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1. 发明授权

US07043287B1 Method for modulating light penetration depth in tissue and diagnostic applications using same 有权
标题翻译：用于调节组织中的透光深度的方法和使用其的诊断应用
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。

2. 发明授权

US07167734B2 Method for optical measurements of tissue to determine disease state or concentration of an analyte 有权
标题翻译：用于光学测量组织以确定分析物的疾病状态或浓度的方法
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。

3. 发明授权

US09053352B2 High throughput, optical method and system for determining the effect of a test substance on non-contiguous living cells 有权
标题翻译：高通量，光学方法和系统，用于确定测试物质对非连续活细胞的影响
公开(公告)号：US09053352B2
公开(公告)日：2015-06-09
申请号：US13294848
申请日：2011-11-11
申请人： Jonathan D. Trumbull , Gary A. Gintant , Stanislaw Kantor , Jeffrey Yen Pan , Gilbert J. Diaz , Jonathon Green , Zhi Su , Jeffrey A. Olson
发明人： Jonathan D. Trumbull , Gary A. Gintant , Stanislaw Kantor , Jeffrey Yen Pan , Gilbert J. Diaz , Jonathon Green , Zhi Su , Jeffrey A. Olson
IPC分类号： G06K9/00 , C12M1/34 , G06T7/00 , G01N15/14 , B01L3/00
CPC分类号： G06K9/00127 , B01L3/5027 , C12M1/3446 , G01N15/1475 , G06T7/0012 , G06T7/0016 , G06T2207/10016 , G06T2207/30024
摘要： A rapid and efficient method and apparatus for detecting electrophysiologic, proarrhythmic, contractile, and other effects of substances such as compounds and drugs in native cellular cardiac preparations, the preparations representing an integrated cell-based pharmacologic response is disclosed. More specifically, a method to (1) rapidly and efficiently detect and verify the effects of chemicals, compounds and drugs on cardiac repolarization, contractility, and excitability using optically based techniques and customized simulation protocols, and (2) rapidly and efficiently screen and select compounds for electrophysiologic and proarrhythmic effects on cardiac myocytes is disclosed.
摘要翻译：公开了一种用于检测天然细胞心脏制剂中化合物和药物等物质如电生理，心律失常，收缩和其他作用的快速有效的方法和装置，所述制剂代表基于细胞的综合药理作用。更具体地说，一种方法（1）使用基于光学的技术和定制的模拟协议，快速有效地检测和验证化学品，化合物和药物对心脏复极化，收缩性和兴奋性的影响，以及（2）快速有效地筛选和选择公开了对心肌细胞的电生理和心律失常作用的化合物。

4. 发明授权

US08326388B2 Method and apparatus for non-invasive measurement of living body characteristics by photoacoustics 有权
标题翻译：通过光声学对生物体特征进行非侵入性测量的方法和装置
公开(公告)号：US08326388B2
公开(公告)日：2012-12-04
申请号：US10532691
申请日：2003-10-28
申请人： Shoichi Kanayama , Kazuhiro Itsumi , Omar S. Khalil , Stanislaw Kantor
发明人： Shoichi Kanayama , Kazuhiro Itsumi , Omar S. Khalil , Stanislaw Kantor
IPC分类号： A61B5/1455
CPC分类号： A61B5/0095 , A61B5/14532 , A61B5/6843
摘要： A method and apparatus for non-invasive measurement of living body information comprises a light source configured to generate light containing a specific wavelength component, an irradiation unit configured to irradiate a subject with the light, and at least one acoustic signal detection unit including piezoelectric devices formed of a piezoelectric single crystal containing lead titanate and configured to detect an acoustic signal which is generated due to the energy of the irradiation light absorbed by a specific substance present in or on a subject.
摘要翻译：一种生物体信息的非侵入式测量方法和装置，具备：生成包含特定波长成分的光的光源，被配置为对被检体照射的照射部，以及包含压电装置的至少一个声信号检测部由包含钛酸铅的压电单晶形成，并且被配置为检测由于存在于被摄体中的特定物质吸收的照射光的能量而产生的声信号。

5. 发明申请

US20070015978A1 Method and apparatus for non-invasive measurement of living body characteristics by photoacoustics 有权
标题翻译：通过光声学对生物体特征进行非侵入性测量的方法和装置
公开(公告)号：US20070015978A1
公开(公告)日：2007-01-18
申请号：US10532691
申请日：2003-10-28
申请人： Shoichi Kanayama , Kazuhiro Itsumi , Omar Khalil , Stanislaw Kantor
发明人： Shoichi Kanayama , Kazuhiro Itsumi , Omar Khalil , Stanislaw Kantor
IPC分类号： A61B5/00
CPC分类号： A61B5/0095 , A61B5/14532 , A61B5/6843
摘要： A method and apparatus for non-invasive measurement of living body information comprises a light source configured to generate light containing a specific wavelength component, an irradiation unit configured to irradiate a subject with the light, and at least one acoustic signal detection unit including piezoelectric devices formed of a piezoelectric single crystal containing lead titanate and configured to detect an acoustic signal which is generated due to the energy of the irradiation light absorbed by a specific substance present in or on a subject.
摘要翻译：一种生物体信息的非侵入式测量方法和装置，具备：生成包含特定波长成分的光的光源，被配置为对被检体照射的照射部，以及包含压电装置的至少一个声信号检测部由包含钛酸铅的压电单晶形成，并且被配置为检测由于存在于被摄体中的特定物质吸收的照射光的能量而产生的声信号。

6. 发明授权

US06662031B1 Method and device for the noninvasive determination of hemoglobin and hematocrit 有权
标题翻译：用于无创测定血红蛋白和血细胞比容的方法和装置
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。

7. 发明申请

US20120134570A1 HIGH THROUGHPUT, OPTICAL METHOD AND SYSTEM FOR DETERMINING THE EFFECT OF A TEST SUBSTANCE ON NON-CONTIGUOUS LIVING CELLS 有权
标题翻译：用于确定测试物质对非连续生活细胞的影响的高通量，光学方法和系统
公开(公告)号：US20120134570A1
公开(公告)日：2012-05-31
申请号：US13294848
申请日：2011-11-11
申请人： Jonathan D. Trumbull , Gary A. Gintant , Stanislaw Kantor , Jeffrey Yen Pan , Gilbert J. Diaz , Jonathon Green , Zhi Su , Jeffrey A. Olson
发明人： Jonathan D. Trumbull , Gary A. Gintant , Stanislaw Kantor , Jeffrey Yen Pan , Gilbert J. Diaz , Jonathon Green , Zhi Su , Jeffrey A. Olson
IPC分类号： G06K9/00 , C40B60/12
CPC分类号： G06K9/00127 , B01L3/5027 , C12M1/3446 , G01N15/1475 , G06T7/0012 , G06T7/0016 , G06T2207/10016 , G06T2207/30024
摘要： A rapid and efficient method and apparatus for detecting electrophysiologic, proarrhythmic, contractile, and other effects of substances such as compounds and drugs in native cellular cardiac preparations, the preparations representing an integrated cell-based pharmacologic response is disclosed. More specifically, a method to (1) rapidly and efficiently detect and verify the effects of chemicals, compounds and drugs on cardiac repolarization, contractility, and excitability using optically based techniques and customized simulation protocols, and (2) rapidly and efficiently screen and select compounds for electrophysiologic and proarrhythmic effects on cardiac myocytes is disclosed.
摘要翻译：公开了一种用于检测天然细胞心脏制剂中化合物和药物等物质如电生理，心律失常，收缩和其他作用的快速有效的方法和装置，所述制剂代表基于细胞的综合药理作用。更具体地说，一种方法（1）使用基于光学的技术和定制的模拟协议，快速有效地检测和验证化学品，化合物和药物对心脏复极化，收缩性和兴奋性的影响，以及（2）快速有效地筛选和选择公开了对心肌细胞的电生理和心律失常作用的化合物。

8. 发明授权

US06615061B1 Optical sensor having a selectable sampling distance for determination of analytes 有权
标题翻译：具有用于测定分析物的可选取样距离的光学传感器
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。

9. 发明授权

US06526298B1 Method for the non-invasive determination of analytes in a selected volume of tissue 有权
标题翻译：在选定体积的组织中非侵入性测定分析物的方法
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。

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