公开(公告)号：US20110223683A1

公开(公告)日：2011-09-15

申请号：US12721173

申请日：2010-03-10

申请人： Fred E. Regnier ,  Nicholas B. Herold ,  Kevin W. Meyer

发明人： Fred E. Regnier ,  Nicholas B. Herold ,  Kevin W. Meyer

IPC分类号： G01N33/53

CPC分类号： G01N33/53 ,  C12Q1/6816 ,  G01N33/6842 ,  G01N33/6848 ,  C12Q2525/107 ,  C12Q2537/143 ,  C12Q2563/167

摘要： A multi-dimensional method for simultaneously analyzing multiple analytes within a sample solution, comprising adding affinity selectors to a sample solution containing analytes to be measured, the affinity selectors having an affinity for one or more of the analytes within the sample solution; allowing immune complexes to form between the affinity selectors and the analytes; partially or totally resolving the formed immune complexes from non-analyte substances within the sample solution; dissociating the resolved immune complexes; separating the analytes and the affinity selectors of the dissociated immune complexes from one another by capturing the analytes through a surface adsorption process; transferring the captured analytes to a detection means; and resolving the analytes with the detection means in accordance with their mass-to-charge ratios.

摘要翻译： 一种用于同时分析样品溶液中的多种分析物的多维方法，包括将亲和选择剂添加到含有待测量待分析物的样品溶液中，所述亲和选择剂对样品溶液中的一种或多种分析物具有亲和力; 允许在亲和选择剂和分析物之间形成免疫复合物; 形成的免疫复合物部分或全部从样品溶液中的非分析物质中分离出来; 解离分离的免疫复合物; 通过表面吸附过程捕获分析物，将解离的免疫复合物的分析物和亲和选择剂彼此分离; 将捕获的分析物转移到检测装置; 并根据其质荷比，用检测装置分析分析物。

公开(公告)号：US08455202B2

公开(公告)日：2013-06-04

申请号：US12721173

申请日：2010-03-10

申请人： Fred E. Regnier ,  Nicholas B. Herold ,  Kevin W. Meyer

发明人： Fred E. Regnier ,  Nicholas B. Herold ,  Kevin W. Meyer

IPC分类号： G01N33/53

CPC分类号： G01N33/53 ,  C12Q1/6816 ,  G01N33/6842 ,  G01N33/6848 ,  C12Q2525/107 ,  C12Q2537/143 ,  C12Q2563/167

摘要： A multi-dimensional method for simultaneously analyzing multiple analytes within a sample solution, comprising adding affinity selectors to a sample solution containing analytes to be measured, the affinity selectors having an affinity for one or more of the analytes within the sample solution; allowing immune complexes to form between the affinity selectors and the analytes; partially or totally resolving the formed immune complexes from non-analyte substances within the sample solution; dissociating the resolved immune complexes; separating the analytes and the affinity selectors of the dissociated immune complexes from one another by capturing the analytes through a surface adsorption process; transferring the captured analytes to a detection means; and resolving the analytes with the detection means in accordance with their mass-to-charge ratios.

摘要翻译： 一种用于同时分析样品溶液中的多种分析物的多维方法，包括将亲和选择剂添加到含有待测量待分析物的样品溶液中，所述亲和选择剂对样品溶液中的一种或多种分析物具有亲和力; 允许在亲和选择剂和分析物之间形成免疫复合物; 形成的免疫复合物部分或全部从样品溶液中的非分析物质中分离出来; 解离分离的免疫复合物; 通过表面吸附过程捕获分析物，将解离的免疫复合物的分析物和亲和选择剂彼此分离; 将捕获的分析物转移到检测装置; 并根据其质荷比，用检测装置分析分析物。

公开(公告)号：US20120309040A1

公开(公告)日：2012-12-06

申请号：US13515102

申请日：2010-12-10

申请人： Ashraf G. Madian ,  Fred E. Regnier

发明人： Ashraf G. Madian ,  Fred E. Regnier

IPC分类号： G01N27/62 ,  G01N21/64 ,  G01N21/47

CPC分类号： G01N33/6848 ,  G01N33/6842

摘要： A diagnostic method for determining the absence or presence of a disease is provided. The method generally includes assaying the amount and/or types of oxidized peptides in a sample from a subject, and comparing these to the amount and types of reference oxidized polypeptides. The method may include the use of stable isotope label, affinity selection, to identify and quantify changes in oxidized peptides or oxidized proteins associated with diseases such as type II diabetes mellitus, breast cancer, and Parkinson's disease, to monitor a patient's response to a therapeutic agent (e.g., an antioxidant), and/or to monitor disease recurrence.

摘要翻译： 提供了用于确定疾病的不存在或存在的诊断方法。 该方法通常包括测定来自受试者的样品中氧化肽的量和/或类型，并将其与参考氧化多肽的量和类型进行比较。 该方法可以包括使用稳定的同位素标记物，亲和力选择来鉴定和量化与诸如II型糖尿病，乳腺癌和帕金森病等疾病相关的氧化肽或氧化蛋白质的变化，以监测患者对治疗的反应 （例如抗氧化剂）和/或监测疾病复发。

公开(公告)号：US20100273178A1

公开(公告)日：2010-10-28

申请号：US12658057

申请日：2010-02-01

申请人： Fred E. Regnier

发明人： Fred E. Regnier

IPC分类号： G01N33/53 ,  C02F1/469 ,  G01N27/26

CPC分类号： G01N33/6848 ,  G01N33/6803 ,  G01N33/6842 ,  G01N33/6851 ,  Y10T436/24 ,  Y10T436/25

摘要： A method for protein identification in complex mixtures that utilizes affinity selection of constituent proteolytic peptide fragments unique to a protein analyte. These “signature peptides” function as analytical surrogates. Mass spectrometric analysis of the proteolyzed mixture permits identification of a protein in a complex sample without purifying the protein or obtaining its composite peptide signature.

摘要翻译： 一种利用蛋白质分析物特有的成分蛋白水解肽片段的亲和选择的复杂混合物中的蛋白质鉴定方法。 这些“签名肽”作为分析代理。 蛋白水解混合物的质谱分析允许在复杂样品中鉴定蛋白质而不纯化蛋白质或获得其复合肽标记。

公开(公告)号：US07449170B2

公开(公告)日：2008-11-11

申请号：US10256326

申请日：2002-09-27

申请人： Fred E. Regnier ,  Roujian Zhang

发明人： Fred E. Regnier ,  Roujian Zhang

IPC分类号： A61K51/00 ,  G01N24/00

CPC分类号： G01N33/6848 ,  C07K1/13 ,  G01N33/532 ,  G01N33/534 ,  G01N33/58 ,  G01N33/6851 ,  G01N2458/15 ,  Y10T436/24

摘要： Compositions and methods for controlling or eliminating isotope effects during fractionation of chemically equivalent but isotopically distinct compounds. Isotope coding agents contain heavy isotopes other than deuterium. The invention facilitates intelligent data acquisiton. After sample fractionation, isotope abundance ratios are calculated using mass spectrometry, and analytes of interest are identified in real time.

摘要翻译： 用于控制或消除化学等效但同位素不同化合物分馏期间同位素效应的组合物和方法。 同位素编码剂含有除氘之外的重同位素。 本发明便于智能数据采集。 样品分馏后，使用质谱法计算同位素丰度比，实时鉴定目标分析物。

公开(公告)号：US07405831B2

公开(公告)日：2008-07-29

申请号：US11345564

申请日：2006-02-01

申请人： David Nolte ,  Manoj Varma ,  Fred E. Regnier

发明人： David Nolte ,  Manoj Varma ,  Fred E. Regnier

IPC分类号： G01B11/02

CPC分类号： G01N21/45 ,  G01B11/2441 ,  G01N21/4788 ,  G01N21/75 ,  G01N2021/757 ,  G01N2021/7779 ,  Y10T436/111666

摘要： An apparatus for assessing topology of a surface of a target including an optical source for generating a probe laser beam. The apparatus also includes a means for scanning the probe laser beam across at least a portion of the surface of the target and a beamsplitter for redirecting a return signal toward the means for detecting the return signal in a substantially quadrature condition. A quadrature interferometric method for determining the presence or absence of a target analyte in a sample comprising a laser probe beam having a wavelength λ and a waist wo to probe at least a portion of a substrate having a reflecting surface that includes at least a first region having a layer of recognition molecules specific to the target analyte and a second region that does not include a layer of recognition molecules specific to the target analyte.

摘要翻译： 一种用于评估包括用于产生探针激光束的光源的目标表面的拓扑的装置。 该装置还包括用于扫描探针激光束穿过目标表面的至少一部分的装置，以及用于将返回信号转向用于检测基本正交条件下的返回信号的装置的分束器。 一种用于确定样品中目标分析物的存在或不存在的正交干涉法，其包括具有波长λ和腰围的激光探针束以探测具有反射的基底的至少一部分 至少包括具有对靶分析物特异性的识别分子层的第一区域和不包括对靶分析物特异性的识别分子层的第二区域。

公开(公告)号：US06685885B2

公开(公告)日：2004-02-03

申请号：US10022670

申请日：2001-12-17

申请人： David D. Nolte ,  Fred E. Regnier ,  Manoj Varma

发明人： David D. Nolte ,  Fred E. Regnier ,  Manoj Varma

IPC分类号： G01N2145

CPC分类号： G01N21/45 ,  Y10T436/111666

摘要： A device for identifying analytes in a biological sample, including a substrate having a surface lying substantially in a first plane, a plurality of targets, each having a wall lying substantially in a second plane offset from the first plane, and a receptor coating applied to one of the surface and the target walls for binding analytes present in the biological sample when the biological sample is applied to the substrate. A laser beam is sequentially directed onto each of the plurality of target, the laser being positioned relative to the substrate such that when the beam is directed onto a target, a first half of the beam is reflected back to the laser from the wall of the target and a second half of the beam is reflected back to the laser from the surface of the substrate adjacent the target. The laser combines the first and second reflected halves to produce a diffraction signal that has a first value when an analyte is not bound to the receptor coating associated with a target and a second value when an analyte is bound to the receptor coating associated with the target, thereby indicating the presence of the analyte.

摘要翻译： 一种用于识别生物样品中的分析物的装置，包括具有基本上位于第一平面中的表面的基底，多个靶，每个具有基本上位于与第一平面偏移的第二平面中的壁，以及受体涂层， 当将生物样品施加到基底上时，用于结合存在于生物样品中的分析物的表面和靶壁之一。 激光束被顺序地引导到多个靶中的每一个上，激光器相对于基板定位，使得当光束被引导到目标上时，光束的前半部分从反射镜的壁反射回到激光器 目标和光束的后半部分从邻近靶的衬底的表面反射回激光器。 激光器组合第一和第二反射半部以产生衍射信号，当分析物不与靶标相关的受体涂层结合时具有第一值，当分析物结合到与靶标相关的受体涂层时，第二值 ，从而表明分析物的存在。

公开(公告)号：US5552041A

公开(公告)日：1996-09-03

申请号：US317161

申请日：1994-10-03

申请人： Noubar B. Afeyan ,  Fred E. Regnier ,  Robert C. Dean, Jr.

发明人： Noubar B. Afeyan ,  Fred E. Regnier ,  Robert C. Dean, Jr.

IPC分类号： B01D15/08 ,  B01D15/34 ,  G01N30/52

CPC分类号： B01J20/285 ,  B01D15/345 ,  B01J20/28092 ,  B01J20/28095 ,  B01J2220/54 ,  G01N2030/528

摘要： Disclosed are chromatography methods and matrix geometries which permit high resolution, high productivity separation of mixtures of solutes, particularly biological materials. The method involves passing fluids through specially designed chromatography matrices at high flow rates. The matrices define first and second interconnected sets of pores and a high surface area for solute interaction in fluid communication with the members of the second set of pores. The first and second sets of pores are embodied, for example, as the interstices among particles and throughpores within the particles. The pores are dimensioned such that, at achievable high fluid flow rates, convective flow occurs in both pore sets, and the convective flow rate exceeds the rate of solute diffusion in the second pore set. This approach couples convective and diffusive mass transport to and from the active surface and permits increases in fluid velocity without the normally expected bandspreading.

公开(公告)号：US08628977B2

公开(公告)日：2014-01-14

申请号：US12990560

申请日：2009-05-01

申请人： Jiri Adamec ,  Wen-Chu Yang ,  Fred E. Regnier

发明人： Jiri Adamec ,  Wen-Chu Yang ,  Fred E. Regnier

IPC分类号： G01N24/00

CPC分类号： G01N33/6842 ,  G01N33/6845

摘要： Reagents and methods are provided that permit simultaneous analysis of multiple diverse small molecule analytes present in a complex mixture. Samples are labeled with chemically identical but isotopically distinct forms of the labeling reagent, and analyzed using mass spectrometry. A single reagent simultaneously derivatizes multiple small molecule analytes having different reactive functional groups.

摘要翻译： 提供了允许同时分析复杂混合物中存在的多种不同小分子分析物的试剂和方法。 样品用化学相同但同位素不同的标记试剂标记，并用质谱分析。 单个试剂同时衍生具有不同反应性官能团的多个小分子分析物。

公开(公告)号：US07910356B2

公开(公告)日：2011-03-22

申请号：US11345477

申请日：2006-02-01

申请人： David D. Nolte ,  Manoj Varma ,  Fred E. Regnier ,  Leilei Peng

发明人： David D. Nolte ,  Manoj Varma ,  Fred E. Regnier ,  Leilei Peng

IPC分类号： C12M1/34

CPC分类号： G01N33/543 ,  C12Q1/6837

摘要： A planar array having plurality of biological recognition molecules including at least two types of biological recognition molecules distributed about a substrate is disclosed. A first type of biological recognition molecules is distributed according to a first frequency and a second type of biological recognition molecules is distributed according to a second frequency. Another planar array having a plurality of biological recognition molecules including at least two kinds of biological recognition molecules is disclosed. The recognition molecules are distributed about a substrate with first kind of biological recognition molecules distributed at a first height or depth relative to a surface of the substrate and a second kind of biological recognition molecules distributed at a second height or depth relative to the surface. An apparatus including a surface normal interferometry platform including a scanning pathway and a plurality of analyzer molecules adapted to detect the presence or absence of a plurality of target analytes is also disclosed. The plurality of analyzer molecules are distributed about the scanning pathway according to a multiplexing scheme. A method including multiplexing a plurality of kinds of capture molecules about a detection pathway is further disclosed. The method also includes contacting a biological sample to the array, detecting the presence or absence of binding of the plurality of kinds of capture molecules and a plurality of target analytes using interferometry.

摘要翻译： 公开了一种具有多个生物识别分子的平面阵列，其包括分布在基底周围的至少两种类型的生物识别分子。 第一类生物识别分子根据第一频率分布，第二类生物识别分子根据第二频率分布。 公开了具有包括至少两种生物识别分子的多个生物识别分子的另一平面阵列。 识别分子围绕基底分布，第一种生物识别分子分布在相对于基底的表面的第一高度或深度处，以及分布在相对于该表面的第二高度或深度处的第二种生物识别分子。 还公开了一种包括包括扫描路径的表面正常干涉测量平台和适于检测多个目标分析物的存在或不存在的多个分析器分子的装置。 多个分析器分子根据复用方案围绕扫描路径分布。 进一步公开了一种包括关于检测通路复用多种捕获分子的方法。 该方法还包括使生物样品与阵列接触，使用干涉测定法检测多种捕获分子和多种目标分析物的结合的存在或不存在。