WO2019227126A1 - Procédé et appareil de commande et de manipulation d'écoulement multiphase dans la microfluidique à l'aide d'intelligence artificielle - Google Patents

Procédé et appareil de commande et de manipulation d'écoulement multiphase dans la microfluidique à l'aide d'intelligence artificielle Download PDF

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Publication number
WO2019227126A1
WO2019227126A1 PCT/AU2019/050220 AU2019050220W WO2019227126A1 WO 2019227126 A1 WO2019227126 A1 WO 2019227126A1 AU 2019050220 W AU2019050220 W AU 2019050220W WO 2019227126 A1 WO2019227126 A1 WO 2019227126A1
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Prior art keywords
droplets
droplet
bubbles
sorting
parameters
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PCT/AU2019/050220
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English (en)
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WO2019227126A9 (fr
Inventor
Nam-Trung Nguyen
Yongsheng Gao
Jun Zhou
Say Hwa TAN
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AI Fluidics Pty Ltd
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Publication date
Priority claimed from AU2018901863A external-priority patent/AU2018901863A0/en
Application filed by AI Fluidics Pty Ltd filed Critical AI Fluidics Pty Ltd
Priority to AU2019277193A priority Critical patent/AU2019277193A1/en
Priority to CN201980009308.3A priority patent/CN112566721A/zh
Publication of WO2019227126A1 publication Critical patent/WO2019227126A1/fr
Publication of WO2019227126A9 publication Critical patent/WO2019227126A9/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • B01L3/502784—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/02—Investigating particle size or size distribution
    • G01N15/0205—Investigating particle size or size distribution by optical means
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/02—Investigating particle size or size distribution
    • G01N15/0205—Investigating particle size or size distribution by optical means
    • G01N15/0227—Investigating particle size or size distribution by optical means using imaging; using holography
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06N—COMPUTING ARRANGEMENTS BASED ON SPECIFIC COMPUTATIONAL MODELS
    • G06N20/00—Machine learning
    • G06N20/10—Machine learning using kernel methods, e.g. support vector machines [SVM]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0652—Sorting or classification of particles or molecules
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0645—Electrodes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N2015/1006—Investigating individual particles for cytology
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N2015/1028—Sorting particles
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06F—ELECTRIC DIGITAL DATA PROCESSING
    • G06F18/00—Pattern recognition
    • G06F18/20—Analysing
    • G06F18/24—Classification techniques
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06V—IMAGE OR VIDEO RECOGNITION OR UNDERSTANDING
    • G06V10/00—Arrangements for image or video recognition or understanding
    • G06V10/70—Arrangements for image or video recognition or understanding using pattern recognition or machine learning
    • G06V10/74—Image or video pattern matching; Proximity measures in feature spaces
    • G06V10/75—Organisation of the matching processes, e.g. simultaneous or sequential comparisons of image or video features; Coarse-fine approaches, e.g. multi-scale approaches; using context analysis; Selection of dictionaries
    • G06V10/753—Transform-based matching, e.g. Hough transform

Definitions

  • a general disadvantage of conventional droplet sorting systems based on electric actuation is that the biological samples have to be labelled with fluorescence dyes.
  • the labelling practice can be time consuming and not very desirable as dyes are not compatible with all cells types and cell behaviour may be affected during live cell imaging. In certain cases, the labelling of cells with fluorescence can only be done with dead cells.
  • the controller may include an artificial intelligence controller incorporating, for example, a machine learning classifier.
  • the controller may include a pressure-driven flow controller or a syringe pump.
  • the controller is configured to control the microfluidic device so that the microfluidic device generates a mono-disperse emulsion of the micro droplets or bubbles.
  • the sensor may include an optical system.
  • the optical system may acquire information such as sizes, shapes, colours of a gas, liquid or solid phase in a fluid flow of the micro droplets or bubbles.
  • the parameters may include any one or more of:
  • the step of controlling may include a training phase involving building a model using training data from a feedback sensor.
  • the training phase may involve determining a training region on a pressure characteristic of a generator performing the step of generating.
  • the training region is between parallel flow and stable region transition lines.
  • the training phase may involve querying in a serpentine manner against a training boundary.
  • Figure 6 shows a comparison between detected droplet area against user input expected droplet area, where two separate experiments (a & b) were carried out to compare the results with separate training sessions and parameters optimization;
  • the microfluidic generator 102 is a microfluidic flow-focusing device fabricated in polydimethylsiloxane (PDMS, Dow Corning) using standard photolithography and soft lithography procedures.
  • the controller 108 is configured to control the microfluidic device 102 so that the microfluidic device 102 generates a mono-disperse emulsion of the microfluidic droplets 104.
  • FIG. 1 Another factor that influences the performance of the predictor 107 is the selection of kernels.
  • a nonlinear Gaussian kernel is used. This is selected after comparison with both linear kernel and nonlinear kernels including polynomial and Gaussian kernels. Experimental results show that the Gaussian kernel is the best one out of all options.
  • predictions can be made by applying the model to unseen testing samples and calculating the required oil and water pressures given desired droplet size with the separation distance fixed.
  • Figure 4 shows the 3D diagram 400 illustrating the droplet areas at different P1 and P2 obtained from the training data.
  • Figure 12 shows a flow regime diagram 1200 obtained to determine the range for droplet generation.
  • the lower blue line 1202 gives the pressure values at stable interface (blue bordered inset 1204) before transitioning into droplet generation (green bordered inset 1206).
  • the red line 1208 depicts the pressure values for onset of parallel flow (red bordered inset 1210). Scale bars in Figure 12 represent dimensions of 100 um.
  • the black squares points are the pressure combinations used for subsequent study of spacer oil influence.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • General Physics & Mathematics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hematology (AREA)
  • Software Systems (AREA)
  • Clinical Laboratory Science (AREA)
  • Theoretical Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pathology (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • General Engineering & Computer Science (AREA)
  • Evolutionary Computation (AREA)
  • Computer Vision & Pattern Recognition (AREA)
  • Computing Systems (AREA)
  • Data Mining & Analysis (AREA)
  • Artificial Intelligence (AREA)
  • Medical Informatics (AREA)
  • Mathematical Physics (AREA)
  • Fluid Mechanics (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Networks Using Active Elements (AREA)

Abstract

La présente invention concerne un système de commande de gouttes ou de bulles microfluidiques. Le système comprend un générateur microfluidique pour générer les micro-gouttelettes ou bulles. Un capteur de rétroaction est prévu pour détecter un ou plusieurs paramètres de rétroaction des micro-gouttelettes ou des bulles générées. Un dispositif de commande est prévu pour commander le générateur microfluidique à l'aide des paramètres de rétroaction détectés.
PCT/AU2019/050220 2018-05-28 2019-03-12 Procédé et appareil de commande et de manipulation d'écoulement multiphase dans la microfluidique à l'aide d'intelligence artificielle WO2019227126A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2019277193A AU2019277193A1 (en) 2018-05-28 2019-03-12 Method and apparatus for controlling and manipulation of multi-phase flow in microfluidics using artificial intelligence
CN201980009308.3A CN112566721A (zh) 2018-05-28 2019-03-12 利用人工智能控制并操纵微流体中多相流的方法和装置

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AU2018901863 2018-05-28
AU2018901863A AU2018901863A0 (en) 2018-05-28 Method and appratus for controlling and manipulation of multi-phase flow in microfluidics using artificial intelligence

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WO2019227126A9 WO2019227126A9 (fr) 2020-06-25

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CN (1) CN112566721A (fr)
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CN112070711A (zh) * 2020-06-04 2020-12-11 清华大学 一种微液滴图像检测法中微液滴的分析方法
WO2022197921A1 (fr) * 2021-03-18 2022-09-22 Brown University Prédiction de la vélocimétrie à l'aide de modèles d'apprentissage automatique
NL1043994B1 (en) * 2021-04-14 2022-10-25 Digi Bio B V A method for identifying the best therapeutics producing candidates using a digital microfuidics based lab-on-a-chip platform

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WO2023086963A1 (fr) * 2021-11-12 2023-05-19 Raven Industries, Inc. Détermination de caractéristiques de gouttelettes
CN114505105B (zh) * 2022-01-13 2022-11-11 电子科技大学 一种基于内存计算的微流控芯片

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WO2018051242A1 (fr) * 2016-09-14 2018-03-22 Ecole Polytechnique Federale De Lausanne (Epfl) Dispositif destiné à des études à haut débit de cellules uniques

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112070711A (zh) * 2020-06-04 2020-12-11 清华大学 一种微液滴图像检测法中微液滴的分析方法
WO2022197921A1 (fr) * 2021-03-18 2022-09-22 Brown University Prédiction de la vélocimétrie à l'aide de modèles d'apprentissage automatique
NL1043994B1 (en) * 2021-04-14 2022-10-25 Digi Bio B V A method for identifying the best therapeutics producing candidates using a digital microfuidics based lab-on-a-chip platform

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Publication number Publication date
AU2019101835A4 (en) 2022-11-24
WO2019227126A9 (fr) 2020-06-25
CN112566721A (zh) 2021-03-26
AU2019277193A1 (en) 2020-10-29

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