Martin James Humphry

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

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.

Superresolution imaging via ptychography

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.

Optical ptychography: a practical implementation with useful resolution

Quantitative phase microscopy offers a range of benefits over conventional phase-contrast techniques. For example, changes in refractive index and specimen thickness can be extrapolated and images can be refocused subsequent to their recording. In this Letter, we detail a lensless, quantitative phase microscope with a wide field of view and a useful resolution. The microscope uses the recently reported coherent diffractive imaging technique of ptychography to generate images from recorded diffraction patterns.

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

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 microscope for three-dimensional imaging

Ptychography is a coherent imaging technique that enables an image of a specimen to be generated from a set of diffraction patterns. One limitation of the technique is the assumption of a multiplicative interaction between the illuminating coherent beam and the specimen, which restricts ptychography to samples no thicker than a few tens of micrometers in the case of visible-light imaging at micron-scale resolution. By splitting a sample into axial sections, we demonstrated in recent work that this thickness restriction can be relaxed and whats-more, that coarse optical sectioning can be realized using a single ptychographic data set. Here we apply our technique to data collected from a modified optical microscope to realize a reduction in the optical sectioning depth to 2 μm in the axial direction for samples up to 150 μm thick. Furthermore, we increase the number of sections that are imaged from 5 in our previous work to 34 here. Our results compare well with sectioned images collected from a confocal microscope but have the added advantage of strong phase contrast, which removes the need for sample staining.

Quantitative electron phase imaging with high sensitivity and an unlimited field of view.

As it passes through a sample, an electron beam scatters, producing an exit wavefront rich in information. A range of material properties, from electric and magnetic field strengths to specimen thickness, strain maps and mean inner potentials, can be extrapolated from its phase and mapped at the nanoscale. Unfortunately, the phase signal is not straightforward to obtain. It is most commonly measured using off-axis electron holography, but this is experimentally challenging, places constraints on the sample and has a limited field of view. Here we report an alternative method that avoids these limitations and is easily implemented on an unmodified transmission electron microscope (TEM) operating in the familiar selected area diffraction mode. We use ptychography, an imaging technique popular amongst the X-ray microscopy community; recent advances in reconstruction algorithms now reveal its potential as a tool for highly sensitive, quantitative electron phase imaging.

Quantitative phase contrast optimised cancerous cell differentiation via ptychography

This paper shows that visible-light ptychography can be used to distinguish quantitatively between healthy and tumorous unstained cells. Advantages of ptychography in comparison to conventional phase-sensitive imaging techniques are highlighted. A novel procedure to automatically refocus ptychographic reconstructions is also presented, which improves quantitative analysis.

Ptychography: a novel phase retrieval technique, advantages and its application

This paper is intended to introduce ptychography, a novel and very promising phase retrieval technique. It is based on the lens-less recording of a series of diffraction patterns caused by coherent object illumination. In the visible region of light, ptychography has successfully been implemented for visible light microscopy and optical metrology. Ptychography has also successfully been applied to X-ray microscopy where it is difficult to manufacture good quality lenses and where, at high X-ray energies, absorption contrast is low but where phase contrast is significant. In the course of this paper theoretical fundamentals of ptychography are explained, advantages in comparison to traditional optical techniques are represented and applications are shown.

Ptychography: a powerful phase retrieval technique for biomedical imaging

This paper discusses ptychography, a coherent diffraction imaging technique. Advantages of ptychography with respect conventional imaging techniques for cell visualisation are highlighted and demonstrated using unstained healthy and tumorous mouse cells as the object under investigation. A novel procedure to automatically refocus a possible slightly out of focus ptychographic data set will be discussed, by which an improved quantitative analysis and discrimination is enabled.