РЕАКТИВ И НАБОР РЕАКТИВОВ ДЛЯ АНАЛИЗА НЕЗРЕЛЫХ ЛЕЙКОЦИТОВ

Изобретение относится к области медицины, в частности к анализу крови, и касается реактива для анализа незрелых лейкоцитов в периферической крови, включающего: полиоксиэтиленовое неионное поверхностно-активное вещество, солюбилизирующее вещество, выбранное из группы, состоящей из производного саркозина, производного холевой кислоты и метилглюканамида, и краситель для окрашивания нуклеиновой кислоты, причем реактив имеет осмотическое давление не ниже чем 10 мОсм/кг и ниже чем 150 мОсм/кг. Предложенный реактив позволяет более точно классифицировать и подсчитывать незрелые лейкоциты. 3 н. и 7 з.п. ф-лы, 11 ил., 1 табл.

СИСТЕМА И СПОСОБ ФИЛЬТРАЦИИ ЧАСТИЦ

Группа изобретений относится к медицинской технике. Устройство фильтрации включает фильтрующий элемент, включающий первую проточную камеру, имеющую вход подачи, рассчитанный на прием подаваемого вещества, включающего частицы и текучую среду, и выход ретентата, вторую проточную камеру, имеющую дистальный конец, имеющий выход фильтрата, и фильтр, расположенный между первой проточной камерой и второй проточной камерой. Фильтр включает первый ряд столбиков и множество пор, образуемых промежутками между смежными столбиками. Каждая пора имеет физический размер пор, определяемый расстоянием между смежными столбиками, образующими пору, и эффективный размер пор меньше физического размера пор. Первая проточная камера, вторая проточная камера и фильтр выполнены с возможностью обеспечения скоростей потока через поры меньше скоростей потока на входе в первую проточную камеру для удерживания биологических частиц, имеющих размер, превышающий эффективный размер пор и меньший, чем физический размер пор, ...

СПОСОБ И СИСТЕМА ДЛЯ КЛЕТОЧНОГО АНАЛИЗА С ПОМОЩЬЮ МАССОВОЙ ЦИТОМЕТРИИ

Группа изобретений относится к области биохимии. Предложены способ и система для клеточного анализа. Способ включает обеспечение группы маркированных клеток, выбор имеющей интересующее свойство клетки в группе, запись локализации клетки, направление лазерного импульса на клетку и генерирование дискретного шлейфа, введение дискретного шлейфа в индуктивно сопряженную плазму и генерирование групп соответствующих маркеру элементарных ионов, обнаружение каждой из групп элементарных ионов одновременно для каждого дискретного шлейфа с помощью массовой цитометрии и корреляцию обнаруженных элементарных ионов с интересующим свойством. Система включает опрашивающее устройство для идентификации локализации подходящей клетки, хранилище данных для записи локализации клетки, систему лазерной абляции для направления лазерного импульса на локализацию клетки и массовый цитометр для обнаружения связанного с подходящей клеткой маркера. Изобретения обеспечивают расширение области клеточного анализа по сравнению ...

НАБОР РЕАГЕНТОВ ДЛЯ АНАЛИЗА ОБРАЗЦА И СПОСОБ АНАЛИЗА ОБРАЗЦА

Предложенная группа изобретений относится к области медицины. Предложен набор реагентов для анализа образца для измерения базофилов и нуклеированных эритроцитов в образце, включающий первый реагент, содержащий катионное поверхностно-активное вещество, неионное поверхностно-активное вещество и ароматическую карбоновую кислоту, и второй реагент, содержащий флуоресцентный краситель, способный окрашивать нуклеиновую кислоту. Предложен способ анализа образца с использованием указанного набора. Предложены также набор реагентов для анализа образца для измерения лейкоцитов и нуклеированных эритроцитов в образце и набор реагентов для анализа образца для измерения базофилов, лейкоцитов, иных чем базофилы, нуклеированных эритроцитов и лейкоцитов в образце. Предложенная группа изобретений обеспечивает точное определение количества форменных элементов образца крови даже по прошествии 50 часов с момента получения образца от пациента. 4 н. и 12 з.п. ф-лы, 27 ил., 5 табл., 9 пр.

СПОСОБ ОЦИФРОВЫВАНИЯ МАЗКА ПУНКТАТА КОСТНОГО МОЗГА

Изобретение относится к способу оцифровывания мазка пунктата костного мозга. Техническим результатом является повышение эффективности оцифровывания мазка пунктата костного мозга. Способ оцифровывания мазка пунктата костного мозга включает: получение релевантной информации о мазке костного мозга; генерацию единого изображения; создание подлежащей оцифровке области, количества ядросодержащих клеток, подлежащих сбору, и количества мегакариоцитов, подлежащих классификации; цифровую маркировку мазка костного мозга; сканирование подлежащей оцифровке области при малом увеличении, маркировку и идентификацию объекта наблюдения, являющегося целью; создание изображения сканируемой области; сканирование мегакариоцитов при малом увеличении, маркировку и идентификацию сканируемых мегакариоцитов; создание изображений сканируемых мегакариоцитов; сканирование ядросодержащих клеток с помощью масляной иммерсии, маркировку и идентификацию сканируемых ядросодержащих клеток, причем количество сканируемых ядросодержащих ...

МАт-НАПРАВЛЯЕМЫЕ ХИМЕРНЫЕ АНТИГЕННЫЕ РЕЦЕПТОРНЫЕ СИСТЕМЫ ДЛЯ СОРТИРОВКИ/ИСТОЩЕНИЯ СКОНСТРУИРОВАННЫХ ИММУННЫХ КЛЕТОК

СКОНСТРУИРОВАННЫЕ ИММУННЫЕ КЛЕТКИ С НОКАУТОМ РЕЦЕПТОРА Т-КЛЕТОК, СНАБЖЕННЫЕ ХИМЕРНЫМИ АНТИГЕННЫМИ РЕЦЕПТОРАМИ, СВЯЗЫВАЮЩИМИСЯ С CD123, ДЛЯ ЛЕЧЕНИЯ РЕЦЕДИВИРУЮЩЕГО/УСТОЙЧИВОГО ОСТРОГО МИЕЛОИДНОГО ЛЕЙКОЗА ИЛИ НОВООБРАЗОВАНИЯ ИЗ БЛАСТНЫХ ПЛАЗМОЦИТОИДНЫХ ДЕНДРИТНЫХ КЛЕТОК

НАБОР РЕАГЕНТОВ ДЛЯ АНАЛИЗА ОБРАЗЦА И СПОСОБ АНАЛИЗА ОБРАЗЦА

... 1. Набор реагентов для анализа образца для измерения базофилов и/или нуклеированных эритроцитов в образце, содержащий: ! первый реагент, содержащий катионное поверхностно-активное вещество, неионное поверхностно-активное вещество и ароматическую карбоновую кислоту, который может лизировать эритроциты и повреждать клеточные мембраны лейкоцитов, так чтобы флуоресцентный краситель мог проникать через нее, и ! второй реагент, содержащий флуоресцентный краситель, способный окрашивать нуклеиновую кислоту. ! 2. Набор реагентов по п.1, в котором флуоресцентный краситель, по меньшей мере, представляет собой один краситель, выбранный из группы, состоящей из флуоресцентного красителя, имеющего общую формулу (I): ! ! где R1 и R2 являются одинаковыми или отличными друг от друга и представляют собой алкильную группу; ! ! ! R3, R4, R5 и R6 являются одинаковыми или отличными друг от друга и представляют собой атом водорода или алкильную группу; и X- представляет собой анион; и флуоресцентный краситель, ...

Ein Reagenz zur Analyse von Leukocyten

Ein Reagenz zur Analyse von Leukocyten

VORRICHTUNG ZUR AUTOMATISCHEN BLUTUNTERSUCHUNG

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.

Anordnung für die individualisierte Patientenblutanalyse

Die Erfindung betrifft eine Anordnung für die individualisierte Patientenblutanalyse. Die Aufgabe der vorliegenden Erfindung, eine Anordnung für die individualisierte in-vitro Patientenblutanalyse, insbesondere für Sepsis-Untersuchungen anzugeben, welche die Nachteile des Standes der Technik vermeidet und an Hand einer Blutmenge von nur 1 bis 2 ml in weniger als 1 Stunde ein aussagekräftiges Untersuchungsergebnis ermöglicht, wird dadurch gelöst, dass eine Anordnung für die individualisierte in-vitro Patientenblutanalyse bereitgestellt wird, die ein Holographie-Modul (1), ein Raman-Spektroskopie-Modul (2), ein Biomarker-Modul (3) und einen Flusssteuerbaustein (4) umfasst, welche daten- und informationsleitend mit einer zentralen Steuer- und Computereinheit (5) in Verbindung stehen, die informationsleitend mit einer Datenbank (6) verbunden ist, wobei die Module (1, 2 und 3) über den Flusssteuerbaustein (4) mit einer gemeinsamen Blutprobenzuführung (73) und weiteren Flüssigkeitsmaterialzuführungen ...

Cell analysis using dynamic biophysical methods

Cell migration assay

Devices and methods for enrichment and alteration of circulating tumour cells and other particles

The invention features devices and methods for detecting, enriching, and analyzing circulating tumor cells and other particles. The invention further features methods of diagnosing a condition, e.g., cancer, in a subject by analyzing a cellular sample from the subject.

Droplet-Based assay system

Droplet-based assay system

Advanced biophysical and biochemical cellular monitoring and quantification using laser force cytology

The present invention is directed to intelligent algorithms, methodologies and computer-implemented methodologies for biophysical and biochemical cellular monitoring and quantification enabling enhanced performance and objective analysis of advanced infectivity assays including neutralization assays and adventitious agent testing using fluidic and optical force-based measurements.

Method for the cytometric analysis of cell samples

A method for the cytometric analysis of cell samples, wherein the microscope is capable of operating in a transmis­sion mode and/or in a fluorescence mode. The cell sample has a fluorescence marker. During a continuous movement of the cell samples, a first image of a sub-region of the cell sample is recorded in transmission or fluorescence mode; and a second image of the cell sample is recorded in fluorescence mode. The two images are associated with each other. Positions and/or con­tours M of cells or cell components of the cell samples are detected in the transmission image. The in­tensities of the fluorescence image are then analysed as a function of these positions and/or contours M. Alternatively, positions and/or contours M are extracted from any one of these two images, and the remaining image is analysed as a function of these positions and/or contours.

Bioprinters

Advanced biophysical and biochemical cellular monitoring and quantification using laser force cytology

Systems and methods for automated single cell cytological classification in flow

Counting particles using an eletrical differentialcounter

Method for counting cells

COUNTING PARTICLES USING AN ELECTRICAL DIFFERENTIAL COUNTER

Method for counting cells

Counting particles using an eletrical differentialcounter

Method for counting cells

Counting particles using an eletrical differentialcounter

Method for counting cells

PROCEDURE FOR AUTOMATIC RECOGNIZING OF CELLS WITH ILLNESS-REFERRED MOLECULAR MARKING KOMPARTIMENTIERUNG

VERFAHREN UND ANORDNUNG ZUR UNTERSUCHUNG VON ZELLEN

HÄMATOLOGI REFERENCE CONTROL AND PROCEDURE FOR THE PRODUCTION

PROCEDURE FOR THE ANALYSIS OF A BLOOD TEST

DURCHFLUSSZYTOMETERPROBENBEHANDLUNGSVERFAHREN

SYSTEM AND PROCEDURE FOR THE EPIDETEKTIONSKOHÄRENZ ANTI- STOKES RAMAN STREUMIKROSKOPIE ONES

TWO-COLORS CAMERA MICROSCOPE AS WELL AS METHODOLOGY TO ANFÄRBEN OF CELLS AS WELL AS ANALYSIS

IMPROVEMENTS IN AND CONCERNING LIGHT BY LINE SYSTEMS AND IMPROVEMENTS IN FROM IT COMING OF CELL RESEARCH PROCEDURE

PROCEDURE FOR CALIBRATING DURCHFLUSSZYTOMETRIEGERAETEN.

PROCEDURE FOR THE ANALYSIS OF CELL COMPONENTS IN A LIQUID.

MULTI-DIMENSIONAL ANALYSIS OF LEUKOCYTES

SYSTEMS AND PROCEDURES FOR THE CELL PARTIAL POPULATION ANALYSIS

RETICULOCYTE REGULATION PROCEDURE AND EQUIPMENT, WHICH USE LIGHT SCATTERING TECHNIQUES

COMPOSITIONS AND PROCEDURES FOR THE FAST ANALYSIS OF RETICULOCYTES

Method for examining a liquid sample and a dispensing apparatus

The invention relates to a method for examining a liquid sample comprising a liquid and at least one cell in the liquid and/or at least one particle in the liquid, wherein, in the method, at least one data element containing information about a sample region is determined. The method is characterised in that the data element is supplied to a trained algorithm, which generates a result dependent on the data element and in that a dispensing process comprising the discharging of at least some of the liquid sample depends on the result.

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 ...

METHODS, SYSTEMS, AND APPARATUS FOR PERFORMING FLOW CYTOMETRY

Abstract An apparatus for detecting an analyte in a sample includes an illumination source for generating electromagnetic energy to illuminate the sample at an interrogation region, a concave collector element having an optical axis, and a focal point, the interrogation region being coincident with the focal point of the concave collector element, a closed flow cell having a flow path defined between a sample inlet and a sample outlet, the flow path passing through the interrogation region and a sorting region disposed downstream of the interrogation region. The portion of the flow path passing through the interrogation region is coaxially aligned with the optical axis of the concave collector element. The apparatus further includes the sample comprising or suspected of comprising the analyte and flowing in the flow path, wherein the analyte generates a detectable signal in response to illumination. The apparatus also includes a detector for detecting the detectable signal.

Multipurpose reagent system for rapid lysis of whole blood samples

Methods for counting cells

Fluidic droplet coalescence

Chip-based piezoelectric resonator and liquid-phase sensor

Microfluidic apparatus for manipulating, imaging and analyzing cells

SUBSTRATES, DEVICES, AND METHODS FOR CELLULAR ASSAYS

Identifying and measuring reticulocytes

Methods and systems for identifying reticulocytes in a blood sample deposited on a substrate include: illuminating the sample with incident light at two different wavelengths, obtaining a two-dimensional image of the sample corresponding to a first one of the wavelengths, and obtaining a two-dimensional image of the sample corresponding to a second one of the wavelengths; analyzing the images to identify a set of representative red blood cells; determining an area of each of the red blood cells in the set; determining a color value of each of the red blood cells in the set; and, for each one of the red blood cells in the set, identifying the red blood cell as a reticulocyte if the area of the red blood cell exceeds an area cutoff value and the color value of the red blood cell is less than a color cutoff value.

Disposable chamber for analyzing biologic fluids

IMPROVEMENTS IN AND RELATING TO LIGHT TRANSFER SYSTEMS AND IMPROVED CELL INVESTIGATION TECHNIQUES ARISING THEREFROM

COMPUTERIZED ANALYSIS FOR ABNORMAL CELLS IN A CELL BLOCK

MEMS-based integrated magnetic particle identification system

Anti-CLL1 specific single-chain Chimeric Antigen Receptors (scCARs) for cancer immunotherapy

The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward CLL1 positive cells. The engineered immune cells endowed with such CARs are particularly suited for immunotherapy for treating cancer, in particular leukemia.

Automated flow cytometry analysis method and system

An automated method and system are provided for receiving an input of flow cytometry data and analyzing the data using a hierarchical arrangement of analytical elements, each of which utilizes a support vector machine to automatically classify the data into different subpopulations to recognize a pattern within the data. The pattern may be used to generate a diagnostic prediction for a patient or to identify patterns within samples collected from multiple subjects.

Apparatus and method for detecting cells or particles in a fluid container

A apparatus for detecting cells or particles in a fluid container comprises a dispenser configured to dispense at least one cell or at least one particle into a defined sub-volume of a fluid with which the fluid container is at least partially filled, and a detection apparatus configured to, in a time-coordinated manner with dispensing the at least one cell or the at least one particle by the dispenser, perform a detection in the defined sub-volume and/or in one or several sub-volumes underneath the defined sub-volume in order to sense the at least one cell or the at least one particle when entering the fluid or immediately after entering the fluid.

High throughput, feedback-controlled electroporation microdevice for efficient molecular delivery into single cells

Systems and methods for cell electroporation and molecular delivery using an intelligent, feedback controlled, microscale electroporation system for transfecting single cells.

Tim protein-bound carrier, methods for obtaining, removing and detecting extracellular membrane vesicles and viruses using said carrier, and kit including said carrier

The present invention addresses the problem of providing a carrier and method for simply and efficiently obtaining or removing extracellular membrane 5 vesicles or viruses present in a sample with high purity while keeping the vesicles or viruses intact, or detecting such vesicles or viruses with high sensitivity. The present invention relates to: "1. a carrier (Tim carrier) with which a protein (Tim protein) selected from T-cell immunoglobulin and mucin domain containing molecule-4 (Tim-4) protein, Tim-3 protein, and Tim-1 protein, is 10 bound; 2. a method for obtaining extracellular membrane vesicles or viruses in a sample; 3. a method for removing extracellular membrane vesicles or viruses in a sample; 4. a method for detecting extracellular membrane vesicles or viruses in a sample; 5. a kit for capturing extracellular membrane vesicles or viruses, wherein the kit includes the Tim carrier; and 6. a kit for capturing 15 extracellular membrane vesicles or viruses, wherein the kit includes ...

Minimally invasive apparatus and method for testing lesions of the oral cavity and similar epithelium

Cytological imaging system and method

CELL MEASURING METHOD

A technology capable of measuring cell-related reactions at a time within a wide range of concentration. Cell groups (200) are disposed in a cell-storing space (110) filled with liquid (120). A specific substance is supplied to the liquid in the cell-storing space (110) to form in the liquid (120) the concentration gradient (131) of the specific substance (130) extending from one end (111) of the cell-storing space (110) toward the other end (112). The cell groups in the cell-storing space (110) is picked up by an imaging device (320) and captured into an information processor, and image obtained by the information processor is divided into a plurality of regions along the above concentration gradient, feature amounts are extracted from image portions in respective regions, and information indicating the interrelation between the extracted feature amounts and the concentration gradient is created.

METHOD FOR CORRECTION OF RELATIVE OBJECT-DETECTOR MOTION BETWEEN SUCCESSIVE VIEWS

... ²²²Motion correction for optical tomographic imaging in three dimensions. An ²object of interest (1) is illuminated to produce an image (111). A lateral ²offset correction value is determined for the image (114). An axial offset ²correction value is determined for the image 115). The lateral offset ²correction value and the axial offset correction value are applied to the ²image to produce a corrected file image (116).² ...

METHODS FOR COUNTING CELLS

The invention features methods of quantifying cells in a sample by lysing the cells followed by the measurement of at least one intracellular component. Methods of the invention are especially useful for quantifying small numbers of cells, e.g., over a large surface area or volume compared to the cell size. In a preferred embodiment, methods of the invention are performed using a microfluidic device.

MICROFLUIDIC APPARATUS FOR MANIPULATING, IMAGING AND ANALYZING CELLS

A microfluidic apparatus for isolating and imaging or analyzing cells of a cytological specimen includes a substrate and a microfluidic cellular isolation element that includes an outer wall, a channel, a partition member and a receptacle. The partition member is positioned within the isolation element interior, and the receptacle is positioned within the partition member interior. The isolation element is configured such that fluid introduced through the outer wall inlet flows through the channel in a first direction, and the partition member is situated such that fluid flows from the channel into the partition member interior through the partition member inlet aperture in a second direction different than the first direction. The receptacle positioned relative to the partition member inlet to catch and retain a cell carried by the fluid.

DROPLET-BASED ASSAY SYSTEM

Systems, including apparatus and methods, for performing assays. These systems may involve separating sample components by partitioning them into droplets or other partitions, amplifying or otherwise reacting the components within the droplets, detecting the amplified components, or characteristics thereof, and/or analyzing the resulting data, among others.

METHOD FOR ANALYSIS OF CELLULAR COMPONENTS OF A FLUID

A method for multi-parameter analysis of cells in a body fluid sample is described which makes use of a plurality of fluorescence measurements, comprising at least two nucleic acid dyes and at least one fluorescently labelled cell surface marker, and a plurality of light scattering measurements. A kit containing the nucleic acid dyes and cell surface marker also is described.

A SYSTEM FOR CELL-BASED SCREENING

The present invention provides systems, methods, screens, and kits for optical system analysis of cells to rapidly determine the distribution, environment, or activity of fluorescently labeled reporter molecules in cells for the purpose of screening large numbers of compounds for those that specifically affect particular biological functions. The invention involves providing cells containing fluorescent reporter molecules in an array of locations and scanning numerous cells in each location with a high magnification fluorescence optical system, converting the optical information into digital data, and utilizing the digital data to determine the distribution, environment or activity of the fluorescently labeled reporter molecules in the cells. The array of locations may be an industry standard 96 well or 384 well microtiter plate or a microplate which is a microplate having cells in a micropatterned array of locations. The invention includes apparatus and computerized method for processing ...

SYSTEM AND METHODS FOR DISCRIMINATING AN AGENT

A system and methods for discriminating an agent. In one embodiment of the present invention, the method includes the steps of (a) constructing a decision tree having a plurality of branches, each branch corresponding to at least one defined action, wherein each branch includes a plurality of successive branches, each successive branch corresponding to at least one defined action, (b) providing a conditioned environment sensitive to the agent, (c) obtaining data from response of the agent to the conditioned environment, (d) extracting features from the obtained data, (e) selecting a branch from the decision tree corresponding to the features, (f) performing on the features at least one defined action corresponding to the branch, (g) producing a classification of the agent, and (h) iteratively repeating steps of (d)-(g) until the agent is discriminated.

AN APPARATUS AND METHODS FOR USING BIOLOGICAL MATERIAL TO DISCRIMINATE AN AGENT

An apparatus and methods for using biological material to discriminate an agent. In one embodiment of the present invention, the method includes the steps of providing at least one cell, exposing at least one cell to an agent, measuring the response of the cell to the agent in terms of a physical quantity related to at least one of the cellular physiological activities of the cell, and identifying the agent from the measured response. The method further includes the step of quantifying the agent from the measured response.

OPTICAL STRETCHER

A novel optical micromanipulation tool uses a laser (10) to trap and deform biological cells, such as cancer cells, in a flow chamber (26) between two counter propragating beams (22, 24) generated by the laser (10).

A METHOD FOR AUTOMATED NON-INVASIVE MEASUREMENT OF SPERM MOTILITY AND MORPHOLOGY AND AUTOMATED SELECTION OF A SPERM WITH HIGH DNA INTEGRITY

A method of automated measurement of motility and morphology parameters of the same single motile sperm. Automated motility and morphology measurements of the same single sperm are performed under different microscope magnifications. The same single motile sperm is automatically positioned and kept inside microscope field of view and in focus after magnification switch. A method of automated non-invasive measurement of sperm morphology parameters under high magnification of imaging. Sperm morphology parameters including subcellular structures are automatically measured without invasive sample staining. A method of automatically selecting sperms with normal motility and morphology and DNA integrity for infertility treatment.

METHODS AND APPARATUS FOR SINGLE BIOLOGICAL NANOPARTICLE ANALYSIS

The present disclosure relates to methods, systems, and devices for performing analyses of biological nanoparticles. More specifically, the present disclosure relates to methods, systems, and devices for performing single biological nanoparticle size determination on a sample while the biological nanoparticle is in transit through a microfluidic chip. In other aspects, the present disclosure relates to methods, systems, and devices for selectively capturing biological nanoparticles on a coated planar surface, the capturing being facilitated by centrifugation.

SYSTEM AND METHOD FOR ISOLATING AND ANALYZING CELLS

A system and method for isolating and analyzing single cells, wherein the system includes: an array of wells defined at a substrate, each well including an open surface and a well cavity configured to capture cells in one of a single-cell format and single-cluster format, and a fluid delivery module including a fluid reservoir superior to the array of wells through which fluid flow is controlled along a fluid path in a direction parallel to the broad face of the substrate; and wherein the method includes: distributing a population of cells and a population of non-cell particles across the array of wells through the fluid reservoir to increase capture efficiency of individual cell-particle pairs within the array of wells, and processing the captured cell-particle pairs at the set of wells.

METHOD AND SYSTEM FOR MICROFLUIDIC PARTICLE ORIENTATION AND/OR SORTING

FUNCTIONAL ANALYSIS OF CANCER CELLS

The invention provides devices and methods for measuring how living cells function. The measurements can be made from tissue biopsy samples to measure functional properties of living cells from a solid tumor. After measuring a functional property of a cell, the cell remains alive and is available for other subsequent analyses. In certain aspects, the invention provides a method for measuring a cancer marker. The method includes obtaining a tissue sample comprising living cells, disaggregating the tissue sample and loading individual live cells into an input channel of a measurement instrument, and flowing the live cells through the measurement instrument to measure a functional property of the live cells.

MICROFLUIDIC METHOD AND SYSTEM FOR THE ISOLATION OF PARTICLES

A microfluidic method and system (1) for the recovery of particles (2); while a sample is fed along a plurality of channels (7), some particles (2) of a given type are trapped at the segments (16) of the channels (7); keeping a fluid flow flowing along the channels (7) further particles (3) of different type are moved away and unloaded through an outlet (6); at this point, a movement device (26), for example provided with a dielectrophoresis system, directly exerts a force on each particle (2) of given type and selectively conveys it to a collection area (25).

FLOW CELL PACKAGE AND METHOD FOR MAKING THE SAME

A flow cell package includes first and second surface-modified patterned wafers and a spacer layer. The first surface-modified patterned wafer includes first depressions separated by first interstitial regions, a first functionalized molecule bound to a first silane or silane derivative in at least some of the first depressions, and a first primer grafted to the first functionalized molecule in the at least some of the first depressions. The second surface-modified patterned wafer includes second depressions separated by second interstitial regions, a second functionalized molecule bound to a second silane or silane derivative in at least some of the second depressions, and a second primer grafted to the second functionalized molecule in the at least some of the second depressions. The spacer layer bonds at least some first interstitial regions to at least some second interstitial regions, and at least partially defines respective fluidic chambers of the flow cell package.

SYSTEM AND METHOD FOR CHARACTERIZING PARTICULATES IN A FLUID SAMPLE

A system for characterizing at least one particle from a fluid sample is disclosed. The system includes a filter disposed upstream of an outlet, and a luminaire configured to illuminate the at least one particle at an oblique angle. An imaging device is configured to capture and process images of the illuminated at least one particle as it rests on the filter for characterizing the at least one particle. A system for characterizing at least one particle using bright field illumination is also disclosed. A method for characterizing particulates in a fluid sample using at least one of oblique angle and bright field illumination is also disclosed.

APPARATUS, SYSTEMS, AND METHOD FOR INCREASING MEASUREMENT ACCURACY IN A PARTICLE IMAGING DEVICE

APPARATUS, SYSTEM, AND METHOD FOR INCREASING MEASUREMENT ACCURACY IN A PARTICLE IMAGING DEVICE

An apparatus, system, and method for increasing measurement accuracy in imaging cytometry. The system may include a light detector configured to measure light emitted by a first particle and light emitted by a second particle, where the measured light from the second particle at least partially overlaps the measured light from the first particle in an overlap region. Additionally, the system may include a processor coupled to the light detector, where the processor is configured to determine a contribution of light from the first particle in the overlap region and determine a contribution of light from the second particle in the overlap region. The processor may also be configured to subtract the contribution of light from the second particle from the contribution of light from the first particle and determine the intensity of light emitted by the first particle.

CELL SORTING USING A HIGH THROUGHPUT FLUORESCENCE FLOW CYTOMETER

In one aspect, a method of sorting cells in a flow cytometry system is disclosed, which includes illuminating a cell with radiation having at least two optical frequencies shifted from one another by a radiofrequency to elicit fluorescent radiation from the cell, detecting the fluorescent radiation to generate temporal fluorescence data, and processing the temporal fluorescence data to arrive at a sorting decision regarding the cell without generating an image (i.e., a pixel-by-pixel image) of the cell based on the fluorescence data. In other words, while the fluorescence data can contain image data that would allow generating a pixel-by-pixel fluorescence intensity map, the method arrives at the sorting decision without generating such a map. In some cases, the sorting decision can be made with a latency less than about 100 microseconds. In some embodiments, the above method of sorting cells can have a sub-cellular resolution, e.g., the sorting decision can be based on characteristics ...

ULTRA-HIGH THROUGHPUT DETECTION OF FLUORESCENT DROPLETS USING TIME DOMAIN ENCODED OPTOFLUIDICS

A high-throughput optofluidic device for detecting fluorescent droplets is disclosed. The device uses time-domain encoded optofluidics to detect a high rate of droplets passing through parallel microfluidic channels. A light source modulated with a minimally correlating maximum length sequences is used to illuminate the droplets as they pass through the microfluidic device. By correlating the resulting signal with the expected pattern, each pattern formed by passing droplets can be resolved to identify individual droplets.

AUTOMATED COLLECTION OF A SPECIFIED NUMBER OF CELLS

Embodiments of the disclosed subject matter provide an automated method and system to isolate and collect cells using computerized analysis of images of cells and their surroundings obtained from a digital imaging device or system. Embodiments of the disclosed subject matter make use of a "microwell array," which can comprise a formed, elastomeric grid of indentations or "wells." Many, most, or all of the wells in a microwell array can contain a releasable, microfabricated element, which can be referred to as a "raft." Embodiments of the disclosed subject matter provide a system and method for cell collection that includes computerized identification and collection of rafts with isolated single cells or a specific group or groups of cells, eliminating the need for continuous human identification and selection.

DOSIMETERS INCLUDING LENSLESS IMAGING SYSTEMS

METHODS AND COMPOSITIONS FOR HIGHLY SENSITIVE ANALYSIS OF MARKERS AND DETECTION OF MOLECULES

Disclosed are methods, kits, and compositions for fluorescent detection of single biomolecules, e.g. proteins, using highly sensitive fluorescent dyes and a flow cell with one interrogation space for irradiation by focused laser beam. The methods, kits, and compositions are useful in determining concentrations of molecules in samples to levels of 1 femtomolar, 1 attomolar, or lower. The methods, kits, and compositions also allow the determination of concentration over a wide range, e.g., 7-log range, without need for sample dilution.

APPARATUS, METHODS AND PROCESSES FOR SORTING PARTICLES AND FOR PROVIDING SEX-SORTED ANIMAL SPERM

A process for evaluating a set of conditions for staining a population of cells for sorting, the population comprising a first type and a second type of cell, the process comprising: (a) staining a fraction of the population of cells with a fluorescent dye under a set of staining conditions; (b) exposing the stained cells to electromagnetic radiation as the stained cells are passed through an interrogation location of a flow cytometer at a rate, R; (c) determining a fluorescence emission characteristic of the exposed cells; (d) using the determined fluorescence characteristic to classify the exposed cells into two or more sub-populations of cells, one of the sub-populations being an enriched sub-population of the first cell type; (e) determining a coefficient of variation for the fluorescence emission characteristic of the cells of the enriched sub-population to provide an indication of sorting efficiency for the staining conditions; and (f) determining whether to modify any staining condition ...

METHODS AND COMPOSITIONS FOR ASSESSING SPERMATOZOA IN A SEMEN SAMPLE

The present invention relates to the field of mammalian reproduction and provides methods, compositions and kits for detecting and assessing spermatozoa and intervening cells in a semen sample which are applicable to human and veterinary uses. Various aspects of the present invention provide for a cytometric multiparametric approach for determining spermatozoa concentration in a semen sample, wherein the cytometric multiparametric approach involves use of one or more spermatozoa-specific detection agents for detection of spermatozoa in the semen sample and one or more intervening cells-specific detection agents.

DETERMINATION OF ANALYTES IN A SAMPLE MATRIX BY SOLVENT EXTRACTION

Determination of Analytes in a Sample Matrix by Solvent Extraction A method for the assay of one or more analytes in a sample matrix comprising the steps of: performing analyte extraction on the sample matrix, said analyte extraction comprising combining the sample matrix with a solvent for an extraction period which is less than that required for reaching equilibrium; and separating the analyte containing solvent from the sample matrix; next measuring a level of analyte present in the separated solvent; and then applying in a computer a calibration by which is established a mathematical relationship between levels of analyte extracted from each of a plurality of reference samples by means of the process employed above in the extraction for the sample matrix and a reference value of the levels of analyte for each reference sample to thereby derive a measure of the level of analyte in the sample matrix. Specifically a method to determine the amount of mycotoxins in cereal grain, especially ...

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.

AUTOMATED FLOW CYTOMETRY ANALYSIS METHOD AND SYSTEM

An automated method and system are provided for receiving an input of flow cytometry data and analyzing the data using a hierarchical arrangement of analytical elements, each of which utilizes a support vector machine to automatically classify the data into different subpopulations to recognize a pattern within the data. The pattern may be used to generate a diagnostic prediction for a patient or to identify patterns within samples collected from multiple subjects.

CLL1-SPECIFIC MULTI-CHAIN CHIMERIC ANTIGEN RECEPTOR

The present invention relates to a new generation of chimeric antigen receptors (CAR) referred to as multi-chain CARs, which are made specific to the antigen CLL1. Such CARs aim to redirect immune cell specificity and reactivity toward malignant cells expressing the tumor antigen CLL1. The alpha, beta and gamma polypeptides composing these CARs are designed to assemble in juxtamembrane position, which forms flexible architecture closer to natural receptors, that confers optimal signal transduction. The invention encompasses the polynucleotides, vectors encoding said multi-chain CAR and the isolated cells expressing them at their surface, in particularly for their use in immunotherapy. The invention opens the way to efficient adoptive immunotherapy strategies for treating cancer, especially leukemia.

Magnetic Sector Mass Spectrometry Based Multi-Parametric Particle Analyzer

An analytical instrument has a sample introduction system for generating a stream of particles from a sample and an ionization system for receiving the particles. The ionization system is operable to atomize the particles received from the sample introduction system and ionize atoms from the atomized particles. The instrument has an ion pretreatment system and a magnetic sector mass analyzer comprising an array detector. The ion pretreatment system is adapted to transport ions generated by the ionization system to the mass analyzer. The mass analyzer is adapted to detect a transient signal of at least one element from individual particles from said stream by performing mass analysis on the ions from the atomized particles. The magnetic sector mass analyzer is adapted determine an amount of said at least one element from an individual particle using the transient signal detected during mass analysis of the ions from said individual particle.

Minimally invasive cytometry system with qcl inspection of single cells for cancer detection

This disclosure concerns a minimally invasive cytometry system including a handling system that presents single cells to at least one QCL laser source. The QCL laser source is configured to deliver light to a cell within the cells in order to induce vibrational bond absorption in one or more analytes within the cell. The cytometry system also includes a detection facility that detects the mid-infrared wavelength light transmitted by the cell and identifies the cell as either cancerous or non-cancerous.

White Blood Cell Analysis System and Method

Systems and methods for analyzing blood samples, and more specifically for performing a white blood cell (WBC) differential analysis. The systems and methods screen WBCs by means of fluorescence staining and a fluorescence triggering strategy. As such, interference from unlysed red blood cells (RBCs) and fragments of lysed RBCs is substantially eliminated. The systems and methods also enable development of relatively milder WBC reagent(s), suitable for assays of samples containing fragile WBCs. In one embodiment, the systems and methods include: (a) staining a blood sample with an exclusive cell membrane permeable fluorescent dye, which corresponds in emission spectrum to an excitation source of a hematology instrument; (b) using a fluorescence trigger to screen the blood sample for WB Cs; and (c) using measurements of (1) axial light loss, (2) intermediate angle scatter, (3) 90° polarized side scatter, (4) 90° depolarized side scatter, and (5) fluorescence emission to perform a differentiation analysis.

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.

Biochip

A biochip including a chip body, a first electrode and a second electrode is provided. The body has a first accommodating cavity, a second accommodating cavity and a micro-fluid channel. The micro-fluid channel is connected with the first accommodating cavity and the second accommodating cavity. The first electrode has a first end and a second end. The first end is used for contacting a first probe of a detection apparatus. The second end is positioned in the first accommodating cavity. The second electrode has a third end and a forth end. The third end is used for contacting a second probe of the detection apparatus. The forth end is positioned in the second accommodating cavity.

Methods for sorting particles

A multi-channel apparatus for classifying particles according to one or more particle characteristics. The apparatus comprises a plurality of flow cytometry units, each of which is operable to classify particles in a mixture of particles by interrogating a stream of fluid containing the particles with a beam of electromagnetic radiation. The flow cytometry units share an integrated platform comprising at least one of the following: (1) a common supply of particles; (2) a common housing; (3) a common processor for controlling operation of the units; (4) a common processor for receiving and processing information from the units; and (5) a common fluid delivery system. The integrated platform can include a common source of electromagnetic radiation. A method of the invention comprises using a plurality of flow cytometry units sharing the integrated platform to perform a flow kilometric operation, such as analyzing or sorting particles.

Liquid crystals with switchable wettability for cell sorting

Disclosed are methods and apparatuses for identifying and sorting cells based on the cells' response to an external stimulus. Cellular adherence to liquid crystals with tunable wettability is measured before and after an induced change in the liquid crystal wettability. The cell-based liquid crystal reorientation can be measured and used for monitoring and sorting of cells in a label-free manner, and thus provides a positive method for selecting cells, such as stem cells, for use in tissue engineering applications.

Cell processing apparatus, sample preparation apparatus, and cell analyzer

A cell processing apparatus includes a storage container that contains liquid L including a biological sample; a filter that prevents a first cell C 1 in the biological sample from passing and allows a second cell C 2 having a smaller diameter than that of the first cell C 1 to pass; and a filtration cylinder for separating, in the storage container and via the filter, the liquid L into a first liquid L 1 mainly including the first cell C 1 and a second liquid L 2 mainly including the second cell C 2 . A measurement target cell filtered by the filter among other cells can be easily collected.

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.

Acoustic waves in microfluidics

Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one set of embodiments, droplets may be sorted using surface acoustic waves. The droplets may contain cells or other species. In some cases, the surface acoustic waves may be created using a surface acoustic wave generator such as an interdigitated transducer, and/or a material such as a piezoelectric substrate. The piezoelectric substrate may be isolated from the microfluidic substrate except at or proximate the location where the droplets are sorted, e.g., into first or second microfluidic channels. At such locations, the microfluidic substrate may be coupled to the piezoelectric substrate (or other material) by one or more coupling regions. In some cases, relatively high sorting rates may be achieved, e.g., at rates of at least about 1,000 Hz, at least about 10,000 Hz, or at least about 100,000 Hz, and in some embodiments, with high cell viability after sorting.

Waveguide-based detection system with scanning light source

The invention provides methods and devices for generating optical pulses in one or more waveguides using a spatially scanning light source. A detection system, methods of use thereof and kits for detecting a biologically active analyte molecule are also provided. The system includes a scanning light source, a substrate comprising a plurality of waveguides and a plurality of optical sensing sites in optical communication with one or more waveguide of the substrate, a detector that is coupled to and in optical communication with the substrate, and means for spatially translating a light beam emitted from said scanning light source such that the light beam is coupled to and in optical communication with the waveguides of the substrate at some point along its scanning path. The use of a scanning light sources allows the coupling of light into the waveguides of the substrate in a simple and cost-effective manner.

Sperm processing methods

A multi-channel apparatus for classifying particles according to one or more particle characteristics. The apparatus comprises a plurality of flow cytometry units, each of which is operable to classify particles in a mixture of particles by interrogating a stream of fluid containing the particles with a beam of electromagnetic radiation. The flow cytometry units share an integrated platform comprising at least one of the following: (1) a common supply of particles; (2) a common housing; (3) a common processor for controlling operation of the units; (4) a common processor for receiving and processing information from the units; and (5) a common fluid delivery system. The integrated platform can include a common source of electromagnetic radiation. A method of the invention comprises using a plurality of flow cytometry units sharing the integrated platform to perform a flow kilometric operation, such as analyzing or sorting particles.

Device for performing a blood, cell, and/or pathogen count and methods for use thereof

Devices and methods for performing a point of care blood, cell, and/or pathogen count or a similar blood test. Disclosed herein are systems that can be used to provide rapid, accurate, affordable laboratory-quality testing at the point of care. The systems described herein are capable of imaging and counting individual cells in a prepared cell sample (e.g., a peripheral blood smear or a blood sample prepared in a microfluidic device) or another prepared cell-containing sample without the need for a microscope or other expensive and cumbersome optics. The systems described herein are designed to eliminate or replace expensive, centralized clinical testing equipment and technical personnel. Such systems may include automated data reporting and decision support.

Apparatus for detecting tumor cells

Among others, the present invention provides apparatus for detecting circulating tumor cells, comprising a system delivery biological subject and a probing and detecting device, wherein the probing and detecting device includes a first micro-device and a first substrate supporting the first micro-device, the first micro-device contacts a biologic material to be detected and is capable of measuring at the microscopic level an electrical, magnetic, electromagnetic, thermal, optical, acoustical, biological, chemical, electro-mechanical, electro-chemical, electro-optical, electro-thermal, electro-chemical-mechanical, bio-chemical, bio-mechanical, bio-optical, bio-thermal, bio-physical, bio-electro-mechanical, bio-electro-chemical, bio-electro-optical, bio-electro-thermal, bio-mechanical-optical, bio-mechanical thermal, bio-thermal-optical, bio-electro-chemical-optical, bio-electro-mechanical-optical, bio-electro-thermal-optical, bio-electro-chemical-mechanical, physical or mechanical property, or a combination thereof, of the biologic subject.

Elemental flow cytometer

An elemental flow cytometer includes a device to vaporize, atomize, and ionize material and an introduction system for introducing packets of discrete entities into said device to vaporize, atomize and ionize materials to vaporize, atomize and ionize the entities in the packets. A spectrometer is adapted to individually analyze elemental composition of one or more of the vaporized, atomized and excited or ionized packets.

Methods and means for manipulating particles

The present invention is concerned with a system for sorting target particles from a flow of particles. The system has a microscope, a light source, a CCD camera, microfluidic chip device with microfluidic channels, a detection apparatus for detecting the target particles with predefined specific features, a response generating apparatus for generating a signal in response to the detection of the target particles, and an optical tweezing system for controlling movement of optical traps, the optical tweezing system is operably linked to the response signal.

High pressure sperm sorting and flow cytometer methods

Cell sorting methods that improve sorting efficiency and productivity by elevating sorting pressures and incorporate certain steps to help the cells better survive such elevated pressures. In the case of sperm, sorting the steps of standardizing sperm samples, staining sperm samples in a single step, calibrating a flow cytometer to place sperm in the leading edge of droplets, and changing a catch fluid distance may be incorporated individually, or in combination to help sperm better survive the sex sorting process.

DEVICES AND METHODS FOR FRACTIONATED PHOTOACOUSTIC FLOW CYTOMETRY

A fractionated photoacoustic flow cytometry (PAFC) system and methods for the in vivo detection of target objects in biofluidic systems (e.g., blood, lymph, urine, or cerebrospinal fluid) of a living organism is described. The fractionated system includes a fractionated laser system, a fractionated optical system, a fractionated acoustic system, and combinations thereof. The fractionated laser system includes at least one laser or laser array for pulsing a target object within the circulatory vessel with fractionated focused laser beams. The fractionated optical system separates one or several laser beams into multiple beams in a spatial configuration on the skin above the circulatory vessel of the living organism. The fractionated acoustic system includes multiple focused ultrasound transducers for receiving photoacoustic signals emitted by the target object in response to the fractionated laser beams. The target objects have intrinsic photoacoustic contrast or may be labeled with photoswitchable or spaser-based probes. Fractioned beams may be used also for diagnostics with other spectroscopic methods (e.g., fluorescence, Raman or scattering) and energy sources both coherent and conventional such as lamp and LED in the broad spectral range from 10 Å to 1 cm (e.g., X-ray, UV, visible, NIR or microwaves) in continuous wave and pulse modes. 1. A fractionated photoacoustic flow cytometry system for the in vivo detection of target objects in a biofluid system of a living organism , comprising:a laser system comprising at least one laser comprising at least one wavelength for providing at least one laser beam to at least one target object within the biofluid system;a fractionated optical system configured to separate the at least one laser beam into fractionated laser beams having a spatial configuration on the skin above the biofluid system of the living organism; andan acoustic system comprising at least one focused ultrasound transducer for receiving more than one ...

Anti-hsp70 specific chimeric antigen receptors (cars) for cancer immunotherapy

The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from an anti-HSP70 monoclonal antibody, conferring specific immunity against HSP70 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating in particular leukemia.

Particle separation

An example system includes an input channel having a first end and a second end to receive particles through the first end, a separation chamber, at least two output channels, and an integrated pump to facilitate flow through the separation chamber. The separation chamber is in fluid communication with the second end of the input channel. The separation chamber has a passive separation structure, the passive separation structure including an array of columns spaced apart to facilitate separation of particles in a flow based on a size of the particles. Each output channel is in fluid communication with the separation chamber to receive separated particles. The integrated pump is positioned within at least one of the input channel or one of the at least two output channels.

Information processing apparatus, information processing method, and program

To provide an information processing apparatus, at least one non-transitory computer-readable storage medium, and a method which evaluate the appropriateness of a clustering result in consideration of characteristics of multidimensional data to be clustered. An information processing apparatus comprising: at least one hardware processor; and at least one non-transitory computer-readable storage medium storing processor-executable instructions that, when executed by the at least one hardware processor, cause the at least one hardware processor to perform: receiving multidimensional data obtained from a plurality of cells; clustering the multidimensional data to generate clustering results indicating a plurality of clusters including a first cluster and a second cluster that share at least a portion of the multidimensional data; and outputting information representing reliability of the clustering results, wherein the information is indicative of a relationship between the first cluster and the second cluster.

METHOD AND SYSTEM FOR CHARACTERIZING PARTICLES USING AN ANGULAR DETECTION IN A FLOW CYTOMETER

The invention relates to a method and system for characterizing particles using a flow cytometer comprising detecting radiated light from the particles using two or more detectors positioned to allow for the detection in two or more angular directions and generating a waveform, as a digital representation for the detected radiated light for each of said angulation direction. The waveforms are transformed using one or more basis functions to obtain one or more coefficients characterizing the waveform. The one or more coefficients characterizing the waveform preferably correspond to properties of the particle(s), thereby enabling analysis of physical properties of the particles (such as size, shape, refractive index) or biological properties of the particles (such as cell type, cell cycle state or localization or distribution of molecules within the cell and/or on the cell surface). In preferred embodiments the method and system are used for a label-free sorting of particles, in particular biological cells. 1. A method for characterizing particles using a flow cytometer comprising:a. passing of one or more particles in a fluid stream through a light beam of the flow cytometer,{'b': '3', 'b. detecting radiated light as one or more particles pass through the light beam using two or more detectors positioned to allow for the detection of the radiated light () in two or more angular directions,'}c. generating for each of the angular directions a waveform which is a digital representation of the detected radiated light for said angular direction, andd. transforming each waveform using one or more basis functions and obtaining one or more coefficients characterizing the waveform.2. Method according to claim 1 , wherein the detected radiated light is a forward scatter signal claim 1 , a side scatter signal and/or a fluorescence light and the two or more detectors are positioned to allow for detection of a forward scatter signal claim 1 , a side scatter signal and/or a ...

Cll1-specific multi-chain chimeric antigen receptor

The present invention relates to a new generation of chimeric antigen receptors (CAR) referred to as multi-chain CARs, which are made specific to the antigen CLL1. Such CARs aim to redirect immune cell specificity and reactivity toward malignant cells expressing the tumor antigen CLL1. The alpha, beta and gamma polypeptides composing these CARs are designed to assemble in juxtamembrane position, which forms flexible architecture closer to natural receptors, that confers optimal signal transduction. The invention encompasses the polynucleotides, vectors encoding said multi-chain CAR and the isolated cells expressing them at their surface, in particularly for their use in immunotherapy. The invention opens the way to efficient adoptive immunotherapy strategies for treating cancer, especially leukemia.

mAb-DRIVEN CHIMERIC ANTIGEN RECEPTOR SYSTEMS FOR SORTING/DEPLETING ENGINEERED IMMUNE CELLS

A polypeptide encoding a chimeric antigen receptor (CAR) comprising at least one extracellular binding domain that comprises a scFv formed by at least a VH chain and a VL chain specific to an antigen, wherein said extracellular binding domain comprises at least one mAb-specific epitope. 1. A polypeptide encoding a chimeric antigen receptor (CAR) comprising at least one extracellular binding domain that comprises a scFv formed by at least a VH chain and a VL chain specific to an antigen , wherein said extracellular binding domain comprises at least one mAb-specific epitope.2. The polypeptide according to claim 1 , wherein said mAb-specific epitope is located between the VH and VL chains.3. The polypeptide according to claim 1 , wherein said VH and VL chains claim 1 , and mAb specific-epitope are bound together by at least one linker and to the transmembrane domain of said CAR by a hinge.4. The polypeptide according to claim 3 , wherein the mAb-specific epitope is joined to the VH and VL chains by two linkers.5. The polypeptide according to claim 1 , wherein the mAb-specific epitope is an epitope to be bound by an epitope-specific mAb for in vitro cell sorting and/or in vivo cell depletion of T cells expressing a CAR comprising such epitope.6. The polypeptide according to claim 1 , wherein the polypeptide comprises one extracellular binding domain claim 1 , wherein said extracellular binding domain further comprises a hinge claim 1 , and said polypeptide further comprisesa transmembrane domain, and,an intracellular domain.7. The polypeptide according to claim 1 , wherein the extracellular binding domain comprises 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , 5 claim 1 , 6 claim 1 , 7 claim 1 , 8 claim 1 , 9 or 10 mAb-specific epitopes.8. The polypeptide according to claim 1 , wherein the extracellular binding domain comprises 1 claim 1 , 2 claim 1 , 3 or claim 1 , 4 mAb-specific epitopes.9. The polypeptide according to claim 1 , wherein the extracellular binding ...

METHOD FOR ASSISTING IN EVALUATING PLURIPOTENT STEM CELL WITHOUT STAINS, STORAGE MEDIUM, AND OPERATION DEVICE

An operation device includes: a communication unit that receives signals of images of a biological sample and outputs data to a display medium, the images being captured by a microscope that converts a phase distribution into an image intensity distribution; and a calculator that calculates a first phase distribution of the biological sample from the image signals. The calculator extracts a region having a phase amount that is not less than a specified phase amount from the first phase distribution, and generates evaluation information by using the region having a phase amount that is not less than the specified phase amount, that is an indicator used when a user evaluates a state of the biological sample; and the communication unit outputs the evaluation information to the display medium. 1. A method for assisting in evaluating a pluripotent stem cell without stains , the method comprising:calculating a first phase distribution of a biological sample from signals of images of the biological sample, the images being captured by a microscope that converts a phase distribution into an image intensity distribution;extracting a region having a phase amount that is not less than a specified phase amount from the first phase distribution; andgenerating evaluation information by using the region having a phase amount that is not less than the specified phase amount, that is an indicator used when a user evaluates a state of the biological sample, and presenting the evaluation information, whereinthe specified phase amount is a phase amount of a mitochondrion in a somatic cell.2. The method for assisting in evaluating a pluripotent stem cell without stains according to claim 1 , whereinthe evaluation information is generated by distinguishing the region having a phase amount that is not less than the specified phase amount from another region in an image of the first phase distribution.3. The method for assisting in evaluating a pluripotent stem cell without stains ...

COMPUTER-IMPLEMENTED METHOD OF ANALYSING DATA FROM MEASURED VALUES OF CHARACTERISTICS OF OBJECTS IN SAMPLES

The invention relates to a computer implemented method of analysing data comprising measured values of characteristics of objects in samples, the data comprising —a first set of data (X) with measured values of characteristics of objects in reference samples; —a test set of data (X) with measured values of the characteristics of objects in a test sample; characterised by the method comprising; —fitting a control model to the first set of data to determine control loadings (P) each representing an independent correlation between characteristics; —projecting the first set of data (X) onto the control loadings (P) for determining a first set control scores (T) and determining one or more confidence intervals for the first set of control scores (T); —projecting the test data onto the control loadings (P) for determining test control scores; —determining if the test control scores are within one or more the confidence intervals. 117.-. (canceled)19. Computer implemented method according to claim 18 , wherein the step of fitting a control model comprises using the computer to conduct a principal component analysis to determine the control loadings (P).20. Computer implemented method according to claim 18 , wherein the first set of data (X) is centered per sample by using a computer for determining per reference sample (i) the mean value (m) of each characteristic and subtracting for each reference sample (i) the corresponding mean value (m) of the characteristic from the measured value in the first set of data (X) of the corresponding characteristic before fitting the control model.21. Computer implemented method according to claim 18 , wherein the test set of data (X) is centered per sample by using a computer for determining per test sample (i) the mean value of each characteristic and subtracting for each test sample (i) the corresponding mean value of the characteristic from the measured value in the test set of data of the corresponding characteristic before ...

Microfluidic Sensing

A device including a microfluidic channel structure formed on a substrate and including a first channel and a fluid actuator within the microfluidic channel structure. A sense region within the first channel is to receive a fluid flow of target biologic particles for counting in a single file pattern, with the sense region having a volume on a same order of magnitude as a volume of a single one of the target biologic particles. 1. A biologic test chip comprising:a substrate;a microfluidic channel structure formed on the substrate and including a first channel;a fluid actuator within the microfluidic channel structure.a sense region within the first channel to receive a fluid flow of biologic particles on a one-at-a-time basis via operation of the fluid actuator, the sense region having a volume on a same order of magnitude as a volume of a single respective one of the biologic particles.2. The chip of claim 1 , wherein the sense region operates according to a volume fraction in which a ratio of the volume of each single biologic particle relative to the volume of the sense region is on an order of tenths.3. The chip of claim 2 , comprising:at least one impedance sensor generally coextensive within the sense region to count biologic particles passing through the sense region.4. The chip of claim 3 , wherein the biologic particles are subject to a dilution factor on the order of tens.5. The chip of claim 4 , wherein the channel structure provides a non-uniform flow portion to align the biological particles into a single file flow pattern through the sense region claim 4 , the non-uniform flow portion including at least one of:an exclusion structure upstream from the sense region to exclude biologic particles larger than the volume of the sense region; andan inlet including a progressively narrowing cross-sectional area in the downstream orientation.6. The chip of claim 5 , wherein the first channel generally defines a first cross-sectional area and the first channel ...

Phenotypic High-Content Assay to Evaluate Drugs

The present invention includes a high throughput screen for an active agent for the treatment of comprising: plating cells at least one pathophysiologically relevant mislocated mutant form of a peroxisomal enzyme; adding a control and compound to each plate from a library of compounds; fixing the cells; contacting the cells with an agent that detects the mislocated mutant form of a peroxisomal enzyme; and imaging the cells in the wells. 1. A method of determining the effectiveness of one or more drug candidates to change the intracellular localization of a target molecule , the method comprising:(a) incubating the one or more drug candidates with a first subset of the cells, and a control agent with a second subset of the cells;(b) fixing and staining the first and second subset of cells, wherein the stain detects the target molecule;(c) generating images of the first and second subset of cells with a camera;(d) measuring the difference in the intracellular localization of the target molecule in the first as compared to a second subset of cells; and(e) determining if the drug candidate modifies the localization of the intracellular localization of the target protein, wherein if the candidate drug modifies the intracellular localization of the target protein when compared to the placebo it is an effective drug candidate.4. The method of claim 1 , further comprising the step of determining cell count claim 1 , nuclear intensity claim 1 , morphology and condensation.5. The method of claim 1 , wherein the localization changes from the cytosol or mitochondria to a peroxisome.6. The method of claim 1 , wherein a candidate drug is selected from at least one of 26-Deoxymonensin B claim 1 , nigericin claim 1 , salinomycin claim 1 , or active derivatives thereof.7. A method of determining the effectiveness of one or more candidate pharmacoperones to treat and/or prevent protein misfolding claim 1 , the method comprising:(a) incubating the one or more candidate pharmacoperones ...

Fine particle measurement device

A fine particle measurement device includes a support stand (20) that has a groove (F) extending in a predetermined direction and is configured to support in the groove an observation container (10), which has an elongate shape and accommodates a liquid sample containing a fine particle therein such that an extending direction of the groove (F) coincides with a longitudinal direction of the observation container (10); and an imaging unit (40) that is configured to capture an image of the fine particle in the observation container (10) at a position where the support stand is out of a field of view, the observation container (10) being supported by the support stand (20).

Method and apparatus to collect, fractionate, and classify airborne particles within specified volumetric regions

A searching procedure based on the detection and separation by specific multiangle scattered light properties of a small set of particles sought from a sample containing far greater concentrations of irrelevant particles is presented whereby all the particulate content of a volumetric fraction of the air of a targeted facility is captured and the particles of potential importance are separated therefrom. The unique size ranges, multiangle light scattering characteristics, and physical properties associated with specific particulates sought (such as bacteria or spores from spore-forming bacteria or asbestos particles, for example), once extracted from the total populations collected, are then processed for further study/classification/actions, as required. For the case of airborne bacteria, such processes could be expected to reduce the incidence of hospital acquired infections, by providing an early warning of their presence and capturing specific exemplars thereof for future analyses. Similarly, the early detection of a bioterrorist attack in progress or the presence of dangerous airborne contaminants, such as asbestos fibers, will have long serving benefits. 120-. (canceled)21: A method to search for , isolate , find , and retrieve vanishingly small populations of a specific class of airborne particles that may be present in a selected region of air containing far greater populations of unimportant particles of varying size and composition , comprising the steps ofa. Defining the specific class of airborne particles sought;b. Collecting all particles present within said selected region of air into a liquid of relatively small volume;c. Fractionating said collected liquid-borne particles by size or other means;d. Classifying and/or identifying said fractionated and collected particles from multiangle measurement of light scattered therefrom;e. Isolating for further study, analysis and/or identification the specific fractions of said collected particles among the ...

MICROBIAL CYTOMETRIC MOCK COMMUNITIES AND USE THEREOF AS STANDARD IN FLOW CYTOMETRY

The present invention is directed to a microbial Cytometric Mock Community for use in flow cytometric analysis, the microbial Cytometric Mock Community comprising or consisting of cells of at least three different microbial species in a pre-defined ratio, wherein the at least three different microbial species are selected such that, when measured using flow cytometry, the specific gate pattern of each microbial species differs significantly from the specific gate pattern of the other microbial species of the microbial Cytometric Mock Community, preferably the at least three different microbial species differ in relative DNA content, relative genomic GC-content, relative cell size, Gram +/− affiliation and/or capacity to form spores. The microbial Cytometric Mock Community shall serve as standardization means that will help ecologists, microbiologists, molecular biologists and flow cytometrists to work on a standardized basis to allow comparison and exchange of data. 1. Microbial Cytometric Mock Community for use in flow cytometric analysis , the microbial Cytometric Mock Community comprising or consisting of cells of at least three different microbial species in a pre-defined ratio , wherein the at least three different microbial species are selected such that , when measured using flow cytometry , the specific gate pattern of each microbial species differs significantly from the specific gate pattern of the other microbial species of the microbial Cytometric Mock Community , preferably the at least three different microbial species differ in overall DNA content , relative genomic GC-content , average cell size , Gram +/− affiliation and/or capacity to form spores.2. Microbial Cytometric Mock Community of claim 1 , wherein the at least three different microbial species comprise or consist of species derived from archaea claim 1 , bacteria claim 1 , fungi claim 1 , protozoa and algae claim 1 , preferably derived from bacterial species.3. Microbial Cytometric Mock ...

Particle Detection Methods and Systems for Practicing Same

Aspects of the present disclosure include methods for detecting events in a flow cytometer. Also provided are methods of detecting cells in a flow cytometer. Other aspects of the present disclosure include methods for determining a level of contamination in a flow cell. Computer-readable media and systems, e.g., for practicing the methods summarized above, are also provided. 123-. (canceled)24. A method for detecting cells in a flow cytometer , comprising:flowing a cellular sample comprising cells through a flow cell of a flow cytometer;detecting optical signals from the cells flowing through the flow cell at a first gain setting; anddetecting optical signals from the cells flowing through the flow cell at the second gain setting, wherein the second gain setting is different from the first gain setting.25. The method according to claim 24 , wherein the second gain setting is greater than the first gain setting.26. The method according to claim 25 , wherein the second gain setting is to account for the cellular sample having a high cell concentration.27. The method according to claim 24 , wherein the second gain setting is less than the first gain setting.28. The method according to claim 27 , wherein the second gain setting is to account for the cellular sample having a low cell concentration.29. The method according to claim 24 , wherein the first and second gain settings comprise a photo diodes gain setting claim 24 , a photo multiplier tubes (PMT) gain setting claim 24 , or both.30. The method according to claim 24 , wherein the cellular sample is a blood sample.31. The method according to claim 24 , comprising:analyzing the optical signals detected at the first gain setting to detect a first cell type; andanalyzing the optical signals detected at the second gain setting to detect a second cell type.32. The method according to claim 31 , wherein the first gain setting is higher than the second gain setting claim 31 , and wherein platelets are detected at the ...

Visual protocol designer

Disclosed is a graphical user interface to quickly build a graphical representation defining the set of instructions in a protocol without the user needing the programming knowledge to encapsulate those instructions in executable code. The graphical representation may include an arrangement of one or more graphical elements, with each graphical element corresponding to instructions or program logic. The user may also specify the set of parameters associated with each of the graphical elements. The arrangement of the one or more graphical elements, along with the set of parameters for each of the graphical elements, may be used to translate the graphical representation of the protocol into executable code for the protocol. The executable code for the protocol may then be executed by various flow cytometry machines in order to perform the protocol.

FLUID PUMPING AND TEMPERATURE REGULATION

Fluid may be pumped within a microfluidic channel across a cell/particle sensor using a microscopic resistor. The microscopic resistor may be selectively actuated so as to heat the fluid within the microfluidic channel to a temperature below a nucleation energy of the fluid so as to regulate a temperature of the fluid for at least when the cell/particle sensor is sensing the fluid. 1. An apparatus comprising:a microfluidic channel to receive a fluid;an analyte sensor within the microfluidic channel;a microscopic resistor in the microfluidic channel; and actuate the microscopic resistor to a fluid pumping state in which fluid adjacent the microscopic resistor is heated to a temperature above a nucleation energy of the fluid to pump the fluid across the cell/particle sensor; and', 'selectively actuate the microscopic resistor to a temperature regulating state in which fluid adjacent the microscopic resistor is heated to a temperature below the nucleation energy of the fluid, wherein the controller is to selectively actuate the microscopic resistor to the temperature regulating state to regulate a temperature of the fluid for at least when the analyte sensor is sensing the fluid., 'a controller to2. The apparatus of further comprising a temperature sensor to output temperature signals indicative of a temperature of the fluid claim 2 , wherein the controller is to selectively actuate the microscopic resistor to the temperature regulating state based upon the temperature signals.3. The apparatus of comprising:a cassette containing a microfluidic diagnostic chip, the microfluidic diagnostic chip comprising the microfluidic channel, the temperature sensor and the microscopic resistor; anda portable electronic device containing the controller, wherein the cassette is releasably connectable to the portable electronic device.4. The apparatus of claim 1 , wherein the controller is to selectively actuate the microscopic resistor so as to apply different amounts of heat when in ...

DIAGNOSTIC CHIP

A microfluidic diagnostic chip may comprise a main fluid channel comprising a main pump, a secondary fluid channel branching off from the main fluid channel, and a secondary pump within the secondary fluid channel wherein the secondary pump is to pull a particle of analyte of a first size from a fluid passing through the main channel, the fluid comprising particles of analyte of the first size and of a number of larger sizes. A method of analyzing an analyte on a microfluidic chip may comprise pumping, with a main microfluidic pump, a fluid comprising an analyte particle through a main microfluidic channel fluidly coupled to a fluid slot and sorting the analyte particle within the fluid through a secondary microfluidic channel by pulling the analyte particle into the secondary microfluidic channel with a secondary microfluidic pump. 1. A microfluidic diagnostic chip , comprising:a main fluid channel comprising a main pump;a secondary fluid channel branching off from the main fluid channel; anda secondary pump within the secondary fluid channel wherein the secondary pump is to pull a particle of analyte of a first size from a fluid passing through the main channel, the fluid comprising particles of analyte of the first size and of a number of larger sizes.2. The microfluidic diagnostic chip of claim 1 , wherein the secondary fluid channel comprises a smaller diameter than the main fluid channel.3. The microfluidic diagnostic chip of claim 2 , wherein the secondary fluid channel comprises a first sensor to count a number of the particles of the first size passing therethrough.4. The microfluidic diagnostic chip of claim 2 , wherein the diameter of the secondary fluid channel excludes the number of larger sizes of particles.5. The microfluidic diagnostic chip of claim 3 , wherein the main fluid channel comprises a second sensor to count particles of the analyte of the first size and larger sizes passing therethrough.6. The microfluidic diagnostic chip of claim 5 , ...

Sequencing of nucleic acids via barcoding in discrete entities

Microfluidic methods for barcoding nucleic acid target molecules to be analyzed, e.g., via nucleic acid sequencing techniques, are provided. Also provided are microfluidic, droplet-based methods of preparing nucleic acid barcodes for use in various barcoding applications. The methods described herein facilitate high-throughput sequencing of nucleic acid target molecules as well as single cell and single virus genomic, transcriptomic, and/or proteomic analysis/profiling. Systems and devices for practicing the subject methods are also provided.

Cell capture in microfluidic devices

A capturing of target cells from a biological sample is achieved by inducing a flow of the biological sample in a flow channel (30, 60) of an upstream microfluidic device (1). Target cells present in the biological sample are captured in cell channels (20) of the upstream microfluidic device(1). Once at least a minimum number of target cells are captured in the cell channels (20), the flow of the biological sample in the flow channel is reduced and are verse flow is applied at the upstream microfluidic device (1) to release the target cells captured in the cell channels (20) of the upstream microfluidic device (1) and enable transfer the target cells into cell channels (120) of a downstream microfluidic device (100).

METHODS AND DEVICES FOR EVALUATING PERFORMANCE OF A DIODE LASER

Methods for evaluating performance a diode laser are provided. In embodiments, methods include receiving a laser beam profile of a diode laser, determining first, second and third laser beam widths at first, second and third laser intensities, respectively, for the laser beam profile, computing a first ratio between the second and third laser beam widths, computing a second ratio between the first and second laser beam widths, evaluating laser performance based on the first and second ratios, and outputting a determination regarding the suitability of the laser for use in a flow cytometry setting. Devices for practicing the subject methods are also provided, and include first and second stages configured to receive a diode laser and beam profiler, respectively. Aspects of the invention further include flow cytometers incorporating a diode laser that has been evaluated by the subject method. 1. A method for evaluating performance of a diode laser , the method comprising:receiving a laser beam profile of the diode laser, the laser beam profile comprising laser beam width data and laser intensity data;determining first, second and third laser beam widths at first, second and third laser intensities, respectively, for the laser beam profile;computing:a first ratio between the second and third laser beam widths; anda second ratio between the first and second laser beam widths; andevaluating laser performance based on the first and second ratios.2. The method according to claim 1 , wherein the diode laser is a semiconductor laser diode.35-. (canceled)6. The method according to claim 1 , wherein evaluating performance of the diode laser comprises assessing the extent to which the laser beam profile deviates from a Gaussian beam shape.7. The method according to claim 6 , wherein assessing the extent to which the laser beam profile deviates from a Gaussian beam shape comprises identifying whether multiple modes are present in the laser beam profile.8. The method according to ...

MICROFLUIDIC SYSTEM AND METHOD WITH FOCUSED ENERGY APPARATUS

A method of inseminating an animal including flowing a stream of a population of sperm cells through a channel, differentiating the sperm cells into two subpopulations of X-chromosome containing sperm cells and Y-chromosome containing sperm cells, selecting a desired subpopulation, ablating an undesired subpopulation, and collecting both the subpopulations of sperm cells including the desired subpopulation and the ablated undesired subpopulation together, wherein the collected population of sperm cells is used to fertilize an egg. 1. A method for producing a sexed composition of sperm comprising non-human animal sperm by identifying a subpopulation of sperm from a population of sperm in a sample fluid , the method comprising:staining the population of sperm in the sample fluid with a dye;defining a gating strategy for differentiating the subpopulation of sperm in the sample fluid in the population of sperm based on one or more physical characteristics of sperm in the population of sperm, wherein the one or more physical characteristics are identifiable within the population of sperm based in part on the dye staining, and wherein the gating strategy comprises identifying one or more desired physical characteristics of the subpopulation of sperm;measuring the one or more physical characteristics for the sperm in the population of sperm;identifying sperm in the subpopulation of sperm based on the measured one or more physical characteristics and the defined gating strategy; andgenerating the sexed composition of sperm comprising the subpopulation of sperm identified based on the measured one or more physical characteristics and the defined gating strategy.2. The method of claim 1 , wherein the population of sperm in the sample fluid comprises bovine sperm.3. The method of claim 1 , wherein the sexed composition of sperm substantially comprises X chromosome-bearing sperm cells.4. The method of claim 1 , wherein the sexed composition of sperm substantially comprises Y ...

COMPOUND OPTICAL FLOW CELLS AND METHOD OF MANUFACTURE AND USE

An improved optical flow cell adapted for use in a flow cytometer for differentiating formed bodies (e.g., blood cells) in liquid suspensions. Preferably manufactured by assembling, aligning, and optically joining at least two elements made from transparent material, the improved flow cell has a seamless internal flow channel of preferably non-circular cross-section in a cylindrical first element through which prepared samples can be metered and an independent second element having an external envelope suited to acquisition of optical parameters from formed bodies in such suspensions, the second element being conforming and alignable to the first element so that non-axisymmetric refractive effects on optical characterizing parameters of formed bodies passing through the flow channel in the first element may be minimized before the two elements are optically joined and fixed in working spatial relationship. 1. A method for making a transparent compound optical flow cell of the type used to characterize formed bodies passing through the flow cell , the optical flow cell having formed therein a rectilinear internal flow channel , the method comprising the steps of:providing a cylindrical monolithic preform comprising a thick-wall glass tube having an axially-extending channel therethrough and a transition temperature, the channel comprising a substantially uniform original cross-section of a desired shape;heating the preform to a predetermined temperature above the transition temperature of the glass tube;axially drawing the preform at a controlled rate, for a controlled time, and at a constant angular orientation, to achieve a desired reduced cross-sectional area of the axially-extending channel;providing an optical element, the optical element comprising a conforming surface that conforms to a segment of the drawn preform, and an exterior non-cylindrical envelope of predetermined form and orientation relative to the conforming surface;assembling the optical element ...

Method and device for examining myocardial toxicity and evaluating cardiomyocytes

Regarding cardiomyocytes and fibroblasts, it is meaningful to develop a device or system whereby, upon the transmission of pulsation from an adjacent cardiomyocyte or fibroblast, cell potential and cell morphology can be accurately measured on a single cell basis and the toxicity of a drug on cardiomyocytes can be examined on the basis of accurately measured cell potential and cell morphology of a single cell. In the present invention, a mass of cardiomyocytes is disposed on a transparent substrate and the qualities of the cardiomyocytes are evaluated depending on the response of the cardiomyocytes to a forced pulsation stimulus that is applied to the pulsating cardiomyocytes. A mass of cardiomyocytes, said mass being disposed on the transparent substrate, is exposed to a flow of a drug-containing liquid so as to allow the drug to act on cells configuring a network. The level of myocardial toxicity of the drug is evaluated by measuring the fluctuations that are obtained by comparing adjacent pulsating cardiomyocytes in the network.

METHODS FOR QUANTITATIVE ASSESSMENT OF MUSCLE FIBERS IN MUSCULAR DYSTROPHY

The disclosure concerns a method for assessing muscular dystrophy-linked protein expression in muscle fibers using digital image analysis of tissue. The method relates to assessing disease severity in individuals with muscular dystrophy. Muscle tissue samples are obtained from patients submitted for evaluation and processed to produce tissue sections mounted on glass slides which have been stained for a muscular dystrophy-linked protein. Digital images of the stained tissue sections are generated and analyzed by applying an algorithm process implemented by a computer to the images. The algorithm process extracts the morphometric and staining features of the muscular dystrophy-linked protein staining in the tissue, and parameters relating to these features are used to score the disease status for each patient submitted for evaluation. The score of disease status is ultimately used to infer disease severity, monitor the efficacy of a therapeutic approach, or select patients as candidates for a therapeutic approach. 1. A method comprising:capturing at least one digital image of at least one stained muscle tissue section;extracting at least one image analysis feature from each muscle fiber in the at least one digital image, wherein the at least one image analysis feature is selected from the group consisting of staining features and morphometric features;combining at least one staining and morphometric feature to derive a score of disease status; andinterpreting the score of disease status to draw inferences associated with the severity of disease.2. The method of claim 1 , wherein the at least one tissue section is stained for at least one muscular marker selected from the group consisting of a muscular dystrophy-linked protein and a muscle fiber membrane biomarker.3. The method of claim 2 , wherein the muscular dystrophy-linked protein is a protein product of a gene that when mutated claim 2 , or otherwise disrupted claim 2 , gives rise to at least one muscular ...

SYSTEM AND METHOD FOR IMMERSION FLOW CYTOMETRY

An immersion cytometry system () having a primary focusing optic immersed in a fluid stream () containing suspended particles (). The system includes a light source () configured to illuminate a sensing region in the fluid stream that includes a focus of the primary optic. Light scattered and/or fluoresced from suspended particles passing through the sensing region is focused by an external tube lens on an external detector. The primary optic in one embodiment is a ball lens. In some embodiments, one or more filter/beam splitters on the optical axis reflect a portion of the signal light towards corresponding detectors, each filter being configured to reflect a preselected waveband of light. 1. A flow cytometry system for detecting particles suspended in a fluid stream , the system comprising:a light source configured to direct light through a sensing region in the fluid stream;a primary focusing optic at least partially immersed in the fluid stream and positioned to receive and focus light scattered by the suspended particles when they are in the sensing region; anda tube lens positioned to receive light from the primary optic and to focus the received light onto a first photo detector, the primary optic and the tube lens defining an optical axis that is aligned with the photo detector;wherein the first photo detector is configured to generate a signal responsive to the light focused by the tube lens onto the first photo detector and to transmit the generated signal to a processing system.2. The immersion flow cytometry system of claim 1 , wherein the primary focusing optic comprises a ball lens.3. The immersion flow cytometry system of claim 2 , wherein the ball lens comprises glass.4. The immersion flow cytometry system of claim 3 , wherein the glass is a flint glass.5. The immersion flow cytometry system of claim 1 , wherein the primary focusing optic is configured to chromatically distort the light claim 1 , such that the location of the focus plane on the ...

MICROFLUIDICS DETECTION

A method of microfluidic detection can include detecting, using an impedance sensor, an impedance of a fluid to indicate whether a threshold amount of fluid has been received in a reservoir of a microfluidic chip. The method can include initiating a test performed by the microfluidic chip on the received fluid when the threshold amount of fluid has been received. 1. A method , comprising:detecting, using an impedance sensor, an impedance of a fluid to indicate that a threshold amount of fluid has been received in a reservoir of a microfluidic chip; andwhen the threshold amount of fluid has been received, initiating a test performed by the microfluidic chip on the received fluid.2. The method of claim 1 , including detecting whether the threshold amount of fluid has been received in response to receiving the fluid in the reservoir.3. The method of claim 1 , including detecting claim 1 , using the impedance sensor claim 1 , a second impedance of the fluid to indicate that the threshold amount has not been received in the reservoir claim 1 , wherein the test is not initiated when the detection of the fluid indicates the threshold amount has not been received.4. The method of claim 1 , wherein detecting the impedance of the fluid comprises:measuring the impedance indicating the amount of the received fluid; andcomparing the amount of the received fluid to the threshold amount.5. The method of claim 1 , including detecting whether the fluid is a particular type of fluid using an additional impedance sensor.6. The method of claim 5 , wherein the test is initiated when the particular type of fluid is detected and the threshold amount has been received.7. A method claim 5 , comprising:receiving fluid in a reservoir of a microfluidic chip;measuring, using an impedance sensor, a value of a parameter of the fluid;comparing, by a processor, the measured value to a threshold value; andwhen the measured value exceeds the threshold value, indicating to the microfluidic chip to ...

FINE PARTICLE MEASUREMENT APPARATUS, INFORMATION PROCESSING APPARATUS, AND INFORMATION PROCESSING METHOD

To provide a technology that an output level difference is corrected with high accuracy in fine particle measurement that optically measures properties of fine particles. The present technology provides a fine particle measurement apparatus including a detector that detects light from fluorescent reference particles that emit fluorescence having a predetermined wavelength bandwidth, and an information processor that specifies a relationship between an applied voltage coefficient corresponding to a feature amount of a predetermined output pulse and a control signal of the detector on the basis of a feature amount of an output pulse detected by the detector and the control signal of the detector at the time of detecting the feature amount of the output pulse, the feature amount of the output pulse being dependent on the control signal of the detector, or the like. 1. A fine particle measurement apparatus , comprising:a detector that detects light from fluorescent reference particles that emit fluorescence having a predetermined wavelength bandwidth; andan information processor that specifies a relationship between an applied voltage coefficient corresponding to a feature amount of a predetermined output pulse and a control signal of the detector on the basis of a feature amount of an output pulse detected by the detector and the control signal of the detector at the time of detecting the feature amount of the output pulse,the feature amount of the output pulse being dependent on the control signal of the detector.2. The fine particle measurement apparatus according to claim 1 , whereinthe detector includes a plurality of PMTs.3. The fine particle measurement apparatus according to claim 2 , whereinthere is an output difference among the plurality of PMTs.4. The fine particle measurement apparatus according to claim 1 , whereinthe feature amount of the output pulse is a height of the output pulse or an area of the output pulse.5. The fine particle measurement apparatus ...

LABEL-FREE CHARACTERIZATION OF PARTICLES SUSPENDED IN A FLUID

Provided are methods and systems that characterize a property of a particle suspended in a fluid sample in a label-free manner. Detection elements are provided fluidically adjacent upstream and downstream from a modulation element. Fluid sample containing particles flows across a first detection element and a first particle parameter detected for each particle that passes the first detection element or a first aggregate particle parameter for a plurality of particles that pass the first detection element. The particles flow from the first detection element to a first modulation element, wherein the first modulation element effects a change in a property of the particles flowing past the first modulation element. A second detection element then detects the particle parameter again or a second aggregate particle parameter for a plurality of particles that pass the second detection element. Comparing the first and second particle or aggregate parameters thereby characterizes the particle property. 1. A label-free method for characterizing a property of a particle suspended in a fluid sample , the method comprising the steps of:flowing a fluid sample containing particles across a first detection element, wherein the particles flow in substantially single file across the first detection element;detecting with the first detection element a particle parameter for at least a portion of the particles that pass the first detection element;flowing the particles from the first detection element to a first modulation element, wherein the first modulation element effects a change in the particle parameter of the particles flowing past the first modulation element;flowing the particles from the first modulation element across a second detection element, wherein the particles flow in substantially single file across the second detection element;detecting with the second detection element the particle parameter for the at least a portion of the particles that pass the second ...

SYSTEMS AND METHODS FOR EVALUATING IMMUNE RESPONSE TO INFECTION

Systems and methods for characterizing immune response to infection using cellular analysis, such as a hematological cellular analyzer. In some instances, the immune response may be characterized as normal or abnormal based on one or more blood cell population parameters. In some instances, abnormal characterization may be used to identify patients with sepsis or at elevated risk of developing sepsis.

METHOD FOR QUANTIFICATION OF PURITY OF SUB-VISIBLE PARTICLE SAMPLES

The method is for quantification of purity of sub-visible particle samples. A sample to be analyzed is place in an electron microscope to obtain an electron microscopy image of the sample. The sample contains objects. The objects that have sizes being different from a size range of primary particles and sizes being within the size range of primary particles are enhanced. The objects are detected as being primary particles or debris. The detected primary particles are excluded from the objects so that the objects contain debris but no primary particles. A first total area (T1) of the detected debris is measured. A second total area (T2) of the detected primary particles is measured. 1. A method for quantification of purity of sub-visible particle samples , comprising:placing a sample to be analyzed in an electron microscope to obtain an electron microscopy image of the sample, the sample containing objects;enhancing the objects in the image having sizes being different from a size range of primary particles and sizes being within the size range of primary particles;detecting the objects in the image as being primary particles or debris;excluding the detected primary particles from the objects so that objects contains debris but no primary particles;measuring a first total area (T1) of the detected debris;measuring a second total area (T2) of the detected primary particles; andcalculating a ratio of the first total area (T1) to the second total area (T2) to determine a quantitative measurement of purity of the sample.2. The method according to wherein the method further comprises enhancing edges of objects in the image that have a size that is substantially similar to a size range of primary particles and analyzing a roundness of the objects to identify primary particles.3. The method according to wherein the method further comprises enhancing edges of objects in the image that have a size that is substantially similar to a size range of primary particles and ...

ADVANCED BIOPHYSICAL AND BIOCHEMICAL CELLULAR MONITORING AND QUANTIFICATION USING LASER FORCE CYTOLOGY

The present invention is directed to intelligent algorithms, methodologies and computer-implemented methodologies for biophysical and biochemical cellular monitoring and quantification enabling enhanced performance and objective analysis of advanced infectivity assays including neutralization assays and adventitious agent testing using fluidic and optical force-based measurements. 1. A method for measuring cellular responses to differential stimuli using optical and/or fluidic forces , wherein the method comprises:receiving a selection of an initial samples comprising biological cells treated with varying known levels of stimuli or analyte,performing optical force-based measurements on the samples,developing a response metric (RM) to describe the cellular response to the stimuli based on one or more optical or fluidic force-based parameters.2. The method of claim 1 , wherein the response metric is used to measure the response of additional unknown samples.3. The method of claim 1 , further comprising analyzing dilutions of the sample until an accurate measurement of the infectivity is determined claim 1 , based upon having an RM that falls within the acceptable target value range.4. (canceled)5. The method of claim 1 , where the optical and fluidic forces are based on laser force cytology.6. The method of further comprising:comparing the response metric of an initial sample to a target value;selecting a second sample based on the results of the first and an algorithm governing the expected or known response;comparing the response metric of the second sample to a target value; andselecting subsequent samples in a similar manner until a sample matching the target response metric or other defined endpoint is identified.7. The method of claim 5 , wherein the optical force-based measurements utilize laser force cytology to assess parameters comprising linear velocity claim 5 , size claim 5 , perimeter claim 5 , size (area claim 5 , diameter claim 5 , volume claim 5 , etc ...

Method for detection of cells in a cytological sample having at least one anomaly

Disclosed is a method for detecting cells having at least one anomaly in a cytological sample on the basis of at least one first digitised digitised-electron-microscopy image of the sample.

IMPEDANCE FLOW CYTOMETRY METHODS

A method of antimicrobial susceptibility testing comprises: preparing samples of microorganisms suspended in an electrolyte, comprising a first sample of the microorganisms unexposed to antimicrobial agents and a second sample of the microorganisms exposed to an antimicrobial agent; passing the first sample through an impedance flow cytometer to obtain a first impedance signal representing one or more components of impedance values of the unexposed microorganisms; passing the second sample through the impedance flow cytometer to obtain a second impedance signal representing one or more components of the impedance values of the exposed microorganisms; comparing the first impedance signal and the second impedance signal; and determining a susceptibility of the microorganisms to the antimicrobial agent based on any differences between the first impedance signal and second impedance signal. A method of impedance flow cytometry comprises: flowing a sample of fluid comprising particles suspended in an electrolyte along a flow channel; applying electrical signals to current paths through the fluid, the current paths comprising at least a first current path, a second current path, a further first current path and a further second current path, wherein the electrical signals applied to the first current path and the further first current path have a frequency, magnitude and phase and the electrical signals applied to the second current path and the further second current path have substantially equal frequency and magnitude and opposite phase to the electrical signals applied to the first current path and the second current path; detecting current flow in the current paths; producing a first summed signal representing the sum of the current flow detected in the first current path and the second current path, and a second summed signal representing the sum of the current flow detected in the further first current path and the further second current path; and obtaining a ...

METHODS AND APPARATUS FOR CENTRAL SOURCE PRESSURE-BASED CYTOMETER FLUIDICS SYSTEM

A system, method, and apparatus are provided for cytometer fluidics. In one example, a pressure regulation system is provided for a cytometer fluidics system. The pressure regulation system includes a pressure regulator and a transducer. The pressure regulator pressurizes sheath fluid in a fluid path. The transducer senses a measured pressure in the fluid path independently of the sheath tank. The transducer converts the measured pressure into a voltage. The transducer communicates the voltage to the pressure regulator. The pressure regulator translates the voltage to a regulated pressure that substantially matches the measured pressure. The pressure regulator is the only pressure regulation source in the cytometry fluidics system. 1. A cytometer fluidics system , comprising:a sheath tank;a manifold assembly coupled to the sheath tank via a first sheath line;a flow cell coupled to the manifold assembly via a second sheath line; anda pressure regulation system coupled to the sheath tank, the pressure regulation system including a pressure regulator that applies a regulated pressure to the sheath tank to maintain a total flow rate of fluids in the cytometer fluidics system, wherein the pressure regulator is an only regulated pressure source in the cytometer fluidics system.2. The cytometer fluidics system of claim 1 , further comprising:a first valve coupled to the first sheath line and in the manifold assembly; andthe pressure regulation system further including a transducer coupled to the first valve and electrically coupled to the pressure regulator, wherein the transducer is configured to sense measured pressure at the first valve and convert the measured pressure to a voltage, and wherein the pressure regulator is configured to receive the voltage from the transducer and convert the voltage to the regulated pressure.3. The cytometer fluidics system of claim 2 , wherein the pressure regulation system maintains the regulated pressure by attempting to match the ...

CELL SORTING DEVICE AND METHOD

A cell sorting system is provided to comprise: an imaging device including abeam scanner scanning abeam along a first direction to obtain a cell image data including fluorescent information or cell image information of a cell, the beam applied to the cell flowing in a channel along a second direction with an angle to the first direction; a data processing and control device in communication with the imaging device, the data processing and control device including a processor configured to process the cell image data obtained by the imaging device to determine one or more properties associated with the cell from the processed cell image data and to produce a control command based on a comparison of the determined one or more properties with a sorting criteria, and a cell sorting device in communication with the imaging device and the data processing and control device. 1. A cell sorting system , comprising:an imaging device including a beam scanner scanning a beam along a first direction to obtain a cell image data including fluorescent information or cell image information of a cell, the beam applied to the cell flowing in a channel along a second direction with an angle to the first direction;a data processing and control device in communication with the imaging device, the data processing and control device including a processor configured to process the cell image data obtained by the imaging device to determine one or more properties associated with the cell from the processed cell image data and to produce a control command based on a comparison of the determined one or more properties with a sorting criteria, wherein the control command is produced during the cell flowing in the channel and is indicative of a sorting decision determined based on one or more cellular attributes ascertained from the cell image data; anda cell sorting device in communication with the imaging device and the data processing and control device, the cell sorting device including two ...

METHOD FOR DETERMINING DESIRED CELL TYPE USING EXPRESSION OF miRNA AS INDICATOR

A method for distinguishing living cells in a living state with high accuracy. A method for distinguishing a desired cell type from a cell group comprising two or more types of cells, using the expression of miRNA as an indicator, wherein the method comprises the following steps: 1. A method for distinguishing a desired cell type from a cell group comprising two or more types of cells , using the expression of miRNA as an indicator , wherein the method comprises the following steps:(1) a step of introducing mRNA comprising a marker gene operably linked to the target sequence of miRNA used as an indicator into a cell group; and(2) a step of distinguishing a cell type, using the translation level of the marker gene as an indicator.2. The method according to claim 1 , wherein the step (1) is a step of simultaneously introducing the target sequence of miRNA used as an indicator and two or more mRNAs comprising different marker genes into cells.3. The method according to or claim 1 , wherein the desired cell type is a cell type in which the expression level of miRNA used as an indicator is low claim 1 , and the step (2) is a step of distinguishing a cell type in which the translation level of the marker gene is high.4. The method according to any one of to claims 1 , wherein the desired cell type is a cell claims 1 , type in which the expression level of miRNA used as an indicator is high claims 1 , and the step (2) is a step of distinguishing a cell type in which the translation level of the marker gene is low.5. The method according to any one of to claims 1 , wherein claims 1 , the target sequence of the miRNA is linked to the 5′-terminal side of the marker gene.6. The method according to any one of to claims 1 , wherein the determination is carried out using a flow cytometer.7. The method according to any one of to claims 1 , wherein the determination claims 1 , is carried out using an image analyzer.8. The method according to any one of to claims 1 , which further ...

System and Method of Automatically Preparing and Analyzing Urine Samples for Identifying Cancer Cells

A system and method of automatically preparing and analyzing urine samples for identifying cancer cells is able to complete conventional diagnostic tasks without lab technicians, cytopathologists, or other medical professionals. The method is provided with at least one source sample, at least one manipulator arm, at least one centrifuge, at least one electronic microscope, and at least one unitary controller. The method is further provided with a cytopathological index containing a visual characteristic database and identification confidence threshold rubrics supporting the automation of visual analyses typically performed manually with a conventional microscope. This method is further provided with a data processing function, wherein data stemming from multiple testing cycles may be collated, formatted, and presented for use by medical professionals in determining and projecting the effectiveness of a course of treatment. 1. A method of automatically preparing and analyzing urine samples for identifying cancer cells , the method comprises the steps of:(A) providing at least one source sample, at least one manipulator arm, at least one centrifuge, at least one electronic microscope, and at least one unitary controller, wherein the unitary controller is communicably coupled to the manipulator arm, the centrifuge, and the electronic microscope, wherein a cytopathological index is stored on the unitary controller;(B) preparing the source sample into a plurality of sample tubes with the manipulator arm, wherein each sample tube includes a sample identification;(C) loading the sample tubes into the centrifuge with the manipulator arm;(D) executing a separation process on the sample tubes with the centrifuge;(E) removing the sample tubes from the centrifuge with the manipulator arm;(F) extracting a plurality of sediment samples with the manipulator arm, wherein each sample tube is associated to a corresponding sediment sample from the plurality of sediment samples;(G) ...

SCANNING INFRARED MEASUREMENT SYSTEM

An analyzer of a component in a sample fluid includes an optical source and an optical detector defining a beam path of a beam, wherein the optical source emits the beam and the optical detector measures the beam after partial absorption by the sample fluid, a fluid flow cell disposed on the beam path defining an interrogation region in the a fluid flow cell in which the optical beam interacts with the sample fluid and a reference fluid; and wherein the sample fluid and the reference fluid are in laminar flow, and a scanning system that scans the beam relative to the laminar flow within the fluid flow cell, wherein the scanning system scans the beam relative to both the sample fluid and the reference fluid. 1. An analyzer of a component , comprising:an optical source that emits a light;a scanning system that scans the light over the component;an optical detector subsystem that measures the light after interaction with the component; anda guiding system that guides the light from the optical source to the optical detector subsystem.2. The analyzer of claim 1 , further comprising an interrogation region disposed on a beam path defined between the optical source and the optical detector subsystem claim 1 , which is a closed claim 1 , liquid-based environment at the time of interrogation and contains the component; wherein the component is a particle or a cell; and a processor that calculates a characteristic of the component based on the measured light.3. The analyzer of claim 1 , wherein the optical detector subsystem is configured to respond preferentially to light at the scanning frequency to measure transmitted light as the light passes through the component or to measure scattered light associated with as the light passes by the component.4. The analyzer of claim 1 , wherein the optical source is a quantum cascade laser (QCL) which emits the light of at least one wavelength.5. The analyzer of claim 1 , wherein the optical source emits the light of mid-infrared or ...

BIOMOLECULE ANALYSIS DEVICE

An object is to provide a biomolecule analyzer capable of collecting and analyzing a biomolecule in a single cell without damaging neighboring cells. 1. A biomolecule analyzer , comprising:a first unit configured to obtain an optical image of a plurality of cells;a second unit configured to disrupt a part or the whole of at least one cell of the plurality of cells;an array device in which regions for capturing a biomolecule in the cell released by the disrupting unit are arranged; anda third unit configured to associate the region in which the biomolecule is captured in the array device with a portion corresponding to the cell disrupted by the disrupting unit in the optical image.2. The biomolecule analyzer according to claim 1 , further comprising a fourth unit configured to place the region of the array device and the cell to be disrupted in close proximity of each other before the cell is disrupted by the disrupting unit.3. The biomolecule analyzer according to claim 1 , further comprising a fifth unit configured to suck the biomolecule in the cell to be released into the region of the array device or allows the biomolecule to migrate into the region.4. The biomolecule analyzer according to claim 1 , wherein the array device is a porous membrane or a bead array having beads packed on the surface thereof.5. The biomolecule analyzer according to claim 1 , wherein a probe molecule for selectively capturing the biomolecule in the cell is immobilized on at least one of the surface and in the inside of the array device.6. The biomolecule analyzer according to claim 5 , wherein the biomolecule in the cell is mRNA claim 5 , and the probe molecule is a DNA probe.7. The biomolecule analyzer according to claim 6 , wherein the DNA probe has a sequence which is different for each position of the array device.8. The biomolecule analyzer according to claim 5 , wherein the biomolecule in the cell is a protein or a peptide claim 5 , and the probe molecule is an antibody.9. The ...

Methods for staining cells for identification and storing

The present invention provides novel methods of cell staining, such as bovine sperm, using electroporation or osmolality treatments at viability-enhancing temperatures. Furthermore, methods of highly efficient cell sorting that are especially suitable in sorting bovine sperm using novel cell staining procedures are also provided.

EARLY WARNING OF CHANGES IN HEALTH AND ROBUSTNESS USING NARROWLY FORWARD SCATTERED LIGHT TO TRACK EASE OF MORPHOLOGICAL CHANGES OF BLOOD CELLS

Early warning of changing health and robustness is given by tracking of ease of morphological changes in blood cells obtained by comparing intensities in a first scattered light intensity angular distribution and intensities in a second scattered light intensity angular distribution, with the light being scattered by blood cells into very narrowly forward scattered light intensity angular range. 1. A method of tracking morphological changes in a suspension of blood cells taken from a blood sample , the suspension of blood cells having a cells per volume concentration , the method comprising:directing light having an incident light central axis at an ensemble of blood cell suspension;determining a first scattered light intensity angular distribution;applying a challenge agent to the suspension of blood cells to morphologically change blood cells in the suspension of blood cells, wherein application of the challenge agent produces a challenge agent and blood suspension mixture;directing light having the incident light central axis at an ensemble of suspended blood cells within the challenge agent and blood sample mixture;determining a second scattered light intensity angular distribution; andcalculating a tracking value based on the first scattered light intensity angular distribution and the second scattered light intensity angular distribution.2. The method of further comprising claim 1 , before directing light at the ensemble of suspended blood cells from the sample of blood cells claim 1 ,obtaining a first blood cell suspension from the sample of blood cells.3. The method of further comprising claim 2 , before applying the challenge agent claim 2 ,obtaining an additional blood cell suspension from the sample of blood cells, the additional blood cell suspension being the sample of blood cells to which the challenge agent is applied.4. The method of wherein the tracking value is obtained by the equation{'br': None, 'i': T=Σ|F', '−S, 'sub': i', 'i, '|,'}{'sub': 'i', ...

Nucleated Red Blood Cell Analysis System and Method

Systems and methods for analyzing blood samples, and more specifically for performing a nucleated red blood cell (nRBC) analysis. The systems and methods screen a blood sample by means of fluorescence staining and a fluorescence triggering strategy, to identify nuclei-containing particles within the blood sample. As such, interference from unlysed red blood cells (RBCs) and fragments of lysed RBCs is substantially eliminated. The systems and methods also enable development of relatively milder reagent(s), suitable for assays of samples containing fragile white blood cells (WBCs). In one embodiment, the systems and methods include: (a) staining a blood sample with an exclusive cell membrane permeable fluorescent dye; (b) using a fluorescence trigger to screen the blood sample for nuclei-containing particles; and (c) using measurements of light scatter and fluorescence emission to distinguish nRBCs from WBCs. 1. A hematology analyzer for conducting a nucleated red blood cell (nRBC) analysis on a blood sample that contains a plurality of nRBCs , the analyzer comprising:an excitation source positioned to excite particles within the blood sample;a plurality of detectors including (1) an axial light loss detector positioned to measure axial light loss from the excited blood sample, (2) an intermediate angle scatter detector positioned to measure intermediate angle scatter from the excited blood sample, (3) a side scatter detector positioned to measure 90° side scatter from the excited blood sample, and (4) a fluorescence detector positioned to measure fluorescence emitted from the excited blood sample; and (a) dilute the blood sample with a reagent that includes a red blood cell (RBC) lysing agent and a cell membrane permeable, nucleic acid binding fluorescent dye;', '(b) incubate the diluted blood sample of step (a) for an incubation period of time', '(c) deliver the incubated sample from step (b) to a flow cell in the hematology analyzer;', '(d) excite the incubated ...

Method for Hematology Analysis

A method whereby one or more fluorescent dyes are used to bind and stain nucleic acids in certain blood cells, such as, for example, white blood cells, nucleated red blood cells, and reticulocytes, and to induce fluorescent emissions upon excitation of photons from a given source of light, such as, for example, a laser, at an appropriate wavelength. More particularly, this invention provides a method whereby a fluorescent trigger is used in a data collection step for collecting events that emit strong fluorescence, in order to separate white blood cells and nucleated red blood cells from red blood cells and platelets without the need for using a lysing agent.

PARTICLE ANALYSIS APPARATUS

A particle analysis apparatus for flow cytometry, which contains a flow cell having a flow channel for flowing a sample solution containing particles to be analyzed, a light source device for emitting an irradiation light, an optical system for irradiating the irradiation light on an irradiation segment in the flow channel, and a light receiving device for detecting the light obtained thereby. A light source of the light source device is LED, and an electrode formed on a light extraction surface thereof mainly contains a plurality of electric conductor lines arranged in parallel to each other.

SYSTEM FOR IDENTIFYING AND TARGETING INDIVIDUAL CELLS WITHIN A HETEROGENEOUS POPULATION FOR SELECTIVE EXTRACTION OF CELLULAR CONTENT

The present disclosure provides a system and method for identifying and targeting individual cells within a cell population for selective extraction of cellular content and a digital microfluidic device having at least one hydrophilic site for receiving cells, an imaging system including a stage for receiving the digital microfluidic device and an imaging module for identifying at least one targeted cell among the cells at the at least one hydrophilic site. The system includes a pulsed laser source for laser lysing the targeted cell thereby releasing the cell content to produce a lysate. A control system controls the pulsed laser source, the imaging system and the digital microfluidic device and is programmed for coordinating steps of i) movement of droplets on the digital microfluidic device, ii) selection of the at least one targeted cell to be lysed located at the at least one hydrophilic site, iii) illumination of the at least one selected targeted cell by the pulsed laser source to lyse the at least one selected targeted cell to produce lysate, and iv) collection of the lysate. 114-. (canceled)15. A method for detection and/or isolation of fetal cells and/or fetal analytes , the method comprising:loading a sample containing cells on at least one site of a digital microfluidic device thereby forming a virtual microwell at each of the at least one site;Immobilizing the cells on the at least one site;selecting at least one immobilized cell;lysing the at least one selected cell using a pulsed laser source to produce lysate within its corresponding virtual microwell;displacing a droplet of liquid to the corresponding virtual microwell for collecting the lysate; andmoving the droplet containing the lysate from the corresponding virtual microwell to a designated site, and optionally detecting and/or isolating fetal analytes in the lysate.16. The method according to wherein the at least one site is hydrophilic claim 15 , partially hydrophilic or become hydrophilic ...

URINE ANALYSIS SYSTEM, IMAGE CAPTURING APPARATUS, URINE ANALYSIS METHOD

A urine analysis system according to an embodiment includes: a testing apparatus that measures particles included in a urine sample according to a flow cytometry method; an image capturing apparatus that captures images of particles in the urine sample to acquire particle images; and a management apparatus that receives a measurement result obtained by the testing apparatus and the particle images acquired by the image capturing apparatus. The management apparatus generates an order to capture an image of the urine sample based on the measurement result obtained by the testing apparatus. The image capturing apparatus executes the image capturing processing of the particles in the urine sample for which the image capturing order has been generated by the management apparatus, and transmits the acquired particle images to the management apparatus. 1. A urine analysis system comprising:a testing apparatus that measures particles included in a urine sample according to a flow cytometry method;an image capturing apparatus that captures images of the urine sample to acquire images of particles in the urine sample; anda management apparatus that receives a measurement result obtained by the testing apparatus and the particle images acquired by the image capturing apparatus, whereinthe management apparatus generates an image capturing order for the urine sample based on the measurement result obtained by the testing apparatus, and the image capturing apparatus executes the image capturing processing of the urine sample for which the image capturing order has been generated by the management apparatus, and transmits the acquired particle images to the management apparatus.2. The urine analysis system according to claim 1 , further comprising a conveyance apparatus that conveys the urine sample from the testing apparatus to the image capturing apparatus based on the image capturing order claim 1 , whereinthe image capturing apparatus includes a suction unit that sucks the ...

REAGENTS, METHODS AND KITS FOR DIAGNOSING PRIMARY IMMUNODEFICIENCIES

This invention relates to the field of primary immunodeficiencies (PID), more specifically to means and method for the diagnosis of PID of the lymphoid system. Provided are unique reagent compositions for the flow cytometric immunophenotyping of leukocytes comprising fluorochrome-conjugated antibodies directed against various specific combinations of markers. Also provided are kits comprising the reagent compositions, and methods using the same. 1. A reagent composition for the flow cytometric immunophenotyping of leukocytes comprising fluorochrome-conjugated antibodies directed against one of the following combination of markers:(a) CD27, IgM, IgA, IgG, IgD, CD19, CD21, CD38, and optionally IgE;(b) CD27, IgM, CD38, CD5, IgD, CD19, CD21, and CD24;(c) CD27, CD45RA, CD8, IgD, CD16, CD56, CD4, IgM, CD19, CD3, CD45, and either TCRαβ or TCRγδ, wherein the antibody within the pairs CD8/IgD, CD16/CD56, CD4/IgM and CD19/TRCαβ or CD19/TCRγδ is conjugated to the same fluorochrome, and wherein between different pairs the fluorochromes are distinguishable;(d) CD27, IgM, IgG3, IgG2, IgG, IgD, CD19, CD21, and CD38; the composition comprising two distinctly labeled antibodies against IgG2 and wherein the antibody within the pairs IgG3/IgG2 and IgG1/IgG2 is conjugated to the same fluorochrome and wherein between different pairs the fluorochromes are distinguishable;(e) CD27, IgM, IgA2, IgA1, IgG4, IgD, CD19, CD21, and CD38; the composition comprising two distinctly labeled antibodies against IgA1 and wherein the antibody within the pairs IgA1/IgG4 and IgA1/IgA2 is conjugated to the same fluorochrome and wherein between different pairs the fluorochromes are distinguishable;(f) CD62L, CD4, CD45RO, CD31, HLA-DR, TCRγδ or TCRαβ, CD3 and CD8;(g) CD27, CD4, CD45RO, CCR7, CD28, TCRγδ or TCRαβ, CD3 and CD8; or(h) CD27, CD45RA, CD45, CD16, CD3, CD8, IgD, CD4, IgM, CD56, CD19, CCR7, CD38, either CD31 or HLA-DR, and either TRCαβ or TCRγδ, wherein the antibody within the pairs CD8/IgD, CD4/IgM ...

Methods and devices for producing cellular suspensions from tissue samples

Aspects of the present disclosure include methods of producing a cellular suspension from a tissue sample by applying resonant acoustic energy to a container comprising the tissue sample in a manner sufficient to produce a cellular suspension from the tissue sample. Resonant acoustic mixers and kits for use in producing a cellular suspension from a tissue sample are also provided.

Microfluidic Device And Method For Detecting Rare Cells

A microfluidic device for detecting rare cells in a fluid sample comprises the rare cell and other cells. The microfluidic device comprises an inlet for receiving the fluid sample, a labyrinth channel structure in fluid communication with the inlet, and an outlet in fluid communication with the labyrinth channel structure for collecting the rare cells separated from the other cells in the fluid sample. The labyrinth channel structure comprises at least one channel through which the fluid sample flows. The at least one channel has a plurality of segments and a plurality of corners with each corner defined between adjacent segments. The presence of the plurality of corners induces separation of the rare cells from the other cells in the fluid sample as the rare cells move to a first equilibrium position within the at least one channel when a ratio of inertial lift forces (F) and Dean flow (F) of the fluid sample is from 2 to 10. 117-. (canceled)18. A microfluidic device for detecting rare cells in a fluid sample comprising the rare cells and other cells , the microfluidic device comprising:an inlet for receiving the fluid sample;a labyrinth channel structure in fluid communication with the inlet, wherein the labyrinth channel structure comprises at least one channel having a rectangular cross-section, a width of from 500 to 1000 μm, and a height of from 1 to 150 μm, the at least one channel having a plurality of segments and a plurality of corners with each corner defined between adjacent segments, wherein the plurality of corners are configured to induce a change in fluid flow direction of the fluid sample and a separation of the rare cells from the other cells in the fluid sample; andan outlet in fluid communication with the at least one channel for collecting the rare cells separated from the other cells in the fluid sample.19. The microfluidic device of claim 18 , wherein the labyrinth channel structure comprises at least 2 corners.20. The microfluidic device of ...

Monitoring device for adjusting light irradiation in particle analysis apparatus

Provided is a monitoring device having a control part for monitoring, wherein the control part for monitoring has a first data processing part, a second data processing part, and an indication value output part. The first data processing part generates, as indication values for optical axis adjustment, the first indication value showing the intensity of a light-receiving signal obtained from the particle analysis apparatus. The second data processing part generates, as indication values for gain adjustment of the light-receiving signal, the second indication value showing the intensity of a light-receiving signal obtained from the particle analysis apparatus, which is different from the aforementioned first indication value. The indication value output part outputs the first and second indication values to a display device.

EFFICIENT CONTOURS AND GATING

Methods and systems for efficient contour and gating in flow cytometry are provided. Event data is compressed to reduce the number of points needed to represent polygon contours for the event data. Selection of a level within the contour then causes the generation of a gate. This allows limited resource devices, such as touchscreen wireless devices, to render and gate flow cytometry data in a resource efficient manner. 1. A computer-implemented method of polygon mesh reduction for flow cytometry events , the method comprising: receiving a requested density level for presenting data for flow cytometry events;', 'generating an initial contour diagram, wherein the initial contour diagram is defined by a plurality of polygons, said plurality of polygons representing regions corresponding to respective density levels for the data in two dimensions, and wherein each polygon is defined as at least a portion of one of a plurality of tiles that divide the initial contour diagram in two dimensions;', 'for a given tile included in the plurality of tiles of the initial contour diagram corresponding to the requested density level, identifying an adjacent tile to the given tile at the requested density level that defines a first polygon matching a second polygon defined by the given tile based at least in part on a tile code for the given tile, wherein the tile code comprises a set of elements, each element encoding a density level for a point defining the second polygon;', 'when the adjacent tile is identified, combining the first polygon and the second polygon into a larger polygon, thereby reducing the number of polygons to form a reduced contour diagram defined by less data than the data for the initial contour diagram; and', 'causing display of the reduced contour diagram for the requested density level., 'under control of one or more processors,'}2. The computer-implemented method of claim 1 , wherein generating the initial contour diagram comprises:receiving a set of data; ...

SYSTEMS AND METHODS FOR CLUSTER MATCHING ACROSS SAMPLES AND GUIDED VISUALIZATION OF MULTIDIMENSIONAL CYTOMETRY DATA

Some embodiments provide methods, systems and computer-readable media that employ adaptive binning and dissimilarity scores based on a quadratic form distance for multidimensional data for matching clusters in data corresponding to different sample. Some embodiments provide methods, systems and computer-readable media for rendering a first interactive display including a two-dimensional plot of at least a portion of a multidimensional data set and a corresponding second interactive display including a plurality of single parameter charts or histograms, each displaying information corresponding to one-dimensional measurements of a different parameter in the multidimensional data set. 1. A computer implemented method of matching clusters in data corresponding to different samples , the method comprising:obtaining or receiving first sample data, second sample data, an identification of one or more clusters in the first sample data, and an identification of one or more clusters in the second sample data;performing multivariate adaptive binning on a combined data set including the first sample data and the second sample data to determine a combined binning pattern;applying the combined binning pattern separately to the first sample data and the second sample data;for at least some combinations of a first identified cluster in the first sample data and a second identified cluster in the second sample data, determining a dissimilarity score for the combination based on a quadratic form distance for multi-dimensional data using the combined binning pattern applied to the first identified cluster and the combined binning pattern applied to the second identified cluster;identifying one or more matched clusters and one or more merging candidates based on comparisons of the determined dissimilarity scores for the combinations; anddetermining, for each merging candidate in the first sample data or the second sample data, whether the merging candidate corresponds to a split of a ...

Particle Detection Using Thin Lenses

An optical excitation system comprises a substrate () comprising at least one delivery means (), for delivering analytes () into at least one region of interest (), at least one radiation carrier () for directing at least one radiation beam from the at least one radiation carrier () into the at least one region of interest (). The substrate () includes a thin lens system () comprising at least a first thin lens (), for collimating radiation from the at least one region of interest () to a remote detection system (). A particle sensor and sensing system comprising the excitation system are also provided, for example a modular particle sensor and modular sensing system, wherein the optical excitation system may be single use and disposable. 1. An optical excitation system for a particle sensor , the system comprising: at least one delivery means for delivering analytes into at least one region of interest, and', 'at least one radiation carrier for carrying radiation and directing at least one radiation beam from the at least one radiation carrier into the at least one region of interest; and, '(a) a substrate comprising'}(b) a thin lens system comprising at least a first thin lens for collimating radiation from the at least one region of interest to a remote detection system.2. The optical excitation system according to claim 1 , wherein the at least a first thin lens is integrated in or on the substrate.3. The optical excitation system according to claim 1 , wherein the thin lens system comprises at least one thin film lens.4. The optical excitation system according to claim 1 , wherein the at least one delivery means comprises at least one microfluidic channel.5. A particle sensor comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'an optical excitation system according to ; and'}a detection system comprising at least a first detector for detecting radiation within a predetermined range of wavelengths.6. The particle sensor according to claim 5 , wherein ...

SYSTEM AND METHOD OF LABEL-FREE CYTOMETRY BASED ON BRILLOUIN LIGHT SCATTERING

The present invention relates to a method and system for a label-free cell analysis based on Brillouin light scattering techniques. Combined with microfluidic technologies according to the present invention, Brillouin spectroscopy constitutes a powerful tool to analyze physical properties of cells in a contactless non-disturbing manner. Specifically, subcellular mechanical information can be obtained by analyzing the Brillouin spectrum of a cell. Furthermore, a novel configuration of Brillouin spectroscopy is provided to enable simultaneous analysis of multiple points in a cell sample. 1. A method for classifying biological cells , the method comprising:providing a container having a biological sample including the biological cells in a media;illuminating the biological sample to generate a Brillouin scattered light from within the biological cells and the media;measuring a Brillouin scattering spectrum at multiple points within each biological cell;extracting one or more metrics related to subcellular physical properties at different spatial points within the biological cells based on the measured Brillouin scattering spectrum; andclassifying the biological cells based on the subcellular physical properties at different spatial points within the biological cells.2. The method of claim 1 , wherein the one or more metrics associated with the Brillouin-scattering spectrum are selected from the group consisting of: Brillouin frequency shift claim 1 , Brillouin spectrum linewidth claim 1 , Brillouin gain or loss spectrum claim 1 , and a combination thereof.3. The method of claim 1 , wherein the physical properties of the sample are selected from the group consisting of: viscoelastic modulus claim 1 , density claim 1 , refractive index claim 1 , electrostriction claim 1 , and a combination thereof.4. The method of claim 1 , wherein the step of extracting subcellular physical properties at different spatial points within the biological cells further comprises:plotting a ...

MICROCHIP, MICROPARTICLE MEASURING DEVICE, AND MICROPARTICLE MEASURING METHOD

There is provided a microchip including a plurality of substrate layers having a flow path in which a liquid containing microparticles flows in at least one of the substrate layers, the microchip at least including: an optical radiation region in which light is radiated to microparticles contained in a fluid flowing in the flow path from a side surface of the substrate layers. 1. A microfluidic device , comprising:a microfluidic structure including a plurality of substrate layers, at least one of which includes a flow path through which a liquid containing microparticles may flow,wherein the microfluidic structure includes a top surface, a bottom surface arranged opposite the top surface, a first side surface arranged between the top surface and the bottom surface, and a second side surface arranged opposite the first side surface, andwherein the microfluidic structure includes an optical measurement region that includes an optical irradiation region at the first side surface that allows light irradiated on the optical irradiation region to interact with the microparticles when present in the flow path, a portion of the flow path, and an optical detection region at the second side surface.2. The microfluidic device according to claim 1 , wherein the microfluidic structure includes a first substrate layer and a second substrate layer having a bonding surface at which the first substrate layer and the second substrate layer are bonded claim 1 , andwherein the optical measurement region does not include the bonding surface.3. The microfluidic device according to claim 2 , wherein the bonding surface is arranged along a first direction from a first end of the plurality of substrate layers to a second end of the plurality of substrate layers claim 2 , andwherein along the first direction, the bonding surface includes at least one notch at the optical measurement region.4. The microfluidic device according to claim 3 , wherein the optical measurement region includes a ...

DEVICES, KITS, AND METHODS FOR LABEL-FREE FOCUSING AND/OR SEPARATION OF SUB-MICRON PARTICLES

The present disclosure provides devices, kits, and methods for focusing/enriching and/or separating/sorting submicron size particles, including biological entities such as exosomes and other submicron size extracellular vesicles. Devices, kits, and methods of the present disclosure utilize ferrohydrodynamic manipulation to focus populations of submicron particles into a stream for enrichment and/or further sort various sub-populations of submicron particles based on size differences. 1. A multi-stage microfluidic device for enriching and/or sorting unlabeled , sub-micron size particles in a sample , the device comprising:a microfluidic channel having a first and second end;a first fluid inlet at the first end of the microfluidic channel and configured to receive a mixed sample fluid comprising the sample with the unlabeled, sub-micron size particles combined with a first ferrofluid, wherein the mixed sample fluid has a first flow rate;a first stage after the first inlet comprising a filter region having one or more filters configured to separate a least a portion of larger microparticles or debris from the mixed sample fluid;a second fluid inlet after the filter region and configured to receive an optional sheathing ferrofluid at a second flow rate, wherein the first ferrofluid and the sheathing ferrofluid each comprise a plurality of magnetic nanoparticles, a surfactant and a carrier fluid;a second stage located after the second fluid inlet configured to flow components of the mixed sample fluid and the optional sheathing ferrofluid, the second stage comprising a magnetic source configured to produce a substantially symmetric magnetic field having a field minimum along an inner longitudinal axis of the microfluidic channel and sufficient to cause a the unlabeled sub-micron sized particles to be focused toward a center of the microfluidic channel of the second stage as a function of the size of the particles; andat least a first and second outlet at the second end ...

Method for detecting the presence of different antinuclear antibody fluorescence pattern types and apparatus for this purpose

A method is for detecting respective potential presence of respective different antinuclear antibody fluorescence pattern types on a biological cell substrate including human epithelioma cells, including: acquiring a first image which represents staining of the cell substrate by a first fluorescent dye, and acquiring a second image which represents staining of the cell substrate by a second fluorescent dye, detecting, on the basis of the first image, respective image segments which in each case represent at least one mitotic cell, selecting, on the basis of the detected image segments, subimages of the first image and subimages corresponding thereto of the second image and detecting, on the basis of the selected subimages of the first image and of the selected subimages of the second image, respective actual presence of respective cellular fluorescence pattern types by means of a convolutional neural network. 1. A method for detecting respective potential presence of respective different cellular fluorescence pattern types on a biological cell substrate comprising human epithelioma cells ,wherein the cellular fluorescence pattern types comprise a plurality of different antinuclear antibody fluorescence pattern types, [ primary antibodies,', 'a first fluorescent dye, and', 'secondary antibodies, which are labelled with a second fluorescent dye,, 'incubating the biological cell substrate with a liquid patient sample, which potentially comprises'}, 'acquiring a first image which represents staining of the biological cell substrate by the first fluorescent dye and acquiring a second image which represents staining of the biological cell substrate by the second fluorescent dye,', 'detecting, on the basis of the first image, respective image segments which in each case represent at least one mitotic cell,', 'selecting, on the basis of the detected image segments, subimages of the first image and subimages corresponding thereto of the second image, and', 'detecting, on the ...

Method for identifying the quantitative cellular composition in a biological sample

The present invention provides an epigenetic haemogram, also referred to as an epigenetic blood cell count that identifies the quantitative, comprehensive picture of cellular composition in a biological sample, wherein advantageously a normalization standard is used. The normalization standard is a nucleic acid molecule comprising at least one marker-region being specific for each of the blood cells to be detected, and at least one control-region being cell-unspecific, wherein said regions are present in the same number of copies on said molecule and/or a natural blood cell sample of known composition. Furthermore, the present invention relates to a kit and the use of a kit for performing the epigenetic assessment of comprehensive, quantitative cellular composition of a biological sample. The biological sample is derived from e.g. a mammalian body fluid, including peripheral, capillary or venous blood samples or subfractions thereof, such as peripheral blood mononuclear cells or peripheral blood monocytes, or a tissue sample, organ sample, or from frozen, dried, embedded, stored or fresh body fluids or tissue samples.

Microfluidic Device For Cell Separation And Uses Thereof

The invention features methods for separating cells from a sample (e.g., separating fetal red blood cells from maternal blood). The method begins with the introduction of a sample including cells into one or more microfluidic channels. In one embodiment, the device includes at least two processing steps. For example, a mixture of cells is introduced into a microfluidic channel that selectively allows the passage of a desired type of cell, and the population of cells enriched in the desired type is then introduced into a second microfluidic channel that allows the passage of the desired cell to produce a population of cells further enriched in the desired type. The selection of cells is based on a property of the cells in the mixture, for example, size, shape, deformability, surface characteristics (e.g., cell surface receptors or antigens and membrane permeability), or intracellular properties (e.g., expression of a particular enzyme). 134-. (canceled)35. A device for enriching fetal blood cells in a liquid sample , comprising:a substrate;a flow chamber having an inlet and an outlet arranged on the substrate; anda plurality of features arranged on the substrate within a first region of the flow chamber to form a sieve configured for size-based separation of blood cells; anda plurality of features arranged on the substrate within a second region of the flow chamber to form an array configured to selectively capture fetal blood cells via one or more binding moieties that selectively bind to specific surface molecules expressed on fetal blood cells when a liquid sample comprising fetal blood cells is flowed through the flow chamber;wherein the features in one or both of the first and second regions are arranged in an array of features comprising at least two rows of features aligned normal to a flow path through the flow chamber, wherein the features are equally spaced within each row in the array, and each successive row of features is shifted in a direction normal to ...

SYSTEMS AND METHODS FOR PANEL DESIGN IN FLOW CYTOMETRY

Embodiments of the present invention encompass systems and methods for determining detection limits for various antibody-dye conjugates for flow cytometry. Exemplary techniques involve a linear superpositioning approach of spillover-induced enlargements of normally distributed measurement errors. 1. A method of designing a probe panel for a flow cytometer , the method comprising:determining a distortion factor that quantifies spillover effect caused by emission of a first label, intended to be measured in a first channel, into a second channel;inputting a maximum expected signal of a first probe-label combination including the first label and a first probe;calculating an increase in detection limit in the second channel based on the distortion factor and the maximum expected signal of the first probe-label combination; andselecting a probe-label combination to include in the probe panel based on the calculated increase in detection limit.2. The method of claim 1 , wherein the distortion factor is an estimate of an increase in detection limit in the second channel as a function of an emission intensity of the first probe-label combination.3. (canceled)4. The method of claim 2 , wherein the increase in detection limit in the second channel is caused by an increase in a measurement error as a function of the emission intensity of the first probe-label combination.5. The method of claim 2 , wherein the distortion factor is calculated using a crosstalk index.6. The method of wherein the distortion factor is mathematically modified by a coefficient representing the coexpression pattern of antigens corresponding to the first probe-label combination and a second probe-label combination claim 1 , the second probe-label combination intended to be measured in the second channel.7. The method of further comprising:determining a distortion factor for each label in a first potential probe panel to calculate a total increase in detection limit in the second channel.8. The method ...

HIGH THROUGHPUT METHODS FOR VIRUS QUANTIFICATION

This invention relates to high throughput methods of determining a viral titer. The instant invention addresses the need for a more rapid and cost effective method of quantitating infectious viral particles in a sample. 1. A method of virus quantification comprising the steps of:1) providing a sample containing a virus;2) preparing serial dilutions of the sample;3) infecting host cells with the virus and incubating the culture;4) reacting an antigen expressed by the virus in infected cells with an antibody labeled with a fluorescent tag;5) determining the number of infected cells; and6) determining the virus titer in the sample.2. The method of claim 1 , wherein the method is carried out in a multi-well plate.3. The method of claim 1 , wherein the number of infected cells in step 5) is determined by CellInsight.4. The method of claim 1 , wherein the number of infected cells is determined by reading the fluorescence tagged cells in each well.5. The method of claim 4 , wherein the fluorescence tag is selected from the group consisting of FITC claim 4 , Hoechst stain claim 4 , DAPI claim 4 , GFP claim 4 , TRITC and Cy5.6. The method of claim 1 , wherein a straight line is plotted using linear regression between number of fluorescence tagged cells and virus titer using a virus reference.7. The method of claim 6 , wherein at least one of the serial dilutions falls within the range of the liner regression line of the reference virus. This application claims priority to U.S. provisional application 62/196,886 filed on Jul. 24, 2015.This invention relates to high throughput methods of determining a viral titer. The instant invention addresses the need for a more rapid and cost effective method of quantitating infectious viral particles in a sample.A particular challenge in the delivery of a gene by a viral vector or a virus for therapeutic purposes is the preparation and accurate quantification of clinical dosage forms. The production of viral vaccines, recombinant proteins ...

Analysis device

An analysis device includes an analysis unit configured to receive scattered light, transmitted light, fluorescence, or electromagnetic waves from an observed object located in a light irradiation region light-irradiated from a light source and analyze the observed object on the basis of a signal extracted on the basis of a time axis of an electrical signal output from a light-receiving unit configured to convert the received light or electromagnetic waves into the electrical signal.

Cell tracking correction method, cell tracking correction device, and storage medium which stores non-transitory computer-readable cell tracking correction program

A processor of a cell tracking correction apparatus is configured to perform processes comprising: estimating a position of at least one cell in images acquired by time-lapse photography, and tracking the position of the cell; generating nearby area images of a nearby area including the cell from the images of photography time points of the time-lapse photography, based on the tracked position of the cell at each of the photography time points of the time-lapse photography; displaying the nearby area images on a display; accepting, via a user interface, an input of a correction amount for correcting the position of the cell with respect to one of the nearby area images displayed on the display unit; and correcting the tracked position of the cell corresponding to the nearby area image, in accordance with the correction amount.

Methods and kits for cell sorting

The present disclosure provides methods, and related kits, for directing cell attachment and spreading on a substrate and inducing isotropic spreading of cells; provides methods, and related kits, for cell sorting; and further provides methods, and related kits, for guided induction of stem cell differentiation.

NOZZLE AND METHOD FOR FLOW CYTOMETRY

The invention relates to a nozzle for flow cytometry, the housing of which is tapering towards an outlet and in which a feed tube is arranged for a core flow liquid, the outlet opening of which is arranged at a distance from the outlet of the housing. The outlet of the housing forms the outlet of the nozzle. The housing of the nozzle extends from its outlet, which is arranged at its first end to its opposite second end, and has an inlet for a sheath flow liquid connected with the internal volume. The nozzle is characterized in that in the housing a leading element that promotes the alignment of particles extends from both sides of the feed tube. 1. A method for producing a liquid flow having a particle-containing core flow surrounded by a sheath flow by introducing a particle-containing core flow liquid into an inlet opening for core flow liquid and introducing a sheath flow liquid into an inlet opening for sheath flow liquid of a nozzle , wherein the sheath flow is generated by a leading element that extends along a longitudinal axis to a larger degree along a first dimension perpendicular to the longitudinal axis up to a distance to the inner wall of a housing it extends in a second dimension that is perpendicular to the longitudinal axis and to the first dimension , wherein the leading element extends from a first end , which lies in the plane of the first end of a feed tube or is offset by a distance from the first end of the feed tube , up to its second end , which is arranged at a distance from the second end of the nozzle.2. The method according to claim 1 , wherein the particles have a cross-section claim 1 , which is smaller in a first dimension that is perpendicular to the longitudinal axis of the housing of the nozzle than in a second dimension that is perpendicular to the longitudinal axis and to the first dimension.3. The method according to claim 1 , wherein at least one property of the particles contained in the core flow is detected in the liquid ...

Device and method for the optical stimulation of an optically activatable biological sample

The invention relates to a device () and a method for the optical stimulation of an optically activatable biological sample (), comprising at least one light source (″), which emits light of at least one predetermined wavelength that impinges directly or indirectly on the sample (). The invention is characterised in that: the at least one light source (″) is thermally coupled to a hollow channel section (); the hollow channel section () is part of a fluid circuit through which fluid flows; a temperature-control unit () and a conveying pump are arranged along the fluid circuit; and the hollow channel section () has at least one limiting wall () onto which the optically activatable biological samples () are thermally coupled in a direct or indirect manner. 116-. (canceled)17. A device for optical stimulation of an optically activatable biological sample with at least one light source , which emits light of at least one selectable wavelength , which impinges onto the sample , wherein:the at least one light source is thermally coupled to a section of a hollow channel;the section of the hollow channel is part of a fluid circuit through which fluid flows;a temperature control and a conveying pump is located along the fluid circuit; andthe section of the hollow channel has at least one boundary wall onto which an optically activatable biological sample is thermally coupled thereto.18. a device according to claim 17 , wherein:at least a part of the at least one light source is located inside the section of the hollow channel.19. A device according to claim 17 , wherein:the section of the hollow channel comprises a hollow cylinder including an inner and outer peripheral surface bounding a volume of the fluid circuit in a radial direction; andthe inner peripheral surface represents at least one boundary wall and is transparent to the light of the at least one light source, and the at least one light source includes an emission aperture which is oriented radially inward.20. A ...

BLOOD ANALYZER AND BLOOD ANALYZING METHOD

Disclosed is a blood analyzer that includes: a sample preparation unit configured to mix a blood specimen and a fluorescent dye for staining nucleic acid to prepare a measurement sample; a light receiver configured to receive fluorescence and scattered light that are generated by light being applied to the measurement sample prepared by the sample preparation unit; and a controller programmed to determine whether or not infection with has occurred, on the basis of a value representing variation of a distribution of first particles in a range where single-ring form of red blood cells appear, the range where single-ring form of red blood cells appear being identified according to fluorescence intensities and scattered light intensities obtained by processing of signals from the light receiver. 1. A blood analyzing method comprising:mixing a blood specimen and a fluorescent dye to prepare a measurement sample in which nucleic acids of Plasmodia parasitizing in red blood cells are stained;irradiating light to the measurement sample;detecting a fluorescence and a scattered light from individual cells in the measurement sample, caused in response to the irradiation; andplotting the individual cells on a coordinate plane having an axis of fluorescence intensity and an axis of scattered light intensity;counting cells plotted in a first region on the coordinate plane where malaria-infected cells are plotted;obtaining a value representing a variation of a distribution of cells appearing in a second region that is a narrowed part of the first range; and{'i': 'Plasmodium', 'determining infection positive responsive to determining that the value representing the variation of the distribution in the second range is less than a threshold value and the number of cells in the first range is greater than a threshold value.'}2. The blood analyzing method of claim 1 , wherein the second region is defined at a lower side with respect to both of the first and second axes claim 1 , ...

PREPROCESSING AND CONVOLUTIONAL OPERATION APPARATUS FOR CLINICAL DECISION-MAKING ARTIFICIAL INTELLIGENCE DEVELOPMENT USING HYPERCUBIC SHAPES BASED ON BIO DATA

The present exemplary embodiments provide a data processing device and method which apply a neural network model to hypercubic data by converting a plurality of dimensions of initial data into a table type data structure and calculating between data matching the table and a designed filter. 1. A data processing method , comprising:preprocessing initial data with table based conversion data; andapplying a filter of a neural network model to the table based conversion data.2. The data processing method according to claim 1 , wherein the preprocessing step includes:converting a first data structure formed by N-dimensional data by N axes (N is a natural number of 2 or larger) into a second data structure formed as a table format.3. The data processing method according to claim 2 , wherein the first data structure includes a hypercube having depth information of four dimension or higher including two dimension and three dimension.4. The data processing method according to claim 2 , wherein in the second data structure claim 2 , (i) coordinate information corresponding to N axes and (ii) value information matching the coordinate information are disposed with reference to a row direction or a column direction.5. The data processing method according to claim 2 , wherein the first data structure includes bio-extraction data indicating a measurement result of flow cytometry of a clinical sample of blood or a biological analysis sample and an analysis technique using flow cytometry and bio extraction data may be expressed by a predetermined standardized format or a flow cytometry standard (FCS) format claim 2 , and the second data structure merges measurement values of some parameters of the bio extraction data and transforms the measurement values into data including a coordinate value for a channel and includes the transformed data and a count value.6. The data processing method according to claim 2 , wherein the preprocessing step includes:designing a filter frame structure ...

Multi-view analysis in automated testing apparatus

Embodiments include a device for testing biological specimen. The device can include a receiving mechanism to receive a carrier. The carrier may include a holding area. The device may include a camera arranged to capture a plurality of images, including a first image and a second image, of the holding area. The device may include a positioning mechanism operable to adjust a relative location of the carrier to the camera. A processor in the device may utilize the camera module to: identify an edge of the first image; cause the positioning mechanism to adjust the relative location of the carrier to the camera in a manner such that, when the camera takes the second image, an edge of the second image aligns with the identified edge of the first image; and perform a set of analytic processes on a combined image from the first and second images.

URINE SEDIMENT ANALYSIS WORKSTATION

A sediment analysis workstation includes an optical microscope, an image recording device connected to an optical unit of the optical microscope and a user interface device connected to the image recording device. The user interface device comprises one or more processors running computer executable instructions that when executed by the one or more processor causes the one or more processor to count particles of a sediment sample based upon a manual input by an operator, and store counted particles of the sediment sample in a memory of the user interface device. Further, a method and a system for counting particles of a sediment sample are disclosed. 1. Sediment analysis workstation comprising:an optical microscope,an image recording device connected to an optical unit of the optical microscope,a user interface device connected to the image recording device,wherein the user interface device comprises one or more processors running computer executable instructions that when executed by the one or more processor causes the one or more processor tocount particles of a sediment sample based upon a manual input by an operator, andstore counted particles of the sediment sample in a memory of the user interface device.2. The workstation as claimed in claim 1 , wherein the user interface device is capable of training operators by employing and displaying a number of pre-classified sediment sample images3. The workstation as claimed in claim 1 , further comprising a support stand claim 1 , wherein the optical microscope claim 1 , the image recording device and the user interface device are carried by the support stand.4. A method for counting particles of a sediment sample comprising:displaying an image of a sediment sample on a screen of a user interface device, andcounting particles of the sediment sample using the user interface device based upon manual input by an operator of the user interface device.5. The method as claimed in claim 4 , wherein the user interface ...

Microparticle measuring apparatus

A microparticle measuring apparatus for highly accurately detecting the position of a microparticle flowing through a flow channel includes a light irradiation unit for irradiating a microparticle flowing through a flow channel with light, and a scattered light detection unit for detecting scattered light from the microparticle, including an objective lens for collecting light from the microparticle, a light splitting element for dividing the scattered light from the light collected by the objective lens, into first and second scattered light, a first scattered light detector for receiving an S-polarized light component, and an astigmatic element disposed between the light splitting element and the first scattered light detector, and making the first scattered light astigmatic. A relationship between a length L from a rear principal point of the objective lens to a front principal point of the astigmatic element, and a focal length f of the astigmatic element satisfies the following formula I. 1.5 f≦L≦ 2.5 f   ( I )

SELECTIVE DELIVERY OF MATERIAL TO CELLS

Isolating or identifying a cell based on a physical property of said cell can include providing a cell suspension; passing said suspension through a microfluidic channel that includes a constriction; passing the cell suspension through the constriction; and, contacting said cell suspension solution with a compound. The constriction can be sized to preferentially deform a relatively larger cell compared to a relatively smaller cell. 1. A method for isolating , identifying , or manipulating a cell based on a physical property of said cell comprising:providing a cell suspension;passing said suspension through a microfluidic channel that includes a constriction, said constriction being sized to preferentially deliver a compound to a group of cells having a relatively different physical property than another group of cells;passing the cell suspension through the constriction; andcontacting said cell suspension solution with a compound.2. The method of claim 1 , wherein the physical property is one or more of size claim 1 , diameter claim 1 , and membrane stiffness.3. The method of claim 1 , wherein said cell suspension comprises one or more of: peripheral blood cells; and at least two different cell types having different physical properties.4. The method of claim 1 , wherein said cell suspension comprises an erythrocyte-depleted population of peripheral blood cells.5. The method of claim 1 , wherein said larger cell comprises a circulating tumor cell and said smaller cell comprises a leukocyte.6. The method of claim 1 , wherein said compound comprises a molecular mass of 0.5 kDa to 5 MDa.7. The method of claim 1 , wherein said compound comprises a molecular mass of 3 kDa to 10 kDa.8. The method of claim 1 , wherein said compound comprises one or more of a detectable marker claim 1 , an active biomolecule claim 1 , and a toxin.9. The method of claim 1 , wherein a detectable marker enters said cell after said cell has passed through said constriction.10. The method of ...

Trajectory-Based Triggering System for Hyperspectral Imaging Flow Cytometer

A hyperspectral imaging flow cytometer can acquire high-resolution hyperspectral images of particles, such as biological cells, flowing through a microfluidic system. A trajectory-based triggering system can be used that will only trigger the acquisition of a hyperspectral image when an appropriate particle or cell is crossing an imaging line, thereby saving valuable resources and time. The hyperspectral imaging flow cytometer can provide detailed spatial maps of multiple emitting species, cell morphology information, and state of health. An optimized system can image about 20 cells per second. The hyperspectral imaging flow cytometer enables many thousands of cells to be characterized in a single session. 1. A hyperspectral imaging flow cytometer , comprising:a microfluidic flow system for injecting a sample of fluorescent particles into a channel, directing the particles to flow through an imaging field in the channel, and sorting the particles into separate bins in response to an analysis of an acquired image of each particle;a trajectory-based triggering system for obtaining a first image of a particle a first time at a first location in the channel, obtaining a second image of the particle at a later second time at a second location in the channel, predicting a third time and a lateral location at which the particle will cross an imaging line downstream from the first and second locations, and providing a trigger;a hyperspectral confocal imaging system having a focal plane downstream from the particle detection system for laterally scanning a focused laser beam along the imaging line at the third time with the laser scanning centered on the predicted lateral location and acquiring a hyperspectral image of fluorescence emitted by the particle in the imaging line in response to the trigger; andan analyzer for real-time multivariate analysis of the acquired hyperspectral image of the particle to direct the microfluidic system to sort the particle into a bin.2. The ...

IMPEDANCE FLOW CYTOMETRY APPARATUS

Impedance flow cytometry apparatus comprises: a flow channel for carrying a flow of fluid comprising particles suspended in an electrolyte from an inlet to an outlet; a first electrode group and a second electrode group, each electrode group providing first and second current paths through fluid flowing in the flow channel; wherein each electrode group comprises: a first signal electrode to provide to the first current path a first electrical signal of frequency, magnitude and phase; a second signal electrode to provide to the second current path a second electrical signal of substantially equal frequency and magnitude as the first electrical signal and of opposite phase to the first electrical signal; and one or more measurement electrodes to detect current flow in the first current path and the second current path and produce a summed signal representing the sum of the current flow in the first current path and the current flow in the second current path; wherein the first electrode group produces a first summed signal and the second electrode group produces a second summed signal; and circuitry to determine a differential signal representing the difference between the first summed signal and the second summed signal. 1. Impedance flow cytometry apparatus comprising:a flow channel for carrying a flow of fluid comprising particles suspended in an electrolyte from an inlet to an outlet;a first electrode group and a second electrode group, each electrode group providing first and second current paths through fluid flowing in the flow channel; a first signal electrode to provide to the first current path a first electric signal of frequency, magnitude and phase;', 'a second signal electrode to provide to the second current path a second electrical signal of substantially equal frequency and magnitude as the first electrical signal and of opposite phase to the first electrical signal; and', 'wherein the first electrode group produces a first summed signal and the ...

ANALYSIS DEVICE AND SEPARATION DEVICE

An analysis device () analyzes a crossover frequency at which a dielectrophoretic force on dielectric particles switches from a repulsive force to an attractive force or from the attractive force to the repulsive force, comprising a flow channel (), a pair of electrodes (), a power supply (), an imaging unit () and an analyzer (). Through the flow channel (), a sample solution containing the dielectric particles in the dielectrophoretic liquid flows. The pair of electrodes () are arranged in the first channel. The power supply () applies a frequency-modulated AC voltage to the first electrodes (). The imaging unit () captures an image of a movement trajectory of each of the dielectric particles flowing between the electrodes () in the flow channel. The analyzer () obtains the crossover frequency of the dielectric particles based on the captured image of the movement trajectory. 1. An analysis device for analyzing a crossover frequency at which a dielectrophoretic force on dielectric particles switches from a repulsive force to an attractive force or from the attractive force to the repulsive force , the analysts device comprising:a first flow channel through which a sample solution containing the dielectric particles in the dielectrophoretic liquid flows,a pair of first electrodes arranged in the first flow channel,a first power supply that applies a frequency-modulated AC voltage to the pair of first electrodes,an imaging unit that captures an image of a movement trajectory of each of the dielectric particles flowing between the pair of first electrodes in the first flow channel; andan analyzer that obtains the crossover frequency of the dielectric particles based on the captured image of the movement trajectory.2. The analysis device according to claim 1 , further comprising a replacement unit that includes:a second flow channel which is disposed at a stage prior to the first flow channel and into which a suspension containing the dielectric particles and the ...

CELL DETECTION DEVICE AND CELL DETECTION METHOD

A cell detection device and a cell detection method is provided with which it is possible to efficiently acquire images of cells to be measured. Cell detection device comprises flow cell through which a measurement specimen that contains particles is caused to flow, particle detector for detecting the particles in the measurement specimen supplied to flow cell, particle sorter for sorting particles that satisfy a detection condition and other particles on the basis of the result of detection performed by particle detector, specimen supply part for supplying, to flow cell, an image-capture specimen that includes detection-condition-satisfying particles that have been sorted by particle sorter, and particle-image-capture part for capturing images of the particles in the sorted image-capture specimen supplied to flow cell. 120-. (canceled)21. A sample analysis method , comprising:introducing a measurement specimen to a flow cell through an inlet;sensing cells in the measurement specimen at a first position in the flow cell;directing target cells among the cells sensed at the first position, to a recirculation flow path at a second position that is downstream of the first position, wherein the recirculation flow path connects the second position and the inlet;supplying the target cells to the flow cell via the recirculation flow path; andcapturing images of the target cells in the flow cell.22. The method according to claim 21 , wherein the recirculation flow path comprises an intermediate reservoir adapted to increase a concentration of the target cells.23. The method according to claim 22 , wherein the intermediate reservoir comprises an elutriator rotor claim 22 , a centrifuge or a filter.24. The method according to claim 21 , wherein the sensing the cells comprises reading an optical characteristics of individual cells.25. The method according to claim 24 , wherein the reading the optical characteristics comprises:irradiating light onto the cells in the measurement ...

SYSTEMS AND METHODS FOR PARTICLE ANALYSIS

The present disclosure provides systems and methods for sorting a cell. The system may comprise a flow channel configured to transport a cell through the channel. The system may comprise an imaging device configured to capture an image of the cell from a plurality of different angles as the cell is transported through the flow channel. The system may comprise a processor configured to analyze the image using a deep learning algorithm to enable sorting of the cell. 1. A cell sorting system comprising:a flow channel configured to transport a cell through the channel;an imaging device configured to capture one or more images of the cell from a plurality of different angles as the cell is transported through the flow channel; anda processor configured to (1) analyze the one or more images using a deep learning algorithm to generate a classification of the cell and (2) enable sorting of the cell based at least in part on the classification of the cell.2. The system of claim 1 , wherein a width or a height of the flow channel is non-uniform along an axis of the flow channel.3. The system of claim 2 , wherein the width or the height of the flow channel gradually increases along a direction of the flow channel through which the cell is transported.4. The system of claim 1 , wherein the flow channel comprises walls that are formed to focus the cell into a streamline.5. The system of claim 4 , wherein the system is configured to focus the cell into the streamline using inertial lift forces or hydrodynamic forces.6. The system of claim 5 , wherein the system is further configured to focus the cell at a height within the flow channel.7. The system of claim 5 , wherein the system is configured to rotate the cell within the streamline.8. The system of claim 4 , wherein the flow channel comprises a square claim 4 , rectangular claim 4 , round claim 4 , or half-ellipsoid cross-section.9. The system of claim 1 , wherein the plurality of angles extend around the cell or over a ...

SPECTRAL MICROSCOPE

In one implementation, a spectral microscope may comprise a substrate with a planar lens, the planar lens including a phase profile including an axial focus and an oblique focus, a light source to excite a signal of a particle among a plurality of particles, and a detector to receive light generated from the light source from the axial focus of the planar lens and a spectral color component of the excited signal of the particle from the oblique focus of the planar lens. 1. A spectral microscope , comprising:a substrate with a planar lens patterned on the substrate, the planar lens including a phase profile including an axial focus and an oblique focus;a chip having a channel, wherein the chip is adjacent to the substrate; and light generated from a light source through the chip and the substrate from the axial focus of the planar lens; and', 'a spectral color component of an excited signal of a particle located in the channel through the chip and the substrate from the oblique focus of the planar lens., 'a detector to receive2. The spectral microscope of claim 1 , wherein the planar lens is a diffractive lens.3. The spectral microscope of claim 1 , wherein the detector is positioned above the substrate.4. The spectral microscope of claim 3 , wherein the light source is positioned below the chip to excite the signal of the particle such that the detector positioned above the substrate is to receive the light from the axial focus of the planar lens and the spectral color component of the particle from the oblique focus of the planar lens.5. The spectral microscope of claim 1 , wherein the planar lens is a partially reflective lens to reflect the spectral color component to the detector.6. The spectral microscope of claim 1 , wherein the detector is positioned in the chip and located adjacent to the channel.7. The spectral microscope of claim 6 , wherein the light source is positioned above the chip to excite the signal of the particle such that the detector positioned ...

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 fluidic chip containing a multiplex bead array, and a detection module, wherein the sample flows within the fluidic 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. 1. A system for detecting analytes in a sample comprising:a. one or more housing units;b. a bead array, wherein the bead array comprises at least one detection bead labelled with a detectable signal and a capture probe attached to the detection bead surface and wherein the bead array is capable of detecting at least two unique analytes in a sample;c. an analyte detection molecule;d. a fluidic chip, the fluidic chip incorporating at least one microfluidic channel that one or more detection beads flows through within the fluidic chip;e. a detection window incorporated in one of the one or more housings, the detection window being operable to facilitate the capture of one or more images of one or more detection beads flowing within the detection window; andf. a detection module, the detection module comprising an optical imaging system and software for image analysis, that allows communication to and from a central database.2. The system of claim 1 , wherein the bead array comprises fluorescent detection beads claim 1 , wherein each detection bead is coupled with a capture probe.3. The system of claim 2 , wherein the bead array comprises detection beads having at least one of varying fluorescent wavelengths and intensities.4. The system of claim 1 , wherein the detection beads comprise a magnetic microbead core.5. The system of claim 1 , wherein the detection beads comprise quantum dots.6. The system of claim 2 , wherein ...

DNA ORIGAMI BEADS FOR FLUORESCENCE QUANTIFICATION IN MICROFLUIDICS

A method is provided for calibrating a microfluidic system comprising, which method is based on using beads having a structure based on DNA origami, wherein said structure comprises a predetermined number of fluorophores. Furthermore, methods for determining the level of an antigen using microfluidics calibrated using fluorescent microbeads as provided herein. Also, methods are provided for determining the presence or state of a haematological disease by calibrated a microfluidics system. 1. A method of calibrating a microfluidic system comprising:a. providing at least one bead having a structure based on DNA origami, wherein said structure comprises a predetermined number of fluorophores;b. measuring the fluorescence of said at least one bead; and 'thereby obtaining a calibration curve of the microfluidic system.', 'c. calibrating the microfluidic system on the basis of the fluorescence measurement of b.'}2. The method according to claim 1 , wherein said microfluidic system is a flow cytometer3. The method according to any one of the preceding claims claim 1 , wherein the structure comprises a predetermined number of fluorophores claim 1 , a single stranded DNA molecule and staple DNA strands claim 1 , wherein the number of staple DNA strands (Ns) is as in formula I:{'br': None, 'i': 'Ns=Lss/n,'}wherein Lss is the length of the single stranded DNA molecule, andwherein n is an integer number comprised between 26 and 34.4. The method according to any one of the preceding claims claim 1 , wherein the single stranded DNA molecule has a length in a range between 1.500-nucleotides and 70.000-nucleotides claim 1 , preferably between 2000-nucleotides and 68.000-nucleotides claim 1 , such as between 5.000 and 65.000-nucleotides claim 1 , for example between 10.000-nucleotides and 60.000-nucleotides claim 1 , such as between 15.000-nucleotides and 55.000-nucleotides claim 1 , preferably between 20.000-nucleotides and 55.000-nucleotides.5. The method according to any one of ...

BLOOD ANALYZER AND ANALYSIS METHOD

A blood analyzer and a blood analysis method thereof are provided. The blood analyzer includes a test sample preparation apparatus, a flow chamber, a measurement apparatus and a data processor. The method adopts a white blood cell measurement channel to detect a test blood sample subjected to hemolysis and fluorescence staining and utilizes data in a blood ghost region to identify reticulocyte particles, thereby realizing differentiation of reticulocytes and large platelets and realizing finer classification and count of reticulocytes without separately designing an optical detection channel in the blood analyzer. A computer readable storage medium is also disclosed, in which a program is stored, and the program can be executed by the data processor to implement the above method. 137-. (canceled)38. A blood analyzer , comprising:a test sample preparation apparatus for preparing a test sample for measurement, wherein the test sample preparation apparatus at least comprises a reaction cell, and the reaction cell is configured for providing a place for mixing and incubation of a test blood sample, a fluorescence staining agent and a hemolytic agent, and the mixing and incubation causes red blood cells in the test blood sample to be lysed and causes cell particles in the sample to be stained;a flow chamber configured for providing an area for the cell particles in the test sample to pass through one by one and to be irradiated with light;a measurement apparatus comprising a light source and an optical detection device, wherein the light source is configured for emitting a light beam to irradiate the flow chamber, the optical detection device is configured for receiving scattered light and fluorescent light generated by the cell particles under the irradiation of light and outputting scattered light information and fluorescent light information, and the scattered light information at least comprises first angle scattered light information which is used for reflecting ...