Abstract: The invention relates to a method and a system to achieve spatially (e.g. three-dimensionally) confined photomodulation at the focal volume (50) in a ample (55) mounted in a microscope system, comprising two or more laser light sources (41, 42) emitting light (32, 34) of different wavelengths adapted to excite a material in an identical number of independent excitation steps to a higher vibrational state from which the material relaxes, either emitting a conversion light to be detected (“photoexcitation”) or modulating the spectral properties of the material (“photomodulation”).

Abstract: Functionalized second harmonic nanoprobes for imaging samples and a method of using such probes to monitor the dynamics different processes using a variety of imaging techniques are provided. The functionalized second harmonic generating (SHG) nanoprobes are comprised of various kinds of nanocrystalline materials that do not possess an inversion symmetry and therefore are capable of generating second harmonic signals that can then be detected by conventional two-photon microscopy, and are provided with functional surface modifications that allow for targeted imaging of a variety of biological and non-biological processes and structures such as cell signaling, neuroimaging, protein conformation probing, DNA conformation probing, gene transcription, virus infection and replication in cells, protein dynamics, tumor imaging and cancer therapy evaluation and diagnosis as well as quantification in optical imaging.

Abstract: Functionalized second harmonic nanoprobes for imaging samples and a method of using such probes to monitor the dynamics different processeses using a variety of imaging techniques are provided. The functionalized second harmonic generating (SHG) nanoprobes are comprised of various kinds of nanocrystalline materials that do not possess an inversion symmetry and therefore are capable of generating second harmonic signals that can then be detected by conventional two-photon microscopy, and are provided with functional surface modifications that allow for targeted imaging of a variety of biological and non-biological processes and structures such as cell signaling, neuroimaging, protein conformation probing, DNA conformation probing, gene transcription, virus infection and replication in cells, protein dynamics, tumor imaging and cancer therapy evaluation and diagnosis as well as quantification in optical imaging.

Abstract: Micro-cavity resonant sensors have outer surfaces that are functionalized using click chemistry, e.g., involving a cycloaddition reaction of an alkyne functional group and an azide functional group. A first polymer linking element binds to an outer surface of the micro-cavity and has an azide functional group, which bonds to an alkyne functional group of a second polymer linking element as a result of a cycloaddition reaction. A functionalization element such as an antibody, antigen or protein for sensing a target molecule is bound to the second linking element.

Abstract: Methods and systems for nanopillar sensors are described. Nanopillars can be defined on a substrate, and metal deposited on the nanopillars. A thermal treatment can reflow the metal on the nanopillars forming metallic bulbs on the top end of the nanopillars. These structures can have enhanced optical detection when functionalized with biological agents, or can detect gases, particles and liquids through interaction with the metal layer on the nanopillars.

Abstract: A method for noninvasive analysis of a retina includes exposing the retina to one or more first sets of at least three illumination light signals. The at least three illumination light signals each have a different wavelength. The method also includes optically collecting a reflected light signal for each of the at least three illumination light signals of the one or more first sets. Each of the reflected light signals is a portion of the respective illumination light signal reflected by the retina. The method further includes detecting the reflected light signals of the one or more first sets as a function of intensity. The method still further includes determining a first opsin density using the detected intensity of each of the reflected light signals of the one or more first sets.

Abstract: Second harmonic nanoprobes for multipurpose imaging of samples and a method of using such probes to monitor nucleotide sequencing in a Multi-SHG Detection Imaging (MSDI) modality and to monitor external electric field using voltage sensitive second harmonic generating (SHG) nanoprobes are provided. The SHG nanoprobes are comprised of various kinds of nanocrystals that do not possess an inversion symmetry and therefore are capable of generating second harmonic signals that can then be detected by conventional two-photon microscopy for in vivo imaging of biological processes and structures such as cell signaling, neuroimaging, protein conformation probing, DNA conformation probing, gene transcription, virus infection and replication in cells, protein dynamics, tumor imaging and cancer therapy evaluation and diagnosis as well as quantification in optical imaging for a wide-range of biological and non-biological processes and devices.

Abstract: The methods described herein are methods to ascertain motion contrast within optical coherence tomography data based upon intensity. The methods of the invention use logarithm operation to convert the multiplicative amplitude or intensity fluctuations (speckle) into the additive variations and recovers the motion contrasts by removing the speckle free signals (static regions) through statistical analysis.

Abstract: Resonant sensors and molecule detection methods utilizing split frequency. Optical energy is introduced into a microcavity, such as a toroid-shaped or spherical microcavity. A portion of the optical energy is backscattered and interacts with the introduced optical energy to form first and second modes of optical energy at respective first and second frequencies, also referred to as split frequency or mode doublets. One or more molecules bind to an outer surface of the microcavity and interact with an evanescent field of optical energy resonating within the microcavity. Binding of one or more molecules to the outer surface is detected based at least in part upon a change of the split frequency relative to a baseline split frequency.

Abstract: An apparatus for and method of performing light sheet microscopy (LISH) and light scanning microscopy (RAPS) in a single device are provided. The dual-mode imaging microscope allows for the use of both LISH and RAPS in a single instrument. This dual-mode device will allow researchers to have access to both types of microscopy, allowing access to the widest possible selection of samples. In addition, the device will reduce the high costs and space requirements associated with owning two different microscopes (LISH and RAPS).

Abstract: The present invention relates to the use of fluorescently labeled nucleic acid probes to identify and image analytes in a biological sample. In the preferred embodiments, a probe is provided that comprises a target region able to specifically bind an analyte of interest and an initiator region that is able to initiate polymerization of nucleic acid monomers. After contacting a sample with the probe, labeled monomers are provided that form a tethered polymer. Triggered probes and self-quenching monomers can be used to provide active background suppression.

Abstract: An apparatus for and method of performing multi-photon light sheet microscopy (MP-LISH), combining multi-photon excited fluorescence with the orthogonal illumination of light sheet microscopy are provided. With live imaging of whole Drosophila and zebrafish embryos, the high performance of MP-LISH compared to current state-of-the-art imaging techniques in maintaining good signal and high spatial resolution deep inside biological tissues (two times deeper than one-photon light sheet microscopy), in acquisition speed (more than one order of magnitude faster than conventional two-photon laser scanning microscopy), and in low phototoxicity are demonstrated. The inherent multi-modality of this new imaging technique is also demonstrated second harmonic generation light sheet microscopy to detect collagen in mouse tail tissue. Together, these properties create the potential for a wide range of applications for MP-LISH in 4D imaging of live biological systems.

Abstract: The methods described herein are methods to ascertain motion contrast within optical coherence tomography data based upon phase variance. The phase variance contrast observes the nanometer scale motion of scatterers associated with Brownian motion and other non-flow motion. The inventive method of calculating motion contrast from the phase variance can differentiate regions of different mobility based on the motion contrast differences, and can use the phase information to characterize mobility properties of the scatterers. In flow regions, the inventive method for acquiring and analyzing motion contrast can identify the regions as well as characterize the motion. Furthermore, the inventive method can determine quantitative flow estimation, the index of refraction variations, and absorption variations within flow regions.

Abstract: A biofunctionalized nanoelectromechanical device (BioNEMS) for sensing single-molecules in solution by measuring the variation in the mechanical displacement of the BioNEMS device during a binding event is provided. The biofunctionalized nanoelectromechanical device according to the invention generally comprises a nanomechanical mechanical resonator, a detector integral with the mechanical resonator for measuring the mechanical displacement of the resonator, and electronics connected to the detector for communicating the results to a user. A system of biofunctionalized nanoelectromechanical devices and a method for utilizing the biofunctionalized nanoelectromechanical device of the present invention are also provided.

Abstract: Micro-cavity gas or vapor sensors and gas or vapor detection methods. Optical energy is introduced into a resonant micro-cavity having a deformable coating such as a polymer. The coating swells or expands when it is exposed to or absorbs a gas or vapor, thereby changing the resonant wavelength of optical energy circulating within the micro-cavity/coating. Expansion or swelling of the coating may be reversible such that it contracts when gas or vapor diffuses from the coating. The coating deformation and/or a change of one or more optical properties of the optical energy circulating within the micro-cavity are used to detect the presence of the gas or vapor or molecules or particulates thereof.

Abstract: The present invention relates generally to the field of magnetic resonance imaging and, more particularly, to devices and methods used in the observation of the diffusion of molecules across a permeable membrane using magnetic resonance techniques. A typical embodiment of the invention is a method of observing the diffusion of a molecule in a container having a permeable membrane that is disposed between a first solution and a second solution in the container, by using magnetic resonance imaging to obtain an image of the diffusion of the molecule in the first solution across the membrane in to the second solution.

Abstract: The present invention relates to the use of fluorescently labeled nucleic acid probes to identify and image analytes in a biological sample. In the preferred embodiments, a probe is provided that comprises a target region able to specifically bind an analyte of interest and an initiator region that is able to initiate polymerization of nucleic acid monomers. After contacting a sample with the probe, labeled monomers are provided that form a tethered polymer. Triggered probes and self-quenching monomers can be used to provide active background suppression.

Abstract: Second harmonic nanoprobes for imaging biological samples and a method of using such probes to monitor the dynamics of biological process using a field resonance enhanced second harmonic (FRESH) technique are provided. The second harmonic generating (SHG) nanoprobes are comprised of various kinds of nanocrystals that do not possess an inversion symmetry and therefore are capable of generating second harmonic signals that can then be detected by conventional two-photon microscopy for in vivo imaging of biological processes and structures such as cell signaling, neuroimaging, protein conformation probing, DNA conformation probing, gene transcription, virus infection and replication in cells, protein dynamics, tumor imaging and cancer therapy evaluation and diagnosis as well as quantification in optical imaging.

Abstract: Micro-cavity gas or vapor sensors and gas or vapor detection methods. Optical energy is introduced into a resonant micro-cavity having a deformable coating such as a polymer. The coating swells or expands when it is exposed to or absorbs a gas or vapor, thereby changing the resonant wavelength of optical energy circulating within the micro-cavity/coating. Expansion or swelling of the coating may be reversible such that it contracts when gas or vapor diffuses from the coating.

Abstract: Micro-cavity resonant sensors have outer surfaces that are functionalized using click chemistry, e.g., involving a cycloaddition reaction of an alkyne functional group and an azide functional group. A first polymer linking element binds to an outer surface of the micro-cavity and has an azide functional group, which bonds to an alkyne functional group of a second polymer linking element as a result of a cycloaddition reaction. A functionalization element such as an antibody, antigen or protein for sensing a target molecule is bound to the second linking element.