公开(公告)号：WO2002082989A1

公开(公告)日：2002-10-24

申请号：PCT/US2002/006831

申请日：2002-03-07

Applicant: ABBOTT LABORATORIES

Inventor： KHALIL, Omar, S. ,  YEH, Shu-Jen ,  KANTOR, Stanislaw ,  HANNA, Charles, F. ,  SHAIN, Eric, B.

IPC: A61B5/00

CPC classification number: A61B5/1495 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/7264

Abstract: 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.

Abstract translation: 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：EP1381306A1

公开(公告)日：2004-01-21

申请号：EP02725082.8

申请日：2002-03-07

Applicant: ABBOTT LABORATORIES

Inventor： KHALIL, Omar, S. ,  YEH, Shu-Jen ,  KANTOR, Stanislaw ,  HANNA, Charles, F. ,  SHAIN, Eric, B.

IPC: A61B5/00

CPC classification number: A61B5/1495 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/7264

Abstract: 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.

公开(公告)号：EP1139862A1

公开(公告)日：2001-10-10

申请号：EP99966375.0

申请日：1999-12-16

Applicant: ABBOTT LABORATORIES

Inventor： JENG, Tzyy-Wen ,  YEH, Shu-Jen ,  LINDBERG, John, M. ,  PEZZANITI, Joseph, Larry ,  KHALIL, Omar, S. ,  OOSTA, Gary, M. ,  HANNA, Charles, F. ,  STALDER, Arnold, F. ,  SZUTS, Ete Z.

IPC: A61B5/00

CPC classification number: A61B5/1455 ,  A61B5/14532

Abstract: A method and apparatus for measuring the concentration of an analyte of interest, e.g. glucose, in blood non-invasively. 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, two similar, but not identical, wavelengths of electromagnetic radiation can be used. 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.

公开(公告)号：EP1282380A2

公开(公告)日：2003-02-12

申请号：EP01933059.6

申请日：2001-05-07

Applicant: Abbott Laboratories

Inventor： KHALIL, Omar, S. ,  WU, Xiaomao ,  YEH, Shu-Jen ,  HANNA, Charles, F. ,  KANTOR, Stanislaw ,  JENG, Tzyy-Wen

IPC: A61B5/00

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

Abstract: 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. It employs 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. An optical signal from a defined subcutaneous volume of human skin is measured as the temperature of this volume is controlled. This allows 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 determination of hemoglobin concentration and hematocrit value is useful for monitoring patients, testing at the point of care, and screening for anemia. This method has the advantage for the determination of analytes in weak cardiac pulse situations, such as, for example, in elderly patients.

公开(公告)号：EP1223854A1

公开(公告)日：2002-07-24

申请号：EP00968888.8

申请日：2000-10-06

Applicant: ABBOTT LABORATORIES

Inventor： KHALIL, Omar, S. ,  YEH, Shu-Jen ,  WU, Xiaomao ,  KANTOR, Stanislaw ,  HANNA, Charles, F. ,  JENG, Tzyy-Wen

IPC: A61B5/00

CPC classification number: A61B5/1455 ,  A61B5/0059 ,  A61B5/14532 ,  A61B5/1491 ,  A61B5/1495 ,  A61B5/6824 ,  A61B2562/0242

Abstract: 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.

公开(公告)号：EP1173091A1

公开(公告)日：2002-01-23

申请号：EP00928652.7

申请日：2000-04-28

Applicant: ABBOTT LABORATORIES

Inventor： WU, Xiaomao ,  KHALIL, Omar, S. ,  JENG, Tzyy-Wen ,  YEH, Shu-Jen ,  HANNA, Charles, F.

IPC: A61B5/00

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

Abstract: A method for determining the concentration of an analyte in a biological sample comprising the steps of: (1) providing an optical measuring instrument (10) that comprises at least one thermally controllable optical measuring element (12) that comes into contact with the surface of the biological sample; (2) applying an inert, thermally conductive, optically transparent coupling agent (100) to the at least one optical measuring element (12) 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.

公开(公告)号：EP1133253A1

公开(公告)日：2001-09-19

申请号：EP99960286.5

申请日：1999-11-10

Applicant: ABBOTT LABORATORIES

Inventor： KHALIL, Omar, S. ,  WU, Xiaomao ,  KANGER, Johannes, S. ,  BOLT, Rene, A. ,  YEH, Shu-Jen ,  HANNA, Charles, F. ,  DE MUL, Frits, Frans Maria

IPC: A61B5/00 ,  G01N21/31 ,  G01N21/25 ,  G01N21/47

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

Abstract: 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：EP1077637A1

公开(公告)日：2001-02-28

申请号：EP99923124.4

申请日：1999-05-17

Applicant: ABBOTT LABORATORIES

Inventor： KHALIL, Omar, S. ,  DEMUL, Frits, F., M. ,  HANNA, Charles, F. ,  STALDER, Arnold, F. ,  YEH, Shu-Jen ,  WU, Xiaomao ,  LOWREY, Michael, G. ,  KANGER, Johannes, S. ,  BOLT, René, A.

IPC: A61B5/00 ,  G01N21/47

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

Abstract: 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.