公开(公告)号：US06675029B2

公开(公告)日：2004-01-06

申请号：US10183660

申请日：2002-06-25

申请人： Stephen L. Monfre ,  Timothy L. Ruchti ,  Thomas B. Blank ,  Brian J. Wenzel

发明人： Stephen L. Monfre ,  Timothy L. Ruchti ,  Thomas B. Blank ,  Brian J. Wenzel

IPC分类号： A61B500

CPC分类号： A61B5/444 ,  A61B5/0062 ,  A61B5/0075 ,  A61B5/1075 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/7264 ,  G01N21/3554 ,  G01N21/359 ,  G01N21/4785 ,  G01N21/49 ,  G01N2201/129

摘要： An apparatus and method for non-destructively estimating a tissue property, such as hydration, of a living subject utilizes in vivo spectral measurements made by irradiating skin tissue with near infrared (NIR) light. The apparatus includes a spectroscopic instrument in conjunction with a subject interface. The resulting spectra are passed to an analyzer for further processing, which includes detecting and eliminating invalid spectral measurements, and preprocessing to increase the signal-to-noise ratio. Finally, an estimation model developed from an exemplary set of measurements is applied to predict the tissue hydration for the sample. The method of tissue hydration measurement provides additional information about primary sources of systematic tissue variability, namely, the water content of the epidermal layer of skin and the penetration depth of the incident light. Tissue hydration measurement is therefore suitable for further spectral analysis and quantification of biological and chemical compounds, such as analytes.

摘要翻译： 用于非破坏性地估计活体受试者的组织性质（例如水合）的装置和方法利用通过用近红外（NIR）光照射皮肤组织进行的体内光谱测量。 该装置包括结合主体界面的光谱仪器。 所得到的光谱被传递到分析器以用于进一步处理，其包括检测和消除无效光谱测量以及预处理以增加信噪比。 最后，应用从示例性测量集合开发的估计模型来预测样品的组织水合。 组织水合测量的方法提供关于系统组织变异性的主要来源的附加信息，即皮肤表皮层的水含量和入射光的穿透深度。 因此，组织水合测量适用于生物和化学化合物（如分析物）的进一步光谱分析和定量。

公开(公告)号：USRE41333E1

公开(公告)日：2010-05-11

申请号：US11046673

申请日：2005-01-27

申请人： Thomas B. Blank ,  Stephen L. Monfre ,  Timothy L. Ruchti ,  Suresh N. Thennadill

发明人： Thomas B. Blank ,  Stephen L. Monfre ,  Timothy L. Ruchti ,  Suresh N. Thennadill

IPC分类号： A61B5/1455

CPC分类号： G01N21/274 ,  A61B5/1075 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/1495 ,  A61B5/7264 ,  A61B2560/0223 ,  A61B2560/0233 ,  G01N21/359 ,  G01N21/4785 ,  G01N21/49

摘要： A method of multi-tier classification and calibration in noninvasive blood analyte prediction minimizes prediction error by limiting co-varying spectral interferents. Tissue samples are categorized based on subject demographic and instrumental skin measurements, including in vivo near-IR spectral measurements. A multi-tier intelligent pattern classification sequence organizes spectral data into clusters having a high degree of internal consistency in tissue properties. In each tier, categories are successively refined using subject demographics, spectral measurement information and other device measurements suitable for developing tissue classifications.The multi-tier classification approach to calibration utilizes multivariate statistical arguments and multi-tiered classification using spectral features. Variables used in the multi-tiered classification can be skin surface hydration, skin surface temperature, tissue volume hydration, and an assessment of relative optical thickness of the dermis by the near-IR fat band. All tissue parameters are evaluated using the NIR spectrum signal along key wavelength segments.

摘要翻译： 非侵入性血液分析物预测中的多层分类和校准方法通过限制共同变化的光谱干扰来最小化预测误差。 组织样品根据受试者的人口统计学和仪器皮肤测量进行分类，包括体内近红外光谱测量。 多层智能图案分类序列将光谱数据组织成具有组织性质内部高度一致性的簇。 在每个层次中，使用主题人口统计学，光谱测量信息和适合于开发组织分类的其它装置测量法来连续地改进类别。 校准的多层分类方法利用多变量统计学参数和使用光谱特征的多层次分类。 用于多层次分类的变量可以是皮肤表面水合，皮肤表面温度，组织体积水合，以及近红外脂肪带对真皮的相对光学厚度的评估。 使用沿关键波长段的NIR光谱信号评估所有组织参数。

公开(公告)号：US06990364B2

公开(公告)日：2006-01-24

申请号：US10297736

申请日：2002-01-25

申请人： Timothy L. Ruchti ,  Suresh N. Thennadil ,  Thomas B. Blank ,  Alexander Lorenz ,  Stephen L. Monfre

发明人： Timothy L. Ruchti ,  Suresh N. Thennadil ,  Thomas B. Blank ,  Alexander Lorenz ,  Stephen L. Monfre

IPC分类号： A61B5/00

CPC分类号： A61B5/1455 ,  A61B5/14532 ,  A61B5/1495 ,  A61B2560/0223 ,  G01N21/31 ,  G01N21/33 ,  G01N21/359 ,  G01N2021/3595

摘要： Methods and apparatus for noninvasive determination of blood analytes, such as glucose, through NIR spectroscopy utilize optical properties of tissue as reflected in key spectroscopic features to improve measurement accuracy and precision. Physiological conditions such as changes in water distribution among tissue compartments lead to complex alterations in the measured absorbance spectrum of skin and reflect a modification in the effective pathlength of light, leading to a biased noninvasive glucose measurement. Changes in the optical properties of tissue are detected by identifying key features responsive to physiological variations. Conditions not conducive to noninvasive measurement of glucose are detected. Noninvasive glucose measurements that are biased by physiological changes in tissue are compensated. In an alternate embodiment, glucose is measured indirectly based on natural physiological response of tissue to glucose concentration. A spectroscopic device capable of such measurements is provided.

摘要翻译： 通过近红外光谱对血液分析物（如葡萄糖）进行无创测定的方法和设备利用关键光谱特征反映的组织光学性质来提高测量精度和精度。 生理条件如组织间隔水分配变化导致测量的皮肤吸收光谱的复杂变化，并反映了有效光线长度的变化，导致偏向的非侵入性葡萄糖测量。 通过识别响应于生理变化的关键特征来检测组织的光学性质的变化。 检测不利于葡萄糖无创测量的条件。 通过组织中的生理变化偏置的非侵入性葡萄糖测量被补偿。 在替代实施方案中，基于组织对葡萄糖浓度的天然生理反应间接测量葡萄糖。 提供能够进行这种测量的光谱装置。

公开(公告)号：US07509153B2

公开(公告)日：2009-03-24

申请号：US10384049

申请日：2003-03-07

申请人： Thomas B. Blank ,  Timothy L. Ruchti ,  Mutua Mattu ,  Marcy Makarewicz ,  Stephen L. Monfre ,  Alexander D. Lorenz

发明人： Thomas B. Blank ,  Timothy L. Ruchti ,  Mutua Mattu ,  Marcy Makarewicz ,  Stephen L. Monfre ,  Alexander D. Lorenz

IPC分类号： A61B5/1455

CPC分类号： A61B5/1455 ,  A61B5/14532 ,  A61B5/1491 ,  A61B5/1495 ,  A61B2560/0223 ,  G01N21/31 ,  G01N21/33 ,  G01N21/359 ,  G01N21/65 ,  G01N2021/3595

摘要： A method and apparatus for noninvasive glucose measurement measures glucose indirectly from the natural response of tissue to variations in analyte concentration. The indirect measurement method utilizes factors affected by or correlated with the concentration of glucose, such as refractive index, electrolyte distribution or tissue scattering. Measurement reliability is greatly improved by stabilizing optical properties of the tissue at the measurement site, thus blood perfusion rates at the sample site are regulated. Perfusion is monitored and stabilized by spectroscopically measuring a control parameter, such as skin temperature, that directly affects perfusion. The control parameter is maintained in a range about a set point, thus stabilizing perfusion. Skin temperature is controlled using a variety of means, including the use of active heating and cooling elements, passive devices, such as thermal wraps, and through the use of a heated coupling medium having favorable heat transfer properties.

摘要翻译： 用于非侵入性葡萄糖测量的方法和装置从组织的自然反应间接测量葡萄糖对分析物浓度的变化。 间接测量方法利用受葡萄糖浓度影响或与葡萄糖浓度相关的因素，如折射率，电解质分布或组织散射。 通过稳定测量部位的组织的光学特性，可以大大提高测量可靠性，从而调节样品位置的血液灌注速率。 通过光谱测量直接影响灌注的控制参数（如皮肤温度）来监测和稳定灌注。 控制参数保持在设定点的范围内，从而稳定灌注。 使用各种手段控制皮肤温度，包括使用主动加热和冷却元件，无源器件，例如热封，以及通过使用具有良好传热特性的加热耦合介质。

公开(公告)号：US06512936B1

公开(公告)日：2003-01-28

申请号：US09665201

申请日：2000-09-18

申请人： Stephen L. Monfre ,  Thomas B. Blank ,  Timothy L. Ruchti ,  Suresh Thennadil

发明人： Stephen L. Monfre ,  Thomas B. Blank ,  Timothy L. Ruchti ,  Suresh Thennadil

IPC分类号： A61B500

CPC分类号： G06K9/6217 ,  A61B5/1075 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/1495 ,  A61B5/7264 ,  A61B2560/0223 ,  A61B2560/0233 ,  G01N21/274 ,  G01N21/359 ,  G01N21/4785 ,  G01N21/49 ,  Y10S128/92

摘要： A method of multi-tier classification and calibration in noninvasive blood analyte prediction minimizes prediction error by limiting co-varying spectral interferents. Tissue samples are categorized based on subject demographic and instrumental skin measurements, including in vivo near-IR spectral measurements. A multi-tier intelligent pattern classification sequence organizes spectral data into clusters having a high degree of internal consistency in tissue properties. In each tier, categories are successively refined using subject demographics, spectral measurement information and other device measurements suitable for developing tissue classifications. The multi-tier classification approach to calibration utilizes multivariate statistical arguments and multi-tiered classification using spectral features. Variables used in the multi-tiered classification can be skin surface hydration, skin surface temperature, tissue volume hydration, and an assessment of relative optical thickness of the dermis by the near-IR fat band. All tissue parameters are evaluated using the NIR spectrum signal along key wavelength segments.

摘要翻译： 非侵入性血液分析物预测中的多层分类和校准方法通过限制共同变化的光谱干扰来最小化预测误差。 组织样品根据受试者的人口统计学和仪器皮肤测量进行分类，包括体内近红外光谱测量。 多层智能图案分类序列将光谱数据组织成具有组织性质内部高度一致性的簇。 在每个层次中，使用主题人口统计学，光谱测量信息和适合于开发组织分类的其它装置测量法来连续地改进类别。 校准的多层分类方法利用多变量统计学参数和使用光谱特征的多层次分类。 用于多层分类的变量可以是皮肤表面水合，皮肤表面温度，组织体积水合，以及近红外脂肪带对真皮的相对光学厚度的评估。 使用沿关键波长段的NIR光谱信号评估所有组织参数。

公开(公告)号：US07519406B2

公开(公告)日：2009-04-14

申请号：US11117104

申请日：2005-04-27

申请人： Thomas B. Blank ,  George M. Acosta ,  Timothy L. Ruchti ,  Mutua Mattu ,  Alexander D. Lorenz ,  Kevin H. Hazen ,  James R. Henderson

发明人： Thomas B. Blank ,  George M. Acosta ,  Timothy L. Ruchti ,  Mutua Mattu ,  Alexander D. Lorenz ,  Kevin H. Hazen ,  James R. Henderson

IPC分类号： A61B5/1455

CPC分类号： A61B5/1455 ,  A61B5/14532 ,  A61B5/1495 ,  A61B5/4869 ,  A61B2560/0223 ,  A61B2560/0233 ,  A61B2562/0242 ,  G01N21/359

摘要： A method and apparatus are provided for noninvasive sampling. More particularly, the method and apparatus relate to control of motion of an optical sample probe interface relative to a tissue sample site. A dynamic probe interface, is used to collect spectra of a targeted sample, control positioning of the sample probe relative to the tissue sample in terms of at least one of x-, y-, and z-axes, and/or control of sample tissue displacement to minimize spectral variations resulting from the sampling process and increase analyte property estimation precision and accuracy.

摘要翻译： 提供了一种用于无创采样的方法和装置。 更具体地，该方法和装置涉及光学样本探针界面相对于组织样本位点的运动的控制。 使用动态探针接口来收集目标样品的光谱，根据x-，y-和z-轴中的至少一个来控​​制样品探针相对于组织样品的定位和/或样品的控制 组织位移以最小化由采样过程导致的频谱变化，并增加分析物质的估计精度和精度。

公开(公告)号：US06777240B2

公开(公告)日：2004-08-17

申请号：US10241344

申请日：2002-09-11

申请人： Kevin H. Hazen ,  James Matthew Welch ,  Stephen F. Malin ,  Timothy L. Ruchti ,  Alexander D. Lorenz ,  Tamara L. Troy ,  Suresh Thennadil ,  Thomas B. Blank

发明人： Kevin H. Hazen ,  James Matthew Welch ,  Stephen F. Malin ,  Timothy L. Ruchti ,  Alexander D. Lorenz ,  Tamara L. Troy ,  Suresh Thennadil ,  Thomas B. Blank

IPC分类号： G01N3100

CPC分类号： G01N21/274 ,  A61B5/0075 ,  A61B5/1075 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/1495 ,  A61B5/7264 ,  A61B2560/0223 ,  A61B2560/0233 ,  G01N21/359 ,  G01N21/4785 ,  G01N21/49 ,  Y10T436/10

摘要： The invention provides a class of samples that model the human body. This family of samples is based upon emulsions of oil in water with lecithin acting as the emulsifier. These solutions that have varying particle sizes may be spiked with basis set components (albumin, urea and glucose) to simulate skin tissues further. The family of samples is such that other organic compounds such as collagen, elastin, globulin and bilirubin may be added, as can salts such as Na+, K+and Cl−. Layers of varying thickness with known index of refraction and particle size distributions may be generated using simple crosslinking reagents, such as collagen (gelatin). The resulting samples are flexible in each analyte's concentration and match the skin layers of the body in terms of the samples reduced scattering and absorption coefficients, &mgr;'s and &mgr;a. This family of samples is provided for use in the medical field where lasers and spectroscopy based analyzers are used in treatment of the body. In particular, knowledge may be gained on net analyte signal, photon depth of penetration, photon radial diffusion, photon interaction between tissue layers, photon density (all as a function of frequency) and on instrument parameter specifications such as resolution and required dynamic range (A/D bits required). In particular, applications to delineate such parameters have been developed for the application of noninvasive glucose determination in the near-IR region from 700 to 2500 nm with an emphasis on the region 1000 to 2500 nm (10,000 to 4,000 cm−1).

摘要翻译： 本发明提供了一类对人体进行建模的样品。 该样品系基于水中的油与卵磷脂作为乳化剂的乳液。 具有不同粒径的这些溶液可以加入基础组分（白蛋白，尿素和葡萄糖）以进一步模拟皮肤组织。 样品家族可以加入其它有机化合物如胶原蛋白，弹性蛋白，球蛋白和胆红素，也可以加入诸如Na +，K +和Cl - 的盐。 可以使用简单的交联试剂如胶原（明胶）产生具有已知折射率和粒度分布的不同厚度的层。 所得样品在每种分析物的浓度上是柔性的，并且根据样品减少的散射和吸收系数mu和μa来匹配身体的皮肤层。 该样品系列用于医疗领域，其中使用激光和基于光谱的分析仪来治疗身体。 特别地，可以获得关于净分析物信号，光子穿透深度，光子径向扩散，组织层之间的光子相互作用，光子密度（全部作为频率的函数）以及仪器参数规格（例如分辨率和所需动态范围） 需要A / D位）。 特别地，已经开发出描绘这些参数的应用，用于在700至2500nm的近红外区域中应用非侵入性葡萄糖测定，重点在1000至2500nm（10,000至4000cm -1）的区域。

公开(公告)号：US07038774B2

公开(公告)日：2006-05-02

申请号：US10870727

申请日：2004-06-16

申请人： Kevin H. Hazen ,  Thomas B. Blank ,  Stephen Monfre ,  Timothy L. Ruchti

发明人： Kevin H. Hazen ,  Thomas B. Blank ,  Stephen Monfre ,  Timothy L. Ruchti

IPC分类号： G01J3/28

CPC分类号： G01N21/359 ,  A61B5/0075 ,  A61B5/1075 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/1495 ,  A61B5/7264 ,  A61B2560/0223 ,  A61B2560/0233 ,  G01J3/28 ,  G01J2003/2866 ,  G01N21/274 ,  G01N21/3563 ,  G01N21/4785 ,  G01N21/49

摘要： Spectrometer instruments are characterized by classifying their spectra into previously defined clusters. The spectra are mapped to the clusters and a classification is made based on similarity of extracted spectral features to one of the previously defined clusters. Calibration models for each cluster are provided to compensate for instrumental variation. Calibration models are provided either by transferring a master calibration to slave calibrations or by calculating a separate calibration for each cluster. In one embodiment, a simplified method of calibration transfer maps clusters to each other, so that a calibration transferred between clusters models only the difference between the two clusters, substantially reducing the complexity of the model.

摘要翻译： 光谱仪器的特点是将其光谱分类为先前定义的簇。 光谱被映射到簇，并且基于提取的光谱特征与先前定义的簇之一的相似性进行分类。 提供每个集群的校准模型以补偿工具变化。 通过将主校准传送到从站校准或通过为每个集群计算单独的校准来提供校准模型。 在一个实施例中，校准传递的简化方法将群集彼此映射，使得在群集之间传递的校准仅模拟两个群集之间的差异，从而显着降低了模型的复杂性。

公开(公告)号：US06864978B1

公开(公告)日：2005-03-08

申请号：US09664973

申请日：2000-09-18

申请人： Kevin H. Hazen ,  Thomas B. Blank ,  Stephen Monfre ,  Timothy L. Ruchti

发明人： Kevin H. Hazen ,  Thomas B. Blank ,  Stephen Monfre ,  Timothy L. Ruchti

IPC分类号： G01N21/35 ,  A61B5/00 ,  A61B5/107 ,  A61B5/145 ,  A61B5/1455 ,  A61B5/1495 ,  G01J3/02 ,  G01J3/28 ,  G01N21/27 ,  G01N21/47 ,  G01N21/49 ,  G06F19/00

CPC分类号： G01N21/359 ,  A61B5/0075 ,  A61B5/1075 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/1495 ,  A61B5/7264 ,  A61B2560/0223 ,  A61B2560/0233 ,  G01J3/28 ,  G01J2003/2866 ,  G01N21/274 ,  G01N21/3563 ,  G01N21/4785 ,  G01N21/49

摘要： Spectrometer instruments are characterized by classifying their spectra into previously defined clusters. The spectra are mapped to the clusters and a classification is made based on similarity of extracted spectral features to one of the previously defined clusters. Calibration models for each cluster are provided to compensate for instrumental variation. Calibration models are provided either by transferring a master calibration to slave calibrations or by calculating a separate calibration for each cluster.A simplified method of calibration transfer maps clusters to each other, so that a calibration transferred between clusters models only the difference between the two clusters, substantially reducing the complexity of the model.

摘要翻译： 光谱仪器的特点是将其光谱分类为先前定义的簇。 光谱被映射到簇，并且基于提取的光谱特征与先前定义的簇之一的相似性进行分类。 提供每个集群的校准模型以补偿工具变化。 校准模型通过将主校准传送到从站校准或通过为每个群集计算单独的校准来提供校准模型。简化的校准传输方法将群集彼此映射，使得群集之间传递的校准仅模拟两个群集之间的差异 ，大大降低了模型的复杂性。

公开(公告)号：US20080146899A1

公开(公告)日：2008-06-19

申请号：US12027934

申请日：2008-02-07

申请人： Timothy L. RUCHTI ,  Kevin H. Hazen ,  Thomas B. Blank

发明人： Timothy L. RUCHTI ,  Kevin H. Hazen ,  Thomas B. Blank

IPC分类号： A61B5/1455

CPC分类号： G01N21/274 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/1495 ,  G01N21/359

摘要： A method and apparatus for easing the use of an optically based noninvasive analyzer is presented. More particularly, a simplified algorithm is used that removes the daily requirement of collecting and using a noninvasive spectrum to update a calibration model. In another embodiment, a guide is used to substantially reduce variation in sample probe placement in relation to a skin tissue sampling site, resulting in the ability to maintain calibration performance with the use of a reference analyte concentration, with or without the use of a reference spectrum collected nearby in time.

摘要翻译： 提出了一种用于缓解光学非侵入式分析仪的使用的方法和装置。 更具体地，使用简化的算法，其消除收集和使用非侵入光谱以更新校准模型的每日需求。 在另一个实施例中，引导件用于相对于皮肤组织取样部位显着减少样本探针放置的变化，从而产生使用参考分析物浓度来维持校准性能的能力，有或没有使用参考 频谱在时间附近收集。