公开(公告)号：US07374944B2

公开(公告)日：2008-05-20

申请号：US10491686

申请日：2002-10-03

申请人： David H. Thompson ,  Christine A. Hrycyna ,  Gil U. Lee ,  Osman A. Basaran ,  Kinam Park ,  Igal Szleifer

发明人： David H. Thompson ,  Christine A. Hrycyna ,  Gil U. Lee ,  Osman A. Basaran ,  Kinam Park ,  Igal Szleifer

IPC分类号： G01N33/00

CPC分类号： B01J19/0046 ,  B01J2219/00317 ,  B01J2219/00378 ,  B01J2219/00387 ,  B01J2219/00432 ,  B01J2219/00527 ,  B01J2219/00585 ,  B01J2219/00596 ,  B01J2219/00641 ,  B01J2219/00653 ,  B01J2219/00659 ,  B01J2219/00711 ,  B01J2219/00716 ,  B01J2219/00725 ,  B82Y30/00 ,  C12Q1/003 ,  G01N33/54366 ,  G01N33/5438 ,  G01N33/6872 ,  G01N2500/00

摘要： Bioanalytical device that includes a biofunctional component and an optional sensor component. The device includes arrays of addressable, durable, asymmetric biofunctional membranes containing protein transducers capable of unidirectional transport of analytes. Suitable protein transducers include members of the ATP-binding cassette family, such as P-glycoprotein.

摘要翻译： 生物分析装置，包括生物功能组件和可选的传感器组件。 该装置包括可寻址的，耐用的不对称生物功能膜阵列，其含有能够单向传送分析物的蛋白质转导体。 合适的蛋白质换能器包括ATP结合盒系列的成员，例如P-糖蛋白。

公开(公告)号：US06368553B1

公开(公告)日：2002-04-09

申请号：US09553230

申请日：2000-04-19

申请人： Gil U Lee

发明人： Gil U Lee

IPC分类号： G01N33543

CPC分类号： G01N33/54373 ,  C12M33/12 ,  Y10S436/806 ,  Y10S436/824

摘要： An ultrasonic energy source is used to provide a variable force for measuring the binding forces between molecular entities and for sensing the presence of an analyte in a test sample. The device includes a surface that has a first binding member attached thereto and one or more particles that have a second binding member attached thereto. A reaction vessel is provided for exposing the surface to the particles whereby, if the first binding member has a binding affinity for the second binding member, a complex is formed between individual first binding members and individual second binding members and the particles thereby become immobilized with respect to the surface. The ultrasonic energy source is positioned for applying a variable ultrasonic force onto the surface, and the position of the particles is monitored as the intensity of the ultrasonic force is varied.

公开(公告)号：US07341696B2

公开(公告)日：2008-03-11

申请号：US11538987

申请日：2006-10-05

申请人： Gil U Lee ,  Carolyn Yanavich

发明人： Gil U Lee ,  Carolyn Yanavich

IPC分类号： B01L11/00

CPC分类号： G01N33/537 ,  G01N33/54326 ,  G01N33/54366 ,  G01N33/54393

摘要： A sensor for a selected analyte in a test sample has (a) a semipermeable membrane with pores for retaining the analyte, where the membrane has been chemically modified by attachment of membrane modifiers; (b) immunoassay labels which have label binding ligands where these label binding ligands will have a binding affinity for the membrane modifiers in the presence of the analyte, and a measurably different binding affinity for the membrane modifiers in the absence of the analyte; and (c) a label detecting system, for detecting the presence of the labels on the membrane.

摘要翻译： 用于测试样品中所选分析物的传感器具有（a）具有用于保持分析物的孔的半透膜，其中膜已经通过附着膜修饰剂进行化学改性; （b）具有标记结合配体的免疫测定标记，其中这些标记结合配体将在分析物存在下对膜修饰剂具有结合亲和力，并且在不存在分析物的情况下对膜改性剂具有可测量的不同结合亲和力; 和（c）标签检测系统，用于检测膜上标签的存在。

公开(公告)号：US06086821A

公开(公告)日：2000-07-11

申请号：US377284

申请日：1999-03-29

申请人： Gil U Lee

发明人： Gil U Lee

IPC分类号： G01N33/543 ,  G01N21/00 ,  B01D35/06 ,  G01N30/96 ,  G01N33/553

CPC分类号： G01N33/54373 ,  C12M33/12 ,  Y10S436/806 ,  Y10S436/824

摘要： An ultrasonic energy source is used to provide a variable force for measuring the binding forces between molecular entities and for sensing the presence of an analyte in a test sample. The device includes a surface that has a first binding member attached thereto and one or more particles that have a second binding member attached thereto. A reaction vessel is provided for exposing the surface to the particles whereby, if the first binding member has a binding affinity for the second binding member, a complex is formed between individual first binding members and individual second binding members and the particles thereby become immobilized with respect to the surface. The ultrasonic energy source is positioned for applying a variable ultrasonic force onto the surface, and the position of the particles is monitored as the intensity of the ultrasonic force is varied.

公开(公告)号：US08715739B2

公开(公告)日：2014-05-06

申请号：US11552324

申请日：2006-10-24

申请人： Gil U. Lee ,  Hao Shang ,  Won-Suk Chang

发明人： Gil U. Lee ,  Hao Shang ,  Won-Suk Chang

IPC分类号： A61K9/50

CPC分类号： B01J2/06 ,  A61K41/0028 ,  A61K41/0052 ,  A61K49/1887 ,  B01J13/12 ,  B01J13/14 ,  B82Y5/00 ,  B82Y25/00 ,  H01F1/0054

摘要： Methods for preparing uniformly sized micropanicles, with an optional polymeric coating generally include: 1) providing nanoparticles, preferably having a size of between 1 nm and 100 nm; 2) adding a hydrophobic surface layer to the nanoparticles; 3) making a suspension of the hydrophobic nanoparticles and a polymerization initiator in an hydrophobic solvent; 4) dissolving a monomer in the hydrophobic solvent; 5) making an emulsion by dispersing droplets of the hydrophobic solvent in a continuous aqueous phase with an emulsifier; 6) sizing the first emulsion to provide a second emulsion of the same components in which the droplets are substantially uniform and between 2 and 20 um in size; 7) evaporating at least a substantial portion of the dispersed hydrophobic droplets to assemble nanoparticles to form micropanicles suspended now in the aqueous phase; 8) replacing the first surfactant with a second surfactant, which is preferably a polymerizable surfactant; 9) adding a polymerizable monomer to the aqueous phase and allowing it to adsorb into the microparticle; 10) polymerizing the monomer(s) to provide a polymer layer on the micropanicles; and 11) functionalizing the polymer surface layer erf the micropanicles with one or more polymer, nanoparticle or biological macromolecular layers.

摘要翻译： 用任选的聚合物涂层制备均匀尺寸的微粒子的方法通常包括：1）提供优选具有1nm至100nm尺寸的纳米颗粒; 2）向纳米颗粒中加入疏水表面层; 3）使疏水性纳米粒子和聚合引发剂在疏水性溶剂中的悬浮液; 4）将单体溶解在疏水溶剂中; 5）通过将疏水性溶剂的液滴与乳化剂分散在连续的水相中来制备乳液; 6）调整第一乳液的尺寸以提供相同组分的第二乳液，其中液滴基本上均匀且尺寸在2-20μm之间; 7）蒸发至少大部分分散的疏水液滴以组装纳米颗粒以形成现在悬浮于水相中的微球; 8）用优选可聚合表面活性剂的第二表面活性剂代替第一表面活性剂; 9）向水相中加入可聚合单体并使其吸附到微粒中; 10）聚合单体以在微粒上提供聚合物层; 和11）使用一种或多种聚合物，纳米颗粒或生物大分子层对聚合物表面层进行功能化。

公开(公告)号：US06180418B2

公开(公告)日：2001-01-30

申请号：US09008782

申请日：1998-01-20

申请人： Gil U. Lee

发明人： Gil U. Lee

IPC分类号： C12Q168

CPC分类号： G01N27/745 ,  C12Q1/6816 ,  G01N33/54326 ,  G01N33/585 ,  C12Q2565/619 ,  C12Q2563/143

摘要： A sensor for a selected target species has (a) a substrate which has been chemically modified by attachment of substrate modifiers; (b) one or more magnetically active beads which have been chemically modified by attachment of bead modifiers, where these bead modifiers will have a binding affinity for the substrate modifiers in the presence of the target species, and a measurably different binding affinity for the substrate modifiers in the absence of the target species; (c) an adjustable source of a magnetic field for exerting a force on the beads; and (d) an imaging system, for observing and counting beads bound to the substrate. In a preferred embodiment, the invention further has a system for identifying clusters of beads, and for removing the effect of such clusters from measurements of the target analyte. As with other assays, the sensor relies on the ability of certain molecules to bind with specific target (analyte) molecules. By coating the beads and the substrate with appropriate molecules, the beads will (or will not) bind specifically to the substrate in the presence (or absence) of the target molecule. When a magnetic field is applied to the substrate, the magnetic beads will be pulled away from the substrate. If the beads are specifically bound to the substrate, however, the beads will be retained on the substrate, indicating the presence (or absence) of the target species.

摘要翻译： 用于所选目标物种的传感器具有（a）通过附着底物改性剂化学改性的基底; （b）已经通过附着珠改性剂化学改性的一种或多种磁性活性珠，其中这些珠改性剂将在靶物质存在下对底物改性剂具有结合亲和性，并且对底物具有可测量的不同结合亲和力 没有目标物种的改性剂; （c）用于在珠上施加力的可调节磁场源; 和（d）用于观察和计数与基底结合的珠子的成像系统。 在优选的实施方案中，本发明还具有用于鉴定珠簇的系统，并且用于从所述目标分析物的测量中除去这些簇的影响。 与其他测定一样，传感器依赖于某些分子与特定靶（分析物）分子结合的能力。 通过用合适的分子涂布珠粒和底物，珠子将（或不会）在靶分子的存在（或不存在）下特异性结合底物。 当将磁场施加到基板时，磁珠将被从基板拉出。 然而，如果珠粒特异性地结合到底物上，则珠粒将保留在底物上，表明目标物质的存在（或不存在）。

公开(公告)号：US06764860B2

公开(公告)日：2004-07-20

申请号：US10054945

申请日：2002-01-25

申请人： Gil U Lee

发明人： Gil U Lee

IPC分类号： G01N33543

CPC分类号： G01N33/54373 ,  C12M33/12 ,  Y10S436/806 ,  Y10S436/824

摘要： An ultrasonic energy source is used to provide a variable force for measuring the binding forces between molecular entities and for sensing the presence of an analyte in a test sample. The device includes a surface that has a first binding member attached thereto and one or more particles that have a second binding member attached thereto. A reaction vessel is provided for exposing the surface to the particles whereby, if the first binding member has a binding affinity for the second binding member, a complex is formed between individual first binding members and individual second binding members and the particles thereby become immobilized with respect to the surface. The ultrasonic energy source is positioned for applying a variable ultrasonic force onto the surface, and the position of the particles is monitored as the intensity of the ultrasonic force is varied.

摘要翻译： 超声能量源用于提供用于测量分子实体之间的结合力的可变力并用于感测测试样品中分析物的存在。 该装置包括具有附接到其上的第一装订构件和附接到其上的具有第二装订构件的一个或多个颗粒的表面。 提供反应容器用于将表面暴露于颗粒，由此如果第一粘合构件对第二粘合构件具有结合亲合力，则在各个第一粘合构件和单独的第二粘合构件之间形成复合物，并且由此将颗粒固定在 尊重表面。 定位超声能量源，以将可变的超声波力施加到表面上，并且随着超声波力的变化，粒子的位置被监测。

公开(公告)号：US5807758A

公开(公告)日：1998-09-15

申请号：US505547

申请日：1995-07-21

申请人： Gil U. Lee ,  David A. Kidwell ,  Richard J. Colton

发明人： Gil U. Lee ,  David A. Kidwell ,  Richard J. Colton

IPC分类号： B81B3/00 ,  C12Q1/68 ,  C12Q1/70 ,  G01N33/543 ,  G01Q90/00 ,  G01N27/00 ,  G01N33/573 ,  C01N33/573

CPC分类号： G01Q60/42 ,  B82Y35/00 ,  G01N27/745 ,  G01N33/54373

摘要： The present invention is a method and apparatus for detecting a target species. The target molecule may be in liquid phase (in solution) or (for some embodiments of the invention) in vapor phase. A sensor according to the present invention monitors whether a target species has selectively bound to groups on the cantilever surface by monitoring the displacement of the cantilever, and hence the force acting on the cantilever. This force acting on the cantilever arises from the force acting on a structure that moves in electric or magnetic field, and that may be selectively bound to the cantilever. In the case of target species having a sufficiently large net electric charge or dipole moment, the target species itself may serve as the structure that moves in an electric field. More typically however, separate modified structures, such as modified magnetic beads or modified beads having a net charge or a dipole moment, will, when selectively bound to the cantilever, exert a force on the cantilever that relates to the presence of the target species.

摘要翻译： 本发明是用于检测目标物种的方法和装置。 靶分子在气相中可以是液相（溶液中）或（对于本发明的一些实施方案）。 根据本发明的传感器通过监测悬臂的位移以及因此作用在悬臂上的力来监视目标物种是否选择性地结合到悬臂表面上的组。 作用在悬臂上的力源自作用在电场或磁场中移动的结构上的力，并且可以选择性地结合到悬臂。 在具有足够大的净电荷或偶极矩的目标物种的情况下，目标物质本身可以用作在电场中移动的结构。 然而，更典型地，单独的改性结构，例如具有净电荷或偶极矩的改性磁珠或改性珠粒，当选择性地结合到悬臂时，将在悬臂上施加与靶物种的存在有关的力。

公开(公告)号：US20100279887A1

公开(公告)日：2010-11-04

申请号：US12452031

申请日：2008-06-14

申请人： Gil U. Lee ,  Benjamin Yellen ,  Randall Morgan Erb

发明人： Gil U. Lee ,  Benjamin Yellen ,  Randall Morgan Erb

IPC分类号： C40B30/04 ,  C40B40/18

CPC分类号： G01N27/745

摘要： A method of separating a target biological analyte from a mixture of substances in a fluid sample employs nonlinear magnetophoresis. Magnetic particles having the capacity to bind to the target analyte are contacted with the fluid sample so that the analyte is immobilized on the surface of at least some of the particles. The magnetic particles are provided adjacent an array of micromagnets patterned on a substrate so that the particles are attracted the micromagnets. The magnetic particles are then subjected to a traveling magnetic field operating at or above a frequency effective to sweep those particles not bound to analyte to an adjacent micromagnet. Those magnetic particles bound to analyte have a larger size or smaller magnetic moment that prevents them from being moved to adjacent micromagnets, thereby affording separation of the analyte.

摘要翻译： 从流体样品中的物质混合物中分离目标生物分析物的方法采用非线性磁电泳法。 具有结合目标分析物的能力的磁性颗粒与流体样品接触，使得分析物固定在至少一些颗粒的表面上。 磁性颗粒被设置在图案化在基板上的微阵列附近，使得颗粒被吸引到微型磁体。 然后磁性颗粒经受有效扫描未结合分析物的颗粒到相邻微型磁体上或高于频率的行进磁场。 与分析物结合的那些磁性颗粒具有更大的尺寸或更小的磁矩，从而防止它们被移动到相邻的微型磁体，从而提供分析物的分离。

公开(公告)号：US07118923B2

公开(公告)日：2006-10-10

申请号：US10734241

申请日：2003-12-15

申请人： Gil U. Lee ,  Carolyn Yanavich

发明人： Gil U. Lee ,  Carolyn Yanavich

IPC分类号： G01N33/543

CPC分类号： G01N33/537 ,  G01N33/54326 ,  G01N33/54366 ,  G01N33/54393

摘要： A sensor for a selected analyte in a test sample has (a) a semipermeable membrane with pores for retaining the analyte, where the membrane has been chemically modified by attachment of membrane modifiers; (b) immunoassay labels which have label binding ligands where these label binding ligands will have a binding affinity for the membrane modifiers in the presence of the analyte, and a measurably different binding affinity for the membrane modifiers in the absence of the analyte; and (c) a label detecting system, for detecting the presence of the labels on the membrane.

摘要翻译： 用于测试样品中所选分析物的传感器具有（a）具有用于保持分析物的孔的半透膜，其中膜已经通过附着膜修饰剂进行化学改性; （b）具有标记结合配体的免疫测定标记，其中这些标记结合配体将在分析物存在下对膜修饰剂具有结合亲和力，并且在不存在分析物的情况下对膜改性剂具有可测量的不同结合亲和力; 和（c）标签检测系统，用于检测膜上标签的存在。