CN1950520A - 用干试剂分离dna的方法和装置 - Google Patents

用干试剂分离dna的方法和装置 Download PDF

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CN1950520A
CN1950520A CNA200580013761XA CN200580013761A CN1950520A CN 1950520 A CN1950520 A CN 1950520A CN A200580013761X A CNA200580013761X A CN A200580013761XA CN 200580013761 A CN200580013761 A CN 200580013761A CN 1950520 A CN1950520 A CN 1950520A
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沃尔特·冈布雷克特
彼得·波利卡
曼弗莱德·斯坦泽尔
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Abstract

本发明涉及一种在去除后续PCR的干扰成分情况下分离DNA的方法，其具有下列措施：所有物质和方法步骤完全整合在一个密闭的一次性使用的单元(所谓的药筒)中，该单元允许加入含DNA的样品；为分离该释出的DNA使用结合DNA的基底。特别是在应用通过白细胞的细胞分解从全血中分离DNA的方法时，用于实施细胞分解和其它反应所需的试剂以室温下稳定的形式储存，并且为分解白细胞和分离DNA，使干储存的分解－试剂溶于水溶液中，并与白细胞接触。在相关的装置中包括用于接受含DNA的生物容器和/或试剂的单元，因而至少提供一个微通道(5)以容纳试剂，而在微通道中试剂以具有可忽略蒸汽压的干混合物存在，其在室温下形成稳定物质。

Description

用干试剂分离DNA的方法和装置
本发明涉及一种用干试剂分离DNA的方法。此外本发明还涉及一种用于实施该方法的相关装置。
在核酸分析要回答如全血的白细胞中人类基因的问题时，在样品制备步骤中首先必需破裂细胞，并接着分离释放出的DNA。这时必需去除能阻碍后续PCR的血液成分如血红蛋白、免疫球蛋白和乳铁蛋白。
在实验室这种操作步骤是按熟知的现有技术进行的。除其它方法外，细胞还可用碱性溶液(NaOH)破裂(所谓溶胞)，并接着将DNA结合到涂有硅胶的磁-珠上。通过施加磁场固定载有DNA的磁-珠并洗涤之。其后如此分离出的DNA可以有珠或无珠地用于PCR(“聚合酶链反应”)。
在现有技术中，该结合DNA的磁-珠以悬浮体混入细胞-溶解-缓冲液中。所有的操作步骤例如均在1.5ml-反应容器(所谓的“Eppendorf”-容器，即微量离心管)中进行。将如10μl的全血加到给定体积的珠-悬浮物中(例如，200μl)。由此血细胞分解并释出DNA。该磁-珠结合DNA并形成一种DNA/珠-复合体。接着该DNA/珠-复合体通过磁场固定在“Eppendorf管”的容器壁上，以致可进行洗涤步骤以去除阻碍PCR的物质。最后可进行PCR。
实施上述方法是依赖于现有的实验室设备如“Eppendorf”-容量(管)、管-支承-设备包括磁体、移液管-设备、适于试剂的冷却容器，并必需由经培训过的人员在遵守安全规定(传染危险、废物处置等)下进行。部分对健康有危害的物质(如NaOH)的各种容积和高准确的计量必需通过移液管进行。这些操作步骤也是很耗时的。
由US 2002/0022261 A1已知一种适于微型遗传分析的体系和相关的操作方法，其中应用一种具有至少一个入口和一个多孔性输送道的药筒，该药筒应有结合DNA的特性。这时进行细胞分解，为此需要时在容器壁上提供有试剂。此外，该壁的结构区可配置有结合DNA的材料，需要时还有磁珠。总之其中给出了一系列用于进行遗传分析测量的各种建议，但仍未实现连续的方法。此外，由EP 0723549 B1己知一种用于分离DNA的混合物，该混合物特别是含硅胶、玻璃细粒和至少一种kaotropisches盐的混合物。
基于最近现有技求，本发明的目的在于，无例外地在整合的微型药筒中实施DNA-分离，并提供一种相关的装置。
本发明的目的是通过权利要求1的措施实现的。相关设备示于权利要求13。该方法的其他方面和相关装置的扩展方案列于从属权利要求中。
在本发明范围内，权利要求2包括具有含DNA的生物容器如细胞、细菌或病毒的分解方法。由此可在特别有利的和实用的实践中以DNA-信息检测全血样品。
本发明除了基于上述现有技求外还基于WO 02/072262 A1中的“分析设备”附图。其中描述了干式储存在“嵌片”的微通道或微空腔中的在室温下稳定的试剂，该试剂在使用前加水而变成溶液。该干试剂按预定剂量提供，以在溶解后产生定量的分析介质。与此相反，在本发明中涉及一种生物容器的细胞分解，例如从全血-样品中分离DNA以进行其后的PCR和/或分析。由样品中分离出的DNA以合适的方法提供。
与至今应用的实验室方法相比，用本发明方法具有下列优点：
·所有物质和方法完全整合在一个密封的一次性使用的药筒中；
·确保该试剂以安全、对健康无害及在室温下可稳定储存的方式储存；
·除注入血液样品外，无需手工操作步骤；
·与有害健康的物质即在药筒中的血液和试剂-废物无直接接触；该药筒是小量并可低成本批量生产。
本发明的装置具有下列特征：
·存在至少一个微通道或微空腔。
·在微通道或微空腔中，该溶解-介质特别是在有适于DNA的基底的成膜剂包体下安置在通道的壁上。
引入到微通道或微空腔中的溶解试剂具有下列特性：
·适于白细胞和/或其它细胞、细菌、病毒的溶解特性；
·具有可忽略的蒸汽压的固体或液体；
·在室温下稳定；
·在微通道壁上或微空腔壁上的优良粘附性。
本发明中重要的是，在连贯的方法链中释放出含于样品中的DNA，收集分离的DNA并以合适的方法送到PCR或测定的地点。
本发明的其它详情和优点由下面按实施例的附图描述并结合权利要求给出。
附图简介
图1示出分析设备(药筒)的俯视图
图2-图6各为图1中沿线II-II的截面图，用于说明由全血中的DNA-分离，其中图2-6各包括不同的功能阶段。
下面的描述是阐明含DNA的样品。这类样品可以是在液体中的DNA的溶液，但是也可以是含DNA的生物容器的悬浮物。在本文中例如细胞、细菌或病毒均视为生物容器。为释放DNA必需分解该生物容器。如果相应于人类基因目的使用全血样品，则需对DNA位于其中的白细胞进行细胞分解。
图1中示出分析设备图，随后也可形成“药筒”和作为集中的或分散的测量设备。特别是形成嵌片(“嵌片实验室”)类的分析设备，该嵌片含有用于处理和分析测量样品的所有介质，本设备按规定操作所需要的相关控制设备/读出设备在本文中未给出。
详述之，该设备由塑料制成的嵌片体1组成，其具有流体的入口和出口。特别是有引入水的入口2(孔)和引入测量样品如血液的入口3(孔)。重要的是通过合适的液流设备2-10，特别是不同几何形状的通道和空腔以传输和汇集测量样品和溶液介质。
详述之，该液流-设备除上述水入口和样品入口2，3外还包括两个试剂通道4，4’以及有出口6的流道5、废物收集通道8和其它液流通道9。用10表示适于样品处理的流道5中的集中混合区。
该样品在混合段10中经处理并经分离含于测量样品中的DNA后，收集释放出的DNA，并送入PCR-腔20以进行PCR(聚合酶链反应)。
在图1装置中特别是用干试剂进行PCR的方法详述于本申请人的具有同样申请优先权的同时申请并名称为“借助用干试剂的PCR的扩增DNA的方法和装置”中。
该嵌片1(“药筒”)除含用于PCR的介质外，还包含具有入口32和出口31的探测模块30以及相关的用于传感器信号读出的电连接。此外，还有用于接纳探测用的试剂的手段如通道4和4’以及用于接纳废物如血和用过的试剂溶液的手段如通道8和9。因此保证了整合性，这样无有害健康的物质向外排出。
由图2-6可看出，图1的具有水入口2和血液入口3的塑料嵌片1包含穿流通道5，通过该通道，可将作为冲洗液的水和作为测量样品的例如血或DNA-溶液或细胞悬浮液/细菌悬浮液/病毒悬浮液引入其它封闭的体系中。经出口6可将废物转送到废物-通道8或废物空腔中。穿流通道5是在塑料嵌片1上，其相对面通过胶粘膜7所覆盖。在穿流通道5的中心区形成混合段10，其中特别是制备用于从全血中DNA-分离的测量样品。
从全血中的DNA-分离是通过白细胞的分解而实现。为此，该细胞用分解-试剂进行化学破裂，并将其中所含的DNA释出和收集。特别是利用已知的前述方法即经所谓的磁-珠，它至少暂时结合细胞分解后的DNA，并通过外磁场浓集。
特别是由图2可看出，在塑料嵌片1的穿流通道5的区域10中安置一个有可溶于水的储存稳定的干试剂11。本文中储存稳定性意指该固体在室温下可储存几个月并还保持对样品起分解作用的特性。
在图2和3中，该干物质11具有在穿流通道壁上的优良粘附性。例如这可通过加入成膜剂来实现。详述之，在混合段10中呈大面积地安置由含磁-珠13的己知分解-试剂组成的混合物11。此外，磁铁15以图例表示，其表明应用磁性以收集其上结合有DNA的磁-珠13。
由图3和图4看出，在图2的装置中经移液管尖17将全血12加入到测量体系中。加入样品后，该入口3用胶粘膜18封闭。
经入口2引入水或缓冲溶液。水或缓冲溶液沿混合段与血液样品12混合，以同样方式溶解或悬浮包括磁-珠13的分解-试剂11，并发生作用。为此该白细胞的细胞壁首先通过溶降-试剂而破裂，接着将这时释放出的DNA结合在磁-珠的表面。
图4是通过水/缓冲溶液稀释该血液样品，并同时溶解该分解-试剂，该分解-试剂用于确保白细胞分解。以同样方式还使存在于通道壁上混合物11的磁-珠进入或悬浮于溶液中，并经磁-珠13结合DNA。由此下列4个重要的方法步骤可在单一过程中实现：
·样品稀释，
·试剂溶解/磁珠悬浮，
·细胞分解，
·DNA结合。
最后按图5进行说明。这时可收集经磁-珠13可受磁性作用的DNA，而PCR-阻碍物质由水或缓冲溶液洗去，并经出口6以废物排出。
作为上述措施的结果，图6中通过磁-珠13结合的DNA在磁铁的磁极上的浓集。该DNA可用于分析，这时首先特别要进行PCR。
另外，在与磁场组合下作为结合DNA的介质可应用移动的即悬浮的磁粒，也可使用不移动的即定位在细胞分解-通道的出口的位置固定的结合DNA的介质。在此实施方案中，由细胞释出的DNA在离开细胞分解通道时通过溢流越过位置固定的结合DNA的介质由液体流中引出，并结合在结合DNA的介质上。作为结合NDA的介质可使用如有结合DNA的捕集分子的水凝胶或类似物质。
通过本发明的方法和相关装置特别可以以一步法实现简单而快速的DNA-分离，这仅需要最小的微流体介质、试剂和方法步骤。
接着可对经分离的DNA进行PCR。采用PCR可将DNA浓度提高到可分析可检测值的水平。这时可将PCR组合到分析过程中。该分析在相应于图1的探测模块30中进行，有关这方面这里不再详述。
总之在本发明中实现了下列措施：
·在微通道或微空腔中引入的物质具有结合DNA的特性。为此应用例如结合DNA的磁-珠；
·该分解-试剂和磁-珠特别是一同包含在一个单一的干基体中；
·有适于全血-样品、细胞悬浮物/细菌悬浮物/病毒悬浮物的入口；
·有加水的手段。例如可以是连接到外水源上的输入口；
·需要时存在用于计量加入如调节所确定的离子强度用的盐的手段；
·需要时存在用于稀释血液样品的手段；
·需要时存在其它手段，特别是通道和空腔，以用于制备所确定的盐溶液/缓冲溶液以洗涤所结合的DNA，如DNA-磁-珠-复合体；
·优选在药筒外部存在以血或血/水混合物、血/缓冲液混合物通流具有分解试剂/珠-试剂涂敷过的微通过或微空腔的手段；
·存在产生磁场以例如在微通道的出口处固定DNA/磁-珠-复合体的手段，该手段优选存在于药筒的外部。
由此确保包括样品制备的整个分析过程是在封闭的体系中完成，该体系是由环境相容的塑料制成的一次性药筒。

Claims (29)

1.一种在去除后续PCR的干扰成分情况下分离DNA的方法，其具有下列措施：
·所有物质和方法步骤完全整合在一个一次性使用的单元(所谓的药筒)中，该单元允许加入含DNA的样品；
·应用干试剂释放DNA；
·应用结合DNA的基底以分离该释出的DNA；
·收集分离的DNA，并将其输送到后续的PCR的位置。
2.权利要求1的方法，其中分解含DNA的生物容器，特别是细胞、细菌或病毒，为实施分解和其它的方法步骤所需的试剂以在室温下稳定的形式储存在该单元中，其特征在于，为分解含DNA的生物容器，使干储存的分解-试剂与生物容器，特别是细胞、细菌或病毒相接触，并结合所释出的DNA并将其输送到PCR的位置。
3.权利要求2的方法，其特征在于，应用白细胞作为含DNA的容器。
4.权利要求3的方法，其特征在于，该干储存的和储存稳定的分解-试剂借助于水而和白细胞接触。
5.权利要求1和2的方法，其特征在于，样品的稀释、干试剂的溶解或悬浮、生物容器的分解和DNA的结合是在一个单一的方法步骤中完成。
6.权利要求1的方法，其特征在于，应用所谓的磁-珠作为结合DNA的基底。
7.权利要求1的方法，其特征在于，应用一种在细胞分解通道出口处的不移动的含DNA-捕集物质的水凝胶作为结合DNA的基底。
8.权利要求6的方法，其特征在于，该释出的DNA通过磁-珠结合，并输送到收集位置或反应位置。
9.权利要求6的方法，其特征在于，该磁-珠通过应用磁场收集。
10.权利要求9的方法，其特征在于，流动的磁-珠通过位置固定的磁场收集。
11.权利要求1的方法，其特征在于，在反应位置该PCR是通过与干储存的水可溶的试剂的热循环来进行。
12.权利要求1的方法，其特征在于，稀释加入到单元中的血样品，并通过试剂通道泵入适于PCR的反应通道。
13.权利要求12的方法，其特征在于，经DNA-分离后，残余的血、血成分和试剂废物保留在单元中，以致不可能发生与有害健康的物质相接触。
14.上述权利要求之一的方法，其特征在于，应用一次性产品作为实施反应的单元，该单元可以小量并低成本批量制备。
15.一种实施权利要求1或权利要求2-14之一的装置，其具有接受样品和/或试剂的单元，其中有至少一个微通道(5)以接受试剂，在微通道(5)中的试剂以具有可忽略蒸汽压的干混合物存在，其在室温下形成稳定物质。
16.权利要求15的装置，其特征在于，通过加入成膜剂该干试剂以层(11)结合。
17.权利要求15的装置，其特征在于，该含DNA的生物容器特别是细胞、细菌、病毒。
18.权利要求17的装置，其特征在于，为实施生物容器的分解，在微通道(5)中的具有可忽略蒸汽压的干物质是分解-试剂，其具有适于白细胞的特异性质。
19.权利要求18的装置，其特征在于，适于分解-物质的通道(5)通到PCR-空腔(20)内。
20.权利要求19的装置，其特征在于，在微通道(5)或微空腔(20)中存在具有结合DNA的特性的基底。
21.权利要求20的装置，其特征在于，该结合DNA的基底是所谓的磁-珠(10)。
22.权利要求21的装置，其特征在于，该分解-试剂(11)和磁-珠(13)包含于一个共同的干基体中。
23.权利要求15-22之一的装置，其特征在于，存在一种用于全血-样品的入口(3)。
24.权利要求15-23之一的装置，其特征在于，存在用于加入水的手段(2)。
25.权利要求15-24之一的装置，其特征在于，存在用于调节开确定的离子强度的干缓冲物质。
26.权利要求15-25之一的装置，其特征在于，存在用于混合血液样品和水或缓冲溶液的手段。
27.权利要求15-26之一的装置，其特征在于，存在具有血、血/水混合物或血/缓冲液混合物通流用的以分解试剂/珠试剂涂敷过的微通道(5)或微空腔(20)的手段。
28.权利要求15-27之一的装置，其特征在于，存在用于产生磁场以在PCR-空腔(20)中固定DNA/磁-珠-复合体的手段。
29.权利要求15-28之一的装置，其特征在于，存在用于热循环的手段。
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Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102574127A (zh) * 2009-10-06 2012-07-11 皇家飞利浦电子股份有限公司 磁性样本净化
CN103547925A (zh) * 2011-01-28 2014-01-29 匡特里克斯公司 用于分子或粒子的超灵敏探测的***、装置以及方法
US9310360B2 (en) 2010-03-01 2016-04-12 Quanterix Corporation Ultra-sensitive detection of molecules or particles using beads or other capture objects
CN105517710A (zh) * 2013-07-05 2016-04-20 极小微技术股份公司 具有整合的干燥物质的液流电池
CN105555406A (zh) * 2013-09-27 2016-05-04 罗伯特·博世有限公司 用于执行聚合酶链式反应的分析单元、用于运行这样的分析单元的方法以及用于制造这样的分析单元的方法
CN105658333A (zh) * 2013-07-29 2016-06-08 阿特莱斯遗传学有限公司 用于核酸扩增和检测的射流卡盘
US9395359B2 (en) 2006-02-21 2016-07-19 Trustees Of Tufts College Methods and arrays for target analyte detection and determination of target analyte concentration in solution
US9551663B2 (en) 2010-03-01 2017-01-24 Quanterix Corporation Methods and systems for extending dynamic range in assays for the detection of molecules or particles
US9678068B2 (en) 2010-03-01 2017-06-13 Quanterix Corporation Ultra-sensitive detection of molecules using dual detection methods
US9809838B2 (en) 2007-08-30 2017-11-07 Trustees Of Tufts College Methods for determining the concentration of an analyte in solution
US9932626B2 (en) 2013-01-15 2018-04-03 Quanterix Corporation Detection of DNA or RNA using single molecule arrays and other techniques
US10393759B2 (en) 2011-04-12 2019-08-27 Quanterix Corporation Methods of determining a treatment protocol for and/or a prognosis of a patient's recovery from a brain injury
CN111565846A (zh) * 2018-01-15 2020-08-21 罗伯特·博世有限公司 在微流体装置中提供物质的溶液的方法
US10989713B2 (en) 2010-03-01 2021-04-27 Quanterix Corporation Methods and systems for extending dynamic range in assays for the detection of molecules or particles
US11237171B2 (en) 2006-02-21 2022-02-01 Trustees Of Tufts College Methods and arrays for target analyte detection and determination of target analyte concentration in solution

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102004021822B3 (de) * 2004-04-30 2005-11-17 Siemens Ag Verfahren und Anordnung zur DNA-Amplifikation mittels PCR unter Einsatz von Trockenreagenzien
JP2006029798A (ja) * 2004-07-12 2006-02-02 Hitachi Software Eng Co Ltd 試薬を内蔵した高反応効率生体物質検査チップ
DE102004050575B3 (de) * 2004-10-15 2006-01-05 Siemens Ag Verfahren zur kombinierten Isolierung von Magnet-Beads aus einer flüssigen Probe und anschließender Thermozyklisierung für die PCR und zugehörige Anordnung
US7851227B2 (en) * 2004-10-15 2010-12-14 Siemens Aktiengesellschaft Method for carrying out an electrochemical measurement on a liquid measuring sample in a measuring chamber that can be accessed by lines, and corresponding arrangement
US7763453B2 (en) 2005-11-30 2010-07-27 Micronics, Inc. Microfluidic mixing and analytic apparatus
US9056291B2 (en) 2005-11-30 2015-06-16 Micronics, Inc. Microfluidic reactor system
EP2007905B1 (en) * 2006-03-15 2012-08-22 Micronics, Inc. Integrated nucleic acid assays
AU2007265628B2 (en) 2006-06-23 2012-12-06 Perkinelmer Health Sciences, Inc. Methods and devices for microfluidic point-of-care immunoassays
EP2137323A4 (en) * 2007-02-28 2011-01-12 Ge Healthcare Bio Sciences STABLE CHEMICAL / BIOLOGICAL REAGENTS AT ROOM TEMPERATURE ON MEMBRANES OR FILTERS
EP2149610B1 (en) * 2007-03-26 2018-05-16 Fundacion Gaiker Device for detecting genetic material by means of polymerase chain reaction
FR2917095B1 (fr) * 2007-06-07 2009-07-17 Biomerieux Sa Dispositif de lyse de microorganismes presents dans un echantillon environnemental ou clinique et d'extraction des acides nucleiques desdits microorganismes aux fins d'analyse.
DE102007026910A1 (de) 2007-06-12 2008-12-18 Siemens Ag Untersuchungseinheit mit integrierter Minilabor-Analyseeinheit
DE102007042986A1 (de) 2007-09-10 2009-04-23 Siemens Ag Medizinisches Gerät und Verfahren zum Betreiben eines medizinischen Geräts
US9034277B2 (en) * 2008-10-24 2015-05-19 Honeywell International Inc. Surface preparation for a microfluidic channel
KR101071449B1 (ko) 2008-11-07 2011-10-10 연세대학교 산학협력단 병원균 검침을 위한 디엔에이 추출용 바이오칩 및 그것을 이용한 디엔에이 추출방법
EP2373804B1 (en) * 2008-12-05 2014-11-12 DNA Polymerase Technology, Inc. Compositions for improving gene amplification
US10196700B2 (en) 2009-03-24 2019-02-05 University Of Chicago Multivolume devices, kits and related methods for quantification and detection of nucleic acids and other analytes
US9464319B2 (en) 2009-03-24 2016-10-11 California Institute Of Technology Multivolume devices, kits and related methods for quantification of nucleic acids and other analytes
US9415392B2 (en) 2009-03-24 2016-08-16 The University Of Chicago Slip chip device and methods
US9447461B2 (en) 2009-03-24 2016-09-20 California Institute Of Technology Analysis devices, kits, and related methods for digital quantification of nucleic acids and other analytes
US20100332254A1 (en) * 2009-06-26 2010-12-30 Michael Maschke In-vitro device support for x-ray based kidney function test
US20100331673A1 (en) * 2009-06-26 2010-12-30 Michael Maschke System and method for reducing patient risk of allergic reaction to contrast agents or medical material
US20100331833A1 (en) * 2009-06-26 2010-12-30 Michael Maschke In-vitro device monitoring during minimally invasive ablation therapy
RU2451747C2 (ru) * 2009-08-13 2012-05-27 Закрытое акционерное общество "Научно-производственная фирма ДНК-Технология" Способ гомогенизации биологических образцов, содержащих магнитные наночастицы, при выделении днк в процессе автоматической пробоподготовки для пцр анализа
US9132423B2 (en) 2010-01-29 2015-09-15 Micronics, Inc. Sample-to-answer microfluidic cartridge
US9040679B2 (en) 2012-04-30 2015-05-26 General Electric Company Methods and compositions for extraction and storage of nucleic acids
US9040675B2 (en) 2012-04-30 2015-05-26 General Electric Company Formulations for nucleic acid stabilization on solid substrates
US9480966B2 (en) 2012-04-30 2016-11-01 General Electric Company Substrates and methods for collection, stabilization and elution of biomolecules
US9044738B2 (en) * 2012-04-30 2015-06-02 General Electric Company Methods and compositions for extraction and storage of nucleic acids
US20140200167A1 (en) 2012-08-01 2014-07-17 Nanomdx, Inc. Functionally integrated device for multiplex genetic identification
EP2914737B1 (en) 2012-10-31 2017-12-06 Cellay, Inc. Methods and kits for performing in situ hybridization
US10518262B2 (en) 2012-12-21 2019-12-31 Perkinelmer Health Sciences, Inc. Low elasticity films for microfluidic use
EP2935559B1 (en) 2012-12-21 2020-09-16 PerkinElmer Health Sciences, Inc. Fluorescence detection system
WO2014100732A1 (en) 2012-12-21 2014-06-26 Micronics, Inc. Fluidic circuits and related manufacturing methods
US10386377B2 (en) 2013-05-07 2019-08-20 Micronics, Inc. Microfluidic devices and methods for performing serum separation and blood cross-matching
US10087440B2 (en) 2013-05-07 2018-10-02 Micronics, Inc. Device for preparation and analysis of nucleic acids
JP6472788B2 (ja) 2013-05-07 2019-02-20 マイクロニクス， インコーポレイテッド 粘土鉱物およびアルカリ性溶液を使用して核酸含有試料を調製するための方法
TWI499779B (zh) 2013-07-04 2015-09-11 Ind Tech Res Inst 檢測晶片及其使用方法
US10946376B2 (en) 2013-07-05 2021-03-16 Thinxxs Microtechnology Ag Carrier element for introducing a dry substance into a flow cell
CA2962861A1 (en) 2014-09-29 2016-04-07 Chipcare Corporation Methods and devices for cell detection
AU2015352119A1 (en) 2014-11-28 2017-07-13 Chipcare Corporation Multiplex bead array assay
CN108473932B (zh) 2015-09-09 2022-07-15 集联健康有限公司 用于样品收集、稳定化和保存的***、方法和装置
US11311885B2 (en) 2016-06-02 2022-04-26 Integrated Nano-Technologies, Inc. System and method for confining reagents within a fluidic device
EP3399034B1 (en) * 2017-05-05 2022-12-28 Siemens Healthcare Diagnostics Inc. Device for extracting nucleic acids from biological sample materials with solvent-free reagents

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6221581B1 (en) 1984-04-27 2001-04-24 Enzo Diagnostics, Inc. Processes for detecting polynucleotides, determining genetic mutations or defects in genetic material, separating or isolating nucleic acid of interest from samples, and useful compositions of matter and multihybrid complex compositions
US5972386A (en) 1995-12-19 1999-10-26 Flinders Technologies Pty, Ltd. Dry solid medium for storage and analysis of genetic material
US5173260A (en) * 1990-09-17 1992-12-22 Eastman Kodak Company Beads fused to a test device support
US5413924A (en) 1992-02-13 1995-05-09 Kosak; Kenneth M. Preparation of wax beads containing a reagent for release by heating
US5498392A (en) 1992-05-01 1996-03-12 Trustees Of The University Of Pennsylvania Mesoscale polynucleotide amplification device and method
EP0572057A1 (en) 1992-05-11 1993-12-01 Johnson & Johnson Clinical Diagnostics, Inc. PCR reagent composition, test kit and methods for amplification and detection with reduced nonspecific amplification of nucleic acids
US5830644A (en) 1992-05-13 1998-11-03 Geron Corporation Method for screening for agents which increase telomerase activity in a cell
US5599660A (en) 1993-01-19 1997-02-04 Pharmacia Biotech Inc. Method and preparation for sequential delivery of wax-embedded, inactivated biological and chemical reagents
DE69433425T2 (de) * 1993-08-30 2004-10-07 Promega Corp Zusammensetzungen und verfahren zur reinigung von nukleinsäuren
CA2143365A1 (en) * 1994-03-14 1995-09-15 Hugh V. Cottingham Nucleic acid amplification method and apparatus
AU2871095A (en) * 1994-06-24 1996-01-19 University Of Houston, The Encapsulated pcr reagents
US6168948B1 (en) * 1995-06-29 2001-01-02 Affymetrix, Inc. Miniaturized genetic analysis systems and methods
US20020022261A1 (en) * 1995-06-29 2002-02-21 Anderson Rolfe C. Miniaturized genetic analysis systems and methods
DE69637047T2 (de) * 1995-07-13 2007-12-27 Applera Corp., Foster City Unabhängiges gerät zur extraktion, amplifikation und nachweis von nukleinsäuren
US5882903A (en) * 1996-11-01 1999-03-16 Sarnoff Corporation Assay system and method for conducting assays
WO1999033559A1 (en) * 1997-12-24 1999-07-08 Cepheid Integrated fluid manipulation cartridge
DE19811731A1 (de) 1998-03-18 1999-09-23 November Ag Molekulare Medizin Verfahren zum Nachweis einer Nukleotidsequenz
US6572830B1 (en) * 1998-10-09 2003-06-03 Motorola, Inc. Integrated multilayered microfludic devices and methods for making the same
US6887693B2 (en) 1998-12-24 2005-05-03 Cepheid Device and method for lysing cells, spores, or microorganisms
EP1180135B1 (en) * 1999-05-28 2005-08-17 Cepheid Apparatus and method for cell disruption
US6361958B1 (en) 1999-11-12 2002-03-26 Motorola, Inc. Biochannel assay for hybridization with biomaterial
WO2002055727A2 (en) 2001-01-09 2002-07-18 Whitehead Biomedical Inst Methods and reagents for the isolation of nucleic acids
DE10111457B4 (de) * 2001-03-09 2006-12-14 Siemens Ag Diagnoseeinrichtung
AU2002252560A1 (en) * 2001-03-30 2002-10-15 Biogen, Inc. Method of identifying renalgenerative agents using differential gene expression
US6617136B2 (en) 2001-04-24 2003-09-09 3M Innovative Properties Company Biological sample processing methods and compositions that include surfactants
US20030073110A1 (en) 2001-07-03 2003-04-17 Masaharu Aritomi Method for isolating nucleic acid and a cartridge for chemical reaction and for nucleic acid isolation
EP1508025A2 (en) * 2002-05-20 2005-02-23 Northrop Grumman Corporation Point source biological agent detection system
US20040018611A1 (en) 2002-07-23 2004-01-29 Ward Michael Dennis Microfluidic devices for high gradient magnetic separation
DE10236460A1 (de) 2002-08-08 2004-02-26 Siemens Ag In Kontaktbelichtung fotostrukturierbares Hydrogel mit Linkergruppen
KR101216828B1 (ko) * 2002-12-30 2013-01-04 더 리전트 오브 더 유니버시티 오브 캘리포니아 병원균 검출과 분석을 위한 방법과 기구
EP1592505A2 (en) 2003-01-21 2005-11-09 Micronics, Inc. Method and system for microfluidic manipulation, amplification and analysis of fluids, for example, bacteria assays and antiglobulin testing
DE102004021822B3 (de) 2004-04-30 2005-11-17 Siemens Ag Verfahren und Anordnung zur DNA-Amplifikation mittels PCR unter Einsatz von Trockenreagenzien

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Publication number Priority date Publication date Assignee Title
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US9387484B2 (en) 2009-10-06 2016-07-12 Koninklijke Philips N.V. Magnetic sample purification
US10989713B2 (en) 2010-03-01 2021-04-27 Quanterix Corporation Methods and systems for extending dynamic range in assays for the detection of molecules or particles
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US11977087B2 (en) 2011-01-28 2024-05-07 Quanterix Corporation Systems, devices, and methods for ultra-sensitive detection of molecules or particles
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US9932626B2 (en) 2013-01-15 2018-04-03 Quanterix Corporation Detection of DNA or RNA using single molecule arrays and other techniques
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US20070219366A1 (en) 2007-09-20
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EP1740722B1 (de) 2008-08-06
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