MICROSCALE DIFFUSION IMMUNOASSAY
    1.
    发明公开
    MICROSCALE DIFFUSION IMMUNOASSAY 审中-公开
    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

    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。

    SIMULTANEOUS PARTICLE SEPARATION AND CHEMICAL REACTION
    3.
    发明公开
    SIMULTANEOUS PARTICLE SEPARATION AND CHEMICAL REACTION 审中-公开
    法同时处理末端颗粒分离和化学反应

    公开(公告)号:EP1018012A1

    公开(公告)日:2000-07-12

    申请号:EP98947035.6

    申请日:1998-09-10

    IPC分类号: G01N33/543

    摘要: This invention provides a method and apparatus for detecting the presence of analyte particles in a sample fluid also comprising larger particles, particularly blood. It exploits diffusion to provide simultaneous filtering of the larger particles and reaction of the analyte particles. A sample stream and a reagent stream join on the upstream end of a laminar flow reaction channel and flow in adjacent laminar streams. The reagents can be in solution or immobilized on a bead. The analyte particles diffuse from the sample stream into the reagent stream, leaving behind the larger particles in the residual sample stream. In the reagent stream the analyte particles react with reagent particles and form product particles, thereby creating a product stream. At the downstream end of the reaction channel, the residual sample stream and the product stream are divided. The product particles are then detected, preferably optically, in the product stream. Prior to detection, the product stream can undergo further filtering or separation, or can join a second reagent stream to form secondary product particles. This apparatus and method can be used to implement competitive immunoassays or sandwich immunoassays using enzymatically or fluoroscently labeled immunoreagents. The apparatus and method can also be used to synthesize products, in which case two reagent streams join in the laminar flow reaction channel.

    DEVICE AND METHOD FOR 3-DIMENSIONAL ALIGNMENT OF PARTICLES IN MICROFABRICATED FLOW CHANNELS
    4.
    发明公开
    DEVICE AND METHOD FOR 3-DIMENSIONAL ALIGNMENT OF PARTICLES IN MICROFABRICATED FLOW CHANNELS 失效
    用于微流体通道中三维排列颗粒的装置和方法

    公开(公告)号:EP0981731A1

    公开(公告)日:2000-03-01

    申请号:EP98909080.8

    申请日:1998-03-09

    IPC分类号: G01N15/14

    摘要: The present invention provides a sheath flow module made from a first plate of material having formed therein a laminar fluid flow channel; at least two inlets, each inlet joining the laminar flow channel at a junction, the first inlet junction being wider than the second inlet junction, and an outlet from the flow channel. A second plate, e.g. a transparent cover plate, seals the module and allows for optical measurements. A first inlet allows for introduction of a first fluid into the flow channel. The first fluid is the sheath fluid. A second inlet allows for introduction of a second fluid into the sheath fluid while it is flowing through the flow channel. The second fluid is the center fluid. Because the second inlet junction is narrower than the first inlet junction, the center fluid becomes surrounded on both sides by the sheath fluid. After all fluids have been introduced and sheath flow has been achieved, the depth of the flow channel can be decreased, leading to vertical hydrodynamic focusing. Optionally, the width of the flow channel can be decreased, leading to horizontal hydrodynamic focusing. The decrease in depth and width can be gradual or abrupt. The device of the present invention can function in two modes, the sheath flow mode and the particle injector mode, depending on the relative densities of the sheath fluid, the center fluid, and any particles in either fluid.

    摘要翻译: 本发明提供了一种由第一板材形成的鞘流模块,其中形成有层流体流动通道; 至少两个入口,每个入口在接合处连接层流通道,第一入口接头宽于第二入口接头,以及流道的出口。 第二块板例如 一个透明的盖板,密封模块并允许进行光学测量。 第一入口允许将第一流体引入流动通道。 第一种流体是鞘液。 当第二流体流过流动通道时,第二入口允许将第二流体引入鞘液中。 第二种流体是中心流体。 由于第二入口接头比第一入口接头窄,中心流体在两侧被鞘液包围。 在所有流体被引入并且已经实现鞘流后,流动通道的深度可以减小,导致垂直流体动力学聚焦。 可选地,流动通道的宽度可以减小,导致水平流体动力学聚焦。 深度和宽度的减小可以是渐变或突变的。 根据鞘液,中心流体以及任一流体中的任何颗粒的相对密度,本发明的装置可以以两种模式起作用,即鞘流模式和颗粒注射器模式。

    ABSORPTION-ENHANCED DIFFERENTIAL EXTRACTION DEVICE
    5.
    发明公开
    ABSORPTION-ENHANCED DIFFERENTIAL EXTRACTION DEVICE 失效
    吸收增强的差分提取装置

    公开(公告)号:EP0910474A1

    公开(公告)日:1999-04-28

    申请号:EP97932185.0

    申请日:1997-06-13

    摘要: This invention provides an extraction device and method for extracting desired particles from a sample stream (2) containing the desired particles. The device comprises a sample stream inlet (1); an extraction stream inlet (5); an extraction channel (7) in fluid communication with the sample stream inlet (1) and the extraction stream inlet (5) for receiving a sample stream (2) from the sample stream inlet (1) in adjacent laminar flow with an extraction stream (4) from the extraction stream inlet (5); a sequestering material within the extraction channel (7) for capturing desired particles (18) in the extraction stream (9); a by-product stream outlet (15) in fluid communication with the extraction channel (7) for receiving a by-product stream (12) comprising at least a portion of the sample stream (2) from which desired particles (18) have been extracted; and a product outlet (14) in fluid communication with the extraction channel (7) for receiving a product comprising the sequestering material and at least a portion of the desired particles (18).

    摘要翻译: 本发明提供用于从含有所需颗粒的样品流(2)中提取所需颗粒的提取装置和方法。 该装置包括样品流入口(1); 提取物流入口(5); 与所述样品流入口(1)和所述萃取流入口(5)流体连通的萃取通道(7),所述萃取通道用于从所述样品流入口(1)接收相邻层流中的样品流(2) 4)来自萃取物流入口(5); 提取通道(7)内的用于捕集提取物流(9)中的期望颗粒(18)的隔离材料; 与提取通道(7)流体连通的副产物流出口(15),用于接收包含样品流(2)的至少一部分的副产物流(12),期望的颗粒(18)从该副产物流 提取; 和与提取通道(7)流体连通的产品出口(14),用于接收包含隔离材料和至少一部分所需颗粒(18)的产品。

    THERAPEUTIC DELIVERY USING COMPOUNDS SELF-ASSEMBLED INTO HIGH AXIAL RATIO MICROSTRUCTURES
    8.
    发明公开
    THERAPEUTIC DELIVERY USING COMPOUNDS SELF-ASSEMBLED INTO HIGH AXIAL RATIO MICROSTRUCTURES 审中-公开
    治疗性给药使用高轴甚至能够共享组装CONNECTIONS微构造

    公开(公告)号:EP1146855A1

    公开(公告)日:2001-10-24

    申请号:EP99966656.3

    申请日:1999-12-21

    IPC分类号: A61K9/00 A61K9/127

    摘要: Therapeutic complexes comprising plural therapeutic compounds self assembled into high axial ratio microstructures are described. The therapeutic complexes satisfy the formula HARM-Th, wherein HARM is a high axial ratio forming material and Th is a therapeutic coupled to or associated with the HARM. The therapeutic complexes also can satisfy the formula HARM- S- Th, wherein S is a spacer. Release of the therapeutic by the complex generally follows either 0-order kinetics or pseudo-first order kinetics. A method for delivering therapeutics to organisms, particularly humans, also is described. The method comprises administering an effective amount of (1) a ligand, such as a therapeutic, self-assembled into a HAR microstructure, or (2) a ligand, such as a therapeutic, coupled to or associated with a material capable of thereafter self-assembling into a high axial ratio microstructure, to the mammal. Nucleic acids are an example of a ligand that can be administered effectively according to this method through noncovalent attachment to the HARM-forming materials.