公开(公告)号：US07033775B2

公开(公告)日：2006-04-25

申请号：US10888033

申请日：2004-07-09

申请人： Edwin F. Ullman ,  Marcel Pirio ,  Mary C. Ericson ,  Daniel B. Wagner ,  Dariush Davalian

发明人： Edwin F. Ullman ,  Marcel Pirio ,  Mary C. Ericson ,  Daniel B. Wagner ,  Dariush Davalian

IPC分类号： G01N33/53

CPC分类号： G01N33/946 ,  G01N33/54386 ,  Y10S435/975 ,  Y10S436/805 ,  Y10S436/811 ,  Y10S436/815 ,  Y10S436/816 ,  Y10S436/817 ,  Y10S436/901

摘要： Methods, compositions and kits are disclosed. The methods are directed to determining the presence of one or more analytes in a sample suspected of containing any one of a plurality of the analytes. A combination is provided comprising in a medium (i) the sample, (ii) a binding partner for each of the analytes, (iii) for each of the analytes, a first reagent comprising a member of a signal producing system, a ligand and an analyte analog, and (iv) a second reagent comprising a binding partner for the ligand. The binding of the binding partner for the ligand is affected by the presence of an analyte and alters the amount of signal produced by the member of the signal producing system. The signal thus is modulated if one or more of the analytes are present in the sample. The amount of the signal is determined and is related to the presence of one or more of the analytes in the sample. The method may be homogeneous or heterogeneous.

公开(公告)号：US06406913B1

公开(公告)日：2002-06-18

申请号：US08471130

申请日：1995-06-06

申请人： Edwin F. Ullman ,  Hrair Kirakossian ,  John S. Pease ,  Yuri Daniloff ,  Daniel B. Wagner

发明人： Edwin F. Ullman ,  Hrair Kirakossian ,  John S. Pease ,  Yuri Daniloff ,  Daniel B. Wagner

IPC分类号： G01T1161

CPC分类号： C07D265/30 ,  C07D279/12 ,  C07D327/06 ,  G01N33/54313 ,  G01N33/5436 ,  G01N33/58 ,  G01N33/582 ,  G01N33/585 ,  G01N33/586 ,  Y10S435/81 ,  Y10S435/968 ,  Y10S435/971 ,  Y10S435/973 ,  Y10S435/975 ,  Y10S436/829

摘要： Methods are disclosed for determining an analyte in a medium suspected of containing the analyte. One method comprises treating a medium suspected of containing an analyte under conditions such that the analyte, if present, causes a photosensitizer and a chemiluminescent compound to come into close proximity. The photosensitizer generates singlet oxygen and activates the chemiluminescent compound when it is in close proximity. The activated chemiluminescent compound subsequently produces light. The amount of light produced is related to the amount of analyte in the medium. Preferably, at least one of the photosensitizer and chemiluminescent compound is associated with a surface which is usually a suspendible particle, and a specific binding pair member is bound thereto. Compositions and kits are also disclosed.

摘要翻译： 公开了用于确定怀疑含有分析物的介质中的分析物的方法。 一种方法包括在允许分析物（如果存在）使光敏剂和化学发光化合物接近的条件下处理疑似含有分析物的介质。 光敏剂产生单线态氧并在化学发光化合物接近时激活化学发光化合物。 活化的化学发光化合物随后产生光。 所产生的光量与介质中分析物的量有关。 优选地，光敏剂和化学发光化合物中的至少一种与通常是悬浮颗粒的表面相关联，并且特异性结合对成员结合到其上。 还公开了组合物和试剂盒。

公开(公告)号：US5618732A

公开(公告)日：1997-04-08

申请号：US434617

申请日：1995-05-04

申请人： John S. Pease ,  Hrair Kirakossian ,  Daniel B. Wagner ,  Edwin F. Ullman

发明人： John S. Pease ,  Hrair Kirakossian ,  Daniel B. Wagner ,  Edwin F. Ullman

IPC分类号： G01N33/532 ,  G01N21/78 ,  G01N33/58 ,  G01N21/64 ,  G01N21/76

CPC分类号： G01N33/582 ,  Y10S435/81 ,  Y10S436/829 ,  Y10S436/905 ,  Y10T436/10

摘要： Methods for labeling a material are disclosed. The methods comprise combining with the material (a) a photosensitizer capable upon irradiation of generating singlet oxygen and (b) a chemiluminescent compound capable of being activated by singlet oxygen wherein the photosensitizer and the chemiluminescent compound are incorporated in a particulate matrix or a non-particulate solid matrix. The particulate matrix can be solid or fluid. The methods allow for generating delayed luminescence, which can be realized upon irradiation of the matrix. The methods have application to the determination of an analyte in a medium suspected of containing the analyte. One method comprises subjecting a medium suspected of containing an analyte to conditions under which a complex of specific binding pair (sbp) members is formed in relation to the presence of the analyte and determining whether the sbp member complex has formed by employing as a label a single composition having both chemiluminescent and photosensitizer properties. Upon activation of the photosensitizer property singlet oxygen is generated and activates the chemiluminescent property. Compositions and kits are also disclosed.

摘要翻译： 公开了标记材料的方法。 所述方法包括与材料（a）结合，所述光敏剂能够在产生单线态氧的照射时和（b）能够被单线态氧活化的化学发光化合物，其中光敏剂和化学发光化合物掺入颗粒基质或非均相中， 颗粒状固体基质。 颗粒基质可以是固体或流体。 这些方法允许产生延迟发光，这可以在照射基质时实现。 该方法可用于确定怀疑含有分析物的介质中的分析物。 一种方法包括使怀疑含有分析物的培养基相对于分析物的存在形成特异性结合对（sbp）成员的复合物的条件，以及通过使用标记a来确定sbp成员复合物是否形成 具有化学发光和光敏剂性质的单一组合物。 激活光敏剂时，产生单线态氧并激活化学发光性能。 还公开了组合物和试剂盒。

公开(公告)号：US5045478A

公开(公告)日：1991-09-03

申请号：US106385

申请日：1987-10-09

申请人： Daniel B. Wagner ,  Uri Piran

发明人： Daniel B. Wagner ,  Uri Piran

IPC分类号： G01N33/532 ,  G01N33/58

CPC分类号： G01N33/586 ,  G01N33/532 ,  Y10S436/829

摘要： Sacs comprising a compound having a hydrophilic peptide radical are prepared and are believed to have improved stability as a result of hydrogen bonding. The sacs, including a detectable marker and derivatized with a ligand may be used as a tracer in an assay.At least a portion of the sac is formed from a compound having the following structural formula:X-Y-Z,whereinX is a hydrophobic radical;Y is a hydrophilic peptide; andZ is a radical which includes a non-hydrolyzable polar group.

摘要翻译： 制备包含具有亲水性肽基团的化合物的囊，并认为由于氢键而具有改善的稳定性。 包括可检测标记物并用配体衍生的囊可以在测定中用作示踪剂。 囊的至少一部分由具有以下结构式的化合物形成：X-Y-Z，其中X是疏水基; Y是亲水性肽; Z是包含非水解极性基团的基团。

公开(公告)号：US5017473A

公开(公告)日：1991-05-21

申请号：US54466

申请日：1987-05-26

申请人： Daniel B. Wagner

发明人： Daniel B. Wagner

IPC分类号： G01N33/542 ,  G01N33/58

CPC分类号： G01N33/582 ,  G01N33/542 ,  Y10S435/81 ,  Y10S435/975 ,  Y10S436/808 ,  Y10S436/81 ,  Y10S436/826

摘要： A method for separation-free solid phase immunoassay of an analyte includes contacting an antianalyte attached to the surface of a solid support with the analyte, a light absorbing material and a tracer for the analyte which includes a label. The resulting mixture is incubated and chemiluminescence is generated. All of the chemiluminescence is absorbed by the light absorbing material except that associated with the bound tracer whereby the only emission detected is due to the bound tracer. Since emission from free tracer in the fluid phase of the assay medium is not detected, separation of the bound and free fractions is unnecessary. The invention includes a kit of materials useful in performing an immunoassay in accordance with the method of the invention.

摘要翻译： 分析物的无分离固相免疫测定的方法包括将附着于固体支持物表面的分析物与分析物接触，吸光材料和用于包括标签的分析物的示踪剂。 将所得混合物孵育并产生化学发光。 所有的化学发光都被光吸收材料吸收，除了与结合的示踪剂相关，因此检测到的唯一发射是由于结合的示踪剂。 由于没有检测到在测定介质的流体相中的游离示踪剂的发射，因此不需要分离结合的和游离的级分。 本发明包括用于根据本发明的方法进行免疫测定的材料试剂盒。

公开(公告)号：US4978625A

公开(公告)日：1990-12-18

申请号：US109689

申请日：1987-10-19

申请人： Daniel B. Wagner ,  Glenn P. Vonk ,  Thomas J. Mercolino

发明人： Daniel B. Wagner ,  Glenn P. Vonk ,  Thomas J. Mercolino

IPC分类号： G01N33/58

CPC分类号： G01N33/586 ,  Y10S436/80 ,  Y10S436/808 ,  Y10S436/829

摘要： In a method for fluorescence immunoassay of an analyte, an antianalyte attached to the surface of a solid support is contacted with the analyte and a tracer which includes a substantially water insoluble fluorescent dye occluded in the nonaqueous portion of a sac. After binding reactions involving the antianalyte, analyte and tracer, the solid support is separated, excitation light is applied and fluorescence from dye in intact sacs bound to the solid support is measured and compared to fluorescence measured when known quantities of analyte are assayed. The invention includes a kit of materials useful in performing an immunoassay in accordance with the method of the invention.

摘要翻译： 在用于分析物的荧光免疫测定的方法中，附着在固体支持物表面的抗分析物与分析物和示踪剂接触，所述示踪剂包括封闭在囊的非水部分中的基本上不溶于水的荧光染料。 在涉及抗分析物，分析物和示踪剂的结合反应之后，分离固体支持物，施加激发光，并测量与固体支持物结合的完整囊中来自染料的荧光，并与测定已知量的分析物时测量的荧光进行比较。 本发明包括用于根据本发明的方法进行免疫测定的材料试剂盒。

公开(公告)号：US4861728A

公开(公告)日：1989-08-29

申请号：US77363

申请日：1987-07-24

申请人： Daniel B. Wagner

发明人： Daniel B. Wagner

IPC分类号： G01N33/72

CPC分类号： G01N33/723 ,  Y10S436/80 ,  Y10S436/815

摘要： A method for determining the percentage of glycosylated hemoglobin in the total hemoglobin of a blood sample includes binding of both glycosylated and nonglycosylated hemoglobin competitively to a nonspecific binder for hemoglobin affixed to a dipstick and reacting the glycosylated hemoglobin with a dihydroxyboryl reagent conjugated to a fluorescent dye. When the binding and reacting steps are complete, the dipstick is washed and its color is measured by absorption of incident light having a wavelength within the absorption range of hemoglobin as an indication of total hemoglobin in the sample. Incident light having a wavelength within the absorption range of the dye is then applied to the dipstick and fluorescence from the dipstick is measured as an indication of glycosylated hemoglobin. The measurements may be made with a reflectometer capable of computing the percentage of glycosylated hemoglobin in the sample from the color and fluorescence measurements. The invention includes a kit of materials useful for performing the assay method of the invention.

摘要翻译： 用于测定血液样品的总血红蛋白中糖基化血红蛋白百分比的方法包括将糖基化和非糖基化血红蛋白竞争性地与非特异性粘合剂结合，用于混合在量油尺上的血红蛋白，并使糖基化血红蛋白与缀合到荧光染料上的二羟基硼烷试剂反应 。 当结合和反应步骤完成时，清洗量油尺，并通过吸收波长在血红蛋白吸收范围内的入射光来测量其颜色，作为样品中总血红蛋白的指示。 然后将具有在染料吸收范围内的波长的入射光施加到量油尺上，并测量来自量油尺的荧光作为糖基化血红蛋白的指示。 可以使用能够从颜色和荧光测量计算样品中糖基化血红蛋白百分比的反射计进行测量。 本发明包括可用于实施本发明的测定方法的一组材料。

公开(公告)号：US4703017A

公开(公告)日：1987-10-27

申请号：US579667

申请日：1984-02-14

申请人： Robert L. Campbell ,  Daniel B. Wagner ,  James P. O'Connell

发明人： Robert L. Campbell ,  Daniel B. Wagner ,  James P. O'Connell

IPC分类号： G01N33/532 ,  G01N33/543 ,  G01N33/544 ,  G01N33/548

CPC分类号： B82Y5/00 ,  G01N33/532 ,  G01N33/543 ,  Y10S436/80 ,  Y10S436/808 ,  Y10S436/809 ,  Y10S436/815 ,  Y10S436/818 ,  Y10S436/829

摘要： Solid phase assay for an analyte wherein binder is supported on a solid support, such as nitrocellulose, and the tracer is comprised of ligand labeled with a colored particulate label, such as a liposome including a dye. The assay has a high sensitivity, and the tracer is visible on the support under assay conditions, whereby tracer can be determined, without instrumentation, and without further treatment thereof.

摘要翻译： 其中粘合剂负载在固体支持物如硝化纤维素上的分析物的固相测定，示踪剂由用着色颗粒标记（例如包括染料的脂质体）标记的配体组成。 该测定具有高灵敏度，并且示踪剂在测定条件下在载体上可见，由此可以测定示踪剂，无需仪器，无需进一步处理。

公开(公告)号：US4301139A

公开(公告)日：1981-11-17

申请号：US50543

申请日：1979-06-21

申请人： Judith Feingers ,  Anthony J. Pick ,  Daniel B. Wagner

发明人： Judith Feingers ,  Anthony J. Pick ,  Daniel B. Wagner

IPC分类号： G01N30/52 ,  G01N33/538 ,  G01N33/78 ,  G01N33/48 ,  B65D7/00

CPC分类号： G01N33/78 ,  G01N33/538 ,  G01N2030/528 ,  G01N30/52 ,  Y10S436/804 ,  Y10S436/808

摘要： A specific binding assay method, and a test device and test kit for use therein, for determining a liqand, such as an antigen or antibody, in, or the ligand binding capacity of, a liquid medium, particularly a body fluid such as serum, wherein the unknown ligand competes with a labeled component, such as a radiolabeled form of the ligand or of a binding analog of the ligand, for binding with a binding partner, and wherein separation of the resulting bound-species and free-species of the labeled component is accomplished by allowing the liquid reaction mixture to be drawn by capillary action into a column comprising a bed of an adsorbent material selective for one of the two species. The improvement comprises using a column containing at least one additional bed of capillarily absorbent material disposed above said adsorbent bed and which is substantially nonadsorbent relative to the one of said two species which said adsorbent bed selectively binds. The use of specific types of capillarily absorbent beds in addition to the selectively adsorbent bed to form multilayer columns overcomes several unforeseen problems encountered in using the previously known column chromatography method for certain assay applications.

摘要翻译： 用于确定液体培养基，特别是体液如血清的液体培养基中的液体，例如抗原或抗体或其配体结合能力的特异性结合测定方法以及用于其中的测试装置和测试试剂盒， 其中未知的配体与标记的组分例如配体的放射性标记形式或配体的结合类似物竞争与结合配偶体结合，并且其中分离得到的结合物种和自由物种的标记的 通过使液体反应混合物通过毛细作用拉伸到包括对两种物质之一选择性的吸附剂材料床的塔中来实现。 该改进包括使用包含至少一个额外的毛细吸收材料床的柱，其设置在所述吸附床上方，并且相对于所述吸附床选择性结合的所述两种物质之一基本上不吸附。 除了选择性吸附床以形成多层柱之外，特定类型的毛细吸收床的使用克服了在某些测定应用中使用先前已知的柱色谱法遇到的几个不可预见的问题。

公开(公告)号：US4940669A

公开(公告)日：1990-07-10

申请号：US49971

申请日：1987-05-15

申请人： Daniel B. Wagner ,  Glenn P. Vonk

发明人： Daniel B. Wagner ,  Glenn P. Vonk

IPC分类号： G01N33/58

CPC分类号： G01N33/586 ,  Y10S436/80 ,  Y10S436/821 ,  Y10S436/829

摘要： A sac, in particular a vesicle, having a detectable metal, in particular a rear earth metal, encapsulated therein. The sac may be sensitized with a ligand and used in an assay. The vesicle is stored and/or used in an aqueous solution which includes the rare earth metal to increase the concentration of metal in the sac.

摘要翻译： 具有可检测金属的囊，特别是囊泡，其囊封在其中。 囊可以用配体致敏并用于测定。 将囊泡储存和/或用于包括稀土金属的水溶液中以增加囊中金属的浓度。