Abstract: An apparatus is provided that includes a light-emitting component, a light-detecting component, a lock-in amplifier, a frequency generator that is operatively linked to the lock-in amplifier and the light-emitting component, a speaker capable of emitting an audio signal wherein the output audio signal varies depending on the detected fluorescence in the sample, and a visible output of relative fluorescent intensity where the visible output varies depending on the detected fluorescence in the sample. The apparatus may also include a laser that is operatively coupled to the lock-in amplifier through a control switch, and focusing lens or an additional type of filter such as an interference filter, a short-pass filter, a notch filter, a long-pass filter or an infrared filter. The apparatus may be used to identify and/or to remove fluorescent or non-fluorescent material from a sample. Associated methods are also disclosed.

Abstract: A disposable high-density, optically readable polydeoxynucleotide array with integral fluorescence excitation and fluorescence emission channels is described. The compact array size allows integration into several types of interventional devices such as catheters, guidewires, needles, and trocars and may be used intraoperatively. Highly sensitive monitoring of the metabolic and disease pathways of cells in vivo under varying chemical, genetic, and environmental conditions is afforded.

Abstract: A method of determining a measure of a tissue state (e.g., glycation end-product or disease state) in an individual. A portion of the tissue of the individual is illuminated with excitation light, then light emitted by the tissue due to fluorescence of a chemical with the tissue responsive to the excitation light is detected. The detected light can be combined with a model relating fluorescence with a measure of tissue state to determine a tissue state. The invention can comprise various light excitation and detection configurations. The invention also can comprise correction techniques that reduce determination errors due to detection of light other than that from fluorescence of a chemical in the tissue. Other biologic information can be used in combination with the fluorescence properties to aid in the determination of a measure of tissue state. The invention also comprises apparatuses suitable for carrying out the method.

Abstract: A method of real-time imaging of dissolved oxygen concentration, comprising adding an oxygen-quenched phosphorescent composition to a sample, exciting phosphorescence in the composition by illuminating the sample with pulses of light, detecting phosphorescence intensity as a function of position in the sample at first and second times following exciting pulses of light, determining oxygen concentration from the phosphorescence detected at the first and second times, generating an image of the oxygen concentration as a function of position, and repeating the exciting, detecting, determining, and image generating steps to produce a series of images showing the oxygen concentration varying over time.

Abstract: A non-invasive measurement of biological tissue reveals information about the function of that tissue. Polarized light is directed onto the tissue, stimulating the emission of fluorescence, due to one or more endogenous fluorophors in the tissue. Fluorescence anisotropy is then calculated. Such measurements of fluorescence anisotropy are then used to assess the functional status of the tissue, and to identify the existence and severity of disease states. Such assessment can be made by comparing a fluorescence anisotropy profile with a known profile of a control.

Abstract: This invention is generally related to a biocompatible sensor for detecting/measuring sugar, especially glucose, in an ocular fluid in a non-invasive or minimally invasive manner and a method for using the biocompatible sensor. A biocompatible sensor of the invention comprises, consists essentially, or consists of an ophthalmic device comprising a molecular sensing moiety which interacts or, reacts with sugar to provide an optical signal which is indicative of sugar level in an ocular fluid.

Abstract: The invention comprises an elongated device adapted for insertion, including self-insertion, through the body, especially the skull. The device has at least one effector or sensor and is configured to permit implantation of multiple functional components through a single entry site into the skull by directing the components at different angles. The device may be used to provide electrical, magnetic, and other stimulation therapy to a patient's brain. The lengths of the effectors, sensors, and other components may completely traverse skull thickness (at a diagonal angle) to barely protrude through to the brain's cortex. The components may directly contact the brain's cortex, but from there their signals can be directed to targets deeper within the brain. Effector lengths are directly proportional to their battery size and ability to store charge. Therefore, longer angled electrode effectors not limited by skull thickness permit longer-lasting batteries which expand treatment options.

Abstract: Disclosed are methods, compositions and kits pertaining to detecting and/or measuring biological analytes. In certain embodiments the disclosure relates to detection and measurement of lactate, pyruvate, oxygen and/or hydrogen peroxide. In some aspects and embodiments provided are biosensors that may be or include nanoparticles, microparticles and/or nano-in-micro matrices. The methods and compositions disclosed may have uses in purpose of diagnosis and treatment of diseases, fitness and health monitoring in sports, in space medicine, in food applications and the food industry, in pharmaceutical applications and the pharmaceutical industry, for fermentation monitoring, and in polymer manufacturing applications. In some embodiments and aspects, the disclosure relates to minimally invasive biosensors and/or biosensors that may be used for continuous monitoring.

Abstract: Microdialysis systems and methods that enable self-diagnostic functions for microdialysis, including continuous monitoring of diffusion, convection, and osmosis, as well as providing intelligent flow rate control, to mitigate variability in analyte recovery. The microdialysis system measures real-time tracer concentration levels in the dialysate and/or real time flow rates of the dialysate. A control circuit may compute the real-time tracer concentration levels in the dialysate and/or real-time flow rates of the dialysate based on real time tracer concentration data from an in-line tracer concentration meter and real-time flow rate data from an in-line flow rate meter. Analyte concentration data for the dialysate may also be measured using an analyte concentration meter. The control circuit may compute a corrected analyte concentration for the dialysate based on the analyte concentration data, the tracer concentration data, and the flow rate data in various embodiments.

Abstract: A system for evaluating the cardiovascular system parameters using indicator dilution and non-invasive or minimally invasive detection and calibration methods are disclosed. Intravascular indicators are stimulated, and emissions patterns detected for computation of cardiac output, cardiac index, blood volume and other indicators of cardiovascular health.

Abstract: A method of multi-spectral opto-acoustic tomography (MSOT) imaging of a target tissue including a target tissue biomarker includes illuminating the target tissue with an illumination device emitting at least one pulsed illumination pattern at several illumination wavelengths, detecting pressure signals from the target tissue biomarker with a detector device, wherein the pressure signals being produced in the target tissue are in response to the illumination, and reconstructing a quantitative tomographic image of a distribution of the target tissue biomarker in the target tissue, wherein the pressure signals are analyzed using a photon propagation model which depends on an illuminating light fluence in the target tissue and on the illumination wavelengths, at least one spectral processing scheme, and an inversion scheme providing the tomographic image.

Abstract: A photodynamic therapy system and methods determine the amount (concentration) of a photosensitizer agent present in the target tissue. The system may also determine the tissue oxygenation. The system may also determine light dosimetry parameters based on the amount of photosensitizer in the tissue and/or the tissue oxygenation.

Abstract: An in-vivo sensing device for detecting in-vivo pathology may include an illumination source for illuminating light onto a tissue external to the device and an optical system for collecting fluorescent light emitted from the tissue onto a light sensor also provided within the device. A method of detecting in-vivo pathology by collecting fluorescent light emitted from a tissue is provided.

Abstract: Systems are disclosed wherein labeled binding molecules can be provided in vivo to tissue having biomolecules that specifically bind the labeled binding molecule. A first optical radiation is emitted into the tissue in vivo to excite the labeled binding molecule bound to the biomolecule in vivo. A second optical radiation that is emitted by the excited labeled binding molecule, in response to the excitation thereof, can be detected in vivo. Related telemetric-circuits and apparatus are also disclosed.

Abstract: A sensor plaster (116) for the transcutaneous measurement of an organ function, more particularly of a kidney function, is proposed. The sensor plaster (116) comprises at least one flexible carrier element (134) having at least one adhesive surface (138) which can be stuck onto a body surface. Furthermore, the sensor plaster (116) comprises at least one radiation source, more particularly a light source (142), wherein the radiation source is designed to irradiate the body surface with at least one interrogation light (162). Furthermore, the sensor plaster (116) comprises at least one detector (146) designed to detect at least one response light (176) incident from the direction of the body surface.

Abstract: The presently-disclosed subject matter is directed to biosensors for detecting molecules of interest, and systems and methods for using same. The biosensors include an antibody and a probe covalently-linked to the antibody. The antibody has an antigen-binding site that selectively binds the molecule of interest and a purine-binding site, which is at a location distinct from that of the antigen-binding site. The probe includes a purine molecule, which is covalently bound at the purine-binding site to the antibody, and a label linked to the purine molecule. Upon binding of the molecule of interest to the biosensor antigen-binding site, the biosensor undergoes a conformational change, which detectably alters a signal of the label such that the molecule of interest can be detected.

Abstract: Disclosed herein are methods of estimating an analyte concentration which include generating a signal indicative of the analyte concentration, generating a signal indicative of a temperature, generating a signal indicative of a pH, and transforming the signal indicative of the analyte concentration utilizing an equation of the form of a modified Michaelis-Menten equation depending on Michaelis-Menten parameters, wherein values of the Michaelis-Menten parameters are set based upon data which includes temperature and pH calibration parameters, the signal indicative of a temperature, and the signal indicative of a pH. Also disclosed herein are measurement devices which employ the aforementioned methods.

Abstract: A replaceable microneedle array for a biomedical monitor is disclosed. The microneedle array includes a plurality of moveable microneedles coated with at least one chemical sensing material coupled with a porous material. The microneedle array also includes a substrate defining wells to house the microneedles. The microneedle array further includes at least one restoring spring element coupled between each microneedle and the substrate such that each of the plurality of microneedles is held at least partially in an associated well.

Abstract: Mitochondrial function is measured. Repetitive or continuous measurements are performed of prompt red fluorescence, emerging from the skin due to PpIX build up, and/or delayed fluorescence of PpIX. An estimate of the rate of PpIX generation is used as an indicator of mitochondrial integrity and ATP availability. Mitochondrial oxygen tension is determined from the delayed fluorescence lifetime of PpIX. When blood supply to the measurement volume is interrupted or reduced, the resulting changes to the mitochondrial oxygen tension allow an estimation of information about the kinetics of oxygen consumption in the mitochondria, such as the maximum rate of oxygen consumption as well as the Michaelis-Menten constant, providing information about the oxygen affinity of the mitochondrial respiratory chain.

Abstract: The present invention generally relates to systems and methods for delivering and/or withdrawing a substance or substances such as blood or interstitial fluid, from subjects, e.g., from the skin and/or from beneath the skin. In one aspect, the present invention is generally directed to devices and methods for withdrawing or extracting blood from a subject, e.g., from the skin and/or from beneath the skin, using devices containing a fluid transporter (for example, one or more microneedles), and a storage chamber having an internal pressure less than atmospheric pressure prior to receiving blood. In some cases, the device may be self-contained, and in certain instances, the device can be applied to the skin, and activated to withdraw blood from the subject. The device, or a portion thereof, may then be processed to determine the blood and/or an analyte within the blood, alone or with an external apparatus.

Abstract: Embodiments of the present invention provide for raising a background current setting for a biosensor above the actual (measured) background current present (i.e., overestimating the background current), particularly in the hypoglycemic range, to improve sensor accuracy and decrease the chance of glucose value overestimation by the sensor.

Abstract: A fluorescent agent accumulation concentration measuring apparatus is configured to include a single-wavelength LED to radiate excitation light to a test bottle loaded in the inside, a barrier filter to transmit only fluorescence from the test bottle, a photoreceptor to receive the fluorescence through the barrier filter and output an electric signal, a detection processing circuit to conduct signal processing of the electric signal from the photoreceptor and detect the fluorescence intensity, and an operation circuit 26 to compare the detection result from the detection processing circuit with an analytical pattern stored in a pattern storage portion and calculate the peak time of the accumulation concentration in a tissue of a sample in the test bottle.

Abstract: Methods and apparatuses for determining the depth and concentration of fluorophores in a turbid medium are disclosed. The method advantageously provides for a rapid estimation of the depth of the fluorophore using characteristics of a temporal point spread function. The concentration of the fluorophore can be determined using the method of the present invention by combining a calculated depth of the fluorophore with a measurement of the intensity of the emitted fluorescence. The intensity can be accurately measured by the apparatus disclosed herein which combine back-reflection and trans-illumination geometries for the source of light injecting and detection.

Abstract: Disclosed is a probe for detecting a substance in the body for detecting a substance in the body in gingival crevicular fluid. The probe includes a gingival sulcus insert section and a sensitive part. The gingival sulcus insert section can be inserted into a gingival sulcus. The sensitive part is arranged on the gingival sulcus insert section and contains a detection substance for permitting optical detection of the substance in the body. A system for detecting a substance in the body is also disclosed. The system for detecting a substance in the body includes the probe for detecting a substance in the body, a light irradiator for irradiating light onto the sensitive part in the probe, and a photodetector for detecting optical information from an inside of the sensitive part upon irradiation of light by the light irradiator.

Abstract: A saccharide-measuring fluorescence sensor substance including a copolymer of at least the following two compounds (I) and (II) is provided: (I) a fluorescent monomer compound represented by the following formula (1): formula (1) wherein: Q, Q? and D3 may be the same or different, may be combined together into a fused ring, and are each a substituent selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, and substituted or unsubstituted alkyl, acyl, oxyalkyl, carboxyl, carboxylate ester, carboxamido, cyano, nitro, amino and aminoalkyl groups; and D1, D2 and D4 each represent a substituent, wherein at least one of D1, D2 and D4 is a substituent group comprising a vinyl group at an end thereof, and wherein the substituent group comprising a vinyl group at an end thereof enables the fluorescent monomer compound to be soluble in water, and (II) at least one hydrophilic, polymerizable monomer having a vinyl group.

Abstract: Embodiments of the present invention are directed to an optical sensor capable of measuring two analytes simultaneously with a single indicator system. In preferred embodiments, the sensor comprises a fluorescent dye having acid and base forms that facilitate ratiometric pH sensing, wherein the dye is further associated with a glucose binding moiety and configured to generate a signal that varies in intensity with the concentration of glucose.

Abstract: The present invention provides an electro-optical sensing device for detecting the presence or concentration of an analyte. More particularly, the invention relates to (but is not in all cases necessarily limited to) optical-based sensing devices which are characterized by being totally self-contained, with a smooth and rounded oblong, oval, or elliptical shape (e.g., a bean- or pharmaceutical capsule-shape) and a size which permits the device to be implanted in humans for in-situ detection of various analytes.

Abstract: A fluorescence optical tomography system and method uses a photon migration model calculator for which absorption and reduced scattering coefficient values are determined for each source/detector pair. The coefficient values may be determined by measurement, in which a time resolved detector detects the excitation wavelength and generates temporal point spread functions from which the coefficient values are found. Alternatively, the coefficient values may be determined by calculating them from a dataset containing a spatial distribution of absorption and reduced scattering coefficients in a volume of interest. The fluorescence detection may be continuous wave, time resolved, or a combination of the two. An estimator uses a detected fluorescence signal and an estimated fluorescence signal to estimate the image values.

Abstract: A metabolite monitoring system configured to deliver drugs and obtain metabolite samples via one common skin perforation and measure metabolite content by way of an optical measuring-cell having a primary flow-path of constant cross-sectional area.

Abstract: Systems, devices, methods, and compositions are described for providing an actively controllable shunt configured to, for example, monitor, treat, or prevent an infection.

Abstract: A device for sensing analyte concentration, and in particular glucose concentration, in vivo or in vitro is disclosed. An optical conduit, preferably an optical fiber has an optical system at the proximal end of the optical conduit. A sensing element is attached to the distal end of the optical conduit, and comprises at least one binding protein adapted to bind with at least one target analyte. The sensing element further comprises at least one reporter group that undergoes a luminescence change with changing analyte concentrations. Optionally, the sensing element includes reference groups with luminescence properties that are substantially unchanged by variations in the analyte concentrations.

Abstract: A device for sensing analyte concentration, and in particular glucose concentration, in vivo or in vitro is disclosed. A sensing element is attached to the distal end of an optical conduit, and comprises at least one binding protein adapted to bind with at least one target analyte. The sensing element further comprises at least one reporter group that undergoes a luminescence change with changing analyte concentrations. Optionally, the optical conduit and sensing element may be housed within a cannulated bevel.

Abstract: A system and method for in vivo diagnosis are provided. A composition including for example a radioactive marking agent and a pharmaceutically acceptable carrier is administered to a patient and an autonomous in vivo device, which may include for example an illumination source an image sensor and a radiation and/or light detector, is used to for example facilitate the difference between. normal and pathological cells in a body lumen.

Abstract: A functionalized tip is incorporated into catheters for the cytometric delivery of cells into the brain and other body parts. For use in the brain, the tip forms part of a neurosurgical probe having a proximal end and a distal end. In addition to the functionalized tip, the probe has at least one cell slurry delivery lumen and a plurality of optical fibers configured along the probe, terminating in the tip to provide the photo-optical capability needed to monitor the viability and physiological behavior of the grafted cells as well as certain characteristics of the cellular environment. Details are also presented of the use of a neurocatheter having a cytometric tip of the type disclosed in the invention, as employed within the context of a feedback and control system for regulating the number of cells delivered to the brain of a patient.

Abstract: Apparatus is provided for detecting a concentration of an analyte in a subject. The apparatus includes a housing (20) adapted to be implanted in the subject. The housing (20) comprising an optical detector (30) adapted to detect a level of fluorescence resonance energy transfer (FRET). The apparatus also comprises live cells (26) genetically engineered to produce, in a patient's body, a sensor protein comprising a fluorescent protein donor, a fluorescent protein acceptor, and a binding protein for the analyte. Other embodiments are also described.

Abstract: A novel class of compounds that includes HPTS-Cys-MA, and methods of making them are disclosed herein. The class of compounds including HPTS-Cys-MA are useful as fluorescent dyes for analyte detection.

Abstract: Embodiments of the present invention are directed to an optical sensor capable of measuring two analytes simultaneously with a single indicator system. In preferred embodiments, the sensor comprises a fluorescent dye having acid and base forms that facilitate ratiometric pH sensing, wherein the dye is further associated with a glucose binding moiety and configured to generate a signal that varies in intensity with the concentration of glucose.

Abstract: Embodiments of the present invention provide for raising a background current setting for a biosensor above the actual (measured) background current present (i.e., overestimating the background current), particularly in the hypoglycemic range, to improve sensor accuracy and decrease the chance of glucose value overestimation by the sensor.

Abstract: In one aspect the present invention provides methods for assessing a physiological state of a mammalian retina in vivo, the methods of this aspect of the invention each include the steps of: (a) irradiating a portion of a mammalian retina, in vivo, with light having a wavelength in the range of from 600 nm to 1000 nm at an intensity sufficient to stimulate two-photon-induced fluorescence in the retina; and (b) assessing a physiological state of the retina by analyzing the fluorescence.

Abstract: Systems and methods are provided for probing an occluded body lumen, including a flexible conduit insertable into the body lumen, at least one delivery waveguide and at least one collection waveguide integrated with the flexible conduit and arranged to deliver and collect radiation about a distal end of said flexible conduit, at least one radiation source connected to a transmission input of the at least one delivery waveguide, at least one optical detector connected to a transmission output of at least one collection waveguide, a spectrometer connected with the at least one optical detector, and constructed and arranged to scan radiation and perform spectroscopy, and a controller programmed to process data from said spectrometer and provide information for directing said flexible conduit through obstacles within the occluded body lumen.

Abstract: Generally, the present invention is directed to a light-guided catheter for direct visualization of placement through the skin. An embodiment of the invention includes a method for transcutaneous viewing and guiding of intracorporeal catheters into a body that comprises inserting a catheter into the body having at least one lumen and internally illuminating the catheter with light capable of propagating through the blood and tissue to an external viewer outside of the body.

Abstract: A graft copolymer having metalloporphyrin ionophores covalently attached in a manner that prevents dimer formation is provided. A method of making the graft copolymer comprises polymerizing a functionalized metalloporphyrin monomer, which includes a polymerizable group, with a co-monomer. Methods for synthesizing the polymerizable metalloporphyrin monomers are provided. The graft copolymer can be incorporated into anion-selective membranes for use in anion-detecting sensors, which have improved longevity and response times.

Abstract: A noninvasive in vivo measuring system and a noninvasive in vivo measuring method are provided. In the noninvasive in vivo measuring system, a Raman-fluorescence measuring unit measures blood sugar concentration, which is measured using Raman spectra before and after applying a pressure on a finger, and outputs a final blood sugar level by correcting the blood sugar concentration measurement according to a Hemoglobin (Hb) concentration measured by an Hb measuring unit.

Abstract: The present invention relates, in general, to a system for analyzing tissue perfusion using the concentration of indocyanine green and a method of measuring the perfusion rate using the system and, more particularly, to a system for measuring tissue perfusion by injecting indocyanine green into a living body, detecting variation in the concentration of indocyanine green with the passage of time, and analyzing the detected variation, and a method of measuring the perfusion rate using the system. The present invention provides a method of measuring perfusion in a living body, which enables accurate measurement for respective regions in a wide range from a perfusion rate decreased to less than 10% of normal perfusion to a perfusion rate increased to greater than normal perfusion using the above-described mechanism of ICG in a living body, which cannot be conducted using the conventional technology.

Abstract: Nanoparticles are functionalized for use as bio-imaging probes using a novel, modular approach. Particle surface modification is based on a phosphonate monolayer platform on which was built a multi-segmented, multi-functional film: the first segment provided hydrolytic stability, the second aqueous suspendability, and the third, selectivity for cell attachment. In vitro imaging experiments visualized nanoparticle—cell surface binding. Peptide-derivatized nano-particles were not displaced from cells by soluble peptide. Methods for coating the host particles and use of rare earth ion-doped particles in imaging methods and photodynamic therapy methods are also disclosed.

Abstract: An apparatus for measuring ocular and/or blood glucose levels comprises (a) an irradiating means (10) for irradiating light onto the eye (1) of a user from outside the cornea of the eye to excite an ocular glucose sensor in contact with an ocular fluid, said sensor being able to emit a total fluorescence having first and a second wavelength bands; (b) an optical path splitting means (11) for splitting said total fluorescence into a first fluorescence and a second fluorescence, said first fluorescence and said second fluorescence traveling along first and second optical paths; (c) a first detecting means (14) located in the first optical path; (d) a second detecting means (17) located in the second optical path; (e) a calculating means for calculating the intensity ratio of the first fluorescence to the second fluorescence and for determining an ocular glucose concentration in the ocular fluid; and (f) an arithmetic means for converting the ocular glucose concentration into a blood glucose concentration.

Abstract: The spectroscopic and photophysical properties of fluorescent probes comprising donor-acceptor derivatives comprising the boric acid group or a derivative of boric acid, B(OH)3 (or borate ion, BO(OH)2?1), arsenious acid, H3 AsO3 (or arsenite ion, H2AsO3?1), telluric acid, H6TeO6 (or tellurate ion, H5 TeO6?1) or germanic acid, Ge(OH)6 (or germanate ion, GeO(OH)3?1) are described. Method of using said probes are also provided.

Abstract: A system for evaluating the cardiovascular system parameters using indicator dilution and non-invasive or minimally invasive detection methods is disclosed. Intravascular indicators are stimulated, and emissions patterns detected for computation of cardiac output, cardiac index, blood volume and other indicators of cardiovascular health.

Abstract: A microscopy system and method allow observing a fluorescent substance accumulated in a tissue. The tissue can be observed at a same time both with visible light and with fluorescent light. It is possible to observe a series of previously recorded fluorescent light images in superposition with the visible light images. An end of the series of images may be automatically determined. A thermal protective filter may be inserted into a beam path of an illuminating system at such automatically determined end of the series. Further, the fluorescent light image may be analyzed for identifying a coherent fluorescent portion thereof. A representation of a periphery line of the coherent portion may be generated, and depths profile data may be obtained only from the coherent portion. An illuminating light beam for exciting the fluorescence may be modulated for improving a contrast of fluorescent images.

Abstract: A cerebral-ischemia supervisory monitor includes: a pair of optical fibers which each have a tip part that can be placed substantially perpendicularly to an exterior surface of a cerebrum; an irradiation portion which is connected to a basic end part of one of the optical fibers, and via this optical fiber, can irradiate the exterior surface of a cerebrum with ultraviolet rays; a light-receiving portion which is connected to the basic end part of the other one of the optical fibers, and via this optical fiber, can receive fluorescence that is emitted when the ultraviolet rays excite cerebral cells; and a display portion which can display an intensity of the fluorescence.