公开(公告)号：US6067463A

公开(公告)日：2000-05-23

申请号：US225430

申请日：1999-01-05

申请人： Tzyy-Wen Jeng ,  Shu-Jen Yeh ,  John M. Lindberg ,  Joseph Larry Pezzaniti ,  Omar S. Khalil ,  Gary M. Oosta ,  Charles F. Hanna ,  Arnold F. Stalder ,  Ete Z. Szuts

发明人： Tzyy-Wen Jeng ,  Shu-Jen Yeh ,  John M. Lindberg ,  Joseph Larry Pezzaniti ,  Omar S. Khalil ,  Gary M. Oosta ,  Charles F. Hanna ,  Arnold F. Stalder ,  Ete Z. Szuts

IPC分类号： G01N21/35 ,  A61B5/00 ,  A61B5/145 ,  A61B5/1455

CPC分类号： A61B5/1455 ,  A61B5/14532

摘要： A method and apparatus for measuring the concentration of an analyte of interest, e.g. glucose, in blood non-invasively, i.e., without penetrating the skin or obtaining a biological sample from the body of a patient. The method and apparatus uses a plurality of measurement channels with appropriate wavelengths of interest to control variations of signal and to separate the contribution of the analyte of interest from those of interfering compounds. The method and apparatus of this invention can also be adapted to allow a portion of a body part to be engorged with blood to bring about greater accuracy in optical measurements. In the method of this invention, at least two similar, but not identical, measurements are made concurrently. For example, at least two measurements can be made with similar, but not identical, wavelengths of electromagnetic radiation. The two wavelengths should not be overlapping to allow maximum non-identity. By making measurements concurrently, each measurement channel in the system experiences variations as they occur substantially simultaneously in all channels. By selecting one of the channels as a reference channel and by normalizing the optical measurements of the other channels to this reference channel, the variations common to all channels are eliminated. Removing these common variations from the optical measurements by normalization, such as by calculating ratios of the measurement of each of the measuring channels to that of the reference channel, will allow the actual changes of the signal for a specific analyte of interest to be measured.

摘要翻译： 用于测量所关注的分析物的浓度的方法和装置，例如， 葡萄糖在血液中非侵入性地，即不渗透皮肤或从患者的身体获得生物样品。 该方法和装置使用具有适当的感兴趣波长的多个测量通道来控制信号的变化并分离感兴趣分析物对干扰化合物的贡献。 本发明的方法和装置还可以适于允许身体部分的一部分被血液吸收以在光学测量中带来更高的精度。 在本发明的方法中，同时进行至少两个相似但不相同的测量。 例如，可以用类似但不相同的电磁辐射波长进行至少两次测量。 两个波长不应重叠，以允许最大的非身份。 通过同时进行测量，系统中的每个测量通道在所有通道中基本上同时发生变化。 通过选择一个通道作为参考通道，并将其他通道的光学测量标准化到该参考通道，可以消除所有通道共用的变化。 通过归一化从光学测量中去除这些常见的变化，例如通过计算每个测量通道的测量与参考通道的测量的比率，将允许测量特定分析物的信号的实际变化。

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：US06662030B2

公开(公告)日：2003-12-09

申请号：US09080470

申请日：1998-05-18

申请人： Omar S. Khalil ,  Frits F. M. de Mul ,  Charles F. Hanna ,  Arnold F. Stalder ,  Shu-jen Yeh ,  Xiaomao Wu ,  Michael G. Lowery ,  Johannes S. Kanger ,  René A. Bolt

发明人： Omar S. Khalil ,  Frits F. M. de Mul ,  Charles F. Hanna ,  Arnold F. Stalder ,  Shu-jen Yeh ,  Xiaomao Wu ,  Michael G. Lowery ,  Johannes S. Kanger ,  René A. Bolt

IPC分类号： A61B500

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

摘要： Devices and methods for non-invasively measuring at least one parameter of a sample, such as the presence or concentration of an analyte, in a body part wherein the temperature is controlled. The present invention measures light that is reflected, scattered, absorbed, or emitted by the sample from an average sampling depth, dav, that is confined within a temperature controlled region in the tissue. This average sampling depth is preferably less than 2 mm, and more preferably less than 1 mm. Confining the sampling depth into the tissue is achieved by appropriate selection of the separation between the source and the detector and the illumination wavelengths. In another aspect, the invention involves a method and apparatus for non-invasively measuring at least one parameter of a body part with temperature stepping. In another aspect, the invention involves a method and apparatus for non-invasively measuring at least one parameter of a body part with temperature modulation. In another aspect, the invention provides an improved method of measuring at least one parameter of a tissue sample comprising the steps of: (a) lowering the temperature of said tissue sample to a temperature that is lower than the normal physiological temperature of the body; and (b) determining at least one optical property of said tissue sample.

摘要翻译： 用于非侵入性地测量样品的至少一个参数（例如分析物的存在或浓度）在其中控制温度的身体部位中的装置和方法。 本发明测量被从组织中的温度控制区域内限定的平均采样深度dav反射，散射，吸收或发射的光。 该平均采样深度优选小于2mm，更优选小于1mm。 通过适当选择源和检测器之间的距离以及照明波长来实现将采样深度限制在组织中。 在另一方面，本发明涉及一种用于非侵入性地测量具有温度步进的身体部位的至少一个参数的方法和装置。 在另一方面，本发明涉及一种用于通过温度调制非侵入性地测量身体部位的至少一个参数的方法和装置。 另一方面，本发明提供了一种测量组织样本的至少一个参数的改进方法，包括以下步骤：（a）将所述组织样本的温度降低到低于身体的正常生理温度的温度; 和（b）确定所述组织样品的至少一种光学性质。

公开(公告)号：US06630673B2

公开(公告)日：2003-10-07

申请号：US10036826

申请日：2001-12-21

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： G01N2147

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.

公开(公告)号：US06241663B1

公开(公告)日：2001-06-05

申请号：US09302207

申请日：1999-04-29

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： A61B500

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 that comprises at least one thermally controllable optical measuring element that comes into contact with the surface of the biological sample; (2) applying an inert, thermally conductive, optically transparent coupling agent to the at least one optical measuring element or to the surface of the biological sample or both so that the coupling agent will be disposed at the interface of the surface of the biological sample and the at least one 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. A coupling agent suitable for this invention must have several properties to enable it to help decrease measurement variation, especially drift. One of the most important properties is sufficiently high optical stability that the optical properties of the coupling agent do not change even during prolonged experiments, such as oral glucose tolerance tests. Secondly, the coupling agent should have sufficiently high thermal conductivity to allow fast, efficient heat transfer between the optical probe and the biological sample. Third, the coupling agent should have sufficiently high viscosity to prevent it from migrating from the measurement area. Yet, it should also have sufficiently low viscosity to allow sufficient contact between the optical probe and the biological sample and to permeate into any small pockets between the probe and the biological sample that would otherwise be filled with the air. Fourth, the coupling agent should be inert. Material from the coupling agent should not diffuse into the biological sample and material from the biological sample should not diffuse into the coupling agent.

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。