Massachusetts Institute of Technology

California Institute of Technology

Hamamatsu-Photonics K.k.

Zahid Yaqoob

Changhuei Yang

Peter T C So

Niyom Lue

Michael S Feld

Toyohiko Yamauchi

Ramachandra Rac Dasari

Jigang Wu

Wonshik Choi

Yongjin Sung

Dushan N Wadduwage

Dominika Lyzwa

Timothy Robert Hillman

Emily McDowell

Vijay Singh

Marinko Sarunic

Peter TC So

Our high phase sensitivity wide-field phase cancellation interferometry system allows single-shot, label-free optical sensing of neural action potentials via imaging of optical path length changes. Single-shot sensing and monitoring of single neurons within a neural network should lead to a more comprehensive understanding neural network processing, which is beneficial for the advancement in the field of neuroscience as well as its biomedical applications and impact. Our system cancels the phase profile of the resting neuron from the phase profile of the spiking neuron, improving the sensitivity by two orders of magnitude. Using a detector with an extremely large well depth and an appropriately biased interferometer increases the sensitivity by another order of magnitude, yielding a measurement that is three orders of magnitude more sensitive than those possible with other microscopes.

Phase cancellation microscopy

Refractive index of biological specimens is a source of intrinsic contrast that can be explored without any concerns of photobleaching or harmful effects caused by extra contrast agents. This feature also contains rich information that can be related to the metabolism of cells at the cellular and subcellular levels. The present invention relates to systems and methods that can provide, without any moving parts, the 3-D refractive index map of continuously flowing biological samples in a micro-fluidic channel, for example.

3-D holographic imaging continuous flow cytometry

The present invention relates to a full-field reflection phase microscope. In a preferred embodiment, the invention can combine low-coherence interferometry and off-axis digital holographic microscopy (DHM). The reflection-based DHM provides highly sensitive and a single-shot imaging of cellular dynamics while the use of low coherence source provides a depth-selective measurement. A preferred embodiment of the system uses a diffraction grating in the reference arm to generate an interference image of uniform contrast over the entire field-of-view albeit low-coherence light source. With improved path-length sensitivity, the present invention is suitable for full-field measurement of membrane dynamics in live cells with sub-nanometer-scale sensitivity.

Single shot full-field reflection phase microscopy

Systems and methods of self-referenced quantitative phase microscopy (SrQPM). The SrQPM systems and methods provide single-shot, full-field imaging capability for increased imaging speed, and near-common-path geometry for increased phase stability, allowing the study of internal structures of biological cells, live cell dynamics, and the like.

Systems and methods for self-referenced quantitative phase microscopy

An optical phase processing system for a scattering medium. A first beam has a direction and a wavefront and the first beam is configured to enter a holographic recording medium. A scattering medium is illuminated by a signal beam generating at least one scattered beam. An interference pattern is recorded from the at least one scattered beam and the first beam. A second beam is generated in a direction opposite to the direction of the first beam, the second beam having a wavefront and a phase substantially opposite to a phase of the wavefront of the first beam, and the second beam is configured to enter the holographic recording medium. The second beam and the interference pattern interact to generate at least one reconstructed beam having a phase substantially opposite to a phase of the at least one scattered beam, and the at least one reconstructed beam is configured to be viewable through the scattering medium.

Optical phase processing in a scattering medium

A method and device realize shallow gratings-based planar beam splitter/combiner. Non-trivial phase shifts between different ports of resulting interferometers are used to acquire full-field phase measurements. The non-trivial phase shifts between different ports of the planar beam splitter/combiner can be adjusted by simply shearing one grating with respect to the second grating. The two shallow diffraction gratings are harmonically-related and can be recorded on a single substrate for compact interferometric based schemes. During the recording process, the two gratings are aligned such that the grating planes and the grating vectors are parallel to that of each other. The relative phase of the recording beams controls the shearing between the recorded harmonically-related shallow phase gratings. The relative shearing of the two gratings defines the non-trivial phase shift between different ports of the compact planar beam splitter/combiner.

Harmonically matched diffraction grating pair

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Cambridge, MA, United States of America

Zahid Yaqoob