Author Affiliations
1University of California, Department of Bioengineering, Los Angeles, California, United States2University of Arizona, James C. Wyant College of Optical Sciences, Tucson, Arizona, United States3University of Connecticut, Department of Biomedical Engineering, Storrs, Connecticut, United States4University of Connecticut, Department of Electrical and Computer Engineering, Storrs, Connecticut, United States5Boston University, Department of Electrical and Computer Engineering, Boston, Massachusetts, United Statesshow less
Fig. 1. The diffraction-limited SBP of standard microscope objective lenses at a 550 nm wavelength under incoherent illumination. The pathology slide image is modified from a public repository of image datasets (Image Data Resource).
52,53 Fig. 2. Array microscopy. (a) Images are captured through parallelized microimaging systems. (b) Schematics of an array microscopy for digital histopathology. In their system, three lenslet arrays are stacked. Each lens group has a diameter of 1.5 mm and a working distance of
. The microlenses are densely packed, and the orientation of the array is slightly tilted to the scanning axis. Therefore, a single-axis scan can provide the whole FOV. (c) Images of a pathology slide with a high SBP (
). (d) Image of a fluorescently stained rat femur (upper) and its enlarged view (bottom) with parallelized scanning fluorescent microscopy. The scale bar for the top image is 1 mm, and the zoom-in images are
. (e) Sequential illumination of the beam for mechanical scanning-free parallel imaging. Panels (b), (c), (d), and (e) are modified from Refs.
7,
9, and
66, respectively.
Fig. 3. Multiscale optical systems. (a) Illustration of multiscale optical designs. (b) Schematic of the AWARE-2 camera consisting of multiscale optics and 98 microcameras. (c) The camera captures a 0.96 gigapixel image. (d) Multiscale optical system for bioimaging. The system can track traces of GFP-labeled immune cells. The scale bars are 1000 and
. Panels (b)–(d) are modified from Refs.
13,
14, and
71, respectively.
Fig. 4. High-SBP imaging with Fourier ptychography. (a) Principles of spatial frequency-domain multiplexing. (b) Simplified diagram of a phase-retrieval algorithm. (c) Recovery of the spatially varying pupil function. (d) High-resolution Fourier ptychography image of red blood cells. Particles are shown in the zoom-in view of malaria-infected red blood cells (arrow). Panels (c) and (d) are modified from Refs.
79 and
80, respectively.
Fig. 5. Structured illumination microscopy. (a) Fourier domain representation of conventional, linear, and nonlinear structured illumination microscopy. In conventional microscopy, the measurable spatial frequency range is given as
. In linear structured illumination, spatial frequency information of the sample is laterally shifted an amount corresponding to the period of the illuminating pattern. Therefore, the high-spatial frequencies beyond the conventional imaging system become observable. In nonlinear structured illumination, the spatial frequency information of the sample is shifted corresponding to integer multiples of the pattern’s frequency. With pattern rotation, a large spatial frequency range can be collected. (b) A mammalian CHO cell imaged by the nonlinear structured illumination microscopy. Panel (b) is modified from Ref.
124.
Fig. 6. Hardware wavefront-engineering-based methods for high-SBP imaging. (a) System schematic of adaptive optical scanning microscopy. (b) The viewing location is given by the tilting angle of the galvanometric mirror, and the corresponding aberrations are corrected by the deformable mirror. (c) A bright-field image of a living
C. elegans in a sub-FOV of the system. (d) Principles of high-resolution wide-FOV focusing with a disordered metasurface and wavefront shaping. (e) Scanning fluorescence microscopy with the metasurface. Immunofluorescence-labeled parasites (
Giardia lamblia cysts) were imaged. The FOV and resolution are comparable to that of the
objective lens and
objective lens, respectively. Panels (a), (b)–(c), (d)–(e) are modified from Refs.
27,
143, and
144, respectively.
Fig. 7. Computational wavefront-engineering-based methods for high-SBP imaging. (a) Computational correction of aberrations in optical coherence tomography and interferometric synthetic aperture microscopy. (b) Computational correction of spatially varying aberrations of a wide-FOV objective lens (
). The system shows diffraction-limited performance over the entire FOV (13 mm in diameter). (c) Correcting spatially varying aberrations. The hardware approach sequentially corrects for aberrations at local positions. Correction of the whole FOV with averaged aberrations results in a degraded performance. By contrast, the computational approach can correct for spatially varying aberrations across the whole FOV without lateral scanning. Panels (a) and (b) are modified from Refs.
30 and
31, respectively.
Fig. 8. Illustration of various high-SBP imaging techniques. The pathology slide image is modified from a public repository of image datasets (Image Data Resource).
52,53 Fig. 9. SBP of high-SBP imaging systems. We note that the cut-off spatial frequency of an incoherent imaging system is double that of the coherent imaging system given the same NA. All frequency-domain methods
15,19,22,24 are coherent imaging methods. In this graph, the SBP values of objective lenses were calculated for incoherent imaging. For coherent imaging, the cut-off spatial frequency of the objective lenses will be halved. The number in the “Ref” column next to the author and year indicates the corresponding reference index.
Strategy | Imaging modality | Spatial resolution | Field of view | Temporal resolution (characterized by the snapshot factor ) | Spatial-domain methods | Array microscopy | Moderate | Large | | FN, field number; , magnification; , lens pitch. | Multiscale optical imaging | Moderate | Large | | Frequency-domain methods | Fourier ptychography | Moderate | Large | | , frequency bandwidth of the collecting objective; , target frequency bandwidth. | Structured illumination microscopy | High | Medium | | , frequency bandwidth of the collecting objective; , target frequency bandwidth. | Wavefront-engineering-based methods | Hardware approach | Moderate | Large | | , number of image patches | Computational approach | Moderate | N/A | N/A |
|
Table 1. Comparative advantages of high-SBP imaging techniques. The FOV and temporal resolution of computational wavefront-engineering-based methods vary with the imager used. Therefore, we did not make conclusive comments.