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    • 1. 发明申请
    • DETECTION METHOD USING NUCLEIC ACID ARRAY
    • 使用核酸序列的检测方法
    • WO2009145349A1
    • 2009-12-03
    • PCT/JP2009/060103
    • 2009-05-27
    • FUJIFILM CorporationNational University Corporation Tokyo Medical and Dental UniversityISHII, YasuyukiINAZAWA, JohjiIMOTO, Issei
    • ISHII, YasuyukiINAZAWA, JohjiIMOTO, Issei
    • C12Q1/68
    • C12Q1/6837C12Q2545/101C12Q2563/107
    • A method of comparing a first nucleic acid sequence of a first cell or cell population with a second nucleic acid sequence of a second cell or cell population, includes: a) labeling the first and second nucleic acid sequences with the same label; b) adding the labeled first and second nucleic acid sequences to separate first and second reaction fields respectively, the first and second reaction fields being provided at a nucleic acid array equipped with a plurality of reaction fields, and carrying out hybridization; c) subjecting the first and second reaction fields to the same washing operation by carrying out the washing operation in the identical liquid bath so as to uniform washing conditions; and d) detecting first and second signals at the first and second reaction fields respectively, and comparing obtained signal intensities of the first and second signals between the first and second reaction fields.
    • 比较第一细胞或细胞群体的第一核酸序列与第二细胞或细胞群体的第二核酸序列的方法包括:a)用相同标记物标记第一和第二核酸序列; b)分别添加标记的第一和第二核酸序列以分离第一和第二反应场,第一和第二反应场在配备有多个反应场的核酸阵列上提供,并进行杂交; c)通过在相同的液浴中进行洗涤操作以使均匀的洗涤条件使第一和第二反应场进行相同的洗涤操作; 以及d)分别在第一和第二反应场检测第一和第二信号,并且比较所获得的第一和第二反应场之间的第一和第二信号的信号强度。
    • 3. 发明公开
    • NUCLEATED ERYTHROCYTE SORTING METHOD
    • 核红细胞分选方法
    • EP3179249A1
    • 2017-06-14
    • EP15830123.4
    • 2015-06-19
    • Fujifilm Corporation
    • ISHII, YasuyukiMATSUBARA, KentaFUKUI, Shinichiro
    • G01N33/49C12Q1/02G01N21/27G01N33/48G01N33/483C12Q1/68
    • G01N33/80C12Q1/02C12Q1/68C12Q1/6883G01N21/27G01N21/31G01N33/48G01N33/483G01N33/49
    • Provided is a method for sorting nucleated red blood cells which is capable of reliably separating fetus-derived nucleated red blood cells from maternal blood. The method includes: a candidate cell selection step of selecting a candidate cell of nucleated red blood cells in accordance with shapes of cells; a white blood cell selection step of setting a search range including the candidate cell and selecting a white blood cell within the search range; a nucleated red blood cell definition step of defining that the candidate cell is a nucleated red blood cell through comparison of spectral characteristics of hemoglobin between the candidate cell and the white blood cell; and a sorting step of sorting the nucleated red blood cells into mother-derived nucleated red blood cells or fetus-derived nucleated red blood cells through comparison of an allele contained in the nucleated red blood cell after the nucleated red blood cell definition step with an allele contained in a white blood cell which has not been selected in the candidate cell selection step or in the white blood cell selected in the white blood cell selection step.
    • 本发明提供一种分选有核红细胞的方法,其能够可靠地从母血中分离胎儿来源的有核红细胞。 该方法包括:候选细胞选择步骤,根据细胞的形状选择有核红细胞的候选细胞; 白细胞选择步骤,设定包含所述候选细胞的搜索范围,选择所述搜索范围内的白细胞; 有核红细胞定义步骤,通过比较所述候选细胞和所述白细胞之间的血红蛋白的光谱特征来定义所述候选细胞是有核红细胞; 以及分选步骤,通过将有核红细胞定义步骤之后的有核红细胞中包含的等位基因与等位基因进行比较,将有核红细胞分选成母源红细胞或胎源源性有核红细胞 包含在候选细胞选择步骤中尚未选择的白细胞中或在白细胞选择步骤中选择的白细胞中。
    • 4. 发明公开
    • METHOD FOR TESTING FETAL CHROMOSOME
    • 检测胎儿染色体的方法
    • EP3178942A1
    • 2017-06-14
    • EP15829324.1
    • 2015-06-19
    • Fujifilm Corporation
    • FUKUI, ShinichiroISHII, YasuyukiMATSUBARA, Kenta
    • C12Q1/68C12Q1/04G01N21/27G01N33/48G01N33/49
    • C12Q1/6883C12Q1/04C12Q1/68G01N1/4077G01N15/1475G01N21/27G01N21/31G01N33/48G01N33/49G01N2001/4083G01N2015/0073G01N2015/1006G01N2015/149G01N2021/3133
    • Provided is a method for inspecting a chromosome of a fetus in which fetus-derived nucleated red blood cells are reliably obtained from maternal blood and are efficiently inspected within a short period of time. The method includes: a collection step of obtaining maternal blood from a pregnant mother; a concentration step of concentrating nucleated red blood cells in the maternal blood; a sorting step of sorting the nucleated red blood cells in the maternal blood, in which the nucleated red blood cells are concentrated through the concentration step, into mother-derived nucleated red blood cells and fetus-derived nucleated red blood cells in accordance with the shapes of nuclei and spectral characteristics at wavelengths included in a light wavelength region of 400 to 650 nm; an amplification step of amplifying a nucleic acid of a chromosome of the nucleated red blood cells; a definition step of defining an amount of the amplified product of the nucleated red blood cells; and a determination step of determining presence or absence of a numerical abnormality of the fetus-derived chromosome.
    • 本发明提供一种检查胎儿染色体的方法,其中从母体血液可靠地获得胎儿来源的有核红细胞,并在短时间内有效地检查胎儿来源的有核红细胞。 该方法包括:从怀孕母亲获取母血的采集步骤; 在母体血液中浓缩有核红细胞的浓缩步骤; 通过浓缩步骤将有核红细胞浓缩的母体血液中的有核红细胞根据形状分类为母源红细胞和源自胎儿的有核红细胞的分选步骤 包括在400至650nm的光波长范围内的波长处的核和光谱特性; 扩增有核红细胞的染色体的核酸的扩增步骤; 定义有核红细胞的扩增产物的量的定义步骤; 以及确定胎儿来源染色体的数值异常的存在或不存在的确定步骤。
    • 6. 发明公开
    • METHOD FOR DETECTING PRESENCE/ABSENCE OF FETAL CHROMOSOMAL ANEUPLOIDY
    • 用于检测胎儿染色体失效的存在/不存在的方法
    • EP3192879A1
    • 2017-07-19
    • EP15840802.1
    • 2015-04-28
    • Fujifilm Corporation
    • INOUE, YukiISHII, YasuyukiOUCHI, Aya
    • C12Q1/68C12N15/09
    • C12Q1/6874C12N15/09C12Q1/68C12Q1/6806
    • Provided is a method for detecting the presence or absence of heteroploidy of fetal chromosomes, the method comprising: a primary amplification step of obtaining a primary amplification products by amplifying chromosomal DNA obtained from a biological sample collected from a pregnant mother; a secondary amplification step of performing multiplex amplification of a plurality of target regions to obtain a secondary amplification product using the primary amplification product as a template; a step of adding a label to both terminals of the secondary amplification product to obtain the labeled secondary amplification product; a tertiary amplification step of performing amplification using a primer pair annealing to the label using the labeled secondary amplification product as a template to obtain a tertiary amplification product; and a step of determining the amplification amount and base sequences of the plurality of target regions from the tertiary amplification product, in which the primary amplification step amplifies the total amount of DNA by 6000 times to 30000 times, and the secondary amplification step amplifies the total amount of DNA by 3 times to 150 times.
    • 提供了检测胎儿染色体异倍性是否存在的方法,所述方法包括:通过扩增从孕妇采集的生物样品获得的染色体DNA获得初级扩增产物的初级扩增步骤; 第二扩增步骤,使用所述一次扩增产物作为模板进行多个目标区域的多重扩增以获得二次扩增产物; 在第二扩增产物的两个末端添加标记以获得标记的第二扩增产物的步骤; 使用标记的第二扩增产物作为模板使用与标记退火的引物对进行扩增的第三扩增步骤,以获得第三扩增产物; 以及从三次扩增产物中确定多个目标区域的扩增量和碱基序列的步骤,其中一次扩增步骤将总DNA量放大6000倍至30000倍,并且二次扩增步骤将总数 DNA的量由3倍增加到150倍。