CN100476437C - 减少钩效应的流通测定装置及检测方法 - Google Patents
减少钩效应的流通测定装置及检测方法 Download PDFInfo
- Publication number
- CN100476437C CN100476437C CNB2003801052766A CN200380105276A CN100476437C CN 100476437 C CN100476437 C CN 100476437C CN B2003801052766 A CNB2003801052766 A CN B2003801052766A CN 200380105276 A CN200380105276 A CN 200380105276A CN 100476437 C CN100476437 C CN 100476437C
- Authority
- CN
- China
- Prior art keywords
- analyte
- zone
- average
- size
- assay device
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/558—Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/536—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase
- G01N33/537—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with separation of immune complex from unbound antigen or antibody
- G01N33/538—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with separation of immune complex from unbound antigen or antibody by sorbent column, particles or resin strip, i.e. sorbent materials
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
- G01N33/5432—Liposomes or microcapsules
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/805—Optical property
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/807—Apparatus included in process claim, e.g. physical support structures
- Y10S436/809—Multifield plates or multicontainer arrays
Abstract
本发明提供了一种用于检测测试样品中分析物的存在或数量的基于膜的测定装置。该装置采用其上具有多个微孔颗粒的层析区。层析区能够以简单、有效和相对廉价的方式有效减小“钩效应”。尤其是,多个微孔颗粒使得较大尺寸的分析物/探针复合物在未复合的分析物之前到达检测区。由于基本上抑制了未复合的分析物与复合物竞争检测区中的结合位点,因此可限制“假阴性”的发生,甚至在分析物浓度较高的时候。
Description
技术领域
多种不同的分析方法和设备普遍用于流通测定中,用于确定测试样品中可能存在的分析物的存在和/或浓度。例如,免疫测定法利用免疫系统机制,其中抗体是响应作为有机体的病原或外源的抗原的存在而产生的。这些抗体和抗原即免疫反应物能够彼此结合,借此产生能够用来确定生物样品中特定抗原的存在或浓度的高度特异性反应机制。
背景技术
有几种公知的免疫测定法,这些方法利用由可检测的成分标记的免疫反应物,从而能够对分析物进行分析检测。例如,“夹心型”测定法一般涉及使测试样品与可检测的探针(例如染色乳胶或放射性同位素)混合,这些探针与分析物的特异性结合部分缀合。缀合探针(conjugatedprobes)与分析物形成复合物。这些复合物然后到达固定抗体区,在此处抗体与分析物之间发生结合,从而形成三元的“夹心复合物”。夹心复合物位于用于检测分析物的区域。此技术用来获得定量或半定量结果。这些夹心型测定的一些实例在Grubb等人的U.S.4,168,146和Tom等人的U.S.4,366,241中有所描述。
然而,许多传统的“夹心型”测定形式在暴露到较高的分析物浓度时都遇到明显不准确的问题。具体地说,当分析物以高浓度存在时,测定样品中的大部分分析物不与缀合探针形成复合物。这样,未复合的分析物在到达检测区之后,就与复合的分析物竞争结合位点。由于未复合的分析物没有用探针标记,因此不能检测到。据此,如果相当大量的结合位点都被未复合的分析物所占据,那么测定就可表现出“假阴性”。该问题被普遍称作“钩效应(hook effect)”
已经提出多种用于减小免疫测定中的“钩效应”的技术。例如,Neumann等人的U.S.6,184,042中描述了一种用于减小夹心测定中的钩效应的技术。该技术涉及在带有至少两种能够结合分析物的受体的固相存在下培养分析物。第一受体是选自抗体、抗体片段及其混合物的结合分子的低聚体。第二受体结合或能够结合到固相上。可溶性低聚抗体的使用据说能够减小“钩效应”。
然而,对以简单、有效和相对廉价的方式来减小“钩效应”的改进技术,仍然存在需求。
发明内容
按照本发明的一个实施方案,公开了一种用于检测测试样品中分析物的存在或数量的流通测定装置。这种流通测定装置包括与能够产生检测信号的缀合检测探针相通的多孔膜。此多孔膜限定出层析区,在层析区内固定有多个微孔颗粒。这些微孔颗粒能够在相互之间限定出多个空间,这些空间的平均尺寸大于微孔的平均尺寸。在一些实施方案中,微孔的平均尺寸比空间的平均尺寸至少小约100%,而在一些实施方案中,至少小约150%,在一些实施方案中,至少小约250%。微孔颗粒可选自聚苯乙烯、聚丙烯酰胺、聚丙烯腈;硅珠、以及这些物质的组合,并且其表面对于分析物可以是化学惰性的。
多孔膜还限定出位于层析区下游的检测区。捕获试剂固定在检测区内,该试剂被构造成能够结合到缀合检测探针上。在检测区内,缀合检测探针能够产生检测信号,其中由所述检测信号来确定测试样品内分析物的量。
按照本发明的另一个实施方案,公开了一种用于检测测试样品中分析物的存在或含量的流通夹心测定装置。这种测定装置包括与能够产生检测信号的缀合检测探针相通的多孔膜。缀合检测探针被构造成在与测试样品中的分析物接触时能够与其结合,从而形成分析物/探针复合物和未复合的分析物。多孔膜限定出层析区,在层析区内固定有众多微孔颗粒。这些微孔颗粒被构造成使未复合的分析物以比分析物/探针复合物慢的速率流过层析区。多孔膜还包括位于层析区下游的检测区。捕获试剂固定在检测区内,所述捕获试剂被构造成能够结合到分析物/探针复合物上,从而复合物在检测区内产生检测信号,其中由检测信号来确定测试样品内分析物的量。
本发明公开了一种用于检测测试样品中分析物的存在或数量的方法。该方法包括:
i)提供一种流通测定装置,该装置包括与能够产生检测信号的缀合检测探针相通的多孔膜,此多孔膜限定出层析区和位于层析区下游的检测区,在层析区内固定有多个微孔颗粒,其中捕获试剂固定在检测区内;
ii)使含有分析物的测试样品与缀合检测探针接触,从而形成分析物/探针复合物和未复合的分析物;以及
iii)使分析物/探针复合物和未复合的分析物到达层析区,然后到达检测区,其中分析物/探针复合物在未复合的分析物之前到达检测区。
下面更详细地论述本发明的其它特征和方面。
附图说明
本发明的全面和可实施的公开内容,包括其最佳方式,针对本领域的普通技术人员,都参照附图在说明书的剩余部分得到更加具体的阐述,其中:
图1是本发明的流通测定装置的一个实施方案的透视图;
图2图示出将抗体共价缀合到羧基化纳米颗粒上的一个实施方案;
图3是本发明的流通测定装置的一个实施方案的示意图,是在未复合的分析物穿过层析区之前示出的;
图4是图3的实施方案的示意图,是在未复合的分析物穿过层析区之后示出的;
图5是图1所示层析区的分解图。
附图标记在本说明书和附图中的重复使用意味着其代表本发明的相同或类似特征或部件。
具体实施方式
定义
正如本文所用的,术语“分析物”通常是指待检测的物质。例如,分析物可包括抗原性物质、半抗原、抗体以及这些物质的组合。分析物包括但不限于毒素、有机化合物、蛋白质、肽、微生物、氨基酸、核酸、激素、类固醇、维生素、药物(包括那些为了治疗目的而施用的药物和那些为了违法目的而施用的药物)、药物中间体或副产物、细菌、病毒颗粒以及任何上述物质的代谢物或抗体。一些分析物的具体实例包括铁蛋白;肌酸激酶MIB(CK-MB);地高辛;苯妥英;苯巴比妥;卡马西平;万古霉素;庆大霉素;茶碱;丙戊酸;奎尼定;促黄体生成激素(LH);促卵泡激素(FSH);雌二醇、黄体酮;C-反应蛋白;lipocalins;IgE抗体;维生素B2微球蛋白;糖化血红蛋白(Gly、Hb);氢化可的松;毛地黄毒苷;N-乙酰普鲁卡因酰胺(NAPA);普鲁卡因酰胺;风疹抗体,例如风疹-IgG和风疹IgM;毒胞质抗体,例如毒胞质IgG(Toxo-IgG)和毒胞质IgM(Toxo-IgM);睾酮;水杨酸盐;乙酰氨基苯酚;乙肝病毒表面抗原(HBsAg);乙肝核心抗原的抗体,例如抗-乙肝核心抗原IgG和IgM(抗-HBC);人免疫缺陷病毒1和2(HIV1和2);人T-细胞白血病病毒1和2(HTLV);乙肝e抗原(HBeAg);乙肝e抗原的抗体(抗-HBe);促甲状腺素(TSH);甲状腺素(T4);全三碘甲状腺原氨酸(全T3);游离三碘甲状腺原氨酸(游离T3);癌胚抗原(CEA);以及α-胎儿蛋白(AFP)。滥用和受控物质的药物包括但不限于麻黄碱;脱氧麻黄碱;巴比妥酸盐,例如异戊巴比妥、司可巴比妥、戊巴比妥、苯巴比妥和巴比妥;苯二氮杂类,例如利眠宁和安定;大麻素类,例如印度大麻和大麻;可卡因;芬太尼;LSD;安眠酮;鸦片制剂,例如海洛因、吗啡、可待因、盐酸二氢吗啡酮、氢可酮、美沙酮、氧可酮、氧吗啡酮和鸦片;苯环利定;和丙氧吩。其它潜在的分析物在Everhart等人的U.S.6,436,651和Tom等人的U.S.4,366,241中有所描述。
本文所用术语“测试样品”通常是指被怀疑含有分析物的材料。测试样品可从源体获得后直接使用,或者进行预处理以改善样品的特性。测试样品可来自任何生物源,例如生理流体,包括血液、间质液、唾液、眼晶状体液、脑脊髓液、汗液、尿液、乳液、腹水、raucous、滑液、腹膜液、阴道液、羊膜液等。测试样品在使用前可预处理,例如用血液制备血浆、稀释粘稠液等。处理方法包括过滤、沉淀、稀释、蒸馏、浓缩、干扰成分的灭活、以及试剂的加入。除了生理流体之外,还可以使用其它液态样品,例如用于环境或食品生产性能测定的水、食品等。此外,被怀疑含有分析物的固体材料也可用作测试样品。在一些情况下,有益的是,改善固体测试样品以形成液态介质或释放分析物。
详细描述
现在详细参照本发明的多个不同实施方案,其中的一个或多个实例在以下列出。每个实例都是为了解释本发明,而对本发明没有限定作用。事实上,对于本领域技术人员显而易见的是,在不脱离本发明的范围或精髓的情况下能够对本发明作出多种修改和变型。例如,作为实施方案的一部分而阐述或描述的特征可用在另一个实施方案上,从而产生又一个实施方案。于是,本发明意在覆盖这样的修改和变型,即它们在所附的权利要求书及其等同物的范围内。
总体上,本发明涉及一种用于检测测试样品中分析物的存在或数量的基于膜的测定装置。该装置采用层析区,多个微孔颗粒位于层析区上。层析区能够以简单、有效和相对廉价的方式有效减小“钩效应”。尤其是,众多微孔颗粒允许大尺寸的分析物/探针复合物在未复合的分析物之前到达检测区。由于基本上抑制了未复合的分析物与复合物在检测区竞争结合位点,因此可以限制“假阴性”的发生,甚至在分析物的浓度较高的情况下。
例如,参照图1,现在更详细地描述按照本发明形成的流通测定装置20的一个实施方案。如图所示,装置20包含任选由刚性材料21支撑着的多孔膜23。通常,多孔膜23可以由测试样品能够通过的任何材料制成。例如,用来形成多孔膜23的材料可包括但不限于天然材料、合成材料、或者天然存在的被合成改性的材料,例如多糖(诸如纸和纤维素衍生物之类的纤维素材料,例如醋酸纤维素和硝基纤维素);聚醚砜;尼龙膜;硅石;均匀分散在多孔聚合物基质中的无机材料,例如去活氧化铝、硅藻土、MgSO4或其它无机精细材料,其中聚合物为例如氯乙烯、氯乙烯-丙烯共聚物和氯乙烯-醋酸乙烯酯共聚物;布,包括天然存在的(例如棉花)及合成的(例如尼龙或人造纤维);多孔凝胶,例如硅胶、琼脂糖、右旋糖苷和明胶;聚合物膜,例如聚丙烯酰胺等等。在一个特定实施方案中,多孔膜23是由硝基纤维素和/或聚酯砜材料形成的。应该理解,术语“硝基纤维素”是指纤维素的硝酸酯,其可以是单独的硝基纤维素,或者是硝酸与其它酸(例如具有1-7个碳原子的脂肪族羧酸)的混合酯。
装置20还可以包含芯吸(wicking)垫28。芯吸垫28通常接收已经通过整个多孔膜23迁移的流体。正如本领域内所公知的,芯吸垫28有助于促进毛细作用和通过膜23的流体流动。
为了在测试样品内启动分析物的检测,使用者可直接将测试样品加入到一部分多孔膜23上,然后样品可通过膜23移动。或者是,测试样品可以先加到与多孔膜23以流体相通的取样垫(未示出)上。可用来形成取样垫的一些适宜材料包括但不限于硝基纤维素、纤维素、多孔聚乙烯垫和玻璃纤维滤纸。如果需要的话,取样垫还可含有扩散地或非扩散地附着到其上的一种或多种测定预处理试剂。
在图示的实施方案中,测试样品从取样垫(未示出)移动到以与取样垫一端相通的方式放置的缀合垫22上。缀合垫22由测试样品能够通过的材料形成。例如,在一个实施方案中,缀合垫22由玻璃纤维形成。虽然仅仅示出一个缀合垫22,但是应该理解,其它缀合垫也可用于本发明。
为了易于准确检测测试样品内分析物的存在或缺乏,将探针施加在装置20的多个不同部位。如以下更详细描述的,探针可用于分析物的检测和校正。通常能够产生可目视检测或通过仪器设备检测的信号的任何物质都可以用作探针。各种合适的物质包括发色团;催化剂;荧光化合物;化学发光化合物;磷光化合物;放射性化合物;直接目视标记物,包括胶状金属(例如金)和非金属颗粒、染料颗粒、酶或底物、或有机聚合物胶乳颗粒;脂质体或含有信号生成物的其它囊泡等等。例如,适合用作探针的一些酶公开在Litman等人的U.S.4,275,149中,该文献在此作为参考全部引入本文。酶/底物系统的一个实例是酶碱性磷酸酶和底物硝基蓝四唑-5-溴-4-氯-3-吲哚基磷酸盐、或者这些物质的衍生物或类似物、或者底物4-甲基伞形基(umbelliferyl)-磷酸盐。其它合适的探针在Jou等人的U.S.5,670,381和Tarcha等人的U.S.5,252,459中有所描述,这些文献在此作为参考全部引入本文。
在一些实施方案中,探针可含有产生可检测信号的荧光化合物。荧光化合物可以是荧光分子、聚合物、树枝状物质、颗粒等等。合适荧光分子的一些实例例如包括但不限于荧光素、铕螯合物、藻胆蛋白质、若丹明以及这些物质的衍生物和类似物。可目视检测的有色化合物也能够用作探针,借此在无需其它信号生成试剂的情况下,提供了样品中分析物的存在或浓度的直接有色读数。
探针,诸如如上所述的探针,可单独使用或与微粒(有时称作“珠”或“微珠”)结合使用。例如,可使用天然存在的微粒,例如晶核、支原体、质粒、质体、哺乳动物细胞(例如红细胞血影)、单细胞微生物(例如细菌)、多糖(例如琼脂糖)等等。此外,还可采用合成微粒。例如,在一个实施方案中,采用用荧光染料或有色染料标记的胶乳微粒。虽然任何胶乳微粒都可用于本发明,但是胶乳微粒一般是由以下物质形成的:聚苯乙烯、丁二烯苯乙烯、苯乙烯-丙烯酸-乙烯基三元共聚物、聚甲基丙烯酸甲酯、聚甲基丙烯酸乙酯、苯乙烯-马来酐共聚物、聚醋酸乙烯酯、聚乙烯基吡啶、聚二乙烯基苯、聚对苯二甲酸丁二酯、丙烯腈、氯乙烯-丙烯酸酯等,或者这些物质的酐、羧基、氨基、羟基或酰肼衍生物。其它合适的微粒在Jou等人的U.S.5,670,381和Tarcha等人的U.S.5,252,459中有所描述,这些文献在此作为参考全部引入本文。一些商业上可购得的合适荧光颗粒的实例包括商品名为“FluoSphere”(Red580/605)和“TransfluoSphere”(543/620)、由Molecular Probes,Inc.出售的荧光羧基化微球,以及也是由MolecularProbes,Inc.出售的“Texas Red”和5-及6-羧基四甲基若丹明。商业上可购得的合适有色胶乳微粒的实例包括由Bang’s Laboratory,Inc.出售的羧基化胶乳珠。
在一些情况下,需要用一些方式来给探针改性,以便使探针能够更容易地结合到分析物上。在这样的情况下,探针用某些粘附到其上的特异性结合部分来改性,以形成缀合探针。特异性结合部分通常是指特异性结合对,即两个不同的分子,其中一个分子化学和/或物理结合到第二个分子上的一员。例如,免疫反应特异性结合部分可包括抗原、半抗原、适体(aptamers)、抗体和这些物质的复合物,包括那些通过DNA重组方法或肽合成而形成的物质。抗体可以是单克隆或多克隆抗体、重组蛋白质或其混合物或片段,以及抗体和其它特异性结合部分的混合物。这些抗体的制备细节和它们用作特异性结合部分的适宜性是本领域技术人员所公知的。其它常用的特异性结合对包括但不限于生物素和亲和素、糖类和凝集素、互补核苷酸序列(包括用于DNA杂交测定中的探针和捕获核酸序列,用于检测靶核酸序列)、互补肽序列(包括用重组方法形成的那些互补肽序列)、效应子和受体分子、激素和激素结合蛋白、酶辅因子和酶、酶抑制剂和酶等。此外,特异性结合对可包括作为原始特异性结合部分类似物的部分。例如,可使用分析物的衍生物或片段,即分析物-类似物,只要它具有至少一个与分析物共同的表位即可。
特异性结合部分一般可利用任何各种公知技术附着到探针上。例如,特异性结合部分对探针(例如微粒)的共价附着,可利用羧基、氨基、醛基、溴乙酰基、碘乙酰基、巯基、环氧基和其它反应性或连接性官能团以及残余的游离基和游离基阳离子来实现,通过这些基团可完成蛋白偶合反应。还可包括作为官能化共聚单体的表面官能团,因为微粒的表面可含有较高表面浓度的极性基团。此外,虽然微粒探针经常在合成之后官能化,在某些情况下例如为聚(苯硫酚),但是微粒能够与蛋白质直接共价连接,而无需进一步改性。例如,参照图2,该图表示出用于共价缀合探针的本发明的一个实施方案。如图所示,缀合的第一个步骤是,用碳二亚胺活化探针表面上的羧基。在第二个步骤中,活化的羧酸基团与抗体的氨基反应,从而形成酰胺键。活化和/或抗体偶合可发生在缓冲液中,例如磷酸盐缓冲的盐水(PBS)(例如pH为7.2)或2-(N-吗啉代)乙磺酸(MES)(例如pH为5.3)。如图所示,所获得的探针然后可例如用乙醇胺封闭,从而形成探针缀合物。除了共价键合之外,其它附着技术,例如物理吸附,也可用于本发明。
如上所示,测试样品中的一些分析物可以不用所需的方式复合到缀合探针上,尤其是当分析物以高浓度存在于测试样品中时。该未复合的分析物随后与复合的分析物在检测区31竞争捕获试剂(如下所述),借此对测定装置20的准确度具有不利影响。为了抵消该影响,多孔膜23包含层析区35,众多微孔颗粒50分布在层析区上。如图3-5所示,微孔颗粒50的存在允许层析区35作为“凝胶渗透”柱,较大的分子以比较小分子快的速率通过层析区35。具体地说,如图5所示,尺寸大于微孔颗粒50的微孔51的分子不能通过,由此被迫流过颗粒50之间的空间52,即通过膜23的孔(如方向箭头L2所示)。由于颗粒50的微孔51在颗粒结构内形成“曲折路径”(即具有复杂形状的路径),因此分子通过微孔51比通过颗粒50之间的空间52花费的时间要长。据此,当通过层析区35时,较大尺寸的分子首先出去。中间尺寸的分子根据其尺寸不同程度地渗透过微孔颗粒50。最后,非常小的分子流过颗粒50的微孔51(如方向箭头L1所示),并最终由此排出层析区35。一般来说,分析物/探针复合物的尺寸大于未复合的分析物的尺寸。因此,复合物能够在未复合的分析物到达检测区31之前到达检测区31并与其上含有的捕获试剂结合。以这种方式,复合的与未复合的分析物之间的竞争得到抑制。
层析区35一般提供一个明显不同的区域(例如,线、点等),尽管本发明肯定包含多个区域。例如,在图示的实施方案中,采用一条线。当采用这条线的时候,线宽通常是可变的。例如,在一些实施方案中,分析物流动方向L上的线宽为,从施加分析物的部位(例如缀合垫22)到检测区31所测总距离的约10%-约100%,并且在一些实施方案中,为约10%-约50%。而且,这条线可位于基本上垂直于测试样品通过装置20的流动的方向上。同样地,在一些实施方案中,这条线可位于基本上平行于测试样品通过装置20的流动的方向上。
用于给定测定中的合适微孔颗粒50的选择标准包括各种因素,例如感兴趣的分析物的性质、测试条件、所采用的探针性质等。一般,期望微孔颗粒50具有相对均匀的孔和粒径分布以及良好的机械和化学稳定性。此外,一般还期望,微孔颗粒50的表面对测定装置20的其它组件保持化学惰性。例如,微孔颗粒50的表面相对于分析物通常是化学惰性的。可用于本发明的微孔颗粒50的一些实例包括但不限于合成的聚合颗粒,例如聚苯乙烯(例如高度交联的聚苯乙烯)、聚丙烯酰胺、聚丙烯腈;硅珠等。一些适宜的合成微孔颗粒50的具体实例在诸如Stoy的U.S.4,110,529;Ley等人的U.S.4,940,734;和Cooke等人的U.S.5,314,923中有所描述,这些文献在此作为参考全部并入本文。在探针也是微孔颗粒的实施方案中,应该理解,层杆区35的微孔颗粒50可以与探针相同。
微孔颗粒50的平均直径通常可按需要来改变。例如,在一些实施方案中,颗粒50的平均直径可为约0.1-约1000微米,在一些实施方案中,为约0.1-约100微米,在一些实施方案中,为约1-约10微米。一般,颗粒50基本上是球形的(即珠),尽管包括但不限于板、棒、条、不规则形状等的其它形状也适用于本发明。正如本领域技术人员所领会的,颗粒50的成分、形状、尺寸和/或密度可广泛变化。
一般来说,颗粒50的微孔51的平均尺寸(即直径)小于由多孔膜23的孔52形成的颗粒50之间的空间。具体地说,微孔51的平均尺寸一般比上述空间的平均尺寸至少小约100%,在一些实施方案中,至少小约150%,在一些实施方案中,至少小约250%。例如,在一些实施方案中,微孔51具有小于约100纳米的平均尺寸,在一些实施方案中,为约5-约100纳米,在一些实施方案中,为约10-约60纳米。作为对照,多孔膜23的孔52一般具有大于约200纳米的平均尺寸,在一些实施方案中,为约200-约5000纳米,在一些实施方案中,为约200-约2500纳米。
测定装置20还可包含检测区31,在检测区31上固定有能够结合到缀合探针上的捕获试剂。例如,在一些实施方案中,捕获试剂可以是生物捕获试剂。这些生物捕获试剂在本领域内是公知的,并且可包括但不限于抗原、半抗原、抗体、蛋白A或G、亲和素、链霉亲和素、二级抗体、以及这些物质的复合物。在许多情况下,期望这些生物捕获试剂能够与探针上存在的特异性结合部分(例如抗体)结合。此外,还期望用各种非生物材料作为捕获试剂。例如,在一些实施方案中,捕获试剂可包括聚电解质。聚电解质可具有净的正或负电荷,以及通常为中性的净电荷。例如,具有净正电荷的聚电解质的一些合适实例包括但不限于聚赖氨酸(在商业上从Sigma-Aldrich Chemical Co.,Inc.of St.Louis,MO购得)、聚乙烯亚胺;环氧氯丙烷官能化的聚胺和/或聚酰胺型胺类,例如聚(二甲基胺-共-环氧氯丙烷);聚二烯丙基二甲基-氯化铵;阳离子纤维素衍生物,例如用季铵盐水溶性单体接枝的纤维素共聚物或纤维素衍生物等等。在一个特定实施方案中,可采用作为含有季铵盐水溶性单体的纤维素衍生物的CelQuatSC-230M或H-100(从National Starch &Chemical,Inc.购得)。此外,具有净负电荷的聚电解质的一些适宜实例包括但不限于聚丙烯酸,例如聚(乙烯-共-甲基丙烯酸,钠盐)等等。还应该理解,其它聚电解质也可使用,例如两亲聚电解质(即具有极性和非极性部分)。例如,合适的两亲聚电解质的一些实例包括但不限于聚(苯乙烯基-b-N-甲基2-乙烯基碘化吡啶鎓)和聚(苯乙烯基-b-丙烯酸),它们可从Polymer Scource,Inc.of Dorval,Canada购得。
捕获试剂用作分析物/探针复合物的固定结合位点。具体地说,分析物,例如抗体、抗原等,一般具有两个结合位点。在到达检测区31之后,这些结合位点之一被缀合探针的特异性结合部分所占据。然而,分析物的游离结合位点能够结合到固定捕获试剂上。在结合到固定捕获试剂上之后,复合探针形成新的三元夹心复合物。
检测区31通常可具有任何数目的不同检测区,以便使用者能够更好地确定测试样品内特定分析物的浓度。每个区域可含有相同的捕获试剂,或者可含有用于捕获多种分析物的不同捕获试剂。例如,检测区31可包括两个或更多个不同的检测区(例如线、点等)。检测区可以线的形式位于基本上垂直于通过测定装置20的测试样品流的方向上。同样,在一些实施方案中,检测区可以线的形式位于基本上平行于通过测定装置20的测试样品流的方向上。
虽然检测区31可指示出分析物的存在,但是仅利用检测区31经常难以确定测试样品内分析物的相对浓度。于是,测定装置20还可包括校正区32。在该实施方案中,校正区32形成在多孔膜23上,并位于检测区31的下游。校正区32配有捕获试剂,该试剂能够结合穿过膜23的长度的任何剩余的未捕获探针。校正区32中所采用的捕获试剂可与检测区31中所用的捕获试剂相同或不同。而且,与检测区31类似,校正区32还可在任何方向上提供任何数目的不同校正区,以便使用者能够更好地确定测试样品内特定分析物的浓度。每个区域可含有相同的捕获试剂,或者可含有用于捕获不同探针的不同捕获试剂。
校正区可以用不同量的捕获试剂预先装载到多孔膜23上,以便在探针迁移后由每个校正区产生不同的信号强度。通过采用不同尺寸的校正区和/或通过改变每个校正区内的捕获试剂的浓度或体积,能够改变每个校正区内结合物的总量。如果需要的话,将过量的探针用于测定装置20,以便每个校正区达到其完全预定的信号强度电位。也就是说,沉积在校正区上的探针的量是预定的,因为校正区上采用的捕获试剂的量设定在预定的已知水平上。
总之,可按照本发明构建各种流通测定装置。关于这一点,现在更详细地描述本发明的多个不同的实施方案。然而,应该理解,下述实施方案仅仅是示范性的,本发明还包括其它实施方案。例如,参照图3-4,这些图表示出一个特定实施方案,其中探针41用于检测,探针43用于校正。在该实施方案中,检测探针41和校正探针43加入到缀合垫22上,并且在以与测试样品相通的方式放置时,由此能够流过装置20(如方向箭头L所指示的)。检测探针41与分析物A的特异性结合部分90缀合,因此,在探针41与分析物A接触之后就结合到其上,从而形成分析物/探针复合物49。
如图3所示,探针/分析物复合物49、任何游离的分析物A以及校正探针43从缀合垫22通过多孔膜23,直到到达层析区35为止,在层析区上有多个微孔颗粒50。较大的复合物49和校正探针43容易流过颗粒50之间的空间52,而较小的未复合的分析物A以较慢的速率流到颗粒50的微孔内。分析物/探针复合物49然后流过装置20,直到其到达检测区31为止,在检测区31,它们结合到捕获试剂91(例如抗体)上,形成夹心复合物53。而且,校正探针43流到校正区32并与捕获试剂(未示出)例如聚电解质结合。其后,如图4所示,未复合的分析物A穿过层析区35,到达检测区31。然而,由于复合物49已经结合到捕获试剂上,因此分析物A穿过检测区31和校正区32,直到其到达芯吸垫28为止。这样,在检测区31,能够由检测探针41的信号强度确定分析物的量。如果需要的话,此信号强度可以用校正区32中的校正探针43的信号强度来校正。信号强度可目视测定或借助于设备例如荧光读数器来测定。
虽然上面已经描述了装置结构的多个不同的实施方案,但是应该理解,本发明的装置一般可具有任何所需的结构,并且不必含有上述所有部件。各种其它装置结构和/或测定形式,例如在Lambotte等人的U.S.5,395,754;Jou等人的U.S.5,670,381;和Malick等人的U.S.6,194,220中有所描述,这些文献在此作为参考全部并入本文。
本发明人已经发现,层析区在测定装置的多孔膜上的存在,能够以简单、有效和相对廉价的方式有效减小“钩效应”。尤其是,多个微孔颗粒位于层析区上,使得较大尺寸的分析物/探针复合物在任何未复合的分析物之前到达检测区。据此,未复合的分析物不与复合物竞争检测区上有用的结合位点。由于抑制了未复合的分析物占据检测区的大多数结合位点,因此可限制“假阴性”的发生,甚至在较高的分析物浓度时。
虽然已经就本发明的具体实施方案详细描述了本发明,但是本领域的技术人员应该理解,在领会上述内容之后,容易构思这些实施方案的替换形式、变型和等同物。因此,本发明的范围应该由所附的权利要求书及其等同物来确定。
Claims (37)
1、一种用于检测测试样品中分析物的存在或数量的流通测定装置,所述流通测定装置包括多孔膜,所述多孔膜与能够产生检测信号的缀合检测探针相通,所述多孔膜限定出:
层析区,在所述层析区内固定有多个微孔颗粒,以及
位于所述层析区下游的检测区,其中捕获试剂固定在所述检测区内,所述捕获试剂被构造成结合到所述缀合检测探针上,其中在所述检测区内,所述缀合检测探针能够产生检测信号,由所述检测信号来确定测试样品内分析物的量;并且
所述微孔颗粒在相互之间限定出多个空间,所述空间的平均尺寸大于所述颗粒的微孔的平均尺寸,且所述缀合检测探针位于所述层析区的上游。
2、如权利要求1所述的流通测定装置,其中所述微孔的平均尺寸比所述空间的平均尺寸至少小100%。
3、如权利要求1所述的流通测定装置,其中所述微孔的平均尺寸比所述空间的平均尺寸至少小150%。
4、如权利要求1所述的流通测定装置,其中所述微孔的平均尺寸比所述空间的平均尺寸至少小250%。
5、如权利要求1所述的流通测定装置,其中所述微孔的平均尺寸小于100纳米。
6、如权利要求1所述的流通测定装置,其中所述微孔的平均尺寸为10-60纳米。
7、如权利要求1所述的流通测定装置,其中所述微孔颗粒选自聚苯乙烯、聚丙烯酰胺、聚丙烯腈、硅珠以及这些物质的组合。
8、如权利要求1所述的流通测定装置,其中所述微孔颗粒的表面对于分析物是化学惰性的。
9、如权利要求1所述的流通测定装置,其中所述缀合检测探针包括选自以下的物质:发色团、催化剂、荧光化合物、化学发光化合物、磷光化合物、放射性化合物、直接目视标记物、脂质体以及这些物质的组合。
10、如权利要求1所述的流通测定装置,其中所述多孔膜还包括能够产生校正信号的校正区,其中由经所述校正信号校正的所述检测信号来确定测试样品内分析物的量。
11、如权利要求10所述的流通测定装置,其中所述多孔膜与校正探针相通,所述校正探针在存在于所述校正区内时产生所述校正信号。
12、如权利要求1所述的流通测定装置,其中所述装置是夹心型测定装置。
13、一种用于检测测试样品中分析物的存在或数量的流通夹心测定装置,所述测定装置包括多孔膜,所述多孔膜与能够产生检测信号的缀合检测探针相通,所述缀合检测探针被构造成在与测试样品中的分析物接触时能够与其结合,从而形成分析物/探针复合物和未复合的分析物,所述多孔膜限定出:
层析区,在所述层析区内固定有多个微孔颗粒,所述微孔颗粒被构造成使所述未复合的分析物以比所述分析物/探针复合物慢的速率流过所述层析区,以及
位于所述层析区下游的检测区,其中捕获试剂固定在所述检测区内,所述捕获试剂被构造成结合到所述分析物/探针复合物上,从而在所述检测区内,所述复合物产生检测信号,其中由所述检测信号来确定测试样品内分析物的量;并且所述微孔颗粒在相互之间限定出多个空间,所述空间的平均尺寸大于所述颗粒的微孔的平均尺寸,且所述缀合检测探针位于所述层析区的上游。
14、如权利要求13所述的流通夹心测定装置,其中所述微孔的平均尺寸比所述空间的平均尺寸至少小100%。
15、如权利要求13所述的流通夹心测定装置,其中所述微孔的平均尺寸比所述空间的平均尺寸至少小150%。
16、如权利要求13所述的流通夹心测定装置,其中所述微孔的平均尺寸比所述空间的平均尺寸至少小250%。
17、如权利要求13所述的流通夹心测定装置,其中所述微孔颗粒选自聚苯乙烯、聚丙烯酰胺、聚丙烯腈、硅珠以及这些物质的组合。
18、如权利要求13所述的流通夹心测定装置,其中所述微孔颗粒的表面对于分析物是化学惰性的。
19、如权利要求13所述的流通夹心测定装置,其中所述多孔膜还包括能够产生校正信号的校正区,其中由经所述校正信号校正的所述检测信号来确定测试样品内分析物的量。
20、如权利要求19所述的流通夹心测定装置,其中所述多孔膜与校正探针相通,所述校正探针在存在于所述校正区内时产生所述校正信号。
21、一种用于检测测试样品中分析物的存在或数量的方法,所述方法包括:
i)提供一种流通测定装置,所述装置包括多孔膜,所述多孔膜与能够产生检测信号的缀合检测探针相通,所述多孔膜限定出层析区和位于所述层析区下游的检测区,在所述层析区内固定有多个微孔颗粒,其中捕获试剂固定在所述检测区内,
ii)使含有分析物的测试样品与所述缀合检测探针接触,从而形成分析物/探针复合物和未复合的分析物,以及
iii)使所述分析物/探针复合物和所述未复合的分析物到达所述层析区,然后到达检测区,其中所述分析物/探针复合物在所述未复合的分析物之前到达所述检测区;并且
所述微孔颗粒在相互之间限定出多个空间,所述空间的平均尺寸大于所述颗粒的微孔的平均尺寸,且所述缀合检测探针位于所述层析区的上游。
22、如权利要求21所述的方法,其中所述微孔的平均尺寸比所述空间的平均尺寸至少小100%。
23、如权利要求21所述的方法,其中所述微孔的平均尺寸比所述空间的平均尺寸至少小150%。
24、如权利要求21所述的方法,其中所述微孔的平均尺寸比所述空间的平均尺寸至少小250%。
25、如权利要求21所述的方法,其中所述微孔颗粒选自聚苯乙烯、聚丙烯酰胺、聚丙烯腈、硅珠以及这些物质的组合。
26、如权利要求21所述的方法,其中所述微孔颗粒的表面对于分析物是化学惰性的。
27、如权利要求21所述的方法,其中还包括测定所述检测区内产生的检测信号的强度。
28、如权利要求21所述的方法,其中所述多孔膜还包括能够产生校正信号的校正区,其中由经所述校正信号校正的所述检测信号来确定测试样品内分析物的量。
29、如权利要求28所述的方法,其中所述多孔膜与校正探针相通,所述校正探针在存在于所述校正区内时产生所述校正信号。
30、如权利要求29所述的方法,其中还包括通过针对多个预定的分析物浓度绘制经校正信号强度校正的检测信号强度来产生校正曲线。
31、如权利要求1所述的流通测定装置,其中所述微孔颗粒的平均直径为0.1-100微米。
32、如权利要求1所述的流通测定装置,其中所述微孔颗粒的平均直径为1-10微米。
33、如权利要求1所述的流通测定装置,其中所述多孔膜包含平均尺寸大于200纳米的孔。
34、如权利要求1所述的流通测定装置,其中所述多孔膜包含平均尺寸为200-5000纳米的孔。
35、如权利要求1所述的流通测定装置,其中所述多孔膜包含平均尺寸为200-2500纳米的孔。
36、如权利要求1所述的流通测定装置,其中所述检测探针与抗体缀合。
37、如权利要求1所述的流通测定装置,其中所述捕获试剂为抗体。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/325,614 | 2002-12-19 | ||
US10/325,614 US7247500B2 (en) | 2002-12-19 | 2002-12-19 | Reduction of the hook effect in membrane-based assay devices |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1720455A CN1720455A (zh) | 2006-01-11 |
CN100476437C true CN100476437C (zh) | 2009-04-08 |
Family
ID=32593827
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB2003801052766A Expired - Fee Related CN100476437C (zh) | 2002-12-19 | 2003-10-29 | 减少钩效应的流通测定装置及检测方法 |
Country Status (12)
Country | Link |
---|---|
US (2) | US7247500B2 (zh) |
EP (1) | EP1573326B1 (zh) |
KR (1) | KR101072756B1 (zh) |
CN (1) | CN100476437C (zh) |
AT (1) | ATE408833T1 (zh) |
AU (1) | AU2003290552A1 (zh) |
CA (1) | CA2508774C (zh) |
DE (1) | DE60323672D1 (zh) |
ES (1) | ES2312837T3 (zh) |
MX (1) | MXPA05005951A (zh) |
TW (1) | TW200424524A (zh) |
WO (1) | WO2004061454A1 (zh) |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7285424B2 (en) | 2002-08-27 | 2007-10-23 | Kimberly-Clark Worldwide, Inc. | Membrane-based assay devices |
US7247500B2 (en) | 2002-12-19 | 2007-07-24 | Kimberly-Clark Worldwide, Inc. | Reduction of the hook effect in membrane-based assay devices |
US7094528B2 (en) | 2004-06-30 | 2006-08-22 | Kimberly-Clark Worldwide, Inc. | Magnetic enzyme detection techniques |
US7521226B2 (en) | 2004-06-30 | 2009-04-21 | Kimberly-Clark Worldwide, Inc. | One-step enzymatic and amine detection technique |
US7906276B2 (en) * | 2004-06-30 | 2011-03-15 | Kimberly-Clark Worldwide, Inc. | Enzymatic detection techniques |
US20060019406A1 (en) * | 2004-07-23 | 2006-01-26 | Ning Wei | Lateral flow device for the detection of large pathogens |
US7504235B2 (en) | 2005-08-31 | 2009-03-17 | Kimberly-Clark Worldwide, Inc. | Enzyme detection technique |
US7829347B2 (en) | 2005-08-31 | 2010-11-09 | Kimberly-Clark Worldwide, Inc. | Diagnostic test kits with improved detection accuracy |
US8758989B2 (en) * | 2006-04-06 | 2014-06-24 | Kimberly-Clark Worldwide, Inc. | Enzymatic detection techniques |
US8012761B2 (en) * | 2006-12-14 | 2011-09-06 | Kimberly-Clark Worldwide, Inc. | Detection of formaldehyde in urine samples |
US7846383B2 (en) * | 2006-12-15 | 2010-12-07 | Kimberly-Clark Worldwide, Inc. | Lateral flow assay device and absorbent article containing same |
US7935538B2 (en) * | 2006-12-15 | 2011-05-03 | Kimberly-Clark Worldwide, Inc. | Indicator immobilization on assay devices |
US7897360B2 (en) | 2006-12-15 | 2011-03-01 | Kimberly-Clark Worldwide, Inc. | Enzyme detection techniques |
US8865454B2 (en) * | 2007-03-22 | 2014-10-21 | Scandinavian Micro Biodevices Aps | Flow through system, flow through device and a method of performing a test |
US8796184B2 (en) | 2008-03-28 | 2014-08-05 | Sentilus, Inc. | Detection assay devices and methods of making and using the same |
DE102009010563A1 (de) | 2009-02-16 | 2010-08-26 | Matthias W. Engel | Vorrichtung zum Nachweis von Analyten in Körperflüssigkeiten |
US20100290948A1 (en) * | 2009-05-15 | 2010-11-18 | Xuedong Song | Absorbent articles capable of indicating the presence of urinary tract infections |
US8956859B1 (en) | 2010-08-13 | 2015-02-17 | Aviex Technologies Llc | Compositions and methods for determining successful immunization by one or more vaccines |
US8486717B2 (en) | 2011-01-18 | 2013-07-16 | Symbolics, Llc | Lateral flow assays using two dimensional features |
US9874556B2 (en) | 2012-07-18 | 2018-01-23 | Symbolics, Llc | Lateral flow assays using two dimensional features |
US20140072959A1 (en) | 2012-09-12 | 2014-03-13 | Force Diagnostics, Inc. | Rapid tests for insurance underwriting |
WO2014134033A1 (en) | 2013-02-26 | 2014-09-04 | Astute Medical, Inc. | Lateral flow assay with test strip retainer |
WO2015038978A1 (en) | 2013-09-13 | 2015-03-19 | Symbolics, Llc | Lateral flow assays using two dimensional test and control signal readout patterns |
CN106153924B (zh) * | 2015-03-23 | 2017-10-27 | 中国科学院宁波材料技术与工程研究所 | 试剂盒、检测系统,其制备方法及应用 |
WO2016164365A1 (en) | 2015-04-06 | 2016-10-13 | Bludiagnostics, Inc. | A test device for detecting an analyte in a saliva sample and method of use |
CN109964127A (zh) | 2016-08-23 | 2019-07-02 | Qoolabs有限公司 | 用于评估重组蛋白表达或报告基因表达的侧向流动检测 |
EP3833735A4 (en) * | 2018-08-06 | 2022-05-11 | Becton, Dickinson and Company | LATERAL FLOW IMMUNOASSAY DEVICE WITH DISCONNECT MEMBRANE |
Family Cites Families (342)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US164659A (en) | 1875-06-22 | Improvement in processes of preparing pickles | ||
US1366241A (en) | 1919-10-03 | 1921-01-18 | Frederick W Burch | Ratchet mechanism for camp-beds |
US3772076A (en) | 1970-01-26 | 1973-11-13 | Hercules Inc | Reaction products of epihalohydrin and polymers of diallylamine and their use in paper |
US3700623A (en) | 1970-04-22 | 1972-10-24 | Hercules Inc | Reaction products of epihalohydrin and polymers of diallylamine and their use in paper |
CS179075B1 (en) | 1974-11-26 | 1977-10-31 | Stoy Vladimir | Mode of manufacture of spherical particles from polymer |
SE388694B (sv) | 1975-01-27 | 1976-10-11 | Kabi Ab | Sett att pavisa ett antigen exv i prov av kroppvetskor, med utnyttjande av till porost berarmaterial bundna eller adsorberande antikroppar |
USRE30267E (en) | 1975-06-20 | 1980-05-06 | Eastman Kodak Company | Multilayer analytical element |
US4094647A (en) | 1976-07-02 | 1978-06-13 | Thyroid Diagnostics, Inc. | Test device |
US4210723A (en) | 1976-07-23 | 1980-07-01 | The Dow Chemical Company | Method of coupling a protein to an epoxylated latex |
US4115535A (en) | 1977-06-22 | 1978-09-19 | General Electric Company | Diagnostic method employing a mixture of normally separable protein-coated particles |
US4275149A (en) | 1978-11-24 | 1981-06-23 | Syva Company | Macromolecular environment control in specific receptor assays |
US4374925A (en) | 1978-11-24 | 1983-02-22 | Syva Company | Macromolecular environment control in specific receptor assays |
US4235601A (en) | 1979-01-12 | 1980-11-25 | Thyroid Diagnostics, Inc. | Test device and method for its use |
US4361537A (en) | 1979-01-12 | 1982-11-30 | Thyroid Diagnostics, Inc. | Test device and method for its use |
US4441373A (en) | 1979-02-21 | 1984-04-10 | American Hospital Supply Corporation | Collection tube for drawing samples of biological fluids |
US4312228A (en) | 1979-07-30 | 1982-01-26 | Henry Wohltjen | Methods of detection with surface acoustic wave and apparati therefor |
US4299916A (en) | 1979-12-26 | 1981-11-10 | Syva Company | Preferential signal production on a surface in immunoassays |
US4849338A (en) | 1982-07-16 | 1989-07-18 | Syntex (U.S.A.) Inc. | Simultaneous calibration heterogeneous immunoassay |
US4533629A (en) | 1981-04-17 | 1985-08-06 | Syva Company | Simultaneous calibration heterogeneous immunoassay |
US5432057A (en) | 1979-12-26 | 1995-07-11 | Syva Company | Simultaneous calibration heterogeneous immunoassay |
US5156953A (en) | 1979-12-26 | 1992-10-20 | Syntex (U.S.A.) Inc. | Simultaneous calibration heterogeneous immunoassay |
US4843000A (en) | 1979-12-26 | 1989-06-27 | Syntex (U.S.A.) Inc. | Simultaneous calibration heterogeneous immunoassay |
US4540659A (en) | 1981-04-17 | 1985-09-10 | Syva Company | Simultaneous calibration heterogeneous immunoassay |
FR2478086A1 (fr) | 1980-02-14 | 1981-09-18 | Ciba Geigy Ag | Procede pour la preparation de composes du triarylmethane |
US4427836A (en) | 1980-06-12 | 1984-01-24 | Rohm And Haas Company | Sequential heteropolymer dispersion and a particulate material obtainable therefrom, useful in coating compositions as a thickening and/or opacifying agent |
US4366241A (en) | 1980-08-07 | 1982-12-28 | Syva Company | Concentrating zone method in heterogeneous immunoassays |
US4385126A (en) | 1980-11-19 | 1983-05-24 | International Diagnostic Technology, Inc. | Double tagged immunoassay |
US4426451A (en) | 1981-01-28 | 1984-01-17 | Eastman Kodak Company | Multi-zoned reaction vessel having pressure-actuatable control means between zones |
US4442204A (en) | 1981-04-10 | 1984-04-10 | Miles Laboratories, Inc. | Homogeneous specific binding assay device and preformed complex method |
US4444592A (en) | 1981-06-02 | 1984-04-24 | The Sherwin-Williams Company | Pigment compositions and processes therefor |
US4363874A (en) | 1981-08-07 | 1982-12-14 | Miles Laboratories, Inc. | Multilayer analytical element having an impermeable radiation nondiffusing reflecting layer |
EP0073593A1 (en) * | 1981-09-01 | 1983-03-09 | E.I. Du Pont De Nemours And Company | Size-exclusion heterogeneous immunoassay |
US4480042A (en) | 1981-10-28 | 1984-10-30 | E. I. Du Pont De Nemours And Company | Covalently bonded high refractive index particle reagents and their use in light scattering immunoassays |
US4477635A (en) | 1982-01-04 | 1984-10-16 | Minnesota Mining And Manufacturing Company | Polymeric triarylmethane dyes |
US4435504A (en) | 1982-07-15 | 1984-03-06 | Syva Company | Immunochromatographic assay with support having bound "MIP" and second enzyme |
US4534356A (en) | 1982-07-30 | 1985-08-13 | Diamond Shamrock Chemicals Company | Solid state transcutaneous blood gas sensors |
US4632559A (en) | 1982-11-29 | 1986-12-30 | Miles Laboratories, Inc. | Optical readhead |
US4537861A (en) | 1983-02-03 | 1985-08-27 | Elings Virgil B | Apparatus and method for homogeneous immunoassay |
GB8314523D0 (en) | 1983-05-25 | 1983-06-29 | Lowe C R | Diagnostic device |
DE3464252D1 (en) | 1983-06-03 | 1987-07-23 | Hoffmann La Roche | Labelled molecules for fluorescence immunoassays and processes and intermediates for their preparation |
CH662421A5 (de) | 1983-07-13 | 1987-09-30 | Suisse Horlogerie Rech Lab | Piezoelektrischer kontaminationsdetektor. |
US4537657A (en) | 1983-08-26 | 1985-08-27 | Hercules Incorporated | Wet strength resins |
US4552458A (en) | 1983-10-11 | 1985-11-12 | Eastman Kodak Company | Compact reflectometer |
EP0205698B1 (en) | 1985-06-28 | 1990-01-03 | EASTMAN KODAK COMPANY (a New Jersey corporation) | Compact reflectometer |
US4595661A (en) | 1983-11-18 | 1986-06-17 | Beckman Instruments, Inc. | Immunoassays and kits for use therein which include low affinity antibodies for reducing the hook effect |
US4703017C1 (en) | 1984-02-14 | 2001-12-04 | Becton Dickinson Co | Solid phase assay with visual readout |
US4698262A (en) | 1984-04-27 | 1987-10-06 | Becton, Dickinson And Company | Fluorescently labeled microbeads |
US4632901A (en) | 1984-05-11 | 1986-12-30 | Hybritech Incorporated | Method and apparatus for immunoassays |
US4586695A (en) | 1984-06-22 | 1986-05-06 | Miller Charlie D | Continuous tube extractor |
FI842992A0 (fi) | 1984-07-26 | 1984-07-26 | Labsystems Oy | Immunologiskt definitionsfoerfarande. |
US4661235A (en) | 1984-08-03 | 1987-04-28 | Krull Ulrich J | Chemo-receptive lipid based membrane transducers |
US4596697A (en) | 1984-09-04 | 1986-06-24 | The United States Of America As Represented By The Secretary Of The Army | Chemical sensor matrix |
US5310687A (en) * | 1984-10-31 | 1994-05-10 | Igen, Inc. | Luminescent metal chelate labels and means for detection |
US5026653A (en) | 1985-04-02 | 1991-06-25 | Leeco Diagnostic, Inc. | Scavenger antibody mixture and its use for immunometric assay |
US4722889A (en) | 1985-04-02 | 1988-02-02 | Leeco Diagnostics, Inc. | Immunoassays using multiple monoclonal antibodies and scavenger antibodies |
CA1272127A (en) | 1985-04-04 | 1990-07-31 | Hybritech Incorporated | Solid phase system for use in ligand-receptor assays |
US4743542A (en) | 1985-04-11 | 1988-05-10 | Ortho Diagnostic | Method for forestalling the hook effect in a multi-ligand immunoassay system |
GB8509492D0 (en) | 1985-04-12 | 1985-05-15 | Plessey Co Plc | Optical assay |
US4963498A (en) | 1985-08-05 | 1990-10-16 | Biotrack | Capillary flow device |
US5238815A (en) | 1985-08-30 | 1993-08-24 | Toyo Soda Manufacturing Co., Ltd. | Enzymatic immunoassay involving detecting fluorescence while oscillating magnetic beads |
US5500350A (en) * | 1985-10-30 | 1996-03-19 | Celltech Limited | Binding assay device |
US4917503A (en) | 1985-12-02 | 1990-04-17 | Lifelines Technology, Inc. | Photoactivatable leuco base time-temperature indicator |
US4868126A (en) | 1985-12-11 | 1989-09-19 | Flow Cytometry Standards Corporation | Method of calibrating a fluorescent microscope using fluorescent calibration microbeads simulating stained cells |
US4714682A (en) | 1985-12-11 | 1987-12-22 | Flow Cytometry Standards Corporation | Fluorescent calibration microbeads simulating stained cells |
CA1291031C (en) | 1985-12-23 | 1991-10-22 | Nikolaas C.J. De Jaeger | Method for the detection of specific binding agents and their correspondingbindable substances |
US5585279A (en) | 1986-01-23 | 1996-12-17 | Davidson; Robert S. | Time-resolved luminescence binding assays using a fluorescent transition metal label other than ruthenium |
US4916056A (en) | 1986-02-18 | 1990-04-10 | Abbott Laboratories | Solid-phase analytical device and method for using same |
US5482830A (en) * | 1986-02-25 | 1996-01-09 | Biostar, Inc. | Devices and methods for detection of an analyte based upon light interference |
US5468606A (en) | 1989-09-18 | 1995-11-21 | Biostar, Inc. | Devices for detection of an analyte based upon light interference |
US4776944A (en) | 1986-03-20 | 1988-10-11 | Jiri Janata | Chemical selective sensors utilizing admittance modulated membranes |
US5591581A (en) * | 1986-04-30 | 1997-01-07 | Igen, Inc. | Electrochemiluminescent rhenium moieties and methods for their use |
DE3789430T2 (de) * | 1986-06-17 | 1994-10-27 | Baxter Diagnostics Inc | Homogenes fluortestverfahren mit abstoss des fluorzenten hintergrundes. |
GB8618133D0 (en) | 1986-07-24 | 1986-09-03 | Pa Consulting Services | Biosensors |
JPH0692969B2 (ja) | 1986-07-30 | 1994-11-16 | 株式会社シノテスト | 免疫的測定方法 |
US5182135A (en) | 1986-08-12 | 1993-01-26 | Bayer Aktiengesellschaft | Process for improving the adherency of metallic coatings deposited without current on plastic surfaces |
US4935346A (en) | 1986-08-13 | 1990-06-19 | Lifescan, Inc. | Minimum procedure system for the determination of analytes |
US4867908A (en) | 1986-08-29 | 1989-09-19 | Becton, Dickinson And Company | Method and materials for calibrating flow cytometers and other analysis instruments |
GB2197065A (en) | 1986-11-03 | 1988-05-11 | Stc Plc | Optical sensor device |
WO1988004777A1 (en) | 1986-12-15 | 1988-06-30 | Ultra Diagnostics Corporation | Monomeric phthalocyanine reagents |
US4857453A (en) | 1987-04-07 | 1989-08-15 | Syntex (U.S.A.) Inc. | Immunoassay device |
US4855240A (en) | 1987-05-13 | 1989-08-08 | Becton Dickinson And Company | Solid phase assay employing capillary flow |
GB8713649D0 (en) | 1987-06-11 | 1987-07-15 | Pa Consulting Services | Biological assay |
US4842783A (en) | 1987-09-03 | 1989-06-27 | Cordis Corporation | Method of producing fiber optic chemical sensors incorporating photocrosslinked polymer gels |
SE8703682L (sv) * | 1987-09-24 | 1989-03-25 | Wallac Oy | Homogen bestaemningsmetod som utnyttjar affinitetsreaktioner |
US5670381A (en) | 1988-01-29 | 1997-09-23 | Abbott Laboratories | Devices for performing ion-capture binding assays |
JP2763635B2 (ja) | 1988-02-08 | 1998-06-11 | ユニバーシティ カレッジ カーディフ コンサルタンツ リミティド | 生体液中のジアミンの検出 |
US5268306A (en) | 1988-02-29 | 1993-12-07 | Boehringer Mannheim Gmbh | Preparation of a solid phase matrix containing a bound specific binding pair |
US5145784A (en) | 1988-05-04 | 1992-09-08 | Cambridge Biotech Corporation | Double capture assay method employing a capillary flow device |
EP0341928A1 (en) | 1988-05-10 | 1989-11-15 | AMERSHAM INTERNATIONAL plc | Improvements relating to surface plasmon resonance sensors |
DE68907519T2 (de) | 1988-05-10 | 1993-10-21 | Amersham Int Plc | Biosensoren. |
GB8811919D0 (en) | 1988-05-20 | 1988-06-22 | Amersham Int Plc | Biological sensors |
GB8813307D0 (en) | 1988-06-06 | 1988-07-13 | Amersham Int Plc | Biological sensors |
US4877586A (en) | 1988-07-27 | 1989-10-31 | Eastman Kodak Company | Sliding test device for assays |
US5075077A (en) | 1988-08-02 | 1991-12-24 | Abbott Laboratories | Test card for performing assays |
AT390517B (de) | 1988-08-04 | 1990-05-25 | Avl Verbrennungskraft Messtech | Optischer sensor und verfahren zu dessen herstellung |
US4973670A (en) | 1988-08-12 | 1990-11-27 | The Dow Chemical Company | Method for preparing hollow latexes |
US5252459A (en) | 1988-09-23 | 1993-10-12 | Abbott Laboratories | Indicator reagents, diagnostic assays and test kits employing organic polymer latex particles |
EP0363504A1 (en) | 1988-10-10 | 1990-04-18 | Dräger Nederland B.V. | Method of providing a substrate with a layer comprising a polyvinylbased hydrogel and a biochemically active material |
US6448091B1 (en) | 1988-11-03 | 2002-09-10 | Igen International, Inc. | Method and apparatus for improved luminescence assays using particle concentration chemiluminescence detection |
SE8902043L (sv) | 1988-11-10 | 1990-05-11 | Pharmacia Ab | Foerfarande foer karakterisering av makromolekyler |
SE8804074D0 (sv) | 1988-11-10 | 1988-11-10 | Pharmacia Ab | Sensorenhet och dess anvaendning i biosensorsystem |
SE462454B (sv) | 1988-11-10 | 1990-06-25 | Pharmacia Ab | Maetyta foer anvaendning i biosensorer |
US5063081A (en) | 1988-11-14 | 1991-11-05 | I-Stat Corporation | Method of manufacturing a plurality of uniform microfabricated sensing devices having an immobilized ligand receptor |
US5003178A (en) | 1988-11-14 | 1991-03-26 | Electron Vision Corporation | Large-area uniform electron source |
ATE115982T1 (de) * | 1988-11-23 | 1995-01-15 | Cytec Tech Corp | Poröse polymerperlen und verfahren. |
US4940734A (en) | 1988-11-23 | 1990-07-10 | American Cyanamid | Process for the preparation of porous polymer beads |
US4895017A (en) | 1989-01-23 | 1990-01-23 | The Boeing Company | Apparatus and method for early detection and identification of dilute chemical vapors |
US5096671A (en) | 1989-03-15 | 1992-03-17 | Cordis Corporation | Fiber optic chemical sensors incorporating electrostatic coupling |
US5120662A (en) | 1989-05-09 | 1992-06-09 | Abbott Laboratories | Multilayer solid phase immunoassay support and method of use |
US5234813A (en) | 1989-05-17 | 1993-08-10 | Actimed Laboratories, Inc. | Method and device for metering of fluid samples and detection of analytes therein |
US5770416A (en) * | 1989-05-26 | 1998-06-23 | Upfront Chromatography A/S | Permeable hollow particles having an outer shell of mechanically rigid porous material |
US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
US5744101A (en) * | 1989-06-07 | 1998-04-28 | Affymax Technologies N.V. | Photolabile nucleoside protecting groups |
GB9008261D0 (en) | 1990-04-11 | 1990-06-13 | Ares Serono Res & Dev Ltd | Method of improving assay sensitivity |
JPH0366384A (ja) | 1989-08-04 | 1991-03-22 | Senjiyu Seiyaku Kk | 生理活性物質放出制御システム |
US5235238A (en) | 1989-08-10 | 1993-08-10 | Dainabot Company, Limited | Electrode-separated piezoelectric crystal oscillator and method for measurement using the electrode-separated piezoelectric crystal oscillator |
AU635314B2 (en) * | 1989-09-08 | 1993-03-18 | Terumo Kabushiki Kaisha | Measuring apparatus |
CA2003942A1 (en) | 1989-09-26 | 1991-03-26 | Julie Lia Rudolph | Solid assay support systems |
JP2979414B2 (ja) * | 1989-09-29 | 1999-11-15 | 富士レビオ株式会社 | 磁性粒子およびそれを用いた免疫測定法 |
GB8923699D0 (en) | 1989-10-20 | 1989-12-06 | Univ Strathclyde | Apparatus for assessing a particular property in a medium |
US5225935A (en) | 1989-10-30 | 1993-07-06 | Sharp Kabushiki Kaisha | Optical device having a microlens and a process for making microlenses |
US5252743A (en) | 1989-11-13 | 1993-10-12 | Affymax Technologies N.V. | Spatially-addressable immobilization of anti-ligands on surfaces |
GB8927503D0 (en) | 1989-12-04 | 1990-02-07 | Kronem Systems Inc | Enzyme-amplified lanthanide chelate luminescence |
US5508171A (en) * | 1989-12-15 | 1996-04-16 | Boehringer Mannheim Corporation | Assay method with enzyme electrode system |
US5252496A (en) * | 1989-12-18 | 1993-10-12 | Princeton Biomeditech Corporation | Carbon black immunochemical label |
US5326692B1 (en) | 1992-05-13 | 1996-04-30 | Molecular Probes Inc | Fluorescent microparticles with controllable enhanced stokes shift |
ATE140794T1 (de) | 1990-05-09 | 1996-08-15 | Abbott Lab | Bindungsnachweisverfahren mit konjugatrückgewinnung |
ES2116977T3 (es) * | 1990-05-11 | 1998-08-01 | Microprobe Corp | Soportes solidos para ensayos de hibridacion de acidos nucleicos y metodos para inmovilizar oligonucleotidos de modo covalente. |
DK138090D0 (da) * | 1990-06-06 | 1990-06-06 | Novo Nordisk As | Diagnostisk analysemetode |
DE4024476C1 (zh) | 1990-08-02 | 1992-02-27 | Boehringer Mannheim Gmbh, 6800 Mannheim, De | |
GB9019123D0 (en) | 1990-09-01 | 1990-10-17 | Fisons Plc | Analytical device |
US5200084A (en) | 1990-09-26 | 1993-04-06 | Immunicon Corporation | Apparatus and methods for magnetic separation |
US5076094A (en) | 1990-10-03 | 1991-12-31 | The United States Of America As Represented By The United States Department Of Energy | Dual output acoustic wave sensor for molecular identification |
US5700636A (en) | 1990-10-19 | 1997-12-23 | Becton Dickinson And Company | Methods for selectively detecting microorganisms associated with vaginal infections in complex biological samples |
US6027944A (en) * | 1990-11-22 | 2000-02-22 | Applied Research Systems Ars Holding Nv | Capillary-fill biosensor device comprising a calibration zone |
US5726064A (en) * | 1990-11-22 | 1998-03-10 | Applied Research Systems Ars Holding Nv | Method of assay having calibration within the assay |
US5510481A (en) * | 1990-11-26 | 1996-04-23 | The Regents, University Of California | Self-assembled molecular films incorporating a ligand |
US5208535A (en) | 1990-12-28 | 1993-05-04 | Research Development Corporation Of Japan | Mr position detecting device |
US5834226A (en) | 1991-01-31 | 1998-11-10 | Xytronyx, Inc. | One-step test for aspartate aminotransferase |
GB9102646D0 (en) | 1991-02-07 | 1991-03-27 | Fisons Plc | Analytical device |
IL97318A0 (en) * | 1991-02-20 | 1992-05-25 | Diagnostic Markers Inc | Method for the very rapid detection of polyamines |
US5466574A (en) | 1991-03-25 | 1995-11-14 | Immunivest Corporation | Apparatus and methods for magnetic separation featuring external magnetic means |
US5795470A (en) * | 1991-03-25 | 1998-08-18 | Immunivest Corporation | Magnetic separation apparatus |
US5196350A (en) | 1991-05-29 | 1993-03-23 | Omnigene, Inc. | Ligand assay using interference modulation |
ATE169340T1 (de) | 1991-05-30 | 1998-08-15 | Abbott Lab | Reagenzien und verfahren zur ausführung eines zweistufigen ioneneinfang-assay |
EP0586574B1 (en) | 1991-05-30 | 1997-12-10 | Abbott Laboratories | Methods and reagents for performing ion-capture digoxin assays |
CA2109924A1 (en) | 1991-05-30 | 1992-12-10 | Janina Adamczyk | Reagents containing a nonspecific binding blocker in ion-capture binding assays |
WO1993001308A1 (en) | 1991-07-10 | 1993-01-21 | Igen, Inc. | Methods and apparatus for improved luminescence assays using particle concentration and chemiluminescence detection |
US5179288A (en) | 1991-09-30 | 1993-01-12 | Ortho Pharmaceutical Corporation | Apparatus and method for measuring a bodily constituent |
US5418136A (en) * | 1991-10-01 | 1995-05-23 | Biostar, Inc. | Devices for detection of an analyte based upon light interference |
EP0608370B1 (en) * | 1991-10-15 | 1998-01-07 | Multilyte Limited | Binding assay employing labelled reagent |
US5424219A (en) * | 1991-10-25 | 1995-06-13 | Cytech Biomedical, Inc. | Method of performing assays for biomolecules and solid supports for use in such methods |
EP0643777A4 (en) | 1992-01-22 | 1995-06-07 | Abbott Lab | CALIBRATION REAGENTS FOR SEMI-QUANTITATIVE BINDING ASSAYS AND DEVICES. |
US5137609A (en) | 1992-01-31 | 1992-08-11 | Biometric Imaging Inc. | Differential separation assay |
US5221454A (en) | 1992-01-31 | 1993-06-22 | Biometric Imaging Inc. | Differential separation assay |
US5445971A (en) * | 1992-03-20 | 1995-08-29 | Abbott Laboratories | Magnetically assisted binding assays using magnetically labeled binding members |
DE69333569T2 (de) | 1992-03-20 | 2005-08-04 | Abbott Laboratories, Abbott Park | Magnetisch assistierte bindungsassays unter verwendung von magnetisch markierten bindungspartnern. |
US6019944A (en) * | 1992-05-21 | 2000-02-01 | Biosite Diagnostics, Inc. | Diagnostic devices and apparatus for the controlled movement of reagents without membranes |
US6156270A (en) * | 1992-05-21 | 2000-12-05 | Biosite Diagnostics, Inc. | Diagnostic devices and apparatus for the controlled movement of reagents without membranes |
JP3311752B2 (ja) * | 1992-07-02 | 2002-08-05 | ソイニ,エルッキ | 生体特異的多変数検定法 |
US5395754A (en) * | 1992-07-31 | 1995-03-07 | Hybritech Incorporated | Membrane-based immunoassay method |
US5321492A (en) | 1992-08-07 | 1994-06-14 | Miles Inc. | Dual function readhead for a reflectance instrument |
GB9217864D0 (en) * | 1992-08-21 | 1992-10-07 | Unilever Plc | Monitoring method |
US5356782A (en) | 1992-09-03 | 1994-10-18 | Boehringer Mannheim Corporation | Analytical test apparatus with on board negative and positive control |
US6399397B1 (en) * | 1992-09-14 | 2002-06-04 | Sri International | Up-converting reporters for biological and other assays using laser excitation techniques |
DK0588153T3 (da) | 1992-09-14 | 1997-06-16 | Siemens Ag | Gassensor |
GB9221329D0 (en) * | 1992-10-10 | 1992-11-25 | Delta Biotechnology Ltd | Preparation of further diagnostic agents |
GB2273772A (en) | 1992-12-16 | 1994-06-29 | Granta Lab Ltd | Detection of macromolecules utilising light diffraction |
US5358852A (en) | 1992-12-21 | 1994-10-25 | Eastman Kodak Company | Use of calcium in immunoassay for measurement of C-reactive protein |
US6200820B1 (en) * | 1992-12-22 | 2001-03-13 | Sienna Biotech, Inc. | Light scatter-based immunoassay |
TW239881B (zh) | 1992-12-22 | 1995-02-01 | Sienna Biotech Inc | |
US5327225A (en) | 1993-01-28 | 1994-07-05 | The Center For Innovative Technology | Surface plasmon resonance sensor |
FI932866A0 (fi) * | 1993-06-21 | 1993-06-21 | Labsystems Oy | Separeringsfoerfarande |
US5422726A (en) * | 1993-02-16 | 1995-06-06 | Tyler; Jonathan M. | Solid state spectrofluorimeter and method of using the same |
US5374531A (en) | 1993-03-22 | 1994-12-20 | Zynaxis, Inc. | Immunoassay for determination of cells |
DE4309393A1 (de) * | 1993-03-23 | 1994-09-29 | Boehringer Mannheim Gmbh | Verringerung des Hook-Effekts in Immuntests mit teilchenförmigem Trägermaterial |
DE4310142A1 (de) * | 1993-03-29 | 1994-10-06 | Boehringer Mannheim Gmbh | Immunologisch aktive Konjugate und ein Verfahren zu ihrer Herstellung |
JP3479100B2 (ja) * | 1993-06-02 | 2003-12-15 | 帝国臓器製薬株式会社 | 免疫化学的簡易半定量方法および装置 |
JPH0710640A (ja) * | 1993-06-25 | 1995-01-13 | Teruo Higa | 機能性セラミックスの製造法 |
US5658443A (en) | 1993-07-23 | 1997-08-19 | Matsushita Electric Industrial Co., Ltd. | Biosensor and method for producing the same |
FR2708348B1 (fr) | 1993-07-28 | 1995-10-06 | Stago Diagnostica | Procédé de dosage d'une substance immunologique au moyen de particules de latex magnétiques et de particules non-magnétiques. |
US5484867A (en) * | 1993-08-12 | 1996-01-16 | The University Of Dayton | Process for preparation of polyhedral oligomeric silsesquioxanes and systhesis of polymers containing polyhedral oligomeric silsesqioxane group segments |
US5837546A (en) | 1993-08-24 | 1998-11-17 | Metrika, Inc. | Electronic assay device and method |
US5512131A (en) * | 1993-10-04 | 1996-04-30 | President And Fellows Of Harvard College | Formation of microstamped patterns on surfaces and derivative articles |
US5464741A (en) | 1993-10-08 | 1995-11-07 | Henwell, Inc. | Palladium (II) octaethylporphine alpha-isothiocyanate as a phosphorescent label for immunoassays |
KR0177182B1 (ko) * | 1993-10-20 | 1999-05-15 | 최근선 | 중공구조를 갖는 유화중합체의 제조방법 |
US5352582A (en) | 1993-10-28 | 1994-10-04 | Hewlett-Packard Company | Holographic based bio-assay |
US5455475A (en) | 1993-11-01 | 1995-10-03 | Marquette University | Piezoelectric resonant sensor using the acoustoelectric effect |
DK0653639T3 (da) * | 1993-11-12 | 2000-07-24 | Unilever Nv | Analyseindretninger og fremgangsmåder til anvendelse deraf |
SG72684A1 (en) * | 1993-11-12 | 2000-05-23 | Unipath Ltd | Reading devices and assay devices for use therewith |
US5527711A (en) | 1993-12-13 | 1996-06-18 | Hewlett Packard Company | Method and reagents for binding chemical analytes to a substrate surface, and related analytical devices and diagnostic techniques |
JP3504750B2 (ja) | 1993-12-22 | 2004-03-08 | オルソ−クリニカル ダイアグノスティクス,インコーポレイティド | 検量関係式の再校正法及び定量試験キット |
US5663213A (en) | 1994-02-28 | 1997-09-02 | Rohm And Haas Company | Method of improving ultraviolet radiation absorption of a composition |
GB9416002D0 (en) * | 1994-08-08 | 1994-09-28 | Univ Cranfield | Fluid transport device |
US6117090A (en) | 1994-08-25 | 2000-09-12 | Caillouette; James C. | Method and apparatus for detecting amine producing organisms in the vagina |
US5599668A (en) * | 1994-09-22 | 1997-02-04 | Abbott Laboratories | Light scattering optical waveguide method for detecting specific binding events |
PT703454E (pt) | 1994-09-23 | 2002-05-31 | Unilever Nv | Metodos de monitorizacao e dispositivos para utilizacao nessa monitorizacao |
US5620850A (en) * | 1994-09-26 | 1997-04-15 | President And Fellows Of Harvard College | Molecular recognition at surfaces derivatized with self-assembled monolayers |
US5571684A (en) | 1994-11-07 | 1996-11-05 | Litmus Concepts, Inc. | Assay for proline iminopeptidase and other hydrolytic activities |
US5728352A (en) | 1994-11-14 | 1998-03-17 | Advanced Care Products | Disposable electronic diagnostic instrument |
KR0151203B1 (ko) | 1994-12-08 | 1998-12-01 | 이헌조 | 다중전극형 바이오센서 |
US5866434A (en) * | 1994-12-08 | 1999-02-02 | Meso Scale Technology | Graphitic nanotubes in luminescence assays |
US5489988A (en) * | 1995-01-03 | 1996-02-06 | Motorola | Environmental sensor and method therefor |
AU4213396A (en) | 1995-01-26 | 1996-08-01 | Nippon Paint Co., Ltd. | Kit for immunologically assaying biological substance and assay process |
US5569608A (en) | 1995-01-30 | 1996-10-29 | Bayer Corporation | Quantitative detection of analytes on immunochromatographic strips |
FR2730810B1 (fr) | 1995-02-21 | 1997-03-14 | Thomson Csf | Capteur chimique hautement selectif |
WO1996026011A1 (en) * | 1995-02-21 | 1996-08-29 | Siddiqi Iqbal W | Apparatus and method for mixing and separation employing magnetic particles |
US5534132A (en) | 1995-05-04 | 1996-07-09 | Vreeke; Mark | Electrode and method for the detection of an affinity reaction |
KR0156176B1 (ko) | 1995-06-01 | 1998-12-01 | 구자홍 | 전기화학식 면역 바이오센서 |
SK160497A3 (en) | 1995-06-05 | 1998-06-03 | Kimberly Clark Co | Novel pre-dyes |
US6413410B1 (en) | 1996-06-19 | 2002-07-02 | Lifescan, Inc. | Electrochemical cell |
AU3094195A (en) | 1995-07-10 | 1997-02-10 | Donald L. Kramer | Light transmittance type analytical system, variable transmittance optical component, and test device |
US5518689A (en) * | 1995-09-05 | 1996-05-21 | Bayer Corporation | Diffused light reflectance readhead |
AUPN527995A0 (en) | 1995-09-07 | 1995-09-28 | Agen Biomedical Limited | Method and apparatus for semiquantification of an analyte |
US5837547A (en) | 1995-12-27 | 1998-11-17 | Caribbean Microparticles Corporation | Flow cytometer calibration method |
US6287871B1 (en) | 1996-03-19 | 2001-09-11 | University Of Utah Research Foundation | System for determining analyte concentration |
US5753517A (en) * | 1996-03-29 | 1998-05-19 | University Of British Columbia | Quantitative immunochromatographic assays |
ATE203828T1 (de) * | 1996-03-29 | 2001-08-15 | Univ British Columbia | Bestimmung der plättchenzahl unter verwendung eines plättchen-körnchenproteins |
US6387707B1 (en) * | 1996-04-25 | 2002-05-14 | Bioarray Solutions | Array Cytometry |
WO1997042883A1 (en) | 1996-05-17 | 1997-11-20 | Mercury Diagnostics, Inc. | Disposable element for use in a body fluid sampling device |
US5951492A (en) | 1996-05-17 | 1999-09-14 | Mercury Diagnostics, Inc. | Methods and apparatus for sampling and analyzing body fluid |
DE19622458C2 (de) * | 1996-05-24 | 1998-03-26 | Senslab Ges Zur Entwicklung Un | Enzymatisch-elektrochemischer Einschritt-Affinitätssensor zur quantitativen Bestimmung von Analyten in wäßrigen Medien und Affinitätsassay |
DE19621133A1 (de) * | 1996-05-24 | 1997-11-27 | Boehringer Mannheim Gmbh | Bestimmungsverfahren mit oligomerisierten Rezeptoren |
EP0901620B1 (en) * | 1996-05-28 | 2002-01-09 | Zeptosens AG | Optical detection apparatus for chemical analyses of small volumes of samples |
US5852229A (en) | 1996-05-29 | 1998-12-22 | Kimberly-Clark Worldwide, Inc. | Piezoelectric resonator chemical sensing device |
US6004530A (en) | 1996-06-04 | 1999-12-21 | Roche Diagnostics Gmbh | Use of metallo-porphyrin conjugates for the detection of biological substances |
US6444423B1 (en) | 1996-06-07 | 2002-09-03 | Molecular Dynamics, Inc. | Nucleosides comprising polydentate ligands |
US5876944A (en) * | 1996-06-10 | 1999-03-02 | Bayer Corporation | Method for amplification of the response signal in a sandwich immunoassay |
EP0910790A1 (en) * | 1996-07-10 | 1999-04-28 | Cambridge Imaging Limited | Improvements in and relating to imaging |
US5660790A (en) * | 1996-08-13 | 1997-08-26 | Litmus Concepts, Inc. | PH and amine test elements |
US6020047A (en) * | 1996-09-04 | 2000-02-01 | Kimberly-Clark Worldwide, Inc. | Polymer films having a printed self-assembling monolayer |
US6194220B1 (en) * | 1996-09-25 | 2001-02-27 | Becton, Dickinson And Company | Non-instrumented assay with quantitative and qualitative results |
US5798273A (en) | 1996-09-25 | 1998-08-25 | Becton Dickinson And Company | Direct read lateral flow assay for small analytes |
US5910940A (en) * | 1996-10-08 | 1999-06-08 | Polaroid Corporation | Storage medium having a layer of micro-optical lenses each lens generating an evanescent field |
US6165798A (en) | 1996-10-10 | 2000-12-26 | University Of British Columbia | Optical quantification of analytes in membranes |
US5922537A (en) * | 1996-11-08 | 1999-07-13 | N.o slashed.AB Immunoassay, Inc. | Nanoparticles biosensor |
US6048623A (en) * | 1996-12-18 | 2000-04-11 | Kimberly-Clark Worldwide, Inc. | Method of contact printing on gold coated films |
US5922550A (en) | 1996-12-18 | 1999-07-13 | Kimberly-Clark Worldwide, Inc. | Biosensing devices which produce diffraction images |
US5962995A (en) | 1997-01-02 | 1999-10-05 | Applied Advanced Technologies, Inc. | Electron beam accelerator |
US6407492B1 (en) * | 1997-01-02 | 2002-06-18 | Advanced Electron Beams, Inc. | Electron beam accelerator |
US5827748A (en) | 1997-01-24 | 1998-10-27 | The United States Of America As Represented By The Secretary Of The Navy | Chemical sensor using two-dimensional lens array |
EP0859230A1 (en) | 1997-02-10 | 1998-08-19 | Cranfield University | Detection of analytes using electrochemistry |
US6391558B1 (en) * | 1997-03-18 | 2002-05-21 | Andcare, Inc. | Electrochemical detection of nucleic acid sequences |
US6180288B1 (en) * | 1997-03-21 | 2001-01-30 | Kimberly-Clark Worldwide, Inc. | Gel sensors and method of use thereof |
US6235471B1 (en) * | 1997-04-04 | 2001-05-22 | Caliper Technologies Corp. | Closed-loop biochemical analyzers |
EP0872736A1 (en) * | 1997-04-18 | 1998-10-21 | Byk Gulden Italia S.p.A. | Assay utilizing magnetic particles |
US6103536A (en) * | 1997-05-02 | 2000-08-15 | Silver Lake Research Corporation | Internally referenced competitive assays |
US6171780B1 (en) * | 1997-06-02 | 2001-01-09 | Aurora Biosciences Corporation | Low fluorescence assay platforms and related methods for drug discovery |
US6613583B1 (en) | 1997-06-27 | 2003-09-02 | Igen International, Inc. | Electrochemiluminescent label based on multimetallic assemblies |
US6136611A (en) | 1997-07-31 | 2000-10-24 | Research International, Inc. | Assay methods and apparatus |
EP0898169B1 (en) | 1997-08-11 | 2002-02-06 | F. Hoffmann-La Roche Ag | Microparticle enhanced light scattering assay and microparticle reagents therefor |
US6080391A (en) * | 1997-08-14 | 2000-06-27 | Novo Nordisk A/S | Reduction of malodour |
CA2302702A1 (en) | 1997-08-29 | 1999-03-04 | William S. Gibbons, Jr. | Method and apparatus for rapid analysis of analytes in biological samples |
US5906921A (en) * | 1997-09-29 | 1999-05-25 | Matsushita Electric Industrial Co., Ltd. | Biosensor and method for quantitative measurement of a substrate using the same |
WO1999018438A1 (en) * | 1997-10-02 | 1999-04-15 | Aclara Biosciences, Inc. | Capillary assays involving separation of free and bound species |
US6617488B1 (en) | 1997-10-14 | 2003-09-09 | Indicator Technologies, Inc. | Method and apparatus for indicating the conditions in an absorbent article |
US6174646B1 (en) * | 1997-10-21 | 2001-01-16 | Konica Corporation | Image forming method |
US6087184A (en) | 1997-11-10 | 2000-07-11 | Beckman Coulter, Inc. | Opposable-element chromatographic assay device for detection of analytes |
US6030792A (en) * | 1997-11-13 | 2000-02-29 | Pfizer Inc | Assays for measurement of protein fragments in biological media |
US5997817A (en) | 1997-12-05 | 1999-12-07 | Roche Diagnostics Corporation | Electrochemical biosensor test strip |
US6074725A (en) * | 1997-12-10 | 2000-06-13 | Caliper Technologies Corp. | Fabrication of microfluidic circuits by printing techniques |
EP1046027A1 (en) | 1997-12-11 | 2000-10-25 | Quidel Corporation | One-step fluorescent immunosensor test |
US6060256A (en) * | 1997-12-16 | 2000-05-09 | Kimberly-Clark Worldwide, Inc. | Optical diffraction biosensor |
SE9704933D0 (sv) | 1997-12-30 | 1997-12-30 | Pharmacia & Upjohn Diag Ab | Metod som utnyttjar en ny kalibrator och test kit som innehåller kalibratorn |
JP3468750B2 (ja) * | 1998-01-22 | 2003-11-17 | ルミネックス コーポレイション | 多数の蛍光シグナルを有する微小粒子 |
DE19811622A1 (de) | 1998-03-17 | 1999-09-23 | Lre Technology Partner Gmbh | Meßgerät zur Bestimmung der Konzentration einer Substanz in einer Flüssigkeit |
EP1064088B1 (en) | 1998-03-19 | 2002-12-04 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Fabrication of multilayer-coated particles and hollow shells via electrostatic self-assembly of nanocomposite multilayers on decomposable colloidal templates |
US6368873B1 (en) * | 1998-04-09 | 2002-04-09 | Applied Biotech, Inc. | Identification of human urine for drug testing |
US6241863B1 (en) | 1998-04-27 | 2001-06-05 | Harold G. Monbouquette | Amperometric biosensors based on redox enzymes |
US6451607B1 (en) | 1998-05-07 | 2002-09-17 | Litmus Concepts, Inc. | External dried-reagent control for analytical test devices |
US6139961A (en) | 1998-05-18 | 2000-10-31 | Rohm And Haas Company | Hollow sphere organic pigment for paper or paper coatings |
JPH11326603A (ja) * | 1998-05-19 | 1999-11-26 | Seiko Epson Corp | マイクロレンズアレイ及びその製造方法並びに表示装置 |
WO1999064864A1 (en) | 1998-06-12 | 1999-12-16 | New Horizons Diagnostics Inc. | Optimizing sensitivity in colloidal colorimetric flow through and lateral flow tests |
US6030840A (en) * | 1998-06-15 | 2000-02-29 | Nen Life Sciences, Inc. | Neutral enhancement of lanthanides for time resolved fluorescence |
US6183972B1 (en) * | 1998-07-27 | 2001-02-06 | Bayer Corporation | Method for the determination of analyte concentration in a lateral flow sandwich immunoassay exhibiting high-dose hook effect |
US6171870B1 (en) * | 1998-08-06 | 2001-01-09 | Spectral Diagnostics, Inc. | Analytical test device and method for use in medical diagnoses |
US6281006B1 (en) | 1998-08-24 | 2001-08-28 | Therasense, Inc. | Electrochemical affinity assay |
US7640083B2 (en) | 2002-11-22 | 2009-12-29 | Monroe David A | Record and playback system for aircraft |
AU6275699A (en) | 1998-09-29 | 2000-04-17 | Fertility Acoustics Inc. | A method of and device for determining ovulation in mammals |
GB9821526D0 (en) * | 1998-10-02 | 1998-11-25 | Genosis Inc | Capture assay |
US6284472B1 (en) | 1998-10-05 | 2001-09-04 | Dade Behring Inc. | Method for extending the range of an immunoassay |
US6338790B1 (en) | 1998-10-08 | 2002-01-15 | Therasense, Inc. | Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator |
BE1012241A3 (fr) | 1998-10-21 | 2000-08-01 | D Tek | Procede de depistage d'analyte et trousse pour la mise en oeuvre d'un tel procede. |
FI982422A0 (fi) * | 1998-11-09 | 1998-11-09 | Arctic Diagnostics Oy | Porfyriiniyhdisteitä, niiden konjugaatit sekä määritysmenetelmiä pohjautuen näiden konjugaattien käyttöön |
US6261779B1 (en) * | 1998-11-10 | 2001-07-17 | Bio-Pixels Ltd. | Nanocrystals having polynucleotide strands and their use to form dendrimers in a signal amplification system |
CA2254223A1 (en) * | 1998-11-16 | 2000-05-16 | Biophys, Inc. | Device and method for analyzing a biologic sample |
US6455861B1 (en) | 1998-11-24 | 2002-09-24 | Cambridge Research & Instrumentation, Inc. | Fluorescence polarization assay system and method |
US6221579B1 (en) * | 1998-12-11 | 2001-04-24 | Kimberly-Clark Worldwide, Inc. | Patterned binding of functionalized microspheres for optical diffraction-based biosensors |
US6579673B2 (en) | 1998-12-17 | 2003-06-17 | Kimberly-Clark Worldwide, Inc. | Patterned deposition of antibody binding protein for optical diffraction-based biosensors |
EP1161490A4 (en) | 1999-02-05 | 2003-04-09 | Univ Maryland | NANOPARTICLES IN LIEU OF LUMINESCENCE PROBES |
WO2000047983A1 (en) | 1999-02-11 | 2000-08-17 | University Of Southern California | Enzyme-linked immuno-magnetic electrochemical biosensor |
US6696304B1 (en) * | 1999-02-24 | 2004-02-24 | Luminex Corporation | Particulate solid phase immobilized protein quantitation |
US6585939B1 (en) * | 1999-02-26 | 2003-07-01 | Orchid Biosciences, Inc. | Microstructures for use in biological assays and reactions |
AU3504700A (en) | 1999-02-26 | 2000-09-14 | Fertility Acoustics Inc. | Analyzing strip having a fluid cell and a method of analyzing a sample |
AU2898500A (en) * | 1999-03-02 | 2000-09-21 | Helix Biopharma Corporation | Biosensor device and method |
US6287783B1 (en) | 1999-03-18 | 2001-09-11 | Biostar, Inc. | Optical assay device and method |
US6511814B1 (en) * | 1999-03-26 | 2003-01-28 | Idexx Laboratories, Inc. | Method and device for detecting analytes in fluids |
US6815218B1 (en) | 1999-06-09 | 2004-11-09 | Massachusetts Institute Of Technology | Methods for manufacturing bioelectronic devices |
AU4712600A (en) * | 1999-06-18 | 2001-01-09 | Umedik, Inc. | Device and method for analyzing a biologic sample |
US6294392B1 (en) | 1999-07-21 | 2001-09-25 | The Regents Of The University Of California | Spatially-encoded analyte detection |
US6372895B1 (en) * | 2000-07-07 | 2002-04-16 | 3M Innovative Properties Company | Fluorogenic compounds |
WO2001023891A1 (fr) | 1999-09-29 | 2001-04-05 | Japan Science And Technology Corporation | Dosage immunologique à haute sensibilité |
US6306665B1 (en) * | 1999-10-13 | 2001-10-23 | A-Fem Medical Corporation | Covalent bonding of molecules to an activated solid phase material |
US6136549A (en) | 1999-10-15 | 2000-10-24 | Feistel; Christopher C. | systems and methods for performing magnetic chromatography assays |
USD450854S1 (en) | 1999-11-04 | 2001-11-20 | Therasense, Inc. | Glucose strip |
WO2001038873A2 (en) | 1999-11-24 | 2001-05-31 | Biotronic Technologies, Inc. | Devices and methods for detecting analytes using electrosensor having capture reagent |
US6331438B1 (en) | 1999-11-24 | 2001-12-18 | Iowa State University Research Foundation, Inc. | Optical sensors and multisensor arrays containing thin film electroluminescent devices |
US6399295B1 (en) | 1999-12-17 | 2002-06-04 | Kimberly-Clark Worldwide, Inc. | Use of wicking agent to eliminate wash steps for optical diffraction-based biosensors |
US6509196B1 (en) * | 2000-01-04 | 2003-01-21 | Response Biomedical Corp. | Compensation for non-specific signals in quantitative immunoassays |
US6255066B1 (en) * | 2000-02-08 | 2001-07-03 | Allan L. Louderback | Bacterial vaginosis screening technique and a diagnostic kit for use therein |
US20010055776A1 (en) | 2000-02-11 | 2001-12-27 | Dale Greenwalt | High throughput cell-based assay kits |
NZ521534A (en) | 2000-02-23 | 2004-10-29 | Besst Test Aps | Method for correlating blood coagulation activity with markers in urine |
US6607922B2 (en) | 2000-03-17 | 2003-08-19 | Quantum Design, Inc. | Immunochromatographic assay method and apparatus |
US6436722B1 (en) * | 2000-04-18 | 2002-08-20 | Idexx Laboratories, Inc. | Device and method for integrated diagnostics with multiple independent flow paths |
WO2001098785A2 (en) | 2000-06-19 | 2001-12-27 | Arizona Board Of Regents | Rapid flow-based immunoassay microchip |
DE60117556T2 (de) | 2000-06-21 | 2006-11-02 | Bioarray Solutions Ltd. | Multianalytische molekularanalyse durch verwendung anwendungsspezifischer zufallspartikelarrays |
DE10042023C2 (de) * | 2000-08-08 | 2003-04-10 | Biognostic Ag | Kapseln, die feste Teilchen signalerzeugender Substanzen einkapseln, und deren Verwendung bei Bioassays zum Nachweis von Zielmolekülen in einer Probe |
AU2002239780A1 (en) * | 2000-10-25 | 2002-06-03 | Tufts University | Polymeric microspheres |
US20020164659A1 (en) | 2000-11-30 | 2002-11-07 | Rao Galla Chandra | Analytical methods and compositions |
DE10062062C1 (de) | 2000-12-13 | 2002-02-28 | Draegerwerk Ag | Elektrochemischer Sensor |
US20030162236A1 (en) | 2001-03-26 | 2003-08-28 | Response Biomedical Corporation | Compensation for variability in specific binding in quantitative assays |
JP2002303629A (ja) | 2001-04-06 | 2002-10-18 | Matsushita Electric Ind Co Ltd | 免疫クロマトデバイス及びそれを用いた被検物質測定方法 |
US20030108949A1 (en) | 2001-07-03 | 2003-06-12 | Gang Bao | Filtration-based microarray chip |
US6818456B2 (en) * | 2001-07-20 | 2004-11-16 | Varian, Inc. | Color contrast system for lateral flow immunoassay tests |
US8367013B2 (en) | 2001-12-24 | 2013-02-05 | Kimberly-Clark Worldwide, Inc. | Reading device, method, and system for conducting lateral flow assays |
US20030119203A1 (en) | 2001-12-24 | 2003-06-26 | Kimberly-Clark Worldwide, Inc. | Lateral flow assay devices and methods for conducting assays |
WO2003058246A1 (en) | 2001-12-24 | 2003-07-17 | Kimberly-Clark Worldwide, Inc. | Flow-through assay with an internal calibration system using polyelectrolyte |
US7214427B2 (en) | 2002-03-21 | 2007-05-08 | Aviva Biosciences Corporation | Composite beads comprising magnetizable substance and electro-conductive substance |
US7285424B2 (en) * | 2002-08-27 | 2007-10-23 | Kimberly-Clark Worldwide, Inc. | Membrane-based assay devices |
US7314763B2 (en) | 2002-08-27 | 2008-01-01 | Kimberly-Clark Worldwide, Inc. | Fluidics-based assay devices |
US7432105B2 (en) * | 2002-08-27 | 2008-10-07 | Kimberly-Clark Worldwide, Inc. | Self-calibration system for a magnetic binding assay |
US20040106190A1 (en) | 2002-12-03 | 2004-06-03 | Kimberly-Clark Worldwide, Inc. | Flow-through assay devices |
US7247500B2 (en) | 2002-12-19 | 2007-07-24 | Kimberly-Clark Worldwide, Inc. | Reduction of the hook effect in membrane-based assay devices |
US20040121334A1 (en) | 2002-12-19 | 2004-06-24 | Kimberly-Clark Worldwide, Inc. | Self-calibrated flow-through assay devices |
US20040197819A1 (en) | 2003-04-03 | 2004-10-07 | Kimberly-Clark Worldwide, Inc. | Assay devices that utilize hollow particles |
US20050112703A1 (en) | 2003-11-21 | 2005-05-26 | Kimberly-Clark Worldwide, Inc. | Membrane-based lateral flow assay devices that utilize phosphorescent detection |
US7943395B2 (en) | 2003-11-21 | 2011-05-17 | Kimberly-Clark Worldwide, Inc. | Extension of the dynamic detection range of assay devices |
US20050136550A1 (en) | 2003-12-19 | 2005-06-23 | Kimberly-Clark Worldwide, Inc. | Flow control of electrochemical-based assay devices |
US20050136500A1 (en) | 2003-12-19 | 2005-06-23 | Kimberly-Clark Worldwide; Inc. | Flow-through assay devices |
US7943089B2 (en) | 2003-12-19 | 2011-05-17 | Kimberly-Clark Worldwide, Inc. | Laminated assay devices |
US20050191704A1 (en) | 2004-03-01 | 2005-09-01 | Kimberly-Clark Worldwide, Inc. | Assay devices utilizing chemichromic dyes |
US20050244953A1 (en) | 2004-04-30 | 2005-11-03 | Kimberly-Clark Worldwide, Inc. | Techniques for controlling the optical properties of assay devices |
-
2002
- 2002-12-19 US US10/325,614 patent/US7247500B2/en not_active Expired - Fee Related
-
2003
- 2003-10-29 CN CNB2003801052766A patent/CN100476437C/zh not_active Expired - Fee Related
- 2003-10-29 MX MXPA05005951A patent/MXPA05005951A/es active IP Right Grant
- 2003-10-29 AT AT03783087T patent/ATE408833T1/de not_active IP Right Cessation
- 2003-10-29 KR KR1020057009930A patent/KR101072756B1/ko active IP Right Grant
- 2003-10-29 DE DE60323672T patent/DE60323672D1/de not_active Expired - Lifetime
- 2003-10-29 ES ES03783087T patent/ES2312837T3/es not_active Expired - Lifetime
- 2003-10-29 CA CA2508774A patent/CA2508774C/en not_active Expired - Fee Related
- 2003-10-29 WO PCT/US2003/034543 patent/WO2004061454A1/en not_active Application Discontinuation
- 2003-10-29 AU AU2003290552A patent/AU2003290552A1/en not_active Abandoned
- 2003-10-29 EP EP03783087A patent/EP1573326B1/en not_active Expired - Lifetime
- 2003-11-26 TW TW092133144A patent/TW200424524A/zh unknown
-
2007
- 2007-07-20 US US11/780,671 patent/US7662643B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
WO2004061454A1 (en) | 2004-07-22 |
US7662643B2 (en) | 2010-02-16 |
CA2508774C (en) | 2011-07-05 |
KR101072756B1 (ko) | 2011-10-11 |
KR20050085270A (ko) | 2005-08-29 |
US20080014659A1 (en) | 2008-01-17 |
EP1573326B1 (en) | 2008-09-17 |
ES2312837T3 (es) | 2009-03-01 |
US7247500B2 (en) | 2007-07-24 |
US20040121480A1 (en) | 2004-06-24 |
ATE408833T1 (de) | 2008-10-15 |
TW200424524A (en) | 2004-11-16 |
CA2508774A1 (en) | 2004-07-22 |
MXPA05005951A (es) | 2005-08-18 |
DE60323672D1 (de) | 2008-10-30 |
AU2003290552A1 (en) | 2004-07-29 |
CN1720455A (zh) | 2006-01-11 |
EP1573326A1 (en) | 2005-09-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN100476437C (zh) | 减少钩效应的流通测定装置及检测方法 | |
CN1879019B (zh) | 检测测试样品中被分析物的存在或数量的流通试验装置和方法 | |
CN100501406C (zh) | 直通型检测装置的内部校准系统 | |
CN101002096A (zh) | 用来检测大病原体的横向流动设备 | |
AU2007319076B2 (en) | Saturation assay | |
CN1720456A (zh) | 自校正流通测定装置 | |
JP2008524582A (ja) | 試料効率の高い横流型免疫学的検定装置 | |
KR20040068976A (ko) | 플로우-스루 분석체용 내부 보정 시스템 | |
JP2004500569A (ja) | 多重アッセイ法のための内部標準および内部対照 | |
JP4274944B2 (ja) | ダイナミックレンジが拡張された粒子利用リガンドアッセイ | |
CN1761880B (zh) | 减少分析装置中的钩状效应 | |
JP2005510706A5 (zh) | ||
TW200305718A (en) | Polyelectrolytic internal calibration system of flow-through assays | |
US7713748B2 (en) | Method of reducing the sensitivity of assay devices | |
AU2014200264A1 (en) | Saturation assay |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20090408 Termination date: 20191029 |