VisionGate, Inc. Intellectual Property Summary

VisionGate is building a comprehensive intellectual property portfolio around the Cell-CT™ platform technology and its many applications in research and cancer diagnostics. This is accomplished through a combination of an aggressive in-house patent filing program and licensing of key issued patents. The U.S. Patent Office has already granted the Company’s most fundamental patents covering the Cell-CT™ and 3D image analysis. In total, VisionGate has 60 approved patents in 13 countries: 27 approved in the U.S. with 20 pending, and 33 internationally approved patents.

VisionGate’s Issued U.S. Patents

United States Patent No. 6,519,355

Feb. 11, 2003

OPTICAL PROJECTION IMAGING SYSTEM AND METHOD FOR AUTOMATICALLY DETECTING CELLS HAVING NUCLEAR AND CYTOPLASMIC DENSITOMETRIC FEATURES ASSOCIATED WITH DISEASE
Inventor: Alan C. Nelson
A system and method for rapidly detecting cells of interest using multi-dimensional, highly quantitative, nuclear and cytoplasmic densitometric features (NDFs and CDFs) includes a flow optical tomography (FOT) instrument capable of generating various optical projection images (or shadowgrams) containing accurate density information from a cell, a computer and software to analyze and reconstruct the projection images into a multi-dimensional data set, and automated feature collection and object classifiers. The system and method are particularly useful in the early detection of cancers such as lung cancer using a bronchial specimen from sputum or cheek scrapings and cervical/ovarian cancer using a cervical scraping; the system can be used to detect rare cells in specimens including blood. (34 claims)

United States Patent No. 6,522,775

Feb. 18, 2003

APPARATUS AND METHOD FOR IMAGING SMALL OBJECTS IN A FLOW STREAM USING OPTICAL TOMOGRAPHY
Inventor: Alan C. Nelson
A flow optical tomography system includes a flow cytometer, and at least one reconstruction cylinder positioned around a capillary tube. A photon source and a photon sensor work together with a pulse height analyzer to provide a first trigger point for the beginning of an object or cell, and a second trigger point for the end of the cell. The trigger signal is received by the reconstruction cylinder. The reconstruction cylinder includes optical point sources having a selectable emission wavelength, disposed in a geometric pattern around the cylinder perpendicular to and concentric with the capillary tube axis that facilitate the acquisition of transmitted, attenuated projection images of the flowing cells. The sensors also collect projections of fluorescence emitted from tagged molecular probes associated with nuclear and/or cytoplasmic structures or cell membranes. The projections are algorithmically processed to provide three-dimensional information about the cells and their disease state. (66 claims)

United States Patent No. 6,591,003

July 8, 2003

OPTICAL TOMOGRAPHY OF SMALL MOVING OBJECTS USING TIME DELAY AND INTEGRATION IMAGING
Inventors: Chee-Wui Chu and Alan C. Nelson
A system and method for three-dimensional reconstruction of an object of interest moving at a constant velocity. The object of interest is centered. The object of interest is imaged with optical point sources located at multiple projection angles around the object of interest, in cooperation with opposing time delay and integration (TDI) image sensors located at a distance from the objects of interest such that there is no focal plane within the objects of interest during imaging. Each of the TDI sensors has a line transfer rate synchronized to the constant velocity of the objects of interest. (20 Claims)

United States Patent No. 6,636,623

Oct. 21, 2003

OPTICAL PROJECTION IMAGING SYSTEM AND METHOD FOR AUTOMATICALLY DETECTING CELLS WITH MOLECULAR MARKER COM-PARTMENTALIZATION ASSOCIATED WITH MALIGNANCY AND DISEASE
Inventors: Alan C. Nelson, Robert W. Webster and Chee-Wui Chu
A system and method for rapidly detecting cells associated with malignancy and disease using molecular marker compartmentalization includes an optical tomography (OT) or a flow optical tomography (FOT) instrument capable of producing various optical projection images (or shadowgrams) containing accurate density information from a cell or cells labeled with tagged molecular probes or stains, a computer and software to analyze and reconstruct the projection images into a multi-dimensional data set, and automated feature collection and object classifiers. The system and method are particularly useful in the early detection of cancers such as lung cancer using cells from sputum or cheek scrapings and cervical/ovarian cancer using a cervical scraping, and the system can be used to detect rare cells in specimens including blood. (32 Claims)

United States Patent No. 6,697,508

Feb. 24, 2004

TOMOGRAPHIC RECONSTRUCTION OF SMALL OBJECTS USING A PRIORI KNOWLEDGE
Inventor: Alan C. Nelson
A system and method for three-dimensional (3D) reconstruction of a cell includes adjusting a current set of projection images according to a set of a priori knowledge to produce adjusted projection images, for example, based on probability masks and/or Bayesian analysis of multiple similar objects in the same sample. A reconstruction algorithm processes the adjusted projection images to generate a 3D image. The 3D image is further adjusted according to the at least one set of a priori knowledge to generate an adjusted 3D image. Criteria for process completion are applied to determine whether the adjusted 3D image is adequate. Otherwise, a set of pseudo projections are computationally created at the same projection angles as the current set of projection images and then compared to the current set of projection images to produce a set of new projections, wherein the new projections are input again to the reconstruction algorithm and the steps of the method are repeated until the adequacy criteria are met. (22 Claims)

United States Patent No. 6,741,730

May 25, 2004

APPARATUS FOR THREE-DIMENSIONAL IMAGING IN THE FOURIER DOMAIN
Inventors: J. Richard Rahn and Alan C. Nelson
A method is described for acquiring two- or more two-dimensional Fourier transforms from different perspectives of a three-dimensional object region. A three-dimensional Fourier transform can then be constructed, permitting the application of image analysis algorithms analogous to those used for two-dimensional images. (23 Claims)

United States Patent No. 6,770,893

Aug. 3, 2004

METHOD AND APPARATUS FOR EMISSION COMPUTED TOMOGRAPHY USING TEMPORAL SIGNATURES
Inventor: Alan C. Nelson
An optical tomographic system is described wherein the localization of secondary emitters within an object of interest can be determined using the temporal signatures of secondary emission arising from the object being illuminated by an external primary source beam that is non-parallel, such as a cone beam, while said beam is moving relative to the object in a controlled manner. A unique set of secondary emitter points can be localized within the object and, when combined with a computed reconstruction of the object from its primary beam projections, can accurately create an image of the secondary emitters in the object. The system would enable the quantitative three-dimensional imaging of fluorescently labeled molecular probes in a biological cell, for example. (20 Claims)

United States Patent No. 6,944,322

Sept. 13, 2005

OPTICAL TOMOGRAPHY OF SMALL OBJECTS USING PARALLEL-BEAM ILLUMINATION AND POST-SPECIMEN OPTICAL MAGNIFICATION
Inventors: Roger H. Johnson and Alan C. Nelson
An optical tomography (OT) system utilizing parallel-beam illumination is disclosed. Detectors are utilized in several projection imaging geometries to obtain multi-perspective data for tomographic image reconstruction of small objects such as biological cells. Magnification is controlled by post-specimen optics. The method permits the optimal use of parallel-beam back projection image reconstruction methods. (56 Claims)

United States Patent No. 6,991,738

Jan. 31, 2006

FLOW-THROUGH DRUM CENTRIFUGE
Inventors: Mark E. Fauver and Alan C. Nelson
A flow-through drum centrifuge for separation of specimen particles and embedding the specimen particles into a gelatinous medium. Optical gel is injected into a drum centrifuge having an inner wall. The optical gel is centrifugated to produce a coating of optical gel on the inner wall. A specimen mixture including solvent flows through the drum centrifuge while the drum centrifuge is rotated such that specimen particles from the specimen mixture are accelerated toward the inner wall, where they are embedded into the coating of optical gel. Solvent is removed from the film of optical gel and specimen particles, which is then injected into a microcapillary tube. (17 Claims)

United States Patent No. 7,197,355

Mar. 27, 2007

VARIABLE-MOTION OPTICAL TOMOGRAPHY OF SMALL OBJECTS
Inventor: Alan C. Nelson
A method for variable-motion optical tomography (VOT), where motion of an object of interest, such as a cell, has a variable velocity that can be varied on a cell-by-cell basis. Cell velocity is controlled in one example by packing cells into a capillary tube, or any other linear substrate, so that the cells are stationary within the capillary tube, but the capillary tube is translated and rotated mechanically through an optical tomography reconstruction cylinder. The capillary tube motion may advantageously be controlled in a start-and-stop fashion and translated and rotated at any velocity for any motion interval, under the control of a computer program. (26 Claims)

United States Patent No. 7,260,253

Aug. 21, 2007

METHOD FOR CORRECTION OF RELATIVE OBJECT-DETECTOR MOTION BETWEEN SUCCESSIVE VIEWS
Inventors: J. Richard Rahn and Alan C. Nelson
An apparatus and method for correction of relative object-detector motion between successive views during optical tomographic imaging in three dimensions. An object of interest is illuminated to produce an image. A lateral offset correction value is determined for the image. An axial offset correction value is determined for the image. The lateral offset correction value and the axial offset correction value are applied to the image to produce a corrected file image. (17 Claims)

United States Patent No. 7,494,809

Feb. 24, 2009

METHOD FOR AUTOMATED CELL ENRICHMENT PREPARATION
Inventor: Alan C. Nelson
A method for automated cell enrichment preparation where biological cells are injected into a first subchamber and flowed through the first subchamber, through a large pore filter and into a second subchamber so that the large pore filter retains particles large particles in the first subchamber, while the biological cells pass through the first filter into the second subchamber and are retained by a small pore filter. After clearing, the biological cells are stained. A solvent exchange leaves the biological cells in solvent and they are released into a concentration module where a portion of the solvent is removed to form an enriched concentrated cell suspension.

United States Patent No. 7,569,789

Aug. 4, 2009

SORTING PARTICLES IN A LAMINAR FLOW MICROFLUIDIC CHANNEL
Inventor: Jon W. Hayenga
An apparatus and method for sorting particles in a laminar flow microfluidic channel includes a cantilevered coaxial flow injector in a microfluidic device, the cantilevered coaxial flow injector including an elongated cantilever element integrated into the microfluidic device. A coaxial channel runs through the elongated cantilever element, where coaxial channel is sized to pass particles of a predetermined size. An actuator is coupled to the elongated cantilever element, for actuating said elongated cantilever element.

United States Patent No. 7,738,945

June 15, 2010

OPTICAL IMAGING OF A THICK SPECIMEN
Inventor: Mark E. Fauver
A system for optical imaging of a thick specimen that permits rapid acquisition of data necessary for tomographic reconstruction of the three-dimensional (3D) image. One method involves the scanning of the focal plane of an imaging system and integrating the range of focal planes onto a detector. The focal plane of an optical imaging system is scanned along the axis perpendicular to said plane through the thickness of a specimen during a single detector exposure. Secondly, methods for reducing light scatter when using illumination point sources are presented. Both approaches yield shadowgrams. This process is repeated from multiple perspectives, either in series using a single illumination/detection subsystem, or in parallel using several illumination/detection subsystems. A set of pseudo-projections is generated, which are input to a three dimensional tomographic image reconstruction algorithm.

United States Patent No. 7,787,112

Aug. 31, 2010

OPTICAL PROJECTION TOMOGRAPHY SYSTEM
Inventor: J. Richard Rahn
An optical projection tomography system is illuminated with a light source. An object-containing tube, a portion of which is located within the region illuminated by the light source, contains an object of interest that has a feature of interest. A detector is located to receive emerging radiation from the object of interest. A lens, including optical field extension elements, is located in the optical path between the object region and the detector, such that light rays from multiple object planes in the object-containing tube simultaneously focus on the detector. The object-containing tube moves relatively to the detector and the lens operate to provide multiple views of the object region for producing an image of the feature of interest at each view.

United States Patent No. 7,835,561

Nov. 15, 2010

METHOD FOR IMAGE PROCESSING AND RECONSTRUCTION OF IMAGES FOR OPTICAL TOMOGRAPHY
Inventor: Michael G. Meyer
A method for reconstructing three-dimensional (3D) tomographic images. A set of pseudo-projection images of an object is acquired. Error corrections are applied to the set of pseudo-projection images to produce a set of corrected pseudo-projection images. The set of corrected pseudo-projection images are processed to produce (3D) tomographic images. (73 claims)