Other

Sandia Corporation

The United States of America as Represented by the United States

Paul L Gourley

Robert M Biefeld

Kent D Choquette

Gordon Cecil Osbourn

Thomas E Zipperian

Weng W Chow

Ian J Fritz

Timothy J Drummond

Mark F Gourley

This invention provides new methods and apparatus for rapidly analyzing a single bioparticle or a plurality of bioparticles to assess their condition. The invention is enabled by an optical microcavity comprising reflective structures to confine light and bioparticles in the same space. Under resonance conditions, an electromagnetic standing wave is established in the microcavity to interact with the bioparticle. Means are provided to bring a bioparticle into the microcavity and to detect changes in the resonance condition with and without the bioparticle in the microcavity. Information about the bioparticle is obtained using the benefits of light interactions as fast, non-contacting, and non-destructive.

Analysis of bioparticles in an optical microcavity

This invention provides new methods and apparatus for rapidly analyzing single bioparticles to assess their material condition and health status. The methods are enabled by a resonant cavity to measure optical properties related to the bioparticle size and refractive index. Refractive index measurements are useful for determining material properties and biomolecular composition of the bioparticle. These properties and composition are dependent on the health state of the bioparticle. Thus, measured optical properties can be used to differentiate normal (healthy) and abnormal (diseased) states of bioparticles derived from cells or tissues. The methods are illustrated with data obtained from a resonator with a gain medium. The invention also provides new methods for multiple measurements in a single device, analyzing and manipulating bioparticles that are much smaller than the wavelength of light, and provides a microfluidic transport chip to enable rapid single bioparticle analysis of large populations of bioparticles.

Micro-optical cavity with fluidic transport chip for bioparticle analysis

A method for distinguishing a normal cell from an abnormal cell, such as, for example a cancer cell or diseased cell, of the same tissue type using mitochondrial correlation microscopy.

Method of detecting cancer in a single cell using mitochondrial correlation microscopy

This invention provides a new method for rapidly analyzing single bioparticles to assess their material condition and state of health. The method is enabled by use of a resonant cavity apparatus to measure an optical property related to the bioparticle size and refractive index. Measuring the refractive index is useful for determining material properties of the bioparticle. The material properties depend on the biomolecular composition of the bioparticle. The biomolecular composition is, in turn, dependent on the state of health of the bioparticle. Thus, measured optical properties can be used to differentiate normal (healthy) and abnormal (diseased) states of bioparticles derived from cells or tissues. The method is illustrated with data obtained from a resonator with a gain medium. The invention also provides new methods for making multiple measurements in a single device and detecting, analyzing, and manipulating bioparticles that are much smaller than the wavelength of light.

Nanolaser spectroscopy and micro-optical resonators for detecting, analyzing, and manipulating bioparticles

Method for detecting cancer in a single cell using mitochondrial correlation microscopy

A method of detecting cancer using a laser biocavity having a semiconductor laser including a microchannel through which cells in fluid traverse, comprising determining the laser wavelength of the laser biocavity with only fluid in the microchannel; determining the wavelength shift of the biocavity when each cell passes through the microchannel; and determining the percentage of cells in G2 phase from the wavelength shift of the cells; wherein an increased percentage of G2 phase cells is an indication of cancer.

Method for measuring the rate of cell reproduction by analysis of nanoliter cell samples

A method for quantifying the concentration of hemoglobin in a cell, and indicia of anemia, comprises determining the wavelength of the longitudinal mode of a liquid in a laser microcavity; determining the wavelength of the fundamental transverse mode of a red blood cell in the liquid in the laser microcavity; and determining if the cell is anemic from the difference between the wavelength of the longitudinal mode and the fundamental transverse mode. In addition to measuring hemoglobin, the invention includes a method using intracavity laser spectroscopy to measure the change in spectra as a function of time for measuring the influx of water into a red blood cell and the cell's subsequent rupture.

Method for determining properties of red blood cells

A resonant-cavity apparatus for cytometry or particle analysis. The apparatus comprises a resonant optical cavity having an analysis region within the cavity for containing one or more biological cells or dielectric particles to be analyzed. In the presence of a cell or particle, a light beam in the form of spontaneous emission or lasing is generated within the resonant optical cavity and is encoded with information about the cell or particle. An analysis means including a spectrometer and/or a pulse-height analyzer is provided within the apparatus for recovery of the information from the light beam to determine a size, shape, identification or other characteristics about the cells or particles being analyzed. The recovered information can be grouped in a multi-dimensional coordinate space for identification of particular types of cells or particles. In some embodiments of the apparatus, the resonant optical cavity can be formed, at least in part, from a vertical-cavity surface-emitting laser. The apparatus and method are particularly suited to the analysis of biological cells, including blood cells, and can further include processing means for manipulating, sorting, or eradicating cells after analysis thereof.

Resonant-cavity apparatus for cytometry or particle analysis

A temperature-insensitive vertical-cavity surface-emitting laser (VCSEL) and method for fabrication thereof. The temperature-insensitive VCSEL comprises a quantum-well active region within a resonant cavity, the active region having a gain spectrum with a high-order subband (n.gtoreq.2) contribution thereto for broadening and flattening the gain spectrum, thereby substantially reducing any variation in operating characteristics of the VCSEL over a temperature range of interest. The method for forming the temperature-insensitive VCSEL comprises the steps of providing a substrate and forming a plurality of layers thereon for providing first and second distributed Bragg reflector (DBR) mirror stacks with an active region sandwiched therebetween, the active region including at least one quantum-well layer providing a gain spectrum having a high-order subband (n.gtoreq.2) gain contribution, and the DBR mirror stacks having predetermined layer compositions and thicknesses for providing a cavity resonance within a predetermined wavelength range substantially overlapping the gain spectrum.

Temperature-insensitive vertical-cavity surface-emitting lasers and

An apparatus and method for microscopic and spectroscopic analysis and processing of biological cells. The apparatus comprises a laser having an analysis region within the laser cavity for containing one or more biological cells to be analyzed. The presence of a cell within the analysis region in superposition with an activated portion of a gain medium of the laser acts to encode information about the cell upon the laser beam, the cell information being recoverable by an analysis means that preferably includes an array photodetector such as a CCD camera and a spectrometer. The apparatus and method may be used to analyze biomedical cells including blood cells and the like, and may include processing means for manipulating, sorting, or eradicating cells after analysis thereof.

Laser apparatus and method for microscopic and spectroscopic analysis

A semiconductor high reflector comprising a number of thin alternating layers of semiconductor materials is electrically tunable and may be used as a temperature insensitive semiconductor laser in a Fabry-Perot configuration.

Semiconductor devices incorporating multilayer interference regions

A semiconductor optical device which includes a superlattice having direct transitions between conduction band and valence band states with the same wave vector, the superlattice being formed from a plurality of alternating layers of two or more different materials, at least the material with the smallest bandgap being an indirect bandgap material.

Growing community of inventors

Albuquerque, NM, United States of America

Paul L Gourley