University of Illinois

Massachusetts Institute of Technology

Lucent Technologies Inc.

Hamamatsu-photonics K.k.

University of Central Florida Research Foundation, Inc.

Gabriel Popescu

Michael S Feld

Ramachandra Rac Dasari

Zhuo Wang

Aristide Dogariu

Changhuei Yang

Adam Wax

Christopher M Fang-Yen

Lynford L Goddard

Takahiro Ikeda

Huafeng Ding

Taewoo Kim

Mustafa A H Mir

S Derin Babacan

Mikhail Eugene Kandel

Paul Scott Carney

Matthew B Wheeler

Chris Edwards

Marcello Rubessa

Amir Arbabi

Christopher Fang-yen

Renjie Zhou

Basanta Bhaduri

Hoa Pham

Raj Rajagopalan

Tan Huu Nguyen

Yuchen He

Nahil A Sobh

A system generates a context mask based on quantitative image data. The system obtains the quantitative image data which was captured via a quantitative imaging of a sample. The quantitative image data is compared to previous quantitative image data through application of the quantitative image data to a neural network trained using the previous quantitative image data and corresponding constructed context masks. The comparison generates the context mask for the quantitative image data. The context mask provides context for the quantitative parameter values that facilities characterization of the sample.

Complex system for contextual mask generation based on quantitative imaging

Hilbert phase microscopy (HPM) as an optical technique for measuring high transverse resolution quantitative phase images associated with optically transparent objects. Due to its single-shot nature, HPM is suitable for investigating rapid phenomena that take place in transparent structures such as biological cells. A preferred embodiment is used for measuring biological systems including measurements on red blood cells, while its ability to quantify dynamic processes on the millisecond scale, for example, can be illustrated with measurements on evaporating micron-size water droplets.

System and method for Hilbert phase imaging

A system and methods for quantitative optical phase imaging of a sample. First second replica field of an image field are generated, characterized by a respective optical phase, cross-polarized and shifted in a shift direction transverse to a normal to the surface of the sample. The replica fields are Fourier transformed, the second replica field is retarded by four successive phase shifts, and, after inverse Fourier transforming, the first and second replica fields pass through an analyzer polarizer and superposing the first and second replica fields on a detector array to create four successive detector signals. The four successive detector signals are solved to derive a gradient of the optical phase of the image field, which may be integrated to obtain a quantitative phase image.

Gradient light interference microscopy for 3D imaging of unlabeled specimens

Methods and a computer program product for applying deconvolution to spatial light interference microscopy for resolution enhancement with respect to the diffraction limit in two and three dimensions. By exploiting the sparsity properties of the phase images, which is prominent in many biological imaging applications, and modeling of the image formation via complex fields, the very fine structures can be recovered which were blurred by the optics. The resolution improvement leads to higher accuracy in monitoring dynamic activity over time. Experiments with primary brain cells, i.e. neurons and glial cells, reveal new subdiffraction structures and motions. This new information can be used for studying vesicle transport in neurons, which may shed light on dynamic cell functioning. Finally, the method may flexibly incorporate a wide range of image models for different applications and can be utilized for all imaging modalities acquiring complex field images.

Sparse deconvolution spatial light microscopy in two and three dimensions

Preferred embodiments of the present invention are directed to systems for phase measurement of biological materials which can be applied to the fields of, for example, cellular physiology and neuroscience. These preferred embodiments are based on principles of phase measurements and imaging technologies. The scientific motivation for using phase measurements and imaging technologies is derived from, for example, cellular biology at the sub-micron level which can include, without limitation, imaging origins of dysplasia, cellular communication, neuronal transmission and implementation of the genetic code. The structure and dynamics of sub-cellular constituents cannot be currently studied in their native state using the existing methods and technologies including, for example, x-ray and neutron scattering.

Systems and methods for phase measurements

Methods and a module for use with a microscope for enhancing image contrast in an image of a phase object. A transmission image of a specimen is formed in an image plane, of which a Fourier transform is generated in a Fourier plane. An amplitude filter is applied to the Fourier transform field, which is then transformed back to an image at a focal plane of a detector array. An image signal from the detector array is processed to generate a contrast-enhanced image of the specimen.

Phase derivative microscopy module having specified amplitude mask

Methods for obtaining a tomographic phase image of a specimen, either in transmission or in scatter. A specimen is illuminated by a temporally incoherent source and light collected in transmission or scattering is used to generate a scattered phase image of the specimen in multiple axial planes. The scattered field is solved for in wavevector space, and a derived instrument function is deconvolved to obtain specimen susceptibility in wavevector space. The specimen susceptibility is transformed to obtain a three-dimensional phase tomogram of the specimen.

White light diffraction tomography of unlabeled live cells

Methods and apparatus for method for characterizing a height profile of a scattering surface relative to a fiducial plane. The scattering surface, which may be an interface between distinct solid, liquid, gaseous or plasma phases, is illuminated with substantially spatially coherent light, and light scattered by the scattering surface is collected and dispersed, such as by a grating, into zeroth- and first-order beams. A spatial Fourier transform of the zeroth- and first-order beams is created, and one of the beams is low-pass filtered. The beams are interfered at a focal plane detector to generate an interferogram, which is transformed to retrieve a spatially resolved quantitative phase image and/or an amplitude image of the scattering surface. Imaging may be performed during an etching process, and may be used to adaptively control a photoetching process in a feedback loop.

Optically monitoring and controlling nanoscale topography

Methods and a computer readable medium for deriving a quantitative phase contrast tomographic image of a specimen. The specimen is illuminated and a focus of the illuminating light is scanned to a plurality of depths within the specimen. Light transmitted through the specimen is spatially Fourier transformed at each of the plurality of depths to form a spatially transformed image, and at least one of the phase and amplitude of a plurality of spatial frequency components of the spatially transformed image is spatially modulated. An intensity image of the specimen plane as modulated with respect to spatial frequency components is detected and deconvolved at a plurality of spatially modulated instances to obtain a three-dimensional phase representation of the specimen at each of the plurality of distances relative to a fiducial plane.

Spatial light interference tomography

Methods mapping a characteristic parameter of a specimen, such as a scattering mean free path and a scattering anisotropy factor, based on a quantitative phase shift measurement. The methods have steps of using spatial light interference microscopy (SLIM) to determine a quantitative phase shift as a function of position in a sample, and applying a generalized scatter-phase transformation to derive at least one of a scattering mean free path (MFP), a scattering anisotropy factor, and a thickness-independent parameter as a function of position in the sample. In some cases, the sample may be a slice of tissue or a cell.

Characteristic parameters of cells and tissue from quantitative phase imaging

A microscope and methods for obtaining a phase image of a substantially transparent specimen. Light collected from a specimen illuminated by a temporally incoherent source is diffracted into a first order and either the zeroth or first order is low-pass filtered in a Fourier transform plane before the orders are recombined at a focal plane detector. By low pass filtering the first order diffracted beam into a plurality of wavelengths, a spectrally- and spatially-resolved quantitative phase image of the specimen is obtained.

Diffraction phase microscopy with white light

Methods and apparatus for rendering quantitative phase maps across and through transparent samples. A broadband source is employed in conjunction with an objective, Fourier optics, and a programmable two-dimensional phase modulator to obtain amplitude and phase information in an image plane. Methods, referred to as Fourier transform light scattering (FTLS), measure the angular scattering spectrum of the sample. FTLS combines optical microscopy and light scattering for studying inhomogeneous and dynamic media. FTLS relies on quantifying the optical phase and amplitude associated with a coherent image field and propagating it numerically to the scattering plane. Full angular information, limited only by the microscope objective, is obtained from extremely weak scatterers, such as a single micron-sized particle. A flow cytometer may employ FTLS sorting.

Spatial light interference microscopy and fourier transform light scattering for cell and tissue characterization

Preferred embodiments of the present invention are directed to systems for phase measurement which address the problem of phase noise using combinations of a number of strategies including, but not limited to, common-path interferometry, phase referencing, active stabilization and differential measurement. Embodiment are directed to optical devices for imaging small biological objects with light. These embodiments can be applied to the fields of, for example, cellular physiology and neuroscience. These preferred embodiments are based on principles of phase measurements and imaging technologies. The scientific motivation for using phase measurements and imaging technologies is derived from, for example, cellular biology at the sub-micron level which can include, without limitation, imaging origins of dysplasia, cellular communication, neuronal transmission and implementation of the genetic code. The structure and dynamics of sub-cellular constituents cannot be currently studied in their native state using the existing methods and technologies including, for example, x-ray and neutron scattering. In contrast, light based techniques with nanometer resolution enable the cellular machinery to be studied in its native state. Thus, preferred embodiments of the present invention include systems based on principles of interferometry and/or phase measurements and are used to study cellular physiology. These systems include principles of low coherence interferometry (LCI) using optical interferometers to measure phase, or light scattering spectroscopy (LSS) wherein interference within the cellular components themselves is used, or in the alternative the principles of LCI and LSS can be combined to result in systems of the present invention.

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Champaign, IL, United States of America

Gabriel Popescu