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1.发明授权Electroosmotic micropumps with applications to fluid dispensing and field sampling 失效电渗雾微乳液，适用于流体分配和现场取样公开(公告)号：US07231839B2
公开(公告)日：2007-06-19
申请号：US10638732
申请日：2003-08-11
申请人： David Huber , Shuhuai Yao , Juan G. Santiago
发明人： David Huber , Shuhuai Yao , Juan G. Santiago
CPC分类号： C01B5/00 , B01L3/0241 , B01L2200/143 , B01L2300/069 , B01L2400/0418 , F04B19/006
摘要： Apparatus and methods according to the present invention preferably utilize electroosmotic pumps in fluid handling and field sampling applications. The electroosmotic pumps used in these applications are capable of generating high pressure and flow without moving mechanical parts and the associated generation of unacceptable electrical and acoustic noise, as well as the associated reduction in reliability. Having multiple small flow channels in parallel provides both a high flow rate and high pressure in liquid handling. These electroosmotic pumps are fabricated with materials and structures that improve performance, efficiency, and reduce weight and manufacturing cost relative to presently available micropumps. These electroosmotic pumps also allow for recapture of evolved gases and deposited materials, which may provide for long-term closed-loop operation. Apparatus and methods according to the present invention also allow active regulation of the fluid handling and field sampling devices through electrical control of the flow through the pump. Electroosmotic pumping enables precise dispensing of samples to form genetic, proteomic, or small molecule arrays. A fluid sensor which can be optical, capacitive or other type of electrical sensor is integrated with the electroosmotic pump for measuring liquid levels in liquid drawing and dispensing operations.
摘要翻译： 根据本发明的设备和方法优选地在流体处理和现场取样应用中使用电渗泵。 在这些应用中使用的电渗泵能够在不移动机械部件的情况下产生高压力和流量，并且相关产生不可接受的电气和噪音噪声以及相关联的可靠性降低。 具有多个小流量通道并联提供液体处理中的高流速和高压力。 这些电渗泵由材料和结构制成，相对于目前可获得的微量泵，其材料和结构提高了性能，效率并降低了重量和制造成本。 这些电渗泵还允许重新捕获可能提供长期闭环操作的放出气体和沉积材料。 根据本发明的装置和方法还允许通过对通过泵的流的电控制来主动调节流体处理和现场取样装置。 电渗抽吸可以精确分配样品以形成遗传，蛋白质组或小分子阵列。 可以将光学，电容或其它类型的电传感器的流体传感器与电渗泵一体化，以测量液体抽取和分配操作中的液位。
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2.发明授权公开(公告)号：US08277628B2
公开(公告)日：2012-10-02
申请号：US12170941
申请日：2008-07-10
申请人： Mostafa Ronaghi , Tarun Khurana , Juan G. Santiago
发明人： Mostafa Ronaghi , Tarun Khurana , Juan G. Santiago
IPC分类号： G01N27/26
CPC分类号： B01L3/502761 , B01J2219/00317 , B01J2219/00459 , B01J2219/00466 , B01J2219/00596 , B01J2219/00648 , B01J2219/00653 , B01J2219/00702 , B01L2200/0668 , B01L2300/0819 , B01L2400/0415
摘要： Disclosed are a method and apparatus that use an electric field for improved biological assays. The electric field is applied across a device having wells, which receive reactants, which carry a charge. The device thus uses a controllable voltage source between the first and second electrodes, which is controllable to provide a positive charge and a negative charge to a given electrode. By controlled use of the electric field charged species in a fluid in a fluid channel are directed into or out of the well by an electric field between the electrodes. The present method involves the transport of fluids, as in a microfluidic device, and the electric field-induced movement of reactive species according to various assay procedures, such as DNA sequencing, synthesis or the like.
摘要翻译： 公开了使用电场进行改进的生物测定的方法和装置。 电场被施加在具有井的装置上，该装置具有承载电荷的反应物。 因此，该器件在第一和第二电极之间使用可控电压源，其可控制以向给定电极提供正电荷和负电荷。 通过控制使用流体通道中的流体中的电场带电物质通过电极之间的电场被引导进入或离开阱。 本方法涉及如在微流体装置中的流体的运输，以及根据各种测定程序（例如DNA测序，合成等）的反应物种的电场诱导运动。
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3.发明授权Method of detecting directly undetectable analytes using directly detectable spacer molecules 有权使用直接可检测的间隔分子检测直接不可检测的分析物的方法公开(公告)号：US07951278B2
公开(公告)日：2011-05-31
申请号：US11880479
申请日：2007-07-20
申请人： Juan G. Santiago , Tarun Khurana
发明人： Juan G. Santiago , Tarun Khurana
IPC分类号： G01N27/26
CPC分类号： G01N27/44726
摘要： The present invention provides a method of indirectly detecting at least one directly undetectable analyte of interest. According to the method, a leading electrolyte and a trailing electrolyte are provided. In addition, a mixture of the at least one directly undetectable analyte and at least two directly detectable spacer molecules is provided. The directly detectable spacer molecules and the directly undetectable analyte are then concentrated and separated into zones using isotachophoresis. A displacement between the zones of directly detectable spacer molecules is then used to determine the presence of the directly undetectable analyte.
摘要翻译： 本发明提供间接检测至少一种直接不可检测的感兴趣分析物的方法。 根据该方法，提供了主要的电解质和拖尾电解质。 此外，提供至少一种直接不可检测的分析物和至少两种直接可检测的间隔分子的混合物。 然后将直接可检测的间隔基分子和直接不可检测的分析物浓缩并使用等速电泳分离成区域。 然后使用直接可检测的间隔分子区域之间的位移来确定直接不可检测的分析物的存在。
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公开(公告)号：US20100210029A1
公开(公告)日：2010-08-19
申请号：US12597742
申请日：2008-04-25
申请人： Carl D. Meinhart , Brian Piorek , Seung Joon Lee , Martin Moskovits , Sanjoy Banerjee , Juan G. Santiago
发明人： Carl D. Meinhart , Brian Piorek , Seung Joon Lee , Martin Moskovits , Sanjoy Banerjee , Juan G. Santiago
CPC分类号： G01N21/658 , G01N21/0332 , G01N21/05 , G01N33/0057 , G01N2021/0346 , G01N2201/06113 , G01N2201/1087 , Y10S977/902
摘要： Provided are methods, devices and systems that utilize free-surface fluidics and SERS for analyte detection with high sensitivity and specificity. The molecules can be airborne agents, including but not limited to explosives, narcotics, hazardous chemicals, or other chemical species. The free-surface fluidic architecture is created using an open microchannel, and exhibits a large surface to volume ratio. The free-surface fluidic interface can filter interferent molecules, while concentrating airborne analyte molecules. The microchannel flow enables controlled aggregation of SERS-active probe particles in the flow, thereby enhancing the detector's sensitivity.
摘要翻译： 提供了利用自由表面流体学和SERS用于具有高灵敏度和特异性的分析物检测的方法，装置和系统。 分子可以是空气传播剂，包括但不限于爆炸物，麻醉剂，危险化学品或其他化学物质。 自由表面流体结构使用开放的微通道产生，并且表现出大的表面与体积比。 自由表面流体界面可以过滤干扰分子，同时浓缩空气中的分析物。 微通道流动使SERS活性探针颗粒在流动中受控聚集，从而提高检测器的灵敏度。
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公开(公告)号：US07316543B2
公开(公告)日：2008-01-08
申请号：US10449564
申请日：2003-05-30
CPC分类号： F04B19/006 , F04B17/00
摘要： An electroosmotic micropump having a plurality of thin, closely-spaced, approximately planar, transversel aligned partitions formed in or on a substrate, among which electroosmotic flow (EOF) is generated. Electrodes are located within enclosed inlet and outlet manifolds on either side of the partition array. Inlet and outlet ports enable fluid to be pumped into and through the micropump and through an external friction load or head. Insulating layer coatings on the formed substrate limit substrate leakage current during pumping operation.
摘要翻译： 一种具有形成在基底中或基底上的多个薄的，紧密间隔的大致平面的横向对准的隔离物的电渗微型泵，其中产生电渗流（EOF）。 电极位于分隔阵列任一侧封闭的入口和出口歧管内。 入口和出口端口使流体能够泵入并穿过微型泵并通过外部摩擦负载或头部。 所形成的衬底上的绝缘层涂层在泵送操作期间限制衬底漏电流。
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公开(公告)号：US07131486B2
公开(公告)日：2006-11-07
申请号：US10385086
申请日：2003-03-10
申请人： Kenneth E. Goodson , Chuan-Hua Chen , David E. Huber , Linan Jiang , Thomas W. Kenny , Jae-Mo Koo , Daniel J. Laser , James C. Mikkelsen , Juan G. Santiago , Evelyn Ning-Yi Wang , Shulin Zeng , Lian Zhang
发明人： Kenneth E. Goodson , Chuan-Hua Chen , David E. Huber , Linan Jiang , Thomas W. Kenny , Jae-Mo Koo , Daniel J. Laser , James C. Mikkelsen , Juan G. Santiago , Evelyn Ning-Yi Wang , Shulin Zeng , Lian Zhang
IPC分类号： F28F7/00
CPC分类号： H01L23/473 , F04B19/006 , F28D15/00 , F28F2260/02 , H01L2224/16225 , H01L2224/32145 , H01L2224/32225 , H01L2224/45169 , H01L2224/48227 , H01L2224/73265 , H01L2225/06562 , H01L2924/01078 , H01L2924/01322 , H01L2924/09701 , H01L2924/10158 , H01L2924/10253 , H01L2924/1461 , H01L2924/3011 , H01L2924/00
摘要： Apparatus and methods according to the present invention preferably utilize electroosmotic pumps that are capable of generating high pressure and flow without moving mechanical parts and the associated generation of unacceptable electrical and acoustic noise, as well as the associated reduction in reliability. These electroosmotic pumps are preferably fabricated with materials and structures that improve performance, efficiency, and reduce weight and manufacturing cost relative to presently available micropumps. These electroosmotic pumps also preferably allow for recapture of evolved gases and deposited materials, which may provide for long-term closed-loop operation. Apparatus and methods according to the present invention also allow active regulation of the temperature of the device through electrical control of the flow through the pump and can utilize multiple cooling loops to allow independent regulation of the special and temporal characteristics of the device temperature profiles. Novel microchannel structures are also described.
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7.发明授权Depth-of-field micron resolution velocimetry with pulsed images of injected solid particles 有权使用注入固体颗粒的脉冲图像进行深度微米分辨率测速公开(公告)号：US07057198B2
公开(公告)日：2006-06-06
申请号：US10713672
申请日：2003-11-13
IPC分类号： G01N15/06
CPC分类号： G01N15/1427 , G01F1/712 , G01N15/1459 , G01N15/1463 , G01N2015/1075 , G01N2015/1447
摘要： Method and apparatus for measuring fluid motion with micron scale spatial resolution, in which fluorescent particles are injected into a fluid body in a test device, the test device is broadly illuminated with pulses of light at the excitation frequency of the fluorescent particles, the fluorescent light is collected by a microscope objective lens, and the light thus collected is relayed through a fluorescent filter to an image recording device, the depth of field of the objective lens defining the thickness of a two-dimensional measurement plane.
摘要翻译： 用于以微米尺度空间分辨率测量流体运动的方法和装置，其中将荧光颗粒注入到测试装置中的流体中，测试装置被广泛地用荧光颗粒的激发频率的光脉冲照射，荧光灯 由显微镜物镜收集，并且将如此收集的光通过荧光过滤器中继到图像记录装置，物镜的景深限定二维测量平面的厚度。
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8.发明申请SIMULTANEOUS EXTRACTION AND SEPARATION OF RNA AND DNA FROM SINGLE CELLS USING ELECTROPHORETIC TECHNIQUES 审中-公开使用电泳技术从单细胞中同时提取和分离RNA和DNA公开(公告)号：US20150191717A1
公开(公告)日：2015-07-09
申请号：US14593925
申请日：2015-01-09
IPC分类号： C12N15/10 , G01N27/447 , C12Q1/68
CPC分类号： A61B1/00009 , A61B1/0005 , A61B1/05 , A61B1/0676 , C12N15/101 , C12Q1/6806 , G01N27/44791 , G06T7/0016 , G06T7/254 , G06T2207/10068 , G06T2207/30032 , C12Q2565/125 , C12Q2565/629
摘要： Devices and methods for preparing RNA and DNA from single cells are disclosed. In particular, the invention relates to a method of simultaneously extracting RNA and DNA from single cells and separating the nucleic acids electrophoretically. An electric field is used to lyse a single target cell, such that the plasma membrane is selectively disrupted without lysing the nuclear membrane. Cytoplasmic RNA is separated from the nucleus by performing isotachophoresis (ITP) in the presence of a sieving matrix that preferentially reduces the mobility of the nucleus. During ITP, the cytoplasmic RNA accumulates at an ITP interface between leading and trailing electrolytes and can later be extracted free of nuclear DNA. The method can be performed in a microfluidic device that fully automates all steps of the process.
摘要翻译： 公开了从单细胞制备RNA和DNA的装置和方法。 特别地，本发明涉及从单个细胞同时提取RNA和DNA并且电泳分离核酸的方法。 电场用于裂解单个靶细胞，使得质膜选择性地破裂而不裂解核膜。 在筛选基质的存在下，通过进行等速电泳（ITP），从细胞质中分离细胞质RNA，其优先降低细胞核的迁移率。 在ITP期间，细胞质RNA在前导电解质和尾部电解质之间的ITP界面处积累，并且可以随后被提取而不含核DNA。 该方法可以在完全自动化该过程的所有步骤的微流体装置中进行。
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9.发明申请公开(公告)号：US20130008789A1
公开(公告)日：2013-01-10
申请号：US13618228
申请日：2012-09-14
申请人： Mostafa Ronaghi , Tarun Khurana , Juan G. Santiago
发明人： Mostafa Ronaghi , Tarun Khurana , Juan G. Santiago
CPC分类号： B01L3/502761 , B01J2219/00317 , B01J2219/00459 , B01J2219/00466 , B01J2219/00596 , B01J2219/00648 , B01J2219/00653 , B01J2219/00702 , B01L2200/0668 , B01L2300/0819 , B01L2400/0415
摘要： Disclosed are a method and apparatus that use an electric field for improved biological assays. The electric field is applied across a device having wells, which receive reactants, which carry a charge. The device thus uses a controllable voltage source between the first and second electrodes, which is controllable to provide a positive charge and a negative charge to a given electrode. By controlled use of the electric field charged species in a fluid in a fluid channel are directed into or out of the well by an electric field between the electrodes. The present method involves the transport of fluids, as in a microfluidic device, and the electric field-induced movement of reactive species according to various assay procedures, such as DNA sequencing, synthesis or the like.
摘要翻译： 公开了使用电场进行改进的生物测定的方法和装置。 电场被施加在具有井的装置上，该装置具有承载电荷的反应物。 因此，该器件在第一和第二电极之间使用可控电压源，其可控制以向给定电极提供正电荷和负电荷。 通过控制使用流体通道中的流体中的电场带电物质通过电极之间的电场被引导进入或离开阱。 本方法涉及如在微流体装置中的流体的运输，以及根据各种测定程序（例如DNA测序，合成等）的反应物种的电场诱导运动。
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公开(公告)号：US20100224494A1
公开(公告)日：2010-09-09
申请号：US12716142
申请日：2010-03-02
IPC分类号： B01D57/02
CPC分类号： G01N27/447 , B01D57/02 , C12N15/101
摘要： A method and system are presented for fast and efficient isolation, purification and quantitation of nucleic acids from complex biological samples using isotachophoresis in microchannels. In an embodiment, a sieving medium may be used to enhance selectivity. In another embodiment, PCR-friendly chemistries are used to purify nucleic acids from complex biological samples and yield nucleic acids ready for further analysis including for PCR. In another embodiment, small RNAs from biological samples are extracted, isolated, preconcentrated and quantitated using on-chip ITP with a high efficiency sieving medium. The invention enables fast concentration and separation (takes 10s to 100s of seconds) of nucleic acids with high selectivity and using lower volumes of reagents (order of 10s of μL to focus less than 1 pg/μL of nucleic acid).
摘要翻译： 提出了一种方法和系统，用于在微通道中使用等速电泳，从复杂生物样品中快速有效地分离，纯化和定量核酸。 在一个实施方案中，可以使用筛分介质来增强选择性。 在另一个实施方案中，使用PCR友好的化学物质从复杂的生物样品中纯化核酸，并产生准备用于进一步分析的核酸，包括用于PCR。 在另一个实施方案中，使用具有高效筛选培养基的片上ITP，提取，分离，预浓缩和定量来自生物样品的小RNA。 本发明使得能够以高选择性快速浓缩和分离（需要10秒至100秒）的核酸，并且使用较低体积的试剂（10μL的浓度以聚焦小于1pg /μL的核酸）。
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