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    • 1. 发明授权
    • Method and apparatus for determining glucose concentration in a
biological sample
    • 用于测定生物样品中葡萄糖浓度的方法和装置
    • US5710630A
    • 1998-01-20
    • US530241
    • 1995-10-10
    • Matthias EssenpreisAlexander KnuettelDirk Boecker
    • Matthias EssenpreisAlexander KnuettelDirk Boecker
    • A61B5/145A61B5/00A61B5/1455G01N21/31G01N21/45G01N21/49G01N33/487G01B9/02
    • A61B5/1455A61B5/14532G01N21/314G01N21/45G01N21/49
    • A method for the analytical determination of the glucose concentration in a biological sample. In a detection step, light is irradiated into the sample and the light emerging therefrom after interaction with the sample emerges therefrom is detected in order to measure a physical light property affected by said interaction. The glucose concentration is determined from this measurement in an evaluation step. To provide a method for determining glucose in reagent-free and non-invasive manner, the invention proposes that a portion of the light emitted by the light source be guided along a reference light path of defined optical path length to the photodetector, that the total measuring light path also has a defined optical length and that the measuring light path after it has traversed the sample is so combined with the reference light path that the measuring light and the reference light interfere with each other. The photodetector measures an interference signal used in the evaluation step to determine the glucose concentration.
    • PCT No.PCT / DE95 / 00573 Sec。 371 1995年10月10日第 102(e)1995年10月10日日期PCT提交1995年4月26日PCT公布。 WO95 / 30368 PCT出版物 日期:1995年11月16日一种用于分析生物样品中葡萄糖浓度的方法。 在检测步骤中,将光照射到样品中,并且检测出与样品相互作用后从其出来的光从其中出来的光,以测量受所述相互作用影响的物理光特性。 在评价步骤中由该测定确定葡萄糖浓度。 为了提供一种以无试剂和非侵入性方式测定葡萄糖的方法,本发明提出将由光源发射的光的一部分沿着限定的光路长度的参考光路引导到光电检测器,总共 测量光路还具有限定的光学长度,并且其经过样本之后的测量光路与参考光路组合,使得测量光和参考光彼此干涉。 光电检测器测量在评估步骤中使用的干扰信号以确定葡萄糖浓度。
    • 2. 发明授权
    • Method for investigating a scattering medium with intensity-modulated
light
    • 用强度调制光调查散射介质的方法
    • US5713352A
    • 1998-02-03
    • US572641
    • 1995-12-14
    • Matthias EssenpreisHans-Peter HaarDirk BoeckerAlexander Knuettel
    • Matthias EssenpreisHans-Peter HaarDirk BoeckerAlexander Knuettel
    • G01N33/483A61B5/145A61B5/1455G01N21/27G01N21/41G01N21/49A61B5/00
    • G01N21/49
    • The invention concerns a method for investigating a scattering medium, especially a biological matrix, with intensity-modulated light. In order, in such a frequency-domain measuring procedure, to reduce the expenditure on electronics without restricting accuracy of measurement, a method is proposed, in which, in order to investigate a scattering medium, especially a biological matrix, with intensity-modulated light, a high-frequency modulation signal is generated by a frequency generator (18), the intensity of a light emitter (10) is modulated with a modulation signal and the light from the light emitter (10) is radiated into the medium, the modulation signal includes frequency chirps during which the modulation frequency is tuned from an initial frequency to a final frequency, the modulation signal is delivered from the frequency generator (18) via at least two different signal paths (23A, 24) to a signal mixer (31), so that during a frequency chirp the input signals of the signal mixer (31) differ by a differential frequency whose magnitude is a function of the difference between the signal transit times over the at least two signal paths (23A, 24) and of the rate of change of the modulation frequency, wherein at least one of the signal paths includes a light path section (20A) passing through the medium as a measurement signal path (23A), and the output signal of the signal mixer (31) is further processed to produce information relating to the scattering medium (FIG. 2).
    • 本发明涉及用强度调制光来研究散射介质,特别是生物基质的方法。 为了在这样的频域测量过程中,为了减少电子设备的开销而不限制测量精度,提出了一种方法,其中为了研究具有强度调制光的散射介质,特别是生物矩阵 ,由频率发生器(18)产生高频调制信号,用调制信号调制发光体(10)的强度,将来自发光体(10)的光照射到介质中,调制 信号包括调制频率从初始频率调谐到最终频率的频率啁啾,调制信号经由至少两个不同的信号路径(23A,24)从频率发生器(18)传送到信号混合器(31 ),使得在频率啁啾期间,信号混合器(31)的输入信号相差一个差分频率,其幅度是在at信号传输时间之间的差值的函数 至少两个信号路径(23A,24)和调制频率的变化率,其中信号路径中的至少一个包括通过介质作为测量信号路径(23A)的光路部分(20A),以及 信号混合器(31)的输出信号被进一步处理以产生与散射介质有关的信息(图3)。 2)。
    • 3. 发明授权
    • Process and device for determining an analyte contained in a scattering
matrix
    • 用于确定包含在散射矩阵中的分析物的方法和装置
    • US5962852A
    • 1999-10-05
    • US875349
    • 1997-07-28
    • Alexander KnuettelDirk BoeckerMatthias Essenpreis
    • Alexander KnuettelDirk BoeckerMatthias Essenpreis
    • A61B5/00G01N21/49
    • A61B5/1455A61B5/0066A61B5/14532G01N21/49
    • Method for determining an analyte in a scattering matrix. In a detection step detection measurements are made in which light is irradiated into the matrix as primary light and light leaving the scattering matrix is detected as secondary light, in order to determine as a measurement quantity a measurable physical property of the light which is variable due to the interaction of the light with the matrix. Information on the presence of the analyte in the matrix is determined in an evaluation step. The determination of optically weakly absorbing analytes against a strongly absorbing interference background is improved by the use of two selection methods for the depth selective detection of the secondary light in combination with one another. Primary light is focused by means of a primary light optically focussing element onto a region of focus lying in the matrix at a predetermined measuring depth and the region of focus is imaged by means of a secondary light optically focusing element onto a light entry aperture arranged in the light path of the secondary light to the detector. In addition to this first depth selection by a confocal arrangement, a second depth selection device is used to detect light reflected from a defined measuring depth as secondary light, with the measuring depth coinciding with the depth of focus.
    • PCT No.PCT / DE97 / 00168 Sec。 371日期1997年7月28日第 102(e)1997年7月28日PCT PCT 1997年1月23日PCT公布。 公开号WO97 / 27469 日期1997年7月31日确定散射矩阵中的分析物的方法。 在检测步骤中,进行检测测量,其中将光作为初级光照射到基质中,并且离开散射矩阵的光被检测为次级光,以便将测量量确定为可变的光的可测量的物理性质 对光与基质的相互作用。 在评估步骤中确定基质中分析物存在的信息。 通过使用两种选择方法来对二次光的深度选择性检测相结​​合,可以改善光吸收弱吸收分析物的强吸收干涉背景的测定。 初级光通过初级光光聚焦元件聚焦在位于矩阵中的预定测量深度的焦点区域上,并且聚焦的区域通过次光光学聚焦元件成像到布置在 次级光到检测器的光路。 除了通过共焦排列的第一深度选择之外,使用第二深度选择装置来检测从限定的测量深度反射的光作为次级光,其测量深度与焦深一致。
    • 4. 发明授权
    • Method and apparatus for determining analytical data concerning the
inside of a scattering matrix
    • 用于确定散射矩阵内部的分析数据的方法和装置
    • US5825488A
    • 1998-10-20
    • US745204
    • 1996-11-08
    • Matthias KohlMark CopeMatthias EssenpreisDirk Boecker
    • Matthias KohlMark CopeMatthias EssenpreisDirk Boecker
    • G01N33/483A61B5/145A61B5/1455G01N21/17G01N21/49G01N33/543G01N21/47
    • G01N21/49
    • A method and an apparatus for determining analytical data concerning the inside of a scattering matrix, in particular of a biological sample. In a detection step detection measurements are carried out in which light is irradiated into the matrix as primary light at an irradiation site (12) through an interface bounding the scattering matrix (6) and light emerging out of the scattering matrix through the interface is detected as secondary light at a detection site (13) at a predetermined measuring distance from the irradiation site, in order to determine as a measurement variable a measurable physical property of the light which varies due to the interaction of the light with the scattering matrix, which measurement variable is a measure of the analytical data to be determined. In an evaluation step the analytical data are determined on the basis of the measurement variable measured in the detection step. In order that such a matrix analysis may be carried out with relatively simple measuring means, at least two detection measurements are carried out in the detection step with different reflection conditions at the interface (5) between the irradiation site (12) and the detection site (13), in each of which the measurement value of the measurement variable is determined.
    • 一种用于确定关于散射矩阵,特别是生物样品的内部的分析数据的方法和装置。 在检测步骤中,进行检测测量,其中在辐射位置(12)处通过界定散射矩阵(6)的界面将光照射到基质中作为初级光,并且检测出通过界面从散射矩阵出射的光 作为在距离照射部位预定测量距离处的检测部位(13)处的二次光,以便将由于光与散射矩阵的相互作用而变化的光的可测量的物理性质确定为测量变量,其中 测量变量是要确定的分析数据的度量。 在评估步骤中,基于在检测步骤中测量的测量变量来确定分析数据。 为了可以用相对简单的测量装置进行这种矩阵分析,在具有不同反射条件的检测步骤中,在照射部位(12)和检测部位(5)之间的界面(5)处进行至少两次检测测量 (13),其中每个测量变量的测量值被确定。
    • 5. 发明授权
    • Method and aparatus for determining an analyte in a biological sample
    • 用于测定生物样品中分析物的方法和装置
    • US5770454A
    • 1998-06-23
    • US737135
    • 1996-11-07
    • Matthias EssenpreisDirk BoeckerHeinz-Michael HeinHans-Peter Haar
    • Matthias EssenpreisDirk BoeckerHeinz-Michael HeinHans-Peter Haar
    • A61B5/00G01N21/49G01N21/00
    • A61B5/1455A61B5/14532G01N21/49A61B2562/0233A61B2562/0242A61B2562/043
    • A method and apparatus for analytical determination of a concentration of an analyte in a biological sample include a series of hardware elements and method steps which perform at least two detection measurements, with each detection measurement including the step of irradiating light at an irradiation site as primary light into the biological sample through a boundary surface. The light is propagated along a light path, and light is detected as it emerges from the biological sample as secondary light through a detection site. The irradiation site and detection site are separated by a measuring distance. At least two detection measurements are performed with at least two different measurement light paths between the irradiation site and the detection site. Each of the detection measurements is a frequency-domain spectroscopic measurement which is performed at at least two different wavelengths of light, and includes a comparison of a phase shift of the secondary light with the primary light as a first measurement variable, and an intensity of the secondary light as a second measurement variable. The method also includes the steps of determining the analyte concentration based upon the first and second measurement variables.
    • PCT No.PCT / DE95 / 00593 Sec。 371日期:1996年11月7日 102(e)日期1996年11月7日PCT提交1995年5月3日PCT公布。 公开号WO95 / 32416 PCT 日期:1995年11月30日用于分析生物样品中分析物浓度的方法和装置包括执行至少两次检测测量的一系列硬件元件和方法步骤,每个检测测量包括将光照射到 照射部位作为通过边界表面进入生物样品的初级光。 光沿光路传播,当从生物样品出现时,通过检测部位作为二次光检测出光。 照射部位和检测部位通过测量距离分开。 在照射部位和检测部位之间至少有两个不同的测量光路进行至少两次检测测量。 每个检测测量是在至少两个不同波长的光下执行的频域光谱测量,并且包括将次级光与初级光的相移作为第一测量变量的比较,以及 次光作为第二测量变量。 该方法还包括基于第一和第二测量变量确定分析物浓度的步骤。
    • 7. 发明授权
    • Method and apparatus for the analysis of glucose in a biological matrix
    • 用于分析生物基质中葡萄糖的方法和装置
    • US5692504A
    • 1997-12-02
    • US592303
    • 1996-02-09
    • Matthias EssenpreisDirk BoeckerHeinz-Michael HeinHans-Peter Haar
    • Matthias EssenpreisDirk BoeckerHeinz-Michael HeinHans-Peter Haar
    • A61B5/145A61B5/00A61B5/1455G01N21/41G01N21/47G01N21/49A61B5/000
    • A61B5/1455A61B5/14532G01N21/41G01N21/47G01N21/49A61B2562/0242G01N2201/0696
    • Method and apparatus for the analytical determination of glucose concentration in a biological matrix, wherein in a detection step light from a light emitter is irradiated into the biological matrix as primary light via a boundary surface of the biological matrix and light emerging from the the biological matrix through a boundary surface is being detected by a light detector in order to determine a measurable physical light property which is changed by interaction with the biological matrix and which correlates with the glucose concentration of said matrix. The glucose concentration is ascertained in an evaluation step on the basis of said change of the physical light property determined in at least one detection step in comparison with a calibration. In order to achieve by such a method good analytical accuracy in reagent-free and non-invasive manner, for instance to observe the change of the concentration of the analyzed substance (monitoring) over an adequate time interval, a measurable parameter corresponding to the light transit-time within the biological matrix between a defined irradiation site and a defined detection site and correlating with the glucose concentration is determined in the detection step.
    • PCT No.PCT / DE94 / 01290 Sec。 371日期1996年2月9日 102(e)日期1996年2月9日PCT 1994年10月29日PCT PCT。 WO95 / 12348 PCT公开号 日期:1995年5月11日用于生物基质中葡萄糖浓度分析测定的方法和装置,其中在检测步骤中,来自发光体的光经由生物基质的边界表面作为主要光照射到生物基质中, 通过光检测器检测生物基质,以便确定通过与生物基质相互作用而改变并与所述基质的葡萄糖浓度相关的可测量的物理光特性。 基于与校准相比在至少一个检测步骤中确定的物理光特性的变化,在评估步骤中确定葡萄糖浓度。 为了通过这种方法实现无试剂和非侵入性的良好的分析精确性,例如在足够的时间间隔内观察分析物质(监测)浓度的变化,对应于光的可测量参数 在检测步骤中确定在确定的照射位点和限定的检测位点之间的生物学基质内的与葡萄糖浓度相关的转运时间。