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1. 发明申请

WO2006086157A1 CELL PERMEABILIZATION AND STABILIZATION REAGENT AND METHOD OF USE 审中-公开
标题翻译：细胞渗透和稳定试剂及其使用方法
公开(公告)号：WO2006086157A1
公开(公告)日：2006-08-17
申请号：PCT/US2006/002612
申请日：2006-01-24
申请人： BECKMAN COULTER, INC.
发明人： RABELLINO, Enrique , VAN AGTHOVEN, Andreas , MALERGUE, Fabrice
IPC分类号： A01N37/18 , A61K38/00
CPC分类号： A61K31/198 , Y10T436/107497
摘要： A cell permeabilization and stabilization reagent and method of use are disclosed. The reagent contains a N-acyl sarcosine or a salt thereof, a pH adjusting agent to adjust pH of the reagent in a range from about 4 to about 6; and an aqueous medium; the reagent having a low ionic strength defined by a conductivity of less than 9.0 mS/cm. The reagent further contains bovine serum albumin and glycerol. The reagent may further include an alkyl sulfate surfactant. Upon incubating the cells with the reagent, the reagent permeates the cellular membrane to allow penetration of an intracellular marker, causes intracellular protein aggregation within the cellular membrane, while preserves a cellular constituent for binding with a cellular marker for subsequent analysis by flow cytometry.
摘要翻译：公开了一种细胞透化和稳定剂及其使用方法。该试剂含有N-酰基肌氨酸或其盐，pH调节剂以将试剂的pH调节在约4至约6的范围内; 和水介质; 该试剂具有由小于9.0mS / cm的电导率限定的低离子强度。试剂还含有牛血清白蛋白和甘油。试剂还可以包括烷基硫酸盐表面活性剂。在将细胞与试剂一起孵育时，试剂渗透细胞膜以允许细胞内标记物穿透，引起细胞膜内的细胞内蛋白质聚集，同时保留用于与细胞标志物结合的细胞成分，以便随后通过流式细胞术分析。

2. 发明申请

WO2013093642A1 METHOD FOR LABELING INTRACELLULAR AND EXTRACELLULAR TARGETS OF LEUKOCYTES 审中-公开
标题翻译：标签白细胞和细胞外目标的方法
公开(公告)号：WO2013093642A1
公开(公告)日：2013-06-27
申请号：PCT/IB2012/003071
申请日：2012-12-21
申请人： BECKMAN COULTER, INC.
发明人： MALERGUE, Fabrice , VAN AGTHOVEN, Andreas
IPC分类号： G01N33/50 , G01N33/569
CPC分类号： G01N33/56972 , G01N33/5091 , G01N33/5094 , G01N2333/70514 , G01N2333/70589 , G01N2333/70596 , G01N2333/91205
摘要： The present invention relates to methods for labeling intracellular and extracellular targets of leukocytes, as well as to kits for performing said methods.
摘要翻译：本发明涉及用于标记白细胞的细胞内和细胞外靶标的方法，以及用于进行所述方法的试剂盒。

3. 发明申请

WO2009017959A1 METHOD OF MEASUREMENT OF MICRONUCLEATED ERYTHROCYTE POPULATIONS 审中-公开
标题翻译：测定微球蛋白尿人群的方法
公开(公告)号：WO2009017959A1
公开(公告)日：2009-02-05
申请号：PCT/US2008/070026
申请日：2008-07-15
申请人： BECKMAN COULTER, INC.
发明人： WOLFERS, Joseph , VAN AGTHOVEN, Andreas , MALERGUE, Fabrice , HERBERT, Michel
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6806
摘要： A method of measuring micronucleated erythrocyte populations is disclosed. The method includes contacting a sample containing erythrocyte populations with a fluorescently labeled antibody specific to immature erythrocytes among erythrocyte populations; adding an aqueous permeation reagent to the sample and incubating the formed permeation sample mixture for an incubation time sufficient to allow the permeation reagent to render cellular membrane of the erythrocyte populations permeable to RNase and dye; adding a RNase reagent to degrade RNA and to inhibit further reaction of permeation reagent; adding a fluorescent nucleic acid dye reagent to stain DNA representing micronuclei in the erythrocyte populations; performing light scatter and fluorescence measurements of the final sample mixture on a flow cytometer; differentiating micronucleated erythrocyte populations from other cell types; and reporting the micronucleated erythrocyte populations of the sample. The method avoids ultracold fixation, centhfugation, and washing cells in sample preparation.
摘要翻译：公开了一种测量微核红细胞种群的方法。该方法包括使含有红细胞群体的样品与红细胞群体中未成熟红细胞特异性的荧光标记抗体接触; 向样品中加入水性渗透试剂，并将形成的渗透样品混合物孵育足以允许渗透试剂使红细胞群的细胞膜可透过核糖核酸酶和染料的孵育时间; 加入RNase试剂降解RNA并抑制渗透试剂的进一步反应; 加入荧光核酸染料试剂染色代表红细胞群体中的微核的DNA; 在流式细胞仪上进行最终样品混合物的光散射和荧光测量; 区分微核红细胞种群与其他细胞类型; 并报告样品的微核红细胞数。该方法避免了样品制备中的超冷固定，离心和洗涤细胞。

4. 发明申请

WO2019060687A1 METHOD OF DETERMINING FETAL RED BLOOD CELLS IN MATERNAL CIRCULATION USING FLOW CYTOMETRY 审中-公开
公开(公告)号：WO2019060687A1
公开(公告)日：2019-03-28
申请号：PCT/US2018/052174
申请日：2018-09-21
申请人： BECKMAN COULTER, INC.
发明人： MALERGUE, Fabrice , VAN AGTHOVEN, Andreas , BUSNEL, Jean Marc
IPC分类号： G01N33/68 , G01N33/72 , G01N33/80
CPC分类号： G01N33/80 , G01N33/6893 , G01N33/72 , G01N2800/22 , G01N2800/368
摘要： This invention provides methods for identifying fetal red blood cells in a blood sample that is suspected of comprising fetal blood. The invention also provides kits that can be used for this purpose.

5. 发明申请

WO2008021653A3 METHOD OF MEASUREMENT OF CELLULAR HEMOGLOBIN 审中-公开
公开(公告)号：WO2008021653A3
公开(公告)日：2008-02-21
申请号：PCT/US2007/073870
申请日：2007-07-19
申请人： BECKMAN COULTER, INC.
发明人： VAN AGTHOVEN, Andreas , MALERGUE, Fabrice
IPC分类号： G01N33/53
摘要： A method of measuring cellular hemoglobin of a blood sample includes mixing a blood sample with a permeation reagent, and incubating the sample mixture to permeate cellular membrane of red blood cells and to cause hemoglobin aggregation within the cells; adding a neutralization reagent to inhibit further reactions of the permeation reagent; performing a cell-by-cell measurement of side scatter signals of the red blood cells in the sample mixture on a flow cytometer; and obtaining cellular hemoglobin (Hgb cell ) of each red blood cell using the obtained side scatter signals. The method further includes measuring cellular hemoglobin of reticulocytes (Hgb retic ) by differentiating reticulocytes using a simultaneous fluorescence measurement. The method also includes measuring cellular percentage of a hemoglobin variant in mature red blood cells or reticulocytes by adding a fluorescent antibody in the neutralization reagent and detecting fluorescence signals of antibody bound hemoglobin variant.

6. 发明申请

WO2004096009A2 DIFFERENTIAL DETERMINATION OF HEMOGLOBINS 审中-公开
标题翻译： HEMOGLOBIN的差异确定
公开(公告)号：WO2004096009A2
公开(公告)日：2004-11-11
申请号：PCT/US2004/010633
申请日：2004-04-07
申请人： BECKMAN COULTER, INC.
发明人： BURSHTEYN, Alexander , VAN AGTHOVEN, Andreas , LUCAS, Frank, J. , RABELLINO, Enrique
IPC分类号： A61B
CPC分类号： G01N33/721 , G01N33/555
摘要： The present invention relates to reagents for analyzing hemoglobin in a sample using a pan-hemoglobin antibody conjugated to a detectable marker and one or more affinity reagents that are conjugated to a detectable marker that specifically bind to hemoglobin types and/or variants. The present invention is further drawn to flow cytometric methods using the reagents.
摘要翻译：本发明涉及用于使用与可检测标记缀合的泛血红蛋白抗体和与特异性结合血红蛋白类型和/或变体的可检测标记缀合的一种或多种亲和试剂来分析样品中血红蛋白的试剂。本发明进一步涉及使用试剂的流式细胞术方法。

7. 发明申请

WO2016040870A1 SYSTEMS AND METHODS TO DETERMINE THE AGE OF CELLS 审中-公开
标题翻译：确定细胞年龄的系统和方法
公开(公告)号：WO2016040870A1
公开(公告)日：2016-03-17
申请号：PCT/US2015/049797
申请日：2015-09-11
申请人： BECKMAN COULTER, INC.
发明人： VAN AGTHOVEN, Andreas , MALERGUE, Fabrice , GODEFROY, Christophe , RABELLINO, Enrique
IPC分类号： G01N33/72 , G01N15/14 , G01N15/00
CPC分类号： G01N33/721 , G01N15/1459 , G01N33/723 , G01N33/726 , G01N2015/0076 , G01N2015/1402 , G01N2015/1477 , G01N2015/1488 , G01N2333/805
摘要： Systems and methods are provided for determining the age of cellular hemoglobin in individual red blood cells in a blood sample by determining the percentage of HbA1c. In embodiments, a method includes measuring side scatter and fluorescence of the individual red blood cells and identifying immature red blood cells and mature red blood cells from the side scatter and fluorescence measurement. In embodiments, data collected includes the exact number of red blood cells, the fraction limits in fluorescence and side scatter units, the mean value of each fraction in fluorescence and side scatter units, the mean FL1 values per fraction in arbitrary units and the mean side scatter values per fraction in arbitrary units. In embodiments, a method also includes deriving a HbA1c content from the measured mean fluorescence of the individual red blood cells and determining the percentage of HbA1c from the HbA1c content and the hemoglobin content of the red blood cells.
摘要翻译：提供系统和方法，用于通过确定HbA1c的百分比来确定血液样品中个体红细胞中细胞血红蛋白的年龄。在实施方案中，一种方法包括测量各个红细胞的侧向散射和荧光，并从侧向散射和荧光测量鉴定未成熟的红细胞和成熟的红细胞。在实施例中，收集的数据包括确切的红细胞数目，荧光和侧面散射单位的分数限度，荧光和侧面散射单位中每个分数的平均值，任意单位的平均FL1值，平均值每个分数的散点值为任意单位。在实施方案中，方法还包括从所测量的各个红细胞的平均荧光中衍生HbA1c含量，并确定HbA1c含量的HbA1c百分比和红细胞的血红蛋白含量。

8. 发明申请

WO2014105837A1 COMPOSITIONS FOR PERMEABILISING FIXED BLOOD CELLS AND USES THEREOF 审中-公开
标题翻译：用于渗透固定的血液细胞的组合物及其用途
公开(公告)号：WO2014105837A1
公开(公告)日：2014-07-03
申请号：PCT/US2013/077518
申请日：2013-12-23
申请人： BECKMAN COULTER, INC. , VAN AGTHOVEN, Andreas
发明人： VAN AGTHOVEN, Andreas
IPC分类号： G01N1/30 , G01N33/53 , G01N33/569
CPC分类号： G01N1/30
摘要： The present invention relates to a cell treatment composition for the permeabilization of fixed blood cells, to the use of said composition, to a method for the treatment of a biological sample comprising fixation of said sample and subsequently contacting said biological sample with said cell treatment composition. The invention further relates and to a kit comprising said cell treatment composition.
摘要翻译：本发明涉及用于固定血细胞透化的细胞处理组合物，所述组合物的用途，用于处理生物样品的方法，包括固定所述样品并随后使所述生物样品与所述细胞处理组合物接触。本发明还涉及一种包含所述细胞处理组合物的试剂盒。

9. 发明申请

WO2010019372A1 REFERENCE CONTROL FOR CELL BY CELL ANALYSIS 审中-公开
标题翻译：细胞分析参考控制
公开(公告)号：WO2010019372A1
公开(公告)日：2010-02-18
申请号：PCT/US2009/051679
申请日：2009-07-24
申请人： BECKMAN COULTER, INC.
发明人： VAN AGTHOVEN, Andreas , MALERGUE, Fabrice
IPC分类号： G01N33/48
CPC分类号： A61K35/407 , G01N33/721 , G01N33/96 , G01N2333/805 , G01N2496/10 , Y10T436/101666 , Y10T436/107497
摘要： A reference control for cell by cell analysis on flow cytometric analyzers contains cellular analogs made of permeated blood cells containing therein aggregated intracellular proteins and preserved antigenic sites thereof, having cellular membrane permeable to antibodies and a suspension medium. The reference control is frozen after being prepared and thawed prior to use. The cellular analogs further contain a fluorescence marker therein. Further disclosed are a method of making the reference control and a method using the reference control, as an internal or stand-alone control, for measurements of cellular hemoglobin and cellular hemoglobin variant of a blood sample.
摘要翻译：用于流式细胞分析仪的细胞分析的参考对照包含由其中含有聚集的细胞内蛋白质和其保留的抗原位点的透过血细胞制成的细胞类似物，其具有可抗抗体的细胞膜和悬浮介质。参考对照在使用前准备并解冻后冷冻。细胞类似物还含有荧光标记物。进一步公开的是进行参考控制的方法和使用参考对照作为血液样品的细胞血红蛋白和细胞血红蛋白变体的测量作为内部或独立控制的方法。

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