ПОРТАТИВНОЕ УСТРОЙСТВО ДЛЯ ПРОВЕРКИ АЛКОГОЛЬНОГО НАПИТКА ЧЕРЕЗ КОНТЕЙНЕР, СИСТЕМА И СВЯЗАННЫЙ С НИМИ СПОСОБ

Изобретение относится к области аутентификации содержимого, такого как напитка, в частности алкогольного напитка. Заявленное портативное устройство для проверки алкогольного напитка в по меньшей мере частично прозрачном контейнере содержит: одиночный источник света, выполненный с возможностью испускания луча монохромного возбуждающего света, имеющего длину волны в диапазоне от 350 до 650 нм; разделитель луча, сориентированный под 45° относительно направления испускания источника света для отражения луча возбуждающего света; фокусную и собирающую линзу; позиционирующее устройство, обеспечивающее ориентацию луча света, исходящего от источника света, по направлению, по существу нормальному к внешней поверхности контейнера. Причем позиционирующее устройство также обеспечивает позиционирование внешней поверхности контейнера на заранее определенном расстоянии от фокусной линзы, при этом заранее определенное расстояние между фокусной линзой и контейнером выбрано таким образом, что луч света сфокусирован ...

СЕНСОР С АКТИВНОЙ ПОВЕРХНОСТЬЮ

Изобретение относится к биологическим и химическим исследованиям аналита. Проточная ячейка содержит подложку, содержащую контактную площадку подложки, сенсор, расположенный сверху подложки и содержащий активную поверхность и контактную площадку сенсора, пассивирующий слой, расположенный сверху активной поверхности сенсора, при этом пассивирующий слой содержит реакционные углубления, формовочный слой, расположенный сверху подложки и покрывающий боковые стороны сенсора, причем формовочный слой имеет высоту формовки относительно верхней поверхности подложки, при этом высота формовки больше высоты активной поверхности сенсора относительно верхней поверхности подложки, и покровный слой, расположенный сверху достаточным образом плоской верхней поверхности формовочного слоя и сверху активной поверхности, при этом покровный слой и формовочный слой вместе образуют промежуток над активной поверхностью сенсора, определяющий проточный канал. Изобретение обеспечивает возможность создания небольшой и ...

ИСТОЧНИК СВЕТА С НАСТРОЕННЫМ СПЕКТРАЛЬНЫМ РАСПРЕДЕЛЕНИЕМ

Группа изобретений относится к медицинской технике. Прожектор белого света для обнаружения люминесценции, например биомаркера, содержит: по меньшей мере один твердотельный светоизлучающий элемент для излучения первичного света и множество преобразующих длину волны материалов для преобразования части первичного света во вторичный свет, выполненное в виде массива независимых преобразующих длину волны областей, при этом различные преобразующие длину волны области содержат преобразующие материалы, создающие различные полосы/пики излучения вторичного света, при этом каждый преобразующий материал выполнен с возможностью преобразования первичного света во вторичный свет, и при этом каждый преобразующий длину волны материал выполнен с возможностью вносить вклад в спектр общего излучения по меньшей мере одной полосой/пиком излучения, а общее излучение вторичного света, обеспеченное упомянутыми преобразующими материалами, предусматривает широкополосный спектр излучения, за исключением по меньшей ...

УСТРОЙСТВО ДЛЯ ОДНОВРЕМЕННОГО КОНТРОЛЯ В РЕАЛЬНОМ МАСШТАБЕ ВРЕМЕНИ МНОЖЕСТВА АМПЛИФИКАЦИЙ НУКЛЕИНОВОЙ КИСЛОТЫ

Изобретение относится к устройствам для качественного и количественного анализа нуклеиновых кислот (ДНК и РНК), которые могут быть использованы в медицинской практике при диагностике инфекционных, онкологических и генетических заболеваний человека и животных, в исследовательских целях при молекулярно-биологических, генетических исследованиях, при мониторинге экспрессии генов. В устройстве использован метод полимеразной цепной реакции (ПЦР) в реальном времени. Устройство для одновременного контроля в реальном масштабе времени множества амплификаций нуклеиновой кислоты содержит термоциклер, включающий теплопроводящий элемент с расположенными в нем углублениями для пробирок с реакционными смесями, термокрышку, теплоизолирующую перегородку и устройство автоматического управления температурным режимом, оптическую систему, включающую источник излучения, коаксиальный волоконно-оптический световод для передачи света возбуждения от источника к пробиркам и от пробирок с реакционными смесями к детектору ...

СВЕТОВОДНЫЙ ТЕСТОВЫЙ ДАТЧИК ДЛЯ ОПРЕДЕЛЕНИЯ ИССЛЕДУЕМОГО ВЕЩЕСТВА В ПРОБЕ ФЛЮИДА (ВАРИАНТЫ) И СПОСОБЫ ЕГО ИЗГОТОВЛЕНИЯ (ВАРИАНТЫ)

Изобретение относится к измерительной технике. Оптический световодный тестовый датчик содержит световод, покрытую реагентом мембрану и сетчатый слой, при этом покрытая реагентом мембрана и сетчатый слой прикреплены к световоду на его выходной концевой части. Световодный тестовый датчик используется для тестирования уровня исследуемого вещества в пробе биологической жидкости совместно со считывающей головкой. Способ изготовления световодного тестового датчика включает обеспечение совокупности световодов, обеспечение полоски покрытой реагентом мембраны и обеспечение полоски сетчатого слоя. Покрытая реагентом мембрана и сетчатый слой прикрепляются к световодам посредством ультразвуковой сварки. Покрытая реагентом мембрана и сетчатый слой могут также прикрепляться к световодам с помощью клеящего элемента. Технический результат - повышение точности тестирования. 8 н. и 6 з.п. ф-лы, 7 ил.

Способ многоцветной иммуноцитохимической диагностики паранеоплазии шейки матки

Изобретение относится к медицине, а именно к лабораторной диагностике, и может быть использовано для многоцветной иммуноцитохимической диагностики паранеоплазии шейки матки. Осуществляют получение клеточной суспензии клинического материала, окрашивание флуоресцентным красителем с последующей флуоресцентной микроскопией. Клеточную суспензию добавляют к смеси антител, специфически направленных к белкам Р16/Р16INK4a, Ki67 и EpCAM/clone BerEp4, меченых флуоресцентными красителями различной длины волны. Смесь включает антитела к белку Ki67, конъюгированные с флуорофором с длиной волны красного спектра, антитела к белку EpCAM/clone BerEp4, конъюгированные с флуорофором с длиной волны зеленого спектра, и антитела к белку Р16/Р16INK4a, конъюгированные с флуорофором с длиной волны синего спектра. Инкубируют в темном месте при комнатной температуре в течение 10-15 минут. После инкубации осуществляют флуоресцентную микроскопию смеси антител и клеточной суспензии, не дожидаясь высыхания. При обнаружении ...

СВЕТОВОДНЫЙ ТЕСТОВЫЙ ДАТЧИК ДЛЯ ОПРЕДЕЛЕНИЯ ИССЛЕДУЕМОГО ВЕЩЕСТВА В ПРОБЕ ФЛЮИДА И СПОСОБЫ ЕГО ИЗГОТОВЛЕНИЯ

... 1. Оптический световодный тестовый датчик, содержащий световод, имеющий входную концевую часть и выходную концевую часть; покрытую реагентом мембрану, расположенную на выходной концевой части световода и прикрепленную к световоду, при этом реагент вступает в реакцию с пробой жидкости для индикации уровня исследуемого вещества в пробе; и сетчатый слой, прикрепленный к мембране. 2. Оптический световодный тестовый датчик, содержащий световод, имеющий входную концевую часть и выходную концевую часть, а также выступы, расположенные на выходной концевой части; сетчатый слой, прикрепленный к выступам на световоде, при этом выступы образуют зазор между выходной концевой частью и сетчатым слоем, и указанный зазор приспособлен для втягивания пробы при использовании датчика; и покрытую реагентом мембрану, прикрепленную к сетчатому слою, расположенному на выходной концевой части световода, реагент которой вступает в реакцию с пробой жидкости для индикации уровня исследуемого вещества в пробе. 3. Способ ...

БЕСКОНТАКТНАЯ СИСТЕМА ИДЕНТИФИКАЦИИ ЯИЦ ДЛЯ ОПРЕДЕЛЕНИЯ ЖИЗНЕСПОСОБНОСТИ ЯИЦ С ИСПОЛЬЗОВАНИЕМ ТРАНСМИССИОННОЙ СПЕКТРОСКОПИИ И СВЯЗАННЫЙ С НЕЙ СПОСОБ

Группа изобретений относится к области идентификации яиц. Система идентификации яиц для определения жизнеспособности птичьего яйца содержит конвейерную систему для перемещения лотка, содержащего яйца, узел излучателя для испускания электромагнитного излучения по направлению к одному из яиц, бесконтактный узел детектора, установленный соосно с узлом излучателя и имеющий спектрометр, процессор, выполненный для обмена данными со спектрометром и для обработки выходного сигнала бесконтактного узла детектора для определения жизнеспособности яйца. При этом бесконтактный узел детектора выполнен с возможностью детектирования электромагнитного излучения, прошедшего через яйцо, и расположен в бесконтактном положении таким образом, что яйцо, расположенное для идентификации, пространственно отделено от бесконтактного узла детектора во время его работы. Также раскрывается система идентификации яиц, содержащая массив пар излучатель-детектор, а также варианты способов определения жизнеспособности яиц.

Способ многоцветной иммуноцитохимической диагностики паранеоплазии шейки матки

Изобретение относится к медицине, а именно к лабораторной диагностике, и может быть использовано для многоцветной иммуноцитохимической диагностики паранеоплазии шейки матки. Осуществляют получение клеточной суспензии клинического материала, окрашивание флуоресцентным красителем с последующей флуоресцентной микроскопией. Клеточную суспензию добавляют к смеси антител, специфически направленных к белкам Р16/Р16INK4a, Ki67 и EpCAM/clone BerEp4, меченых флуоресцентными красителями различной длины волны. Смесь включает антитела к белку Ki67, конъюгированные с флуорофором с длиной волны красного спектра, антитела к белку EpCAM/clone BerEp4, конъюгированные с флуорофором с длиной волны зеленого спектра, и антитела к белку Р16/Р16INK4a, конъюгированные с флуорофором с длиной волны синего спектра. Инкубируют в темном месте при комнатной температуре в течение 10-15 минут. После инкубации осуществляют флуоресцентную микроскопию смеси антител и клеточной суспензии, не дожидаясь высыхания. При обнаружении ...

СПОСОБ И УСТРОЙСТВО ДЛЯ ПЛАНИРОВАНИЯ СКАНИРОВАНИЯ С ИСПОЛЬЗОВАНИЕМ УЛЬТРАФИОЛЕТОВОГО ИЗЛУЧЕНИЯ

... 1. Способ определения местоположения образца ткани, по существу, круглой формы, размещенного на твердом носителе, включающий:подачу света заданной длины волны на образец ткани, в котором этот свет вызывает автофлуоресценцию;идентификацию местоположения центра образца ткани на основе автофлуоресцентного света;корреляцию координат местоположения центра образца ткани на твердом носителе на основе двумерной системы координат; исоставление карты координат образца ткани на твердом носителе для различения областей, содержащих образец ткани, и незаполненных областей на твердом носителе.2. Способ по п.1, в котором этап идентификации включает захват автофлуоресцентного света от образца ткани для создания его цифрового изображения.3. Способ по п.1, в котором этап корреляции включает оценивание пиксельных значений автофлуоресцентного света от образца ткани.4. Способ по п.3, в котором оценивание пиксельных значений включает преобразование пространственной пиксельной информации цифрового изображения ...

КОРРЕКЦИЯ ФАЗИРОВАНИЯ

Anordnung zur Messung der NADH-Eigenfluoreszenz von Zellkulturen

Hochleistungsfluoreszenzbildgebungsmodul für Assays zur genomischen Testung

Bildgebungssystem, umfassend:a) zwei verschiedene, axial versetzte Oberflächen;b) eine Objektivlinse; undc) mindestens einen Bildsensor, wobei das Bildgebungssystem eine numerische Apertur (NA, numerical aperture) von weniger als 0,6 und ein Sichtfeld (FOV, field of vision) von mehr als 1,0 mm2aufweist, und wobei das Bildgebungssystem Bilder der zwei verschiedenen, axial versetzten Oberflächen aufnehmen kann, die im Wesentlichen die gleiche optische Auflösung aufweisen, ohne einen optischen Kompensator in einen Strahlengang zwischen der Objektivlinse und dem mindestens einen Bildsensor zu bewegen.

Mehrfarbige-Fluoreszenz-Analysevorrichtung

Eine Mehrfarbige-Fluoreszenz-Analysevorrichtung 1 gemäß der vorliegenden Erfindung ist mit Folgendem versehen: einer Bestrahlungseinheit 41 zum Einstrahlen von Anregungslicht mit mehreren Anregungswellenlängenbändern auf eine Probe s, einer ersten faseroptischen Platte 424 zum Leiten von Licht einschließlich der von der Probe s durch die Bestrahlung mit dem Anregungslicht emittierten Fluoreszenz und zum Emittieren von diesem von einem ersten Emissionsteil 425b, einer zweiten faseroptischen Platte 431 zum Empfangen vom ersten Emissionsteil 425b emittierten Lichts an einem zweiten Einfallsteil 434a, zum Leiten von diesem und zum Emittieren von diesem von einem zweiten Emissionsteil 434b, einem einzelnen Dielektrischer-Mehrschichtfilm-Interferenzfilter 432, das an einer Endfläche des zweiten Emissionsteils 434b bereitgestellt ist, zumindest einen Teil der Fluoreszenz durchlässt und Licht aus mehreren Transmissionswellenlängenbändern, welche die Anregungswellenlängenbänder nicht einschließen ...

Measurement of different fluorescence spectra on object in case of age-related degeneration of lens with cataract by exciting object region for fluorescence and their confocal imaging on inlet slit of spectrograph

An object is illuminated for a fluorescence excitation simultaneously with spatially separated and chromatically different excitation rays. The object region/ranges excited for the fluorescence are confocally imaged on an inlet slit of a spectrograph. The fluorescence spectra obtained from the same detector system are then registered. A field aperture (12) is formed as slit-shaped and confocal to entry slit (25) and the separating location between the different-wavelength filter ranges (14,15) of excitation filter (13) is made as light impermeable. An Independent claim is included for: (a) a device for measuring of different fluorescence spectra of an object ...

Anordnung zur Erkennung des Vorhandenseins von Pathogenen

Bei der Anordnung zur Erkennung des Vorhandenseins von Pathogenen auf einer Oberfläche eines flächigen Substrats weist eine Oberfläche des Substrats lokal definiert eine multivariate Oberflächenstruktur mit voneinander abweichenden Größen, Geometrien und/oder Ausrichtungen von 2- bis 3-dimensionalen Strukturelementen auf, wobei die einzelnen Strukturelemente eine laterale Ausdehnung im Bereich 10 nm bis 50 µm aufweisen. Es sind eine Lichtquelle zur Bestrahlung der 2- bis 3-dimensional strukturierten Oberfläche sowie mehrere Detektoren, die zur orts- und spektral aufgelösten Erfassung der an der 2- bis 3-dimensional strukturierten Oberfläche gestreuten, reflektierten und/oder transmittierten elektromagnetischen Strahlung vorhanden. Die Detektoren sind mit einer elektronischen Auswerteeinheit verbunden, die zur Auswertung von mit den Detektoren orts- und spektralaufgelösten Intensitäten der gestreuten, reflektierten, transmittierten elektromagnetischen Strahlung, welche durch Streu-, Absorptions ...

Method of determining the degree of freshness of food products is based on the wavelength and radiation intensity of emitted florescent radiation

The method is used to determine how fresh a food product is. The method uses at least one power source from which energy is directed to the item to be examined in such a manner that the item is caused to autofluoresce and emit florescent radiation. A detector detects the florescent radiation emitted from the item. The emitted radiation generates detector signals in the detector in dependence on the wavelength of the radiation and/or radiation intensity. The detector signals are compared with reference values and, taking a quality criterium as a basis, provide an indication of the degree of freshness of the food product. An independent claim is also included for an apparatus for carrying out the method.

Integrated electrochemical and optical sensor with inductor

Electrochemical and luminescent sensor structures integrated on common substrate

A method of analysing a sample of biological material that includes modifying fluorescent labels in the sample or the environmental conditions of the sample

A method or apparatus for analysing a sample of biological material that includes fluorescent labels. The apparatus uses a processing means. The method comprises the steps of: a) irradiating the sample with excitation energy; b) detecting fluorescent radiation emitted from the labels in the sample; c) Modifying either of: fluorescent labels in the sample or the environmental conditions of the sample with the apparatus in response to a user input after irradiation step (a) or in response to analysis by the processing means after the step (b). The modification in the step (c) may comprise irradiation of a portion of the sample with an energy beam such that the fluorescence of the labels in that portion is reduced. Steps (a) to (c) may be repeated, whereby the time period of repetition may depend on the analysis by the by the processing means. The modification of step (c) may involve modifying optical properties of photo-switchable labels, or it may include forming an opening in a membrane ...

Mutant apoprotein of photoprotein with low calcium sensitivity

Skin-print fluorescence analysis method and apparatus

Diagnostic Apparatus

A diagnostic apparatus for in vivo diagnosis of disease, optionally an ophthalmological disease and/or a tumour. The apparatus comprises: a monochromator 6 configured to receive light containing a range of wavelengths and create a plurality of substantially continuous bandwidths of light across an excitation range of a biological target 14; a direction means configured to focus the light created by the monochromator on the target in vivo; a detection means 24 configured to detect autofluorescence emitted by the target upon exposure to each bandwidth; and a processing means 26 configured to diagnose disease based upon the detected autofluorescence. The apparatus may be configured to diagnosis a tumour situated on the skin or in a lung. The direction means may focus the monochromator light on the eye or eyelid for diagnosing an ophthalmological disease based upon detected autofluorescence. The apparatus may be configured to detect one or more micro-organisms such as amoeba, bacterium such ...

Skin-print fluorescence analysis method and apparatus

Improvements to fluid borne particle analysers

Method and device

The presence or concentration of analyte (1, Fig. 1) in liquid sample 2 is determined from quenching of an autofluorescence signal of substrate 4, perhaps in lateral flow device 37. Substrate 4 may be inherently fluorescent, not comprising added fluorophores, and may be porous, formed from fibres of cellulose, nitrocellulose, lignin, collagen, cotton or silk. Analyte may be selectively bound by quenching substance 10, which causes quenching of the substrate autofluorescence signal and which may comprise gold nanoparticles, at conjugate pad 39. Analyte quenching complexes 17 may be selectively bound by immobilised binding agent 8 at test region 7. Autofluorescence may be excited by light from an emitter absorbed in a first wavelength range. Analyte concentration may be determined from quenching of the autofluorescence signal combined with absorbance of the quenching substance, measured by photodetectors.

Mehtods and compositions that utilize transciptome sequencing data in machine learning-based classification

Method and device

System for spore detection

VERFAHREN UND VORRICHTUNG ZUR AUTOMATISCHEN ANALYSE VON BIOLOGISCHEN PROBEN

FLUORIMETRI MULTI-PARAMETER ANALYSIS IN A PARALLEL MULTI-FOCUS ARRANGEMENT

PROCEDURE FOR THE REGULATION OF RIPE ONES AND QUALITY OF PLANT SEEDS AND DEVICE FOR SORTING THE SAME

Rapid thermal cycling for sample analyses and processing

Apparatus and method for thermal processing of nucleic acid in a thermal profile is provided. The apparatus employs a reactor holder for holding reactor(s) each accommodating reaction material containing the nucleic acid. The apparatus comprises a first bath; and a second bath, bath mediums in the baths being respectively maintainable at two different temperatures T ...

Time-resolved laser-induced fluorescence spectroscopy systems and uses thereof

The invention provides systems for characterizing a biological sample by analyzing emission of fluorescent light from the biological sample upon excitation and methods for using the same. The system includes a laser source, collection fibers, a demultiplexer and an optical delay device.

Biosensor for simultaneous detection of zearalenone and ochratoxin A , preparation and detection method thereof

Abstract The invention displays a biosensor for simultaneous detection of zearalenone (ZEN) and ochratoxin A (OTA) , and it is a preparation and detection method thereof. The invention belongs to the technical field of detecting harmful substances. The biosensor was fabricated with ZEN aptamers, OTA aptamer and graphene oxide. The innovation of the biosensor is that it can not only detect ZEN and OTA without interfering with each other at the same time, but also has high sensitivity. Compared with other biosensors, the present invention has the following benefits: simple operation steps, low-cost and short detection time. 70 - l 512nm d 60 * 0 499nm ZEN OTA AFBI AFM1 FB Patulin sample Figure 7 ...

Methods for spectrally resolving fluorophores of a sample and systems for same

Aspects of the present disclosure include methods for spectrally resolving light from fluorophores having overlapping fluorescence spectra in a sample. Methods according to certain embodiments include detecting light with a light detection system from a sample having a plurality of fluorophores having overlapping fluorescence spectra and spectrally resolving light from each fluorophore in the sample. In some embodiments, methods include estimating the abundance of one or more of the fluorophores in the sample, such as on a particle. In certain instances, methods include identifying the particle in the sample based on the abundance of each fluorophore and sorting the particle. Methods according to some embodiments includes spectrally resolving the light from each fluorophore by calculating a spectral unmixing matrix for the fluorescence spectra of each fluorophore. Systems and integrated circuit devices (e.g., a field programmable gate array) for practicing the subject methods are also provided ...

Image reconstruction method and device, and microscope imaging device

Provided are an image reconstruction method and device, and a microscope imaging device. The method involves: calculating the gray-scale value of each optical fiber center in an optical fiber bundle (04) in a reconstructed image according to a gray-scale value, at the position of each optical fiber center, determined from one or more sample images; and using the gray-scale value of the optical fiber center to perform spatial interpolation to obtain the gray-scale values of other pixel points in the optical fiber bundle (04) in the reconstructed image so as to form the reconstructed image. In the image reconstruction method, gray-scale values of pixel points of an entire image are obtained merely by means of calculating the gray-scale values of pixel points at the positions of optical fiber centers and based on spatial interpolation, thereby reducing the calculation amount for calculating a gray-scale value of each pixel point, and greatly accelerating the rate of image reconstruction. Furthermore ...

A method for the presumptive detection of substances

A method and apparatus for monitoring a condition in chlorophyll containing matter

Apparatus and method for non-invasively detecting diseases that affect structural properties in biological tissues

Apparatus and methods for spectroscopic analysis of biological tissues to classify an individual as diabetic or non-diabetic, or to determine the probability, progression or level of a disease or medical condition in an individual.

Apparatus for single-molecule detection

An apparatus for detecting an object capable of emitting light. The apparatus includes a light source (102) and a waveguide (110). The waveguide (110) includes a core layer (112) and a first cladding layer (114). At least one nanowell (120) is formed in at least the first cladding layer (114). The apparatus further includes a light detector (106). The light detector (106) can detect light emitted from a single molecule object contained in the at least one nanowell (120).

Method to increase the number of detectable photons during the imaging of a biological marker

The present invention relates a method to determine the presence of a photon producing biological marker in a cell, tissue or organism of interest. The method is based on Fluorescence by Unbound Excitation from Luminescence (FUEL) and comprises the steps of a) providing conditions suitable for the biological marker to produce at least one first photon by luminescence; b) providing a FUEL probe pair-upper (FPP-U) disposed in proximity to the cell, tissue or organism, wherein the at least one first photon of step a) excites the FPP-U, which emits at least one second photon. The FPP-U may be selected from the group of quantum dots, carbon nanotubes, fluorescent proteins, diamond nanocrystals and metalloporphyrins. This method is charcterized in that said biological marker and said FPP-U are not bound and in that each of the at least one second photon (s) are of a longer wavelength than each of the at least one first photon (s).

Method for evaluating toxicity of chemical using alga

Provided is a method for evaluating the toxicity of a chemical using an alga, comprising: (a) a thawing step for thawing frozen alga cells by heating, and diluting a suspension of the thus obtained cells by adding a medium thereto; (b) a recovery culture step for culturing the alga cells obtained in the thawing step to thereby recover the alga cells from the effects of freezing and thawing; (c) a confirmation step for collecting a portion of the alga cells after the recovery culture step, diluting the same by adding a medium, measuring the delayed luminescence of the alga cells, and then regarding the obtained luminescence dose as to the initial data; (d) an exposure step for mixing the alga cells after the confirmation step with a solution containing a test substance to give an exposure sample, and then culturing the exposure sample; (e) a measurement step for measuring the delayed luminescence of the exposure sample after the exposure step, and regarding the obtained luminescence dose ...

System and method for detecting and classifying biological particles

Method and apparatus for portable product authentication

Non-fluorescent quencher compounds and biomolecular assays

Fluorescent proteins, nucleic acids encoding them and methods for making and using them

Methods and systems for point-of-care coagulation assays by optical detection

This invention relates to an optical system and method for performing turbidity assay, e.g. coagulation of blood or plasma, comprising a standard optical reference (78), a sample handling structure (88), a light source (96) and an optical detection unit (94). The standard optical reference (78), such as a fluorophore-doped glass, provides constant optical signal under controlled optical conditions. The sample handling structure (88), such as a microfluidic system with reaction chamber, can be placed beneath or above the standard optical reference (78). During operation, the coagulating plasma/blood changes its optical absorbance and reflection properties, which results in changes in optical signal that reaches the optical reading unit (94). The variation of the optical signal, such as fluorescence signal indicates the kinetics of the turbidity varying process, such as plasma/blood coagulation process. This invention is used for performing turbidity assay with optical system, including photometry ...

METHODS FOR RAPID MULTIPLEXED AMPLIFICATION OF TARGET NUCLEIC ACIDS

Abstract A fast, multiplexed PCR system is described that can rapidly generate amplified nucleic acid products, for example, a dull SDTR profile, from a target nucleic acid. Such systems include, for example, microfluidic biochips and a custom built thermal cycler, which are also described. The resulting STR profiles can satisfy forensic guidelines for signal strength, inter-loci peak height balance, heterozygous peak height ratio, incomplete non-template nucleotide addition, and stutter. 2143555v1 ...

Fluorometer with multiple detection channels

An optical sensor may have multiple detection channels to detect different characteristics of a fluid. For example, an optical sensor used in industrial cleaning and sanitizing applications may have multiple detection channels to detect when a system is both clean and properly sanitized. In one example, an optical sensor includes an optical emitter that directs light into a fluid, a first optical detector that detects light transmitted through the fluid, a second optical detector that detects light scattered by the fluid, and a third optical detector that detects fluorescent emissions emitted by the fluid. The optical emitter and optical detectors can be positioned around an optical analysis area. Depending on the application, the optical emitter may be positioned to direct light adjacent a wall of the optical analysis area rather than at a center of the optical analysis area, which may increase the strength of signal on the detection channels.

Recognition of cellular target binding by a bioactive agent using intracellular bioluminescence resonance energy transfer

The present invention provides compositions and methods for detection and analysis of intracellular binding of a bioactive agent to a cellular target. In particular, provided herein are bioactive agents tethered to fluorophores, cellular targets fused to bioluminescent reporters, or portions, components, or subunits of bioluminescent reporters, and methods of detecting and analyzing the interaction of bioactive agents with cellular targets therewith.

Viability staining method

The invention relates to a method of detecting viable cells in a cell sample, using a membrane permeable fluorescent label that permeates both viable and non- viable cells and a membrane impermeant quencher that selectively permeates non-viable cells.

System and method for controlling depth of imaging in tissues using fluorescence microscopy under ultraviolet excitation following staining with fluorescing agents

The present disclosure relates to a method for analyzing tissue specimens. In one implementation the method involves obtaining a tissue sample and exposing the sample to one or more fluorophores as contrast agents to enhance contrast of subcellular compartments of the tissue sample. The tissue sample is illuminated by an ultraviolet (UV) light having a wavelength between about 200 nm to about 400 nm, with the wavelength being selected to result in penetration to only a specified depth below a surface of the tissue sample. Inter-image operations between images acquired under different imaging parameters allow for improvement of the image quality via removal of unwanted image components. A microscope may be used to image the tissue sample and provide the image to an image acquisition system that makes use of a camera. The image acquisition system may create a corresponding image that is transmitted to a display system for processing and display.

Luminescence imaging scanner

Systems, devices, and methods for accurately imaging chemiluminescence and other luminescence are disclosed. A compact, flat-bed scanner having a light-tight enclosure, one or more detector bars of linear charge-coupled device (CCD) or complementary metal oxide semiconductor (CMOS) imaging chips, and high working numerical aperture (NA) optics scans closely over a sample in one direction and then the opposite direction. Averages or other combinations of intensity readings for each pixel location (x, y) between the two or more passes are averaged together in order to compensate for luminescence that varies over time. On-chip pixel binning and multiple clock frequencies can be used to maximize the signal to noise ratio in a CCD-based scanner.

Method and apparatus for sensing the presence of microbes

SYSTEM AND METHOD FOR DETECTING AND CLASSIFYING BIOLOGICAL PARTICLES

A continuous wave laser excites a biological particle. Detection channels are created to detect light scattered by the biological particle, and to detect any auto~fluorescence emitted by the biological particle. Additional channels can also detect light emitted by auto-fluorescence of the biological particle when simultaneously excited by light at harmonics of the laser's fundamental wavelength. The biological particle is identified using Mie scattering and auto~fluorescence. Ratio-metric calculations generated by calculating ratios of detected peak heights or integrated pulse values in the channels provides additional information for identifying and classifying the biological particle. A warning or alert can be provided if the identified biological particle is a particle of interest.

DETECTION DEVICE AND METHODS OF USE

An imaging system for exciting and measuring fluorescence on or in samples comprising fluorescent materials (e.g. fluorescent labels, dyes or pigments). In one embodiment, a device is used to detect fluorescent labels on nucleic acid. In a preferred embodiment, the device is configured such that fluorescent labels in a plurality of different DNA templates are simultaneously detected.

SERIAL-LINE-SCAN-ENCODED MULTI-COLOR FLUORESCENCE MICROSCOPY AND IMAGING FLOW CYTOMETRY

A system for performing high-speed, high-resolution imaging cytometry utilizes a line-scan sensor. A cell to be characterized is transported past a scan region. An optical system focuses an image of a portion of the scan region onto at least one linear light sensor, and repeated readings of light falling on the sensor are taken while a cell is transported though the scan region. The system may image cells directly, or may excite fluorescence in the cells and image the resulting light emitted from the cell by fluorescence. The system may provide a narrow band of illumination at the scan region. The system may include various filters and imaging optics that enable simultaneous multicolor fluorescence imaging cytometry. Multiple linear sensors may be provided, and images gathered by the individual sensors may be combined to construct an image having improved signal-to-noise characteristics.

AMYLOID BINDING AGENTS

There are provided compounds and methods for the detection of amyloids and treatment of diseases related to amyloids including Alzheimer's disease and other related amyloid-based neurodegenerative diseases.

CELLULAR LIBRARIES OF PEPTIDE SEQUENCES (CLIPS) AND METHODS OF USING THE SAME

METHOD OF ASSESSING SKIN AND OVERALL HEALTH OF AN INDIVIDUAL

The present invention relates to a method of determining skin health of an area of skin and overall health of an individual by exposing the area of skin to a first exposure radiation to induce the area of skin to emit a first fluorescent emission, measuring the intensity of the first fluorescent emission, exposing the area of skin to a second exposure radiation to induce the area of skin to emit a second fluorescent emission, measuring the intensity of the second fluorescent emission, calculating a ratio of these intensities, and comparing the ratio to a control ratio.

IMAGE RECONSTRUCTION METHOD, DEVICE AND MICROSCOPIC IMAGING DEVICE

Provided are an image reconstruction method and device, and a microscope imaging device. The method involves: calculating the gray-scale value of each optical fiber center in an optical fiber bundle (04) in a reconstructed image according to a gray-scale value, at the position of each optical fiber center, determined from one or more sample images; and using the gray-scale value of the optical fiber center to perform spatial interpolation to obtain the gray-scale values of other pixel points in the optical fiber bundle (04) in the reconstructed image so as to form the reconstructed image. In the image reconstruction method, gray-scale values of pixel points of an entire image are obtained merely by means of calculating the gray-scale values of pixel points at the positions of optical fiber centers and based on spatial interpolation, thereby reducing the calculation amount for calculating a gray-scale value of each pixel point, and greatly accelerating the rate of image reconstruction. Furthermore ...

SYSTEMS AND METHODS FOR DETECTION OF CONTAMINANTS ON SURFACES

A contaminant detection system for a portable computer with the computer having a camera, an integral screen and central processing unit (CPU; a. an enclosure having at least one grasper disposed for coupling the system to the portable computer; b. a light emitter capable of generating light of with least one excitation wavelength for a contaminant present in its output spectrum with output of the emitter oriented into the field of view of the camera; c. electronic communication between the computer and the emitter; c. software loaded onto the computer capable of (1) activating the emitter, (2) comparing a scene recorded by the camera to at least one emission wavelength for the specific contaminant corresponding to the excitation wavelength, and (3) displaying an output on the computer's screen corresponding to the areas within the camera's field of view where the contaminant is present in amounts greater than a detection threshold.

METHOD AND APPARATUS FOR SPECTROSCOPIC ANALYSIS, IMPLEMENTNG INFRARED AND FLUORESCENCE MULTICHANNEL PROCESSING OF SPECTRAL DATA

Procédé d'analyse d'au moins un échantillon, mettant en oeuvre une méthode d'analyse de données spectroscopiques basée sur un modèle statistique multivoies, comportant : a) l'éclairage dudit ou de chaque échantillon à analyser par une première source de lumière et par une deuxième source de lumière, ladite au moins une deuxième source de lumière étant distincte de ladite première source de lumière; b) l'acquisition de spectres de fluorescence dudit ou de chaque échantillon, lesdits spectres de fluorescence résultant de l'éclairage dudit ou de chaque échantillon par un ou plusieurs rayonnements lumineux émis par ladite première source de lumière; c) l'acquisition de spectres de transmittance et/ou de réflectance dudit ou de chaque échantillon, lesdits spectres de transmittance et/ou de réflectance résultant de l'éclairage dudit ou de chaque échantillon par un ou plusieurs rayonnements lumineux émis par ladite deuxième source de lumière; d) l'organisation desdits spectres de fluorescence ...

INTEGRATED DEVICE FOR DETECTING AND ANALYZING MOLECULES

System and methods for analyzing single molecules and performing nucleic acid sequencing. An integrated device may include multiple pixels with sample wells configured to receive a sample, which when excited, emits radiation. The integrated device includes a surface having a trench region recessed from a portion of the surface and an array of sample wells, disposed in the trench region. The integrated device also includes a waveguide configured to couple excitation energy to at least one sample well in the array and positioned at a first distance from a surface of the trench region and at a second distance from the surface in a region separate from the trench region. The first distance is smaller than the second distance. The system also includes an instrument that interfaces with the integrated device. The instrument may include an excitation energy source for providing excitation energy to the integrated device by coupling to an excitation energy coupling region of the integrated device ...

POINT-OF-CARE NUCLEIC ACID AMPLIFICATION AND DETECTION

Devices are disclosed for amplifying and detecting analytes, including oligonucleotide targets. The devices may be used for point of care nucleic acid testing. Methods and assays of using the devices are also disclosed.

DETECTION OF CELLS IN A LIQUID SAMPLE

The invention relates to a method for counting cells, such as bacteria and/or somatic cells in liquid samples, such as in dairy products, preferably raw milk. Disclosed is a method comprising a combination of steps that apply dimeric nucleic acid dyes that normally do not penetrate cells (=cell-impermeant dyes), which are rendered cell-permeant by using the right combination of pH, buffer and temperature.

SYSTEMS AND METHODS FOR DISTINGUISHING FERTILE PLANT SPECIMENS FROM STERILE PLANT SPECIMENS

Analyzing reflections and/or emissions of electromagnetic radiation to distinguish fertile plant specimens from sterile plant specimens. In an aspect, the presence of wavelengths associated with pollen in the electromagnetic radiation reflections and/or emissions indicates a plant specimen is fertile, and the absence of wavelengths associated with pollen in the reflections and/or emissions indicates a plant specimen is sterile. In other aspects, spectral signature differences in the reflections and/or emissions that are indicative of other properties besides pollen (e.g., petal color, etc.) are utilized to distinguish between fertile and sterile plant specimens.

METHOD AND APPARATUS FOR PORTABLE PRODUCT AUTHENTICATION

A method and apparatus for on-site verification of product authentication and quality includes a microplate having a substrate with a light-emissive compound thereon. The substrate provides immobilization of the light-emissive compounds and provides a three-dimensional environment similar to free solution for reactions with the product sample to occur. The microplate may include any material having desired light reflective properties and a surface to retain the light-emissive compounds therein. A metered amount of light- emissive compound is placed on the microplate by any desired metering method, such as hand-metering by skilled technicians, automatic metering using robotic equipment, or printing using for example, piezoelectric dispensing technology. In this respect, the light-emissive compound is placed on a microplate, with the microplate. Once the light-emissive compound is applied to the substrate, the microplate may be sent to the test site where product testing is to be performed ...

FAST THERMO-OPTICAL PARTICLE CHARACTERISATION

The present invention relates to a method and an apparatus for a fast thermo-optical characterisation of particles. In particular, the present invention relates to a method and a device to measure the stability of (bio)molecules, the interaction of molecules, in particular biomolecules, with, e.g. further (bio)molecules, particularly modified (bio)molecules, particles, beads, and/or the determination of the length/size (e.g. hydrodynamic radius) of individual (bio)molecules, particles, beads and/or the determination of length/size (e.g. hydrodynamic radius).

3D REFRACTIVE INDEX TOMOGRAPHY AND STRUCTURED ILLUMINATION MICROSCOPY SYSTEM USING WAVEFRONT SHAPER AND METHOD THEREOF

An ultra-high-speed 3D refractive index tomography and structured illumination microscopy system using a wavefront shaper and a method using the same are provided. A method of using an ultra-high-speed 3D refractive index tomography and structured illumination microscopy system that utilizes a wavefront shaper includes adjusting an irradiation angle of a plane wave incident on a sample by using the wavefront shaper, measuring a 2D optical field, which passes through the sample, based on the irradiation angle of the plane wave, and obtaining a 3D refractive index image from information of the measured 2D optical field by using an optical diffraction tomography or a filtered back projection algorithm.

ANALYSIS OF COMPOUNDS FOR PAIN AND SENSORY DISORDERS

The invention generally relates to optical methods for characterizing the effects of compounds on pain and other sensory phenomena. The effect of compounds on pain and other sensory phenomena may be characterized using dorsal root ganglion (DRG) neurons or sensory neurons expressing optogenetic proteins that allow neural activity to be stimulated and detected optically. The invention provides cell-based optical assays for studying the molecular and cellular bases of pain and sensory phenomena and as platforms to screen and validate drugs, e.g., for pre-clinical trials.

NON-CONTACT EGG IDENTIFICATION SYSTEM FOR DETERMINING EGG VIABILITY USING TRANSMISSION SPECTROSCOPY, AND ASSOCIATED METHOD

An egg identification system (100) for determining viability of an avian egg (1) is provided. Such a system (100) includes an emitter assembly (200) configured to emit electromagnetic radiation toward an egg (1). A detector assembly (300) is axially aligned with the emitter assembly (200) to detect electromagnetic radiation transmitted through the egg (1). The detector assembly (300) is spaced-apart from the egg (1) during operation thereof such that the detector assembly (300) does not contact the egg (1). The detected electromagnetic radiation is processed using transmission spectroscopy analysis, such as infrared spectroscopy or fluorescence spectroscopy, to determine whether the egg (1) is viable, e.g. non dead, rotted or clear. An associated method is also provided.

MULTIPLEX BEAD ARRAY ASSAY

The present disclosure relates to a system, method, and kit for particle detection and analysis. Devices disclosed herein may include at least an optical source, a fludic chip containing a multiplex bead array, and a detection module, wherein the sample flows within the fludic chip past a detection window, where the cells or particles are imaged by an image acquisition and analysis module that may include an optical detector. The image acquisition and analysis module counts the labeled particles and software allows for analysis of bead population.

EVALUATION OF CAS9 MOLECULE/GUIDE RNA MOLECULE COMPLEXES

Disclosed herein are methods for evaluation, selection, optimization, and design of Cas9 molecule/gRNA molecule complexes.

FLUOROMETER WITH MULTIPLE DETECTION CHANNELS

An optical sensor may have multiple detection channels to detect different characteristics of a fluid. For example, an optical sensor used in industrial cleaning and sanitizing applications may have multiple detection channels to detect when a system is both clean and properly sanitized. In one example, an optical sensor includes an optical emitter that directs light into a fluid, a first optical detector that detects light transmitted through the fluid, a second optical detector that detects light scattered by the fluid, and a third optical detector that detects fluorescent emissions emitted by the fluid. The optical emitter and optical detectors can be positioned around an optical analysis area. Depending on the application, the optical emitter may be positioned to direct light adjacent a wall of the optical analysis area rather than at a center of the optical analysis area, which may increase the strength of signal on the detection channels.

FLUOROMETER WITH MULTIPLE DETECTION CHANNELS

An optical sensor may have multiple detection channels to detect different characteristics of a fluid. For example, an optical sensor used in industrial cleaning and sanitizing applications may have multiple detection channels to detect when a system is both clean and properly sanitized. In one example, an optical sensor includes an optical emitter that directs light into a fluid, a first optical detector that detects light transmitted through the fluid, a second optical detector that detects light scattered by the fluid, and a third optical detector that detects fluorescent emissions emitted by the fluid. The optical emitter and optical detectors can be positioned around an optical analysis area. Depending on the application, the optical emitter may be positioned to direct light adjacent a wall of the optical analysis area rather than at a center of the optical analysis area, which may increase the strength of signal on the detection channels.

COMPARING THE STRUCTURES OF TWO BIOMOLECULES

The present disclosure provides methods to assess structural similarity of a first biomolecule and a second biomolecule by detecting one or more responses of the first and second biomolecule to thermodynamic stress conditions induced by osmotic and dielectric changes including, detecting a shift in fluorescence emission and /or a change in the intensity of the emission.

APPARATUS AND METHOD FOR ANALYZING BIOLOGICAL INDICATORS

A biological indicator analyzer includes a plurality of wells, a plurality of organism detector features, and a user input feature such as a touch screen. Each well is configured to receive a respective biological indicator. Each organism detector feature is configured to detect whether a biological indicator disposed in a corresponding well of the plurality of wells contains a living organism. The touch screen is configured to receive user input and provide information to the user indicating a status of biological indicator analysis. The biological indicator analyzer may be used to analyze a biological indicator that was positioned in a sterilization chamber of a sterilizing cabinet along with at least one medical device that is to be sterilized. The analysis may indicate whether the sterilization cycle in the sterilization chamber as successful.

PLASTIC MICROFLUIDIC SEPARATION AND DETECTION PLATFORMS

Plastic electrophoresis separation chips are provided comprising a plural ity of microfluidic channels and a detection window, where the detection win dow comprises a thin plastic; and the detection window comprises a detection region of each microfluidic channel. Such chips can be bonded to a support provided an aperture is provided in the support to allow detection of sample s in the electrophoresis chip at the thin plastic detection window. Further, methods for electrophoretically separating and detecting a plurality of sam ples on the plastic electrophoresis separation chip are described.

METHODS FOR IDENTIFYING STEM CELLS BY DETECTING FLUORESCENCE OF CELLS AND SYNCYTIA

Methods are disclosed for the characterization of the stage of development or pathology of a tissue sample, and for identifying pluripotent metakaryotic stem cells, comprising detecting fluorescence of cells and syncytia in fixed samples treated with a non-fluorescent Schiff's base reagent in the absence of extraneous or exogenously added fluorescent dyes.

SPECTROSCOPIC FINGER-PRINTING OF RAW MATERIAL

Herein is reported a method for the selection of cultivation component batches to be used in the cultivation of a mammalian cell expressing a protein of interest wherein at least two different components are employed in the cultivation comprising the following steps: a) providing spectra of different batches of a first component obtained with a first spectroscopic method and spectra of a second component obtained with a second different spectroscopic method and the cultivation supernatant yield of the protein of interest obtained in a cultivation using combinations of these different batches of the first and the second component, b) processing the spectra, filtering the spectra, smoothing the spectra, and transforming the spectra to their first derivative, c) identifying patterns in the spectra, d) identifying a relation of the patterns identified in d) with the yield of the cultivation, e) providing a spectrum of a further batch of the first component obtained with the first spectroscopic ...

MEASURING MULTI-ANALYTE SAMPLES USING AN IN-LINE FLOW CELL

Methods and systems for analyzing ratios of analytes within a flowing sample are provided. The flowing sample can be processed in real-time to determine a time interval over which a predetermined amount of a group of analytes passes by a fixed point in a flow cell. The predetermined amount can be routed to a sample container for future processing. The sample can comprise diluted blood and the analytes can comprise a component of hemoglobin, such as A1c, and the total amount of hemoglobin, of which the predetermined amount is metered.

A METHOD AND DEVICE FOR DETERMINING CONTENT OF THE MIDDLE AND PROTEIN BOUND UREMIC TOXINS IN A BIOLOGICAL FLUID

This invention relates to a novel method and a device for determining middle and protein bound uremic toxins in the biological fluids. More specifically, the present invention relates to an optical method utilizing fluorescence, preferable fluorescence of the spent dialysate, and a specific model, including a unique set of optical spectral components at certain wavelengths, to determine, preferable on-line, the concentration of the middle and protein bound uremic toxins such as beta2-microglobulin (B2M), and indoxyl sulfate (IS).

CYTOLOGICAL METHOD USING THE AUTO FLUORESCENCE OF WHITE CORPUSCLES FOR THE EARLY DIAGNOSIS AND THE MONITORING OF INFECTIONS

La présente invention concerne une méthode in vitro pour diagnostiquer l'état infectieux d'un individu à partir d'un échantillon de globules blancs issu d'un prélèvement biologique d'un organe potentiellement infecté par un micro-organisme pathogène dudit individu, comprenant au moins les deux étapes suivantes : i) mesurer l'intensité cellulaire moyenne de l'autofluorescence dudit échantillon, et ii) comparer l'intensité mesurée à l'étape i) avec une valeur contrôle, de manière à déterminer l'état infectieux dudit individu. La méthode diagnostique de l'invention utilise un matériel optique de routine permettant de travailler dans des domaines de longueurs d'onde compatibles avec l'autofluorescence cellulaire, et constitue ainsi une aide rapide, fiable et peu coûteuse au diagnostic ou au suivi d'une infection chez un individu.

METHOD AND SYSTEM FOR PORTABLE CELL DETECTION AND ANALYSIS USING MICROFLUIDIC TECHNOLOGY

The present invention is a method and a system of cell detection and analysis. The present invention may incorporate at least an optical source, a fluidic chip and a detection module. Cells may be caused to flow within the fluidic chip and specifically past a detection window section accessible by the optical source. The flowing cells may be identified and/or analyzed. The detection module may specifically count the cells of interest as they flow past the detection window section of the chip. The detection module may further be operable to generate or otherwise capture images of the cells as they flow past the window and to use these images collectively for the purpose of analyzing the cells. The present invention may be portable and operable in remote locations.

A METHOD AND APPARATUS THAT UTILISES FLUORESCENCE TO DETERMINE PLANT OR BOTANICAL ORIGIN CHARACTERISTICS OF HONEY

Method for determining the botanical origin of honey: (a) estimating the botanical origin of standard honey samples, by: (i) obtaining key chemical concentrations; (ii) assigning the botanical origin as a value on the abundance of chemical compounds characteristic of botanical groups; (b) generating the fluorescence signature of standard honey samples, by: (i) measuring the intensity and wavelength of the fluorescent light emitted from a diluted light-excited honey solution; (ii) combining excitation and emitted light as 2-dimensional excitation-emission matrix (EEM); (c) constructing a predictive mathematical model from standard honey data; (d) generate the fluorescence EEM signature of an unknown honey sample or samples, as outlined in step (b); and (e) using the unknown honey fluorescence EEM data from step (d) with the mathematical model of step (c) to predict and assign value of botanical origin of honey.

NOVEL SUBSTRATES THE FLUORESCENCE OF WHICH IS SUPPRESSED, PREPARATION THEREOF, AND USE THEREOF FOR IDENTIFYING, DETECTING, AND ASSAYING LEGIONELLA PNEUMOPHILIA

La présente invention concerne d'une façon générale l'utilisation d'un peptide R-(X)n-Fluo-Rep -(Gly)m-Z-NH2 pour détecter et doser l'activité de la protéase Msp de Legionella pneumophila. Ladite invention a aussi pour objet un nouveau procédé de détection et de quantification de Legionella pneumophila dans tout milieu susceptible d'être contaminé par cette bactérie, par exemple les eaux chaudes sanitaires et les circuits des tours aéroréfrigérantes.

PLANT PHENOMETRICS SYSTEMS AND METHODS AND DEVICES RELATED THERETO

Chlorophyll fluorescence may be studied in response to a variety of environmental cues or conditions by growing phototrophic organisms under actinic illumination. Such illumination may be punctuated or disrupted to gain information about the photosynthetic properties or performance of the phototrophic organism. Instruments or devices for carrying out the method are also described.

METHODS FOR RAPID MULTIPLEXED AMPLIFICATION OF TARGET NUCLEIC ACIDS

... ²²A fast, multiplexed PCR system is described that can rapidly generate ²amplified nucleic acid ²products, for example, a full STR profile, from a target nucleic acid. Such ²systems include, for ²example, microfluidic biochips and a custom built thermal cycler, which are ²also described. The ²resulting STR profiles can satisfy forensic guidelines for signal strength, ²inter-loci peak height ²balance, heterozygous peak height ratio, incomplete non-template nucleotide ²addition, and ²stutter.² ...

MAN-PORTABLE DEVICE FOR DETECTING HAZARDOUS MATERIAL

A man portable device for detecting the presence of hazardous material includes a pulsed or time-modulated light source and an objective scannable across the surface of a sample for projecting light from the light source onto a succession of spots on the surface of the sample. A spectrometer performs a spectral analysis of the induced fluorescence to create a first dataset defining a first vector as a function of wavelength. A time domain detector for measuring the time decay of the induced fluorescence collected simultaneously creates a second dataset defining a second vector as a function of time. A computer identifies hazardous material by performing independent multivariate analysis on the first and second vectors as the objective is scanned across the sample surface based on fluorescent signal models for hazardous materials in the spectral and time domains.

MEASUREMENT OF SALIVA FLUORESCENCE INTENSITY AS AN INDICATOR OF RENAL IMPAIRMENT

A method is disclosed for the measurement of the fluorescence intensity of human saliva samples as a screening procedure for the differentiation of renal function versus renal failure. The method is based upon saliva being an alternative route for the elimination of fluorescent metabolites that accumulate during renal failure.

ADVANCED SYNCHRONOUS LUMINESCENCE SYSTEM

A method and apparatus for determining the condition of tissue or otherwise making chemical identifications includes exposing the sample to a light source (22), and using a synchronous luminescence system (38, 50) to produce a spectrum that can be analyzed for tissue condition.

Verfahren und Vorrichtung zur unterscheidenden Identifizierung und Analyse mikrobiologischer Systeme

Durchflusskammer an einem automatischen Mess- und Zählgerät für die Teilchen einer Dispersion

Procedure and micro disk reader for investigation of biological cells or cell cultures.

Ein Verfahren zum Untersuchen von biologischen Zellen oder Zellkulturen in einem Mikroplatten-Reader (1) umfasst das Aufnehmen von zumindest einer Mikroplatte (2) mit biologischen Zellen oder Zellkulturen enthaltenden Wells (3) mit einer Aufnahmeeinrichtung (4); das Positionieren dieser Wells (3) gegenüber Aktionsquellen (5´, 5´´, 5´´´); das Herbeiführen einer Wechselwirkung zwischen Aktionsquellen (5´,5´´,5´´´) und Zellen oder Zellkulturen in bestimmten Wells (3) zum Hervorrufen oder Erzeugen eines messbaren Signals; das Positionieren der Wells (3) gegenüber Messeinrichtungen (5´´, 6, 7, 8) des Mikroplatten-Readers (1) und das Erfassen von integralen Mess-Signalen mit zumindest einer der Messeinrichtungen (5´´, 6, 7, 8). Mit einer Beleuchtungsquelle (9) des Mikroplatten-Readers (1) werden die biologischen Zellen oder Zellkulturen in den bestimmten Wells (3) der Mikroplatte(n) (2) beleuchtet und mit einer bildgebenden Kamera (10) abgebildet. Mit einem Prozessor (11´, 11´´) wird jedes der ...

Control of the gas atmosphere in micro disk readers.

Betrifft einen Mikroplatten-Reader (1) und ein entsprechendes Verfahren, wobei der Mikroplatten-Reader (1) zumindest eine Messeinrichtung (2´,2´´,2´´´) und eine Aufnahmeeinrichtung (5) zur Aufnahme von zumindest einer Mikroplatte (4) und zum Positionieren der Proben enthaltenden Wells (3) dieser Mikroplatte(n) (4) gegenüber der zumindest einen Messeinrichtung (2´,2´´,2´´´) umfasst. Die zumindest eine Messeinrichtung (2´,2´´,2´´´) dient zum Detektieren von Licht, das von Proben in Wells (3) einer in diesen Mikroplatten-Reader (1) eingesetzten Mikroplatte (4) ausgesendet wird, und/oder das von mit Licht durchstrahlten Proben in Wells (3) einer in diesen Mikroplatten-Reader (1) eingesetzten Mikroplatte (4) beeinflusst wird. Der erfindungsgemässe Mikroplatten-Reader (1) ist dadurch gekennzeichnet, dass er eine Kontrolleinheit (6) zur Steuerung der Zusammensetzung einer Gasatmosphäre (7) um die den Proben enthaltenden Wells (3) von in diesen Mikroplatten-Reader (1) eingesetzten Mikroplatten ...

СПОСОБ ОБРАБОТКИ НАБОРОВ ФЛУОРЕСЦЕНТНЫХ ИЗОБРАЖЕНИЙ И УСТРОЙСТВО ДЛЯ ЕГО ОСУЩЕСТВЛЕНИЯ

В заявке описаны способ и устройство, предназначенные для обработки флуоресцентных частичных изображений, представляющих одну и ту же область объекта, и работающие независимо от постороннего света. С помощью камеры (10) создают два частичных изображения объекта в красном и зеленом цветах. Из этих двух частичных изображений попиксельно формируют изображение-частное, и для этого изображения-частного определяют, с какой частотой встречаются точки изображения, имеющие заданное отношение красного и зеленого цветов. Для полученной таким образом кривой распределения определяют среднее значение и ширину. Эти две конечные величины кривой распределения используют для вычисления порогового значения. Затем с применением этого порогового значения модифицируют изображение-частное таким образом, чтобы повысить контраст в отношении интересующих деталей.

System for creation of formulations and generation of denaturation graphs

A system for automatically creating a denaturation curve is disclosed. In accordance with certain embodiments, a movement system including a unit having a plurality of cannulas is used. The cannulas are in fluid communication with a fluid system, which allows the cannulas to draw in and dispense fluid. A measurement system is included which draws fluid from a well into a detector to determine a characteristic of the fluid. A controller is used to control these systems and also to create a denaturation graph from the measured characteristics. In another embodiment, a plurality of formulations may be created using the system.

Method and detection system for detection of aflatoxin in corn with fluorescence spectra

A system and method for fluorescence spectral imaging of target material to detect the presence of a contaminant (such as aflatoxin in corn) is provided. An ultraviolet light source is coupled a light-excluding compartment. The fluorescence from the UV excited target passes through a filter (liquid crystal tunable, acoustic-optic tunable, a filter wheel, or other wavelength splitting device) and a lens, to a spectral imaging camera. Fluorescence spectral image data from the camera is analyzed by a computer and presented in human-readable form. Aflatoxin detection in contaminated corn kernels is based on peak fluorescence and peak fluorescence shift in the spectral range from 451 nm to 500 nm. Aflatoxin contamination level within the target material is quantified based on peak fluorescence and peak fluorescence shift and computed corn kernel pixel statistics.

Kits for assaying enzyme-mediated oxidative demethylation

Methods of assaying enzyme-mediated oxidative demethylation are provided according to embodiments of the present invention which includes combining, under reaction conditions, an oxidative demethylation enzyme, a substrate for the oxidative demethylation enzyme and a formaldehyde detection reagent. Detection of fluorescence is indicative of formaldehyde generated by oxidative demethylation of the substrate by the enzyme, the fluorescence resulting from reaction of formaldehyde and the formaldehyde detection reagent.

Pathogen and particle detector system and method

A particle detector has a sample area of cross section no in excess of about 2 mm for containing environmental fluid, a light source on one side of the sample area for directing a collimated or nearly collimated beam of light through the sample air or water so that part of the light beam will be scattered by any particles present in the air or water while the remainder remains unscattered, and a beam diverting device on the opposite side of the sample area for diverting or blocking at least the unscattered portion of the beam of light and directing at least part of the scattered light onto a detector. The detector produces output pulses in which each pulse has a height proportional to particle size and a pulse height discriminator obtains the size distribution of airborne particles detected in the air or water sample at a given time from the detector output. The detector may also include a device for discriminating between biological agents and inorganic particles.

Method of classifying microorganisms using UV irradiation and excitation fluorescence

A method and device for detecting, differentiating from background and providing partial identification (i.e., classification) for biological particles found in aerosols or surface dust. The method is based on the phenomenon that luminescent excitation-emission (EEM) graphs of microorganisms obtained before and after perturbation by irradiation with ultraviolet light show characteristic patterns which differ according to the type of particle. For example, Bacillus endospores may be distinguished from vegetative bacteria, and gram positive vegetative bacteria may be distinguished from gram negative bacteria, and all these may be distinguished from many types of background particles, e.g. house dust, road dust, and pollen.

Systems and devices for isothermal biochemical reactions and/or analysis

An isothermal reaction and analysis system may include a receiver to receive sample holders, a thermal control subsystem to control a temperature of the receiver, an excitation subsystem, a detection subsystem and an analysis subsystem. Excitation sources and/or detectors are positioned to enhance data collection. Sample holders may include filters, selectively blocking and passing wavelengths or bands of electromagnetic radiation.

Multiple laminar flow-based particle and cellular separation with laser steering

The invention provides a method, apparatus and system for separating cellular components, and can be combined with holographic optical trapping manipulation or other forms of optical tweezing. One exemplary method includes providing a first flow having a plurality of components; providing a second flow; contacting the first flow with the second flow to provide a first separation region; and differentially sedimenting a first cellular component of the plurality of components into the second flow while concurrently maintaining a second cellular component of the plurality of components in the first flow. The second flow having the first cellular component is then differentially removed from the first flow having the second cellular component. Holographic optical traps may also be utilized in conjunction with the various flows to move selected components from one flow to another, as part of or in addition to a separation stage.

Method and apparatus for detection of livign phytoplankton cells in water

The invention relates to a method and an apparatus for detecting living phytoplankton cells and/or microorganisms in or out of water, particularly ballast water, bodies of water, sewage, or water in swimming and bathing devices. Said method is characterized by the following steps: the variable fluorescence (Fv) is calculated by forming the difference between the maximum fluorescence (Fm) and the minimum fluorescence (Fo) in a measuring space or detecting part or all of the dynamic shape of a fluorescence induction curve in a measuring space, particularly measuring; and calculating the number of living phytoplankton cells and/or microorganisms of a reference species in the measuring space in accordance with the variable fluorescence (Fv).

Method and device for monitoring retinopathy

There is provided a method of monitoring retinopathy in a subject. The method involves measuring autofluorescence of a retina of the subject in response to high intensity blue light over a total time period to obtain an autofluorescence intensity profile. The autofluorescence intensity profile is processed to assess the retinopathy status of the retina.

Biomarkers for prognoses of pulmonary diseases

The present invention relates to biomarkers that may be used to evaluate the prognoses of patients suffering from pulmonary diseases and assist in the determination of appropriate therapeutic regimens. It is based, at least in part, on the discovery that a number of T-cell antigens are differentially expressed in chronic lung disease patients depending on the prognosis of the patient. Non-limiting examples of these antigens include CD28, CD4, CD25, CD45, CD27 and CCR7 and combinations thereof. Use of these biomarker antigens, optionally in conjunction with pulmonary function tests, provides an indication of which patients are likely to suffer a severely adverse outcome within the year and/or be refractory to treatment.

Two-Photon Endoscopic Scanning Assembly for Inflammatory Disease Detection

An endscopic imaging device is described that achieves longitudinal axis (z-axis) scanning into a tissue or sample, using a piezoelectric microactuator. In some configurations, additional lateral (xy-plane) scanning is also achieved, to allow for the creation of full three-dimensional imaging, ex vivo or in vivo. The techniques may be used to image and diagnosis allergic rhinitis and eosinophilic esophagitis in tissue.

Method and apparatus to detect coronary artery calcification or disease

Coronary artery calcification (CAC) occurs at an earlier age in diabetes and is a risk factor for coronary artery disease (CAD) in subjects with or without diabetes. One postulated mechanism for the increased CAC is the accelerated accumulation of advanced glycation end products (AGEs) in the vasculature. As certain collagen AGEs fluoresce, skin intrinsic fluorescence (SIF) can act as a novel maker of collagen AGEs levels. The present invention provides methods and apparatuses for detecting SIF that can be a useful marker of CAD risk and a therapeutic target.

Method for measuring luminescence at a luminescence detection workstation

A luminescence detecting apparatus and method for analyzing luminescent samples is disclosed. Luminescent samples are placed in a plurality of sample wells in a tray, and the tray is placed in a visible-light impervious chamber containing a charge coupled device camera. The samples may be injected in the wells, and the samples may be injected with buffers and reagents, by an injector. In the chamber, light from the luminescent samples pass through a collimator, a Fresnel field lens, a filter, and a camera lens, whereupon a focused image is created by the optics on the charge-coupled device (CCD) camera. The use of a Fresnel field lens, in combination with a collimator and filter, reduces crosstalk between samples below the level attainable by the prior art. Preferred embodiments of the luminescence detecting apparatus and method disclosed include central processing control of all operations, multiple wavelength filter wheel, and robot handling of samples and reagents. Preferred embodiments of processing software integrated with the invention include elements for mechanical alignment, outlier shaving, edge detection and masking, manipulation of multiple integration times to expand the dynamic range, crosstalk correction, dark subtraction interpolation and drift correction, multi-component analysis applications specifically tailored for luminescence, and uniformity correction.

Plastic Microfluidic Separation and Detection Platforms

Plastic electrophoresis separation chips are provided comprising a plurality of microfluidic channels and a detection window, where the detection window comprises a thin plastic; and the detection window comprises a detection region of each microfluidic channel. Such chips can be bonded to a support provided an aperture is provided in the support to allow detection of samples in the electrophoresis chip at the thin plastic detection window. Further, methods for electrophoretically separating and detecting a plurality of samples on the plastic electrophoresis separation chip are described.

Fine particle measuring apparatus

A fine particle measuring apparatus is provided. The fine particle measuring apparatus includes a detection unit configured to detect light emitted from a fine particle and a processing unit having a memory device storing instructions which when executed by the processing unit, cause the processing unit to calculate a corrected intensity value of the detected light and generate spectrum data based on the corrected intensity value.

Method and apparatus for measuring optical properties of particles of a dispersion

Disclosed is apparatus for measuring optical properties of particles of a flowable dispersion using a measuring cuvette. The dispersion flows through the central inner chamber of the cuvette. Two laser light beams, which are offset 90 degrees to one another, illuminate the inner chamber of the cuvette, so as to illuminate a particle, regardless of its orientation, in a way that balances out form factor errors.

METHOD AND DEVICE FOR DETECTING BIOLOGICAL MATERIAL

The invention relates to a method for detecting biological material in an airstream, in which method 2565860. Method according to claim 1 , characterized in that there are at least two and preferably at least three index areas ( claim 1 , claim 1 , ).3. Method according to or claim 1 , characterized in that the indices are compared to relative conditions between each index and absolute conditions for at least some of the indices claim 1 , on the basis of which claim 1 , when the conditions are met claim 1 , an alarm is given.43. Method according to any of - claims 1 , characterized in that the sampling frequency is 100 kHz-2 MHz claims 1 , preferably 300-800 kHz.54. Method according to any of - claims 1 , characterized in that the said index frequency is 0.1-10 s claims 1 , preferably 0.8-1.5 s.65. Method according to any of - claims 1 , characterized in that claims 1 , in the at least 2-dimensional memory claims 1 , the dimensions are the fluorescence of the particles and the light scattered by the particles.76. Method according to any of - claims 1 , characterized in that claims 1 , in the at least 2-dimensional memory claims 1 , the dimensions are the light scattered by the particles and the product of the fluorescence of the particles and the light scattered by the particles.8. Method according to claim 1 , characterized in that the correlations of the discrete values are used for calculating the indices.98372432. Method according to any of - claims 1 , characterized in that the analysis means form classifications maps () on the basis of the fluorescence signal () and the scattering signal () for detecting biological material.109. Method according to any of - claims 1 , characterized in that the alarm is given in three steps claims 1 , as the following stages{'b': '16', 'biological material is detected in the airstream (),'}{'b': '74', 'when the alarm value exceeds the preselected criterion, the alarm and display means () give an alarm, and'}{'b': '16', 'samples ...

PROCESSES FOR DETECTION OF NUCLEIC ACIDS

This invention provides for compositions for use in real time nucleic acid detection processes. Such real time nucleic acid detection processes are carried out with energy transfer elements attached to nucleic acid primers, nucleotides, nucleic acid probes or nucleic acid binding agents. Real time nucleic acid detection allows for the qualitative or quantitative detection or determination of single-stranded or double-stranded nucleic acids of interest in a sample. Other processes are provided by this invention including processes for removing a portion of a homopolymeric sequence, e.g., poly A sequence or tail, from an analyte or library of analytes. Compositions useful in carrying out such removal processes are also described and provided. 1. (canceled)2. A process for detecting qualitatively or quantitatively the presence of a single-stranded or double-stranded nucleic acid of interest in a sample , said process comprising the steps of: (i) a sample suspected of containing said nucleic acid of interest;', (A) a nucleic acid sequence complementary to at least a portion of said nucleic acid of interest and', '(B) a first energy transfer element;, '(ii) a nucleic acid primer that comprises, '(iii) labeled nucleotide or nucleotides comprising a second energy transfer element; and', '(iv) reagents for carrying out nucleic acid strand extension,', the nucleic acid primer is not fixed or immobilized to a solid support; and', 'said first energy transfer element is an energy transfer donor and said second energy transfer element is an energy transfer acceptor, or said first energy transfer element is an energy transfer acceptor and said second energy transfer element is an energy transfer donor;, 'wherein'}], '(a) providing'}(b) forming a reaction mixture comprising (i), (ii), (iii) and (iv) above;(c) contacting under hybridization conditions said nucleic acid primer with said nucleic acid of interest;(d) extending said nucleic acid primer by more than one nucleotide, ...

Microarray-based sample analysis system

A microarray-based sample analysis (MBSA) system includes a cartridge holder adapted to receive a replaceable cartridge that is configured to receive a detachable, replaceable sample analysis unit containing one or more reaction chambers for sample analysis; a fluid control subsystem that controls fluid flow; and an optical subsystem configured to capture an image of the microarray.

BIODETECTION BY NUCLEIC ACID-TEMPLATED CHEMISTRY

The invention provides compositions and methods for the detection of biological targets, (e.g. nucleic acids and proteins) by nucleic acid templated chemistry, for example, by generating fluorescent, chemiluminescent and/or chromophoric signals. 121.-. (canceled)22. A method for detecting a biological target , the method comprising:(a) providing a first probe, the first probe comprising (1) a first binding moiety having binding affinity to the biological target, (2) a first oligonucleotide sequence, and (3) a first reactive group associated with the first oligonucleotide sequence;(b) providing a second probe, the second probe comprises (1) a second binding moiety having binding affinity to the biological target, (2) a second oligonucleotide sequence, and (3) a second reactive group associated with the second oligonucleotide sequence, wherein the second oligonucleotide is capable of hybridizing to the first oligonucleotide sequence and the second reactive group is reactive to the first reactive group when brought into reactive proximity of one another;(c) combining the first probe and the second probe with a sample to be tested for the presence of the biological target under conditions where the first and the second binding moieties bind to the biological target;(d) allowing the second oligonucleotide to hybridize to the first oligonucleotide to bring into reactive proximity the first and the second reactive groups; and(e) detecting a reaction between the first and the second reactive groups thereby determining the presence of the biological target.23. The method of wherein the first probe further comprises a first linker between the first binding moiety and the first oligonucleotide sequence.24. The method of wherein the second probe further comprises a second linker between the second binding moiety and the second oligonucleotide sequence.25. The method of wherein the biological target is selected from the group consisting of an autoantibody claim 22 , a cell and a ...

FLUORESCENCE MEASUREMENT

A sensor for fluorescence measurement comprising: a light source arranged for emitting light to a sample region, wherein the light source intensity is modulatable; an indicator system located at the sample region, said indicator system comprising: a receptor for an analyte; and a fluorophore associated with said receptor, wherein the fluorophore has a fluorescence lifetime that changes in response to the presence of analyte at the receptor; a single photon avalanche diode arranged to receive fluorescence light emitted from said sample region in response to the light incident on the sample region from the light source, and to generate an output signal; a driver arranged to modulate the light source intensity at a first frequency; a bias voltage source arranged to apply a bias voltage to the single photon avalanche diode, wherein the bias voltage is modulated at a second frequency, different from the first frequency, and wherein the bias voltage is above the breakdown voltage of the single photon avalanche diode; and a signal processor arranged to determine information related to a fluorescence lifetime of the fluorophore based on at least the output signal of the single photon avalanche diode. 1. A fluorescence sensor comprising:a light source arranged for emitting light to a sample region, wherein the light source intensity is modulatable;an indicator system located at the sample region, said indicator system comprising: a receptor for an analyte; and a fluorophore associated with said receptor, wherein the fluorophore has a fluorescence lifetime that changes in response to the presence of analyte at the receptor;a single photon avalanche diode arranged to receive fluorescence light emitted from said sample region in response to the light incident on the sample region from the light source, and to generate an output signal;a driver arranged to modulate the light source intensity at a first frequency;a bias voltage source arranged to apply a bias voltage to the ...

FLUORESCENT PROTEINS, NUCLEIC ACIDS ENCODING THEM AND METHODS FOR MAKING AND USING THEM

The invention is directed to polypeptides having a fluorescent activity, e.g., an auto-fluorescent activity, polynucleotides encoding the polypeptides, and methods for making and using these polynucleotides and polypeptides. The polypeptides of the invention can be used as noninvasive fluorescent markers in living cells and intact organs and animals. The polypeptides of the invention can be used as, e.g., in vivo markers/tracers of gene expression and protein localization, activity indicators, fluorescent resonance energy transfer (FRET) markers, cell lineage markers/tracers, reporters of gene expression and as markers/tracers in protein-protein interactions. 1. An isolated or recombinant nucleic acid comprising a nucleic acid sequence having at least 75% sequence identity to SEQ ID NO:17 over a region of at least about 100 residues ,wherein the nucleic acid encodes a fluorescent polypeptide and the sequence identities are determined by analysis with a sequence comparison algorithm or by a visual inspection.2. The isolated or recombinant nucleic acid of claim 1 , wherein the nucleic acid comprises a nucleic acid sequence having at least 75% sequence identity to SEQ ID NO:17 over a region of at least about 200 residues.3. The isolated or recombinant nucleic acid of claim 1 , wherein the nucleic acid comprises a nucleic acid sequence having at least 75% sequence identity to SEQ ID NO:17 over a region of at least about 300 residues.4. The isolated or recombinant nucleic acid of claim 1 , wherein the nucleic acid comprises a nucleic acid sequence having at least 75% sequence identity to SEQ ID NO:17 over a region of at least about 400 residues.5. The isolated or recombinant nucleic acid of claim 1 , wherein the nucleic acid comprises a nucleic acid sequence having at least 75% sequence identity to SEQ ID NO:17 over a region of at least about 500 residues.6. The isolated or recombinant nucleic acid of claim 1 , wherein the nucleic acid comprises a nucleic acid sequence ...

Soluble Quencher to reduce Background in qPCR assays

Soluble Quencher to reduce Background in qPCR assays The invention is in the field of is in the field of analytical technology. In particular, it is useful for conducting (RT-)quantitative PCR (qPCR) reactions for detection of DNA and RNA involving fluorescent probes. The distinguishing feature of the invention is to decrease the background not of an individual probe, but of all probes carrying the same fluorescent label. This is achieved by adding a soluble quenching dye to the qPCR reaction mix. The soluble quenching dye has an absorption of at least 40% of its maximal absorbance at the excitation wavelength and/or at the emission wave length of the fluorescent dye label This dye then acts as a “soluble shield” and allows to reduce the fluorescent background brought in by a large number of identically labeled probes. Depending on the nature (i.e. absorption spectrum) of the quenching dye, it is possible to selectively reduce the background of a single detection channel, while maintaining the signal strength of the other detection channels: This provides more flexibility, in case not all channels exhibit the same high background. 1. Method for determining the presence of a test nucleic acid in a sample , comprising the steps ofa) amplifying the test nucleic acid by an amplification reaction,b) labeling the amplified nucleic acid by providing a fluorescent dye label with an excitation wavelength and an emission wave length,c) adding a soluble quenching dye, said soluble quenching dye having an absorption of at least 40% of its maximal absorbance at the excitation wavelength and/or at the emission wave length of the fluorescent dye label,d) detecting the labeled nucleic acid dye by detecting emitted light at the emission wavelength of the label,wherein the concentration of said soluble quenching dye is 1% (w/v) or less.2. Method according to wherein the amplification reaction is a PCR reaction.3. Method according to claim 1 , wherein the fluorescent dye label is an ...

METHOD FOR DETECTION OF UROTHELIAL CANCER

It is to provide a method for detecting urothelial cancer simply and with high accuracy. It is a method for detecting urothelial cancer comprising administering 5-aminolevulinic acid (ALA), a derivative thereof, or a salt of these to a test subject, collecting urine from the test subject, and detecting the presence of fluorescence or amount of fluorescence in the collected urine. 1. A method for detecting urothelial cancer comprising administering 5-aminolevulinic acid (ALA) , a derivative thereof , or a salt of these to a test subject , collecting urine from the test subject , and detecting fluorescence in a cell of the collected urine.2. A method for detecting urothelial cancer comprising separating a cell from urine collected from a test subject administered with 5-aminolevulinic acid (ALA) , a derivative thereof , or a salt of these , and detecting fluorescence in the separated cell.3. The method for detecting urothelial cancer according to claim 1 , comprising administering 5-aminolevulinic acid (ALA) claim 1 , a derivative thereof claim 1 , or a salt of these in an amount of 0.05 to 20 mg per kg of a test subject in ALA hydrochloride equivalent.4. The method for detecting urothelial cancer according to claim 1 , comprising orally administering 5-aminolevulinic acid (ALA) claim 1 , a derivative thereof claim 1 , or a salt of these.5. The method for detecting urothelial cancer according to claim 1 , wherein the test subject is a human suspected to have urothelial cancer.6. An agent for detecting urothelial cancer claim 1 , comprising 5-aminolevulinic acid (ALA) claim 1 , a derivative thereof claim 1 , or a salt of these to be used in the method according to .7. The method for detecting urothelial cancer according to claim 2 , comprising administering 5-aminolevulinic acid (ALA) claim 2 , a derivative thereof claim 2 , or a salt of these in an amount of 0.05 to 20 mg per kg of a test subject in ALA hydrochloride equivalent.8. The method for detecting urothelial ...

Methods for Fractionation, Analysis and Collection of Microvesicles From Patient Samples

A methods are provided for the flow cytometry profiling of microvesicles, including exosomes. 1. A methods are provided for the flow cytometry profiling of microvesicles , including exosomes.2. The method of claim 1 , wherein the profiling is performed with nanoFACs.3. The method of claim 2 , wherein the nanoFACs utilizes a flow cytometer tuned for maximal resolution of small particles by adding both a filter and a small particle detector claim 2 , as well as tuning the nozzle height to eliminate drop drive noise.4. The method of claim 1 , comprising analysis of the quantity and/or quality of microvesicles for monitoring of tumor responses to cytotoxic therapies.5. The method of claim 1 , comprising analysis of the quantity and/or quality of microvesicles for monitoring immune responses to tumor vaccines.6. The method of claim 1 , comprising analysis of the quantity and/or quality of microvesicles for monitoring immune cells following transplantation.7. The method of claim 1 , comprising analysis of the quantity and/or quality of microvesicles for biodosimetry to assess the level of radiation exposure.8. The method of claim 1 , comprising utilizing a point of care device for purposes of identifying individuals with radiation exposure or specific infections.9. The method of claim 1 , comprising staining a population of microvesicles with a detectably labeled affinity reagent specific for a marker of interest claim 1 , prior to analysis.10. The method of claim 1 , wherein the method further comprises selecting a therapeutic regimen based on the analysis.11. A kit for use in the methods of . Exosomes are 40-150 nm vesicles secreted by a wide range of mammalian cell types. Exosomes are one of many different sub-populations of microvesicles that can be isolated from biofluids such as blood, urine and cerebrospinal fluid (CSF) and from which high quality RNA and DNA can be extracted and purified for analysis. Exosomes are shed by cells under both normal and pathological ...

SYSTEMS AND METHODS FOR COUNTING CELLS AND BIOMOLECULES

The invention generally relates to analytical and monitoring systems useful for analyzing and measuring cells and biological samples. More particularly, the invention relates to systems and methods for imaging, measuring, counting, analyzing, and monitoring microscopic particles such as cells and biological molecules in solution samples. 1. A system for imaging microscopic objects , comprising:a sample chamber configured to hold a suspension of objects to be imaged in a sample, wherein the chamber comprising an optically clear window allowing exposure of the sample;at least one fluorescent light source capable of providing a fluorescent excitation light beam to the sample through the window;a bright-field light source capable of providing a bright-field light beam to the sample; andat least one light detection device for detecting a light signal from the sample thereby forming at least one image of the microscopic objects, wherein the fluorescent excitation light beam is at an incident angle other than normal to the window's plane of surface.2. The system of claim 1 , wherein the system comprises at least two fluorescent light sources capable of simultaneously providing two excitation light beams having the same or different wavelengths to the sample.3. The system of claim 2 , wherein the system comprises four fluorescent light sources capable of simultaneously providing four excitation light beams having the same or different wavelengths to the sample.4. The system of claim 1 , wherein the fluorescent excitation light beam is at an incident angle of about 10° to about 80° in relation to the window's plane of surface.56-. (canceled)7. The system of claim 1 , wherein the fluorescent excitation light beam is at an incident angle of about 45° in relation to the window's plane of surface.810-. (canceled)11. The system of claim 2 , wherein the at least two fluorescent excitation light beams have different incident angles in relation to the window's plane of surface.1210. ...

FLUORESCENT NANOSCOPY DEVICE AND METHOD

A method for analysis of an object dyed with fluorescent coloring agents. Separately fluorescing visible molecules or nanoparticles are periodically formed in different object parts, the laser produces the oscillation thereof which is sufficient for recording the non-overlapping images of the molecules or nanoparticles and for decoloring already recorded fluorescent molecules, wherein tens of thousands of pictures of recorded individual molecule or nanoparticle images, in the form of stains having a diameter on the order of a fluorescent light wavelength multiplied by a microscope amplification, are processed by a computer for searching the coordinates of the stain centers and building the object image according to millions of calculated stain center co-ordinates corresponding to the co-ordinates of the individual fluorescent molecules or nanoparticles. Two-dimensional and three-dimensional images are provided for proteins, nucleic acids and lipids with different coloring agents. 1. A device for imaging a dyed object comprising:at least one objective lens;an excitement component, wherein the excitement component excites fluorescence of the dyed object; andat least one camera in combination with the at least one objective lens detecting fluorescence light of the dyed object through the at least one objective lens;wherein the device is adapted to generate fluorescent molecules or nanoparticles within the dyed object and/or force the fluorescent molecules or nanoparticles to lose color, such that a mean distance between a plurality of the fluorescent molecules or nanoparticles allow identification by the at least one camera of the plurality of the fluorescent molecules or nanoparticles as separate spots.2. The device according to claim 1 , further comprising a computer in combination with the at least one camera claim 1 , the computer including a recordable medium recording the fluorescence light received from the at least one camera claim 1 , and including software ...

DEVICE, SYSTEM AND METHOD FOR RAPID DETERMINATION OF A MEDICAL CONDITION

Provided is a system and method for determination of a medical condition, the system including a disposable cartridge adapted to receive a volume of a body fluid, the cartridge comprising a plurality of sections, at least one of the sections adapted to react at least one reactant with the bodily fluid to form a pretreated sample; and an optics unit comprising at least one excitation illumination adapted to convey radiation to the pre-treated sample, at least one multi-spectral emission detector and at least one of a photon counter and an integrator, wherein the at least one excitation illumination and the at least one multi-spectral emission detector are disposed on the same side of the cartridge; and wherein the optics unit is adapted to detect a plurality of spectrally distinct signals generated by interaction of the radiation and the pre-treated sample in the cartridge, thereby determining said medical condition. 132-. (canceled)34. A system according to claim 33 , further comprising a computer claim 33 , said computer adapted to receive data related to said plurality of spectrally distinct signals and a processor claim 33 , adapted to process said data and to output at least one output related to said medical condition.35. A system according to claim 33 , wherein each signal of said plurality of spectrally distinct signals is associated with at least one predetermined biological marker.36. A system according to claim 33 , wherein said a plurality of sections comprises at least one of:a) a body fluid aspiration section adapted to receive the body fluid directly or indirectly from the patient;b) a pre-analytical sample processing section;c) a sample excitation/interaction section; andd) a spent sample disposal section.37. A system according to claim 36 , wherein said pre-analytical sample processing section comprises at least one of the following:i. an incubator element adapted to incubate said body fluid with at least one antibody;ii. an incubator element adapted ...

Fluorescent Sensor and Methods

Binding an analyte can cause a change in fluorescence emission of a sensor. The change in fluorescence can be related to the amount of analyte present. The sensor can include a semiconductor nanocrystal linked to a fluorescent moiety. Upon excitation, the fluorescent moiety can transfer energy to the semiconductor nanocrystal, or vice versa. 1. A composition comprising:a first fluorescent moiety;a second fluorescent moiety associated with the first fluorescent moiety;wherein the first fluorescent moiety is capable of transferring energy to the second fluorescent moiety when excited, and the first fluorescent moiety or the second fluorescent moiety includes a semiconductor nanocrystal.236.-. (canceled) This application claims priority to provisional U.S. application No. 60/707,979, filed Aug. 15, 2005, which is hereby incorporated by reference.This invention was made with government support under Grant No. CHE0209898 awarded by the NSF, and grant number KK1043, awarded by the ARO. The government has certain rights in the invention.The invention relates to a fluorescent sensor, and methods of making and using the sensor.A fluorescent sensor can produce a detectable change in fluorescence response upon interacting with an analyte. Fluorescent sensors can provide desirable properties such as water solubility, low detection limits, and high selectivity for a desired analyte. The analyte can be a small molecule or ion (such as, for example, H (i.e., pH), Ca, glucose, or O).Semiconductor nanocrystals can be conjugated to energy-donor or energy-acceptor molecules for chemosensing by the Förster Resonance Energy Transfer (FRET) mechanism. The semiconductor nanocrystal can be rendered water soluble by a functionalized polymer, which also provides a framework to chemically attach dyes and receptors that are useful for chemosensing and bio-labeling studies.The nanocrystal can be excited by illumination with an excitation wavelength of light. The conjugated dye molecule absorbs ...

NEAR-IR INDOCYANINE GREEN DOPED MULTIMODAL SILICA NANOPARTICLES AND METHODS FOR MAKING THE SAME

The subject invention provides novel fluorescent core-shell nanoparticles comprising an encapsulated fluorescent core comprising an ionically bound fluorescent dye and a metal oxide shell. In one exemplary embodiment of the invention a core containing indocyanine green (ICG) with a silica shell that displays excellent photostability for generation of a near infrared fluorescence signal. The fluorescent core-shell nanoparticle can be further modified to act as an MRI, x-ray, or PAT contrast agent. The ICG nanoparticles can also be used as photodynamic therapeutic agent. Other embodiments of the invention directed to methods of making the novel core-shell nanoparticles and to the use of the core-shell nanoparticles for in vitro or in vivo imaging. 134-. (canceled)35. A fluorescent core-shell nanoparticle comprising:a core comprising a water insoluble matrix with an ionically bound fluorescent dye having at least one anionic sites; anda shell comprising a metal oxide, wherein the nanoparticle is less than 100 nm in diameter.36. The nanoparticle of claim 35 , wherein the metal oxide comprises silicon dioxide.37. The nanoparticle of claim 35 , wherein the water insoluble matrix comprises an ionically crosslinked biocompatible polymer having cationic sites claim 35 , wherein ion-pairing with the fluorescent dye ionically binds the dye within the polymer.38. The nanoparticle of claim 35 , wherein the water insoluble matrix comprises an insoluble salt of a multivalent cation wherein ion-pairing with the fluorescent dye binds the dye within the salt.39. The nanoparticle of claim 35 , wherein the water soluble fluorescent dye is indocyanine green (ICG).40. The nanoparticle of claim 35 , further comprising: a metal deposition on said shell; at least one moiety that exhibits magnetic properties; at least one moiety that exhibits paramagnetic properties; at least one moiety that exhibits X-ray opacity; a contrast agent for photoacoustic tomography (PAT) imaging; or any ...

MICROBEAD KIT AND METHOD FOR QUANTITATIVE CALIBRATION AND PERFORMANCE MONITORING OF A FLUORESCENCE INSTRUMENT

Fluorescently labeled microsphere calibration and quality control particles for use in establishing standardized fluorescence detector setup, monitoring daily QC of flow cytometers and quantitative calibration of the fluorescence detectors in traceable units of measure (molecules equivalent soluble fluorescence; MESF). 1. A calibration kit comprising:a. a set of populations of microbeads;b. each of said microbead populations having a median fluorescence intensity within a linear detection range of a fluorescence detector to be calibrated;c. each of said microbead populations being spectrally different and determinable from other microbead populations in the same set to allow discrimination thereof;d. at least two microbead populations of said set having spectrally different and determinable quantities of one or more internally-bound fluorophores measurable by a fluorescence detector to be calibrated; ande. at least one microbead population of said set, comprising a spectrally different and determinable quantity of one or more fluorophores bound to a surface of the microbeads in the microbead population, measurable by a fluorescence detector to be calibrated.2. A microbead calibration kit according to claim 1 , wherein the microbead populations are provided in a single liquid suspension.3. A microbead calibration kit according to claim 1 , wherein at least one microbead population contains a determinable quantity of one or more spectrally different and determinable fluorophores measurable by a fluorescence detector to be calibrated claim 1 , and has spectral properties that are sufficiently different from an experimental sample to allow reliable discrimination thereof claim 1 , and is provided in a separate suspension to allow mixing with the experimental sample as an internal control.4. A microbead calibration kit according to claim 1 , wherein said microbeads have a diameter in the range from about 0.5 microns to about 70 microns.5. A microbead calibration kit ...

METHOD FOR DETECTING SPECIFIC NUCLEIC ACID SEQUENCES

The present invention relates to a method and test kit for detecting specific nucleic acid sequences, comprising the steps of: 1. matrix-dependent new synthesis of the target nucleic acid; 2. target-specific probe hybridization; and 3. detection of the hybridization event. The invention is characterized in that, in the first step, an oligonucleotide 1, which is marked by a marker 1 and is entirely or partially complementary to the target sequence, acts as a primer in the matrix-dependent new synthesis of the target nucleic acid and, in the second step, an oligonucleotide 2, which is marked by a marker 2 and, owing to its melting temperature being lower than that of the oligonucleotide 1, is not involved in the first step, partially or completely hybridizes with the DNA new synthesis product of oligonucleotide 1.The detection of the hybridization reaction can take place both fluorometrically in the form of a homogeneous assay and, for verification of the result, subsequently immunologically. The detection reaction always takes place in time after the matrix-dependent new synthesis has been carried out. 1. A method for detecting a specific nucleic acid sequence , the method comprising:a) synthesizing a DNA target nucleic acid in a matrix-dependent de novo manner,b) hybridizing the target nucleic acid with a probe, andc) detecting the hybridizing,wherein:a primer in a) comprises an oligonucleotide 1 labeled with a label 1, which is completely or partly complementary to the target nucleic acid, andthe probe in b) comprises an oligonucleotide 2 labeled with a label 2, which has a lower melting temperature than oligonucleotide 1 and does not participate in the synthesizing, but which hybridizes partly or completely with the target nucleic acid.2. The method of claim 1 , wherein the detecting is performed in a reaction cavity in which the synthesizing and hybridizing are also performed.3. The method of claim 1 , wherein the detecting is performed on a solid phase claim 1 , ...

Systems and Methods for Calibration Using Dye Signal Amplification

The present teachings relate to a method of generating calibration information during a real-time polymerase chain reaction (RT-PCR) or other amplification reaction. A sample well plate or other support can contain one or more dyes or other reference materials that are subjected to the same RT-PCR thermal cycles or other conditions used to conduct amplification or other reactions on a biological sample. A set of maxima values and a set of minimum values, and/or other calibration information useful for adjusting emission data for sample dyes can be recorded, for example, for 10 cycles, 20 cycles, or each cycle of a complete RT-PCR run. Such testing of dye response under realistic operating conditions can enable more accurate characterization of plate, dye, filter, or instrument response and therefore more accurate calibration corrections and other and/or adjustments. 1. A method of generating calibration information for an amplification reaction , comprising:performing a first amplification reaction on at least one reference material in a sample support of an analytical instrumentperforming a second amplification reaction on a sample in a sample support of the analytical instrument;receiving first emission data generated by the at least one reference material during the first amplification reaction;receiving second emission data generated by the sample during the second amplification reaction;generating calibration information based on the received first emission data; andadjusting the received second emission data as a function of the calibration information.2. The method of claim 1 , wherein the at least one reference material comprises at least one dye.3. The method of claim 1 , wherein the at least one reference material comprises at least one fluorescent dye.4. The method of claim 1 , wherein the first and second amplification reactions claim 1 , each comprise a polymerase chain reaction.5. The method of claim 1 , wherein the calibration information generated ...

Method to Increase the Number of Detectable Photons During the Imaging of a Biological Marker

The present invention relates a method to determine the presence of a photon producing biological marker in a cell, tissue or organism of interest. The method is based on Fluorescence by Unbound Excitation from Luminescence (FUEL) and comprises the steps of a) providing conditions suitable for the biological marker to produce at least one first photon by luminescence; b) providing a FUEL probe pair-upper (FPP-U) disposed in proximity to the cell, tissue or organism, wherein the at least one first photon of step a) excites the FPP-U, which emits at least one second photon. The FPP-U may be selected from the group of quantum dots, carbon nanotubes, fluorescent proteins, diamond nanocrystals and metalloporphyrins. This method is charcterized in that said biological marker and said FPP-U are not bound and in that each of the at least one second photon(s) are of a longer wavelength than each of the at least one first photon(s). 1. A method to determine the presence of a photon producing luminescent biological marker in a cell , tissue or organism of interest comprising the steps:a) providing conditions suitable for a FPP-L to produce at least one first photon;b) providing a FPP-U disposed in proximity to said cell, tissue or organism, wherein said at least one first photon of step a) excites said FPP-U, which emits at least one second photon;wherein said FPP-L and said FPP-U are not bound and in that each of said at least one second photon (s) are of a longer wavelength than each of said at least one first photon (s).2. The method of claim 1 , wherein said FPP-L is the biological marker.3. The method according to claim 2 , wherein said biological marker is bioluminescent.4. The method according to claim 2 , wherein said biological marker is chemiluminescent.5. The method according to claim 2 , wherein said biological marker is fluorescent.6. The method according to claim 1 , wherein said biological marker emits photons with a wavelength of less than 650 nm.7. The method ...

FLUORESCENT DYES

The present invention provides dyes and labeled reagents that may be used in the detection or quantification of desirable target molecules, such as proteins, nucleic acids and cellular organelles. Dyes are provided that may be used free in solution where the binding of the dye to the target molecule provides signal generation. Dyes provided in this invention can comprise reactive groups that may be used to attach the dyes to probes that will bind to desirable target molecules. The novel dyes of the present invention have been substituted with specific groups to provide beneficial properties. 130-. (canceled)34. A method of identifying a specific organelle or region in a cell of interest , the method comprising{'claim-ref': {'@idref': 'CLM-00037', 'claim 37'}, '(a) incubating the cell of interest with the compound of , and'}(b) identifying the location of the organelle or region in the cell of interest by identifying the compound that stains the organelle or region.37. A target molecule comprising the compound of .38. The target molecule of claim 37 , wherein the target molecule is a nucleoside claim 37 , a nucleotide claim 37 , an oligonucleotide claim 37 , a polynucleotide claim 37 , a peptide nucleic acid claim 37 , a protein claim 37 , an oligopeptide claim 37 , an enzyme claim 37 , an antibody claim 37 , a cytokine claim 37 , avidin claim 37 , streptavidin claim 37 , digoxigenin claim 37 , an oligosaccharide claim 37 , a polysaccharide claim 37 , a lipid claim 37 , a liposome claim 37 , a glycolipid claim 37 , or a dye.39. The target molecule of claim 37 , wherein the target molecule is a protein claim 37 , an oligopeptide claim 37 , a nucleotide claim 37 , an oligonucleotide claim 37 , or a polynucleotide.41. The compound of claim 40 , wherein said reactive group comprises a nucleophilic reactive group claim 40 , an electrophilic reactive group claim 40 , a terminal alkene claim 40 , a terminal alkyne claim 40 , a coordinate group or an alkylating agent.42. The ...

NUCLEIC ACID ANALYSIS DEVICE

Provided is a device that can process a plurality of nucleic acid detection protocols in parallel, and in which any nucleic acid detection protocol of a new sample can be additively performed even when other nucleic acid detection protocols are being run. The nucleic acid detection device of the present invention includes: a thermostat bath () that has a vessel-accommodating hole for accommodating a reaction vessel; a detector () that detects fluorescence from the reaction vessel (); a gate () provided at a portion where the vessel is loaded into the vessel-accommodating hole; and a grip unit () that loads the vessel into the vessel-accommodating hole. 1. A nucleic acid analysis device comprising:a temperature adjusting mechanism that has a vessel-accommodating hole for accommodating a reaction vessel;a detector that detects fluorescence from the reaction vessel accommodated in the temperature adjusting mechanism;an open/close gate provided at a portion where the vessel is loaded into the vessel-accommodating hole; anda reaction vessel gripping mechanism that grips the reaction vessel and is movable in three axis directions orthogonal to each other, and that loads the reaction vessel into a vessel-accommodating section.2. The nucleic acid analysis device of claim 1 ,wherein the temperature adjusting mechanism has a plurality of vessel-accommodating holes, and is capable of adjusting different temperatures for the vessel-accommodating holes.3. The nucleic acid analysis device of claim 1 , wherein the open/close gate is provided in a chassis that keeps the vessel in a dark-room state.4. The nucleic acid analysis device of claim 1 , further comprising a joint mechanism provided in a preceding stage of the device and joined to a nucleic acid extraction mechanism.5. The nucleic acid analysis device of claim 1 , wherein the temperature adjusting mechanism is capable of rotational motion.6. The nucleic acid analysis device of claim 1 , wherein the temperature adjusting ...

PHOSPHOLINK NUCLEOTIDES FOR SEQUENCING APPLICATIONS

The present invention provides labeled phospholink nucleotides that can be used in place of naturally occurring nucleotide triphosphates or other analogs in template directed nucleic acid synthesis reactions and other nucleic acid reactions and various analyses based thereon, including DNA sequencing, single base identification, hybridization assays, and others. 1. A method of determining an identity of a nucleotide in a template nucleic acid sequence , said method comprising:a. providing said template nucleic acid sequence complexed with a polymerase enzyme capable of template dependent synthesis of a complementary nascent sequence as a first complex;b. contacting said first complex with a labeled phospholink nucleotide, wherein said labeled phospholink nucleotide comprises a bead comprising at least one fluorophore, wherein said bead is encapsulated in an organic, inorganic, or polymeric material, and wherein said labeled phospholink nucleotide is complementary to a known nucleotide; andc. detecting whether said labeled phospholink nucleotide is incorporated into said nascent sequence, wherein incorporation of said labeled phospholink nucleotide is indicative that said complementary nucleotide is in a position in the template nucleic acid that is being processed by the polymerase enzyme.2. The method of claim 1 , wherein said first complex is contained in a microfluidic flow cell claim 1 , and wherein said detecting step comprises detecting a temporary retention of said bead at a stationary location of said flow cell.3. The method of claim 2 , wherein said microfluidic flow cell comprises a surface claim 2 , and wherein said polymerase of said first complex is immobilized on said surface of said microfluidic flow cell.4. The method of claim 1 , wherein said first complex is contained in a zero-mode waveguide.5. The method of claim 1 , wherein said bead comprises multiple fluorophores.6. The method of claim 5 , wherein said detecting step comprises detecting a ...

SYSTEMS AND METHODS FOR DETECTION OF CELLULAR STRESS

There are provided methods for detection and measurement of stress in a cell, the method including introducing a labeled tRNA into the cell and detecting a change in subcellular localization of the labeled tRNA in the cell, based on the signal emitted from the labeled tRNA. There are further provided methods and systems for the generation of a stress index of a living cell. There are further provided methods and systems for detection of stress in a living cell, comprising detection of changes in subcellular localization of labeled tRNA in a cell, wherein the detection is performed in real time. 1. A method for detection of stress in a cell , the method comprising:introducing a labeled tRNA into the cell;detecting the subcellular localization of the tRNA over the course of a predetermined period of time, wherein the detection is based on a signal emitted from the labeled tRNA; anddetecting a change in the subcellular localization of the labeled tRNA in the cell, wherein the change is indicative of stress in the cell.2. The method of claim 1 , wherein said subcellular localization comprises nuclear localization claim 1 , cytoplasmic localization claim 1 , or both.3. The method of claim 2 , wherein increased subcellular nuclear localization of the tRNA is indicative of increased stress.4. The method of claim 2 , wherein decreased subcellular cytoplasmic localization of the tRNA is indicative of increased stress.5. The method of claim 2 , wherein the cytoplasmic localization comprises localization in or near intracellular organelles claim 2 , endoplasmic reticulum (ER) claim 2 , stress granules claim 2 , vacuoles claim 2 , mitochondria claim 2 , lysosomes claim 2 , autophagosomes claim 2 , or any combinations thereof.6. The method of claim 1 , wherein the labeled tRNA comprises fluorescently labeled tRNA claim 1 , said fluorescently labeled tRNA comprises Cy3-tRNA claim 1 , Rho-110tRNA claim 1 , Cy5-tRNA claim 1 , alexa-based fluorophores claim 1 , small organic ...

NANOPROBES FOR DETECTION OR MODIFICATION OF MOLECULES

The disclosure provides probes for one or more target molecules. In particular examples, the probes include a molecular linker and first and second functional groups linked and spaced by the molecular linker, wherein the functional groups are capable of interacting with one another or with the target biomolecule in a predetermined reaction, and wherein the molecular linker maintains the first and second functional groups sufficiently spaced from one another such that the functional groups do not substantially interact in an absence of the target biomolecule. In the presence of the target biomolecule the functional groups interact (with each other, with the target biomolecule, or both), and in some examples a detectable signal is produced. In some examples, the functional groups can detect or modify a target molecule. Also provided are methods of using the probes, for example to detect or modify a target molecule. 1. A method of detecting a target biomolecule , comprising: a molecular linker comprising a tether and a molecular rod, wherein the length of the rod is shorter than the persistence length of the rod material and the length of the tether is greater than the persistence length of the tether material;', 'a first functional group comprising an acceptor fluorophore at one end of the molecular linker; and', 'a second functional group comprising a donor fluorophore at the other end of the molecular linker, wherein the first and second functional groups are linked and spaced by the molecular linker, wherein the functional groups are capable of interacting with one another or with the target biomolecule in a predetermined reaction, wherein the molecular linker links the first and second functional groups sufficiently spaced from one another such that the functional groups do not substantially interact in an absence of the target biomolecule but interact in a presence of the target biomolecule to provide a signal of the presence of the biomolecule,, 'contacting a ...

NUCLEIC ACID BASE ANALOGS WITH QUENCHING AND FLUORESCENT ACTIVITIES AND APPLICATIONS THEREOF

It is an object of the present invention to provide quenching or fluorescent nucleic acid base analogs and applications thereof. The quencher of the present invention has a 2-nitropyrrole structure represented by Formula I: 2. The quencher according to claim 1 , wherein Rin Formula I is ribose or deoxyribose.3. (canceled)9. The method according to claim 7 , wherein the fluorescent molecule is selected from the group consisting of:indocarbocyanine (Cy3), indodicarbocyanine (Cy5), 5-carboxyfluorescein (5-FAM), 6-carboxyfluorescein (6-FAM), 5-carboxytetramethylrhodamine (5-TAMRA), 6-carboxytetramethylrhodamine (6-TAMRA), 5-dimethylaminonaphthalene-1-sulfonic acid (DANSYL), 5-carboxy-2′,4,4′,5′,7,7′-hexachlorofluorescein (5-HEX), 6-carboxy-2′,4,4′,5′,7,7′-hexachlorofluorescein (6-HEX), 5-carboxy-2′,4,7,7′-tetrachlorofluorescein (5-TET), 6-carboxy-2′,4,7,7′-tetrachlorofluorescein (6-TET), 5-carboxy-X-rhodamine (5-ROX), and 6-carboxy-X-rhodamine (6-ROX).11. (canceled)16. The method according to claim 11 , wherein the fluorescent molecule is selected from the group consisting of:indocarbocyanine (Cy3), indodicarbocyanine (Cy5), 5-carboxyfluorescein (5-FAM), 6-carboxyfluorescein (6-FAM), 5-carboxytetramethylrhodamine (5-TAMRA), 6-carboxytetramethylrhodamine (6-TAMRA), 5-dimethylaminonaphthalene-1-sulfonic acid (DANSYL), 5-carboxy-2′,4,4′,5′,7,7′-hexachlorofluorescein (5-HEX), 6-carboxy-2′,4,4′,5′,7,7′-hexachlorofluorescein (6-HEX), 5-carboxy-2′,4,7,7′-tetrachlorofluorescein (5-TET), 6-carboxy-2′,4,7,7′-tetrachlorofluorescein (6-TET), 5-carboxy-X-rhodamine (5-ROX), and 6-carboxy-X-rhodamine (6-ROX).18. The method according to claim 11 , wherein the change in fluorescent spectrum is observed with the naked eye.19. The method according to claim 11 , wherein the base pair of the nucleic acid is formed in the process of transcription claim 11 , reverse transcription claim 11 , replication claim 11 , or translation. The present application claims priority to Japanese Patent ...

Metal Nanoparticle Structures For Enhancing Fluorescence-Based Arrays

Provided, among other things, is a multiplex assay comprising: conducting a fluorescence-developing assay on microtabs having at least one surface that shows plasmonic enhancement, wherein a plurality of the microtabs have unique probes affixed to their plasmonically enhanced surfaces; and measuring the fluorescence associated with the substrates and identifying the correlated probe by for the microtab. The microtabs can be, for example, MTPs that send a unique identifier, and the correlated probe can be identified by querying the MTPs for their identifier. 115-. (canceled)16. A fluorescence enhancing substrate comprising:a substrate;a first coating of AS/ES on the substrate, wherein the coating is thicker than monolayer; andmetal particles deposited or formed on the AS/ES coating, said particles effective to enhance a surface-mediated fluorescence assay by 5-fold or more.17. The fluorescence enhancing substrate of claim 16 , wherein the metal particles stabilized or protected with a coating or further coating of polymer.18. The fluorescence enhancing substrate of claim 16 , wherein the substrate is a microtab.19. A fluorescence enhancing substrate comprising:a polymeric assay bead having surface pores; andmetal particles deposited or formed on the surface of the bead, said particles effective to enhance a surface-mediated fluorescence assay by 5-fold or more.20. An assay comprising:{'claim-ref': {'@idref': 'CLM-00016', 'claim 16'}, 'conducting a fluorescence-developing assay in a plurality of wells of a microtiter plate or with a nucleic acid/protein array, the microtiter wells or different regions of the array comprising substrates according to , wherein a plurality of the substrates have unique probes affixed thereto; and'}measuring the fluorescence associated with the substrates and identifying the correlated probe by location.21. A multiplex assay comprising:{'claim-ref': {'@idref': 'CLM-00016', 'claim 16'}, 'conducting a fluorescence-developing assay on ...

Cellular Libraries of Peptide Sequences (CLiPS) and Methods of Using the Same

The present invention provides compositions including peptide display scaffolds that present at least one candidate peptide and at least one detectable moiety in at least one of the N-terminal and C-terminal candidate peptide presenting domains that when expressed in a cell are accessible at a surface of the cell outermembrane. In addition, the present invention also provides kits and methods for screening a library of cells presenting the candidate peptides in peptide display scaffolds to identify a ligand for an enzyme. 146.-. (canceled)47. A cell comprising a peptide display scaffold disposed in an outer membrane of the cell , the peptide display scaffold comprising a fusion protein comprising the formula:{'br': None, 'sub': 1', '1', '2, '[D-C]-TM-[D]'}wherein TM is a circularly permuted bacterial outer membrane protein;{'sub': '1', 'Ccomprises a candidate peptide; and'}{'sub': 1', '2', '1', '2', '1', '1', '2, 'Dand Dare first and second detectable moieties, wherein Dand Dare not the same and wherein D-Cand Dare exposed at an extracellular surface of the cell outer membrane and one or both of the N- and C-termini of the fusion protein are exposed at the extracellular surface of the cell outer membrane.'}48. The cell of claim 47 , wherein the fusion protein comprises at least one linker claim 47 , wherein the linker is between Cand TM or between Dand TM.49. The cell of claim 47 , wherein the fusion protein comprises a linker between Cand TM and a linker between Dand TM.50. The cell of claim 47 , wherein claim 47 , wherein detectable moieties Dand Dare first and second affinity tags which are not the same.51. The cell of claim 47 , wherein C1 comprises a member of a library of candidate peptide substrates for an enzyme.52. The cell of claim 47 , wherein at least one of detectable moieties D1 and D2 is a fluorescent protein.53. The cell of claim 47 , wherein D-Cis located at an N-terminal domain of the fusion protein and Dis located at a C-terminal domain of the ...

Non-Fluorescent Quencher Compounds and Biomolecular Assays

Bis-diazo, triaryl and aryldiazo-N-arylphenazonium quencher moieties, substituted with electron-withdrawing and electron-donating substituents which induce polarity in the delocalized aryl/diazo ring systems, are useful as labels when attached to biomolecules such as polynucleotides, nucleosides, nucleotides and polypeptides. The quencher moieties are non-fluorescent and accept energy transfer from fluorescent reporter labels by any energy-transfer mechanism, such as FRET. 354-. (canceled)56. The compound of claim 55 , wherein the electron-withdrawing groups are each claim 55 , independently of one another claim 55 , selected from NO claim 55 , CN claim 55 , CF claim 55 , COH claim 55 , COR′ claim 55 , C(O)NH claim 55 , N(O)NHR′ claim 55 , C(O)NR′R′ claim 55 , CHO claim 55 , C(O)R′ claim 55 , SOR′ claim 55 , SOCF claim 55 , SOOR′ claim 55 , SOH claim 55 , NO and C-Caryl claim 55 , wherein each R′ is independently H claim 55 , C-Calkyl or C-Caryl.57. The compound of claim 55 , wherein the electron-donating groups are each claim 55 , independently of one another claim 55 , selected from O claim 55 , S claim 55 , NR″R″ claim 55 , NHR″ claim 55 , NH claim 55 , NHC(O)R″ claim 55 , OR″ claim 55 , OH claim 55 , OC(O)R″ claim 55 , SR″ claim 55 , SH claim 55 , Br claim 55 , I claim 55 , Cl claim 55 , F claim 55 , R″ and C-Caryl claim 55 , wherein each R″ is independently H claim 55 , C-Calkyl or C-Caryl.58. The compound of claim 55 , wherein Ris NO.59. The compound of claim 55 , wherein at least one of R claim 55 , R claim 55 , R claim 55 , R claim 55 , R claim 55 , R claim 55 , R claim 55 , R claim 55 , R claim 55 , R claim 55 , R claim 55 , R claim 55 , Rand Ris OCH.60. The compound of claim 55 , wherein the reactive linking group comprises an electrophile.61. The compound of claim 60 , wherein the electrophile of the reactive linking group is a carboxylic acid or an ester.62. The compound of claim 55 , wherein the reactive linking group is linked to the quencher moiety Q1 ...

Fluorimetric Process for Evaluating the Influence of A Condition on A Biological Sample and Applications Thereof

The present invention relates to a process for determining the influence of a condition on a biological sample comprising a step consisting in establishing the kinetic profile of the fluorescence emitted, during the excitation at a suitable excitation wavelength, of a fluorescent compound bound to said biological sample, said sample having been, prior to said excitation, subjected to said condition and said process not necessitating the utilization of a fluorescence donor component and of a different fluorescence acceptor component. The present invention also relates to the various applications of such a process. 116-. (canceled)17. A process for determining the influence of a physical or chemical condition on a biological sample , comprising:establishing a kinetic profile of a fluorescence emitted, during excitation at a suitable excitation wavelength, of a fluorescent compound bound to said biological sample, said sample having been, prior to said excitation, subjected to said condition and said process not necessitating the utilization of a fluorescence donor component and a different fluorescence acceptor component.18. The process according to claim 17 , further comprising:a. subjecting said biological sample to said condition;b. placing said fluorescent compound in contact with said sample, the steps (a) and (b) being in any order;c. exciting said fluorescent compound at the appropriate excitation wavelength for a period t the starting point whereof is t0;d. establishing the kinetic profile of the fluorescence emitted by said fluorescent compound during the excitation period t, the fluorescence measured at t0 serving as the reference value; ande. optionally, comparing the kinetic profile obtained in step (d) with a reference kinetic profile.19. A process for determining the influence of a physical or chemical condition on a biological sample claim 17 , comprising:a. dividing said biological sample into a first portion A and a second portion B;b. subjecting said ...

OPTICAL MAPPING OF GENOMIC DNA

A method for single-molecule optical DNA profiling using an exceptionally dense, yet sequence-specific coverage of DNA with a fluorescent probe, using a DNA methyltransferase enzyme to direct the DNA labeling, followed by molecular combing of the DNA onto a polymer-coated surface and subsequent sub-diffraction limit localization of the fluorophores. The result is a ‘DNA fluorocode’; a simple description of the DNA sequence, with a maximum achievable resolution of less than 20 bases, which can be read and analyzed like a barcode. The method generates a fluorocode for genomic DNA from the lambda bacteriophage using a DNA methyltransferase to direct fluorescent labels to four-base sequences reading 5′-GCGC-3′. A consensus fluorocode is constructed that allows the study of the DNA sequence at the level of an individual labeling site and is generated from a handful of molecules and entirely independently of any reference sequence. 147.-. (canceled)48. A method for sub-diffraction limit precision mapping of a polynucleotide , e.g. a DNA , the method comprising:sequence-specifically labeling the polynucleotide, said labeling comprising reacting the polynucleotide with a polynucleotidemethyltransferase enzyme and a methyltransferase cofactor, and subsequently incubating the polynucleotide with a fluorophore,isolating the emission from individual fluorophores along the polynucleotide, said isolating comprising recording a movie of the fluorescence emission signal of said fluorophores while undergoing photobleaching, photoswitching or another stochastic photophysical process, anddetermining the positions of the individual fluorophores with sub-diffraction limit accuracy by a processor with one of or both software assisted measurement system and control algorithm configured to measure said fluorescence emission signal, followed bytranslating said positions of the individual fluorophores to sequence-specific locations on said polynucleotide by comparison of an image of the ...

FLUORESCENT COMPOUNDS, COMPOSITIONS, AND METHODS FOR USING THE COMPOUNDS AND COMPOSITIONS

Low pKa fluorescent compounds, compositions that include the compounds, bioconjugates made from the compounds, and methods for making and using the compounds and bioconjugates. 2. The compound of claim 1 , wherein Ris chloro and Ris hydrogen.3. The compound of claim 1 , wherein Ris chloro and Ris chloro.4. The compound of claim 1 , wherein A is OH.5. The compound of claim 1 , wherein A is N(CH).6. A nucleic acid probe prepared from a suitably reactive oligonucleotide and a compound of or its active ester.7. The probe of further comprising a second fluorescent compound.8. The probe of claim 6 , wherein the second fluorescent compound has an emission spectrum that overlaps with the absorption spectrum of the compound of .9. The probe of claim 6 , wherein the second fluorescent compound has an absorption spectrum that overlaps with the emission spectrum of the compound of .10. The probe of further comprising a quencher moiety.12. The method of claim 11 , wherein the probe is a hybridization probe.13. The method of claim 11 , wherein the probe is a hydrolysis probe.15. The kit of claim 14 , wherein the probe is a hybridization probe.16. The kit of claim 14 , wherein the probe is a hydrolysis probe.18. The composition of claim 17 , wherein the fluorescent compound is a seminaphthofluorescein. This application claims the benefit of U.S. Patent Application No. 61/491,087, filed May 27, 2011; is a continuation-in-part of U.S. patent application Ser. No. 11/789,431, filed Apr. 23, 2007, which claims the benefit of U.S. Patent Application No. 60/794,193, filed Apr. 21, 2006, and is a continuation-in-part of U.S. patent application Ser. No. 11/207,580, filed Aug. 19, 2005, now U.S. Pat. No. 7,608,460, which claims the benefit of U.S. Provisional Application No. 60/602,684, filed Aug. 19, 2004, and U.S. Provisional Application No. 60/674,393, filed Apr. 22, 2005; and is a continuation-in-part of U.S. patent application Ser. No. 12/480,574, filed Jun. 8, 2009, now U.S. Pat. No. ...

Highly Sensitive System and Method for Analysis of Troponin

The invention provides methods, compositions, kits, and systems for the sensitive detection of cardiac troponin. Such methods, compositions, kits, and systems are useful in diagnosis, prognosis, and determination of methods of treatment in conditions that involve release of cardiac troponin. 123-. (canceled)24. A method for determining cardiovascular health of a human subject , comprising:{'sup': 'th', '(a) determining a threshold concentration at least one of Cardiac Troponin I (cTnI) and cardiac troponin T (cTnT) in blood, serum or plasma in a healthy population, wherein the threshold concentration represents the 99percentile of cTnI or cTnT in the healthy population;'}(b) measuring the blood, serum or plasma concentration of the at least one of cTnI and cTnT from the subject in an assay having a limit of detection for cTnI or cTnT of less than 3 pg/mL;(c) determining cardiac damage in the subject when the concentration of the at least one of cTnI and cTnT in the sample greater than the threshold concentration.25. The method of claim 24 , wherein the threshold concentration is within the range of 1 pg/ml to 10 pg/ml.26. The method of claim 24 , wherein the threshold concentration is less than about 7 pg/ml.27. The method of claim 24 , wherein the threshold concentration is less than about 8 pg/ml.28. The method of claim 24 , wherein the threshold concentration is less than about 9 pg/ml.29. The method of claim 24 , wherein the threshold concentration is less than about 10 pg/ml.30. The method of claim 24 , wherein the sample is taken during a stress test.31. The method of claim 24 , wherein the sample is taken after a stress test.32. The method of claim 24 , wherein the assay detects single molecules of the at least one of cTnI and cTnT claim 24 , or complexes or fragments thereof.33. The method of claim 32 , comprising binding the at least one of cTnI and cTnT claim 32 , or complexes or fragments thereof claim 32 , with a label comprising a fluorescent moiety and ...

Multimodal detection of tissue abnormalities based on raman and background fluorescence spectroscopy

Methods and apparatus for classifying tissue use features of Raman spectra and background fluorescent spectra. The spectra may be acquired in the near-infrared wavelengths. Principal component analysis and linear discriminant analysis of reference spectra may be used to obtain a classification function that accepts features of the Raman and background fluorescence spectra for test tissue and yields an indication as to the likelihood that the test tissue is abnormal. The methods and apparatus may be applied to screening for skin cancers or other diseases.

DETECTION OF BACTERIAL CONTAMINATION IN A SAMPLE

Methods for detecting one or more target bacteria in a test sample are provided. It is shown herein that photosensitizers combined with intense light exposure reduce fluorescing background due to non-bacterial particles. This permits detection of subsequently labeled target bacterial cells (e.g., using a fluorescently labeled antibody) against a largely black background. In particular examples, the methods include incubating the test sample in a growth medium that permits growth of bacteria present in the sample, contacting the sample with a photo-sensitizer; exposing the sample to light under conditions sufficient for the photo-sensitizer to photobleach contaminating non-bacterial particulates present in the sample. The bacteria can then be substantially separated from the sample, thereby generating an isolated bacterial sample. The method can also include contacting the isolated bacterial sample with a binding agent specific for the one or more target bacteria, and detecting the one or more target bacteria. 1. A method of detecting one or more target bacteria in a test sample , comprising:incubating the test sample in a growth medium that permits growth of bacteria present in the test sample;contacting the test sample with a photo-sensitizer;exposing the test sample to light, under conditions sufficient for the photo-sensitizer to photobleach contaminating non-bacterial particulates present in the sample;separating the bacteria from the test sample, thereby generating an isolated bacterial sample;contacting the isolated bacterial sample with a specific binding agent specific for the one or more target bacteria, under conditions sufficient for the specific binding agent to bind to the one or more target bacteria;detecting the one or more target bacteria; anddesignating the test sample as containing the one or more target bacteria target bacteria when the specific binding agent is detected.2. The method of claim 1 , wherein the growth medium comprises brain heart ...

DATING BLOODSTAINS AND BIOLOGICAL FLUIDS WITH FLUORESCENCE LIFETIME TECHNIQUES

Methods of aging biological samples through the use of fluorescence lifetime are disclosed herein. These methods provide aging of samples such as bloodstains using endogenous fluorophores and conformational protein changes. Advantageously, the methods provide the average fluorescence lifetime across a region of interest in a biological sample, thereby minimizing problems with sampling and providing accurate results. 1. A method for determining the age of a biological sample , the method comprising measuring a fluorescence lifetime value of the biological sample.2. The method of wherein the measuring of the fluorescence lifetime value comprises detecting a conformational change of at least one endogenous fluorophore in the biological sample.3. The method of wherein the endogenous fluorophore is selected from the group consisting of fluorescent amino acids claim 2 , porphyrins claim 2 , lipofuscin claim 2 , nicotinamide adenine dinucleotide phosphate-oxidase claim 2 , FAD-binding proteins claim 2 , and chlorophylls.4. The method of wherein the measuring of the fluorescence lifetime value comprises detecting a conformational change of at least one protein in the biological sample.5. The method of wherein the protein is selected from the group consisting of albumin claim 4 , globulin claim 4 , fibrinogen claim 4 , hemoglobin claim 4 , bilirubin claim 4 , melanin claim 4 , lignin claim 4 , elastin claim 4 , collagen claim 4 , and combinations thereof.6. The method of wherein the fluorescence lifetime value comprises the fluorescence lifetime of a tryptophan residue of the protein in the biological sample.7. The method of wherein the biological sample is a biological fluid.8. The method of wherein the biological fluid is selected from the group consisting of blood claim 7 , breast milk claim 7 , bile claim 7 , cerebrospinal fluid claim 7 , gastric juice claim 7 , mucus claim 7 , saliva claim 7 , semen claim 7 , sweat claim 7 , tear claim 7 , urine claim 7 , and ...

COMPOSITIONS AND METHODS FOR LEUKOCYTE DIFFERENTIAL COUNTING

The present invention provide compositions and methods for classifying leukocytes in a leukocyte population using fluorescence detection. The methods include contacting a leukocyte population in a sample having one or more leukocyte types with a diagnostic composition, exciting the leukocyte population with a light source; and measuring emitted light from each of the one or more leukocyte types to classify the leukocyte population. 1. A diagnostic composition , said diagnostic composition comprising:a first dye having a cationic charge;a second dye having less of a cationic charge compared to said first dye; anda third dye being reactive to a protein, having an affinity to a protein or having an anionic charge.2. The diagnostic composition of claim 1 , wherein said first dye has at least two cationic charges.3. The diagnostic composition of claim 1 , wherein said second dye has one cationic charge.4. The diagnostic composition of claim 2 , wherein said first dye is propidium iodide.5. The diagnostic composition of claim 3 , wherein said second dye is Basic Orange 21.6. The diagnostic composition of claim 1 , wherein said third dye is fluorescein isothiocyanate.7. A method for classifying leukocytes in a leukocyte population with fluorescence detection claim 1 , said method comprising:contacting a leukocyte population in a sample having one or more leukocyte types with a diagnostic composition, said diagnostic composition comprising:a first dye having a cationic charge;a second dye having less cationic charge compared to said first dye; anda third dye being reactive to a protein, having an affinity to a protein or having an anionic charge to stain the leukocyte population to form a stained leukocyte population;exciting the stained leukocyte population with a light source; andmeasuring emitted light from each of the one or more leukocyte types to classify the leukocyte population.8. The method for classifying of claim 7 , wherein the number of leukocyte types in the ...

MICROCHIP AND METHOD OF PRODUCING THE SAME

Provided is a microchip including a plurality of substrates, a reaction zone configured to function as a reaction site of a reaction, and a circumferential path on a circumferential part of the reaction zone with an inside of the circumferential path being at a pressure negative to atmospheric pressure, in which the circumferential path is disposed on at least one side of at least one of the substrates bonded together. 1. A microchip , comprising:a plurality of substrates bonded together;a reaction zone, provided on at least one of the substrates, configured to function as a reaction site of a reaction; anda circumferential path on a circumferential part of the reaction zone with an inside of the circumferential path being at a pressure negative to atmospheric pressure, disposed on at least one side of at least one of the substrates bonded together.2. The microchip according to claim 1 , wherein a section form of the circumferential path is curved to block unnecessary light for optical detection.3. The microchip according to claim 2 , whereinthe circumferential paths are disposed on both surfaces of at least one of the substrates on which the reaction site is formed.4. The microchip according to claim 3 , whereinthe circumferential path has thermal insulating properties.5. The microchip according to claim 3 , whereinthe circumferential path has a cutout.6. The microchip according to claim 3 , whereineach of the circumferential paths is connected to a communicating flow channel, and a fluid flows from the communicating flow channel to the circumferential path.7. The microchip according to claim 3 , which is used for a nucleic acid amplification reaction.8. A method of producing a microchip claim 3 , the method comprising:bonding substrate layers on which a circumferential path is formed around a circumferential part of a reaction zone configured to function as a reaction site on a surface of a substrate that is one of the substrate layers, at a pressure negative to ...

ILLUMINATION SIMULATOR FOR ALGAE GROWTH

Systems and methods are provided for using a growth vessel to simulate algae growth and/or productivity in a reference environment, such as an open pond, a closed photobioreactor, or a hybrid system. Based on predicted algae sample trajectories in the reference environment, an illumination profile is developed. An algae sample in the growth vessel can then be exposed to the illumination profile under controlled conditions. Properties of algae in the reference environment can then be characterized based on the sample exposed to the illumination profile. 1. A method for prediction of algal behavior in a reference environment based on growth of algae sample in a controlled environment , comprising:calculating a particle trajectory for a particle in a reference volume, the particle trajectory comprising at least a plurality of position values in the reference volume, the plurality of position values having associated times, the position values including at least a depth value relative to a surface of the reference volume;determining an illumination profile based on the particle trajectory by obtaining an illumination intensity corresponding to the plurality of position values and associated times;exposing an algae sample comprising an algal strain in a vessel to light intensity corresponding to the illumination profile for a period of time corresponding to a sample culturing period, the algae sample having a sample depth, a sample volume, and an optical density, a product of the optical density and the sample depth being less than about 10.0 cm, the sample volume being less than the reference volume; andcharacterizing at least one algae property for algae in the reference volume based on at least one measured algae property of the algae sample.2. The method of claim 1 , wherein calculating a particle trajectory comprises:measuring a velocity field for a fluid flow in the reference volume; andconstructing a particle trajectory in the fluid flow using a stochastic process ...

DIAGNOSTIC INSTRUMENT AND FLOW PROCESS

A diagnostic instrument having a cellular analysis system capable of running standardized immune monitoring panels. The system could include an automated and integrated specimen sampling method through a continuous flow process. The instrument could include a probe washer station, scheduler, cassette autoloader, bar coding system, and/or containment area common interface. An improved optimization test is proposed for instrument and flow cytometer quality assurance. The proposed method analyzes population separation for measuring instrument performance and/or sample quality. Such a method may also use population separation for measuring sample and/or run quality. 120.-. (canceled)21. A system for analyzing a cellular sample in a specimen tube , the system comprising:a well;a mixing station including a rocker that displaces the specimen tube in a rocking motion;a probe displaceable above the rocker and above the well;a flow cytometer coupled to the well; anda processor to control the mixing station, the probe, and the flow cytometer, the rocker to orient the specimen tube upright;', 'the probe to transfer the cellular sample from the upright specimen tube to the well;', 'and', 'the flow cytometer to aspirate from the well and to analyze the cellular sample., 'wherein the processor directs22. The system of wherein the specimen tube is held in a tube cassette claim 21 , wherein the mixing station further includes a cassette holder to support the tube cassette claim 21 , and wherein the rocker is coupled to the cassette holder and displaces the specimen tube by displacing the cassette holder.23. The system of further comprising an autoloader coupled to the mixing station claim 22 , the autoloader including a cassette queue to hold the tube cassette claim 22 , wherein the autoloader delivers the tube cassette to the cassette holder of the mixing station.24. The system of wherein the specimen tube includes a cap and the processor directs the probe to pierce the cap to ...

Optical instrument comprising multi-notch beam splitter

An instrument is provided that can monitor nucleic acid sequence amplification reactions, for example, PCR amplification of DNA and DNA fragments. The instrument includes a multi-notch filter disposed along one or both of an excitation beam path and an emission beam path. Methods are also provided for monitoring nucleic acid sequence amplifications using an instrument that includes a multi-notch filter disposed along a beam path.

ARRANGEMENTS AND METHODS FOR PROVIDING MULTIMODALITY MICROSCOPIC IMAGING OF ONE OR MORE BIOLOGICAL STRUCTURES

Method and apparatus according to an exemplary embodiment of the present invention can be provided. For example, first data associated with a first signal received from at least one region of at least one sample can be provided based on a first modality, and second data associated with a second signal received from the at least one sample can be provided based on a second modality which is different from the first modality. Third data associated with a reference can be received. Further data can be generated based on the first, second and third data. In addition, third data associated with a second signal received from the at least one sample can be obtained. Each of the third data can be based on a further modality which is different from the first modality and the second modality, and the further data can be further determined based on the third data. Further, the first modality can be a spectral-encoded modality, and the second modality can be a non-spectral-encoding modality. 123-. (canceled)24. An apparatus comprising:at least one source first arrangement configured to provide an electro-magnetic radiation; andat least one second arrangement configured to provide (i) first data associated with a first signal received from at least one region of at least one sample based on a first modality, (ii) second data associated with a second signal received from the at least one sample based on a second modality which is different from the first modality, and (iii) at least one third data associated with a third signal received from the at least one sample, wherein each of the at least one third data is based on a third modality which is different from at least one of the first modality or the second modality,wherein at least two of the first, second and third signals are caused by the electro-magnetic radiation provided by the at least one first arrangement.25. The apparatus according to claim 24 , further comprising at least one third arrangement which is configured to ...

Multi-photon Tissue Imaging

A multimodal method for imaging tissue comprising: aligning an excitation light source with at least a portion of the tissue; selecting at least two modalities of image acquisition; imaging the tissue portion with each of the modalities of image acquisition; and constructing a dual mode image using images from each of the modalities of image acquisition. A multimodal system for imaging tissue comprising: an excitation light source or light sources; an optical and alignment system for directing the excitation beam or beams to a sample and receiving an emission beam from the sample; at least one detector for receiving the emission beam from the sample; and a spectral filtering or dispersing device for providing at least two imaging modalities at the at least one detector; and a processor for analyzing the detected emission beam and constructing a dual mode image using images from each of the modalities of image acquisition. 1. A multimodal method for imaging tissue comprising:aligning an excitation light source with at least a portion of the tissue;selecting at least two modalities of image acquisition, the at least two modalities comprising at least two modalities selected from the group consisting of two photon excitation fluorescence, two photon autofluorescence, fluorescence lifetime imaging, autofluorescence lifetime imaging, second harmonic generation, third harmonic generation, coherent anti-stokes Raman scattering (CARS), broadband or multiplex CARS, stimulated Raman scattering, stimulated emission, nonlinear absorption, and micro-Raman microscopy;imaging the tissue portion with each of the modalities of image acquisition; andconstructing a dual mode image using images from each of the modalities of mage acquisition.2. The method of wherein the tissue comprises eye tissue.3. The method of wherein the eye tissue comprises trabecular meshwork (TM) eye tissue.4. The method of wherein the eye tissue comprises at least one of the group comprising:cornea, ...

Integrated Nucleic Acid Analysis

The present disclosure provides fully integrated microfluidic systems to perform nucleic acid analysis. These processes include sample collection, nucleic acid extraction and purification, amplification, sequencing, and separation and detection. The present disclosure also provides optical detection systems and methods for separation and detection of biological molecules. In particular, the various aspects of the invention enable the simultaneous separation and detection of a plurality of biological molecules, typically fluorescent dye-labeled nucleic acids, within one or a plurality of microfluidic chambers or channels. The nucleic acids can be labeled with at least 6 dyes, each having a unique peak emission wavelength. The present systems and methods are particularly useful for DNA fragment sizing applications such as human identification by genetic fingerprinting and DNA sequencing applications such as clinical diagnostics.

NUCLEIC ACID ANALYSIS DEVICE, NUCLEIC ACID ANALYSIS APPARATUS, AND NUCLEIC ACID ANALYSIS METHOD

In a nucleic acid analysis device which detects a fluorescent dye on a nucleic acid sample immobilized on a surface of a substrate by exciting the fluorescent dye with an evanescent wave, the detection of a fluorescence signal with a high SN ratio is realized even for a long nucleic acid sample. 1. A nucleic acid analysis device , in which a plurality of regions for immobilizing a nucleic acid sample are provided on a surface of a support base and a single molecule of a nucleic acid sample is immobilized on at least one of , the regions , and which performs sequence determination by performing an extension reaction of the immobilized nucleic acid sample , wherein the immobilization of the single molecule of the nucleic acid sample on the support base is performed at two or more points.2. The nucleic acid analysis device according to claim 1 , wherein the regions are subjected to a surface treatment so that the nucleic acid sample can be immobilized thereon.3. The nucleic acid analysis device according to claim 2 , wherein two or more different surface treatments are performed for at least one of the regions.4. The nucleic acid analysis device according to claim 2 , wherein the surface treatment varies between at least some of the regions.5. The nucleic acid analysis device according to claim 1 , wherein a metal structure is disposed in the regions.6. The nucleic acid analysis device according to claim 5 , wherein a microparticle is immobilized on the metal structure.7. The nucleic acid analysis device according to claim 6 , wherein the metal structure has a circular planar shape and has a diameter smaller than that of the microparticle.8. The nucleic acid analysis device according to claim 5 , wherein the metal structure is made of any of gold claim 5 , silver claim 5 , aluminum claim 5 , chromium claim 5 , titanium claim 5 , tungsten claim 5 , platinum claim 5 , and nickel.9. The nucleic acid analysis device according to claim 1 , wherein the regions are arranged ...

BIOLOGICAL SUBSTANCE DETECTION METHOD

A biological substance detection method for detecting a biological substance specifically in a pathological specimen, comprising a step of immunologically staining the pathological specimen using a fluorescent label, a step of staining the pathological specimen with a staining reagent for morphology observation purposes (eosin) to observe the morphology of the pathological specimen, a step of irradiating the stained pathological specimen, with excited light to cause the emission of a fluorescent and detecting the biological substance in the pathological specimen. In the step of immunologically staining the pathological specimen, a special fluorescent particle for which the excitation wavelength appears in a region that is different from the excitation wavelength region of eosin is used as the fluorescent label. 1. A biological substance detection method of specifically detecting a biological substance in a pathological section , the method comprising;immunostaining the pathological section with a fluorescent label;staining the pathological section with a. staining reagent for morphological observation; anddetecting the biological substance in the pathological section through fluorescence emission by irradiation of the stained pathological section with excitation light, whereinin the immunostaining of the pathological section, a fluorescent nanoparticle comprising phosphor or a semiconductor and having an excitation wavelength region different from an excitation wavelength region of the staining reagent is used as the fluorescent label.2. The biological substance detection method of specifically detecting a biological substance in a pathological section , the method comprising:immunostaining the pathological section with a fluorescent label;staining the pathological section with a staining reagent for morphological observation; anddetecting the biological substance in the pathological section through fluorescence emission by irradiation, of the stained pathological ...

METHODS OF QUANTIFYING EXOSOME IN CELL CULTURE AND METHOD OF INCREASING RECOVERY RATE OF EXOSOME USING THE SAME

A method of detecting and recovering of exosomes in a sample, as well as a method of determining the recovery rate of exosomal recovery, and a method of screening for a material that induces secretion of the exosomes in a sample, which methods employ the use of a protease. 1. A method of detecting exosomes containing fluorescent material , the method comprising:incubating recombinant exosomes comprising a fluorescent material in a cell culturing medium comprising a protease;filtering the culturing medium using a filter;and;detecting fluorescence of the recombinant exosomes.2. The method of claim 1 , wherein the method further comprises incubating the recombinant exosomes in a cell culture medium comprising glycosidase.3. The method of claim 1 , wherein the fluorescent material is a fluorescent protein or a photoprotein.4. The method of claim 1 , wherein the protease is pepsin claim 1 , peptidase claim 1 , trypsin claim 1 , protease K claim 1 , calpain claim 1 , papain claim 1 , metalloproteinase claim 1 , chymotrypsin claim 1 , or elastase.5. The method of claim 2 , the glycosidase is endoglycosidase F1 claim 2 , endoglycosidase F2 claim 2 , endoglycosidase F3 claim 2 , glucosidase claim 2 , galactosidase claim 2 , sucrase claim 2 , maltase claim 2 , O-glycosidase claim 2 , neuraminidase claim 2 , PNGase claim 2 , glucosaminidase claim 2 , or flucosidase.6. A method of screening for a substance that promotes secretion of exosomes claim 2 , the method comprising:contacting a a transformed cell that secretes recombinant exosomes comprising a fluorescent material with a candidate material to be screened; incubating the cell and candidate material in a cell culturing medium comprising a protease, wherein recombinant exosomes are secreted into the cell culturing medium;filtering the recombinant exosomes from the cell culturing medium using a filter; andmeasuring fluorescence of the filtered recombinant exosomes.7. The method of further comprising comparing the ...

COMPACT WIDE-FIELD FLUORESCENT IMAGING ON A MOBILE DEVICE

Wide-field fluorescent imaging on a mobile device having a camera is accomplished with a compact, light-weight and inexpensive optical components that are mechanically secured to the mobile device in a removable housing. Battery powered light-emitting diodes (LEDs) contained in the housing pump the sample of interest from the side using butt-coupling, where the pump light is guided within the sample holder to uniformly excite the specimen. The fluorescent emission from the sample is then imaged using an additional lens that is positioned adjacent to the existing lens of the mobile device. A color filter is sufficient to create the dark-field background required for fluorescent imaging, without the need for expensive thin-film interference filters. 1. A fluorescent imager for use with a mobile device having a camera element comprising:a housing configured for securement to the mobile device;an array of capillary tubes disposed in the housing, the array of capillary tubes containing fluorescently labeled particles;an excitation light source disposed in the housing and oriented to side illuminate the array of capillary tubes;a filter holder disposed in the housing and configured to hold filter media therein; anda lens disposed in the housing, wherein the housing is configured to attach to the mobile device to place the lens adjacent to the camera element.2. The fluorescent imager of claim 1 , wherein the mobile device comprises a mobile phone.3. The fluorescent imager of claim 1 , wherein the housing is configured for removeable securement to the mobile device.4. The fluorescent imager of claim 1 , further comprising a filter disposed in the filter holder and wherein the filter holder is one of fixed or moveable.5. The fluorescent imager of claim 1 , further comprising a battery configured to power the excitation light source.6. The fluorescent imager of claim 1 , wherein the fluorescently labeled particle comprises a pathogen or cell.7. The fluorescent imager of claim ...

System for Glycated Protein Detection

A method of detecting the presence of glycated proteins or peptides (GPs) in a sample comprises carrying out the steps of assessing the sample for fluorescence, subjecting the sample to UV radiation, and reassessing the sample for an increase in fluorescence relative to any fluorescence assessed in said first assessing step, an increase in fluorescence at said reassessing step being indicative of the presence of GPs. The method may be useful for detecting disease such as diabetes.

Use of bacterial beta-lactamase for in vitro diagnostics and in vivo imaging, diagnostics and therapeutics

Provided herein are methods for detecting, quantifying, differentiating, diagnosing and imaging pathogenic bacteria or condition associated therewith using substrates for bacterial enzymes. Fluorescent, luminescent or colorimetric signals emitted by substrates or enzyme products in the presence of the bacteria are compared to controls to detect and locate the pathogenic bacteria. Provided is a method for screening therapeutic agents to treat the pathophysiological conditions by measuring a signal emitted from the substrates or products in the presence and absence of the potential therapeutic agent and a diagnostic method for detecting a mycobacterial infection in a subject by contacting biological samples with a substrate and imaging for signals emitted from a mycobacterial beta-lactamase product. Also provided are fluorogenic substrates or substrates comprising a colored dye or a chemical reagent effective to induce a color or pH change.

AFFINITY METHODS AND COMPOSITIONS EMPLOYING ELECTRONIC CONTROL OF PH

Methods and apparatuses for detection of target molecules are provided. 1. A method of detecting a target analyte , the method comprising ,providing into a chamber a sample comprising a mixture of molecules including one or more target analyte;generating a pH gradient in the chamber with one or more proton and/or hydroxyl injector, thereby positioning analytes in the chamber based on the isoelectric point (pI) of the analytes, wherein the target analyte is precipitated and/or adhered to the chamber once positioned at the location in the chamber corresponding to the target analyte pI; anddetecting the precipitated analyte.2. The method of claim 1 , wherein the precipitated or adhered analyte is captured in or adjacent to an opening in the surface of the chamber.3. The method of claim 1 , wherein the detecting comprises contacting the precipitated analyte with an affinity agent that specifically binds the analyte.4. The method of claim 3 , wherein the binding of the affinity agent to the target analyte is detected by contacting the bound affinity agent with a secondary antibody and subsequently detecting the presence of the secondary antibody with a detectable label.5. A method of purifying a target analyte from a mixture claim 3 , the method comprising claim 3 ,providing into a chamber a sample comprising a mixture of molecules including one or more target analyte, wherein the chamber comprises a solid support linked to an affinity agent specific for the target analyte, wherein the solid support is positioned at a location in the chamber substantially corresponding to the pI of the target analyte following generation of a pH gradient;generating the pH gradient in the chamber with a proton and/or hydroxyl injector, thereby positioning analytes in the chamber based on the isoelectric point (pI) of the analytes, such that the position of the target analyte is in proximity to the solid support, thereby binding the target analyte to the affinity agent;washing the chamber, ...

BIOLOGICAL MOLECULE DETECTING APPARATUS AND BIOLOGICAL MOLECULE DETECTING METHOD

A laser beam is emitted onto fluorescent molecules within a solution to orient the fluorescent molecules. The direction in which the laser beam is emitted is switched to switch the transition moment direction of the fluorescent particles to be parallel or perpendicular to the vibrating direction of linearly polarized excitation light. Thereby, the fluorescent molecules of free molecules and binding molecules can be switched between an excited and a non excited state. There is a difference in the speeds at which the orientation directions change for molecules which have undergone and molecules which have not undergone antigen antibody reactions. Therefore, the fluorescence contributed by fluorescent molecules associated with free molecules and the fluorescence contributed by fluorescent molecules associated with binding molecules can be calculated respectively, to measure the concentration of a detection target substance with high sensitivity. 112-. (canceled)13. A biological molecule detecting apparatus that causes a detection target substance , a specific binding substance that specifically binds to the detection target substance , and fluorescent molecules to bind to each other within a solution , and detects fluorescence emitted by the fluorescent molecules to detect or quantify the detection target substance , comprising:a light source that emits excitation light having a light component which is linearly polarized in a specific direction that excites the fluorescent molecules;orientation control means for switching the orientation of the fluorescent molecules within the solution to orientations in at least two directions;a light receiving section that detects the fluorescence emitted by the fluorescent molecules; anda calculating section that detects or quantifies the detection target substance based on the fluorescence detected by the light receiving section.14. A biological molecule detecting apparatus as defined in claim 13 , wherein:the orientation control ...

MULTIPLEX MEASURE OF ISOTYPE ANTIGEN RESPONSE

The application discloses methods for simultaneous detection and quantifying multiple target analytes, including immunoglobulin isotypes and sub-classes, single and multiple protein antibodies within a test sample in a single reaction vessel. The method uses reaction wells as on a multi-well plate, each single well comprising microarrays of: calibration spots, having a predetermined quantity of a target analyte; and capture spots, having multiple agent antibodies, including isotypes and subclasses that specifically bind the target analytes. The captured analytes and the calibration spots are detected with fluorescently labeled antibodies specific for each analyte. The application also discloses methods for detecting and quantifying biomarkers, therapeutic proteins and patient derived antibodies; the use of secondary reagents to determine immunoglobulin classes Ig G, A, M, E and sub-classes including IgG1, IgG2, IgG3, IgG4 and IgA. The intensity of each fluorescent signal allows measurement of a specific immune response to a therapeutic protein and associated analytes. 1. A method for simultaneously detecting and quantifying two or more target analytes in a test sample comprising two or more target analytes , contained in a single reaction vessel , the method comprising the following steps: i) a first calibration matrix comprising a plurality of first calibration spots, each of the first calibration spots comprising a predetermined amount of a first target analyte, the first target analyte being an antibody isotype or an antibody sub-class;', 'ii) a second calibration matrix comprising a plurality of second calibration spots, each of the second calibration spots comprising a predetermined amount of a second target analyte, the second target analyte being an antibody isotype or an antibody sub-class;', 'iii) a first capture matrix comprising a plurality of first capture spots, each of said first capture spots comprising a predetermined amount of a first agent that ...

Biomarkers for Diagnosing Schizophrenia and Bipolar Disorder

The invention relates to the identification and selection of novel biomarkers and the identification and selection of novel biomarker combinations which are differentially expressed in blood and useful in diagnosing schizophrenia and/or bipolar disorder as well as monitoring therapeutic efficacy of treatment for schizophrenia or bipolar disorder. The measurement of expression levels of the products of the biomarkers and combinations of biomarkers of the invention can be used to diagnose schizophrenia and/or bipolar disorder. Measurement of the expression level of products of biomarkers of the invention using polynucleotides and proteins which specifically and/or selectively hybridize to the products of the biomarkers of the invention are also encompassed within the scope of the invention as are compositions and kits containing said polynucleotides and proteins. Further encompassed by the invention is the use of the polynucleotides and proteins to monitor the efficacy of therapeutic regimens. 1. A composition comprising a collection of two or more isolated polynucleotides , said polynucleotides which selectively hybridize to at least two biomarkers of the invention , wherein the biomarkers are selected from the group consisting of the genes: adenylosuccinate synthase (ADSS); apolipoprotein B mRNA editing enzyme , catalytic polypeptide-like 3B (APOBEC3B); ataxia telangiectasia mutated (includes complementation groups A , C and D) (ATM); Charcot-Leyden crystal protein (CLC); C-terminal binding protein 1 (CTBP1); chemokine (C—X—C motif) ligand 1 (melanoma growth stimulating activity , alpha) (CXCL1); death associated transcription factor 1 (DATF1); 5100 calcium binding protein A9 (calgranulin B) (S100A9) , and as set out in Table 1 , and wherein the composition is used to measure the level of expression of said biomarker.2. A composition comprising a collection of two or more isolated polynucleotides which bind selectively to the RNA products of at least two biomarkers ...

MEASURING DEVICE, MEASURING SYSTEM, MEASURING METHOD, CONTROL PROGRAM, AND RECORDING MEDIUM

A measuring device () of the present invention includes a detector control module () for obtaining, from a scanning mechanism including an excitation light source () for emitting excitation light and a detector () for receiving fluorescence generated from the measurement target upon irradiation with the excitation light, measurement data of the fluorescence, a position information obtaining module () for obtaining, from a driving mechanism for controlling relative positions of the scanning mechanism and the measurement target, information of a position where the measurement target is irradiated with the excitation light when the measurement data is obtained, and a fluorescence characteristic management module () for preparing fluorescence characteristic data including the measurement data and the position information. 118-. (canceled)19. A measuring device comprising:measurement data obtaining means for obtaining, from a scanning mechanism including an excitation light irradiation unit for irradiating a measurement target with excitation light and a light receiving unit for receiving fluorescence generated from the measurement target upon irradiation with the excitation light, measurement data representing optical characteristics of the fluorescence;position information obtaining means for obtaining, from a driving mechanism for controlling relative positions of the scanning mechanism and the measurement target, position information indicating an irradiation position where the measurement target is irradiated with the excitation light when the measurement data is obtained; andfluorescence characteristic management means for preparing fluorescence characteristic data including the measurement data obtained by the measurement data obtaining means and the position information obtained by the position information obtaining means.20. The measuring device according to claim 19 , wherein the fluorescence characteristic management means prepares claim 19 , each time the ...

PH-RESPONSIVE FLUORESCENT FALSE NEUROTRANSMITTERS AND THEIR USE

This invention relates to compounds having the following structure: 2. The compound of claim 1 ,{'sub': '6', 'wherein Ris H, alkyl, alkenyl, or alkynyl,'}or a pharmaceutically acceptable salt thereof.3. The compound of claim 1 ,{'sub': 4', '2', '2', '2', '5', '2', '2', '2, 'wherein Ris H or —CHCHNH; and Ris —H or —CHCHNH,'}or a pharmaceutically acceptable salt thereof.4. The compound of claim 3 , wherein Ris H or halogen.9. The process of claim 8 ,{'sub': '6', 'wherein in the compound, Ris H, alkyl, alkenyl, or alkynyl.'}15. A method of determining the pH within a vesicle in a cell comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a) contacting the cell with the compound of for a time sufficient for the compound to be taken up into the vesicle;'}b) quantitating fluorescence of the compound in the vesicle at a first excitation wavelength; andc) quantitating fluorescence of the compound in the vesicle at a second excitation wavelength,wherein the ratio of the fluorescence quantitated in step b) and the fluorescence quantitated in step c) is compared to a predetermined reference curve so as to determine the pH within the vesicle in a cell.1620-. (canceled)21. A method for detecting an active monoamine transporter in a sample comprising:a) providing a sample;b) quantitating fluorescence of the sample;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'c) contacting the sample with the compound of for a time sufficient that an active monoamine transporter present in the sample can uptake the compound;'}d) washing the sample so as to remove any of the compound that has not been transported by the active monoamine transporter; ande) quantitating fluorescence of the sample,wherein an increase in the fluorescence of the sample quantitated in step e) over the fluorescence quantitated in step b) indicates the presence of an active monoamine transporter.2226-. (canceled)27. A process of identifying a compound which is an inhibitor of a monoamine transporter ...

Targeted, NIR Imaging Agents for Therapy Efficacy Monitoring, Deep Tissue Disease Demarcation and Deep Tissue Imaging

Compounds and methods related to NIR molecular imaging, in-vitro and in-vivo functional imaging, therapy/efficacy monitoring, and cancer and metastatic activity imaging. Compounds and methods demonstrated pertain to the field of peripheral benzodiazepine receptor imaging, metabolic imaging, cellular respiration imaging, cellular proliferation imaging as targeted agents that incorporate signaling agents. 2. The method of claim 1 , wherein said sample is at least one of cells claim 1 , tissue claim 1 , cellular tissue claim 1 , serum claim 1 , cell extract claim 1 , bodily fluids.3. The method of claim 2 , wherein the bodily fluids are breast milk claim 2 , sputum claim 2 , vaginal fluids claim 2 , urine.4. The method of claim 1 , wherein the administering step is in vivo or in vitro.5. The method of claim 1 , wherein said molecular event is at least one of peripheral benzodiazepine receptor expression claim 1 , cell proliferation claim 1 , glucose uptake claim 1 , epidermal growth factor receptor expression claim 1 , microglial activation claim 1 , apoptosis claim 1 , matrix metalloproteinase activation.6. The method of claim 1 , wherein said signaling agent is a near infrared signaling agent.7. The method of claim 1 , wherein said detecting step comprises near infrared detection.8. The method of claim 8 , wherein the near infrared detection included near infrared imaging.9. The method of claim 1 , further comprising the step of:analyzing said signal to diagnose a disease state.10. The method of claim 7 , wherein the disease state is cancer claim 7 , neurodegenerative disease claim 7 , cancer claim 7 , multiple sclerosis claim 7 , epilepsy.11. The method of claim 9 , wherein the disease state is brain cancer or breast cancer.12. The method of claim 1 , wherein the signaling agent is a cyanine dye.1419-. (canceled)22. The compound of claim 21 , wherein the signaling moiety is a dye.2328-. (canceled)3055-. (canceled)5770-. (canceled) This application claims priority to ...

METHODS AND RELATED DEVICES FOR SINGLE MOLECULE WHOLE GENOME ANALYSIS

Provided are methods of labeling and analyzing features along at least one macromolecule such as a linear biopolymer, including methods of mapping the distribution and frequency of specific sequence motifs or the chemical or proteomic modification state of such sequence motifs along individual unfolded nucleic acid molecules. The present invention also provides methods of identifying signature patterns of sequence or epigenetic variations along such labeled macromolecules for direct massive parallel single molecule level analysis. The present invention also provides systems suitable for high throughput analysis of such labeled macromolecules. 139-. (canceled)40. A method for analyzing a double stranded DNA , comprising:nicking one strand of the DNA at a nick site;labeling the DNA at or about the nick site;ligating the labeled DNA with a ligase; anddetecting the label.41. The method of claim 40 , wherein said nicking is accomplished with a site-specific nicking enzyme.42. The method of claim 41 , wherein said nicking claim 41 , labeling claim 41 , ligating claim 41 , and detecting are each performed at multiple sites on the DNA.43. The method of claim 42 , further comprising transporting the ligated DNA into a nanochannel and maintaining the DNA in elongated form in the nanochannel.44. The method of claim 40 , wherein the label is fluorescent.45. The method of claim 40 , wherein the label is a fluorescently-labeled base.46. The method of claim 40 , wherein after said nicking the DNA has a break in a single strand claim 40 , into which at least one nucleotide is introduced.47. The method of claim 46 , wherein said nick separates first and second pieces of the nicked strand and wherein prior to said ligating said at least one nucleotide is joined to said first piece but not to said second piece.48. The method of claim 46 , wherein said at least one nucleotide is labeled.49. The method of claim 48 , further comprising transporting the labeled DNA into a nanochannel ...

DETECTION OF ANTIGEN-SPECIFIC PERIPHERAL BLOOD MONONUCLEAR CELLS AND METHODS FOR DIAGNOSING IMMUNE DISORDERS

The present invention relates to a method for detecting the presence or the absence, and optionally quantifying and/or isolating, antigen-specific peripheral blood mononuclear cells. This method, which involves flow cytometry, is based on the use of a fluorescently-labeled antibody specifically recognizing peripheral blood mononuclear cells, and of fluorescently-labeled beads coated with at least one antigen that is specifically recognized by antigen-specific peripheral blood mononuclear cells. The method according to the invention is for example useful for diagnosing immune disorders such as transplant rejections and autoimmune disorders. 2. A method according to claim 1 , wherein said peripheral blood mononuclear cells are B lymphocytes.3. The method according to claim 1 , wherein said antibody specifically recognizing B lymphocytes is an anti-CD19 antibody.4. The method according to claim 1 , wherein said antigen that is specifically recognized by said antigen-specific PBMC is an HLA antigen encoded by the major histocompatibility complex (MHC).5. The method according to claim 1 , wherein said bead is a latex bead.6. The method according to claim 1 , further comprising the step of calculating the percentage of PBMC that correspond to said antigen-specific PBMC.7. The method according to claim 1 , wherein said sample is blood.8. The method according to claim 1 , wherein said sample is from a patient suffering from claim 1 , or at risk of suffering from claim 1 , an immune disorder.9. The method according to claim 8 , wherein said immune disorder is selected from the group consisting of a transplant rejection claim 8 , a transfusion reaction claim 8 , an autoimmune disorder and an allergic reaction.10. The method according to claim 1 , wherein:said sample is from a patient who has received, or who is in need of receiving, a transplant from a donor; andsaid antigen is an antigen encoded by the MHC of the donor, but that is not encoded by the MHC of the patient.11. ...

AGGREGATION INDUCED EMISSION LUMINOGEN-BASED URINARY PROTEIN DETECTION DEVICE FOR MONITORING HUMAN HEALTH

The presently disclosed invention relates to a portable device for detecting one or more urinary proteins based on aggregation-induced emission (AIE) luminogen and quantifying the total urinary proteins in a urine sample in order for monitoring human health, in particular, to a device that utilizes a water-soluble AIE luminogen to detect one or more urinary protein aggregation in order to determine the content of both the target protein and the total urinary proteins in a subject. The device is useful at home or at clinical level for monitoring human health on regular basis. 1. A portable urinary protein detection device for detecting and quantifying total urinary proteins in a urine sample using water soluble aggregation-induced emission luminogen , the device comprising a light-insulating case , a light source , a sample container , a cell holder , a photo-detector , a signal amplifier , a plurality of output components , and associated integrated circuit ,wherein said light source, said cell holder, said photo-detector, said signal amplifier, and associated integrated circuit are enclosed in said case to isolate from external light during said detecting;said light source is a LED light source capable of generating a light having a narrow bandwidth which matches the excitation wavelength of said water soluble aggregation-induced emission luminogen and is outside the emission spectrum of said aggregation-induced emission luminogen;said sample container is configured to house said water soluble aggregation-induced emission luminogen and said urine sample for emission to take place under exposure to said light source;said cell holder is configured to fix the position of said sample container during said detecting;said photo-detector is configured to detect fluorescence signal emitted from said water soluble aggregation-induced emission luminogen and said urine sample in said sample container under the exposure to said light source and convert the fluorescence signal ...

FILTERLESS TIME-DOMAIN DETECTION OF ONE OR MORE FLUOROPHORES

A device and method are described in which the lifetime of a fluorescent species or fluorophores is detected in the absence of any optical filter. Based on the measured fluorescent lifetimes, molecules or compounds attached to a fluorophores such as small organic molecules, polymers, peptides, saccharides and nucleic acids can be identified or assayed. 1. A detection circuit for fluorescent species , comprisinga fluorescent chemical species excitation arrangement;a filterless fluorescent chemical species detection arrangement;a control circuit configured to independently enable or disable the fluorescent species excitation arrangement and the fluorescent species detection arrangement; anda signal processing circuit, operatively connected with the fluorescent chemical species detection arrangement and configured to generate time varying characteristics as a function of the output of the fluorescent species detection arrangement, the time varying characteristics being indicative of the fluorescent species.2. The detection circuit of claim 1 , wherein the control circuit is configured to:disable the filterless fluorescent chemical species detection arrangement while enabling the fluorescent chemical species excitation arrangement; andenable the filterless fluorescent species detection arrangement while disabling the filterless fluorescent species excitation arrangement,thus allowing controlled excitation and controlled detection of the fluorescent chemical species.3. The detection circuit of claim 2 , wherein the controlled excitation and the controlled detection are performed at a resolution better than the fluorescent lifetime of the fluorescent chemical species.4. The detection circuit of claim 2 , wherein the fluorescent chemical species excitation arrangement comprises a light emitting device (LED) configured to emit light at a wavelength in correspondence of an excitation wavelength of the fluorescent chemical species claim 2 , and the filterless fluorescent ...

Methods and Compositions for Rapid Multiplex Amplification of STR Loci

Provided are methods for multiplex polymerase chain reaction (PCR) amplification of short tandem repeat (STR) loci that can be used to rapidly generate a highly specific STR profile from target nucleic acids. The resulting STR profiles are useful for human identification purposes in law enforcement, homeland security, military, intelligence, and paternity testing applications. 1. A method of multiplex amplification of STR loci from a sample containing nucleic acids , comprising:(a) contacting in solution said sample with at least six different primer pairs for STR loci, wherein at least one primer of each primer pair is labeled with a fluorescent dye and wherein the resultant STR multiplex has a Multiplex Density equal to or greater than 3.20;(b) simultaneously amplifying by polymerase chain reaction (PCR) in one reaction chamber using said at least 6 primer pairs to produce amplified nucleic acid products; and(c) detecting said nucleic acid products by laser induced fluorescence.2. A method of multiplex amplification of STR loci from a sample containing nucleic acids , comprising:(a) contacting in one solution said sample with at least six different primer pairs for STR loci, wherein at least one primer of each primer pair is labeled with a fluorescent dye, and wherein and at least six different fluorescent dye-labels are used, and wherein the resultant STR multiplex has a Multiplex Density equal to or greater than 2.0;(b) simultaneously amplifying by polymerase chain reaction (PCR) in one reaction chamber using said at least 6 primer pairs to produce amplified nucleic acid products; and(c) detecting said nucleic acid products by laser induced fluorescence.3. The method of wherein the resultant STR multiplex has a Multiplex Density equal to or greater than 3.2.4. A method of multiplex amplification of STR loci from a sample containing nucleic acids claim 2 , comprising:(a) contacting in solution said sample with at least six different primer pairs for STR loci, ...

BIOSENSOR USING WHISPERING GALLERY MODES IN MICROSPHERES

A biosensor for detecting the presence of a target analyte is disclosed. The biosensor is formed from microspheroidal particles which have had a binding partner for the target analyte immobilized on their surfaces. The binding partners may be nucleotides; peptides, proteins, enzymes, antibodies and so on. When the analyte binds to its partner, the whispering gallery mode (WGM) profiles of the micro spheroidal particles change such that the profile peaks undergo a red- or blue-shift. The immobilized binding partners may include fluorophores and the like so that they emit fluorescence, phosphorescence, incandescence and the like. These fluorophores may take the form of a nanocrystal or quantum dot. 1. A method of detecting multiple analytes in a sample , said method comprising:(a) contacting multiple sets of microspheroidal particles with a sample putatively comprising said analytes, wherein each particle within a set of microspheroidal particles comprises an optically detectable label and an immobilized putative binding partner or binding partners of an analyte, wherein each set of microspheroidal particles has a different immobilized binding partner or binding partners of an analyte, a different microspheroidal particle size, and a different optically detectable label, and wherein each particle set has a defined Whispering Gallery Mode (WGM) profile, wherein binding of an analyte to said immobilized binding partner or binding partners results in a change in said WGM profile indicated by a spectral shift in the optically detectable label of a set of microspheroidal particles, which is indicative of the presence of said analyte, and(b) detecting binding of analytes to said multiple sets of microspheroidal particles by detecting spectral shifts in the WGM profiles of each set of microspheroidal particles, wherein said spectral shifts are in one or more emission peaks of each optically detectable label.2. The method of claim 1 , wherein one or more optically detectable ...

Enzyme detection

An enzyme detection product ( 1 ) for detecting the presence of an enzyme in a sample. The product ( 1 ) comprises: a reaction zone ( 16 ) for receiving the sample; a visualization zone ( 10 ) for presenting a signal in response to the detection of the activity of the enzyme; and a membrane ( 11 ). The membrane ( 11 ) is interposable between the reaction zone ( 16 ) and the visualization zone ( 10 ) and prevents passage from the reaction zone ( 16 ) to the visualization zone ( 10 ) the components having a size greater than a threshold size. The reaction zone ( 16 ) comprises a reactant capable of reacting with the enzyme in order to generate a reaction product having a size less than a threshold size.

ISOLATION OF PELLET-FORMING MICROORGANISMS

The present disclosure provides technologies for identifying, characterizing and/or sorting pellet-forming microorganisms such as bacteria and/or fungi (e.g., yeast) in liquid culture, and particularly under fermentation conditions. In some embodiments, the pellet-forming microorganisms produce one or more commercial products. For example, in some embodiments the pellet-forming microorganisms produce one or more organic acids, carotenoid compounds, essential fatty acids, industrial enzymes, active pharmaceuticals, extracellular carbohydrates, and insecticidal compounds, etc. In many embodiments, the organisms are sorted while in their pellet form. 1. A method comprising steps of:a. obtaining a sample containing genetically diverse microorganisms in pellet form;b. detecting one or more optically detectable parameters of individual pellets within the sample; andc. sorting individual pellets into separate containers based on the detected one or more parameters.2. (canceled)3. (canceled)4. The method of claim 1 , wherein the sample containing genetically diverse microorganisms in pellet form comprises microorganisms related as progeny of a parent microorganism claim 1 , which progeny were generated through application of a mutagenic protocol.5. The method of claim 1 , wherein the sample containing genetically diverse microorganisms comprises microorganisms related to the natural heterogeneity found within a parent microorganism.6. (canceled)7. (canceled)8. The method of claim 1 , wherein the optically detectable parameter is selected from the group consisting of size of the microorganism pellets claim 1 , optical density of the microorganism pellets claim 1 , intensities of one or more fluorescent emissions claim 1 , and combinations thereof.9. The method of claim 8 , wherein one of said fluorescent emissions is autofluorescence of the pelleted microorganism.10. The method of claim 8 , wherein one of said fluorescent emissions quantifies a fluorescent dye present in or ...

Methods And Compositions For Cellular Imaging And Cancer Cell Detection Using Light Harvesting Conjugated Polymer-Biomolecular Conjugates

The invention is a compound represented by any one of Structural Formulas (I)-(IV), or a salt thereof, wherein the values and alternative values for the variables are as defined in the Detailed Description of the Invention. Methods using a compound of Structural Formula (I)-(IV), or a salt thereof, are also presented. 2. The compound of claim 1 , wherein:{'sup': '3', 'sub': 1', '12', '1', '12, 'R′ and Rare each independently a saturated or unsaturated hydrocarbon, a (C-C)alkoxyl, or a (C-C)alkyl group substituted with a quaternary amine, a disubstituted amine or an amide;'}Ar is fluorene, phenyl, napthyl, thiophenyl, benzothiadiazole, carbazole, or pyridinyl;{'sub': 2', '3, 'the terminating group is —C≡CH, —NH, —SH, —COOH or —N; and'}{'sub': 12', '48, 'L and L′ are each independently (C-C)alkyl, polyethylene glycol (PEG) having from 5-15 repeat units, polyethyleneimine (PEI) having from 1-100 repeat units, or PEG having from 5-15 repeat units conjugated to PEI having from 1-100 repeat units.'}4. The compound of claim 3 , or a salt thereof claim 3 , wherein the terminating group is —C≡CH.10. The method of claim 9 , wherein the gene of step (a) is a plasmid.13. The method of claim 12 , wherein the gene encodes a fluorescent protein that fluoresces at a different wavelength than the hyperbranched conjugated polyelectrolyte.14. The method of claim 13 , wherein the fluorescent protein is expressed in the cell.15. The method of claim 12 , wherein the visualization by fluorescence is completed with a fluorescence microscope claim 12 , confocal microscope claim 12 , or a fluorescence imager.16. The method of claim 12 , wherein the gene is one or more genes that are identical to one another or are different from one another.17. The method of claim 13 , wherein the visualization by fluorescence is completed with a fluorescence microscope claim 13 , confocal microscope claim 13 , or a fluorescence imager.18. The method of claim 14 , wherein the visualization by fluorescence is ...

METHOD FOR AUTOMATED TISSUE ANALYSIS

The invention provides an improved method for identifying and interpreting tissue specimens and/or cells derived from tissue specimens. A panel of cell-based reagents provides a number of readouts of cellular states or biomarkers that together define a profile of a diversity of cellular states or biomarkers in a tissue specimen representing the ‘systems” nature of biology. This cellular profile is interpreted using informatics tools, to identify similarities between specimens, in vivo medical conditions, and suggest options for treating medical conditions. 121-. (canceled)23. The method of claim 22 , wherein the panel of fluorescently labeled reagents is selected from the group consisting of fluorescently labeled antibodies claim 22 , fluorescently labeled peptides claim 22 , fluorescently labeled proteins claim 22 , fluorescently labeled aptamers claim 22 , fluorescently labeled oligonucleotides claim 22 , fluorescently labeled chemicals claim 22 , fluorescent chemicals claim 22 , and a combination thereof.24. The method of claim 22 , wherein at least one biomarker is a nucleic acid biomarker.25. The method of claim 22 , wherein the medical state of the one or more isolated tissue samples is the presence or absence of a disease claim 22 , the presence or absence of a cancer and/or the presence or absence of toxicity.26. The method of claim 25 , wherein the tissue is liver.27. The method of claim 26 , wherein the panel of fluorescently labeled reagents comprises:a) a set of fluorescently labeled reagents specific for at least four hepatocyte biomarkers;b) a set of fluorescently labeled reagents specific for at least four stromal cell biomarkers; i) a set of fluorescently labeled reagents specific for at least three hepatocyte cell biomarkers; and', 'ii) a set of fluorescently labeled reagents specific for at least three stromal cell biomarkers;', 'or, 'c) a combination ofd) a combination thereof.28. The method of claim 27 , wherein the panel of fluorescently labeled ...

METHOD AND DEVICE FOR DETERMINING CONTENT OF THE MIDDLE AND PROTEIN BOUND UREMIC TOXINS IN A BIOLOGICAL FLUID

This invention relates to a novel method and a device for determining middle and protein bound uremic toxins in the biological fluids. More specifically, the present invention relates to an optical method utilizing fluorescence, preferable fluorescence of the spent dialysate, and a specific model, including a unique set of optical spectral components at certain wavelengths, to determine, preferable on-line, the concentration of the middle and protein bound uremic toxins such as beta2-microglobulin (B2M), and indoxyl sulfate (IS). 1. A method for determining content of the middle and protein bound uremic toxins in a biological fluid comprising:a. introducing the sample of the biological fluid into a fluorimetrical cuvette;b. applying light with predetermined wavelengths to the sample and recording an fluorescence signal of the sample;c. calculating the concentration of the substance in the sample from the transforming function.2. The method according to claim 1 , comprising introducing flowing stream of the biological fluid through fluorometrical flow-cuvette.3. The method according to claim 1 , comprising outputting the concentration of the substance to a display device or to a printer.4. The method according to claim 1 , wherein the excitation wavelength from the light source is in the wavelength range of 190-890 nm.5. The method according to claim 1 , wherein the emission wavelength detected by the light detector is operating in wavelength range of 190-900 nm.6. The method according to claim 1 , wherein the substance is β2-microglobulin.7. The method according to claim 1 , wherein the light source is operating in the wavelength range of 360-380 nm claim 1 , and the fluorescence light detector is operating in the wavelength range of 440-470 nm claim 1 , suitable for beta2-microglobulin measurements.8. The method according to claim 1 , wherein the substance is indoxyl sulfate.9. The method as in claim 1 , wherein the light source is operating in the wavelength range ...

METHOD AND DEVICE FOR ANALYSING MOLECULAR INTERACTIONS, AND USES THEREOF

The invention relates to a method for analysing an interaction between a first molecule and a second molecule bonded to a particle, including the following steps: contacting the first molecule with the second molecule bonded to the particle under conditions enabling the interaction thereof; applying a predetermined liquid flow to the particle bonded to the second molecule; observing a movement of the particle bonded to the second molecule caused by the applied flow; analysing the interaction according to the movement observed and the applied flow, the particle having a greater hydrodynamic resistance than the first and/or second molecule, and a mass Péclet number of greater than 1. The invention also relates to a device for analysing an interaction between a first molecule and at least one second molecule, as well as to the use of the method or of the device in screening a candidate molecule for developing a drug. 2. The method according to claim 1 , wherein the movement of the particle is observed by means of the physical and/or chemical properties of the particle.3. The method according to claim 2 , wherein the observation is carried out by a method selected from the group comprising an optical method claim 2 , a chemical method claim 2 , an electrochemical method and a magnetic method.4. The method according to claim 3 , wherein the observation is carried out by an optical method selected from the group comprising the use of a fluorescence emitter and of a means for detecting fluorescence claim 3 , detection of absorption claim 3 , detection of reflection claim 3 , detection of scattering and detection of diffraction.5. The method according to claim 4 , wherein the fluorescence emitter is the particle itself or a label associated with the particle and/or with at least one molecule selected from the first molecule and the second molecule.6. The method according to claim 1 , wherein the predetermined liquid flow is such that it makes it possible to apply to the ...

Diarylamine-based fluorogenic probes for detection of peroxynitrite

Provided herein are improved fluorogenic compounds and probes that can be used as reagents for measuring, detecting and/or screening peroxynitrite. The fluorogenic compounds of the invention can produce fluorescence colors, such as green, yellow, red, or far-red. Also provided herein are fluorogenic compounds for selectively staining peroxynitrite in the mitochondria of living cells. Provided also herein are methods that can be used to measure, directly or indirectly, the presence and/or amount of peroxynitrite in chemical samples and biological samples such as cells and tissues in living organisms. Also provided are high-throughput screening methods for detecting or screening peroxynitrite or compounds that can increase or decrease the level of peroxynitrite in chemical and biological samples.

OPTICAL SYSTEM FOR FLUORESCENCE DETECTION AND FINE PARTICLE ANALYZING APPARATUS

An optical system for fluorescence detection includes two parabolic mirrors, a first parabolic mirror and a second parabolic mirror, and fluorescent light beams that are incident from different directions are reflected by the first parabolic mirror as parallel light beams to the second parabolic mirror and are converged at one point by the second parabolic mirror. 1. An optical system for fluorescence detection comprising:two parabolic mirrors, a first parabolic mirror and a second parabolic mirror,wherein fluorescent light beams that are incident from different directions are reflected by the first parabolic mirror as parallel light beams to the second parabolic mirror and are converged at one point by the second parabolic mirror.2. The optical system for fluorescence detection according to claim 1 ,wherein the first parabolic mirror and the second parabolic mirror have reflecting surfaces whose curvatures are different from each other.4. The optical system for fluorescence detection according to claim 1 ,wherein the first parabolic mirror has a numerical aperture NA of 0.5 or more.5. The optical system for fluorescence detection according to claim 1 , further comprising:a plane mirror that reflects one of the fluorescent light beams reflected by the first parabolic mirror to the second parabolic mirror.6. The optical system for fluorescence detection according to claim 1 ,wherein the first parabolic mirror and the second parabolic mirror are disposed with a space therebetween.7. A fine particle analyzing apparatus comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the optical system for fluorescence detection according to .'}8. The fine particle analyzing apparatus according to claim 7 , further comprising:two or more light sources;a plurality of light detectors; anda detection unit,wherein the light sources emit an excitation light beam, and a light beam emitted from a fine particle that is irradiated with the excitation light beam is detected by the ...

Fluoroscopy Apparatus, Fluoroscopy System, and Fluorescence-Image Processing Method

A fluoroscopy apparatus including: an illumination unit having a light source radiating illumination light and excitation light onto an observation target, a fluorescence-imaging unit acquiring a fluorescence image by imaging fluorescence generated at the observation target by the excitation light, a white-light-imaging unit acquiring a reference image by imaging light returning from the observation target by the illumination light, and an image-correction unit obtaining a correction fluorescence image by raising the luminance value of the fluorescence image to the power of a reciprocal of a first and second exponent obtained by a power approximation of a distance characteristic of luminance versus observation distance, for the fluorescence image, and that obtains a corrected fluorescence image by dividing the correction fluorescence image by the correction reference image. 1. A fluoroscopy apparatus comprising:an illumination portion having a light source that radiates illumination light and excitation light onto a subject;a fluorescence-imaging unit that acquires a fluorescence image by imaging fluorescence generated at the subject by the radiation of the excitation light from the illumination portion;a return-light imaging unit that acquires a reference image by imaging return light returning from the subject by the radiation of the illumination light from the illumination portion; andan image-correction unit that corrects the fluorescence image acquired by the fluorescence-imaging unit by using the reference image acquired by the return-light imaging unit,wherein the image-correction unit obtains the correction reference image by raising a luminance value of the reference image to the power of the second correction factor that is obtained such that ratios of a luminance of the fluorescence image to a luminance of the reference image, in which the luminance value of the reference image has been raised to the power of a second correction factor, match each other ...

Fluoroscopy Apparatus, Fluoroscopy System, and Fluorescence-Image Processing Method

A fluoroscopy apparatus including: an illumination unit having a light source radiating illumination light and excitation light onto an observation target, a fluorescence-imaging unit acquiring a fluorescence image by imaging fluorescence generated at the observation target by the excitation light, a white-light-imaging unit acquiring a reference image by imaging light returning from the observation target by the illumination light, and an image-correction unit obtaining a correction fluorescence image by raising the luminance value of the fluorescence image to the power of a reciprocal of a first and second exponent obtained by a power approximation of a distance characteristic of luminance versus observation distance, for the fluorescence image, and that obtains a corrected fluorescence image by dividing the correction fluorescence image by the correction reference image.

DUAL-ACCEPTOR TIME-RESOLVED-FRET

Methods for determining the presence or absence of a plurality of analytes in a sample with dual-acceptor time-resolved fluorescence resonance energy transfer are provided. 1. A method of determining the presence or absence , independently , of two analytes in a sample , comprising:contacting the sample with a first analyte-specific binding partner and a second analyte-specific binding partner, wherein the first and second analyte-specific binding partners are each conjugated to a lanthanide chelate moiety;exposing the sample to light in a wavelength range capable of exciting the lanthanide in the chelates in the first and second analyte-specific binding partners; anddetermining, independently, if the first analyte-specific binding partner and the second analyte-specific binding partner bind to the first analyte and second analyte, respectively, thereby determining the presence or absence, independently of the two analytes in the sample.2. A method of determining whether or not an enzyme has activity on two different substrates comprising:providing a sample comprising two different substrates;contacting the sample with an enzyme under conditions sufficient to produce a first analyte from the first substrate and a second analyte from the second substrate;contacting the sample with a first analyte-specific binding partner and a second analyte-specific binding partner, wherein the first and second analyte-specific binding partners are each conjugated to a lanthanide chelate moiety;exposing the sample to light in a wavelength range capable of exciting the lanthanide in the chelates in the first and second analyte-specific binding partners; anddetermining, independently, if the first analyte-specific binding partner and the second analyte-specific binding partner bind to the first analyte and second analyte, respectively, thereby determining whether or not the enzyme has activity on the first and second substrates.3. A method of determining whether or not two enzymes , ...

METHOD FOR DETERMINING CANCER ONSET OR CANCER ONSET RISK

A highly accurate and quantitative method for determining cancer onset or cancer onset risk by a quantitative tissue staining method in biological tissues using an antibody capable of recognizing a cancer growth regulatory factor or cancer metastasis regulatory factor such as PAR1 antibody, which inhibits the cancer cell mobility and infiltration is provided. Cancer onset or cancer onset risk is determined using the tissue staining method comprising the steps of: labeling an antibody which recognizes a cancer growth regulatory factor or cancer metastasis regulatory factor with a fluorescent material, and contacting the fluorescent-labeled antibody with a tissue sample; irradiating a tissue site in contact with the antibody with excitation light to acquire a fluorescence image; acquiring an autofluorescence image in a vicinity region of a short wavelength side or long wavelength side of an acquisition region of fluorescence wavelength emitted by the fluorescent material, in the same field of vision and in the same focal point as those of the fluorescence image; acquiring a corrected fluorescence image by image processing to eliminate a fluorescent brightness of the autofluorescence image from the fluorescent brightness of the fluorescence image; counting the number of cells at the tissue site in contact with the antibody; measuring a mean fluorescent brightness of a single fluorescent particle; and calculating the number of fluorescent particles per cell. 1. A method for determining cancer onset or cancer onset risk , comprising using a tissue staining method comprising the following steps (a) to (d):(a) labeling an antibody which recognizes a cancer growth regulatory factor or cancer metastasis regulatory factor with a fluorescent material, and contacting the fluorescent-labeled antibody with a tissue sample;(b) irradiating a tissue site in contact with the antibody with excitation light to acquire a fluorescence image;(c) acquiring an autofluorescence image in a ...

Microfluidic device for generating neural cells to simulate post-stroke conditions

This application provides devices for modeling ischemic stroke conditions. The devices can be used to culture neurons and to subject a first population of the neurons to low-oxygen conditions and a second population of neurons to normoxic conditions. The neurons are cultured on a porous barrier, and on the other side of the barrier run one or more fluid-filled channels. By flowing fluid with different oxygen levels through the channels, one can deliver desired oxygen concentrations to the cells nearest those channels.

SUBSTRATES THE FLUORESCENCE OF WHICH IS SUPPRESSED, PREPARATION THEREOF, AND USE THEREOF FOR IDENTIFYING, DETECTING, AND ASSAYING LEGIONELLA PNEUMOPHILIA

The present disclosure includes the use of an R—(X)-Fluo-Rep-(Gly)-Z—NHpeptide for detecting and assaying the activity of the major surface protease of . This disclosure also includes a method for detecting and quantifying in any medium likely to be contaminated with the bacterium, for example a domestic hot water supply and cooling tower circuits. 117-. (canceled)19. The peptide according to claim 18 , wherein the Fluo radical is selected from the group consisting of (L)-(I-pyrenyl)-alanine claim 18 , (L)-Nε(retroAbz)-Lys claim 18 , (L)-(7-methoxycoumarin-4-yl)-alanine claim 18 , (L)-((6 claim 18 ,7-dimethoxy-coumarin-4-yl)-alanine claim 18 , (L)-Nβ(pyrenylacetyl)-Dap claim 18 , (L)-Nγ(pyrenylacetyl))-Dab claim 18 , (L)-Nδ-(pyrenylacetyl)-Orm claim 18 , (L)-Nε-(pyrenylacetyl)-Lys claim 18 , (L)-S—(I-pyrenemethyl)-Cys and (L)-O—(I-pyrenemethyl)-Ser.20. The peptide according to claim 19 , wherein the Fluo radical is (L)-(I-pyrenyl)-alanine.21. The peptide according to claim 18 , wherein the Rep radical is (3-NO)Tyr.22. The peptide according to claim 18 , wherein Z is selected from the group consisting of (L)-Lys claim 18 , (L)-homo-Lys claim 18 , (L)-Orn claim 18 , (L)-Arg and (L)-homo-Arg.25Legionella pneumophila. A method for detecting protease activity of a Major Secreted Protein (Msp) of in a sample of a solution comprising: {'br': None, 'sub': n', 'm', '2, 'R—(X)-Fluo-Rep-(Gly)-Z—NH\u2003\u2003(I)'}, 'a) placing in contact the sample with a compound of formula (I);'} Fluo is an α-amino acid of configuration (L), having on its side chain a fluorigenic group,', {'sub': 2', '2', '2, 'Rep is an amino acid of configuration (L) selected from (3-NO)Tyr and (4-NO)Phe, on the understanding that when Fluo is pyrenylalanine, Rep is (3-NO)Tyr,'}, 'R is a group selected from the groups acetyl, succinyl and methoxysuccinyl,', 'X is an α-amino acid of configuration (L) selected from the group consisting of: Gly, Ser, homo-Ser, Lys, homo-Lys, Arg, homo-Arg and Orn,', 'Z is a ...

Automatic slide loading device for micro array scanner and its methods of use

An automatic slide loading device for microarray scanner comprises slide holders ( 1 ), a carrier device ( 2 ) and a positioning chamber ( 3 ), wherein the slide holder ( 1 ) can hold microarray slides ( 6 ) and the slide holder ( 1 ) is placed out of the scanning platform of the microarray scanner when the microarray scanner is in off work state, wherein the carrier device ( 2 ) is connected to the positioning chamber ( 3 ) and the carrier device ( 2 ) can load the slide holder ( 1 ) into the positioning chamber ( 3 ), wherein the positioning chamber ( 3 ) is placed above the scanning platform of the microarray scanner and is used to precisely locate the working surface of the microarray slides ( 6 ) in the slide holder ( 1 ).

System and Method For Detecting Multiple Molecules in One Assay

A rapid diagnostic system that delivers a panel of serologic assay results using a small amount of blood, serum, or plasma is described. The system includes a disposable cartridge, including an integral lens portion coupled to a planar waveguide, and a reader instrument, based on planar waveguide imaging technology. The cartridge incorporates a microarray of recombinant antigens and antibody controls in a fluidic channel, providing multiple parallel fluorescence assay results for a single sample. 1. A system for performing an assay on a sample , the system comprising: a planar waveguide with upper and lower planar surfaces defining an optical axis therebetween, the optical axis being perpendicular to a normal vector of the upper and lower surfaces, the upper planar surface having a plurality of capture molecules bound thereto,', 'an integral portion, coupled to the planar waveguide, for focusing a light beam, propagating parallel to but offset from the optical axis, to the planar waveguide such that focusing light within the integral lens portion and incident on the upper planar surface has a non-zero, internal propagation angle β relative to the upper planar surface, and', 'a sample chamber for receiving and containing the sample such that the sample comes into contact with the plurality of capture molecules; and, 'a cartridge having'} a receiving mechanism for positioning the cartridge therein,', 'the light source for providing the light beam at an angle parallel to the optical axis,', 'a detector for detecting a light signal from a portion of the planar surface on which the plurality of capture molecules is bound, and', 'an analysis module for receiving and analyzing the light signal from the detector., 'a reader instrument including'}3. The system of claim 2 , wherein the cylindrical lens portion is truncated such that it does not extend beyond the distance L.4. The system of claim 1 , wherein the plurality of capture molecules include at least one molecule ...

COMPOSITIONS FOR USE IN DETECTION OF MULTIPLE ANALYTES

Methods, compositions and kits are disclosed. The methods are directed to determining the presence or relative amounts of two or more components in a medium. A combination is provided comprising a medium suspected of containing the components, at least two sensitizer reagents and at least one reactive reagent activatable by singlet oxygen. The sensitizer reagents are capable of generating singlet oxygen and are distinguishable by wavelength of sensitization. The combination of sensitizer reagents and reactive reagents allows differential detection of the components. The sensitizer reagents are differentially activated. The amount of signal generated as a result of the activation of said reactive reagent is determined wherein the amount thereof is related to the amount of each of the components in the medium.

REAL TIME GENE EXPRESSION PROFILING

The invention relates to methods of monitoring the amplification of one or more nucleic acid sequences of interest. More particularly, the invention relates to methods of monitoring the amplification of sequences of interest in real time. The methods disclosed herein provide methods for monitoring the amplification of one sequence or two or more sequences from a single sample, as well as methods for monitoring the amplification of one or more than one sequence from two or more samples. The monitoring methods of the invention permit improved determination of the abundance of one or more target nucleic acids, especially target RNA species, in one or more original samples. 1. (canceled)2. A method for determining the threshold cycle , C , for members of a set of nucleic acid sequences of interest in an amplification reaction , the method comprising:(a) contacting a nucleic acid sample in a reaction vessel with a set of pairs of oligonucleotide primers, wherein:each said pair comprises a first oligonucleotide primer that specifically hybridizes with a nucleic acid molecule comprising said nucleic acid sequence of interest, and a second oligonucleotide primer that specifically hybridizes with a sequence comprised by the complement of said nucleic acid sequence of interest, wherein the primer extension product of one oligonucleotide primer, when separated from its complement, can serve as a template for the synthesis of the extension product of the other primer; each said pair of oligonucleotides is specific for one nucleic acid sequence of interest; each oligonucleotide primer pair in said set is selected so that it generates a distinctly sized amplification product in a subsequent amplification regimen;b) subjecting the mixture resulting from step (a) to an amplification regimen comprising a plurality of iterative cycles of nucleic acid strand separation, oligonucleotide primer annealing and polymerase extension of annealed primers in the presence of a fluorescent label ...

METHOD OF DETECTING A BIOLOGICAL ACTIVITY

The present invention provides method of detecting a predetermined biological activity. The method includes using an aqueous mixture comprising a first indicator reagent with a first absorption spectrum and a second indicator reagent. The second indicator reagent is converted by the predetermined biological activity to a second biological derivative with a second emission spectrum. The first absorbance spectrum includes detectable absorbance in at least a portion of wavelengths present in the second emission spectrum. The first indicator reagent is received and concentrated from an aqueous liquid by a substrate, facilitating the detection of the second biological derivative. 1. A method of detecting a biological activity , comprising: a sample that may comprise a source of one or more predetermined biological activities;', 'a first indicator system comprising a first indicator reagent with a first absorbance spectrum, wherein the first indicator reagent can be converted by a first predetermined biological activity to a first biological derivative;', 'a second indicator system comprising a second indicator reagent that is converted by a predetermined biological activity to a second biological derivative with a second emission spectrum;', 'a substrate that receives and concentrates the first indicator reagent from an aqueous mixture; and', 'an instrument that detects the first indicator reagent or the second biological derivative, wherein the instrument comprises an optical path;, 'providing'}forming a first aqueous mixture comprising the sample, the first indicator reagent, and the second indicator reagent;bringing the first aqueous mixture into fluid communication with the substrate to form a second aqueous mixture in which a concentration of the first indicator reagent is lower than the concentration of the first indicator reagent in the first aqueous mixture; anddetecting a presence or absence of fluorescence from the second biological derivative, wherein ...

Luminescent Lanthanide Chelates Having Three Chromophores and Their Use

The present application discloses a luminescent lanthanide chelate of formula (I) with lanthanides such as europium, as well as the corresponding luminescence lanthanide chelating ligand. The application also discloses a detectable molecule comprising a biospecific binding reactant (such as an antibody) conjugated to the luminescent lanthanide chelate as well as a method of carrying out a biospecific binding assay, the use of such a detectable molecule in a specific bioaffinity based binding assay utilizing time-resolved fluorometric determination of a specific luminescence, and a solid support material conjugated with the luminescent lanthanide chelate.

Flow Cytometry For High Throughput Screening

The present invention, provides a flow cytometry apparatus for the detection of particles from a plurality of samples comprising: means for moving a plurality of samples comprising particles from a plurality of respective source wells into a fluid flow stream; means for introducing a separation gas between each of the plurality of samples in the fluid flow stream; and means for selectively analyzing each of the plurality of samples for the particles. The present invention also provides a flow cytometry method employing such an apparatus.

Method of calibrating and correcting color-bleed factors for color separation in dna analysis

A method includes calibrating color bleed factors of optical detector channels of a sample processing apparatus through processing a color bleed calibration substance which includes a plurality of different size fragments replicated from different groups of DNA loci, wherein fragments in a same group are labeled with a same fluorescent dye, and fragments in different groups are labeled with different fluorescent dyes having different emission spectra, wherein the different size fragments are processed during different acquisition times.

FLUORESCENCE MICROSCOPE IN MICROWAVE CAVITY

The present invention relates to an optical imaging system communicatively connected to a microwave energy producing source wherein the combination provides for increases in chemical reaction times and the ability to monitor the reactions in real time with sufficient resolution to view the location of intracellular components labeled with luminescent molecules as well as interaction with other biomolecules and responses to localized environmental variables in living cells and tissues during the application of a microwave field. 1. A microwave/optical imaging system comprising:a) an enclosed container comprising a microwave cavity and having at least one opening therein;b) a sample plate positioned within the microwave cavity for holding at least one sample, wherein the sample plate comprises at least one layer of metallic material deposited on the sample plate surface, wherein the metallic material is formed into a patterned shape, wherein the patterned shape is selected from the group consisting of a triangle, square, rectangle, trapezoid, polygon, parabola, elliptical, sector of a circle and a combinations thereof, wherein the sample comprises a detector molecule or components of a detectable reaction;c) a microwave energy producing source communicatively connected to the microwave cavity for delivering microwave energy into the cavity and directed towards the sample; andd) an optical imaging device communicatively connected to the microwave cavity and positioned for directing excitation light from an electromagnetic energy producing source to the sample and capturing luminescent emissions emitted from the sample.2. The system of claim 1 , wherein the microwave cavity includes a stage for holding the sample plate.3. The system of claim 1 , wherein the detector molecule is a fluorophore.4. The system of claim 1 , wherein the delivered microwave energy has a frequency of from 2 GZ to 3 GZ claim 1 , and a power level in a range between about 10 mwatts and 700 watts.5 ...