurement Science and Technology, 13, R85 (2002), which is hereby incorporated by reference in its entirety. Another limitation is that interferometric imaging may be subjected to uncontrollable phase fluctuations between different measurements. Hence, a priori and accurate knowledge of the specimen location may be needed for setting a reference point in the image recovery process (also known as phase referring). Another limitation is that previously reported attempts require mechanical scanning, either for rotating the sample or for changing the illumination angle. Therefore, precise optical alignments, mechanical control at the sub-micron level, and associated maintenances are needed for these systems. In terms of the spatial-bandwidth product, these systems present no advantage as compared to a conventional microscope with sample scanning and image stitching. Another limitation is that previous interferometric synthetic aperture techniques are difficult to incorporate into most existing microscope platforms without substantial modifications. Furthermore, color imaging capability has not been demonstrated on these platforms. Color imaging capability has proven pivotal in pathology and histology applications.
In microscopy, a large spatial-bandwidth product is highly desirable for biomedical applications such as digital pathology, haematology, phytotomy, immunohistochemistry, and neuroanatomy. A strong need in biomedicine and neuroscience to digitally image large numbers of histology slides for analysis has prompted the development of sophisticated mechanical scanning microscope systems and lensless microscopy set-ups. Typically, these systems increase their spatial-bandwidth product using complex mechanical means that have high precision and accurate components to control actuation, optical alignment and motion tracking. These complex components can be expensive to fabricate and difficult to use.
Previous lensless microscopy methods such as digital in-line holography and contact-imaging microscopy also present certain drawbacks. For example, conventional digital in-line holography does not work well for contiguous samples and contact-imaging microscopy requires a sample to be in close proximity to the sensor. Examples of digital in-line holography devices can be found in Denis, L., Lorenz, D., Thiebaut, E., Fournier, C. and Trede, D., “Inline hologram reconstruction with sparsity constraints,” Opt. Lett. 34, pp. 3475-3477 (2009); Xu, W., Jericho, M., Meinertzhagen, I., and Kreuzer, H., “Digital in-line holography for biological applications,” Proc. Natl Acad. Sci. USA 98, pp. 11301-11305 (2001); and Greenbaum, A. et al., “Increased space-bandwidth product in pixel super-resolved lensfree on-chip microscopy,” Sci. Rep. 3, page 1717 (2013), which are hereby incorporated by reference in their entirety. Examples of contact-imaging microscopy can be found in Zheng, G., Lee, S. A., Antebi, Y., Elowitz, M. B. and Yang, C., “The ePetri dish, an on-chip cell imaging platform based on subpixel perspective sweeping microscopy (SPSM),” Proc. Natl Acad. Sci. USA 108, pp. 16889-16894 (2011); and Zheng, G., Lee, S. A., Yang, S. & Yang, C., “Sub-pixel resolving optofluidic microscope for on-chip cell imaging,” Lab Chip 10, pages 3125-3129 (2010), which are hereby incorporated by reference in their entirety.