公开(公告)号：US11450121B2

公开(公告)日：2022-09-20

申请号：US16019421

申请日：2018-06-26

Applicant: The Regents of the University of California

Inventor： Dino Di Carlo ,  Aydogan Ozcan ,  Omai B. Garner ,  Hector E. Munoz ,  Carson Riche

IPC: G06V20/69 ,  G06T7/00 ,  G16B40/10 ,  G06V10/46 ,  C12Q1/6844

Abstract: An optical readout method for detecting a precipitate (e.g., a precipitate generated from the LAMP reaction) contained within a droplet includes generating a plurality of droplets, at least some which have a precipitate contained therein. The droplets are imaged using a brightfield imaging device. The image is subject to image processing using image processing software executed on a computing device. Image processing isolates individual droplets in the image and performs feature detection within the isolated droplets. Keypoints and information related thereto are extracted from the detected features within the isolated droplets. The keypoints are subject to a clustering operation to generate a plurality of visual “words.” The word frequency obtained for each droplet is input into a trained machine learning droplet classifier, wherein the trained machine learning droplet classifier classifies each droplet as positive for the precipitate or negative for the precipitate.

公开(公告)号：US11347000B2

公开(公告)日：2022-05-31

申请号：US15737743

申请日：2016-06-17

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Aydogan Ozcan ,  Brandon Berg ,  Bingen Cortazar ,  Derek Tseng ,  Steve Wei Feng ,  Haydar Ozkan ,  Omai Garner ,  Dino Di Carlo

IPC: G02B6/06 ,  G06N20/00 ,  H04N5/225 ,  G01N21/25 ,  G01N33/53 ,  G01N35/00

Abstract: A micro-plate reader for use with a portable electronic device having a camera includes an opto-mechanical attachment configured to attach/detach to the portable electronic device and includes an array of illumination sources. A slot in the opto-mechanical attachment is dimensioned to receive an optically transparent plate containing an array of wells. Optical fibers are located in the opto-mechanical attachment and transmit light from each well to a reduced size header having, wherein the fiber array in the header has a cross-sectional area that is ≤10× the cross-sectional area of the wells in the plate. A lens located in the opto-mechanical attachment transmits light from the header fibers to the camera. Software executed on the portable electronic device or other computer is used to process the images to generate qualitative clinical determinations and/or quantitative index values for the separate wells.

公开(公告)号：US20220026340A1

公开(公告)日：2022-01-27

申请号：US17496758

申请日：2021-10-07

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

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

IPC: G01N15/14 ,  G16B99/00 ,  G01N33/574 ,  C12Q1/02 ,  B01L3/00 ,  G01N33/487

Abstract: A system is disclosed that enables the automated measurement of cellular mechanical parameters at high throughputs. The microfluidic device uses intersecting flows to create an extensional flow region where the cells undergo controlled stretching. Cells are focused into streamlines prior to entering the extensional flow region. In the extensional region, each cell's deformation is measured with an imaging device. Automated image analysis extracts a range of independent biomechanical parameters from the images. These may include cell size, deformability, and circularity. The single cell data that is obtained may then be used to in a variety of ways. Scatter density plots of deformability and circularity may be developed and displayed for the user. Mechanical parameters such as deformability and circularity may be gated or thresholded to identify certain cells of interest or sub-populations of interest. Similarly, the mechanical data obtained using the device may be used as cell signatures.

公开(公告)号：US20210341376A1

公开(公告)日：2021-11-04

申请号：US17200728

申请日：2021-03-12

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

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：US20210138105A1

公开(公告)日：2021-05-13

申请号：US17144158

申请日：2021-01-08

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

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

IPC: A61L26/00 ,  A61L27/18 ,  A61L27/58 ,  A61K47/62 ,  A61K9/06 ,  A61K31/795 ,  A61L27/22 ,  A61L27/52 ,  A61L27/54 ,  A61L27/56

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：US10967296B2

公开(公告)日：2021-04-06

申请号：US16676352

申请日：2019-11-06

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

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

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

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：US10912860B2

公开(公告)日：2021-02-09

申请号：US15701113

申请日：2017-09-11

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

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

IPC: A61L26/00 ,  A61L27/18 ,  A61L27/58 ,  A61K47/62 ,  A61K9/06 ,  A61K31/795 ,  A61L27/22 ,  A61L27/52 ,  A61L27/54 ,  A61L27/56

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：US20200305773A1

公开(公告)日：2020-10-01

申请号：US16071252

申请日：2017-01-20

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Dino Di Carlo ,  Westbrook Weaver ,  Donald Griffin ,  Jaekyung Koh

IPC: A61B5/145 ,  A61B5/1473 ,  A61B5/00 ,  A61B5/1459 ,  A61B5/1455

Abstract: A biocompatible analyte sensing material for intradermal or subcutaneous application includes a collection of microgel particles having one or more network crosslinker components and an endogenous or exogenous annealing agent that links the microgel particles together in situ to form a covalently-stabilized scaffold of microgel particles having interstitial spaces therein. A plurality of analyte-specific fluorophores are conjugated to the microgel particles, wherein the analyte-specific fluorophores, in the presence of the analyte and subject to excitation radiation, emit fluorescent light. The analyte sensing material may, in some embodiments, be applied to an excision made in the skin or injected into the skin of a subject.

公开(公告)号：US20200085859A1

公开(公告)日：2020-03-19

申请号：US16596312

申请日：2019-10-08

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

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

IPC: A61K31/795 ,  A61K9/06 ,  A61K47/62

Abstract: Disclosed herein are therapeutic polymer gel systems for promoting healing of a wound or surgical site in a subject. The therapeutic polymer gel forms a microporous network and may be applied or injected in a fluid form and annealed or crosslinked after application to the wound or surgical site. The microporous gel may optionally contain various therapeutic agents throughout the therapeutic polymer gel which are released.

公开(公告)号：US10473644B2

公开(公告)日：2019-11-12

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: G01N21/00 ,  G01N33/50 ,  G01N33/58 ,  G01N21/64 ,  G01L1/24 ,  B01L3/00 ,  G01N33/487

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.