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1. 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。

2. 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。

3. 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。

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

US06788965B2 Intelligent system for detecting errors and determining failure modes in noninvasive measurement of blood and tissue analytes 有权
标题翻译：用于检测血液和组织分析物的非侵入性测量中的错误和确定失败模式的智能系统
公开(公告)号：US06788965B2
公开(公告)日：2004-09-07
申请号：US10211478
申请日：2002-08-01
申请人： Timothy L. Ruchti , Christopher C. Briggs , Thomas B. Blank , Alexander D. Lorenz , Mutua Mattu , Marcy Makarewicz
发明人： Timothy L. Ruchti , Christopher C. Briggs , Thomas B. Blank , Alexander D. Lorenz , Mutua Mattu , Marcy Makarewicz
IPC分类号： A61B500
CPC分类号： A61B5/1459 , A61B5/0064 , A61B5/0075 , A61B5/01 , A61B5/14532 , A61B5/14546 , A61B5/1495 , A61B5/441 , A61B5/7264 , G01N21/274 , G01N21/359 , G06N3/004
摘要： An intelligent system for detecting errors and determining failure modes operates on an absorbance spectrum of in vivo skin tissue. Application of the system results in improved prediction accuracy through rejection of invalid and poor samples. System components include a noninvasive blood glucose meter, such as a near IR spectrometer, an error detection system (EDS); a system for diagnosing and mitigating errors; and a reporting method. In the EDS, a pattern classification engine and hierarchy of levels analyzes, detects and diagnoses instrument, interface and sample errors manifested in the spectrum to determine suitability of an absorbance spectrum for blood glucose measurement. The final component of the system evaluates the error condition, diagnoses the specific mode of failure (if necessary) and reports actions to be taken. Sub-components and levels of the EDS can operate independently of the other system elements to the benefit of a noninvasive glucose measurement system.
摘要翻译：用于检测错误并确定故障模式的智能系统对体内皮肤组织的吸收光谱进行操作。该系统的应用通过排除无效和差的样本提高了预测精度。系统组件包括无创血糖仪，例如近红外光谱仪，误差检测系统（EDS）; 用于诊断和减轻错误的系统; 和报告方法。在EDS中，模式分类引擎和级别层次分析，检测和诊断谱图中出现的仪器，界面和样本误差，以确定血糖测量的吸收光谱的适用性。系统的最终组件评估错误状况，诊断具体的失败模式（如有必要）并报告要采取的操作。 EDS的子组件和级别可以独立于其他系统元件运行，以有益于非侵入性葡萄糖测量系统。

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

US06640117B2 Method and apparatus for minimizing spectral effects attributable to tissue state variations during NIR-based non-invasive blood analyte determination 有权
标题翻译：用于最小化归因于基于NIR的非侵入性血液分析物测定期间的组织状态变化的光谱效应的方法和装置
公开(公告)号：US06640117B2
公开(公告)日：2003-10-28
申请号：US09955531
申请日：2001-09-17
申请人： Marcy R. Makarewicz , Mutua Mattu , Thomas B. Blank , Stephen L. Monfre , Timothy L. Ruchti
发明人： Marcy R. Makarewicz , Mutua Mattu , Thomas B. Blank , Stephen L. Monfre , Timothy L. Ruchti
IPC分类号： A61B500
CPC分类号： A61B5/1495 , A61B5/14532 , A61B5/1455 , A61B5/1491
摘要： A method and apparatus for minimizing confounding effects in a noninvasive in-vivo spectral measurement caused by fluctuations in tissue state monitors a selected tissue state parameter spectroscopically and maintains the selected parameter within a target range, at which spectral effects attributable to the changes in the selected parameter are minimized. The invention includes both active and passive control. A preferred embodiment of the invention provides a method and apparatus for minimizing the confounding effects in near IR spectral measurements attributable to shifts in skin temperature at a tissue measurement site. Spectroscopic monitoring of skin temperature at the measurement site provides near-instantaneous temperature readings by eliminating thermal time constants. A thermistor positioned at the measurement site provides active control. The spectrometer and the temperature control device are incorporated into a single instrument for noninvasive measurement of blood glucose concentration.
摘要翻译：用于最小化由组织状态的波动引起的非侵入性体内光谱测量中的混杂效应的方法和装置通过光谱方式监测所选择的组织状态参数，并将所选择的参数保持在目标范围内，在该范围内，归因于所选择的变化的光谱效应参数最小化。本发明包括主动和被动控制。本发明的一个优选实施例提供了一种方法和装置，用于最小化归因于组织测量部位的皮肤温度变化的近红外光谱测量中的混杂效应。光谱监测测量点的皮肤温度通过消除热时间常数提供近乎瞬时的温度读数。位于测量位置的热敏电阻提供主动控制。光谱仪和温度控制装置被并入单个仪器中用于非侵入性测量血糖浓度。

8. 发明授权

US06839584B2 Method and apparatus for minimizing spectral interference due to within and between sample variations during in-situ spectral sampling of tissue 失效
标题翻译：用于在组织的原位光谱采样期间最小化由于样品变化之内和之间的光谱干扰的方法和装置
公开(公告)号：US06839584B2
公开(公告)日：2005-01-04
申请号：US09954856
申请日：2001-09-17
申请人： Marcy Makarewicz , Mutua Mattu , Thomas B. Blank , George Acosta , Edward Handy , William Hay , Timothy Stippick , Benjamin Richie
发明人： Marcy Makarewicz , Mutua Mattu , Thomas B. Blank , George Acosta , Edward Handy , William Hay , Timothy Stippick , Benjamin Richie
IPC分类号： A61B20060101 , A61B5/00
CPC分类号： A61B5/14532 , A61B5/061 , A61B5/1459 , A61B5/6824 , A61B2562/146
摘要： An apparatus and method for reproducibly interfacing a living tissue sample to the measurement probe of a spectrometer instrument in-situ minimizes spectral interference related to sampling variations. A minimal contact subject interface includes supports replaceably mounted on a base. An optical coupling means, such as a fiber optic probe, contacts the measurement site through a probe aperture in the base. During use, a subject rests an extremity on the support elements, so that the extremity is reproducibly positioned and supported in relation to the optical coupling means. The supports have a small contact area, minimizing contact with the skin at the measurement site. The interface module is adjustable to fit any subject.By reproducibly positioning and supporting the body appendage using minimal contact supports, spectral interference due to variations in placement, applied pressure, and temperature transients secondary to contact with the interface module are greatly minimized.
摘要翻译：将生物组织样本可再现地将光谱仪器的测量探针接地的设备和方法原位最小化与采样变化相关的光谱干扰。最小接触主体界面包括可替换地安装在基座上的支撑件。诸如光纤探针的光学耦合装置通过基座中的探针孔接触测量部位。在使用期间，被摄体将支撑元件的末端置于支撑元件上，使得末端相对于光耦合装置可再现地定位和支撑。支架具有很小的接触面积，使测量点与皮肤接触最小化。接口模块是可调整的，适合任何物体。通过使用最小的接触支持可重复地定位和支撑身体附件，由于与接口模块接触的位置变化，施加的压力和温度瞬变引起的频谱干扰大大降低。

9. 发明授权

US06415167B1 Fiber optic probe placement guide 失效
标题翻译：光纤探头放置指南
公开(公告)号：US06415167B1
公开(公告)日：2002-07-02
申请号：US09563782
申请日：2000-05-02
申请人： Thomas B. Blank , George Acosta , Mutua Mattu , Stephen L. Monfre
发明人： Thomas B. Blank , George Acosta , Mutua Mattu , Stephen L. Monfre
IPC分类号： A61B500
CPC分类号： A61B5/0059 , A61B5/061 , A61B5/14532 , A61B5/1455 , A61B5/6824 , A61B2562/12 , A61B2562/146
摘要： A fiber optic probe placement guide minimizes sampling errors during optical sampling of a tissue measurement site by allowing repeatable placement of the fiber optic probe at a targeted tissue measurement site. A mount, contoured to conform to the shape of the tissue measurement site, typically the arm of a human subject, contains an aperture for receiving a fiber optic probe. A temperature probe on the contact surface of the guide allows for monitoring of surface temperature within the vicinity of the tissue measurement site. Crosshair slots in the mount align with corresponding crosshairs at the tissue measurement site. The fiber optic probe placement guide is affixed to the tissue measurement site by means of adhesive tape or fastenable straps. Guideposts on the external surface of the mount are received by corresponding receptacles on a subject interface bearing the fiber optic probe to facilitate alignment of the fiber optic probe with the aperture.
摘要翻译：光纤探针放置导向器通过允许将光纤探针重复放置在目标组织测量部位来最小化组织测量部位的光学采样期间的采样误差。通常是组织测量部位的形状，通常是人体受试者的臂的形状的安装件包含用于接收光纤探针的孔。引导件的接触表面上的温度探头允许监测组织测量部位附近的表面温度。安装座上的十字准线槽与组织测量部位的相应十字准线对齐。光纤探针放置导板通过胶带或可固定带固定在组织测量部位。安装座外表面上的导轨由承载光纤探头的主体接口上的相应插座接收，以便光纤探头与孔径对准。

10. 发明授权

US06738652B2 Classification and screening of test subjects according to optical thickness of skin 失效
标题翻译：根据皮肤的光学厚度对检查对象进行分类和筛选
公开(公告)号：US06738652B2
公开(公告)日：2004-05-18
申请号：US10297787
申请日：2002-12-09
申请人： Mutua Mattu , Thomas B. Blank , Marcy R. Makarewicz , Branden Rosenhan
发明人： Mutua Mattu , Thomas B. Blank , Marcy R. Makarewicz , Branden Rosenhan
IPC分类号： A61B500
CPC分类号： A61B5/441 , A61B5/0059 , A61B5/1075 , A61B5/442 , A61B5/4869 , A61B5/4872 , A61B5/7264 , A61B2560/0223 , A61B2562/0242
摘要： A method for classifying live subjects according to optical thickness of the skin is based on noninvasive, near-infrared reflectance measurements on skin tissue. An indicator of skin optical thickness is derived through analysis of the water, fat, and protein marker bands in the near infrared spectrum. The skin thickness indicator may then be used to evaluate the suitability of the subject for calibration on a standardized set of optical probes. The optical probes in the standardized set are designed to cover a range of penetration depths by varying the distance distribution between illuminator and detector fibers on each probe tip.
摘要翻译：根据皮肤的光学厚度对活体进行分类的方法是基于皮肤组织上的无创的近红外反射测量。通过分析近红外光谱中的水，脂肪和蛋白质标记带，得出皮肤光学厚度的指标。然后可以使用皮肤厚度指示器来评估受试者在标准化的一组光学探针上的校准的适合性。标准化组中的光学探针被设计成通过改变每个探针尖端上的照射器和检测器光纤之间的距离分布来覆盖一定范围的穿透深度。

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