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：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：US06615061B1

公开(公告)日：2003-09-02

申请号：US09366084

申请日：1999-08-03

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

摘要： A method and apparatus for the measurement of trans-cutaneous diffuse reflectance at a single sampling distance for determining the concentration of an analyte in a biological sample, such as, for example, human tissue. The determination of the concentration of the analyte has been found to depend on the sampling distance and reaches an optimal result at a defined sampling distance for a given analyte and a given sample. The method involves measuring the light re-emitted from the sample at a distance from a light introduction site and correlating the intensity of the re-emitted light to the concentration of an analyte. For a given sample, the distance between the light collection site and a light introduction site (i.e., the sampling distance) corresponds to the depth from the surface into the sample at which scattering and absorption events significantly affect the intensity of re-emitted light (i.e., the sampling depth). Prior knowledge about the sample determines the optimal sampling depth for performing a measurement for a specific analyte and the corresponding sampling distance needed to reach that optimal sampling depth. Optimization of the sampling distance, as well as the correlation relationship, can be established in a calibration procedure.

摘要翻译： 一种用于在单个采样距离处测量透皮漫反射率以确定生物样品（例如人体组织）中的分析物的浓度的方法和装置。 已经发现分析物浓度的确定取决于采样距离，并且在给定分析物和给定样品的定义的采样距离处达到最佳结果。 该方法包括测量从光引入位置一段距离处从样品再发射的光并将再发射的光的强度与分析物的浓度相关联。 对于给定的样品，光采集位置和光引入位点之间的距离（即采样距离）对应于从表面到样品的深度，其中散射和吸收事件显着影响再发射光的强度（ 即采样深度）。 关于样品的现有知识决定了对特定分析物进行测量的最佳采样深度以及达到该最佳采样深度所需的相应采样距离。 可以在校准过程中建立采样距离的优化以及相关关系。

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：US06526298B1

公开(公告)日：2003-02-25

申请号：US09693122

申请日：2000-10-20

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

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

IPC分类号： A61B500

CPC分类号： A61B5/1495 ,  A61B5/0059 ,  A61B5/14532 ,  A61B5/14546 ,  A61B5/1455 ,  A61B5/1491 ,  A61B5/6824 ,  A61B2562/0233 ,  A61B2562/0242 ,  A61B2562/043 ,  G01N21/4795

摘要： A method for the determination of concentrations of analytes, e.g., glucose, and other metabolites in human tissue, wherein the temperature of a defined cutaneous volume of tissue, e.g., human skin, is controlled. The method involves calculating the concentration of an analyte in the tissue by taking into consideration the values of optical parameters of a sample of tissue measured in the defined cutaneous volume of the tissue at various temperatures. The selection of the defined volume is a function of the sampling distance along the surface of the tissue, the wavelength of light used to illuminate the tissue, and the temperature in the defined volume of tissue, which is a function of the temperature at the surface of the tissue. In one embodiment of the method of this invention, an optical signal re-emitted from a defined cutaneous volume of the tissue is measured, as the temperature of this volume is maintained at a constant value. In another embodiment of the method of this invention, the temperature of the defined cutaneous volume of the tissue is varied within a defined physiological range to change the depth of penetration of light into the tissue, thereby achieving a depth profile for the optical signal. The method of this invention is useful for monitoring the concentrations of analytes in tissues, testing at the point of care, and screening for diseases, such as, for example, diabetes. The method of this invention utilizes changes in temperature and selection of wavelengths to define cutaneous volumes below the surface of the tissue, in which volumes the concentration of an analyte can be determined.

摘要翻译： 用于测定人组织中分析物（例如葡萄糖）和其它代谢物的浓度的方法，其中控制例如人皮肤的组织的定义的皮肤体积的温度。 该方法包括通过考虑在各种温度下在组织的定义的皮肤体积中测量的组织样品的光学参数的值来计算组织中分析物的浓度。 定义体积的选择是沿着组织表面的采样距离，用于照亮组织的光的波长和组织的限定体积中的温度的函数，其是表面温度的函数 的组织。 在本发明的方法的一个实施例中，当该体积的温度保持在恒定值时，测量从组织的规定皮肤体积重新发射的光学信号。 在本发明方法的另一实施例中，组织的限定皮肤体积的温度在规定的生理范围内变化，以改变光进入组织的深度，从而实现光信号的深度分布。 本发明的方法可用于监测组织中分析物的浓度，在护理点进行测试和筛选疾病，例如糖尿病。 本发明的方法利用温度的变化和波长的选择来限定组织表面以下的皮肤体积，其中可以确定分析物的浓度。