公开(公告)号：US20200306413A1

公开(公告)日：2020-10-01

申请号：US16077985

申请日：2017-02-14

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Dino Di Carlo ,  Westbrook Weaver ,  Tatiana Segura ,  Jaekyung Koh ,  Philip Scumpia ,  Donald R. Griffin

IPC: A61L27/52 ,  A61K39/39 ,  A61L27/54 ,  A61L27/56

Abstract: A hydrogel material for modulating an immune response in a human subject or other mammal includes a collection of microgel particles having one or more network cross linker components, wherein the microgel particles, when exposed to an endogenous or exogenous annealing agent, links the microgel particles together in situ to form a covalently-stabilized scaffold of microgel particles having interstitial spaces formed between the microgel particles and wherein the collection of microgel particles further includes at least one of an antigen and an adjuvant.

公开(公告)号：US10407709B2

公开(公告)日：2019-09-10

申请号：US14819302

申请日：2015-08-05

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Dino Di Carlo ,  Soojung C. Hur ,  Albert J. Mach

IPC: C12Q1/24 ,  G01N1/40 ,  B01L3/00 ,  C12M1/00 ,  C12M3/06 ,  G01N33/58 ,  G01N33/50 ,  C12Q1/68

Abstract: A method of isolating cells includes providing a microfluidic device having at least one microfluidic channel coupled to an inlet and an outlet, the at least one microfluidic channel comprises at least one expansion region disposed along the length thereof. The at least one expansion region is an abrupt increase in a cross-sectional dimension of the at least one microfluidic channel configured to generate a vortex within the at least one expansion region in response to fluid flow. A solution containing a population of cells at least some of which have diameters ≥10 μm flows into the inlet. A portion of cells is trapped within vortex created within the at least one expansion region. The trapped cells may then released from the expansion region.

公开(公告)号：US10295455B2

公开(公告)日：2019-05-21

申请号：US15471851

申请日：2017-03-28

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Dino Di Carlo ,  Daniel R. Gossett ,  Henry T. K. Tse ,  Aram Chung

IPC: G01N15/14 ,  G01N33/50 ,  G01N21/64 ,  G06K9/46 ,  G06T7/00 ,  G01N15/00 ,  G01N15/10

Abstract: A system for deforming and analyzing a plurality of particles carried in a sample volume includes a substrate defining an inlet, configured to receive the sample volume, and an outlet; and a fluidic pathway fluidly coupled to the inlet and the outlet. The fluidic pathway includes a delivery region configured to receive the plurality of particles from the inlet and focus the plurality of particles from a random distribution to a focused state, a deformation region defining an intersection located downstream of the delivery region and coupled to the outlet, and wherein the deformation region is configured to receive the plurality of particles from the delivery region and to transmit each particle in the plurality of particles into the intersection from a single direction, a first branch fluidly coupled to the deformation region and configured to transmit a first flow into the intersection, and a second branch fluidly coupled to the deformation region and configured to transmit a second flow, substantially opposing the first flow, into the intersection, wherein the first flow and the second flow are configured to induce extension of one or more particles in the plurality of particles.

公开(公告)号：US20180356396A1

公开(公告)日：2018-12-13

申请号：US16105627

申请日：2018-08-20

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Dino Di Carlo ,  Peter Tseng ,  Ivan Pushkarsky

IPC: G01N33/50 ,  G01N33/487 ,  B01L3/00 ,  G01N33/58

CPC classification number: G01N33/5026 ,  B01L3/5085 ,  B01L2300/0654 ,  B01L2300/0829 ,  B01L2300/168 ,  G01L1/247 ,  G01N21/6458 ,  G01N33/487 ,  G01N33/582 ,  G01N2021/6419 ,  G01N2021/6441

Abstract: A system for assaying forces applied by cells includes an optically transparent substrate comprising a soft material having a Young's modulus within the range of about 3 kPa to about 100 kPa. An array of molecular patterns is disposed on a surface of the optically transparent substrate, the molecular patterns include fluorophore-conjugated patterns adherent to cells. The system includes at least one light source configured to excite the fluorophore-conjugated patterns and an imaging device configured to capture fluorescent light emitted from the fluorophore-conjugated patterns. Dimensional changes in the size of the patterns are used to determine contractile forces imparted by cells located on the patterns.

公开(公告)号：US10144911B2

公开(公告)日：2018-12-04

申请号：US15536122

申请日：2015-12-15

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Dino Di Carlo ,  Coleman Murray ,  Edward Pao ,  Peter Tseng

IPC: B03C1/00 ,  C12M1/00 ,  B03C1/03 ,  G01N15/06 ,  B03C1/033 ,  B03C1/247 ,  B03C1/253 ,  B03C1/28 ,  G01N35/00 ,  G01N15/00

Abstract: A system is provided for the quantitative magnetic separation of magnetic objects (e.g., particles or cells). The system uses magnetic ratcheting over arrays of ferromagnetic elements having gradient spacing manifested in various pitch zones that are encountered by the magnetic objects as they traverse the array. The system can be used to separate and concentrate magnetic objects based on iron oxide content. For cells, different phenotypes may be separated based, for example, on surface expression of proteins or molecules that are bound to magnetic particles. The system includes a substrate or chip having the array of ferromagnetic elements with increasing lateral pitch and an externally driven magnet device that generates a cycling magnetic field. Magnetic objects with higher IOC separate and equilibrate along the array at larger pitches. The system can be used for the differential sorting of particles and cells of interest.

公开(公告)号：US10082497B2

公开(公告)日：2018-09-25

申请号：US15300021

申请日：2015-03-27

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Dino Di Carlo ,  Peter Tseng ,  Ivan Pushkarsky

IPC: G01J3/30 ,  G01N33/50 ,  G01N33/487 ,  B01L3/00 ,  G01N21/64

CPC classification number: G01N33/5026 ,  B01L3/5085 ,  B01L2300/0654 ,  B01L2300/0829 ,  B01L2300/168 ,  G01L1/247 ,  G01N21/6458 ,  G01N33/487 ,  G01N33/582 ,  G01N2021/6419 ,  G01N2021/6441

Abstract: A system for assaying forces applied by cells includes an optically transparent substrate comprising a soft material having a Young's modulus within the range of about 3 kPa to about 100 kPa. An array of molecular patterns is disposed on a surface of the optically transparent substrate, the molecular patterns include fluorophore-conjugated patterns adherent to cells. The system includes at least one light source configured to excite the fluorophore-conjugated patterns and an imaging device configured to capture fluorescent light emitted from the fluorophore-conjugated patterns. Dimensional changes in the size of the patterns are used to determine contractile forces imparted by cells located on the patterns.

公开(公告)号：US20180078671A1

公开(公告)日：2018-03-22

申请号：US15829440

申请日：2017-12-01

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Donald R. Griffin ,  Westbrook Weaver ,  Tatiana Segura ,  Dino Di Carlo ,  Philip Scumpia

IPC: A61L26/00 ,  A61L27/54 ,  A61L27/22 ,  A61L27/56 ,  A61L27/52

CPC classification number: A61L26/008 ,  A61L26/0019 ,  A61L26/0047 ,  A61L26/0066 ,  A61L26/0085 ,  A61L26/009 ,  A61L27/18 ,  A61L27/227 ,  A61L27/52 ,  A61L27/54 ,  A61L27/56 ,  A61L27/58 ,  A61L2300/252 ,  A61L2300/412 ,  A61L2400/06 ,  A61L2430/00 ,  A61L2430/34 ,  C08L71/02

Abstract: A microporous gel system for certain applications, including biomedical applications, includes an aqueous solution containing plurality of microgel particles including a biodegradable crosslinker. In some aspects, the microgel particles act as gel building blocks that anneal to one another to form a covalently-stabilized scaffold of microgel particles having interstitial spaces therein. In certain aspects, annealing of the microgel particles occurs after exposure to an annealing agent that is endogenously present or exogenously added. In some embodiments, annealing of the microgel particles requires the presence of an initiator such as exposure to light. In particular embodiments, the chemical and physical properties of the gel building blocks can be controlled to allow downstream control of the resulting assembled scaffold. In one or more embodiments, cells are able to quickly infiltrate the interstitial spaces of the assembled scaffold.

公开(公告)号：US20170362563A1

公开(公告)日：2017-12-21

申请号：US15536122

申请日：2015-12-15

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Dino Di Carlo ,  Coleman Murray ,  Edward Pao ,  Peter Tseng

IPC: C12M1/00 ,  B03C1/247 ,  G01N15/06 ,  B03C1/03 ,  B03C1/28 ,  B03C1/253 ,  B03C1/033 ,  G01N35/00 ,  G01N15/00

CPC classification number: C12M47/04 ,  B03C1/03 ,  B03C1/0332 ,  B03C1/247 ,  B03C1/253 ,  B03C1/288 ,  B03C2201/18 ,  B03C2201/26 ,  G01N15/0656 ,  G01N35/0098 ,  G01N2015/0053

Abstract: A system is provided for the quantitative magnetic separation of magnetic objects (e.g., particles or cells). The system uses magnetic ratcheting over arrays of ferromagnetic elements having gradient spacing manifested in various pitch zones that are encountered by the magnetic objects as they traverse the array. The system can be used to separate and concentrate magnetic objects based on iron oxide content. For cells, different phenotypes may be separated based, for example, on surface expression of proteins or molecules that are bound to magnetic particles. The system includes a substrate or chip having the array of ferromagnetic elements with increasing lateral pitch and an externally driven magnet device that generates a cycling magnetic field. Magnetic objects with higher IOC separate and equilibrate along the array at larger pitches. The system can be used for the differential sorting of particles and cells of interest.

公开(公告)号：US09815060B2

公开(公告)日：2017-11-14

申请号：US15346442

申请日：2016-11-08

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Dino Di Carlo ,  Daniel R. Gossett ,  Henry T. K. Tse

IPC: B01L3/00 ,  B01D12/00 ,  G01N15/14

CPC classification number: B01L3/502776 ,  B01D12/00 ,  B01L3/502746 ,  B01L3/502761 ,  B01L2200/0652 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2400/0487 ,  B01L2400/084 ,  G01N2015/149

Abstract: A method of exchanging fluids with suspended particles includes providing a microfluidic device with a first inlet channel operatively coupled to a source of particles and a second inlet channel operatively coupled to an exchange fluid. A transfer channel is connected at a proximal end to the first inlet channel and the second inlet channel. First and second outlet channels are connected to a distal end of the transfer channel. The source of particles is flowed at a first flow rate into the first inlet channel while the exchange fluid is flowed at a second flow rate into the second inlet channel wherein the ratio of the second flow rate to the first flow rate is at least 1.5. Particles are collected in one of the first and second outlet channels while fluid substantially free of particles is collected in the other of the first and second outlet channels.

公开(公告)号：US20160257990A1

公开(公告)日：2016-09-08

申请号：US15029231

申请日：2014-10-17

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Dino Di Carlo ,  Janay Kong

IPC: C12Q1/68

CPC classification number: C12Q1/6804 ,  C12Q1/6844 ,  C12Q2563/159 ,  C12Q2563/173

Abstract: A method of detecting a target and quantifying the concentration of the same within a sample includes generating a plurality of fractionated volumes, wherein at least some of the fractionated volumes contain the target bound to a first detector molecule connected to a first reaction component (R1) and a second detector molecule connected to a second reaction component (R2). The fractionated volumes that contain the target, first detector molecule, second detector molecule, and a probe or other reporter molecule emit light and are imaged. Fractionated volumes emitting radiation can be used to detect the presence of the target within the sample. The number of fractionated volumes emitting a positive emission signal can be counted from the image and the concentration (or range of calculations) of the target can be calculated based at least in part on the number of fractionated volumes emitting a positive emission signal from the image.

Abstract translation: 检测靶标并在样品中定量其浓度的方法包括产生多个分馏体积，其中至少部分分馏体积包含与连接到第一反应组分（R1）的第一检测分子结合的靶标， 和连接到第二反应组分（R2）的第二检测器分子。 包含目标，第一检测器分子，第二检测器分子和探针或其他报告分子的分级体积发光并成像。 可以使用发射辐射的分级体积来检测样品中目标物的存在。 可以从图像中计数发射正发射信号的分级体积的数量，并且可以至少部分地基于从图像发射正发射信号的分级体积的数量来计算目标的浓度（或计算范围） 。