CN111602052A - 一种血液检测方法及血液分析系统 - Google Patents
一种血液检测方法及血液分析系统 Download PDFInfo
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- CN111602052A CN111602052A CN201980008302.4A CN201980008302A CN111602052A CN 111602052 A CN111602052 A CN 111602052A CN 201980008302 A CN201980008302 A CN 201980008302A CN 111602052 A CN111602052 A CN 111602052A
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Abstract
本发明公开了一种血液检测方法,包括:用第一试剂处理血液样本以获得待测试样,所述第一试剂包括溶血剂,所述溶血剂将所述血液样本中的红细胞裂解为其光散射特性显著不同于血小板的碎片;使待测试样中的粒子逐个通过光学检测系统的检测区,获取所述待测试样的光学信息;和根据所述光学信息中的至少两种获得血小板的光学信息。本发明的方法通过裂解血液样本中的红细胞获取血小板计数,并可同时区分白细胞亚群。
Description
PCT国内申请,说明书已公开。
Claims (44)
- PCT国内申请,权利要求书已公开。
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PCT/CN2019/084660 WO2019206300A1 (zh) | 2018-04-28 | 2019-04-26 | 一种血液检测方法及血液分析系统 |
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US (1) | US12092633B2 (zh) |
EP (1) | EP3789764A4 (zh) |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022115982A1 (zh) * | 2020-12-01 | 2022-06-09 | 深圳迈瑞生物医疗电子股份有限公司 | 样本分析方法、样本分析仪及计算机可读存储介质 |
CN115015178A (zh) * | 2022-08-05 | 2022-09-06 | 天津迈科隆生物科技有限公司 | 一种光学检测装置及血液分析仪 |
WO2023125942A1 (zh) * | 2021-12-31 | 2023-07-06 | 深圳迈瑞生物医疗电子股份有限公司 | 血液细胞分析仪、方法以及感染标志参数的用途 |
TWI848718B (zh) * | 2023-05-23 | 2024-07-11 | 晶鑠科技有限公司 | 血紅素糖化終產物檢測儀器及其檢測容器 |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
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CN110249223B (zh) * | 2017-02-17 | 2020-10-20 | 深圳迈瑞生物医疗电子股份有限公司 | 血液细胞分析方法及血液细胞分析仪 |
CN118347920A (zh) * | 2020-05-14 | 2024-07-16 | 深圳迈瑞生物医疗电子股份有限公司 | 样本分析仪及样本分析方法 |
CN114252386A (zh) * | 2020-09-23 | 2022-03-29 | 深圳迈瑞生物医疗电子股份有限公司 | 样本检测方法和样本分析仪 |
CN118451329A (zh) | 2021-12-31 | 2024-08-06 | 深圳迈瑞生物医疗电子股份有限公司 | 血液细胞分析仪、方法以及感染标志参数的用途 |
CN116952805A (zh) | 2022-04-14 | 2023-10-27 | 深圳迈瑞生物医疗电子股份有限公司 | 样本分析仪以及血小板计数方法 |
CN114636684A (zh) * | 2022-05-20 | 2022-06-17 | 深圳市帝迈生物技术有限公司 | 流式荧光分析设备 |
Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4336029A (en) * | 1980-08-15 | 1982-06-22 | Ortho Diagnostic Systems Inc. | Method and reagents for quantitative determination of reticulocytes and platelets in whole blood |
WO1996004544A1 (en) * | 1994-08-01 | 1996-02-15 | Abbott Laboratories | Method and apparatus for performing automated analysis |
CN1322146A (zh) * | 1999-09-03 | 2001-11-14 | 巴克斯特国际公司 | 具有检测程序的血液处理方法 |
EP1542008A1 (en) * | 2002-06-24 | 2005-06-15 | Sysmex Corporation | Method of classifying and counting leucocytes |
CN1834659A (zh) * | 2005-03-17 | 2006-09-20 | 希森美康株式会社 | 试料分析装置和试料分析方法以及血液分析装置 |
CN1981187A (zh) * | 2004-05-14 | 2007-06-13 | 霍尼韦尔国际公司 | 便携式样本分析仪盒 |
CN101490547A (zh) * | 2006-07-17 | 2009-07-22 | 海莫库公司 | 血小板的计数 |
CN102155927A (zh) * | 2011-03-22 | 2011-08-17 | 浙江大学 | 一种基于激光自准直的二维微角度测量装置 |
CN102230994A (zh) * | 2011-06-29 | 2011-11-02 | 武汉电信器件有限公司 | 法拉第磁光隔离器 |
CN102243339A (zh) * | 2011-07-04 | 2011-11-16 | 武汉电信器件有限公司 | 光隔离器 |
CN106525666A (zh) * | 2015-09-14 | 2017-03-22 | 希森美康株式会社 | 血液分析装置、血液分析方法及信息处理装置 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4099917A (en) | 1977-07-21 | 1978-07-11 | Technicon Instruments Corporation | Process for preparing a cell suspension from blood for discrimination of white blood cells and platelets from other blood particles |
US4882284A (en) | 1987-04-13 | 1989-11-21 | Ortho Pharmaceutical Corporation | Method for quantitating and differentiating white blood cells |
US5817519A (en) | 1995-12-28 | 1998-10-06 | Bayer Corporation | Automated method and device for identifying and quantifying platelets and for determining platelet activation state using whole blood samples |
TW379284B (en) | 1996-04-12 | 2000-01-11 | Toa Medical Electronics | Agent for detecting reticulocyte |
US6114173A (en) | 1997-04-03 | 2000-09-05 | Bayer Corporation | Fully automated method and reagent composition therefor for rapid identification and characterization of reticulocytes erythrocytes and platelets in whole blood |
JP2005024472A (ja) * | 2003-07-04 | 2005-01-27 | Sysmex Corp | 幼若血小板測定装置 |
US7390662B2 (en) * | 2005-11-09 | 2008-06-24 | Beckman Coulter, Inc. | Method and apparatus for performing platelet measurement |
US7344890B2 (en) | 2005-11-09 | 2008-03-18 | Beckman Coulter, Inc. | Method for discriminating platelets from red blood cells |
JP4806330B2 (ja) | 2006-10-30 | 2011-11-02 | シスメックス株式会社 | 網状赤血球及び血小板測定用試薬、網状赤血球及び血小板測定用試薬キット並びに網状赤血球及び血小板測定方法 |
JP4711009B2 (ja) * | 2008-10-16 | 2011-06-29 | ソニー株式会社 | 光学的測定装置 |
CN101988082B (zh) * | 2009-07-31 | 2015-04-08 | 深圳迈瑞生物医疗电子股份有限公司 | 白细胞分类计数试剂、试剂盒及其制备方法和白细胞分类计数的方法 |
JP6206404B2 (ja) * | 2012-06-06 | 2017-10-04 | ソニー株式会社 | 微小粒子測定装置におけるデータ補正方法及び微小粒子測定装置 |
US9176112B2 (en) | 2012-12-31 | 2015-11-03 | Beckman Coulter, Inc. | Systems and methods for platelet count with clump adjustment |
CN104749144A (zh) * | 2013-12-31 | 2015-07-01 | 深圳迈瑞生物医疗电子股份有限公司 | 血细胞检测试剂及血细胞处理方法和识别方法 |
EP3258274B1 (en) * | 2016-06-17 | 2019-11-06 | Sysmex Corporation | Method of controlling a blood analyzer for measuring platelets |
FR3062514A1 (fr) * | 2017-02-02 | 2018-08-03 | Commissariat A L'energie Atomique Et Aux Energies Alternatives | Formation de reliefs a la surface d'un substrat |
-
2019
- 2019-04-26 CN CN201980008302.4A patent/CN111602052B/zh active Active
- 2019-04-26 WO PCT/CN2019/084660 patent/WO2019206300A1/zh unknown
- 2019-04-26 EP EP19792205.7A patent/EP3789764A4/en active Pending
-
2020
- 2020-10-27 US US17/081,195 patent/US12092633B2/en active Active
Patent Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4336029A (en) * | 1980-08-15 | 1982-06-22 | Ortho Diagnostic Systems Inc. | Method and reagents for quantitative determination of reticulocytes and platelets in whole blood |
WO1996004544A1 (en) * | 1994-08-01 | 1996-02-15 | Abbott Laboratories | Method and apparatus for performing automated analysis |
CN1322146A (zh) * | 1999-09-03 | 2001-11-14 | 巴克斯特国际公司 | 具有检测程序的血液处理方法 |
EP1542008A1 (en) * | 2002-06-24 | 2005-06-15 | Sysmex Corporation | Method of classifying and counting leucocytes |
CN1981187A (zh) * | 2004-05-14 | 2007-06-13 | 霍尼韦尔国际公司 | 便携式样本分析仪盒 |
CN1834659A (zh) * | 2005-03-17 | 2006-09-20 | 希森美康株式会社 | 试料分析装置和试料分析方法以及血液分析装置 |
CN101490547A (zh) * | 2006-07-17 | 2009-07-22 | 海莫库公司 | 血小板的计数 |
CN102155927A (zh) * | 2011-03-22 | 2011-08-17 | 浙江大学 | 一种基于激光自准直的二维微角度测量装置 |
CN102230994A (zh) * | 2011-06-29 | 2011-11-02 | 武汉电信器件有限公司 | 法拉第磁光隔离器 |
CN102243339A (zh) * | 2011-07-04 | 2011-11-16 | 武汉电信器件有限公司 | 光隔离器 |
CN106525666A (zh) * | 2015-09-14 | 2017-03-22 | 希森美康株式会社 | 血液分析装置、血液分析方法及信息处理装置 |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022115982A1 (zh) * | 2020-12-01 | 2022-06-09 | 深圳迈瑞生物医疗电子股份有限公司 | 样本分析方法、样本分析仪及计算机可读存储介质 |
WO2023125942A1 (zh) * | 2021-12-31 | 2023-07-06 | 深圳迈瑞生物医疗电子股份有限公司 | 血液细胞分析仪、方法以及感染标志参数的用途 |
CN115015178A (zh) * | 2022-08-05 | 2022-09-06 | 天津迈科隆生物科技有限公司 | 一种光学检测装置及血液分析仪 |
TWI848718B (zh) * | 2023-05-23 | 2024-07-11 | 晶鑠科技有限公司 | 血紅素糖化終產物檢測儀器及其檢測容器 |
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