We report an imaging method, termed Fourier ptychographic microscopy (FPM), which iteratively stitches together a
number of variably illuminated, low-resolution intensity images in Fourier space to produce a wide-field, high-resolution
complex sample image. By adopting a wavefront correction strategy, the FPM method can also correct for aberrations and
digitally extend a microscope’s depth of focus beyond the physical limitations of its optics. As a demonstration, we built a
microscope prototype with a resolution of 0.78 µm, a field of view of ∼120 mm^2 and a resolution-invariant depth of focus
of 0.3 mm (characterized at 632 nm). Gigapixel colour images of histology slides verify successful FPM operation. The
reported imaging procedure transforms the general challenge of high-throughput, high-resolution microscopy from one
that is coupled to the physical limitations of the system’s optics to one that is solvable through computation.

Wide-field, high-resolution Fourier ptychographic microscopy

X-ray crystallography has been central to the development of many fields of science over the past century. It has now matured to a point that as long as good-quality crystals are available, their atomic structure can be routinely determined in three dimensions. However, many samples in physics, chemistry, materials science, nanoscience, geology, and biology are noncrystalline, and thus their three-dimensional structures are not accessible by traditional x-ray crystallography. Overcoming this hurdle has required the development of new coherent imaging methods to harness new coherent x-ray light sources. Here we review the revolutionary advances that are transforming x-ray sources and imaging in the 21st century.

/pdf/beyond-crystallography-diffractive-imaging-using-coherent-x-3q2ojmlt88.pdf

Beyond crystallography: Diffractive imaging using coherent x-ray light sources

Fourier Ptychography is a new computational microscopy technique that achieves gigapixel images with both wide field of view and high resolution in both phase and amplitude. The hardware setup involves a simple replacement of the microscope's illumination unit with a programmable LED array, allowing one to flexibly pattern illumination angles without any moving parts. In previous work, a series of low-resolution images was taken by sequentially turning on each single LED in the array, and the data were then combined to recover a bandwidth much higher than the one allowed by the original imaging system. Here, we demonstrate a multiplexed illumination strategy in which multiple randomly selected LEDs are turned on for each image. Since each LED corresponds to a different area of Fourier space, the total number of images can be significantly reduced, without sacrificing image quality. We demonstrate this method experimentally in a modified commercial microscope. Compared to sequential scanning, our multiplexed strategy achieves similar results with approximately an order of magnitude reduction in both acquisition time and data capture requirements.

/pdf/multiplexed-coded-illumination-for-fourier-ptychography-with-139xpi0ny9.pdf

Multiplexed coded illumination for Fourier Ptychography with an LED array microscope.

In this perspective, the authors present the basic features of lens-free computational imaging tools and report performance comparisons with conventional microscopy methods. They also discuss the challenges that these computational on-chip microscopes face for their wide-scale biomedical application.

/pdf/imaging-without-lenses-achievements-and-remaining-challenges-1tjjxwd1cx.pdf

Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy

Progress in imaging and metrology depends on exquisite control over and comprehensive characterization of wave fields. As reflected in its name, coherent diffractive imaging relies on high coherence when reconstructing highly resolved images from diffraction intensities alone without the need for image-forming lenses. Fully coherent light can be described adequately by a single pure state. Yet partial coherence and imperfect detection often need to be accounted for, requiring statistical optics or the superposition of states. Furthermore, the dynamics of samples are increasingly the very objectives of experiments. Here we provide a general analytic approach to the characterization of diffractive imaging systems that can be described as low-rank mixed states. We use experimental data and simulations to show how the reconstruction technique compensates for and characterizes various sources of decoherence quantitatively. Based on ptychography, the procedure is closely related to quantum state tomography and is equally applicable to high-resolution microscopy, wave sensing and fluctuation measurements. As a result, some of the most stringent experimental conditions in ptychography can be relaxed, and susceptibility to imaging artefacts is reduced. Furthermore, the method yields high-resolution images of mixed states within the sample, which may include quantum mixtures or fast stationary stochastic processes such as vibrations, switching or steady flows.

Reconstructing state mixtures from diffraction measurements

http://xrm.phys.northwestern.edu/research/pdf_papers/2009/maiden_ultramic_2009.pdf

An improved ptychographical phase retrieval algorithm for diffractive imaging.

Generally, methods of three-dimensional imaging such as confocal microscopy and computed tomography rely on two essentials: multiple measurements (at a range of focus positions or rotations) and a weakly scattering specimen (to avoid distortion of the focal spot in the confocal microscope or to satisfy the projection approximation in tomography). Here we show that an alternative form of multi-measurement imaging, ptychography, can be extended to three dimensions and can successfully recover images in the presence of multiple scattering and when the projection approximation is not applicable. We demonstrate our technique experimentally using visible light, where it has applications in imaging thick samples such as biological tissues; however the results also have important implications for x ray and electron imaging.

Ptychographic transmission microscopy in three dimensions using a multi-slice approach

Diffractive imaging, in which image-forming optics are replaced by an inverse computation using scattered intensity data, could, in principle, realize wavelength-scale resolution in a transmission electron microscope. However, to date all implementations of this approach have suffered from various experimental restrictions. Here we demonstrate a form of diffractive imaging that unshackles the image formation process from the constraints of electron optics, improving resolution over that of the lens used by a factor of five and showing for the first time that it is possible to recover the complex exit wave (in modulus and phase) at atomic resolution, over an unlimited field of view, using low-energy (30 keV) electrons. Our method, called electron ptychography, has no fundamental experimental boundaries: further development of this proof-of-principle could revolutionize sub-atomic scale transmission imaging.

/pdf/ptychographic-electron-microscopy-using-high-angle-dark-430ychofqj.pdf

Ptychographic electron microscopy using high-angle dark-field scattering for sub-nanometre resolution imaging

Coherent diffractive imaging of objects is made considerably more practicable by using ptychography, where a set of diffraction patterns replaces a single measurement and introduces a high degree of redundancy into the recorded data. Here we demonstrate that this redundancy allows diffraction patterns to be extrapolated beyond the aperture of the recording device, leading to superresolved images, improving the limit on the finest feature separation by more than a factor of 3.

Andrew Maiden

Papers

An improved ptychographical phase retrieval algorithm for diffractive imaging.

Ptychographic transmission microscopy in three dimensions using a multi-slice approach

Ptychographic electron microscopy using high-angle dark-field scattering for sub-nanometre resolution imaging

Superresolution imaging via ptychography.

An annealing algorithm to correct positioning errors in ptychography.