Massachusetts Institute of Technology

Hamamatsu-Photonics K.k.

Connecticut Children's Medical Center

Ramachandra Rac Dasari

Michael S Feld

Changhuei Yang

Gabriel Popescu

Christopher M Fang-Yen

Lev T Perelman

Richard P Rava

Rebecca Rae Richards-Kortum

Carter Kittrell

Adam P Wax

Irving Itzkan

Takahiro Ikeda

Joseph J Baraga

Ishan Barman

Kyungwon An

Paola Taroni

Lucene Tong

Robert M Cothren

Jeon Woong Kang

Luis H Galindo

Anand V Mehta

Young D Park

Christopher Fang-yen

Narahara Chari Dingari

Peter T C So

Zahid Yaqoob

Yang Wang

Stephen Fulghum

Vadim Backman

Jun Wu

Martin Hunter

Tulio Alberto Valdez

Wonshik Choi

Yongjin Sung

Niyom Lue

Jason T Motz

Rajan Gurjar

Nicolas Spegazzini

Chae-Ryon Kong

Condon Lau

Rishikesh Pandey

Chung-Chieh Yu

Peter TC So

Systems and methods are presented for the diagnosis of middle ear pathological conditions based on spectral signatures. Preferred embodiments provide for detection of one or more analytes from the tympanic membrane. Devices use spectral measurements including spectral imaging to non-invasively identify middle ear pathological conditions including cholesteatoma and acute otitis media by providing real-time information of differentially expressed molecules. Devices and methods can also be used to non-invasively detect and quantify blood analytes from the tympanic membrane.

Systems and methods for diagnosis of middle ear conditions and detection of analytes in the tympanic membrane

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

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 relates to the optical measurement of blood analytes, such as glycated hemoglobin (HbA1c) and serum albumin as a functional metric of mean blood glucose in the diagnosis of diabetic patients. Non-enhanced Raman spectroscopy is employed as the analytical method for quantitative detection of blood analytes. Using processing techniques, non-enzymatic glycosylation (glycation) of the analytes results in measurable and highly reproducible changes in the acquired spectral data, which enable the accurate measurements and classification of glycated and unglycated analytes.

Raman spectroscopy for detection of glycated analytes

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

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

The methods of the present invention are directed at an accurate phase-based technique for measuring arbitrarily long optical distances with sub-nanometer precision. A preferred embodiment of the present invention method employs a interferometer, for example, a Michelson interferometer, with a pair of harmonically related light sources, one continuous wave (CW) and a second source having low coherence. By slightly adjusting the center wavelength of the low coherence source between scans of the target sample, the phase relationship between the heterodyne signals of the CW and low coherence light is used to measure the separation between reflecting interfaces with sub-nanometer precision. As the preferred embodiment of this method is completely free of 2&#x3c0; ambiguity, an issue that plagues most phase-based techniques, it can be used to measure arbitrarily long optical distances without loss of precision.

System and method for measuring optical distance

The present invention relates to systems and methods of field-based light scattering spectroscopy. These systems and methods provide for the diagnosis of tissue by measuring the size and distribution of cellular characteristics. Field based measurements provide phase information resulting from the interaction of scatterers within the material and the incident wavefront. These measurements can be used to provide three dimensional images of tissue.

Methods and systems using field-based light scattering spectroscopy

Growing community of inventors

Lexington, MA, United States of America

Ramachandra Rac Dasari