公开(公告)号：USD332834S

公开(公告)日：1993-01-26

申请号：US570565

申请日：1990-08-21

申请人： Charles F. Hanna ,  Thomas F. Zurek ,  Omar S. Khalil

设计人： Charles F. Hanna ,  Thomas F. Zurek ,  Omar S. Khalil

公开(公告)号：US5006309A

公开(公告)日：1991-04-09

申请号：US184726

申请日：1988-04-22

申请人： Omar S. Khalil ,  Charles F. Hanna ,  Thomas F. Zurek ,  Denise A. Grigalauski

发明人： Omar S. Khalil ,  Charles F. Hanna ,  Thomas F. Zurek ,  Denise A. Grigalauski

IPC分类号： B01L3/00 ,  G01N33/543

CPC分类号： G01N33/54366 ,  B01L3/5023 ,  B01L2200/027 ,  B01L2300/0809 ,  B01L2400/0406 ,  B01L2400/049 ,  Y10T436/255 ,  Y10T436/2575

摘要： A disposable device suitable for performing automated solid-state diagnostic assays which employs microparticles to complex an analyte and where the microparticle complex becomes retained and immobilized on a fibrous matrix such that the presence of analyte on the microparticles can be detected by an optical device. A device is disclosed having a shallow sample well for receiving a sample and reagents for forming a reaction mixture, a read well having (a) an entrance port and wash receiving structure for receiving a quantity of sample and assay reagents, (b) a fibrous matrix for retaining and immobilizing microparticle/analyte complexes for detection, the fibrous matrix positioned below the wash receiving structure, and having an average spatial separation of fibers greater than the average diameter of the microparticles and (c) a structure below the fibrous matrix for assisting the flow of sample and assay reagents through the fibrous matrix, such as an absorbent material or vacuum below the fibrous matrix and a passage means communicating between the shallow sample well and the read well where the sample and reaction mixtures can be transferred and washed from the shallow sample well into the read well without being contacted by any apparatus.

摘要翻译： 一种适用于执行自动化固态诊断测定的一次性装置，其使用微粒来复合分析物，并且其中微粒复合物保留并固定在纤维基质上，使得微粒上的分析物的存在可以通过光学装置检测。 公开了一种装置，其具有用于接收样品的浅样品阱和用于形成反应混合物的试剂，读数井具有（a）用于接收一定量的样品和测定试剂的入口和洗涤接收结构，（b）纤维 用于保持和固定用于检测的微粒/分析物复合物的基质，所述纤维基质位于洗涤接收结构下方，并且具有大于微粒平均直径的纤维的平均空间分离，和（c）纤维基质下面的结构用于辅助 通过纤维基质（例如吸收材料或纤维基质下方的真空）的样品和测定试剂的流动以及在浅样品阱和读数井之间连通的通道装置，其中样品和反应混合物可以从 浅样品很好地进入读取井，而不被任何装置接触。

公开(公告)号：US5244630A

公开(公告)日：1993-09-14

申请号：US425651

申请日：1989-10-23

申请人： Omar S. Khalil ,  Charles F. Hanna ,  Denise G. Huff ,  Thomas F. Zurek

发明人： Omar S. Khalil ,  Charles F. Hanna ,  Denise G. Huff ,  Thomas F. Zurek

IPC分类号： B01L3/00 ,  C12M1/34 ,  G01N21/78 ,  G01N33/543 ,  G01N33/576 ,  G01N33/94 ,  G01N35/02 ,  G01N35/10

CPC分类号： B01L3/50255 ,  G01N33/54313 ,  G01N33/54366 ,  G01N33/5762 ,  G01N33/94 ,  G01N35/1002 ,  B01L2300/069 ,  B01L2300/0829 ,  B01L2400/0406 ,  Y10S435/805 ,  Y10T436/255 ,  Y10T436/2575

摘要： A disposable device suitable for performing automated solid-phase diagnostic assays which employs microparticles to complex an analyte and where the microparticle complex becomes retained and immobilized on a fibrous matrix such that the presence of analyte on the microparticles can be detached by optical means. A device is disclosed having a plurality of well pairs comprising a sample well for receiving a sample and reagents for forming a reaction mixture, a read well comprising (a) an entrance port and holder for receiving and holding a quantity of sample and assay reagents, (b) a fibrous matrix for retaining and immobilizing microparticle/analyte complexes for detection, said fibrous matrix positioned below said holder, and having an average spatial separation of fibers greater than the average diameter of said microparticles, (c) absorbent material positioned below said fibrous matrix for assisting the flow of sample and assay reagents through said fibrous matrix, (d) walls or ribs for creating a substantially light-tight real surrounding the wells, (e) a vent for venting air entrapped in the absorbent material and which is displaced by fluids absorbed therein, and (f) a passage between the sample well and the read well whereby sample and reaction mixtures can be transferred and washed from said sample well into said read well without being contacted by any apparatus.

摘要翻译： 一种适用于执行自动化固相诊断测定的一次性装置，其使用微粒来复合分析物，并且其中微粒复合物保留并固定在纤维基质上，使得微粒上的分析物的存在可以通过光学方式分离。 公开了一种具有多个阱对的装置，其包括用于接收样品的样品阱和用于形成反应混合物的试剂，读数井包括（a）用于接收和保持一定量样品和测定试剂的入口和保持器， （b）用于保持和固定用于检测的微粒/分析物复合物的纤维基质，所述纤维基质位于所述保持器下方，并且具有大于所述微粒平均直径的纤维的平均空间分离，（c）位于所述 用于辅助样品和测定试剂通过所述纤维基质流动的纤维基质，（d）用于产生围绕所述孔的基本上不透光的真空的壁或肋，（e）用于排出被捕获在吸收材料中的空气的通风口， 被吸收在其中的流体所取代，和（f）样品井和读数井之间的通道，从而可以将样品和反应混合物转移并洗涤 在不用任何设备接触的情况下，将样品良好地称入所述读取孔中。

公开(公告)号：US5198368A

公开(公告)日：1993-03-30

申请号：US643596

申请日：1991-01-18

申请人： Omar S. Khalil ,  Charles F. Hanna ,  Thomas F. Zurek

发明人： Omar S. Khalil ,  Charles F. Hanna ,  Thomas F. Zurek

IPC分类号： B01L3/00 ,  G01N33/543

CPC分类号： B01L3/5023 ,  G01N33/54313 ,  G01N33/54366 ,  B01L2200/027 ,  B01L2300/0809 ,  B01L2400/0406 ,  Y10S435/81 ,  Y10S436/805 ,  Y10S436/807 ,  Y10S436/809 ,  Y10S436/81 ,  Y10T436/255 ,  Y10T436/2575

摘要： A method for performing a microparticle diagnostic assay in a device having a shallow sample well for receiving a sample and reagents for forming a reaction mixture, a read well positioned adjacent to said sample well and separated from said sample well by a wall which is constructed and arranged such that when wash fluid is injected into said sample well, sample and reaction mixtures are washed from said shallow sample well, over the wall and into said read well. The steps of the method comprise forming microparticle analyte complexes in said shallow sample well; washing said microparticle analyte complexes from said shallow sample well over the wall and into said read well where a fibrous matrix retains and immobilizes said microparticle analyte complexes; adding to said read well an indicator substance capable of forming an assay signal when said microparticle analyte complexes are present; and detecting said assay signal produced by said indicator substance.

摘要翻译： 一种用于在具有用于接收样品的浅样品井和用于形成反应混合物的试剂的装置中进行微粒诊断测定的方法，与所述样品阱相邻定位并与所述样品阱分离的读取井通过构建和 排列成使得当将洗涤液注入所述样品孔中时，将样品和反应混合物从所述浅样品井，壁上和所述读取孔中洗涤。 该方法的步骤包括在所述浅样品阱中形成微粒分析物复合物; 从所述浅样品中将所述微粒分析物复合物在所述壁上清洗并进入所述读取孔，其中纤维基质保留并固定所述微粒分析物复合物; 当所述微粒分析物复合物存在时，向所述读取孔中加入能够形成测定信号的指示物质; 以及检测由所述指示物质产生的所述测定信号。

公开(公告)号：US5089424A

公开(公告)日：1992-02-18

申请号：US425643

申请日：1989-10-23

申请人： Omar S. Khalil ,  Thomas F. Zurek ,  Kevin R. Genger ,  Curtis J. Pepe ,  Yi-Her Jou ,  Stephen M. Cotter

发明人： Omar S. Khalil ,  Thomas F. Zurek ,  Kevin R. Genger ,  Curtis J. Pepe ,  Yi-Her Jou ,  Stephen M. Cotter

IPC分类号： G01N21/76 ,  G01N33/52 ,  G01N33/543 ,  G01N33/576

CPC分类号： G01N33/54346 ,  G01N33/521 ,  G01N33/525 ,  G01N33/54366 ,  G01N33/54386 ,  G01N33/5764

摘要： Apparatus and method for performing a chemiluminescence assay involving the immobilization of a chemiluminescent reaction complex to a solid, porous element. The solid, porous element is preferably treated to provide an immobilizing interaction with the chemiluminescent reaction complex wherein the chemiluminescent reaction complex is thereby immobilized to the solid, porous element. The activating and reading of the chemiluminescent reaction are separately performed by evenly distributing a concentrated chemiluminescent activating solution to form a puddle on the surface of the porous element to which the chemiluminescent reaction complex is immobilized.

摘要翻译： 用于进行化学发光测定的装置和方法，涉及将化学发光反应复合物固定在固体多孔元件上。 优选处理固体多孔元件以提供与化学发光反应复合物的固定相互作用，其中化学发光反应复合物由此固定在固体多孔元件上。 化学发光反应的激活和读取分别通过均匀分布浓缩的化学发光活化溶液在化学发光反应复合物固定的多孔元件的表面上形成一个水坑。

公开(公告)号：US06662031B1

公开(公告)日：2003-12-09

申请号：US09566415

申请日：2000-05-08

申请人： Omar S. Khalil ,  Xiaomao Wu ,  Shu-jen Yeh ,  Charles F. Hanna ,  Stanislaw Kantor ,  Tzyy-Wen Jeng

发明人： Omar S. Khalil ,  Xiaomao Wu ,  Shu-jen Yeh ,  Charles F. Hanna ,  Stanislaw Kantor ,  Tzyy-Wen Jeng

IPC分类号： A61B500

CPC分类号： G01N21/4795 ,  A61B5/0059 ,  A61B5/14535 ,  A61B5/14546 ,  A61B5/1455 ,  A61B5/1491 ,  A61B5/6824 ,  A61B2562/0233 ,  A61B2562/0242 ,  A61B2562/043

摘要： A method for the determination of hemoglobin and hematocrit by means of an apparatus that is capable of controlling the temperature of a defined subcutaneous volume of human skin. The method involves a calculation of hemoglobin concentration and hematocrit value that takes into consideration the values of optical parameters of the sample at various pre-set temperatures. The apparatus and method employ steady state optical measurements of samples, such as, for example, human tissue, by means of a reflectance tissue photometer and localized control of the temperature of the sample. According to the method of this invention, an optical signal from a defined subcutaneous volume of human skin is measured as the temperature of this volume is controlled. The method and apparatus of this invention allow determination of hemoglobin concentration and hematocrit value non-invasively in a population of subjects having different skin colors by means of steady state reflectance measurements. The method of this invention for determination of hemoglobin concentration and hematocrit value is useful for monitoring patients, testing at the point of care, and screening for anemia. In contrast to other attempts in the prior art that rely on signals of cardiac pulses, the method of this invention has the advantage for the determination of analytes in weak cardiac pulse situations, such as, for example, in elderly patients.

摘要翻译： 用于通过能够控制人皮肤的规定的皮下体积的温度的装置来测定血红蛋白和血细胞比容的方法。 该方法涉及在各种预设温度下考虑样品的光学参数的值的血红蛋白浓度和血细胞比容值的计算。 该装置和方法利用反射组织光度计对样品（例如人体组织）进行稳态光学测量并且对样品的温度进行局部控制。 根据本发明的方法，当控制该体积的温度时，测量来自人体皮肤的确定的皮下体积的光学信号。 本发明的方法和装置允许通过稳态反射测量在具有不同皮肤颜色的受试者群体中非侵入性地测定血红蛋白浓度和血细胞比容值。 用于测定血红蛋白浓度和血细胞比容值的本发明的方法对于监测患者，在护理点进行测试和筛查贫血是有用的。 与依靠心脏脉冲信号的现有技术的其他尝试相反，本发明的方法具有测定弱心脏脉搏情况下的分析物的优点，例如老年患者。

公开(公告)号：US06654620B2

公开(公告)日：2003-11-25

申请号：US09835705

申请日：2001-04-16

申请人： Xiaomao Wu ,  Omar S. Khalil ,  Tzyy-Wen Jeng ,  Shu-Jen Yeh ,  Charles F. Hanna

发明人： Xiaomao Wu ,  Omar S. Khalil ,  Tzyy-Wen Jeng ,  Shu-Jen Yeh ,  Charles F. Hanna

IPC分类号： A61B550

CPC分类号： G01N21/4795 ,  A61B5/14532 ,  A61B5/14546 ,  A61B5/1455 ,  A61B5/1491 ,  A61B5/6824 ,  A61B2562/0233 ,  A61B2562/0242 ,  A61B2562/043

摘要： A method for determining the concentration of an analyte in a biological sample comprising the steps of: (1) providing an optical measuring instrument comprising a thermally controllable optical measuring element that comes into contact with the surface of the biological sample; (2) applying a coupling agent to the optical measuring element or to the surface of the biological sample or to both so that the coupling agent will be disposed at the interface of the surface of the biological sample and the optical measuring element; (3) measuring optical properties of the biological sample by means of the optical measuring instrument; and (4) correlating the optical properties of the biological sample with the concentration of the analyte in the biological sample. The coupling agent can be selected from the group consisting of silicone oil, mineral oil, polyethylene glycols, and oils from natural resources.

摘要翻译： 一种用于确定生物样品中分析物浓度的方法，包括以下步骤：（1）提供光学测量仪器，其包括与生物样品表面接触的热可控光学测量元件;（2） 偶联剂到光学测量元件或生物样品的表面或两者以使得偶联剂将被布置在生物样品的表面与光学测量元件的界面处;（3）测量光学特性 通过光学测量仪器生物样品; 和（4）将生物样品的光学性质与生物样品中分析物的浓度相关联。偶联剂可以选自硅油，矿物油，聚乙二醇和来自天然资源的油。

公开(公告)号：US07167734B2

公开(公告)日：2007-01-23

申请号：US09834440

申请日：2001-04-13

申请人： Omar S. Khalil ,  Shu-jen Yeh ,  Stanislaw Kantor ,  Charles F. Hanna ,  Eric B. Shain

发明人： Omar S. Khalil ,  Shu-jen Yeh ,  Stanislaw Kantor ,  Charles F. Hanna ,  Eric B. Shain

IPC分类号： A61B5/00

CPC分类号： A61B5/1495 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/7264

摘要： A method for collecting optical data at two morphologically similar, substantially non-overlapping, and preferably adjacent, areas on the surface of a tissue, while the temperature in each area is being maintained or modulated according to a temperature program. The optical data obtained are inserted into a mathematical relationship, e.g., an algorithm, that can be used to predict a disease state (such as the diabetes mellitus disease state) or the concentration of an analyte for indicating a physical condition (such as blood glucose level). This invention can be used to differentiate between disease status, such as, for example, diabetic and non-diabetic. The method involves the generation of a calibration (or training) set that utilizes the relationship between optical signals emanating from the skin under different thermal stimuli and disease status, e.g., diabetic status, established clinically. This calibration set can be used to predict the disease state of other subjects. Structural changes, as well as circulatory changes, due to a disease state are determined at two morphologically similar, but substantially non-overlapping areas on the surface of human tissue, e.g., the skin of a forearm, with each area being subjected to different temperature modulation programs. In addition to determination of a disease state, this invention can also be used to determine the concentration of an analyte in the tissues. This invention also provides an apparatus for the determination of a disease state, such as diabetes, or concentration of an analyte, such as blood glucose level, by the method of this invention.

摘要翻译： 一种用于在组织表面上的两个形态上类似的，基本上不重叠的，优选相邻的区域收集光学数据的方法，同时根据温度程序维持或调节每个区域中的温度。 所获得的光学数据被插入到数学关系中，例如算法，其可用于预测疾病状态（例如糖尿病状态）或用于指示身体状况的分析物的浓度（例如血糖 水平）。 本发明可用于区分疾病状况，例如糖尿病和非糖尿病。 该方法包括产生校准（或训练）组，其利用在不同热刺激下发生的光学信号与疾病状态（例如临床确立的糖尿病状态）之间的关系。 该校准集可用于预测其他受试者的疾病状态。 由于疾病状态引起的结构变化以及循环变化在人组织表面上的两个形态相似但基本上非重叠的区域确定，例如前臂的皮肤，每个区域经受不同的温度 调制程序。 除了确定疾病状态之外，本发明还可以用于确定组织中分析物的浓度。 本发明还提供了一种用于通过本发明的方法测定疾病状态的装置，例如糖尿病或分析物的浓度，例如血糖水平。

公开(公告)号：US07043287B1

公开(公告)日：2006-05-09

申请号：US09419461

申请日：1999-10-15

申请人： Omar S. Khalil ,  Shu-Jen Yeh ,  Xiaomao Wu ,  Stanislaw Kantor ,  Charles F. Hanna ,  Tzyy-Wen Jeng

发明人： Omar S. Khalil ,  Shu-Jen Yeh ,  Xiaomao Wu ,  Stanislaw Kantor ,  Charles F. Hanna ,  Tzyy-Wen Jeng

IPC分类号： A61B5/00

CPC分类号： A61B5/14532 ,  A61B5/0059 ,  A61B5/1455 ,  A61B5/1495 ,  A61B2562/0242

摘要： Devices and methods for non-invasively measuring at least one parameter of a sample, such as the presence of a disease condition, progression of a disease state, presence of an analyte, or concentration of an analyte, in a biological sample, such as, for example, a body part. In these devices and methods, temperature is controlled and is varied between preset boundaries. The methods and devices measure light that is reflected, scattered, absorbed, or emitted by the sample from an average sampling depth, dav, that is confined within a region in the sample wherein temperature is controlled. According to the method of this invention, the sampling depth dav, in human tissue is modified by changing the temperature of the tissue. The sampling depth increases as the temperature is lowered below the body core temperature and decreases when the temperature is raised within or above the body core temperature. Changing the temperature at the measurement site changes the light penetration depth in tissue and hence dav. Change in light penetration in tissue as a function of temperature can be used to estimate the presence of a disease condition, progression of a disease state, presence of an analyte, or concentration of an analyte in a biological sample. According to the method of this invention, an optical measurement is performed on a biological sample at a first temperature. Then, when the optical measurement is repeated at a second temperature, light will penetrate into the biological sample to a depth that is different from the depth to which light penetrates at the first temperature by from about 5% to about 20%.

摘要翻译： 用于非侵入性地测量样品的至少一个参数的装置和方法，例如疾病状况的存在，疾病状态的进展，分析物的存在或分析物的浓度， 例如，身体部位。 在这些装置和方法中，控制温度并在预设的边界之间变化。 方法和装置测量由样品中的平均采样深度d> av is is is is is is is measure measure measure measure measure measure measure measure measure measure measure measure measure measure measure or or wherein wherein wherein wherein wherein wherein。。。。。。。。 根据本发明的方法，通过改变组织的温度来改变人体组织中的采样深度d>。。 当温度降低到体芯温度以下时，采样深度增加，当温度升高到体芯内温度以上时，采样深度降低。 改变测量部位的温度会改变组织中的光穿透深度，从而改变组织的光穿透深度。 可以使用作为温度的函数的组织中的光穿透的变化来估计生物样品中疾病状况，疾病状态的进展，分析物的存在或分析物的浓度的存在。 根据本发明的方法，在第一温度下对生物样品进行光学测量。 然后，当在第二温度下重复光学测量时，光将穿透生物样品至与第一温度下的光渗透约5％至约20％的深度不同的深度。

公开(公告)号：US06353226B1

公开(公告)日：2002-03-05

申请号：US09198094

申请日：1998-11-23

申请人： Omar S. Khalil ,  Xiaomao Wu ,  Johannes Sake Kanger ,  Rene′ Alexander Bolt ,  Shu-Jen Yeh ,  Charles F. Hanna ,  Frits Frans Maria de Mul

发明人： Omar S. Khalil ,  Xiaomao Wu ,  Johannes Sake Kanger ,  Rene′ Alexander Bolt ,  Shu-Jen Yeh ,  Charles F. Hanna ,  Frits Frans Maria de Mul

IPC分类号： A61B500

CPC分类号： A61B5/1455 ,  A61B5/14532 ,  A61B2562/0233 ,  A61B2562/0242 ,  A61B2562/043 ,  G01N21/49

摘要： Apparatus and method for non-invasively measuring at least one optical parameter of a sample, particularly a sample of tissue that comprises a plurality of layers. The at least one parameter can be used to determine the presence or concentration of an analyte of interest in the sample of tissue. The apparatus and method of the present invention (1) measure light that is substantially reflected, scattered, absorbed, or emitted from a shallower layer of the sample of tissue, (2) measure light that is substantially reflected, scattered, absorbed, or emitted from a deeper layer of the sample of tissue, (3) determine at least one optical parameter for each of these layers, and (4) account for the effect of the shallower layer on the at least one optical parameter of the deeper layer. Specifying the sampling depth allows determinations of the optical properties of a specific layer of the sample of the tissue, e.g., dermis, and decreases interference from other layers, e. g., stratum corneum and epidermis, in these determinations.

摘要翻译： 用于非侵入性地测量样品，特别是包括多个层的组织样品的至少一个光学参数的装置和方法。 可以使用至少一个参数来确定组织样品中感兴趣的分析物的存在或浓度。 本发明的装置和方法（1）测量从组织样本的较浅层基本反射，散射，吸收或发射的光，（2）测量基本上被反射，散射，吸收或发射的光 从组织样本的较深层，（3）确定这些层中的每一层的至少一个光学参数，以及（4）考虑较浅层对较深层的至少一个光学参数的影响。 指定采样深度允许确定组织样品（例如真皮）的特定层的光学性质，并减少来自其它层的干扰，例如， 在这些决定中，例如角质层和表皮。