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1. 发明授权

US07620674B2 Method and apparatus for enhanced estimation of an analyte property through multiple region transformation 有权
标题翻译：用于通过多区域变换增强对分析物特性的估计的方法和装置
公开(公告)号：US07620674B2
公开(公告)日：2009-11-17
申请号：US10976530
申请日：2004-10-29
申请人： Timothy L. Ruchti , Alexander D. Lorenz , Kevin H. Hazen
发明人： Timothy L. Ruchti , Alexander D. Lorenz , Kevin H. Hazen
IPC分类号： G06F17/14 , G06F7/38
CPC分类号： A61B5/1455 , A61B5/14532 , A61B5/1495 , A61B2560/0223 , G01N21/359
摘要： The invention comprises transformation of a section of a data block independently of the transformation of separate or overlapping data blocks to determine a property related to the original matrix, where each of the separate or overlapping data blocks are derived from an original data matrix. The transformation enhances parameters of a first data block over a given region of an axis of the data matrix, such as signal-to-noise, without affecting analysis of a second data block derived from the data matrix. This allows for enhancement of analysis of an analyte property, such as concentration, represented within the original data matrix. A separate decomposition and factor selection for each selected data matrix is performed with subsequent score matrix concatenization. The combined score matrix is used to generate a model that is subsequently used to estimate a property, such as concentration represented in the original data matrix.
摘要翻译：本发明包括独立于单独或重叠的数据块的变换的数据块的一部分的变换，以确定与原始矩阵相关的属性，其中每个分离的或重叠的数据块是从原始数据矩阵导出的。该变换增强了数据矩阵的轴的给定区域（例如信号到噪声）上的第一数据块的参数，而不影响从数据矩阵导出的第二数据块的分析。这允许增强在原始数据矩阵内表示的分析物质（例如浓度）的分析。对于每个选择的数据矩阵进行单独的分解和因子选择，随后的得分矩阵连接。组合得分矩阵用于生成随后用于估计属性的模型，例如在原始数据矩阵中表示的浓度。

2. 发明授权

US07509153B2 Method and apparatus for control of skin perfusion for indirect glucose measurement 失效
标题翻译：用于控制间接葡萄糖测量的皮肤灌注的方法和装置
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。

3. 发明授权

US07436511B2 Analyte filter method and apparatus 失效
标题翻译：分析物过滤方法和装置
公开(公告)号：US07436511B2
公开(公告)日：2008-10-14
申请号：US11188064
申请日：2005-07-22
申请人： Timothy L. Ruchti , Alexander D. Lorenz , Kevin H. Hazen
发明人： Timothy L. Ruchti , Alexander D. Lorenz , Kevin H. Hazen
IPC分类号： G01J3/28 , G01J3/42 , G01J3/427 , G01N33/48 , A61B5/00
CPC分类号： G01N21/274 , G01J3/28 , G01J3/433 , G01N21/359 , G01N2201/129 , G01N2201/1293
摘要： The invention comprises a method and apparatus for enhancing the analysis of noninvasive spectra, resulting in improved analytical performance. More particularly, the invention comprises a method and apparatus for processing noninvasive spectra with an analyte filter that preferably rejects variation likely to be detrimental to the measurement system, while passing signal that probabilistically is unique to the target analyte. Subsequently, the analyte filtered data are used to estimate an analyte property, such as a glucose concentration, in the presence of noise, interferences, state changes, and/or across analyzers.
摘要翻译：本发明包括用于增强非侵入光谱分析的方法和装置，从而提高分析性能。更具体地，本发明包括用分析物过滤器处理非侵入光谱的方法和装置，其优选地拒绝可能对测量系统有害的变化，同时传递概率地对目标分析物是唯一的信号。随后，分析物过滤的数据用于在存在噪声，干扰，状态变化和/或跨分析仪的情况下估计分析物质（例如葡萄糖浓度）。

4. 发明授权

US07206623B2 Optical sampling interface system for in vivo measurement of tissue 失效
公开(公告)号：US07206623B2
公开(公告)日：2007-04-17
申请号：US10170921
申请日：2002-06-12
申请人： Thomas B. Blank , George Acosta , Mutua Mattu , Marcy Makarewicz , Stephen L. Monfre , Alexander D. Lorenz , Timothy L. Ruchti
发明人： Thomas B. Blank , George Acosta , Mutua Mattu , Marcy Makarewicz , Stephen L. Monfre , Alexander D. Lorenz , Timothy L. Ruchti
IPC分类号： A61B5/00
CPC分类号： A61B5/0059 , A61B5/0071 , A61B5/0075 , A61B5/01 , A61B5/061 , A61B5/14532 , A61B5/1455 , A61B5/1495 , A61B5/6824 , A61B5/6833 , A61B5/6843 , A61B2560/0233 , A61B2562/12 , A61B2562/146
摘要： An optical sampling interface system minimizes and compensates error resulting from sampling variations and measurement site state fluctuations. Components include: An optical probe placement guide having an aperture wherein the optical probe is received, facilitates repeatable placement accuracy on surface of a tissue measurement site with minimal, repeatable disturbance to surface tissue. The aperture creates a tissue meniscus that minimizes interference due to surface irregularities and controls variation in tissue volume sampled; an occlusive element placed over the tissue meniscus isolates the meniscus from environmental fluctuations, stabilizing hydration at the site and thus, surface tension; an optical coupling medium eliminates air gaps between skin surface and optical probe; a bias correction element applies a bias correction to spectral measurements, and associated analyte measurements. When the guide is replaced, a new bias correction is determined for measurements done with the new placement. Separate components of system can be individually deployed.

5. 发明授权

US07317938B2 Method of adapting in-vitro models to aid in noninvasive glucose determination 失效
标题翻译：适应体外模型以帮助非侵入性葡萄糖测定的方法
公开(公告)号：US07317938B2
公开(公告)日：2008-01-08
申请号：US10978116
申请日：2004-10-29
申请人： Alexander D. Lorenz , Timothy L. Ruchti
发明人： Alexander D. Lorenz , Timothy L. Ruchti
IPC分类号： A61B5/00
CPC分类号： A61B5/1455 , A61B5/14532 , A61B2560/0233 , G01N21/278 , G01N21/359
摘要： The invention relates to a noninvasive analyzer and a method of using information determined at least in part from in-vitro spectra of tissue phantoms or analyte solutions to aid in the development of a noninvasive glucose concentration analyzer and/or in the analysis of noninvasive spectra resulting in glucose concentration estimations in the body. The preferred apparatus is a spectrometer that includes a base module and a sample module that is semi-continuously in contact with a human subject and that collects spectral measurements which are used to determine a biological parameter in the sampled tissue, such as glucose concentration. Collection of in-vitro samples is, optionally, performed on a separate instrument from the production model allowing the measurement technology to be developed on a research grade instrument and used or transferred to a target product platform or production analyzer for noninvasive glucose concentration estimation.
摘要翻译：本发明涉及非侵入性分析仪和使用至少部分地从组织模型或分析物溶液的体外光谱确定的信息的方法，以帮助非侵入性葡萄糖浓度分析仪的开发和/或在非侵入性光谱的分析中得到在体内的葡萄糖浓度估计。优选的装置是一种光谱仪，其包括基本模块和与人类受试者半连续接触的样本模块，并收集用于确定采样组织中的生物学参数（如葡萄糖浓度）的光谱测量。体外样品的收集可选地在与生产模型分开的仪器上进行，允许在研究级仪器上开发测量技术，并将其用于或转移到用于非侵入性葡萄糖浓度估计的目标产物平台或生产分析仪。

6. 发明授权

US07233816B2 Optical sampling interface system for in vivo measurement of tissue 有权
公开(公告)号：US07233816B2
公开(公告)日：2007-06-19
申请号：US10917802
申请日：2004-08-12
申请人： Thomas B. Blank , George Acosta , Mutua Mattu , Marcy Makarewicz , Stephen L. Monfre , Alexander D. Lorenz , Timothy L. Ruchti
发明人： Thomas B. Blank , George Acosta , Mutua Mattu , Marcy Makarewicz , Stephen L. Monfre , Alexander D. Lorenz , Timothy L. Ruchti
IPC分类号： A61B5/00
CPC分类号： A61B5/0059 , A61B5/0071 , A61B5/0075 , A61B5/01 , A61B5/061 , A61B5/14532 , A61B5/1455 , A61B5/1495 , A61B5/6824 , A61B5/6833 , A61B5/6843 , A61B2560/0233 , A61B2562/12 , A61B2562/146
摘要： An optical sampling interface system minimizes and compensates error resulting from sampling variations and measurement site state fluctuations. Components include: An optical probe placement guide having an aperture wherein the optical probe is received, facilitates repeatable placement accuracy on surface of a tissue measurement site with minimal, repeatable disturbance to surface tissue. The aperture creates a tissue meniscus that minimizes interference due to surface irregularities and controls variation in tissue volume sampled; an occlusive element placed over the tissue meniscus isolates the meniscus from environmental fluctuations, stabilizing hydration at the site and thus, surface tension; an optical coupling medium eliminates air gaps between skin surface and optical probe; a bias correction element applies a bias correction to spectral measurements, and associated analyte measurements. When the guide is replaced, a new bias correction is determined for measurements done with the new placement. Separate components of system can be individually deployed.

7. 发明授权

US07010336B2 Measurement site dependent data preprocessing method for robust calibration and prediction 失效
公开(公告)号：US07010336B2
公开(公告)日：2006-03-07
申请号：US10384023
申请日：2003-03-07
申请人： Alexander D. Lorenz , Timothy L. Ruchti , Thomas B. Blank , Kevin H. Hazen
发明人： Alexander D. Lorenz , Timothy L. Ruchti , Thomas B. Blank , Kevin H. Hazen
IPC分类号： A61B5/00
CPC分类号： G01N21/359 , A61B5/0075 , A61B5/14532 , A61B5/1455 , A61B5/1495 , G01N21/49
摘要： A solution for reducing interference in noninvasive spectroscopic measurements of tissue and blood analytes is provided. By applying a basis set representing various tissue components to a collected sample measurement, measurement interferences resulting from the heterogeneity of tissue, sampling site differences, patient-to-patient variation, physiological variation, and instrumental differences are reduced. Consequently, the transformed sample measurements are more suitable for developing calibrations that are robust with respect to sample-to-sample variation, variation through time, and instrument related differences. In the calibration phase, data associated with a particular tissue sample site is corrected using a selected subset of data within the same data set. This method reduces the complexity of the data and reduces the intra-subject, inter-subject, and inter-instrument variations by removing interference specific to the respective data subset. In the measurement phase, the basis set correction is applied using a minimal number of initial samples collected from the sample site(s) where future samples will be collected.

8. 发明授权

US07606608B2 Optical sampling interface system for in-vivo measurement of tissue 有权
标题翻译：用于体内测量组织的光学取样界面系统
公开(公告)号：US07606608B2
公开(公告)日：2009-10-20
申请号：US11008001
申请日：2004-12-08
申请人： Thomas B. Blank , George Acosta , Mutua Mattu , Marcy Makarewicz , Stephen L. Monfre , Alexander D. Lorenz , Timothy L. Ruchti , Kevin H. Hazen , Donovan D. Berry , Roxanne E. Abul-Haj
发明人： Thomas B. Blank , George Acosta , Mutua Mattu , Marcy Makarewicz , Stephen L. Monfre , Alexander D. Lorenz , Timothy L. Ruchti , Kevin H. Hazen , Donovan D. Berry , Roxanne E. Abul-Haj
IPC分类号： A61B5/1455
CPC分类号： G01N21/359 , A61B5/14532 , A61B5/1455 , A61B5/1495 , A61B5/6833
摘要： An optical sampling interface system is disclosed that minimizes and compensates for errors that result from sampling variations and measurement site state fluctuations. Embodiments of the invention use a guide that does at least one of, induce the formation of a tissue meniscus, minimize interference due to surface irregularities, control variation in the volume of tissue sampled, use a two-part guide system, use a guide that controls rotation of a sample probe and allows z-axis movement of the probe, use a separate base module and sample module in conjunction with a guide, and use a guide that controls rotation. Optional components include an occlusive element and a coupling fluid.
摘要翻译：公开了一种光学采样接口系统，其最小化并补偿由采样变化和测量位置状态波动引起的误差。本发明的实施例使用至少一个引导组织弯液面的形成的引导件，使由于表面不规则性引起的干扰最小化，控制组织体积的变化，使用两部分引导系统，使用指导控制样品探针的旋转并允许探针的z轴移动，使用独立的基本模块和样品模块与导轨结合使用，并使用控制旋转的指南。可选组件包括闭塞元件和耦合流体。

9. 发明授权

US07519406B2 Noninvasive analyzer sample probe interface method and apparatus 有权
标题翻译：无创分析仪样品探针接口方法和装置
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。

10. 发明授权

US07039446B2 Indirect measurement of tissue analytes through tissue properties 失效
标题翻译：通过组织特性间接测量组织分析物
公开(公告)号：US07039446B2
公开(公告)日：2006-05-02
申请号：US10349573
申请日：2003-01-22
申请人： Timothy L. Ruchti , Thomas B. Blank , Alexander D. Lorenz , Stephen L. Monfre , Kevin H. Hazen , Suresh N. Thennadil
发明人： Timothy L. Ruchti , Thomas B. Blank , Alexander D. Lorenz , Stephen L. Monfre , Kevin H. Hazen , Suresh N. Thennadil
IPC分类号： A61B5/00
CPC分类号： A61B5/1455 , A61B5/0071 , A61B5/0075 , A61B5/14532 , A61B5/1495 , A61B2560/0223 , G01N21/274 , G01N21/31 , G01N21/33 , G01N21/359 , G01N21/65 , G01N2021/3595
摘要： Methods and system for noninvasive determination of tissue analytes utilize tissue properties as reflected in key features of an analytical signal to improve measurement accuracy and precision. Physiological conditions such as changes in water distribution among tissue compartments lead to complex alterations in the measured analytical signal of skin, leading to a biased noninvasive analyte measurement. Changes in the tissue properties are detected by identifying key features in the analytical signal responsive to physiological variations. Conditions not conducive to the noninvasive measurement are detected. Noninvasive measurements that are biased by physiological changes in tissue are compensated. In an alternate embodiment, the analyte is measured indirectly based on natural physiological response of tissue to changes in analyte concentration. A system capable of such measurements is provided.
摘要翻译：非侵入性测定组织分析物的方法和系统利用分析信号的关键特征反映的组织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分析信号的复杂变化，导致偏向的非侵入性分析物测量。通过识别响应于生理变化的分析信号中的关键特征来检测组织性质的变化。检测到不利于非侵入性测量的条件。由组织中生理变化偏向的无创测量得到补偿。在替代实施方案中，基于组织对分析物浓度变化的天然生理反应间接测量分析物。提供能够进行这种测量的系统。

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