公开(公告)号：US11820863B2

公开(公告)日：2023-11-21

申请号：US16303769

申请日：2017-05-26

Applicant: SPHERE FLUIDICS LIMITED

Inventor： Xin Li ,  Clive A. Smith ,  Alexandra Clay ,  Frank F. Craig

IPC: C08G65/332 ,  C08G65/00 ,  C08G65/333 ,  C08G65/334 ,  C12Q1/6806 ,  C09K23/00

CPC classification number: C08G65/3322 ,  C08G65/007 ,  C08G65/3348 ,  C08G65/33344 ,  C08G65/33396 ,  C09K23/007 ,  C12Q1/6806

Abstract: The present invention provides a surfactant having a formula selected from the group consisting of: B—((X)x—(CH2)a-A)n(VI), (A-(CH2)a—(X)x—B—(X)x—(CH2)a-A)n (IV), (A-(CH2)a—(X)x—B)n (V), and (B)n—(X)x—(CH2)a-A (VII), wherein A is a perfluoropolyether; a is a positive integer; X is either a covalent bond or a linking group; x is a positive integer; B is a polyalkylene oxide unit; n is a positive integer greater than 1 and, in compounds comprising more than one A, B, X, a and x, each may be the same or different. The present invention also relates to methods of making such surfactants, uses of such surfactants and emulsions comprising such surfactants.

公开(公告)号：US12190572B2

公开(公告)日：2025-01-07

申请号：US17266447

申请日：2019-08-06

Applicant: Sphere Fluidics Limited

Inventor： Nicholas Dayrell-Armes ,  David Holmes ,  Frank F Craig ,  Marian Rehak ,  Dimitris Josephides ,  Robert Salter ,  William Whitley ,  Sinan Gokkaya ,  Raphael Ruis

IPC: G06V10/82 ,  B01L3/00 ,  G01N15/14 ,  G01N15/1433 ,  G06F18/2431 ,  G06T7/70 ,  G06V10/44 ,  G06V10/764 ,  G06V20/69 ,  G01N15/10

Abstract: A method of processing droplets in a microfluidic system. The method may comprise capturing a time sequence of images of a droplet as it passes through a channel in a microfluidic system. The method may further comprise processing each image of the sequence of images using a convolutional neural network to count a number of cells or other entities visible in each image the droplet. The method may further comprise processing the count of the number of cells or other entities visible in each image of the droplet to determine an estimated number of cells or other entities in the droplet. The method/system may further comprise controlling a microfluidic process performed on the droplet responsive to the estimated number of cells or other entities in the droplet. Implementations of the method use the changing orientation and disposition of droplet contents in combination with machine learning to improve monoclonality assurance.

公开(公告)号：US20230193137A1

公开(公告)日：2023-06-22

申请号：US17922283

申请日：2021-05-04

Applicant: Sphere Fluidics Limited

Inventor： Xin LI ,  Clive Smith ,  Ben Mackworth

IPC: C09K23/42

CPC classification number: C09K23/42

Abstract: The present invention provides a surfactant of formula (I): (A)m-X-(B)n (I) wherein X is a linking group; each A is N independently a fluorocarbon or a perfluoropolyether; each B is independently (II) wherein a is an integer between 3 and 50 and each R is independently C1-6 alkyl, CH2CH2OC1-6 alkyl or CH2CH(CH3)OC1-6 alkyl; m is an integer between 1 and 10; and n is an integer between 1 and 10.

公开(公告)号：US11656167B2

公开(公告)日：2023-05-23

申请号：US16716369

申请日：2019-12-16

Applicant: Sphere Fluidics Limited

Inventor： Clive Adrian Smith ,  Xin Li ,  Frank F. Craig

IPC: G01N15/10 ,  B01L3/00 ,  G01N15/14 ,  H01J49/00 ,  H01J49/04

CPC classification number: G01N15/1031 ,  B01L3/50273 ,  B01L3/502715 ,  B01L3/502784 ,  G01N15/1056 ,  G01N15/1404 ,  B01L2200/0652 ,  B01L2300/0627 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2400/0424 ,  B01L2400/0427 ,  B01L2400/084 ,  G01N2015/1081 ,  G01N2015/149 ,  G01N2015/1486 ,  H01J49/0031 ,  H01J49/04

Abstract: A method for aligning sequences of droplets in streams of an emulsion comprising target droplets and tag droplets, a tag droplet comprising first and second tags. A target droplet is split into first and second target droplets and a tag droplet is split into first and second tag droplets. Each of the first and second tag droplets comprise the first and second tags. The first target droplet and first tag droplet are in a first stream of droplets, and the second target droplet and second tag droplet are in a second stream of droplets. The method detects the first tag droplets and first target droplets in the first stream and the second tag droplets and second target droplets in the second stream, determines a first sequence of droplets in the first stream and a second sequence of droplets in the second stream, and compares these to align the sequences.

公开(公告)号：US11077441B2

公开(公告)日：2021-08-03

申请号：US15578455

申请日：2016-06-03

Applicant: SPHERE FLUIDICS LIMITED

Inventor： Frank F. Craig ,  Marian Rehak ,  David Holmes ,  Clive A. Smith ,  Xin Liu ,  Giuseppe Benazzi ,  Xin Li ,  Vinayaka Pawate ,  Robert Frank Marchington ,  Richard Francis Day ,  Michael Stuart Hazell

IPC: B01L3/00 ,  G01N35/08 ,  G01N15/14 ,  C12M1/00

Abstract: Instruments and cartridges for processing droplets in emulsions containing biological entities such as cells. A method of such processing comprises providing a plurality of the entities in a fluid; preparing a droplet from the fluid; determining whether the droplet contains one or more entities of said plurality of entities, or whether said droplet does not contain a said entity; sorting said droplet dependent on an outcome of the determination; and dispensing the sorted droplet into a reservoir. The dispensing may comprise identifying and extracting the sorted droplet from a first fluidic flow path of said fluid by transferring the sorted droplet from into a second fluidic flow path and then ejecting the sorted droplet into a reservoir by applying pressure to the second fluidic flow path. The droplet contents may be tracked so that the contents of an individual droplet can be sorted, selectively dispensed, and retrieved.

公开(公告)号：US20200215546A1

公开(公告)日：2020-07-09

申请号：US16625021

申请日：2018-06-21

Applicant: SPHERE FLUIDICS LIMITED

Inventor： Dimitris JOSEPHIDES ,  Marian REHAK ,  David HOLMES ,  Frank F. Craig

IPC: B01L3/00

Abstract: This invention generally relates to methods and systems for dispensing a droplet, in particular a picolitre volume droplet containing one or more entities. We disclose herein a microfluidic droplet dispensing system comprising: a droplet feed line to carry droplets for dispensing; a dispensing line to carry dispensing fluid for dispensing the droplets; a droplet outlet line coupled to a droplet outlet; a first junction having a first input to receive a flow from said droplet feed line, having a second input to receive a flow from said dispensing line and having an output to said droplet outlet line; a waste line coupled to said droplet output line between said first junction and said droplet output; a first pressure source to provide pressurised dispensing fluid to said dispensing line to eject droplets from said droplet output; a droplet dispensing valve between said first pressure source and said dispensing line to control the ejection of droplets from said droplet output; wherein the system further comprises: a second pressure source to provide pressurised dispensing fluid to a droplet protect line; a second junction having a first input from said droplet feed line, having a second input from said droplet protect line, and having an output; and a volume flow throttle coupled between the output of said second junction and the first input of said first junction to restrict a volume flow from said second junction into said first junction.

公开(公告)号：US20180250677A1

公开(公告)日：2018-09-06

申请号：US15754754

申请日：2016-09-06

Applicant: SPHERE FLUIDICS LIMITED

Inventor： Xin LI ,  Xin Liu ,  Alexandra Clay

IPC: B01L3/00 ,  B01L3/02

CPC classification number: B01L3/502776 ,  B01L3/0241 ,  B01L3/502715 ,  B01L3/502784 ,  B01L2200/0647 ,  B01L2200/0673 ,  B01L2300/0816 ,  B01L2300/0867 ,  B01L2300/161 ,  B01L2400/0463 ,  B01L2400/0487

Abstract: A microfluidic structure for spacing out and aligning entities in an aqueous suspension is provided. The structure comprises: a channel for guiding entities in an aqueous suspension; a first comb of first inlets arranged on a first side of the channel for introducing a spacing medium into the channel; and a second comb of second inlets arranged on a second side of the channel for introducing the spacing medium into the channel; wherein the first side is opposite the second side, and wherein one of the first inlets has a corresponding, respective one of the second inlets at a substantially similar longitudinal position along the channel.

公开(公告)号：US12110441B2

公开(公告)日：2024-10-08

申请号：US16768121

申请日：2018-11-29

Applicant: SPHERE FLUIDICS LIMITED

Inventor： Xin Li ,  Clive A. Smith ,  Alexandra Clay ,  Colin Pilkington

IPC: C09K23/18 ,  B01D11/04 ,  B01D17/04 ,  B01D17/12 ,  B01L3/00 ,  C08G65/00 ,  C09K23/00 ,  C09K23/16

CPC classification number: C09K23/18 ,  B01D11/0492 ,  B01D11/0496 ,  B01D17/045 ,  B01D17/12 ,  B01L3/5021 ,  C08G65/007 ,  C09K23/007 ,  C09K23/16

Abstract: A surfactant of formula (I):

A-(L1)a-(C2)b-(L2)c-X  (I)

wherein
A is a perfluoropolyether;
L1 is CONR', wherein R′ is selected from H and C1-6 alkyl;
a is 0 or 1;
b is 0 or an integer between 1 and 10;
L2 is a linking group;
c is 0 or 1; and
X is a charged group.

公开(公告)号：US11919001B2

公开(公告)日：2024-03-05

申请号：US16625021

申请日：2018-06-21

Applicant: SPHERE FLUIDICS LIMITED

Inventor： Dimitris Josephides ,  Marian Rehak ,  David Holmes ,  Frank F. Craig

IPC: B01L3/00

CPC classification number: B01L3/502784 ,  B01L3/502761 ,  B01L3/502715 ,  B01L2200/027 ,  B01L2200/0652 ,  B01L2200/0673 ,  B01L2400/0487

Abstract: This invention generally relates to methods and systems for dispensing a droplet, in particular a picolitre volume droplet containing one or more entities. We disclose herein a microfluidic droplet dispensing system comprising: a droplet feed line to carry droplets for dispensing; a dispensing line to carry dispensing fluid for dispensing the droplets; a droplet outlet line coupled to a droplet outlet; a first junction having a first input to receive a flow from said droplet feed line, having a second input to receive a flow from said dispensing line and having an output to said droplet outlet line; a waste line coupled to said droplet output line between said first junction and said droplet output; a first pressure source to provide pressurised dispensing fluid to said dispensing line to eject droplets from said droplet output; a droplet dispensing valve between said first pressure source and said dispensing line to control the ejection of droplets from said droplet output; wherein the system further comprises: a second pressure source to provide pressurised dispensing fluid to a droplet protect line; a second junction having a first input from said droplet feed line, having a second input from said droplet protect line, and having an output; and a volume flow throttle coupled between the output of said second junction and the first input of said first junction to restrict a volume flow from said second junction into said first junction.

公开(公告)号：US20230243729A1

公开(公告)日：2023-08-03

申请号：US18133980

申请日：2023-04-12

Applicant: Sphere Fluidics Limited

Inventor： Clive Adrian Smith ,  Xin Li ,  Frank F. Craig

IPC: G01N15/10 ,  B01L3/00 ,  G01N15/14

CPC classification number: G01N15/1031 ,  B01L3/502784 ,  G01N15/1404 ,  B01L3/502715 ,  B01L3/50273 ,  G01N15/1056 ,  B01L2400/0424 ,  B01L2300/0864 ,  B01L2400/0427 ,  B01L2400/084 ,  G01N2015/1486 ,  G01N2015/149 ,  B01L2200/0652 ,  B01L2300/0627 ,  B01L2300/0816 ,  G01N2015/1081 ,  H01J49/0031

Abstract: A method for aligning sequences of droplets in streams of an emulsion comprising target droplets and tag droplets, a tag droplet comprising first and second tags. A target droplet is split into first and second target droplets and a tag droplet is split into first and second tag droplets. Each of the first and second tag droplets comprise the first and second tags. The first target droplet and first tag droplet are in a first stream of droplets, and the second target droplet and second tag droplet are in a second stream of droplets. The method detects the first tag droplets and first target droplets in the first stream and the second tag droplets and second target droplets in the second stream, determines a first sequence of droplets in the first stream and a second sequence of droplets in the second stream, and compares these to align the sequences.