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1. 发明授权

US06454945B1 Microfabricated devices and methods 有权
标题翻译：微型装置和方法
公开(公告)号：US06454945B1
公开(公告)日：2002-09-24
申请号：US09703764
申请日：2000-11-01
申请人： Bernhard H. Weigl , Paul Yager , James P. Brody , Mark R. Holl , Fred K. Forster , Eric Altendorf , Paul C. Galambos , Margaret Kenny , David Schutte , Gregory Hixson , Diane Zebert , Andrew Kamholz , Caicai Wu
发明人： Bernhard H. Weigl , Paul Yager , James P. Brody , Mark R. Holl , Fred K. Forster , Eric Altendorf , Paul C. Galambos , Margaret Kenny , David Schutte , Gregory Hixson , Diane Zebert , Andrew Kamholz , Caicai Wu
IPC分类号： B02D1100
CPC分类号： B01D11/0492 , A61M1/14 , B01D11/0496 , B01L3/5027 , B01L3/502761 , B01L3/502776 , B01L2200/0636 , B01L2300/0816 , B01L2300/0867 , B01L2400/0406 , B01L2400/0487 , G01N15/1484 , Y10T436/25375
摘要： This invention provides microfabricated systems for extraction of desired particles from a sample stream containing desired and undesired particles. The sample stream is placed in laminar flow contact with an extraction stream under conditions in which inertial effects are negligible. The contact between the two streams is maintained for a sufficient period of time to allow differential transport of the desired particles from the sample stream into the extraction stream. In a preferred embodiment the differential transport mechanism is diffusion. The extraction system of this invention coupled to a microfabricated diffusion-based mixing device and/or sensing means allows picoliter quantities of fluid to be processed or analyzed on devices no larger than silicon wafers. Such diffusion-based mixing or sensing devices are preferably channel cell systems for detecting the presence and/or measuring the quantity of analyte particles in a sample stream.
摘要翻译：本发明提供了用于从含有所需和不需要的颗粒的样品流中提取所需颗粒的微制造系统。在惯性效应可忽略的条件下，将样品流与提取流层流接触。保持两个物流之间的接触足够的时间，以便将期望的颗粒从样品流中差分输送到萃取物流中。在优选实施例中，差分传送机构是扩散。本发明的提取系统耦合到基于微制造的基于扩散的混合装置和/或感测装置允许在不大于硅晶片的装置上处理或分析皮升数量的流体。这种基于扩散的混合或感测装置优选是用于检测样品流中分析物颗粒的存在和/或测量量的通道电池系统。

2. 发明授权

US5972710A Microfabricated diffusion-based chemical sensor 失效
标题翻译：微型基于扩散的化学传感器
公开(公告)号：US5972710A
公开(公告)日：1999-10-26
申请号：US829679
申请日：1997-03-31
申请人： Bernhard H. Weigl , Paul Yager , James P. Brody , Mark R. Holl , Margaret Kenny , David Schutte , Gregory Hixson , M. Diane Zebert , Andrew Kamholz , Caicai Wu , Eric Altendorf
发明人： Bernhard H. Weigl , Paul Yager , James P. Brody , Mark R. Holl , Margaret Kenny , David Schutte , Gregory Hixson , M. Diane Zebert , Andrew Kamholz , Caicai Wu , Eric Altendorf
IPC分类号： G01N37/00 , B01F5/04 , B01F13/00 , B01J19/00 , B01L3/00 , G01N15/06 , G01N15/14 , G01N30/00 , G01N30/38 , G01N30/60 , G01N30/74 , G01N31/20 , G01N35/08 , G01N21/64
CPC分类号： B01F5/0403 , B01F13/0059 , B01F13/0093 , B01J19/0093 , B01L3/502776 , G01N30/0005 , B01J2219/00828 , B01J2219/00831 , B01J2219/00952 , B01L2200/0636 , B01L2300/0654 , B01L2300/0816 , B01L2300/0861 , B01L2300/0867 , B01L2300/087 , B01L2400/0487 , G01N15/14 , 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) a laminar flow channel; b) two inlets in fluid connection with the laminar flow channel for respectively conducting into the laminar flow channel (1) an indicator stream which may comprise an indicator substance which indicates the presence of the analyte particles by a detectable change in property when contacted with the analyte particles, and (2) the sample stream; c) wherein the laminar flow channel 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 the indicator stream to the substantial exclusion of the larger particles in the sample stream to form a detection area; and d) an outlet for conducting the streams out of the laminar flow channel to form a single mixed stream.
摘要翻译：提供了一种通道细胞系统，用于检测样品流中存在和/或测量分析物颗粒的存在，其包括：a）层流通道; b）与层流通道流体连接的两个入口，用于分别导入层流通道（1）中，指示物流可包含指示物质，其指示物质与当与分析物颗粒，和（2）样品流; c）其中层流通道具有足够小的深度以允许流的层流，并且足够的长度允许分析物的颗粒扩散到指示物流中，从而基本排除样品流中的较大颗粒，形成检测区; 和d）用于将物流从层流通道导出以形成单一混合流的出口。

3. 发明授权

US5948684A Simultaneous analyte determination and reference balancing in reference T-sensor devices 失效
标题翻译：参考T传感器设备中的同时分析物测定和参考平衡
公开(公告)号：US5948684A
公开(公告)日：1999-09-07
申请号：US900926
申请日：1997-07-25
申请人： Bernhard H. Weigl , Mark R. Holl , Diane Zebert , Margaret Kenny , Caicai Wu
发明人： Bernhard H. Weigl , Mark R. Holl , Diane Zebert , Margaret Kenny , Caicai Wu
IPC分类号： G01N31/20 , B01F5/04 , B01F13/00 , B01J19/00 , B01L3/00 , G01N15/10 , G01N15/14 , G01N21/64 , G01N30/00 , G01N30/38 , G01N30/60 , G01N30/74 , G01N35/00 , G01N35/08 , G01N37/00
CPC分类号： B01F13/0093 , B01F13/0059 , B01F5/0403 , B01J19/0093 , B01L3/502776 , G01N15/10 , G01N15/1484 , G01N30/0005 , B01L2200/0636 , B01L2200/148 , B01L2300/0816 , B01L2400/0406 , B01L2400/0415 , B01L2400/0457 , B01L2400/0487 , G01N15/14 , G01N15/1404 , G01N2035/00237 , G01N30/38 , G01N30/6095 , G01N30/74 , G01N35/085 , Y10T436/117497 , Y10T436/118339 , Y10T436/25375 , Y10T436/2575
摘要： A reference T-sensor system is provided for detecting the presence and/or measuring the concentration of analyte particles in a sample stream. The system includes: a) a laminar flow channel; b) three or more inlet means in fluid connection with the laminar flow channel for respectively conducting into the laminar flow channel (1) an indicator stream which may include an indicator substance which indicates the presence of the analyte particles, (2) the sample stream, and (3) a reference stream, which can be a control stream and/or internal standard stream; c) wherein the laminar flow channel has a depth and/or width sufficiently small to allow laminar flow of the streams and a length sufficient to allow particles of the analyte to diffuse into the indicator stream to form a detection area; and d) outlet means for conducting the streams out of the laminar flow channel preferably to form a single mixed stream. Also provided are methods of using the device to improve accuracy and increase convenience of measuring the concentration of analytes in a sample. Monitoring reference stream(s) in laminar flow with sample stream(s) allows for calibration or for monitoring or correcting for the effects of experimental conditions which might otherwise degrade accuracy. A reference stream which serves as both a control stream and an internal standard stream is convenient and economical. The device of this invention also needs less frequent calibration than previously-known fluid analysis devices because the devices and methods of this invention provide for continuous and simultaneous quality control and internal standardization.
摘要翻译：提供了一种参考T传感器系统，用于检测样品流中分析物颗粒的存在和/或测量浓度。该系统包括：a）层流通道; b）与层流通道流体连接的三个或更多个入口装置，用于分别导入层流通道（1）中，指示物流可包括指示物质，其指示分析物颗粒的存在，（2）样品流，和（3）参考流，其可以是控制流和/或内部标准流; c）其中层流通道具有足够小的深度和/或宽度以允许流的层流，并且具有足以允许分析物的颗粒扩散到指示物流中以形成检测区域的长度; 以及d）用于将流引导出层流通道的出口装置优选地形成单一混合流。还提供了使用该装置来提高测量样品中分析物浓度的准确性和增加方便性的方法。用样品流监测层流中的参考流允许校准或监测或校正实际条件的影响，否则可能会降低准确度。用作控制流和内部标准流的参考流是方便和经济的。由于本发明的装置和方法提供连续和同时的质量控制和内部标准化，本发明的装置还需要比先前知道的流体分析装置更少的校准。

4. 发明授权

US06582963B1 Simultaneous analyte determination and reference balancing in reference T-sensor devices 有权
标题翻译：参考T传感器设备中的同时分析物测定和参考平衡
公开(公告)号：US06582963B1
公开(公告)日：2003-06-24
申请号：US09702645
申请日：2000-10-31
申请人： Bernhard H. Weigl , Mark R. Holl , Diane Zebert , Margaret Kenny , Caicai Wu
发明人： Bernhard H. Weigl , Mark R. Holl , Diane Zebert , Margaret Kenny , Caicai Wu
IPC分类号： G01N3508
CPC分类号： B01F13/0093 , B01F5/0403 , B01F13/0059 , B01J19/0093 , B01L3/502776 , B01L2200/0636 , B01L2200/148 , B01L2300/0816 , B01L2400/0406 , B01L2400/0415 , B01L2400/0457 , B01L2400/0487 , G01N15/10 , G01N15/14 , G01N15/1404 , G01N15/1484 , G01N30/0005 , G01N30/38 , G01N30/6095 , G01N30/74 , G01N35/085 , G01N2035/00237 , Y10T436/117497 , Y10T436/118339 , Y10T436/25375 , Y10T436/2575
摘要： A reference T-sensor system is provided for detecting the presence and/or measuring the concentration of analyte particles in a sample stream. The system includes: a) a laminar flow channel; b) three or more inlets in fluid connection with the laminar flow channel for respectively conducting into the laminar flow channel (1) an indicator stream which may include an indicator substance which indicates the presence of analyte particles by a detectable change in property when contacted with the analyte particles, (2) the sample stream, and (3) a reference stream, which can be a control stream and/or an internal standard stream; c) wherein the laminar flow channel has a depth and/or width sufficiently small to allow laminar flow of the streams and a length sufficient to allow particles of the analyte to diffuse into the indicator stream to form a detection area; and (d) an outlet for conducting the streams out of the laminar flow channel preferably to form a single mixed stream.
摘要翻译：提供了一种参考T传感器系统，用于检测样品流中分析物颗粒的存在和/或测量浓度。该系统包括：a）层流通道; b）与层流通道流体连接的三个或更多个入口，用于分别导入层流通道（1）中，指示物流可包括指示剂物质，其指示当与分析物颗粒，（2）样品流，和（3）参考流，其可以是对流和/或内标流; c）其中层流通道具有足够小的深度和/或宽度以允许流的层流，并且具有足以允许分析物的颗粒扩散到指示物流中以形成检测区域的长度; 和（d）用于将流从层流通道引导出来以形成单一混合流的出口。

5. 发明授权

US06171865B2 Simultaneous analyte determination and reference balancing in reference T-sensor devices 有权
标题翻译：参考T传感器设备中的同时分析物测定和参考平衡
公开(公告)号：US06171865B2
公开(公告)日：2001-01-09
申请号：US09366821
申请日：1999-08-04
申请人： Bernhard H. Weigl , Mark R. Holl , Diane Zebert , Margaret Kenny , Caicai Wu
发明人： Bernhard H. Weigl , Mark R. Holl , Diane Zebert , Margaret Kenny , Caicai Wu
IPC分类号： G01N3508
CPC分类号： B01F13/0093 , B01F5/0403 , B01F13/0059 , B01J19/0093 , B01L3/502776 , B01L2200/0636 , B01L2200/148 , B01L2300/0816 , B01L2400/0406 , B01L2400/0415 , B01L2400/0457 , B01L2400/0487 , G01N15/10 , G01N15/14 , G01N15/1404 , G01N15/1484 , G01N30/0005 , G01N30/38 , G01N30/6095 , G01N30/74 , G01N35/085 , G01N2035/00237 , Y10T436/117497 , Y10T436/118339 , Y10T436/25375 , Y10T436/2575
摘要： A reference sensor system is provided for detecting the presence and/or measuring the concentration of analyte particles in a sample stream. The system includes: a) a laminar flow channel; b) three or more inlet means in fluid connection with the laminar flow channel for respectively conducting into the laminar flow channel (1) an indicator stream which may include an indicator substance which indicates the presence of the analyte particles, (2) the sample stream, and (3) a reference stream, which can be a control stream and/or internal standard stream; and, c) wherein the laminar flow channel has a depth and/or width sufficiently small to allow laminar flow of said streams and a length sufficient to allow particles of the analyte to diffuse into the indicator stream to form a detection area. Branching channels may be provided as outlet means for conducting the streams out of the laminar flow channel. Also provided are methods of using the device to improve accuracy and increase convenience of measuring the concentration of analytes in a sample. Monitoring reference stream(s) in laminar flow with sample stream(s) allows for calibration or for monitoring or correcting for the effects of experimental conditions which might otherwise degrade accuracy. A reference stream which serves as both a control stream and an internal standard stream is convenient and economical. The device of this invention also needs less frequent calibration than previously-known fluid analysis devices because the devices and methods of this invention provide for continuous and simultaneous quality control and internal standardization.
摘要翻译：提供了一种用于检测样品流中分析物颗粒的存在和/或测量浓度的参考传感器系统。该系统包括：a）层流通道; b）与层流通道流体连接的三个或更多个入口装置，用于分别导入层流通道（1）中，指示物流可包括指示物质，其指示分析物颗粒的存在，（2）样品流，和（3）参考流，其可以是控制流和/或内部标准流; 和c）其中所述层流通道的深度和/或宽度足够小以允许所述物流的层流并且足够长度以允许所述分析物的颗粒扩散到所述指示物流中以形成检测区域。可以提供分支通道作为用于将流引导出层流通道的出口装置。还提供了使用该装置来提高测量样品中分析物浓度的准确性和增加方便性的方法。用样品流监测层流中的参考流允许校准或监测或校正实际条件的影响，否则可能会降低准确度。用作控制流和内部标准流的参考流是方便和经济的。由于本发明的装置和方法提供连续和同时的质量控制和内部标准化，本发明的装置还需要比先前知道的流体分析装置更少的校准。

6. 发明授权

US5932100A Microfabricated differential extraction device and method 失效
标题翻译：微型微分提取装置及方法
公开(公告)号：US5932100A
公开(公告)日：1999-08-03
申请号：US663916
申请日：1996-06-14
申请人： Paul Yager , James P. Brody , Mark R. Holl , Fred K. Forster , Paul C. Galambos
发明人： Paul Yager , James P. Brody , Mark R. Holl , Fred K. Forster , Paul C. Galambos
IPC分类号： B01D11/00 , B01D11/02 , B01D11/04 , B01D43/00 , B01F13/00 , B01J19/00 , G01N1/02 , G01N1/10 , G01N1/40 , G01N15/06 , G01N30/00 , G01N35/00 , G01N37/00
CPC分类号： B01D11/0492 , B01D11/0496 , B01F13/0059 , B01F13/0093 , B01J19/0093 , G01N15/06 , G01N30/0005 , B01F2005/0031 , B01J2219/00783 , B01J2219/00828 , B01J2219/00889 , B01J2219/00905 , B01J2219/00952 , B01J2219/0097 , B01J2219/00995 , G01N2001/4072 , G01N2035/00237 , Y10S366/01 , Y10T436/255
摘要： This invention provides a microfabricated extraction system and methods for extracting desired particles from a sample stream containing desired and undesired particles. The sample stream is placed in laminar flow contact with an extraction stream under conditions in which inertial effects are negligible. The contact between the two streams is maintained for a sufficient period of time to allow differential transport of the desired particles from the sample stream into the extraction stream. In a preferred embodiment the differential transport mechanism is diffusion. The extraction system of this invention coupled to a microfabricated diffusion-based mixing device and/or sensing device allows picoliter quantities of fluid to be processed or analyzed on devices no larger than silicon wafers.
摘要翻译：本发明提供了一种微加工提取系统和从含有所需和不需要的颗粒的样品流中提取所需颗粒的方法。在惯性效应可忽略的条件下，将样品流与提取流层流接触。保持两个物流之间的接触足够的时间，以便将期望的颗粒从样品流中差分输送到萃取物流中。在优选实施例中，差分传送机构是扩散。本发明的提取系统耦合到基于微制造的基于扩散的混合装置和/或感测装置允许在不大于硅晶片的装置上处理或分析皮升数量的流体。

7. 发明授权

US5974867A Method for determining concentration of a laminar sample stream 失效
标题翻译：确定层流样品流浓度的方法
公开(公告)号：US5974867A
公开(公告)日：1999-11-02
申请号：US961345
申请日：1997-10-30
申请人： Fred K. Forster , Paul C. Galambos , Bernhard H. Weigl , Mark R. Holl
发明人： Fred K. Forster , Paul C. Galambos , Bernhard H. Weigl , Mark R. Holl
IPC分类号： B01F13/00 , B01J19/00 , G01N11/04 , G01N13/00 , G01N35/08 , G01N21/78
CPC分类号： B01F13/0059 , B01F13/0093 , B01J19/0093 , G01N11/04 , G01N13/00 , B01F2005/0031 , G01N35/085 , Y10S366/01
摘要： Methods and apparatuses including programmed computers are provided for determining the initial concentration of diffusible particles in a sample stream introduced into a system wherein the sample stream which contains the diffusible particles flows in adjacent laminar flow with an indicator stream containing an indicator substance capable of exhibiting an observable change at a known concentration of the diffusible particles.
摘要翻译：提供包括编程计算机的方法和装置用于确定引入系统的样品流中的可扩散颗粒的初始浓度，其中包含可扩散颗粒的样品流在相邻层流中流动，其中含有指示物质的指示物流能够显示出在可扩散颗粒的已知浓度下可观察到的变化。

8. 发明授权

US06134950A Method for determining concentration of a laminar sample stream 有权
标题翻译：确定层流样品流浓度的方法
公开(公告)号：US06134950A
公开(公告)日：2000-10-24
申请号：US373478
申请日：1999-08-12
申请人： Fred K. Forster , Paul C. Galambos , Bernhard H. Weigl , Mark R. Holl
发明人： Fred K. Forster , Paul C. Galambos , Bernhard H. Weigl , Mark R. Holl
IPC分类号： B01F13/00 , B01J19/00 , G01N11/04 , G01N13/00 , G01N35/08 , G01N11/02
CPC分类号： B01F13/0059 , B01F13/0093 , B01J19/0093 , G01N11/04 , G01N13/00 , B01F2005/0031 , G01N35/085 , Y10S366/01
摘要： A method and apparatus including programmed computers are provided for determining the viscosity of a first stream in a laminar flow and a second stream in a laminar flow, the flow rates, the centerline of the flow channel, and the position of the interface between the streams with respect to the centerline, and for calculating viscosity ratio of the first stream to the second.
摘要翻译：提供了包括编程计算机的方法和装置，用于确定层流中的第一流和层流中的第二流的粘度，流量，流动通道的中心线以及流之间的界面的位置相对于中心线，并且用于计算第一流与第二流的粘度比。

9. 发明授权

US5716852A Microfabricated diffusion-based chemical sensor 失效
公开(公告)号：US5716852A
公开(公告)日：1998-02-10
申请号：US625808
申请日：1996-03-29
申请人： Paul Yager , Bernhard H. Weigl , James P Brody , Mark R. Holl
发明人： Paul Yager , Bernhard H. Weigl , James P Brody , Mark R. Holl
IPC分类号： G01N37/00 , B01F5/04 , B01F13/00 , B01J19/00 , B01L3/00 , G01N15/06 , G01N15/14 , G01N30/00 , G01N30/38 , G01N30/60 , G01N30/74 , G01N31/20 , G01N35/08 , G01N21/64
CPC分类号： B01F5/0403 , B01F13/0059 , B01F13/0093 , B01J19/0093 , B01L3/502776 , G01N30/0005 , B01J2219/00828 , B01J2219/00831 , B01J2219/00952 , B01L2200/0636 , B01L2300/0654 , B01L2300/0816 , B01L2300/0861 , B01L2300/0867 , B01L2300/087 , B01L2400/0487 , G01N15/14 , 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) a laminar flow channel; b) two inlet means in fluid connection with said laminar flow channel for respectively conducting into said laminar flow channel (1) an indicator stream 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 (2) said sample stream; c) wherein said laminar flow channel has a depth sufficiently small to allow laminar flow of said streams and a length sufficient to allow particles of said analyte to diffuse into said indicator stream to the substantial exclusion of said larger particles in said sample stream to form a detection area; and d) outlet means for conducting said streams out of said laminar flow channel to form a single mixed stream.

10. 发明授权

US06482306B1 Meso- and microfluidic continuous flow and stopped flow electroösmotic mixer 失效
标题翻译：介质和微流体连续流动和停止流动电渗流混合器
公开(公告)号：US06482306B1
公开(公告)日：2002-11-19
申请号：US09404454
申请日：1999-09-22
申请人： Paul Yager , Mark R. Holl , Andrew Kamholz , Catherine Cabrera , Katerina Macounova
发明人： Paul Yager , Mark R. Holl , Andrew Kamholz , Catherine Cabrera , Katerina Macounova
IPC分类号： B01F1300
CPC分类号： B01F13/0076 , B01F13/0001 , B01F13/0005 , B01F13/0077 , B01L3/5027 , Y10T137/2087 , Y10T137/2191
摘要： An electroösmotic mixing device and a method for mixing one or more fluids for use in meso- or microfluidic device applications. The mixing device provides batch or continuous mixing of one or more fluids in meso- or microfluidic channels. An electric field is generated in the channel in substantial contact with chargeable surfaces therein. No alterations of the geometry of existing flow paths need be made, and the degree of mixing in the device can be controlled by the length of the electrodes, the flow rate past the electrodes, and the voltage applied to those electrodes. The degree of mixing is affected by choice of materials for the chargeable surface (in some cases by the selection of materials or coatings for channel walls) and the ionic strength of the fluids and the type and concentration of ions in the fluids. The ionic strength of fluids to be mixed is sufficiently low to allow electroosmotic flow. The method and device of this invention is preferably applied to fluids to having low ionic strength less than or equal to about 1 mM.
摘要翻译：一种电渗混合装置和用于混合用于中等或微流体装置应用的一种或多种流体的方法。混合装置在中等或微流体通道中提供一种或多种流体的间歇或连续混合。在通道中产生与其中的可充电表面实质接触的电场。不需要改变现有流路的几何形状，并且可以通过电极的长度，通过电极的流速和施加到这些电极的电压来控制装置中的混合程度。混合的程度受到可充电表面的材料选择（在某些情况下通过选择通道壁的材料或涂层）以及流体的离子强度以及流体中离子的类型和浓度的影响。要混合的流体的离子强度足够低以允许电渗流。本发明的方法和装置优选应用于具有小于或等于约1mM的低离子强度的流体。

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