公开(公告)号：WO2008051432A2

公开(公告)日：2008-05-02

申请号：PCT/US2007/022219

申请日：2007-10-18

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE ,  LAHAV, Michal ,  WINKLEMAN, Adam ,  NAROVLYANSKY, Max ,  PEREZ-CASTILLEJOS, Raquel ,  WEISS, Emily, A. ,  RODRIGUEZ, Leonard, N. J. ,  WHITESIDES, George, M.

Inventor： LAHAV, Michal ,  WINKLEMAN, Adam ,  NAROVLYANSKY, Max ,  PEREZ-CASTILLEJOS, Raquel ,  WEISS, Emily, A. ,  RODRIGUEZ, Leonard, N. J. ,  WHITESIDES, George, M.

IPC: G03F7/00

CPC classification number: G03F7/0002 ,  B82Y10/00 ,  B82Y40/00 ,  Y10T428/24479

Abstract: In one aspect, methods of patterning of thin films of an ionotropic polymer (e.g., poly(acrylic acid)) are provided. These processes can create micron or sub-micron-scale patterns of ionotropic polymers such as cation crosslinked poly(acrylic acid) (CCL- PAA). In one embodiment, patterning may be performed within microfluidic channels by flowing a solution of crosslinking agent (e.g., metal cations such as Ag + , Ca 2+ , Pd 2+ , Al 3+ , La 3+ , and Ti 4+ ) that can crosslink a portion of an ionotropic polymer in contact with the solution. In another embodiment, methods of patterning ionotropic polymers involve photolithography. Upon patterning a positive photoresist (e.g., diazonaphthoquinone- novolac resin) on a film of CCL-PAA, the exposed regions of CCL-PAA can be etched by an aqueous solution. Advantageously, the patterned, crosslinked polymer may also serve as both a reactant and a matrix for subsequent chemistry. For example, in some embodiments, the initial crosslinking cation can be exchanged for a second cation that could not be patterned photolithographically. Patterned films of CCL-PAA can also be used to host and template the reduction of metallic cations to metallic nanoparticles, and to fabricate porous, low-k dielectric substrates.

Abstract translation: 一方面，提供了离子型聚合物（例如聚（丙烯酸））的薄膜图案化方法。 这些方法可以产生离子型聚合物如阳离子交联的聚（丙烯酸）（CCL-PAA）的微米级或亚微米级的图案。 在一个实施方案中，可以通过使交联剂溶液（例如，金属阳离子如Ag 2+，Ca 2+，Pd 2+， 2+，3+，3+，3+，和3++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ 与溶液接触。 在另一个实施方案中，构图离子型聚合物的方法涉及光刻。 在CCL-PAA膜上形成正性光致抗蚀剂（例如重氮萘酚 - 酚醛清漆树脂）之后，CCL-PAA的曝光区域可以通过水溶液进行蚀刻。 有利地，图案化的交联聚合物也可以用作反应物和用于后续化学的基质。 例如，在一些实施方案中，可以将初始交联阳离子交换为不能光刻图案化的第二阳离子。 CCL-PAA的图案化膜也可用于将金属阳离子还原为金属纳米颗粒，并制备多孔，低k电介质基底。

公开(公告)号：WO2006113727A3

公开(公告)日：2007-02-15

申请号：PCT/US2006014583

申请日：2006-04-19

Applicant: HARVARD COLLEGE ,  LINDER VINCENT ,  SIA SAMUEL K ,  WHITESIDES GEORGE M ,  NAROVLYANSKY MAX ,  SIEGEL ADAM

Inventor： LINDER VINCENT ,  SIA SAMUEL K ,  WHITESIDES GEORGE M ,  NAROVLYANSKY MAX ,  SIEGEL ADAM

IPC: G01N21/59 ,  B01L3/00 ,  G01N33/543 ,  G01N33/553

CPC classification number: G01N33/54366 ,  B01L3/502746 ,  B01L2300/0636 ,  B01L2300/0654 ,  B01L2300/0816 ,  B01L2300/0861 ,  B01L2300/0883 ,  B01L2400/0406 ,  G01N21/01 ,  G01N21/82 ,  G01N33/54373

Abstract: The present invention relates generally to microfluidic structures, and more specifically, to microfluidic structures and methods including meandering and wide channels. Microfluidic systems can provide an advantageous environment for performing various reactions and analyses due to a reduction in sample and reagent quantities that are required, a reduction in the size of the operating system, and a decrease in reaction time compared to conventional systems. Unfortunately, the small size of microfluidic channels can sometimes result in difficulty in detecting a species without magnifying optics (such as a microscope or a photomultiplier). A series of tightly packed microchannels, i.e., a meandering region, or a wide channel having a dimension on the order of millimeters, can serve as a solution to this problem by creating a wide measurement area. Although this invention mainly describes the use of meandering and wide channels in heterogeneous immunoassays on a microfluidic chip, this invention could be used for amplifying optical signals for other types of reactions and/or assays.

Abstract translation: 本发明一般涉及微流体结构，更具体地涉及包括曲折和宽通道的微流体结构和方法。 微流控系统可以提供用于执行各种反应和分析的有利环境，这是由于与常规系统相比所需的样品和试剂量的减少，操作系统尺寸的减小以及反应时间的减少。 不幸的是，微量流体通道的小尺寸有时会导致在不放大光学器件（例如显微镜或光电倍增管）的情况下检测物质的困难。 一系列紧密包装的微通道，即曲折区域或具有大约毫米数量级的宽通道可以通过创建宽的测量区域来解决这个问题。 尽管本发明主要描述了在微流体芯片上的异源免疫测定中使用曲折和宽通道，但是本发明可用于放大用于其他类型反应和/或测定的光学信号。

公开(公告)号：WO2006102516A3

公开(公告)日：2006-09-28

申请号：PCT/US2006/010605

申请日：2006-03-23

Applicant: CALIFORNIA INSTITUTE OF TECHNOLOGY ,  PRESIDENT AND FELLOWS OF HARVARD COLLEGE ,  SQUIRES, Todd, M. ,  NAROVLYANSKY, Max

Inventor： SQUIRES, Todd, M. ,  NAROVLYANSKY, Max

IPC: G01N27/447 ,  B01L3/00

Abstract: The invention features microfluidic devices that contain structures that impart differential resistance to a fluid flow. The structures are disposed adjacent to intersections of channels. Devices of the invention provide differential resistance, e.g., under electric-field-driven flow and pressure-driven flow.

公开(公告)号：WO2010102279A1

公开(公告)日：2010-09-10

申请号：PCT/US2010/026499

申请日：2010-03-08

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE ,  NEI, Zhihong ,  NIJHUIS, Christian ,  CHEN, Xin ,  MARTINEZ, Andres, W. ,  NAROVLYANSKY, Max ,  WHITESIDES, George, M.

Inventor： NEI, Zhihong ,  NIJHUIS, Christian ,  CHEN, Xin ,  MARTINEZ, Andres, W. ,  NAROVLYANSKY, Max ,  WHITESIDES, George, M.

IPC: B01L3/00

CPC classification number: B01L3/5027 ,  B01L3/502 ,  B01L2300/0645 ,  B01L2300/0887 ,  G01N27/3272

Abstract: Microfluidic, electrochemical devices are described. The microfluidic, electrochemical device comprises one or more electrode(s) on a substrate and a patterned porous, hydrophilic layer having a fluid-impermeable barrier which substantially permeates the thickness of the porous, hydrophilic layer and defines boundaries of one or more hydrophilic channels within the patterned porous, hydrophilic layer, wherein the hydrophilic channel(s) comprises a hydrophilic region which is in fiuidic communication with the electrode(s). In some embodiments, the electrodes comprise a working electrode, a counter electrode, and a reference electrode. In some embodiments, the microfluidic, electrochemical device further comprises a fluid sink. The method of assembling the microfluidic, electrochemical device is described. The method of using the device for electrochemical analysis of one or more analytes is also described.

Abstract translation: 描述了微流体，电化学装置。 微流体电化学装置包括在基底上的一个或多个电极和图案化的多孔亲水层，其具有基本上渗透多孔亲水层的厚度的流体不可渗透屏障，并限定一个或多个亲水性通道的边界 所述图案化的多孔亲水层，其中所述亲水性通道包括与所述电极流体连通的亲水区域。 在一些实施例中，电极包括工作电极，对电极和参考电极。 在一些实施例中，微流体，电化学装置还包括流体槽。 描述了组装微流体，电化学装置的方法。 还描述了使用该装置进行一种或多种分析物的电化学分析的方法。

公开(公告)号：WO2006125176A8

公开(公告)日：2007-03-01

申请号：PCT/US2006019533

申请日：2006-05-19

Applicant: HARVARD COLLEGE ,  DAMEAN NICOLAE ,  SIA SAMUEL K ,  LINDER VINCENT ,  NAROVLYANSKY MAX ,  WHITESIDES GEORGE M

Inventor： DAMEAN NICOLAE ,  SIA SAMUEL K ,  LINDER VINCENT ,  NAROVLYANSKY MAX ,  WHITESIDES GEORGE M

IPC: G01N33/543 ,  B01L3/00

CPC classification number: G01N21/255 ,  B01L3/5027 ,  G01J3/02 ,  G01J3/0208 ,  G01J3/0256 ,  G01N21/05 ,  G01N2021/0346 ,  G01N2201/0638 ,  G02B21/0032

Abstract: The present invention generally relates to systems and methods for acquiring multiple spectra from a sample, for example, a microfluidic sample. In some aspects of the invention, spectra from a series of locations within a sample are recorded and analyzed, and optionally correlated with an image of the sample. The spectra can be obtained by passing a plurality of light beams through a sample, e.g., using an array of microlenses, diffracting the light beams passing through the sample with a transmission grating, before or after passing the light through the sample, and detecting the resulting light, e.g., as an image. The light beams may pass through the sample before or after passing through the transmission grating. The image can appear as an array of discrete spectra, where each spectrum is associated with a region of the sample where a light beam passed through the sample. The spectra can be analyzed to determine information about the region where the light beam passed through the sample. In some cases, the array of microlenses may be movable and/or replaceable with a second array of microlenses. Also, in some instances, the transmission grating may be movable and/or replaceable with a second transmission grating.

Abstract translation: 本发明一般涉及用于从样品例如微流体样品获取多个光谱的系统和方法。 在本发明的一些方面，记录和分析来自样品中的一系列位置的光谱，并且可选地与样品的图像相关。 可以通过使多个光束通过样品获得光谱，例如使用微透镜阵列，在通过样品之前或之后通过透射光栅衍射穿过样品的光束，并且检测 产生光，例如，作为图像。 光束可以在通过透射光栅之前或之后通过样品。 该图像可以显示为离散光谱阵列，其中每个光谱与光束通过样品的样品区域相关联。 可以分析光谱以确定关于光束通过样品的区域的信息。 在一些情况下，微透镜阵列可以是可移动的和/或可替代的第二阵列的微透镜。 此外，在一些情况下，透射光栅可以是可移动的和/或可以用第二透射光栅代替。

公开(公告)号：WO2006113727A2

公开(公告)日：2006-10-26

申请号：PCT/US2006/014583

申请日：2006-04-19

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE ,  LINDER, Vincent ,  SIA, Samuel, K. ,  WHITESIDES, George, M. ,  NAROVLYANSKY, Max ,  SIEGEL, Adam

Inventor： LINDER, Vincent ,  SIA, Samuel, K. ,  WHITESIDES, George, M. ,  NAROVLYANSKY, Max ,  SIEGEL, Adam

IPC: G01N21/59 ,  B01L3/00 ,  G01N33/543 ,  G01N33/553

CPC classification number: G01N33/54366 ,  B01L3/502746 ,  B01L2300/0636 ,  B01L2300/0654 ,  B01L2300/0816 ,  B01L2300/0861 ,  B01L2300/0883 ,  B01L2400/0406 ,  G01N21/01 ,  G01N21/82 ,  G01N33/54373

Abstract: The present invention relates generally to microfluidic structures, and more specifically, to microfluidic structures and methods including meandering and wide channels. Microfluidic systems can provide an advantageous environment for performing various reactions and analyses due to a reduction in sample and reagent quantities that are required, a reduction in the size of the operating system, and a decrease in reaction time compared to conventional systems. Unfortunately, the small size of microfluidic channels can sometimes result in difficulty in detecting a species without magnifying optics (such as a microscope or a photomultiplier). A series of tightly packed microchannels, i.e., a meandering region, or a wide channel having a dimension on the order of millimeters, can serve as a solution to this problem by creating a wide measurement area. Although this invention mainly describes the use of meandering and wide channels in heterogeneous immunoassays on a microfluidic chip, this invention could be used for amplifying optical signals for other types of reactions and/or assays.

Abstract translation: 本发明一般涉及微流体结构，更具体地涉及包括曲折和宽通道的微流体结构和方法。 微流控系统可以提供用于执行各种反应和分析的有利环境，这是由于与常规系统相比所需的样品和试剂量的减少，操作系统尺寸的减小以及反应时间的减少。 不幸的是，微量流体通道的小尺寸有时会导致在不放大光学器件（例如显微镜或光电倍增管）的情况下检测物质的困难。 一系列紧密包装的微通道，即曲折区域或具有大约毫米数量级的宽通道可以通过创建宽的测量区域来解决这个问题。 尽管本发明主要描述了在微流体芯片上的异源免疫测定中使用曲折和宽通道，但是本发明可用于放大用于其他类型反应和/或测定的光学信号。

公开(公告)号：WO2008051432A3

公开(公告)日：2009-04-09

申请号：PCT/US2007022219

申请日：2007-10-18

Applicant: HARVARD COLLEGE ,  LAHAV MICHAL ,  WINKLEMAN ADAM ,  NAROVLYANSKY MAX ,  PEREZ-CASTILLEJOS RAQUEL ,  WEISS EMILY A ,  RODRIGUEZ LEONARD N J ,  WHITESIDES GEORGE M

Inventor： LAHAV MICHAL ,  WINKLEMAN ADAM ,  NAROVLYANSKY MAX ,  PEREZ-CASTILLEJOS RAQUEL ,  WEISS EMILY A ,  RODRIGUEZ LEONARD N J ,  WHITESIDES GEORGE M

IPC: G03F7/00

CPC classification number: G03F7/0002 ,  B82Y10/00 ,  B82Y40/00 ,  Y10T428/24479

Abstract: In one aspect, methods of patterning of thin films of an ionotropic polymer (e.g., poly(acrylic acid)) are provided. These processes can create micron or sub-micron-scale patterns of ionotropic polymers such as cation crosslinked poly(acrylic acid) (CCL- PAA). In one embodiment, patterning may be performed within microfluidic channels by flowing a solution of crosslinking agent (e.g., metal cations such as Ag+, Ca2+, Pd2+, Al3+, La3+, and Ti4+) that can crosslink a portion of an ionotropic polymer in contact with the solution. In another embodiment, methods of patterning ionotropic polymers involve photolithography. Upon patterning a positive photoresist (e.g., diazonaphthoquinone- novolac resin) on a film of CCL-PAA, the exposed regions of CCL-PAA can be etched by an aqueous solution. Advantageously, the patterned, crosslinked polymer may also serve as both a reactant and a matrix for subsequent chemistry. For example, in some embodiments, the initial crosslinking cation can be exchanged for a second cation that could not be patterned photolithographically. Patterned films of CCL-PAA can also be used to host and template the reduction of metallic cations to metallic nanoparticles, and to fabricate porous, low-k dielectric substrates.

Abstract translation: 一方面，提供了离子型聚合物（例如聚（丙烯酸））的薄膜图案化方法。 这些方法可以产生离子型聚合物如阳离子交联的聚（丙烯酸）（CCL-PAA）的微米级或亚微米级的图案。 在一个实施方案中，可以在微流体通道内通过使交联剂（例如金属阳离子如Ag +，Ca 2+，Pd 2+，Al 3+，La 3+和Ti 4+）的溶液流过微流体通道，所述溶液可以将部分离子型聚合物与 解决方案。 在另一个实施方案中，构图离子型聚合物的方法涉及光刻。 在CCL-PAA膜上形成正性光致抗蚀剂（例如重氮萘酚 - 酚醛清漆树脂）之后，CCL-PAA的曝光区域可以通过水溶液进行蚀刻。 有利地，图案化的交联聚合物也可以用作反应物和用于后续化学的基质。 例如，在一些实施方案中，可以将初始交联阳离子交换为不能光刻图案化的第二阳离子。 CCL-PAA的图案化膜也可用于将金属阳离子还原为金属纳米颗粒，并制备多孔，低k电介质基底。

公开(公告)号：WO2006125176A1

公开(公告)日：2006-11-23

申请号：PCT/US2006/019533

申请日：2006-05-19

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE ,  DAMEAN, Nicolae ,  SIA, Samuel, K. ,  LINDER, Vincent ,  NAROVLYANSKY, Max ,  WHITESIDES, George, M.

Inventor： DAMEAN, Nicolae ,  SIA, Samuel, K. ,  LINDER, Vincent ,  NAROVLYANSKY, Max ,  WHITESIDES, George, M.

IPC: G01N33/543 ,  B01L3/00

CPC classification number: G01N21/255 ,  B01L3/5027 ,  G01J3/02 ,  G01J3/0208 ,  G01J3/0256 ,  G01N21/05 ,  G01N2021/0346 ,  G01N2201/0638 ,  G02B21/0032

Abstract: The present invention generally relates to systems and methods for acquiring multiple spectra from a sample, for example, a microfluidic sample. In some aspects of the invention, spectra from a series of locations within a sample are recorded and analyzed, and optionally correlated with an image of the sample. The spectra can be obtained by passing a plurality of light beams through a sample, e.g., using an array of microlenses, diffracting the light beams passing through the sample with a transmission grating, before or after passing the light through the sample, and detecting the resulting light, e.g., as an image. The light beams may pass through the sample before or after passing through the transmission grating. The image can appear as an array of discrete spectra, where each spectrum is associated with a region of the sample where a light beam passed through the sample. The spectra can be analyzed to determine information about the region where the light beam passed through the sample. In some cases, the array of microlenses may be movable and/or replaceable with a second array of microlenses. Also, in some instances, the transmission grating may be movable and/or replaceable with a second transmission grating.

Abstract translation: 本发明一般涉及用于从样品例如微流体样品获取多个光谱的系统和方法。 在本发明的一些方面，记录和分析来自样品中的一系列位置的光谱，并且可选地与样品的图像相关。 可以通过使多个光束通过样品获得光谱，例如使用微透镜阵列，在通过样品之前或之后通过透射光栅衍射穿过样品的光束，并且检测 产生光，例如，作为图像。 光束可以在通过透射光栅之前或之后通过样品。 该图像可以显示为离散光谱阵列，其中每个光谱与光束通过样品的样品区域相关联。 可以分析光谱以确定关于光束通过样品的区域的信息。 在一些情况下，微透镜阵列可以是可移动的和/或可替代的第二阵列的微透镜。 此外，在一些情况下，透射光栅可以是可移动的和/或可以用第二透射光栅代替。

公开(公告)号：WO2006102516A2

公开(公告)日：2006-09-28

申请号：PCT/US2006010605

申请日：2006-03-23

Applicant: CALIFORNIA INST OF TECHN ,  HARVARD COLLEGE ,  SQUIRES TODD M ,  NAROVLYANSKY MAX

Inventor： SQUIRES TODD M ,  NAROVLYANSKY MAX

IPC: G01N27/447 ,  B01L3/00

CPC classification number: G01N27/44743 ,  B01L3/502784 ,  B01L2200/0605 ,  B01L2200/0636 ,  B01L2200/0673 ,  B01L2300/0816 ,  B01L2400/0421 ,  B01L2400/0487 ,  B01L2400/086 ,  C12M23/16 ,  C12M25/14

Abstract: The invention features microfluidic devices that contain structures that impart differential resistance to a fluid flow. Differential resistance may be generated parallel, e.g., along the length of a channel, or perpendicular to the length of a channel, to the direction of flow in a channel. Devices of the invention provide differential resistance, e.g., under electric-field-driven flow and pressure-driven flow.

Abstract translation: 本发明的特征在于包含赋予流体流动差异电阻的结构的微流体装置。 差分电阻可以平行地产生，例如，沿着通道的长度，或垂直于通道的长度，与通道中的流动方向平行地产生。 本发明的装置提供差分电阻，例如在电场驱动的流动和压力驱动的流动下。