公开(公告)号：WO2011046615A2

公开(公告)日：2011-04-21

申请号：PCT/US2010/002756

申请日：2010-10-15

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  VAN DAM, R. Michael ,  KIM, Chang-Jin ,  CHEN, Supin ,  DING, Huijiang ,  SHAH, Gaurav, Jitendra ,  KENG, Pei, Yuin

Inventor： VAN DAM, R. Michael ,  KIM, Chang-Jin ,  CHEN, Supin ,  DING, Huijiang ,  SHAH, Gaurav, Jitendra ,  KENG, Pei, Yuin

IPC: B01J19/00 ,  B01L3/00 ,  B81B1/00

CPC classification number: C07B39/00 ,  B01J19/0093 ,  B01J2219/00783 ,  B01J2219/00853 ,  B01J2219/00873 ,  B01L3/502784 ,  B01L2300/1827 ,  B01L2400/0427 ,  B01L2400/0487 ,  C07B59/001 ,  C07B59/002 ,  C07B59/005 ,  C07B2200/05 ,  C07C201/12 ,  C07C227/16 ,  C07D473/18 ,  C07H1/00

Abstract: Disclosed herein are methods of performing microchemical reactions and electro- wetting-on-dielectric devices (EWOD devices) for use in performing those reactions. These devices and method are particularly suited for preparing radiochemical compounds, particularly compounds containing 18 F.

Abstract translation: 本文公开了用于执行这些反应的微量化学反应和电润湿介电装置（EWOD装置）的方法。 这些装置和方法特别适用于制备放射化学化合物，特别是含有18F的化合物。

公开(公告)号：WO2009092106A1

公开(公告)日：2009-07-23

申请号：PCT/US2009/031582

申请日：2009-01-21

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  VAN DAM, R. Michael ,  LIU, Kan ,  SHEN, Kwang-fu Clifton ,  TSENG, Hsian-rong

Inventor： VAN DAM, R. Michael ,  LIU, Kan ,  SHEN, Kwang-fu Clifton ,  TSENG, Hsian-rong

IPC: B01F5/06

CPC classification number: B01F13/0071 ,  B01F15/0462 ,  Y10T137/8593

Abstract: The invention may provide a microfluidic mixer having a droplet generator and a droplet mixer in selective fluid connection with the droplet generator. The droplet generator comprises first and second fluid chambers that are structured to be filled with respective first and second fluids that can each be held in isolation for a selectable period of time. The first and second fluid chambers are further structured to be reconfigured into a single combined chamber to allow the first and second fluids in the first and second fluid chambers to come into fluid contact with each other in the combined chamber for a selectable period of time prior to being brought into the droplet mixer.

Abstract translation: 本发明可以提供具有液滴发生器和与液滴发生器选择性流体连接的液滴混合器的微流体混合器。 液滴发生器包括第一和第二流体室，其被构造成填充相应的第一和第二流体，每个第一和第二流体可以隔离地保持一段可选择的时间段。 第一和第二流体室进一步构造成重新配置成单个组合室，以允许第一和第二流体室中的第一和第二流体在组合腔室中彼此流体接触，以在可选择的时间段内 被带入液滴混合器。

公开(公告)号：WO2018093794A2

公开(公告)日：2018-05-24

申请号：PCT/US2017/061611

申请日：2017-11-14

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： VAN DAM, R. Michael ,  HA, Noel Seunghyun ,  JONES, Jason ,  LY, Jimmy ,  LIU, Stephen ,  CHEUNG, Shilin

Abstract: A microfluidic chip device for the purification of radiochemical compounds includes a chip having an injection channel and intersecting branch channels with a plurality of valves are located along the injection channel and branch channels and configured to retain a plug of solution containing the radiochemical compound. The chip further includes a serpentine channel segment (for separation) coupled to the output of the injection channel. A high voltage power source advances the plug of solution through the purification region and into the downstream fraction collection channel. The chip includes a downstream fraction collection channel coupled to the serpentine channel segment and having an optical and radiation detection regions. One or more branch fraction channels intersect with the fraction collection channel and include valves located therein so that the radiochemical compound that is detected using a radiation detector is directed into the desired branch fraction channel for subsequent use.

公开(公告)号：WO2018067965A1

公开(公告)日：2018-04-12

申请号：PCT/US2017/055585

申请日：2017-10-06

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： WANG, Jia ,  VAN DAM, R. Michael

IPC: B01L3/00 ,  B01F5/04 ,  B01F15/02

Abstract: A microfluidic synthesis platform includes a microfluidic chip holder that has a computer controlled heating element and cooling element therein. A microfluidic chip is mountable in the microfluidic chip holder. The microfluidic chip is formed by a hydrophobic substrate having patterned thereon a hydrophilic reactionxxxxxxx site and a plurality of hydrophilic channels or pathways extending outward from the hydrophilic reaction site and terminating at respective loading sites on the substrate, wherein the hydrophilic channels or pathways are tapered with an increasing width in an inward direction toward the hydrophilic reaction site. A fixture is provided for holding a plurality of non-contact reagent dispensing devices above the microfluidic chip at locations corresponding to the loading sites of the plurality of hydrophilic channels or pathways, the fixture further holding a moveable collection tube disposed above the hydrophilic reaction site of the microfluidic chip for removing droplets containing reaction products.

Abstract translation: 微流体合成平台包括其中具有计算机控制的加热元件和冷却元件的微流体芯片保持器。 微流体芯片可安装在微流体芯片固定器中。 微流体芯片由其上图案化有亲水性反应xxxxxxxx位点和多个亲水性通道或路径的疏水性基底形成，所述亲水性通道或路径从亲水性反应位点向外延伸并终止于基底上各自的加载位点，其中亲水性通道或路径与 在朝向亲水性反应部位的向内方向上增加宽度。 提供用于将多个非接触试剂分配装置保持在微流体芯片上方对应于多个亲水通道或通路的加载位置的位置处的固定装置，固定装置还保持设置在微流体芯片的亲水性反应位点上方的可移动收集管 用于去除含有反应产物的液滴的微流控芯片。

公开(公告)号：WO2015188165A1

公开(公告)日：2015-12-10

申请号：PCT/US2015/034583

申请日：2015-06-05

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  SOFIE BIOSCIENCES, INC.

Inventor： VAN DAM, R. Michael ,  MOORE, Melissa ,  MARAGLIA, Brandon ,  THOMPSON, Daniel

IPC: A61B6/03 ,  A61B6/00

CPC classification number: G01N33/60 ,  A61B6/037 ,  A61B6/48 ,  A61B6/542 ,  C07B59/00 ,  G21F5/015 ,  G21G1/0005 ,  G21H5/02

Abstract: A self-shielded, bench-top radiochemistry system, including a radioactive isotope dispensing module configured to draw an isotope out of a vial and dispense one or more metered doses of the isotope to a concentration module that concentrates the metered dose into a droplet amount of isotope and a synthesizer module that delivers the droplet amount of isotope along with one or more reagents to an electrowetting on dielectrics (EWOD) chip to produce a radiolabeled molecule.

Abstract translation: 一种自我屏蔽的台式放射化学系统，包括放射性同位素分配模块，其配置为将同位素从小瓶中抽出并将一个或多个计量剂量的同位素分配到浓缩模块，浓缩模块将计量剂量浓缩成液滴量 同位素和合成器模块，其将液滴量的同位素与一种或多种试剂一起递送到电介质（EWOD）芯片上的电润湿以产生放射性标记的分子。

公开(公告)号：WO2018093794A3

公开(公告)日：2018-05-24

申请号：PCT/US2017/061611

申请日：2017-11-14

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： VAN DAM, R. Michael ,  HA, Noel Seunghyun ,  JONES, Jason ,  LY, Jimmy ,  LIU, Stephen ,  CHEUNG, Shilin

IPC: B01J19/00 ,  B01J8/00 ,  G21C1/00 ,  C07B59/00

Abstract: A microfluidic chip device for the purification of radiochemical compounds includes a chip having an injection channel and intersecting branch channels with a plurality of valves are located along the injection channel and branch channels and configured to retain a plug of solution containing the radiochemical compound. The chip further includes a serpentine channel segment (for separation) coupled to the output of the injection channel. A high voltage power source advances the plug of solution through the purification region and into the downstream fraction collection channel. The chip includes a downstream fraction collection channel coupled to the serpentine channel segment and having an optical and radiation detection regions. One or more branch fraction channels intersect with the fraction collection channel and include valves located therein so that the radiochemical compound that is detected using a radiation detector is directed into the desired branch fraction channel for subsequent use.

公开(公告)号：WO2018067976A1

公开(公告)日：2018-04-12

申请号：PCT/US2017/055607

申请日：2017-10-06

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： HA, Noel Seunghyun ,  VAN DAM, R. Michael ,  LY, Jimmy

IPC: B01L3/00 ,  G01N27/447 ,  G01N27/453

Abstract: A volumetric microfluidic injector for capillary electrophoresis(CE) for highly repeatable sample injection has been designed and built to eliminate known injection bias in hydrodynamic injection. A defined volume from 1-10 nL or 0.1-100 nL of sample is confined in a defined region of a micro-valve PDMS microfluidic injector chip and electrophoretic potential is applied to drive sample into a separation device such as an embedded fused silica capillary for separation and detection. Using a 75 μm ID capillary, the RSD of an absorbance peak area as low as 1.32% (n=11) is obtained. As a comparison, the time-dependent injection was tested using the same chip which resulted in an inferior repeatability.

Abstract translation: 用于高度重复性样品注入的毛细管电泳（CE）的体积微流体注射器已被设计和构建，以消除流体动力学注射中已知的注射偏差。 将1-10nL或0.1-100nL样品的限定体积限定在微阀PDMS微流体注射器芯片的限定区域中，并且施加电泳电势以将样品驱入分离装置，例如嵌入的熔融石英毛细管用于 分离和检测。 使用75μmID毛细管，获得吸光度峰面积低至1.32％（n = 11）的RSD。 作为比较，使用相同的芯片对时间依赖性注射进行了测试，结果导致重复性较差。

公开(公告)号：WO2018048873A2

公开(公告)日：2018-03-15

申请号：PCT/US2017/050236

申请日：2017-09-06

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： CHAO, Philip Hong-Sean ,  VAN DAM, R. Michael

IPC: A61K51/04 ,  A61M1/00

CPC classification number: A61K51/02 ,  A61B6/037 ,  A61K51/0446 ,  A61K51/0459 ,  A61K51/0491 ,  B01L3/502753 ,  B01L2300/0681 ,  B01L2300/0883 ,  B01L2300/12 ,  C07B59/00

Abstract: A method of formulating or concentrating a radiolabeled molecule or compound includes providing a microfluidic device having a sample layer containing a microfluidic channel formed therein, a porous membrane having a pore size of less than 0.5 µm disposed on the sample layer and covering the microfluidic channel, and a gas flow layer having a gas-carrying channel formed therein, wherein the porous membrane is interposed between the sample layer and the gas flow layer. A fluid containing the radiolabeled molecule or compound is delivered into the microfluidic channel. Heat is applied to evaporate the fluid. A gas is passed through gas-carrying channel to remove evaporated fluid from the microfluidic device.

Abstract translation: 配制或浓缩放射性标记的分子或化合物的方法包括提供微流体装置，所述微流体装置具有其中形成有微流体通道的样品层，孔径小于0.5μm的多孔膜 在样品层上并覆盖微流体通道，以及在其中形成有气体携带通道的气流层，其中多孔膜置于样品层和气流层之间。 含有放射性标记的分子或化合物的液体被输送到微流体通道中。 施加热量以蒸发流体。 气体通过载气通道从微流体装置中除去蒸发的流体。

公开(公告)号：WO2018048856A1

公开(公告)日：2018-03-15

申请号：PCT/US2017/050214

申请日：2017-09-06

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： HA, Noel S. ,  VAN DAM, R. Michael

IPC: A61K38/16 ,  A61K51/00 ,  A61K51/04 ,  A61K51/08 ,  A61K51/10 ,  C07C317/08

CPC classification number: A61K51/082 ,  A61K38/00 ,  A61K51/088 ,  C07B59/008 ,  C07K1/13

Abstract: A method of radiolabeling a biomolecule using a microfluidic device includes loading one or more droplets containing a 18F-labeled prosthetic group on or into the microfluidic device and evaporating the droplet(s) containing the 18F-labeled prosthetic group. One or more droplets containing the biomolecule are loaded on or into the microfluidic device and reacts with the 18F-labeled prosthetic group that remains after evaporation. The reaction product is then collected from the microfluidic device. In another embodiment, a droplet containing radiometal ions or a radiometal complex is loaded in the microfluidic device, evaporated, and reacted with a droplet containing a biomolecule derivatized with a chelating group. In yet another embodiment, a droplet containing an 18F- labeled salt is loaded onto the microfluidic device, evaporated, and reacted with a droplet containing a biomolecule conjugated with an isotopic exchange labeling site.

Abstract translation: 使用微流体装置放射性标记生物分子的方法包括将一个或多个含有18 F标记的辅基的液滴装载到微流体装置上或微流体装置中，并蒸发含有18 F标记的假体的微滴 组。 含有生物分子的一个或多个液滴装载在微流体装置上或微流体装置中，并与蒸发后残留的18 F-标记的假体基团反应。 然后从微流体装置收集反应产物。 在另一个实施方案中，将包含放射性金属离子或放射性金属络合物的液滴加载在微流体装置中，蒸发，并与含有用螯合基团衍生的生物分子的液滴反应。 在又一个实施方案中，将含有18 F-标记的盐的液滴加载到微流体装置上，蒸发，并与含有与同位素交换标记位点缀合的生物分子的液滴反应。