University of California

Other

University of Massachusetts

Michael W Berns

Bruce J Tromberg

Tatiana B Krasieva

Nancy L Allbritton

Christopher E Sims

Gavin D Meredith

Elliot Botvinick

Lars Othar Svaasand

Alexander Dvornikov

Yona Tadir

Daryl Preece

Arlene E Gwon

J Stuart Nelson

Edward K Wong

Yagang Liu

Thoru Pederson

Gerard Boss

Sol Kimel

Richard C Haskell

Glen Profeta

Craig Rappaport

Tsong T Tsay

Samarenda K Mohanty

Lara O Svaasand

Gregory J Sonek

Chao L Lee

Matthew Ficinski

Veronica Gomez-Godinez

Ryan M Spitler

Shirli Cohen

Matthew Ono

Brad J Monk

Linda Zhixia Shi

Pegah Pouladian

Samarendra K Mohanty

Nicole Wakida

Jared Stephens

Toyohiko Yamauchi

Systems and methods are provided for Quantitative Phase Microscopes (QPM) having laser systems including one or more of laser scissors and laser tweezers. In one embodiment, the system includes one or more structural elements, such as a stage and dichroic plate for operation of a QPM with laser scissors/tweezers. Another embodiment is directed to a method of operating a QPM system having laser scissors/tweezers. One or more solutions are provided for biodmedical applications of a QPM system including simulation and analysis of trauma on cellular structures and organelles. Processes are also provided for simulation and analysis of traumatic injury, including imaging and analysis of astrocytes.

Systems and methods for laser scissors and tweezers with a quantitative phase microscope (QPM)

A device for DNA repair phototherapy is provided. A method of use for the device to provide DNA phototherapy to damaged DNA is also disclosed.

Methods and device for stimulating DNA repair

The invention generally relates to methods for treating and/or reducing the severity of a wound in a subject. Provided are wound therapies combining low level light therapy (LLLT) and a nitric oxide (NO) donor to treat and/or reduce the severity of the wound. The LLLT and NO donor may be administered concurrently or sequentially. Also provided are wound treatment systems and kits including a light source and a NO donor, which are administered to a wounded subject. Further provided are pharmaceutical compositions that comprise a NO donor and are formulated to be administered in conjunction with LLLT.

Methods and systems of treating wounds

This invention relates to optomechanical systems and methods for altering, modifying or disrupting a target object. Such systems and methods are used for, for example, ablating the endogenous nucleus in a cell.

Systems and methods for identifying and disrupting cellular organelles

An apparatus for in vivo electroporating a plasmid into a retina of any eye includes a first electrode with a first polarity of voltage placed in contact with a cornea of the eye, a second electrode with an opposite second voltage at least in part behind the retina, and a pulsed voltage source for providing a pulsed DC voltage with an optimized field strength amplitude, frequency, number of pulses, group repetition rate and duration of pulse and group repetition, which are optimized for transfection of the channelrhodospsin-2 (ChR2) gene into the retinal ganglion cells. An in vivo method for treating retinal ganglion cells in an eye without use of viral transfection includes the steps of nonviral in vivo delivering a channelrhodospsin-2 (ChR2) gene to target the specific (retinal ganglion) cells of a retina by intravitreous injection of plasmid DNA, electroporating the plasmid into the retina and use of image intensification device for stimulating the retinal ganglion cells with ambient lighting conditions.

Method and apparatus for optogenetic treatment of blindness including retinitis pigmentosa

A single optical fiber having a distal end is optically coupled to the laser and distilling terminated with an axicon lens optically coupled to the single optical fiber to form a microscopic distal tip to provide a spatially shaped elongated laser focused spot for microprocessing and/or microdissection of a microscale object. A pulsed or continuous laser beam or superposition of pulsed and continuous laser beams is generated, controllably spatially shaped, selectively oriented, selectively moved via movement of a single optical fiber terminated with the axicon lens, and the oriented, spatially shaped laser beam applied via the single optical fiber terminated with the axicon lens to a living or nonliving microscopic object for manipulation, micro-dissection, alteration/ablation, and excitation of the living or nonliving microscopic object.

Apparatus and method for micromanipulation of microscale objects using laser light delivered through a single optical fiber and axicon lens

A microscope fluid applicator includes an immersion fluid reservoir for storing immersion fluid and an applicator tip coupled to the immersion fluid reservoir. The microscope fluid applicator is releasably engaged to a moveable turret on a microscope. The microscope fluid applicator may be secured to an objective lens port on a turret of a microscope via threads. Immersion fluid is ejected from the applicator tip onto a sample holder. The turret may be rotated to place an immersion fluid objective into the immersion fluid. The sample may then be viewed through the immersion fluid. Any excess immersion fluid that is dispensed from the applicator tip may be collected in a fluid collector to prevent contamination of the microscope optics and other components.

Microscope immersion fluid applicator

The activity of intracellular chemical reactions of molecules is measured by the use of fluorescently labeled substrate molecules that undergo a change in electrophoretic mobility upon chemical reaction such as that catalyzed by an enzyme. Specificity is achieved by using labeled substrate molecules that can be acted upon only by specific enzymes. Thus the activity of a specific enzyme or class of enzymes can be determined. Measurements are made with the intracellular presence of such substrate molecules, at some time of interest, typically after exposure of the cell to a stimulus that activates a particular enzymatic pathway. To ensure accuracy, measurements must be made in a timely manner so as to minimize chemical reactions occurring subsequent to the time of interest. Fast controllable laser lysis is used to obtain the contents of a single cell into which reporter substrate molecules have been introduced. The cell contents are then subjected to capillary electrophoresis and enzymatic activity is determined by comparing amounts of substrate molecules to amounts of enzymatically altered substrate molecules which are separated by the electrophoresis and identified by the presence of a fluorescent label.

Method and apparatus for detecting enzymatic activity using molecules that change electrophoretic mobility

The invention is a technique for dynamic measurements of the heat transfer coefficient to the outer layer of the skin surface using a high thermal conductivity metal in an insulating block as the standardized target. The coefficient is dependent on the specific design of the cryogen valve and nozzle, and values up to 11 500 W/m K values were measured for a 100 ms long spurts. The values for longer spurts are dependent on air humidity, as ice/snow formation then tends to form a thermally insulating layer. The average value of the heat transfer coefficient for a 200 ms long spurt was determined to 8000 W/m K for conditions of normal room humidity and temperature. The technique enables an improved prediction of the temperature profile and cooling efficiency during therapy, and may thereby contribute to an improved therapeutic outcome.

Method and apparatus for measuring the heat transfer coefficient during cryogen spray cooling of tissue

An illuminator and a reflectance microscope or system utilizing the illuminator for eliminating the need of a special light source, a reflected light vertical illuminator, and condenser lenses. The system may utilize an ordinary light source. The illuminator includes embedded chromophoric and diffusion properties. The illuminator further has a size and a shape to enable proximate positioning relative to the specimen to be observed. The illuminator further has an opening or aperture through which the specimen may be viewed. As such, the opening of the illuminator permits placement of the illuminator between the objective lens and the specimen. This positioning enables reflectance type or dark field microscopy with a simple and durable illuminator without complex optics. A method of using the reflectance microscope includes illuminating a specimen by the illuminator on a same side of the specimen as is the objective lens relative to a plane of the specimen normal to the optical path.

Diffuse optics illuminator for reflectance microscopy and method of providing diffuse light for reflectance microscopy

A method for the laser photoablation of ocular lens tissue comprises the steps of determining a volume of the lens tissue to be photoablated and directing a pulsed, infrared laser beam at the volume with an amount of energy effective for photoablating the determined region without causing substantial damage to surrounding tissue regions. The laser beam is initially directed at a focal point below an anterior surface of the ocular lens and such focal point is moved towards the ocular lens anterior surface in order to ablate the determined volume. The laser is preferably an Nd:YLF laser operating at a frequency of about 1053 nanometers and a pulse repetition rate of about 1000 Hertz with a pulse width of about 60 picoseconds. Each pulse has an energy of about 30 microjoules. The laser operates with a focused beam diameter of about 20 microns and operates with a &ldquo;zone of effect&rdquo; of no greater than about 50 microns. The method provides for the correction of myopia, hyperopia or presbyopia and enables the removal of incipient cataract.

Method of laser photoablation of lenticular tissue for the correction of vision problems

Fast lysis of a single cell or cellular component thereof is performed by generating a shock wave in a medium in which the cell or cellular component thereof is positioned. The cell or cellular component thereof is either positioned by laser tweezers or cultured as an adhered cell or cellular component thereof to minimize manipulation trauma. The disclosed method completely lyses a single cell or cellular component thereof in a controllable manner in milliseconds or less followed immediately by the loading of the cellular contents into a capillary for analyte separation and detection. The cell or cellular component thereof is adjacent the inlet of an electrophoretic column through which a gravity siphon flow of the medium is maintained. The lysed contents of the cell or cellular component thereof enter the electrophoretic column in less than 33 msec, are separated and analyzed by laser induced fluorescence. The method takes advantage of the shock wave produced by a highly focused laser pulse which is created in a medium adjacent to the cell or cellular component thereof. In the illustrated embodiment the laser pulse is focused in the glass substrate at or near a glass-to-buffer interface of a cell chamber in which the cell or cellular component thereof to be lysed has been cultured.

Fast controllable laser lysis of cells for analysis

An inexpensive, simple and easy-to-use illuminator element--consisting of chromophores, particularly fluorophores, and/or light-scattering bodies in a stable, typically a polymer plastic, matrix--completely replaces an infinite set of condensers for a optical microscope, and works equally well with microscope objective lenses of any and all numerical apertures. Illuminator elements of a fluorescent type are employed in combination with a primary source of light that is external to the illuminator element itself, and that is preferably but a simple incandescent light bulb. Nonetheless to be energized with spectrally impure light, each illuminator element produces spectrally pure light(s) of a predetermined color or colors, including a pseudo-white light. Sets of illuminator elements permit the ready production of colored light(s) of any desired spectral characteristics from primary light sources that are no more sophisticated, nor any more expensive, than common electric light bulbs. An illuminator element substantially eliminates most image artifacts while supporting imaging of a quality comparable to the best images obtainable with highest quality condensers correctly matched to the numerical aperture of a microscope's objective lens. Illumination fully comparable to Koehler illumination is obtained virtually effortlessly simply by placing an illuminator element near, and normally directly upon, a specimen that is typically mounted upon a microscope slide.

Illuminator elements for conventional light microscopes

The present invention comprises a method for use of a biosensor for in-situ microthermometry. This biosensor is a substantially spherical vesicle impregnated with a dopant which varies its optical emission spectrum as a function of the local environmental temperature of the biosensor in the temperature range to be observed. In the preferred embodiment of the present invention, this dopant is the fluorescent dye 6-dodecanoyl-2-dimethylamino-naphthalene (Laurdan.TM.). This method for in-situ measurement of temperature in a biological system uses such a vesicle by introduction of the vesicle into the biological system to be measured and manipulation of the vesicle to the location where temperature is to be measured. The temperature is then calculated from the optically measured generalized polarization at that location and the known relationship between temperature and generalized polarization for the membrane of the vesicle.

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Bonsall, CA, United States of America

Michael W Berns