公开(公告)号：US20190064038A1

公开(公告)日：2019-02-28

申请号：US16121398

申请日：2018-09-04

申请人： Berkeley Lights, Inc.

发明人： Mark P. White ,  Randall D. Lowe, Jr.

IPC分类号： G01N1/34 ,  G01N27/447 ,  B01L3/00 ,  C12Q1/6806 ,  B03C5/02 ,  B03C5/00

摘要： Aspects of the present disclosure are directed to the manipulation of a cell nucleus in a micro-fluidic device as well as compositions, systems, and kits for performing such methods. In some aspects, the disclosure provides methods for placing one or more selected cell nuclei into an isolation region of a sequestration pen in a micro-fluidic device. The isolated nucleus/nuclei may then be retrieved from the isolation region of the sequestration pen and used in any desired downstream assay or process.

公开(公告)号：US20190060907A1

公开(公告)日：2019-02-28

申请号：US16024624

申请日：2018-06-29

申请人： BERKELEY LIGHTS, INC.

发明人： X. Robert BAO ,  Jason M. MCEWEN ,  Brian A. RABKIN

IPC分类号： B01L3/00 ,  G01N35/10

CPC分类号： B01L3/502792 ,  B01L3/502784 ,  B01L2200/0673 ,  B01L2400/0427 ,  B01L2400/0496 ,  G01N35/10 ,  G01N2035/00237 ,  G01N2035/1034

摘要： Systems and methods are described herein for improved droplet generation within microfluidic apparatuses. Electrowetting forces of varying configurations may be used to separate droplets from a fluidic reservoir in a reproducible and rapid manner. In many embodiments, separation of droplets from the fluidic reservoir is performed without the use of highly specialized surfactants.

公开(公告)号：US20180298318A1

公开(公告)日：2018-10-18

申请号：US16010176

申请日：2018-06-15

申请人： Berkeley Lights, Inc.

发明人： Volker L.S. Kurz ,  Troy A. Lionberger ,  Erik K. Sackmann ,  Kai W. Szeto ,  Paul M. Lebel ,  Brandon R. Bruhn ,  Keith J. Breinlinger ,  Eric D. Hobbs ,  Andrew W. McFarland ,  J. Tanner Nevill ,  Xiaohua Wang

IPC分类号： C12M3/06 ,  B01L3/00 ,  C12M1/00 ,  C12M1/26

CPC分类号： C12M23/16 ,  B01L3/502761 ,  B01L2200/0668 ,  B01L2300/1822 ,  B01L2400/0415 ,  B01L2400/0427 ,  B01L2400/0442 ,  B01L2400/0454 ,  B01L2400/086 ,  C12M23/20 ,  C12M33/12

摘要： Apparatuses and methods are described for the use of optically driven bubble, convective and displacing fluidic flow to provide motive force in microfluidic devices. Alternative motive modalities are useful to selectively dislodge and displace micro-objects, including biological cells, from a variety of locations within the enclosure of a microfluidic device.

公开(公告)号：US20180193835A1

公开(公告)日：2018-07-12

申请号：US15912164

申请日：2018-03-05

申请人： Berkeley Lights, Inc.

发明人： Eric D. Hobbs ,  Justin K. Valley

IPC分类号： B01L3/00 ,  B03C5/00 ,  B03C5/02 ,  H01L27/146 ,  H01L29/732

CPC分类号： B01L3/502715 ,  B01L3/502707 ,  B01L3/50273 ,  B01L3/502761 ,  B01L2200/0647 ,  B01L2300/0816 ,  B01L2300/0819 ,  B01L2400/0415 ,  B01L2400/0424 ,  B03C5/005 ,  B03C5/026 ,  H01L27/14681 ,  H01L29/732

摘要： A microfluidic device can include a base an outer surface of which forms one or more enclosures for containing a fluidic medium. The base can include an array of individually controllable transistor structures each of which can comprise both a lateral transistor and a vertical transistor. The transistor structures can be light activated, and the lateral and vertical transistors can thus be photo transistors. Each transistor structure can be activated to create a temporary electrical connection from a region of the outer surface of the base (and thus fluidic medium in the enclosure) to a common electrical conductor. The temporary electrical connection can induce a localized electrokinetic force generally at the region, which can be sufficiently strong to move a nearby micro-object in the enclosure.

公开(公告)号：US10010882B2

公开(公告)日：2018-07-03

申请号：US14520568

申请日：2014-10-22

申请人： Berkeley Lights, Inc.

发明人： Mark P. White ,  Eric D. Hobbs ,  J. Tanner Nevill ,  Daniele Malleo ,  Steven W. Short

IPC分类号： B01L3/00 ,  G01N33/558

CPC分类号： B01L3/502761 ,  B01L2200/0647 ,  B01L2200/0652 ,  B01L2200/0668 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2300/087 ,  B01L2400/0424 ,  B01L2400/0433 ,  B01L2400/0454 ,  G01N33/558 ,  G01N2469/20

摘要： A microfluidic device can comprise at least one swept region that is fluidically connected to unswept regions. The fluidic connections between the swept region and the unswept regions can enable diffusion but substantially no flow of media between the swept region and the unswept regions. The capability of biological micro-objects to produce an analyte of interest can be assayed in such a microfluidic device. Biological micro-objects in sample material loaded into a microfluidic device can be selected for particular characteristics and disposed into unswept regions. The sample material can then be flowed out of the swept region and an assay material flowed into the swept region. Flows of medium in the swept region do not substantially affect the biological micro-objects in the unswept regions, but any analyte of interest produced by a biological micro-object can diffuse from an unswept region into the swept region, where the analyte can react with the assay material to produce a localized detectable reaction. Any such detected reactions can be analyzed to determine which, if any, of the biological micro-objects are producers of the analyte of interest.

公开(公告)号：US09908115B2

公开(公告)日：2018-03-06

申请号：US14961215

申请日：2015-12-07

申请人： Berkeley Lights, Inc.

发明人： Eric D. Hobbs ,  Justin K. Valley

IPC分类号： G01N15/06 ,  B01L3/00 ,  H01L21/00 ,  G01N25/18 ,  B03C5/00 ,  B03C5/02 ,  H01L27/146 ,  H01L29/732

CPC分类号： B01L3/502715 ,  B01L3/502707 ,  B01L3/50273 ,  B01L3/502761 ,  B01L2200/0647 ,  B01L2300/0816 ,  B01L2300/0819 ,  B01L2400/0415 ,  B01L2400/0424 ,  B03C5/005 ,  B03C5/026 ,  H01L27/14681 ,  H01L29/732

摘要： A microfluidic device can include a base an outer surface of which forms one or more enclosures for containing a fluidic medium. The base can include an array of individually controllable transistor structures each of which can comprise both a lateral transistor and a vertical transistor. The transistor structures can be light activated, and the lateral and vertical transistors can thus be photo transistors. Each transistor structure can be activated to create a temporary electrical connection from a region of the outer surface of the base (and thus fluidic medium in the enclosure) to a common electrical conductor. The temporary electrical connection can induce a localized electrokinetic force generally at the region, which can be sufficiently strong to move a nearby micro-object in the enclosure.

公开(公告)号：US20170276679A1

公开(公告)日：2017-09-28

申请号：US15406289

申请日：2017-01-13

申请人： Berkeley Lights, Inc.

发明人： Kevin T. Chapman ,  Mark P. White ,  Xiaohua Wang ,  Minha Park ,  Guido K. Stadler ,  Randall D. Lowe, Jr. ,  Xiao Guan ,  Jason M. McEwen ,  Gang Wang ,  George L. Fox ,  Peggy A. Radel

IPC分类号： G01N33/574 ,  C12Q1/68 ,  G01N33/543 ,  B01L3/00

摘要： A method of preparing an antibody therapeutic is provided comprising: (a) providing a dissociated cell sample from at least one solid tumor sample obtained from a patient; (b) loading the dissociated cell sample into a microfluidic device having a flow region and at least one isolation region fluidically connected to the flow region; (c) moving at least one B cell from the dissociated cell sample into at least one isolation region in the microfluidic device, thereby obtaining at least one isolated B cell; and (d) using the microfluidic device to identify at least one B cell that produces antibodies capable of binding to cancer cells. The cancer cells can be the patient's own cancer cells. Also provided are methods of treating patients, methods of labeling or detecting cancer, engineered T or NK cells comprising antibodies or fragments thereof, and engineered antibody constructs.

公开(公告)号：US20170165667A1

公开(公告)日：2017-06-15

申请号：US15359115

申请日：2016-11-22

申请人： Berkeley Lights, Inc.

发明人： Kristin G. Beaumont ,  Nan-Linda Ding ,  Volker L.S. Kurz ,  Troy A. Lionberger ,  Randall D. Lowe ,  Daniele Malleo ,  Andrew W. McFarland ,  J. Tanner Nevill ,  Xiaohua Wang

IPC分类号： B01L3/00 ,  B01J19/00 ,  G01N27/447

CPC分类号： B01L3/502753 ,  B01J19/0093 ,  B01L3/5023 ,  B01L3/502707 ,  B01L3/502738 ,  B01L3/502761 ,  B01L2200/0668 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2300/16 ,  B01L2400/0424 ,  B01L2400/0677 ,  B01L2400/08 ,  G01N27/44791

摘要： In situ-generated microfluidic isolation structures incorporating a solidified polymer network, methods of preparation and use, compositions and kits therefor are described. The ability to introduce in real time, a variety of isolating structures including pens and barriers offers improved methods of micro-object manipulation in microfluidic devices. The in situ-generated isolation structures may be permanently or temporarily installed.

公开(公告)号：US09617145B2

公开(公告)日：2017-04-11

申请号：US14520510

申请日：2014-10-22

申请人： Berkeley Lights, Inc.

发明人： Keith J. Breinlinger ,  Daniele Malleo ,  Gaetan L. Mathieu ,  J. Tanner Nevill ,  Alexander H. Slocum ,  Mark P. White

IPC分类号： B03C7/02 ,  B81B7/02 ,  B03C5/00 ,  B03C5/02 ,  G01N33/00 ,  G01N27/447 ,  B01L3/00 ,  G01N33/50

CPC分类号： B81B7/02 ,  B01L3/502761 ,  B01L2200/027 ,  B01L2200/0652 ,  B01L2200/0668 ,  B01L2300/044 ,  B01L2300/0636 ,  B01L2300/0645 ,  B01L2300/0816 ,  B01L2300/0819 ,  B01L2300/0829 ,  B01L2300/0851 ,  B01L2300/0864 ,  B01L2300/087 ,  B01L2300/0877 ,  B01L2400/0424 ,  B01L2400/0433 ,  B01L2400/0454 ,  B01L2400/086 ,  B03C5/005 ,  B03C5/026 ,  B03C7/023 ,  B03C2201/26 ,  C12M23/16 ,  C12M41/46 ,  C12M47/02 ,  G01N27/447 ,  G01N27/44756 ,  G01N27/44791 ,  G01N33/5023 ,  G01N33/543 ,  G01N33/54326 ,  G01N35/10

摘要： A group of micro-objects in a holding pen in a micro-fluidic device can be selected and moved to a staging area, from which the micro-objects can be exported from the micro-fluidic device. The micro-fluidic device can have a plurality of holding pens, and each holding pen can isolate micro-objects located in the holding pen from micro-objects located in the other holding pens or elsewhere in the micro-fluidic device. The selected group of micro-objects can comprise one or more biological cells, such as a clonal population of cells. Embodiments of the invention can thus select a particular group of clonal cells in a micro-fluidic device, move the clonal cells to a staging area, and export the clonal cells from the micro-fluidic device while maintaining the clonal nature of the exported group.

公开(公告)号：US09588117B2

公开(公告)日：2017-03-07

申请号：US14583351

申请日：2014-12-26

申请人： Berkeley Lights, Inc.

发明人： Kevin T. Chapman

IPC分类号： G01N33/569 ,  G01N33/68

CPC分类号： G01N33/56972 ,  G01N33/56911 ,  G01N33/56961 ,  G01N33/56966 ,  G01N33/6854 ,  G01N2458/00 ,  G01N2469/10

摘要： In some cases, the described systems and methods include obtaining a cell sample containing multiple antibody-producing cells. In such cases, the cells can be tagged with a cross-linking reagent having a first portion configured to bind to a marker on the antibody-producing cells and a second portion configured to bind to an antigen of interest. In some instances, the tagged antibody-producing cells are exposed to the antigen of interest such that the antigen becomes bound to the cells. In some such instances, the antibody-producing cells are also allowed to produce an antibody, such that a portion of the antibody-producing cells produce an antigen-specific antibody that binds to the antigen of interest. To identify cells that produce the antigen-specific antibody, the tagged cells can be exposed to a labeled secondary antibody that is configured to bind to the antigen-specific antibody. Other implementations are also described.

摘要翻译： 在一些情况下，所描述的系统和方法包括获得含有多个产生抗体的细胞的细胞样品。 在这种情况下，可以用交联试剂对细胞进行标记，所述交联试剂具有构建成结合抗体产生细胞上的标记的第一部分和被配置成与感兴趣的抗原结合的第二部分。 在一些情况下，标记的产生抗体的细胞暴露于感兴趣的抗原，使得抗原与细胞结合。 在一些这样的情况下，也允许产生抗体的细胞产生抗体，使得产生一部分抗体的细胞产生与感兴趣的抗原结合的抗原特异性抗体。 为了鉴定产生抗原特异性抗体的细胞，标记的细胞可以暴露于被配置为结合抗原特异性抗体的标记的二抗。 还描述了其他实现。