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1. 发明授权

US4358394A Process for preparing whole blood reference controls having long term stability 失效
标题翻译：制备具有长期稳定性的全血参照对照的方法
公开(公告)号：US4358394A
公开(公告)日：1982-11-09
申请号：US292091
申请日：1981-08-12
申请人： Harold R. Crews , David L. Chastain, Jr. , Stephen L. Ledis
发明人： Harold R. Crews , David L. Chastain, Jr. , Stephen L. Ledis
IPC分类号： G01N33/96 , G01N33/48 , C09K3/00
CPC分类号： G01N33/96 , G01N2496/05 , Y10T436/101666 , Y10T436/105831
摘要： A process for preparing whole blood reference controls having long term stability up to six months for devices using electronic means for whole blood determinations including platelet count and mean cell volume and red blood distribution width. The preconditioning diluent for the red blood cells consists essentially of an aqueous solution of lactose, sodium azide, and a non-ionic surfactant and is pH buffered and osmolality adjusted. The media of the whole blood control includes lactose, fungicides and antibiotics, and supplementary agents including purine nucleosides. It also includes additional components which alter red blood cell membranes including bile salts and cholic acid derivatives, phenothiazine compounds and the salts thereof having antihistamine properties, and 4-aminobenzoic acid ester derivatives and their salts having local anesthetic properties. In the process, the red blood cells are separated from the whole blood and preconditioned by the diluent to attain desired size distribution width and volume. The preconditioned red blood cells then are mixed in the media in suitable number for yielding the desired cell count for the whole blood reference control.
摘要翻译：一种用于制备全血参照对照的方法，对于使用电子方法进行全血测定的装置，包括血小板计数和平均细胞体积以及红血液分布宽度，对于长达6个月的长期稳定性。用于红细胞的预处理稀释剂基本上由乳糖，叠氮化钠和非离子表面活性剂的水溶液组成，并且是pH缓冲和重量摩尔渗透压浓度调节的。全血控制的媒体包括乳糖，杀真菌剂和抗生素，以及嘌呤核苷等补充剂。它还包括改变红细胞膜的其它组分，其包括胆汁盐和胆酸衍生物，吩噻嗪化合物及其具有抗组胺特性的盐，以及4-氨基苯甲酸酯衍生物及其具有局部麻醉性质的盐。在此过程中，将红细胞与全血分离并用稀释剂预处理，以获得所需的大小分布宽度和体积。然后将预处理的红细胞以适当的数量在培养基中混合，以产生用于全血参照对照的所需细胞计数。

2. 发明授权

US4264470A Selecting goat erythrocytes to simulate human platelets in hematologic reference controls 失效
标题翻译：选择山羊红细胞以在血液参照对照中模拟人血小板
公开(公告)号：US4264470A
公开(公告)日：1981-04-28
申请号：US36795
申请日：1979-05-07
申请人： David L. Chastain, Jr. , Harold R. Crews , Stephen L. Ledis
发明人： David L. Chastain, Jr. , Harold R. Crews , Stephen L. Ledis
IPC分类号： A61K35/14 , A61K38/16 , G01N33/49 , G01N33/96 , G01N33/48 , G01N35/00
CPC分类号： G01N33/96 , G01N2496/05 , Y10T436/101666 , Y10T436/106664 , Y10T436/107497 , Y10T436/108331
摘要： A method is described for preparing a human platelet analog for use as a reference control in particle analysis instrumentation of the Coulter type. Goat erythrocytes from individual goats which have been selected with respect to age, sex, selective breeding, a controlled environment, prior veterinary treatment, and diet are altered in size and/or combined with samples from several goats, as needed, to obtain a blend for use as a reference control for automated particle counting equipment in which the goat erythrocytes simulate in number, size and distribution the platelets in human whole blood. The controls are useful as a free-standing reference for determination of human platelets only, or can be added to whole blood reference controls for multi-parameter instruments.
摘要翻译：描述了一种制备人血小板类似物以用作库尔特型粒子分析仪器中的参考对照的方法。根据需要，根据年龄，性别，选择性育种，受控环境，先前的兽医治疗和饮食选择的来自单个山羊的山羊红细胞的大小和/或根据需要与来自几只山羊的样品组合以获得混合物用作自动粒子计数设备的参考对照，其中山羊红细胞模拟人全血中血小板的数量，大小和分布。这些对照作为仅用于确定人血小板的独立参考文献是有用的，或者可以添加到多参数仪器的全血参考对照中。

3. 发明授权

US4299726A Process for preparing whole blood reference controls having long term stability, preconditioning diluent and media therefor 失效
标题翻译：制备具有长期稳定性，预处理稀释剂和培养基的全血参照对照的方法
公开(公告)号：US4299726A
公开(公告)日：1981-11-10
申请号：US036794
申请日：1979-05-07
申请人： Harold R. Crews , David L. Chastain, Jr. , Stephen L. Ledis
发明人： Harold R. Crews , David L. Chastain, Jr. , Stephen L. Ledis
IPC分类号： G01N1/00 , G01N33/49 , G01N33/96 , G01N33/48 , C09K3/00
CPC分类号： G01N33/96 , G01N2496/05 , Y10T436/101666 , Y10T436/106664
摘要： A process for preparing whole blood reference controls having long term stability up to six months for devices using electronic means for whole blood determinations including platelet count and mean cell volume and red blood distribution width. The preconditioning diluent for the red blood cells consists essentially of an aqueous solution of lactose, sodium azide, and a non-ionic surfactant and is pH buffered and osmolality adjusted. The media of the whole blood control includes lactose, fungicides and antibiotics, and supplementary agents including purine nucleosides. It also includes additional components which alter red blood cell membranes including bile salts and cholic acid derivatives, phenothiazine compounds and the salts thereof having antihistamine properties, and 4-aminobenzoic acid ester derivatives and their salts having local anesthetic properties. In the process, the red blood cells are separated from the whole blood and preconditioned by the diluent to attain desired size distribution width and volume. The preconditioned red blood cells then are mixed in the media in suitable number for yielding the desired cell count for the whole blood reference control.
摘要翻译：一种用于制备全血参照对照的方法，对于使用电子方法进行全血测定的装置，包括血小板计数和平均细胞体积以及红血液分布宽度，对于长达6个月的长期稳定性。用于红细胞的预处理稀释剂基本上由乳糖，叠氮化钠和非离子表面活性剂的水溶液组成，并且是pH缓冲和重量摩尔渗透压浓度调节的。全血控制的媒体包括乳糖，杀真菌剂和抗生素，以及嘌呤核苷等补充剂。它还包括改变红细胞膜的其它组分，其包括胆汁盐和胆酸衍生物，吩噻嗪化合物及其具有抗组胺特性的盐，以及4-氨基苯甲酸酯衍生物及其具有局部麻醉性质的盐。在此过程中，将红细胞与全血分离并用稀释剂预处理，以获得所需的大小分布宽度和体积。然后将预处理的红细胞以适当的数量在培养基中混合，以产生用于全血参照对照的所需细胞计数。

4. 发明授权

US4286963A Differential lymphoid-myeloid determination of leukocytes in whole blood 失效
标题翻译：全血中白细胞的差异淋巴样骨髓测定
公开(公告)号：US4286963A
公开(公告)日：1981-09-01
申请号：US96697
申请日：1979-11-23
申请人： Stephen L. Ledis , David L. Chastain, Jr. , Harold R. Crews
发明人： Stephen L. Ledis , David L. Chastain, Jr. , Harold R. Crews
IPC分类号： G01N33/50 , G01N33/72 , G01N33/48
CPC分类号： G01N33/5094 , G01N33/721 , Y10T436/108331
摘要： This invention relates to a lytic diluent and a method for rapid lysing of red blood cells in whole blood for a differential determination of lymphoid and myeloid populations of leukocytes, and measurement of hemoglobin, particularly for use in automatic particle counting systems.The diluent is a mixture of at least one quaternary ammonium salt having surface active properties, and an additive in suitable proportions, buffered to an acid pH of 3.5 to 5.0. The additive includes 2-phenoxyethanol and other short chain alkanols substituted by one phenyl or phenoxy, as well as certain polyhydroxy compounds.When the reagent is employed in lower concentrations, an alkaline reagent comprising a quaternary ammonium salt and an alkali metal cyanide, buffered to an alkaline pH, may be added to complete the chromagen formation.
摘要翻译：本发明涉及裂解稀释剂和用于快速裂解全血中的红细胞的方法，用于差异测定白细胞的淋巴和骨髓群体，以及血红蛋白的测量，特别是用于自动粒子计数系统。稀释剂是具有表面活性的至少一种季铵盐和适当比例的添加剂的混合物，其缓冲至pH 3.5至5.0。添加剂包括2-苯氧基乙醇和由一个苯基或苯氧基取代的其它短链烷醇以及某些多羟基化合物。当试剂以较低浓度使用时，可以加入缓冲至碱性pH的季铵盐和碱金属氰化物的碱性试剂以完成色素形成。

5. 发明授权

US5731206A Method and reagent system for isolation, identification and/or analysis of leukocytes from whole blood samples 失效
标题翻译：用于从全血样品中分离，鉴定和/或分析白细胞的方法和试剂系统
公开(公告)号：US5731206A
公开(公告)日：1998-03-24
申请号：US630868
申请日：1996-03-29
申请人： Stephen L. Ledis , Harold R. Crews , Timothy J. Fischer , Ted Sena
发明人： Stephen L. Ledis , Harold R. Crews , Timothy J. Fischer , Ted Sena
IPC分类号： G01N33/48 , G01N33/50 , G01N31/00
CPC分类号： G01N33/5094 , Y10T436/101666 , Y10T436/107497 , Y10T436/108331
摘要： A lytic reagent composition and a kit of a lytic reagent system are disclosed for the rapid isolation, identification and/or analysis of at least five subpopulations of leukocytes from a whole blood sample. The composition and system have application to any environment in which the study and/or analysis of the leukocyte fraction of whole blood requires their isolation in their native or near native state. The lytic reagent composition of this invention comprises saponin and a carboxylic acid of the formula RCOOH wherein R is H or a C.sub.1-3 aliphatic hydrocarbon radial optionally substituted by one or more carbonyl and/or hydroxy groups. The kit of a lytic reagent system comprises the lytic reagent composition and a quench reagent.
摘要翻译：公开了溶解试剂组合物和溶解试剂体系试剂盒，用于从全血样品中快速分离，鉴定和/或分析至少五个白细胞亚群。该组合物和系统适用于任何环境，其中全血白细胞分数的研究和/或分析需要其天然或接近天然状态的分离。本发明的溶解试剂组合物包含皂角苷和式RCOOH的羧酸，其中R是H或被一个或多个羰基和/或羟基取代的C 3-脂肪烃。裂解试剂系统的试剂盒包含裂解试剂组合物和淬灭试剂。

6. 发明授权

US4751179A Method and reagents for differential determination of four populations of leukocytes in blood 失效
标题翻译：用于差异测定血液中四种白细胞数量的方法和试剂
公开(公告)号：US4751179A
公开(公告)日：1988-06-14
申请号：US615966
申请日：1984-05-31
申请人： Stephen L. Ledis , Harold R. Crews , Ted Sena
发明人： Stephen L. Ledis , Harold R. Crews , Ted Sena
IPC分类号： G01N33/49 , A01N1/02 , C12Q1/04 , C12Q1/06 , C12Q1/24 , G01N1/00 , G01N1/30 , G01N33/48 , G01N33/50
CPC分类号： G01N33/5094 , G01N33/48 , Y10T436/101666 , Y10T436/107497
摘要： This invention describes a reagent system, including saponin in a lysing reagent and a rapidly active cross-linking agent such as glutaraldehyde as a fixing reagent, which reproducably affects whole blood to cause the red blood cells to stromatolyze and modifies the leukocytes to generate data to define four distinct clusters for detection and classification by flow analysis instrumentation. The clusters represent the four major leukocyte types found in blood: lymphocytes, monocytes, neutrophils and eosinophils, thus providing a method of leukocyte differential analysis. The parameters used for the leukocyte classification include combinations of two or more of DC (Coulter) volume, high frequency (RF) size, opacity (RF size/DC volume), light scatter at various angular ranges, and fluorescence at various wavelengths of illumination.
摘要翻译：本发明描述了一种试剂系统，其包括裂解试剂中的皂角苷和作为固定剂的戊二醛的快速活性交联剂，其可全面影响全血，使红细胞进行基质分解并修饰白细胞以产生数据通过流量分析仪器定义四个不同的簇进行检测和分类。这些簇代表血液中发现的四种主要白细胞类型：淋巴细胞，单核细胞，嗜中性粒细胞和嗜酸性粒细胞，从而提供白细胞差异分析方法。用于白细胞分类的参数包括DC（Coulter）体积，高频（RF）尺寸，不透明度（RF尺寸/ DC体积），各种角度范围内的光散射和各种照明波长的荧光两种或更多种的组合。

7. 发明授权

US4346018A Multi-purpose blood diluent and lysing agent for differential determination of lymphoid-myeloid population of leukocytes 失效
标题翻译：多用途血液稀释液和裂解剂用于差异测定白细胞淋巴样骨髓细胞群体
公开(公告)号：US4346018A
公开(公告)日：1982-08-24
申请号：US159782
申请日：1980-06-16
申请人： James H. Carter , Stephen L. Ledis , Harold R. Crews
发明人： James H. Carter , Stephen L. Ledis , Harold R. Crews
IPC分类号： G01N33/48 , G01N15/12 , G01N33/49 , G01N33/50 , G01N33/72
CPC分类号： G01N33/721 , G01N33/5094 , G01N2015/0069 , Y10T436/107497
摘要： An isotonic multipurpose blood diluent, and a method for use of this diluent with a weak lysing reagent system which is especially suitable for routine enumeration of traditional hemogram values, and also the determination of lymphoid-myeloid populations of leukocytes, particularly in automatic particle counting systems.This blood diluent is capable of affording accurate, reproducible test results. It is an osmotically balanced aqueous solution of preselected pH containing Procaine hydrochloride for maintaining erythrocyte morphology during operation, N-(2-acetamido)iminodiacetic acid (ADA) as a blood cell stabilizing agent, and bacteriostatic agents including sodium 1-hydroxypyridine-2-thione, dimethylolurea and chlorhexidene diacetate which, together with the ADA, allow preferential determination of myeloid-lymphoid leukocytes, and other hematological values.The lysing agent is a mixture of an aqueous solution of at least one quaternary ammonium salt having surface active properties, and an alkali metal cyanide.
摘要翻译：一种等渗多用途血液稀释剂，以及一种使用该稀释液与弱溶解试剂系统的方法，该方法特别适用于常规计数传统的血红蛋白值，以及白细胞淋巴样骨髓细胞的测定，特别是在自动粒子计数系统。该血液稀释剂能够提供准确，可重复的测试结果。它是含有普鲁卡因盐酸盐的预选pH的渗透平衡水溶液，用于在手术期间保持红细胞形态，作为血细胞稳定剂的N-（2-乙酰氨基）亚氨基二乙酸（ADA））和抑菌剂包括1-羟基吡啶-2- 硫酮，二羟甲基脲和氯己酮二乙酸酯，其与ADA一起允许优先测定骨髓淋巴样白血球和其他血液学值。裂解剂是具有表面活性的至少一种季铵盐的水溶液和碱金属氰化物的混合物。

8. 发明授权

US4213876A Multi-purpose blood diluent for use in electronic blood analysis instrumentation 失效
标题翻译：多用途血液稀释剂用于电子血液分析仪器
公开(公告)号：US4213876A
公开(公告)日：1980-07-22
申请号：US936570
申请日：1978-08-22
申请人： Harold R. Crews , Dave Chastain, Jr. , Stephen L. Ledis
发明人： Harold R. Crews , Dave Chastain, Jr. , Stephen L. Ledis
IPC分类号： G01N33/48 , G01N15/12 , G01N33/49 , G01N33/50 , G01N33/72 , G01N33/16 , C09K3/00
CPC分类号： G01N33/5094 , G01N15/12 , G01N33/721 , Y10T436/10 , Y10T436/101666 , Y10T436/105831 , Y10T436/108331
摘要： A multi-purpose blood diluent especially suitable for use in electronic enumeration and sizing of blood cells, determination of hemoglobin concentration and their collective indices and platelet parameters in a single blood sample by means of suitable electronic instrumentation. The diluent is characterized as azide-free and capable of affording accurate, reproducible hematological test results from the said suitable electronic instrumentation. The diluent employs a chelating agent which functions as a bacteriostat and fungistat agent to prevent adverse growth of micro-organisms and a compatible stabilizing agent to maintain desired morphology of red blood cells and an inorganic metallic sulfate for suppressing turbidity caused by abnormal globulins and/or high leukocyte counts which are encountered in certain blood samples. Because of the capability for use of the diluent in platelet determinations by the instrumentation, the diluent further is free of detergent action which would cause bubbles capable of interfering with the enumeration of platelets by the instrumentation. A modified and adjusted embodiment of the diluent enables its use in veterinary laboratory testing applications.
摘要翻译：一种多用途的血液稀释剂，特别适合用于血液细胞的电子计数和上浆，通过合适的电子仪器测定血液样品中血红蛋白浓度及其集体指数和血小板参数。稀释剂的特征在于不含叠氮化物，并且能够提供来自所述合适的电子仪器的精确，可再现的血液学检测结果。稀释剂使用螯合剂，其用作抑菌剂和抑霉剂，以防止微生物和相容的稳定剂的不利生长，以维持红细胞所需的形态和无机金属硫酸盐，以抑制异常球蛋白和/或在某些血液样本中遇到的高白细胞计数。由于通过仪器对血小板测定使用稀释剂的能力，所以稀释剂进一步没有洗涤剂作用，这将引起气泡能够干扰仪器对血小板的计数。稀释剂的改进和调整的实施方案使其能够在兽医实验室测试应用中使用。

9. 发明授权

US5155044A Lysing reagent system for isolation, identification and/or analysis of leukocytes from whole blood samples 失效
标题翻译：用于从全血样品中分离，鉴定和/或分析白细胞的裂解试剂系统
公开(公告)号：US5155044A
公开(公告)日：1992-10-13
申请号：US808041
申请日：1991-12-12
申请人： Stephen L. Ledis , Harold R. Crews , Timothy J. Fischer , Ted Sena
发明人： Stephen L. Ledis , Harold R. Crews , Timothy J. Fischer , Ted Sena
IPC分类号： G01N33/50 , G01N33/569
CPC分类号： G01N33/5094 , G01N33/56972 , Y10T436/101666 , Y10T436/107497 , Y10T436/108331
摘要： A method and reagent system are disclosed for the rapid isolation, identification and/or analysis of leukocytes from a whole blood sample. The method and reagent system of this invention has application to any environment in which the study and/or analysis of the leukocyte fraction of whole blood requires their isolation in their native or near native state. One of the environments in which this invention can be used to advantage is in the performance of white cell differentiation on automated instrumentation designed for that purpose. In one of the preferred embodiments of this invention, the lytic reagent can contain a mixture of both formic and acetic acid, with the formic acid comprising the major component thereof and the acetic acid being present in only minor quantities, (if at all). This reagent system is used to selectively effect stromatolysis of red blood cells and create subtle modifications to the leukocyte population to enable their automated differentiation into five (5) sub-populations. The advantage and uniqueness of this reagent system is the surprising speed at which it is able to effect the foregoing objectives (generally less than 10 seconds at room temperature) and the ability to further differentiate the leukocyte population (notably, the granulocyte population). Following stromatolysis, a quenching agent is added to retard the reactivity of the lytic reagent system and, thus, inhibit any further dramatic changes to the leukocyte population. The treatment of the whole blood sample in the foregoing manner is further unique in that the leukocyte fraction of the sample has retained its characteristic immunochemical response.
摘要翻译：公开了用于从全血样品快速分离，鉴定和/或分析白细胞的方法和试剂系统。本发明的方法和试剂系统适用于其中全血白细胞分数的研究和/或分析需要在其天然或接近天然状态下分离的任何环境。本发明可用于有利的环境之一是在为此设计的自动化仪器上实现白细胞分化。在本发明的一个优选实施方案中，溶解剂可以含有甲酸和乙酸的混合物，其中甲酸包含其主要组分，乙酸仅以少量存在（如果有的话）。该试剂系统用于选择性地影响红细胞的间质分解，并对白细胞群体产生微妙的修饰，使其能够自动分化为五（5）个亚种群。该试剂系统的优点和独特之处在于其能够达到上述目的（通常在室温下通常小于10秒）以及进一步区分白细胞群体（特别是粒细胞群体）的能力的惊人速度。在层间裂解后，加入淬灭剂以延缓溶解试剂体系的反应性，从而抑制白细胞群体的任何进一步的剧烈变化。以上述方式对全血样品的处理是进一步的独特之处在于，样品的白细胞部分保持了其特有的免疫化学应答。

10. 发明授权

US4962038A Multi-purpose blood diluent and lysing agent for differential determination of lymphoid-myeloid population of leukocytes 失效
标题翻译：多用途血液稀释液和裂解剂用于差异测定白细胞淋巴样骨髓细胞群体
公开(公告)号：US4962038A
公开(公告)日：1990-10-09
申请号：US735245
申请日：1985-05-17
申请人： James H. Carter , Stephen L. Ledis , Harold R. Crews
发明人： James H. Carter , Stephen L. Ledis , Harold R. Crews
IPC分类号： G01N15/12 , G01N33/50 , G01N33/72
CPC分类号： G01N33/5094 , G01N15/1209 , G01N33/721 , Y10T436/10 , Y10T436/101666 , Y10T436/107497 , Y10T436/108331
摘要： An isotonic multipurpose blood diluent, and a method for use of this diluent with a weak lysing reagent system which is especially suitable for routine enumeration of traditional hemogram values, and also the determination of lymphoid-myeloid populations of leukocytes, particularly in automatic particle counting systems.This blood diluent is capable of affording accurate, reproducible test results. It is an osmotically balanced aqueous solution of preselected pH containing Procaine hydrochloride for maintaining erythrocyte morphology during operation, N-(2-acetamido)iminodiacetic acid (ADA) as a blood cell stabilizing agent, and bacteriostatic agents including sodium 1-hydroxypyridine-2-thione, and dimethylolurea which, together with the ADA, allow preferential determination of myeloid-lymphoid leukocytes, and other hematological values.The lysing agent is a mixture of an aqueous solution of at least one quaternary ammonium salt having surface active properties, and an alkali metal cyanide.
摘要翻译：一种等渗多用途血液稀释剂，以及一种使用该稀释液与弱溶解试剂系统的方法，该方法特别适用于常规计数传统的血红蛋白值，以及白细胞淋巴样骨髓细胞的测定，特别是在自动粒子计数系统。该血液稀释剂能够提供准确，可重复的测试结果。它是含有普鲁卡因盐酸盐的预选pH的渗透平衡水溶液，用于在手术期间保持红细胞形态，作为血细胞稳定剂的N-（2-乙酰氨基）亚氨基二乙酸（ADA））和抑菌剂包括1-羟基吡啶-2- 硫醇和二羟甲基脲，其与ADA一起允许优先测定骨髓淋巴样白血球和其他血液学值。裂解剂是具有表面活性的至少一种季铵盐的水溶液和碱金属氰化物的混合物。

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