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Abstract In 1969, Emil Wolf proposed diffraction tomography using coherent holographic imaging to extract 3D information from transparent, inhomogeneous objects. In the same era, the Wolf equations were first used to describe the propagation correlations associated with partially coherent fields. Combining these two concepts, we present Wolf phase tomography (WPT), which is a method for performing diffraction tomography using partially coherent fields. WPT reconstruction works directly in the space–time domain, without the need for Fourier transformation, and decouples the refractive index (RI) distribution from the thickness of the sample. We demonstrate the WPT principle using the data acquired by a quantitative-phase-imaging method that upgrades an existing phase-contrast microscope by introducing controlled phase shifts between the incident and scattered fields. The illumination field in WPT is partially spatially coherent (emerging from a ring-shaped pupil function) and of low temporal coherence (white light), and as such, it is well suited for the Wolf equations. From three intensity measurements corresponding to different phase-contrast frames, the 3D RI distribution is obtained immediately by computing the Laplacian and second time derivative of the measured complex correlation function. We validate WPT with measurements of standard samples (microbeads), spermatozoa, and live neural cultures. The high throughput and simplicity of this method enables the study of 3D, dynamic events in living cells across the entire multiwell plate, with an RI sensitivity on the order of 10 −5 . 

Differential phase sensitive methods, such as Nomarski microscopy, play an important role in quantitative phase imaging due to their compatibility with partially coherent illumination and excellent optical sectioning ability. In this Letter, we propose a new system, to the best of our knowledge, to retrieve differential phase information from transparent samples. It is based on a 4f optical system with an amplitude-type spatial light modulator (SLM), which removes the need for traditional differential interference contrast (DIC) optics and specialized phase-only SLMs. We demonstrate the principle of harmonically decoupled gradient light interference microscopy using standard samples, as well as static and dynamic biospecimens.

 

“Living” cell sheets or bioelectronic chips have great potentials to improve the quality of diagnostics and therapies. However, handling these thin and delicate materials remains a grand challenge because the external force applied for gripping and releasing can easily deform or damage the materials. This study presents a soft manipulator that can manipulate and transport cell/tissue sheets and ultrathin wearable biosensing devices seamlessly by recapitulating how a cephalopod’s suction cup works. The soft manipulator consists of an ultrafast thermo-responsive, microchanneled hydrogel layer with tissue-like softness and an electric heater layer. The electric current to the manipulator drives microchannels of the gel to shrink/expand and results in a pressure change through the microchannels. The manipulator can lift/detach an object within 10 s and can be used repeatedly over 50 times. This soft manipulator would be highly useful for safe and reliable assembly and implantation of therapeutic cell/tissue sheets and biosensing devices. 

Multiple scattering and absorption limit the depth at which biological tissues can be imaged with light. In thick unlabeled specimens, multiple scattering randomizes the phase of the field and absorption attenuates light that travels long optical paths. These obstacles limit the performance of transmission imaging. To mitigate these challenges, we developed an epi-illumination gradient light interference microscope (epi-GLIM) as a label-free phase imaging modality applicable to bulk or opaque samples. Epi-GLIM enables studying turbid structures that are hundreds of microns thick and otherwise opaque to transmitted light. We demonstrate this approach with a variety of man-made and biological samples that are incompatible with imaging in a transmission geometry: semiconductors wafers, specimens on opaque and birefringent substrates, cells in microplates, and bulk tissues. We demonstrate that the epi-GLIM data can be used to solve the inverse scattering problem and reconstruct the tomography of single cells and model organisms.

 

Optogenetics has emerged as an exciting tool for manipulating neural activity, which in turn, can modulate behavior in live organisms. However, detecting the response to the optical stimulation requires electrophysiology with physical contact or fluorescent imaging at target locations, which is often limited by photobleaching and phototoxicity. In this paper, we show that phase imaging can report the intracellular transport induced by optogenetic stimulation. We developed a multimodal instrument that can both stimulate cells with subcellular spatial resolution and detect optical pathlength (OPL) changes with nanometer scale sensitivity. We found that OPL fluctuations following stimulation are consistent with active organelle transport. Furthermore, the results indicate a broadening in the transport velocity distribution, which is significantly higher in stimulated cells compared to optogenetically inactive cells. It is likely that this label‐free, contactless measurement of optogenetic response will provide an enabling approach to neuroscience.