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1. 发明申请

WO2000072020A1 MICROSCALE DIFFUSION IMMUNOASSAY 审中-公开
公开(公告)号：WO2000072020A1
公开(公告)日：2000-11-30
申请号：PCT/US2000/013864
申请日：2000-05-19
申请人： UNIVERSITY OF WASHINGTON
发明人： WEIGL, Bernhard, H. , YAGER, Paul , KAMHOLZ, Andrew , HATCH, Anson
IPC分类号： G01N33/558
CPC分类号： G01N33/558 , G01N30/0005
摘要： Methods and apparatuses are provided for determining presence and concentration of analytes by exploiting molecular binding reactions and differential diffusion rates. Analyte particles and binding particles are allowed to diffuse toward each other, and slowing of the diffusion front is detected when they meet. From the position of the diffusion front, presence and concentration of analyte particles can be determined. One embodiment provides a competitive immunoassay in a microfluidic format. This diffusion immunoassay (DIA) relies on measuring the concentration of labeled antigen along one dimension of a microchannel after allowing it to diffuse for a short time into a region containing specific antibodies. A simple microfluidic device, the T-Sensor, was used to implement a DIA to measure the concentration of phenytoin, a small drug molecule. Concentrations of analyte over the range of 50 to 1600 nM can be measured in less than a minute. The assay is homogenous, rapid, requires only microliter volumes of reagents and sample, and is applicable to a wide range of analytes, including therapeutic drugs, molecular biological markers, and environmental contaminants. Methods for separating particles of similar size in a diffusion separator are also provided.
摘要翻译：提供了通过开发分子结合反应和差异扩散速率来确定分析物的存在和浓度的方法和装置。允许分析物颗粒和结合颗粒彼此扩散，并且当它们相遇时检测到扩散前沿的减慢。从扩散前沿的位置可以确定分析物颗粒的存在和浓度。一个实施方案提供了以微流体形式的竞争性免疫测定。这种扩散免疫测定（DIA）依赖于在允许其在短时间内扩散到含有特异性抗体的区域之后测量沿着微通道的一个维度的标记抗原的浓度。使用简单的微流体装置T-Sensor来实施DIA来测量苯妥英（一种小药物分子）的浓度。可以在不到一分钟的时间内测量分析物在50至1600nM范围内的浓度。该测定法是均匀的，快速的，仅需要微量体积的试剂和样品，并且适用于广泛的分析物，包括治疗药物，分子生物标志物和环境污染物。还提供了在扩散分离器中分离类似尺寸的颗粒的方法。

2. 发明公开

EP1320741A1 MICROFLUIDIC DEVICES FOR ROTATIONAL MANIPULATION OF THE FLUIDIC INTERFACE BETWEEN MULTIPLE FLOW STREAMS 审中-公开
标题翻译：微流体装置用于转动操纵流体边界几个流之间
公开(公告)号：EP1320741A1
公开(公告)日：2003-06-25
申请号：EP01973129.8
申请日：2001-09-18
申请人： University of Washington
发明人： KAMHOLZ, Andrew , MUNSON, Matthew , SCHILLING, Eric , HAWKINS, Kenneth , WEIGL, Bernhardt, H. , BARDELL, Ronald L.
IPC分类号： G01N15/06 , G01N21/64 , G01N30/00 , G01N35/08 , B01D11/00
CPC分类号： F15C1/14 , B01F5/0646 , B01F5/0647 , B01F13/0059 , B01F13/0093 , B01F15/0203 , B01F15/0233 , B01F2005/0031 , B01F2215/0431 , B01J19/0093 , B01L3/502776 , B01L2200/0621 , B01L2200/0636 , B01L2300/0867 , B01L2300/087 , B01L2300/0874 , B01L2300/161 , B01L2400/0406 , B01L2400/0457 , B01L2400/0655 , B01L2400/0688 , F16K99/0001 , F16K2099/0074 , F16K2099/0078 , F16K2099/008 , F16K2099/0084 , G01N21/07 , G01N2035/00237 , G01N2035/00495 , Y10T436/11 , Y10T436/117497 , Y10T436/118339 , Y10T436/25 , Y10T436/2575
摘要： Multifluidic devices and methods are provided for enhancing detection of a diffusion pattern formed by particles diffusing between at least two fluid streams (I) parallel laminar flow such that an interface is formed between them by increasing the dimension of the streams in the diffusion direct. This may be accomplished by flowing the streams through a transforming turn, or by flowing the streams through a channel having diverging walls. Devices and methods are also provided for enhancing diffusion between two streams comprising changing the interface between said streams from a narrow interface to a broad interface.

3. 发明公开

EP0890094A1 MICROFABRICATED DIFFUSION-BASED CHEMICAL SENSOR 失效
标题翻译：化学传感器对扩散BASIS MICRO MADE
公开(公告)号：EP0890094A1
公开(公告)日：1999-01-13
申请号：EP97936008.0
申请日：1997-03-31
申请人： UNIVERSITY OF WASHINGTON
发明人： WEIGL, Bernhard, H. , YAGER, Paul , BRODY, James, P. , HOLL, Mark, R. , KENNY, Margaret , SCHUTTE, David , HIXSON, Gregory , ZEBERT, M., Diane , KAMHOLZ, Andrew , WU, Caicai , ALTENDORF, Eric
IPC分类号： G01N37 , B01F5 , B01F13 , B01J19 , B01L3 , G01N15 , G01N30 , G01N31 , G01N35
CPC分类号： B01F5/0403 , B01F13/0059 , B01F13/0093 , B01J19/0093 , B01J2219/00828 , B01J2219/00831 , B01J2219/00952 , B01L3/502776 , B01L2200/0636 , B01L2300/0654 , B01L2300/0816 , B01L2300/0861 , B01L2300/0867 , B01L2300/087 , B01L2400/0487 , G01N15/14 , G01N30/0005 , G01N30/38 , G01N30/6095 , G01N30/74 , G01N35/085 , Y10S366/01 , Y10T436/25375 , Y10T436/2575
摘要： A channel-cell system is provided for detecting the presence and/or measuring the presence of analyte particles in a sample stream comprising a laminar flow channel (100), two inlet means (30, 20) in fluid connection with said laminar flow channel (100) for respectively conducting into the laminar flow channel (100) an indicator stream (70) which may comprise an indicator substance which indicates the presence of said analyte particles by a detectable change in property when contacted with said analyte particles, and the sample stream (80), wherein the laminar flow channel (100) has a depth sufficiently small to allow laminar flow of the streams and a length sufficient to allow particles of the analyte to diffuse into said indicator stream (70) to the substantial exclusion of said larger particles in the sample stream (80) to form a detection area; and outlet means (60) for conducting the streams out of the laminar flow channel (100) to form a single mixed stream.

4. 发明公开

EP1179181A1 MICROSCALE DIFFUSION IMMUNOASSAY 审中-公开
标题翻译：微量扩散免疫测定
公开(公告)号：EP1179181A1
公开(公告)日：2002-02-13
申请号：EP00932644.8
申请日：2000-05-19
申请人： University of Washington
发明人： WEIGL, Bernhard, H. , YAGER, Paul , KAMHOLZ, Andrew , HATCH, Anson
IPC分类号： G01N33/558 , G01N33/557 , G01N33/543 , G01N15/06 , G01N33/00 , G01N33/48 , G01N21/00 , G01N21/29 , G01N21/41 , G01N21/47 , B01D11/00 , B01D11/04
CPC分类号： G01N33/558 , G01N30/0005
摘要： Methods and apparatuses are provided for determining presence and concentration of analytes by exploiting molecular binding reactions and differential diffusion rates. Analyte particles and binding particles are allowed to diffuse toward each other, and slowing of the diffusion front is detected when they meet. From the position of the diffusion front, presence and concentration of analyte particles can be determined. One embodiment provides a competitive immunoassay in a microfluidic format. This diffusion immunoassay (DIA) relies on measuring the concentration of labeled antigen along one dimension of a microchannel after allowing it to diffuse for a short time into a region containing specific antibodies. A simple microfluidic device, the T-Sensor, was used to implement a DIA to measure the concentration of phenytoin, a small drug molecule. Concentrations of analyte over the range of 50 to 1600 nM can be measured in less than a minute. The assay is homogenous, rapid, requires only microliter volumes of reagents and sample, and is applicable to a wide range of analytes, including therapeutic drugs, molecular biological markers, and environmental contaminants. Methods for separating particles of similar size in a diffusion separator are also provided.
摘要翻译：提供了通过利用分子结合反应和差异扩散速率来确定分析物的存在和浓度的方法和设备。允许分析物颗粒和结合颗粒朝向彼此扩散，并且当它们相遇时检测到扩散前沿的减慢。从扩散前沿的位置可以确定分析物颗粒的存在和浓度。一个实施方案提供微流体形式的竞争性免疫测定。该扩散免疫测定法（DIA）依赖于在允许其短时间扩散到含有特异性抗体的区域中后，沿着微通道的一维测量标记抗原的浓度。使用简单的微流体装置T传感器来实施DIA以测量苯妥英（一种小分子药物）的浓度。在不到一分钟的时间内可以测量50至1600 nM范围内的分析物浓度。该检测方法均匀，快速，只需要微升体积的试剂和样品，适用于各种分析物，包括治疗药物，分子生物标志物和环境污染物。还提供了用于在扩散分离器中分离相似尺寸的颗粒的方法。

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