Abstract: A microendoscope, and a microendoscopy method related to the microendoscope, each include a tube housing, where an end of the tube housing is shaped and finished to facilitate collection of light emitted from a sample when examined using the microendoscope. In addition, a catadioptric lens assembly, an endomicroscope that includes the catadioptric lens assembly and a microendoscopy method for microscopic analysis that uses the endomicroscope are predicated upon a second element and a third element within the catadioptric lens assembly that each has a dichroic coating. The placement of the dichroic coating on the second element and the third element provides for different magnification factors as a function of illumination wavelength when using the microendoscopy method.

Abstract: An optical lens comprising a lens body that transmits light in an optical path there through, wherein the lens body consists of an anterior surface, a posterior surface, and a medium there between, further wherein one of the anterior surface and the posterior surface has a single curvature and the other of the anterior surface and the posterior surface has at least two optical zones each having a different curvature. An optical system, comprising a multi-photon endoscope having a distal end, and the optical lens disposed in the distal end. A method for obtaining an image of an object comprising providing the multi-photon endoscope, propagating light from the endoscope scanner one optical zone of the lens to focus the light at a focus location, and propagating light from the scanner through a different optical zones of the lens to focus the light at a different focus location.

Abstract: A microendoscope, and a microendoscopy method related to the microendoscope, each include a tube housing, where an end of the tube housing is shaped and finished to facilitate collection of light emitted from a sample when examined using the microendoscope. In addition, a catadioptric lens assembly, an endomicroscope that includes the catadioptric lens assembly and a microendoscopy method for microscopic analysis that uses the endomicroscope are predicated upon a second element and a third element within the catadioptric lens assembly that each has a dichroic coating. The placement of the dichroic coating on the second element and the third element provides for different magnification factors as a function of illumination wavelength when using the microendoscopy method.

Abstract: An optical apparatus that provides extraordinary light transmission through a sub-wavelength-sized light transmitting region of the apparatus includes a core region of dielectric material having a complex dielectric constant, ?1, surrounded by a metallic cladding material having a complex dielectric constant, ?2, wherein the core region has a maximum dimension, 2a, further wherein 2a is less than ?, where ? is the free-space wavelength of light incident on an input side of the apparatus, and further wherein |?1| is greater than 0.5|?2|, ?1 has a positive real part, and ?2 has a negative real part, whereby the incident light will be transmitted by and exit the apparatus from an output side with extraordinary transmission.

Abstract: An optical scanner, scanner apparatus, or scanner assembly, which may be particularly advantageous for use in a multiphoton microscope, includes a first drivable bending component, a second drivable bending component mounted perpendicularly to the first component, and at least one optical waveguide coupled one or both of the first and second bending components, wherein the at least one optical waveguide provides both a propagation path for a multiphoton excitation radiation delivery between a light source and a target and a multiphoton-induced emission radiation delivery between the target and a detector. A GRIN relay lens. A multiphoton microscope incorporating the scanner and the GRIN relay lens.

Abstract: An optical scanner, scanner apparatus, or scanner assembly, which may be particularly advantageous for use in a multiphoton microscope, includes a first drivable bending component, a second drivable bending component mounted perpendicularly to the first component, and at least one optical waveguide coupled one or both of the first and second bending components, wherein the at least one optical waveguide provides both a propagation path for a multiphoton excitation radiation delivery between a light source and a target and a multiphoton-induced emission radiation delivery between the target and a detector. A GRIN relay lens. A multiphoton microscope incorporating the scanner and the GRIN relay lens.

Abstract: Embodiments of the invention include an optical system and an optical system module, coupled to a distal end of a fluorescence emission endoscope apparatus, an optical waveguide-based fluorescence emission endoscopy system, and a method for remotely-controlled, multi-magnification imaging of a target or fluorescence emission collection from a target with a fluorescence emission endoscope apparatus. An exemplary system includes an objective lens disposed in a distal end of an endoscope apparatus. The lens is adapted to transmit both a visible target illumination and a fluorescence-emission-inducing target illumination as well as fluorescence-emission and visible light from the target. The system can thus simultaneously provide low magnification, large field of view imaging and high magnification, high-resolution multiphoton imaging with a single lens system.

Abstract: An optical lens comprising a lens body that transmits light in an optical path there through, wherein the lens body consists of an anterior surface, a posterior surface, and a medium there between, further wherein one of the anterior surface and the posterior surface has a single curvature and the other of the anterior surface and the posterior surface has at, least two optical zones each having a different curvature. An optical system, comprising a multi-photon endoscope having a distal end, and the optical lens disposed in the distal end. A method for obtaining an image of an object comprising providing the multi-photon endoscope, propagating light from the endoscope scanner one optical zone of the lens to focus the light at a focus location, and propagating light from the scanner through a different optical zones of the lens to focus the light at a different focus location.

Abstract: The invention generally relates to fluorescent nanoparticles and more specifically to silica-based fluorescent nanoparticles of less than 30 nm with covalently attached organic dyes. The invention provides a fluorescent monodisperse silica nanoparticle comprising fluorophore center core and a silica shell wherein the radiative properties of the nanoparticle are dependent upon the chemistry (composition) of the core and presence of the silica shell. In one aspect of the invention, the core-shell architecture provides an enhancement in fluorescence quantum efficiency. The invention generally provides control of photophysical properties of dye molecules encapsulated within silica particles with sizes down to 30 nm and below. This control is accomplished through changes in silica chemistry and particle architecture on the nanometer size scale and results in significant brightness enhancement compared to free dye.

Abstract: An optical scanner, scanner apparatus, or scanner assembly, which may be particularly advantageous for use in a multiphoton microscope, includes a first drivable bending component, a second drivable bending component mounted perpendicularly to the first component, and at least one optical waveguide coupled one or both of the first and second bending components, wherein the at least one optical waveguide provides both a propagation path for a multiphoton excitation radiation delivery between a light source and a target and a multiphoton-induced emission radiation delivery between the target and a detector. A GRIN relay lens. A multiphoton microscope incorporating the scanner and the GRIN relay lens.

Abstract: An optical apparatus that provides extraordinary light transmission through a sub-wavelength-sized light transmitting region of the apparatus includes a core region of dielectric material having a complex dielectric constant, ?1, surrounded by a metallic cladding material having a complex dielectric constant, ?2, wherein the core region has a maximum dimension, 2a, further wherein 2a is less than ?, where ? is the free-space wavelength of light incident on an input side of the apparatus, and further wherein |?1| is greater than 0.5|?2|, ?1 has a positive real part, and ?2 has a negative real part, whereby the incident light will be transmitted by and exit the apparatus from an output side with extraordinary transmission.

Abstract: The present invention is directed to a method of sequencing a target nucleic acid. The method provides a complex comprising a polymerase enzyme, a target nucleic acid molecule, and a primer, wherein the complex is immobilized on a support Fluorescent label is attached to a terminal phosphate group of the nucleotide or nucleotide analog. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The time duration of the signal from labeled nucleotides or nucleotide analogs that become incorporated is distinguished from freely diffusing labels by a longer retention in the observation volume for the nucleotides or nucleotide analogs that become incorporated than for the freely diffusing labels.

Abstract: The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid. Each type of labeled nucleotide comprises an acceptor fluorophore attached to a phosphate portion of the nucleotide such that the fluorophore is removed upon incorporation into a growing strand. Fluorescent signal is emitted via fluorescent resonance energy transfer between the donor fluorophore and the acceptor fluorophore as each nucleotide is incorporated into the growing strand. The sequence is deduced by identifying which base is being incorporated into the growing strand.

Abstract: The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site.

Abstract: Apparatus and methods relating to non-imaging, multiphoton fluorescence and optical second harmonic generation (SHG) (and higher harmonic generation) emission and detection. A weakly focused excitation beam is used to generate fluorescence emission in a volume of between about 0.1 cm3 to one cubic centimeter (1 cm3), which is significantly larger than the conventional MPM focal volume. A method for shaping and/or controlling (confining) the focal volume of a non-imaging, fluorescence emission excitation field in a target medium involves decoupling the axial dimension dependence of the focal volume from the lateral spot size of the excitation field. The method involves the step of spatially separating at least some of the spectral components of a short duration, multichromatic excitation field outside of the focal volume and spatially recombining the spectral components in a short duration, high intensity, weakly focused field incident on the target medium.

Abstract: Embodiments of the invention include an optical system and an optical system module, coupled to a distal end of a fluorescence emission endoscope apparatus, an optical waveguide-based fluorescence emission endoscopy system, and a method for remotely-controlled, multi-magnification imaging of a target or fluorescence emission collection from a target with a fluorescence emission endoscope apparatus. An exemplary system includes an objective lens disposed in a distal end of an endoscope apparatus. The lens is adapted to transmit both a visible target illumination and a fluorescence-emission-inducing target illumination as well as fluorescence-emission and visible light from the target. The system can thus simultaneously provide low magnification, large field of view imaging and high magnification, high-resolution multiphoton imaging with a single lens system.

Abstract: The present invention is directed to a method of applying radiation through an optical fiber for detecting disease within a plant or animal or other penetrable tissue, or imaging a particular tissue of a plant or animal. In addition, fluorescence and nonlinear scattering signals can be detected and localized within a subject by such application of radiation through an optical fiber. The radiation is effective to promote simultaneous multiphoton excitation. The optical fibers are used alone to examine internal regions of tissue, in conjunction with an optical biopsy needle to evaluate sub-surface tissue, or with an endoscope to evaluate tissue within body cavities. The present invention also relates to a device for coupling in radiation from an ultrashort mode-locked laser into the beam path of a microscope.

Abstract: The present invention is directed to a method of detecting a neurodegenerative disease in a mammal by activating brain tissue of the mammal by application of radiation under conditions effective to promote a simultaneous multiphoton excitation of the brain tissue and to emit a fluorescence characteristic. The fluorescence characteristic is then compared to a standard fluorescence emitted by exciting healthy brain tissue of the mammal under the same conditions used to carry out the activating step. Brain tissue where the fluorescence characteristic differs from the standard fluorescence is identified as potentially having a neurodegenerative disease. Another aspect of the present invention is directed to a method of producing an image of brain tissue from a mammal by activating brain tissue of a mammal with radiation applied under conditions effective to promote a simultaneous multiphoton excitation of the brain tissue and to produce fluorescence.

Abstract: The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site.

Abstract: The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site.