Massachusetts Institute of Technology

Hamamatsu-photonics K.k.

Other

The Brigham and Women's Hospital, Inc.

Michael S Feld

Carter Kittrell

Ramachandra Rac Dasari

Robert M Cothren, Jr

Irving Itzkan

Richard P Rava

Lev T Perelman

Changhuei Yang

Gabriel Popescu

Yang Wang

Rebecca Rae Richards-Kortum

Christopher M Fang-Yen

Jun Wu

Irene Georgakoudi

Wonshik Choi

Lucene Tong

Kyungwon An

Martin R Prince

Adam P Wax

Joseph J Baraga

Vadim Backman

Gary B Hayes

Stephen Fulghum

Ramachandra Rao Dasari

Takahiro Ikeda

Wei-Chuan Shih

Martin Hunter

Paola Taroni

Robert M Cothren

George Zonios

Ramasamy Manoharan

Young D Park

Jill M Tobin

Anand V Mehta

Robert L Willett

Christopher Fang-yen

Ramanchandra R Dasari

Rajan Gurjar

Qingguo Zhang

Markus G Mueller

Jacques Van Dam

Thomas D Wang

Toyohiko Yamauchi

Zahid Yaqoob

Thomas Scecina

Jeon Woong Kang

Ishan Barman

Luis H Galindo

Narahara Chari Dingari

Jason T Motz

Kate Bechtel

Ramachandra Roa Dasari

Cynthia De Los Santos-Pacheco

Leo T Kenny

James J Childs

Annika Enejder

Kaz Tanaka

Andrew J Berger

James F Brennan, Iii

Condon Lau

Chung-Chieh Yu

Firooz Partovi

Barry Sachs

Joseph A Izatt

Douglas Albagli

Chae-Ryon Kong

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

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

The present invention further relates to the selection of the specific filter combinations, which can provide sufficient information for multivariate calibration to extract accurate analyte concentrations in complex biological systems. The present invention also describes wavelength interval selection methods that give rise to the miniaturized designs. Finally, this invention presents a plurality of wavelength selection methods and miniaturized spectroscopic apparatus designs and the necessary tools to map from one domain (wavelength selection) to the other (design parameters). Such selection of informative spectral bands has a broad scope in miniaturizing any clinical diagnostic instruments which employ Raman spectroscopy in particular and other spectroscopic techniques in general.

Portable raman diagnostic system

The present invention relates to systems and methods for quantitative three-dimensional mapping of refractive index in living or non-living cells, tissues, or organisms using a phase-shifting laser interferometric microscope with variable illumination angle. A preferred embodiment provides tomographic imaging of cells and multicellular organisms, and time-dependent changes in cell structure and the quantitative characterization of specimen-induced aberrations in high-resolution microscopy with multiple applications in tissue light scattering.

Distribution of refractive index measurement by synthetic aperture tomography

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

The present invention relates to a spectroscopic imaging system using autofluorescence and reflectance images to diagnose tissue. A preferred embodiment of the invention uses a plurality of light sources to illuminate a tissue region to provide the fluorescence and reflectance images, respectively.

Tri modal spectroscopic imaging

The present invention relates to systems and methods for the measurement of analytes such as glucose. Raman and reflectance spectroscopy are used to measure a volume, of material such as a blood sample or tissue within a subject and determine a concentration of a blood analyte based thereon. The present invention further relates to a calibration method, constrained regularization (CR), and demonstrates its use for analyzing spectra including, for example, the measurement glucose concentrations using transcutaneous Raman spectroscopy.

Intrinsic Raman spectroscopy

Tomographic phase microscopy

The present invention utilizes a plurality of spectroscopic systems and methods to measure characteristics of tissue useful in the diagnosis of disease. In a preferred embodiment, a combination of fluorescence, reflectance and light scattered spectra can be measured and processed to provide biochemical, architectural and morphological state of tissue. The methods and systems can be used particularly in the early detection of carcinoma within tissue in vivo and in vitro.

System and methods of fluorescence, reflectance and light scattering spectroscopy for measuring tissue characteristics

The present invention relates to the use of Raman spectroscopy for quantitative, non-invasive transcutaneous measurement of blood analytes, such as glucose. Raman spectroscopy is used to measure glucose transcutaneously, in patients whose blood glucose levels were monitored. Raman spectra were collected transcutaneously along with glucose reference values provided by standard capillary blood analysis. A partial least squares calibration was created from the data from each subject and validated using leave-one-out cross validation.

Raman spectroscopy for non-invasive glucose measurements

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.

The system and method of the present invention relates to using spectroscopy, for example, Raman spectroscopic methods for diagnosis of tissue conditions such as vascular disease or cancer. In accordance with a preferred embodiment of the present invention, a system for measuring tissue includes a fiber optic probe having a proximal end, a distal end, and a diameter of 2 mm or less. This small diameter allows the system to be used for the diagnosis of coronary artery disease or other small lumens or soft tissue with minimal trauma. A delivery optical fiber is included in the probe coupled at the proximal end to a light source. A filter for the delivery fibers is included at the distal end. The system includes a collection optical fiber (or fibers) in the probe that collects Raman scattered radiation from tissue, the collection optical fiber is coupled at the proximal end to a detector. A second filter is disposed at the distal end of the collection fibers. An optical lens system is disposed at the distal end of the probe including a delivery waveguide coupled to the delivery fiber, a collection waveguide coupled to the collection fiber and a lens.

Systems and methods for spectroscopy of biological tissue

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Newton, MA, United States of America

Michael S Feld