ES2539699T3 - Aparato desechable para la realización de recuentos celulares sanguíneos - Google Patents
Aparato desechable para la realización de recuentos celulares sanguíneos Download PDFInfo
- Publication number
- ES2539699T3 ES2539699T3 ES99908614.3T ES99908614T ES2539699T3 ES 2539699 T3 ES2539699 T3 ES 2539699T3 ES 99908614 T ES99908614 T ES 99908614T ES 2539699 T3 ES2539699 T3 ES 2539699T3
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- Prior art keywords
- sample
- analysis
- reagents
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- chamber
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/54—Labware with identification means
- B01L3/545—Labware with identification means for laboratory containers
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L9/00—Supporting devices; Holding devices
- B01L9/56—Means for indicating position of a recipient or sample in an array
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
- G01N35/00722—Communications; Identification
- G01N35/00732—Identification of carriers, materials or components in automatic analysers
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/089—Virtual walls for guiding liquids
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/06—Valves, specific forms thereof
- B01L2400/0633—Valves, specific forms thereof with moving parts
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/08—Regulating or influencing the flow resistance
- B01L2400/084—Passive control of flow resistance
- B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/2813—Producing thin layers of samples on a substrate, e.g. smearing, spinning-on
- G01N2001/282—Producing thin layers of samples on a substrate, e.g. smearing, spinning-on with mapping; Identification of areas; Spatial correlated pattern
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
- G01N35/00722—Communications; Identification
- G01N35/00732—Identification of carriers, materials or components in automatic analysers
- G01N2035/00821—Identification of carriers, materials or components in automatic analysers nature of coded information
- G01N2035/00851—Identification of carriers, materials or components in automatic analysers nature of coded information process control parameters
Abstract
Un recipiente (10) para contener quiescentemente una muestra de fluido biológico para su análisis, comprendiendo dicho recipiente: una cámara (12; 62) que tiene una primera pared (26) y una segunda pared transparente (28), y un espesor a través del plano (t) definido como la distancia más corta entre la superficie interior (30) de dicha primera pared (26) y la superficie interior (32) de dicha segunda pared (28), en el que pueden obtenerse imágenes de una muestra de fluido que reside quiescentemente en dicha cámara (12; 62) a través de dicha segunda pared (28); una pluralidad de reactivos (54; 64; 66), siendo cada reactivo (54; 64; 66) operable para permitir el análisis del fluido biológico, en el que dichos reactivos (54; 64; 66) están posicionados cada uno en dicha cámara (12; 62) en una ubicación espacial conocida; y una etiqueta (14) unida a dicho recipiente (10), conteniendo dicha etiqueta (14) información de utilidad para dicho análisis, incluyendo dicha información dichas ubicaciones espaciales conocidas; caracterizado por que: el tamaño relativo de dicho espesor a través del plano (t) en cada lado de dicha ubicación espacial conocida de cada reactivo con respecto a la separación lateral entre las ubicaciones de los diferentes reactivos es tal que los reactivos (54; 64; 66) se difundirán en la muestra de fluido quiescente, y alcanzarán un equilibrio a lo largo del espesor a través del plano (t), y durante un periodo de tiempo posterior suficiente para llevar a cabo el análisis, teniendo la difusión lateral de cada reactivo (54; 64; 66) un efecto despreciable, o ninguno, sobre el análisis mediante el uso de cualquiera de los demás reactivos (54; 64; 66).
Description
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E99908614
16-06-2015
aquellos casos en los que la cantidad información que se va a comunicar es considerable, puede ser más deseable que la etiqueta 14 dirija al dispositivo analítico a un archivo de datos (almacenado en el dispositivo analítico o accesible en remoto por el dispositivo analítico a través de un módem, una conexión en red, etc.) que contiene la información apropiada. En este caso, puede decirse que la etiqueta 14 contiene indirectamente la información al proporcionar la ruta necesaria hacia la información. Aquí, de nuevo, la etiqueta 14 podría ser un código de barras o una banda magnética, que en este caso comunica un código particular que es interpretado por el dispositivo analítico como asociado con un archivo de datos determinado. Podría conseguirse el mismo resultado mediante la incorporación de una característica física 56 en el recipiente (por ejemplo, una muesca, una lengüeta, etc. - véase la FIG. 5) que sea interpretable por el dispositivo analítico. Alternativamente pueden usarse otras etiquetas 14 que funcionen comunicando información al dispositivo analítico.
El recipiente 10 también incluye preferiblemente una etiqueta legible por una persona 58 para facilitar la manipulación en el laboratorio o en la clínica. La etiqueta legible por una persona 58 puede incluir información tal como el nombre del paciente, la fecha de recogida de la muestra, una dirección de la oficina, una advertencia apropiada (por ejemplo, "Riesgo biológico - manipular con precaución"), marcas comerciales, etc. Los laterales 60 del recipiente 10 son adecuados para interactuar con un medio de transporte (no mostrado) contenido en el dispositivo analítico. El medio de transporte es operable para mover el recipiente 10 con respecto a un dispositivo de toma de imágenes (no mostrado) contenido en el dispositivo analítico.
Según se ha establecido anteriormente, la considerable utilidad del recipiente 10 permite la realización de una gran diversidad de análisis con una única muestra, mediante el uso de un único dispositivo analítico. Los ejemplos proporcionados a continuación se ofrecen de forma que pueda obtenerse una apreciación completa del recipiente 10 de la presente invención.
Ejemplo I: análisis hematológicos
Haciendo referencia a la FIGS. 1 y 4, para permitir un análisis de los glóbulos blancos sanguíneos (GB) en una muestra de sangre completa anticoagulada, el recipiente 10 incluye aproximadamente 0,8 microgramos (μg) de un colorante sensible dispuesto en el depósito 16. El EDTA es un ejemplo de un agente anticoagulante que puede ser usado con la muestra, y una tinción supravital de resaltado fluorescente, tal como naranja de acridina, naranja básico 21, o similares, son ejemplos de colorante sensibles que pueden ser añadidos al depósito 16. Con el fin de evaluar los GB, es preferible tener una región en la cámara 12 que tenga una pluralidad de campos de selección con un espesor a través del plano del orden de 20 micrómetros de magnitud. El espesor a través del plano de la cámara 12 se elige de aproximadamente 20 micrómetros por un par de razones. En primer lugar, un volumen de evaluación de 0,02 μl, (formado por un campo de la cámara 12 en particular con un área transversal de 1 milímetro (mm) y un espesor de 20 micrómetros) normalmente contiene 50 - 200 GB, lo que es una cantidad favorable con fines de evaluación. En segundo lugar, un espesor a través del plano de 20 micrómetros proporciona una cámara 12 óptima para la formación de los rouleaux y de lagunas. Las direcciones de coordenadas de los campos de selección son comunicadas al dispositivo analítico a través de la etiqueta 14. Por lo tanto, en el ejemplo, la pluralidad de características operativas que permiten el análisis de la muestra de fluido biológico incluyen: 1) el reactivo sensible dispuesto en el depósito 16; 2) la(s) región(es) de la cámara 12 que tiene(n) una pluralidad de campos de selección con un espesor a través del plano en particular; y 3) las direcciones de coordenadas de esos campos en la cámara
12.
El operario coloca aproximadamente 20 μl de sangre completa anticoagulada en el depósito 16 y se asegura el tapón 34. El recipiente se agita suavemente hasta que se mezclan adecuadamente el reactivo y la muestra de sangre completa. Una bola de mezcla 36 dispuesta en el depósito 16 facilita la mezcla. El recipiente 10 se inserta en el dispositivo analítico, y posteriormente se acciona la válvula 20 para liberar la muestra en la cámara 12 a través del canal 18. Una vez que la muestra está distribuida en la cámara 12, la muestra permanece quiescentemente. El único movimiento de la muestra en la cámara 12 será posiblemente el movimiento Browniano de los constituyentes que forman la muestra, y el movimiento no imposibilita la presente invención. Nótese que para unos análisis simples, tales como un recuento de GB en los que el tiempo no es importante, podría depositarse directamente una muestra en la cámara 12, obviando así la necesidad de un depósito 16 y de una válvula 20.
Inmediatamente después de que la muestra haya sido insertada en la cámara, la muestra aparecerá opaca cuando se examine con luz transmitida, o más preferiblemente, mediante una fluorescencia epi-iluminada. El aspecto opaco es causado por los glóbulos rojos sanguíneos (GR), que forman una masa solapante previa a la formación de los rouleaux. Después de permanecer sustancialmente inmóviles durante aproximadamente treinta (30) segundos, en la cámara 12, los GR se agregarán espontáneamente en rouleaux, dejando lagunas entre los rouleaux. Es en estas lagunas donde pueden encontrarse y evaluarse los otros constituyentes de la muestra sanguínea (por ejemplo, los GB y las plaquetas). Si se desea un recuento de GB, puede evaluarse un campo de un milímetro cuadrado de la cámara 12 de 20 micrómetros de espesor, que contiene 0,02 μl de la muestra de sangre completa. Se elige una muestra de 0,02 μl para mantener el número de GB razonable (una muestra de sangre completa normal contiene aproximadamente 7.000 GB por μl de muestra; una muestra de 0,02 μl de sangre completa normal contiene aproximadamente 140 GB). Se evaluarían varios de estos campos hasta que se cuenten las suficientes células como para conseguir un número que tenga una precisión estadística suficiente, lo que en la práctica es
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Claims (1)
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imagen1
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
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US7721498P | 1998-03-07 | 1998-03-07 | |
US77214P | 1998-03-07 | ||
US09/256,486 US6723290B1 (en) | 1998-03-07 | 1999-02-23 | Container for holding biologic fluid for analysis |
US256486 | 1999-02-23 | ||
PCT/US1999/004520 WO1999044743A1 (en) | 1998-03-07 | 1999-03-02 | Disposable apparatus for performing blood cell counts |
Publications (1)
Publication Number | Publication Date |
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ES2539699T3 true ES2539699T3 (es) | 2015-07-03 |
Family
ID=26759028
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES99908614.3T Expired - Lifetime ES2539699T3 (es) | 1998-03-07 | 1999-03-02 | Aparato desechable para la realización de recuentos celulares sanguíneos |
Country Status (9)
Country | Link |
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US (4) | US6723290B1 (es) |
EP (1) | EP1069951B1 (es) |
JP (1) | JP3593315B2 (es) |
CN (1) | CN1188217C (es) |
AU (1) | AU747817B2 (es) |
CA (1) | CA2321690C (es) |
ES (1) | ES2539699T3 (es) |
NO (1) | NO20004448L (es) |
WO (1) | WO1999044743A1 (es) |
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- 1999-03-02 EP EP99908614.3A patent/EP1069951B1/en not_active Expired - Lifetime
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- 1999-03-02 WO PCT/US1999/004520 patent/WO1999044743A1/en active IP Right Grant
- 1999-03-02 JP JP2000534334A patent/JP3593315B2/ja not_active Expired - Fee Related
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JP3593315B2 (ja) | 2004-11-24 |
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US20130209332A1 (en) | 2013-08-15 |
CN1302229A (zh) | 2001-07-04 |
JP2003526081A (ja) | 2003-09-02 |
NO20004448D0 (no) | 2000-09-06 |
CA2321690A1 (en) | 1999-09-10 |
EP1069951A1 (en) | 2001-01-24 |
US8367012B2 (en) | 2013-02-05 |
CA2321690C (en) | 2005-07-05 |
US20040156755A1 (en) | 2004-08-12 |
EP1069951A4 (en) | 2007-05-02 |
US20080187466A1 (en) | 2008-08-07 |
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