公开(公告)号：EP1733226B1

公开(公告)日：2015-07-29

申请号：EP05732677.9

申请日：2005-04-07

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

Inventor： WARDLAW, Stephen, C.

IPC: G01N33/48

CPC classification number: G01N33/48764 ,  B01L3/5027 ,  B01L3/502738 ,  B01L2200/025 ,  B01L2200/12 ,  B01L2300/0877 ,  B01L2300/0887 ,  B01L2400/0406 ,  G01N1/2813 ,  G01N1/312 ,  G01N21/03 ,  G01N33/492 ,  G01N35/00009 ,  G01N2015/008 ,  G01N2015/1006 ,  G01N2015/1486 ,  G01N2021/0346 ,  G01N2021/0364 ,  Y10T436/101666 ,  Y10T436/25375

公开(公告)号：EP2320228A1

公开(公告)日：2011-05-11

申请号：EP10184460.3

申请日：1999-02-22

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

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

IPC: G01N33/48 ,  G01N15/05

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. (Drawing - Figure 3 )

公开(公告)号：EP1063515B1

公开(公告)日：2006-08-16

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

公开(公告)号：EP1079224A3

公开(公告)日：2004-01-02

申请号：EP00117717.9

申请日：2000-08-17

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

Inventor： Wardlaw, Stephen C.

IPC: G01N1/40 ,  G01N33/487 ,  G01N33/49 ,  G02B21/34 ,  B01L3/00 ,  G06K9/00 ,  G01N15/10

CPC classification number: B01L3/508 ,  G01N33/491 ,  G02B21/34 ,  Y10T436/25 ,  Y10T436/2575

Abstract: Formed constituents in an aqueous based fluid biologic material sample are separated from the aqueous constituent of the sample, and are concentrated in an examining instrument's focal plane where they can be examined under magnification. Examples of fluids that can be analyzed in this fashion include urine; cerebrospinal fluid; pleural fluid; ascites; fluids aspirated from cysts such as thyroid and breast cysts; cytologic specimens which have been placed in an aqueous fluid; platelet-rich plasma; and the like. The sample is placed in a chamber having a layer of a hydrophilic hydrogel covering a surface of the chamber. An opposite surface of the chamber is transparent, and may be formed by a microscope slide cover slip, or the like. The volume of hydrogel in the chamber is sufficient so that, when the hydrogel absorbs essentially all of the aqueous fraction of the sample, the hydrogel will expand and fill the chamber. The capture surface of the expanded hydrogel is preferably planar, and any formed constituents in the sample will be captured on the capture surface of the hydrogel layer, and will not be absorbed into the hydrogel. Formed constituents, such as: cells; bacteria; crystals; protozoa; ova; parasites; and the like, can be differentially highlighted by use of labeled antibodies, selective stains, or the like, so as to enable optical examination and differentiation of various formed constituents which may be in the sample. Formed constituents may be harvested from the capture surface of the expanded hydrogel layer for more detailed examination and analysis. The capture surface of the hydrogel may be provided with a plurality of beads for use in locating the capture surface with an optical scanning instrument, and for re-establishing previously scanned fields of view.

公开(公告)号：EP1063515A2

公开(公告)日：2000-12-27

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.

Abstract translation: 用于测定红细胞（ESR）沉降速率的方法包括以下步骤：将全血的抗凝样品放在透明的毛细管中，并对血液样品和管进行离心。 在血液样品离心过程中，以已知的时间间隔测定血液样品中红细胞/血浆界面的位置。 测定离心中的点，其中相对于经过的离心时间，红细胞/血浆界面的位置变得非线性; 并且计算在上述点到样品离心的基本完成时间之间发生的随后经过的离心时间观察到的连续非线性界面位置的斜率。 如果在环境重力条件下进行沉降速率测量，则反映样品的沉降速率的值可以从计算的斜率和计算斜率的Y截距得出，从而得到常规的重力沉降速率值 在血液样品离心过程中测定的红细胞/血浆界面位置。

公开(公告)号：EP0813086A3

公开(公告)日：1999-01-27

申请号：EP97108539.4

申请日：1997-05-27

Applicant: Levine, Robert Aaron ,  Wardlaw, Stephen Clark

Inventor： Levine, Robert Aaron ,  Wardlaw, Stephen Clark

IPC: G02B21/34

CPC classification number: B01L3/5021 ,  G01N33/491 ,  G01N2015/055 ,  G02B21/34 ,  Y10S435/81 ,  Y10S435/97 ,  Y10S436/805 ,  Y10S436/81

Abstract: Centrifuged anticoagulated blood samples are analyzed under magnification in a centrifuge tube containing a layer-elongating insert, which tube is placed on a calibrated slide. The slide includes a slot in which the tube is placed. A calibrated scale is disposed adjacent to the slot for use in measuring various blood sample parameters, such as hematocrit, platelet count, and the like. Anemia and/or low platelet counts are indicative of potentially serious complications of malaria. Their detection will prompt a physician to consider the liklihood of serious illness due to malaria. The presence or absence of blood-borne parasites can also be determined using the procedures of this invention. Thus the device allows a blood sample to be analyzed for malaria parasites, and also allows measurement of hematicrit and platelet counts. The scale can be presented in a normal image when a simple lens magnification, such as a magnifying glass, is used to view the tube and slide; and can also be presented in mirror image when compound lens magnification, such as a microscope, is used to view the tube and slide.

公开(公告)号：EP0844482A2

公开(公告)日：1998-05-27

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.

Abstract translation: 抗凝全哺乳动物血液样本中的溶液与试剂thatwill减少自然排斥力确实哺乳动物红细胞对彼此的组合。 将处理过的血液样品，然后在一个管含有血沉棕黄层膨胀插入件从而在物理上扩展在管中的血液样品@小号血沉棕黄层成分的轴向范围离心。 通过减少红细胞的倾向排斥海誓山盟，红细胞和血沉棕黄层之间更清晰的分界就可以实现。 其可具有被添加到血样凝集试剂的作用，从而会提高。 上述过程和试剂使人们有可能在第一次准确地设定分析离心抗凝牛全血样品，并从那里得到的血细胞比容和差别白细胞计数。 此外，否则显示出趋势流人类血液样品因此可以精确地设定通过加入非常久远凝集试剂适当红细胞排斥作用还原试剂的组合进行分析。

公开(公告)号：EP0557595A2

公开(公告)日：1993-09-01

申请号：EP92120505.0

申请日：1992-12-01

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

Inventor： Levine, Robert A. ,  Wardlaw, Stephen C. ,  Rodriguez, Rodolfo ,  Britz, Judith ,  Mercolino, Thomas J.

IPC: G01N33/543 ,  G01N33/58 ,  G01N33/538 ,  G01N33/68 ,  G01N33/569

CPC classification number: G01N33/5375 ,  G01N33/538 ,  Y10S436/829

Abstract: An improved assay of target components in a sample utilizes specific gravity-altering particles which are attached to the target components by specific antibodies. The attached specific gravity-altering particles are preferably liposomes which will buoy or sink the targets to a common level in the specimen sample when the latter has been centrifuged in a transparent tube. The liposomes can provide an accentuated and more pronounced indication of the presence of the targets in the sample due to their ability to contain many multiples of fluorescent or non-fluorescent dye molecules with minimal steric interference with the attached antibodies' binding ability.

Abstract translation: 样品中靶组分的改进测定利用通过特异性抗体连接到靶组分的比重改变颗粒。 附着的比重改变颗粒优选是脂质体，当将后者已经在透明管中离心时，其将目标浮标或沉降到样品样品中的共同水平。 脂质体可以提供样品中靶标存在的突出和更明显的指示，因为它们具有包含许多倍数的荧光或非荧光染料分子的能力，其具有与所附抗体结合能力的最小空间干扰。

公开(公告)号：EP0493838A1

公开(公告)日：1992-07-08

申请号：EP91122385.7

申请日：1991-12-30

Applicant: Levine, Robert Aaron ,  Wardlaw, Stephen Clark

Inventor： Levine, Robert Aaron ,  Wardlaw, Stephen Clark

IPC: G01N33/48 ,  B01L3/14 ,  A61B5/14

CPC classification number: G01N33/491 ,  B01L3/50215 ,  Y10T436/25375 ,  Y10T436/2575

Abstract: Constituent layers are harvested from a centrifuged multi-constituent material in an evacuated glass (2) or clear plastic tube which contains a float (6). When possibly contaminated materials, such as blood, are being tested, the use of an evacuated tube allows the measurements to be made without the technician being exposed to the blood. The tubes are large enough to hold approximately one ml of blood, and are filled with an inert gas at low pressure. The floats are formed with a through bore (7) into which cell bands to be harvested will settle during centrifugation. The cell bands (A-E) are stabilized by a layer of a flowable material which settles onto the plasma layer during centrifugation and forms a pellicle thereon. The cell layers to be harvested are aspirated from the float bore by means of a hypodermic needle (131) or cannula inserted into the tube and float bore.

Abstract translation: 在真空玻璃（2）中的离心多组分材料或含有浮子（6）的透明塑料管中收获成分层。 当可能被污染的材料（例如血液）被测试时，使用真空管允许在没有技术人员暴露于血液的情况下进行测量。 管足够大以容纳约1ml血液，并在低压下填充惰性气体。 浮子形成有通孔（7），待收获的细胞带在离心过程中将沉降。 细胞条带（A-E）通过可流动的材料层稳定，该层可在离心过程中沉降到等离子体层上，并在其上形成防护薄膜组件。 要通过皮下注射针（131）或插入管中的插管和浮子孔从浮子孔吸出要收获的细胞层。

公开(公告)号：EP0423706A3

公开(公告)日：1992-03-18

申请号：EP90119804.4

申请日：1990-10-16

Applicant: Levine, Robert Aaron ,  Wardlaw, Stephen Clark

Inventor： Levine, Robert A. ,  Wardlaw, Stephen C. ,  Manion, Kristen L.

IPC: B01L3/14 ,  G01N15/05 ,  G01N33/48 ,  A61B5/14

CPC classification number: B01L3/5021 ,  G01N15/05 ,  G01N33/491

Abstract: Blood constituents are separated by centrifugation in a transparent tube which contains a float for physically elongating certain of the constituents. The centrifuged sample in the tube is positioned on a layer measuring device with which red cell and buffy coat constituent band heights can be measured in ambient light. The buffy coat constituent measurements are made under optical magnification. The measuring device has a mathmatically derived red cell layer nomogram printed thereon, and a separate scale for measuring buffy coat constituent bands. Conversion tables are provided for converting the measured buffy coat constituent band lengths into constituent cell counts. The measuring device includes tube-engaging portions for properly positioning the tube during the measurements, and the red cell scale automatically compensates for the presence of the float and densification of red cells needed for proper banding.