公开(公告)号：EP2267443A1

公开(公告)日：2010-12-29

申请号：EP10184474.4

申请日：1999-02-22

Applicant: Wardlaw Partners LP ,  Becton, Dickinson & Company ,  Wardlaw, Stephen Clark ,  Levine, Robert Aaron

Inventor： Wardlaw, Stephen Clark ,  Levine, Robert Aaron ,  Rodriguez, Rodilfo, R.

IPC: G01N33/48 ,  G01N15/05 ,  G01N15/14

CPC classification number: G01N15/1475 ,  G01N33/5094 ,  G01N2015/0076 ,  G01N2015/0092 ,  G01N2015/1472 ,  G01N2015/1497 ,  Y10T436/10 ,  Y10T436/101666

Abstract: Target nucleated cells, and target cells containing remnant ribosomal material, which are present in a quiescent anticoagulated whole blood sample are optically detected, enumerated, and analyzed in a sample chamber (14) that has a varying through plane thickness due to convergent opposing sample chamber walls. At least one of the convergent walls (8) of the chamber is transparent so that the blood sample can be observed. The chamber's varying thickness produces a first lesser thickness region (A) in the chamber wherein individual red cells (32) and quiescent monolayers (31) of red cells in the sample will reside after the sample is introduced into and fills the chamber. Larger formed constituents such as white blood cells (34) and nucleated red blood cells present in the sample will reside in greater thickness regions (B) of the chamber, and non-nucleated red cells which reside in such greater thickness regions will agglomerate to form rouleaux (33). By admixing fluorescent dyes with the blood sample, target cells in the sample can be enumerated and differentiated by means of a scanning instrument (54) which is able to measure different wave length color signals emitted from the target cells in the sample, and differentiate the target cells one from another by reason of the nature of the emitted color signals.

Abstract translation: 存在于静止抗凝全血样品中的目标有核细胞和含有残留核糖体材料的靶细胞在由于收敛的相对样品室而具有不同的平面厚度的样品室（14）中被光学检测，列举和分析 墙壁。 室的收敛壁（8）中的至少一个是透明的，使得可以观察血液样本。 室的不同厚度在腔室中产生第一较小厚度的区域（A），其中样品中的红细胞中的各个红细胞（32）和静止单层（31）将在样品被引入并填充室之后驻留。 样品中存在的白细胞（34）和成核红细胞等较大的成分将存在于室的较大厚度区域（B）中，并且驻留在这样较厚的区域中的未成核红细胞将聚集形成 rouleaux（33）。 通过将荧光染料与血液样品混合，样品中的靶细胞可以通过能够测量从样品中的靶细胞发射的不同波长颜色信号的扫描仪器（54）进行计数和分化，并区分 由于发射的颜色信号的性质，目标细胞彼此之间。

公开(公告)号：EP1949310A2

公开(公告)日：2008-07-30

申请号：EP06817200.6

申请日：2006-10-17

Applicant: Wardlaw Partners, LP ,  Levine, Robert Aaron ,  Wardlaw, Stephen Clark

Inventor： WARDLAW, Stephen C.

IPC: G06M11/00 ,  G01N33/49

CPC classification number: G01N15/1463 ,  B01L3/5027 ,  B01L3/508 ,  B01L2200/0684 ,  B01L2300/0822 ,  G01N2015/0073 ,  G01N2015/008 ,  G01N2015/0084 ,  G01N2015/1486 ,  G02B21/34 ,  Y10T436/101666

Abstract: A method and an apparatus for enumerating one or more specific elements within a biologic fluid sample are provided. An embodiment of the method includes the steps of: a) providing a chamber formed between a first planar member that is transparent and a second planar member, which members are separated from one another by a substantially uniform height; b) introducing the biologic fluid sample into the chamber, wherein the chamber height is sized such that the sample extends between the first and second members, and sized relative to the specific elements within the sample such that the specific elements non-uniformly distribute within the sample upon introduction into the chamber; c) examining substantially all of the sample within the chamber and enumerating all of at least one of the specific elements; d) determining the volume of sample contained within the chamber; and e) determining the number of the at least one of the specific elements per unit volume.

公开(公告)号：EP0877094B1

公开(公告)日：2006-09-27

申请号：EP98107881.9

申请日：1998-04-29

Applicant: Levine, Robert Aaron ,  Wardlaw, Stephen Clark

Inventor： Levine, Robert Aaron ,  Wardlaw, Stephen Clark

IPC: C12Q1/68

CPC classification number: C12Q1/6851 ,  C12Q1/6834 ,  C12Q1/6846

公开(公告)号：EP1564540A2

公开(公告)日：2005-08-17

申请号：EP05011231.7

申请日：1998-03-10

Applicant: Wardlaw, Stephen Clark

Inventor： Wardlaw, Stephen Clark

IPC: G01N15/04 ,  G01N15/05

CPC classification number: B04B5/02 ,  B04B5/0407 ,  B04B13/00 ,  G01N15/042 ,  G01N15/05 ,  G01N2015/047

Abstract: A method for determining the thickness of a gravimetrically compacted layer of a target component in an anticoagulated whole blood sample which sample is contained in a transparent tube (9), said method comprising the steps of:

a) placing the tube on a centrifuge platen (3);
b) spinning the platen so as to commence gravimetric compaction of the target component into a discernable target component layer in the tube;
c) performing a thickness reading of the target component layer formed between adjacent interfaces in the anticoagulated whole blood sample while the tube is being centrifuged on the platen; and
d) recording said layer thickness reading.

Abstract translation: 一种用于确定抗凝血全血样品中的样品的重量分压层的厚度的方法，该样品包含在透明管（9）中，所述方法包括以下步骤：a）将管置于离心机压板 3）; b）旋转压板以开始将目标组分重量压缩成管中可辨别的目标组分层; c）在所述管在所述台板上离心时，对所述抗凝全血样品中的相邻界面之间形成的所述目标成分层进行厚度读取; 和d）记录所述层厚度读数。

公开(公告)号：EP1063974B1

公开(公告)日：2004-12-01

申请号：EP99907152.5

申请日：1999-02-19

Applicant: Wardlaw, Stephen Clark ,  Levine, Robert Aaron ,  Wardlaw Partners LP

Inventor： Wardlaw, Stephen C

IPC: A61K9/44 ,  G01N15/14 ,  G06K9/00

CPC classification number: G01N33/5002 ,  G01N15/1468 ,  G01N15/1475 ,  G01N21/03 ,  G01N2015/0076 ,  G01N2015/0092 ,  G01N2015/1472 ,  G01N2015/1497 ,  Y10S435/96 ,  Y10S436/80 ,  Y10S436/805 ,  Y10S436/807 ,  Y10S436/808 ,  Y10S436/809 ,  Y10T436/13 ,  Y10T436/25375

Abstract: Formed constituents of a quiescent anticoagulated whole blood sample are optically of visually analyzed in a sample chamber (14) which has a varying through plane thickness due to convergent opposing sample chamber walls (4, 8). At least one of the convergent walls of the chamber is transparent so that the blood sample constituents can be observed. The chamber's varying thickness produces a first lesser thickness region (A) in the chamber wherein a quiescent monolayer of red blood cells in the sample will reside after the sample is introduced into and fills the chamber. Larger formed constituents such as white blood cells in the sample are unable to enter the aforesaid lesser thickness region of the chamber. The red cells which reside in the greater thickness regions (B, C) will agglomerate to form rouleaux and lacunae. The exact thickness of the chamber at any particular location in the chamber can be predetermined, or can be determined in situ as the sample is being analysed. By admixing certain dyes with the blood sample, various characteristics and other information can be derived from the various formed constituents in the sample by means of a scanning instrument (54) which is able to measure various color and other signals emitted from the sample at various locations (1, 3, 5) within the chamber, or by means of visual examination of the sample in the chamber. The thickness of the lacunae areas of the sample can be calculated by the instrument as a function of signal emission strength from the dyes or stains. The emissions can be the result of sample fluorescence or can be the result of signal density through the sample. Particle volumes can be measured as a function or signal emission suppression caused by the particles. Erythrocyte sedimentation rates (ESR) can also be derived from a blood sample disposed in the sampling chamber.

公开(公告)号：EP1063513A3

公开(公告)日：2002-01-30

申请号：EP00113287.7

申请日：2000-06-21

Applicant: Wardlaw, Stephen Clark ,  Levine, Robert Aaron

Inventor： Wardlaw,Stephen C.

IPC: G01N15/04

CPC classification number: G01N15/042 ,  G01N15/05 ,  G01N2015/045

Abstract: Centrifuged material layer volumes are measured and quantified during centrifugation of the material layers contained in a sample tube in a centrifuge assembly, which sample tube is disposed on a centrifuge platen. The material layers in the sample tube are periodically illuminated during centrifugation by a pulsed light source which differentially excites one or more fluorescent dyes or stains which are admixed with the sample being analyzed. This kinetic procedure is particularly useful in performing differential blood cell and platelet counts. A fluorscent target reference device is positioned on the centrifuge platen along with a detectable platen position sensor. The centrifuge assembly includes a processor controller which receives information from the platen position sensor, and from the target reference device, and which controls operation of the light source.

公开(公告)号：EP1063515A3

公开(公告)日：2001-05-16

申请号：EP00113376.8

申请日：2000-06-23

Applicant: Wardlaw, Stephen Clark ,  Levine, Robert Aaron

Inventor： Wardlaw, Stephen C.

IPC: G01N15/05 ,  G01N15/04

CPC classification number: G01N15/042 ,  G01N15/05 ,  Y10T436/25375

Abstract: A method for determining the sedimentation rate of erythrocytes (ESR) comprises the steps of placing an anticoagulated sample of whole blood in a transparent capillary tube and subjecting the blood sample and the tube to centrifugation. The position of the erythrocyte/plasma interface in the blood sample is determined at known time intervals during centrifugation of the blood sample. A point during centrifugation wherein the position of the erythrocyte/plasma interface becomes non-linear relative to elapsed centrifugation time is determined; and the slope of successive non-linear interface positions which are observed at subsequent elapsed centrifugation times occurring between the aforesaid point, to the time of substantial completion of centrifugation of the sample, is calculated. A value which reflects the sedimentation rate of the sample, if the sedimentation rate measurement were performed under ambient gravity conditions, can be derived from the calculated slope and the Y intercept of the calculated slope, thereby arriving at a conventional gravity sedimentation rate value from the erythrocyte/plasma interface positions determined during centrifugation of the blood sample.

公开(公告)号：EP1062507A1

公开(公告)日：2000-12-27

申请号：EP99909542.5

申请日：1999-02-22

Applicant: Wardlaw, Stephen Clark ,  Levine, Robert Aaron ,  Wardlaw Partners LP ,  Becton Dickinson and Company

Inventor： WARDLAW, Stephen, C. ,  LEVINE, Robert, A. ,  RODRIGUEZ, Rodilfo, R.

IPC: G01N33/48

CPC classification number: G01N15/1475 ,  G01N33/5094 ,  G01N2015/0076 ,  G01N2015/0092 ,  G01N2015/1472 ,  G01N2015/1497 ,  Y10T436/10 ,  Y10T436/101666

Abstract: Target nucleated cells, and target cells containing remanant ribosomal material, which are present in a quiescent anticoagulated whole blood sample are optically detected, enumerated, and analyzed in a sample chamber (14) that has a varying through plane thickness due to convergent opposing sample chamber walls. At least one of the convergent walls (8) of the chamber is transparent so that the blood sample can be observed. The chamber's varying thickness produces a first lesser thickness region (A) in the chamber wherein individual red cells (32) and quiescent monolayers (31) of red cells in the sample will reside after the sample is introduced into and fills the chamber. Larger formed constituents such as white blood cells (34) and nucleated red blood cells present in the sample will reside in greater thickness regions (B) of the chamber, and non-nucleated red cells which reside in such greater thickness regions will agglomerate to form rouleaux (33). By admixing fluorescent dyes with the blood sample, target cells in the sample can be enumerated and differentiated by means of a scanning instrument (54) which is able to measure different wave length color signals emitted from the target cells in the sample, and differentiate the target cells one from another by reason of the nature of the emitted color signals.

公开(公告)号：EP0844482A3

公开(公告)日：1999-12-29

申请号：EP97120380.7

申请日：1997-11-20

Applicant: Wardlaw, Stephen Clark ,  Levine, Robert Aaron

Inventor： Wardlaw, Stephen Clark ,  Levine, Robert Aaron

IPC: G01N33/50 ,  G01N15/04 ,  G01N15/05

CPC classification number: G01N33/50 ,  G01N15/05

Abstract: A sample of anticoagulated mammalian whole blood is admixed with a combination of reagents that will reduce the natural repulsive forces that mammalian erythrocytes have for each other. The treated blood sample is then centrifuged in a tube containing a buffy coat expanding insert thereby physically expanding the axial extent of the blood sample s buffy coat components in the tube. By reducing the tendency of the erythrocytes to repel each other, a clearer demarcation between the erythrocytes and the buffy coat can be achieved. The effect of agglutinating reagents which may have been added to the blood sample will also be enhanced. The aforesaid procedure and reagents make it possible for the first time to accurately analyze a centrifuged sample of anticoagulated bovine whole blood and obtain hematocrit and differential white cell counts therefrom. Additionally, human blood samples which otherwise exhibit a streaming tendency can also be accurately analyzed by the addition of a combination of the appropriate erythrocyte repulsion-reducing reagents along with agglutinating reagents.

公开(公告)号：EP0919812A2

公开(公告)日：1999-06-02

申请号：EP98122238.3

申请日：1998-11-23

Applicant: Wardlaw, Stephen Clark ,  Levine, Robert Aaron

Inventor： Rimm, David L. ,  Wardlaw, Stephen C. ,  Levine, Robert A. ,  Fiedler, Paul

IPC: G01N33/574 ,  G01N15/04 ,  B01L3/14

CPC classification number: G01N15/042 ,  G01N33/56972 ,  G01N33/57484 ,  G01N2015/045

Abstract: A method for analyzing blood enables one to isolate, detect, enumerate and confirm under magnification the presence or absence of target cancer cells and/or hematologic progenitor cells which are known to circulate in blood. The analysis is performed in a sample of centrifuged anticoagulated whole blood. The analysis involves both morphometric and epitopic examination of the blood sample while the blood sample is disposed in a centrifuged blood sampling tube. The epitopic analysis of the presence or absence of cancer cells relies on the detection of epitopes which are known to present only on cancer cells; and the epitopic analysis of the presence or absence of hematologic progenitor cells relies on the detection of epitopes which are known to present only on hematologic progenitor cells. The targeted epitopes on the target cell types are epitopes which are also known to be absent on normal circulating blood cells; and the target cancer cell epitopes are epitopes which are known to be absent on target hematologic progenitor cells. Fluorophors with distinct emissions are coupled with antibodies which are directed against the targeted epitopes. The morphometric analysis is performed by staining the cells in the blood sample with an intracellular stain such as acridine orange which highlights the intracellular cell structure. Both the morphometric and epitopic analyses are preferably performed at or near the platelet layer of the expanded buffy coat in the centrifuged blood sample. The morphometric analysis and/or the epitopic analysis may be performed under magnification both visually and/or photometrically.

Abstract translation: 一种用于分析血液的方法允许一个分离，检测，枚举和在放大下确认是已知的在血液中循环靶癌细胞和/或血液祖细胞的存在或不存在。 该分析的离心抗凝全血样本中进行。 而血样品在离心血液采样管设置在所述分析涉及血样品的两个形态和表位的检查。 癌细胞的存在或不存在的表位分析依赖于所述检测是已知的，以只存在于肿瘤细胞的表位的; 和血液祖细胞的存在或不存在的表位分析依赖于所述检测是已知的，以只存在于血液祖细胞表位。 在目标细胞类型的靶向的表位，因此其已知是对正常的循环血液细胞中不存在的表位; 和靶癌细胞表位是其已知是对靶血液祖细胞中不存在的表位。 具有不同的排放量的荧光团耦合与作为针对靶向表位的抗体。 的形态测定分析进行通过在细胞内染色与染色血液样品中的细胞：例如吖啶橙其中突出胞内细胞结构。 两者形态和表位分析是在或接近离心血样中的所述膨胀的血沉棕黄层的血小板层优选地执行。 的形态测定分析和/或表位分析可以在放大下两个视觉上和/或光度计来执行。