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WO2024148321A1 - Dispositif microfluidique 3d et procédé de séparation de particules par taille à partir d'une suspension - Google Patents

Dispositif microfluidique 3d et procédé de séparation de particules par taille à partir d'une suspension Download PDF

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Publication number
WO2024148321A1
WO2024148321A1 PCT/US2024/010576 US2024010576W WO2024148321A1 WO 2024148321 A1 WO2024148321 A1 WO 2024148321A1 US 2024010576 W US2024010576 W US 2024010576W WO 2024148321 A1 WO2024148321 A1 WO 2024148321A1
Authority
WO
WIPO (PCT)
Prior art keywords
outlet
center
section
flow channel
particles
Prior art date
Application number
PCT/US2024/010576
Other languages
English (en)
Inventor
Guigen Zhang
Original Assignee
University Of Kentucky Research Foundation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University Of Kentucky Research Foundation filed Critical University Of Kentucky Research Foundation
Publication of WO2024148321A1 publication Critical patent/WO2024148321A1/fr

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502761Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D21/00Separation of suspended solid particles from liquids by sedimentation
    • B01D21/26Separation of sediment aided by centrifugal force or centripetal force
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D2221/00Applications of separation devices
    • B01D2221/10Separation devices for use in medical, pharmaceutical or laboratory applications, e.g. separating amalgam from dental treatment residues
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0647Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0652Sorting or classification of particles or molecules
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/088Channel loops

Definitions

  • This document relates to a new and improved three-dimensional (3D) microfluidic device and related method for separating particles by size from a suspension sample.
  • the 3D device and method advantageously provide stable alignment, focusing, fractionation and separation of conventional particles as well as bioparticles (cells and vesicles) with high precision and certainty.
  • inertial-based microfluidics have been researched for years for particle separation and fractionation, most of these inertial-focusing-based microfluidic channels take the design with a horizontal-oriented cross-section (i.e., a cross-section that is greater in width than height) To obtain a high flowrate, these channels sometime are made as wide as 500 pm or more to provide a large cross-section area. This horizontal orientation inadvertently introduces difficulties for inertial focusing to work, because in such wider channels, the focusing positions are difficult to reach, adding uncertainty in particle separation and fractionation applications. Although multiple inlets with differential flowrates have been utilized to address some of the problems, to date wide adaptation of microfluidic technologies has not occurred because these devices require real-time monitoring and tuning using a microscope to function properly.
  • This document relates to 3D microfluidic devices with a vertical orientation (i.e., a cross-section that is greater in height than width), an intermediate spiral section and a plurality of discrete outlets that function together to allow for sorting, fractionation and separation of conventional particles and biological particles, such as cells and vesicles, from a suspension.
  • the device and method also provide an unprecedented tunable gating and bracketing capability without requiring any real-time monitoring and tuning under a microscope. For example, when the device and method are used to isolate circulating tumor cells (CTCs) in blood samples, such bracketing capability will aid the distinction of CTCs from other white blood cells, as well as differentiation between vital and non-vital CTCs
  • a new and improved 3D microfluidic device comprising, consisting of or consisting essentially of a flow channel including (a) an inlet, (b) an inlet section, extending along a first tangent, (c) an intermediate spiral section, (d) an outlet section, extending along a second tangent, and (e) a 3D outlet system including a plurality of outlets .
  • the flow channel may be formed by four walls - a first sidewall, a second sidewall, a top wall and a bottom wall.
  • the outlet system may include four outlets, including an upper outlet bordering the top wall, a lower outlet bordering the bottom wall, and sandwiched in between, a center left outlet bordering the first sidewall, and a center right outlet bordering the second sidewall.
  • the cross-section areas of the upper and lower outlets typically are of the same size, and that of the center left and right outlets are of the same size, with the former a few times larger than the latter.
  • the flow channel may have a width of between about 1 pm and about 250 pm and an aspect ratio of channel cross sectional area (H/W) of from about 1.5 to about 4.5.
  • outlet 24 includes (a) two larger outlets 40 including an upper outlet 42 and a lower outlet 44, (b) a first or center left outlet 46 and (c) a second or center right outlet 48.
  • the upper outlet 42 borders the top wall 50 and the lower outlet 44 borders the bottom wall 52.
  • the method allows one to customize and tune the device 10 for the separation of different size particles through the center left outlet 46, the center right outlet 48, the upper outlet 42 and the lower outlet 44. Further, this is accomplished in a number of ways without requiring any real-time monitoring and tuning under a microscope. Those ways include, but are not necessarily limited to, one or more of the following:

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Fluid Mechanics (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

Un dispositif microfluidique comprend un canal d'écoulement comprenant (a) une entrée, (b) une section d'entrée, s'étendant le long d'une première tangente, (c) une section en spirale intermédiaire, (d) une section de sortie, s'étendant le long d'une seconde tangente, et (e) un système de sortie tridimensionnel comprenant une pluralité de sorties. Le canal d'écoulement comporte une section transversale rectangulaire ayant une hauteur H et une largeur W, où H > W. Le dispositif est utile dans un procédé d'alignement, de focalisation, de fractionnement et de séparation stables de particules classiques ainsi que de bioparticules (cellules et vésicules) à partir d'une suspension.
PCT/US2024/010576 2023-01-06 2024-01-05 Dispositif microfluidique 3d et procédé de séparation de particules par taille à partir d'une suspension WO2024148321A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202363478720P 2023-01-06 2023-01-06
US202363478727P 2023-01-06 2023-01-06
US63/478,720 2023-01-06
US63/478,727 2023-01-06

Publications (1)

Publication Number Publication Date
WO2024148321A1 true WO2024148321A1 (fr) 2024-07-11

Family

ID=91804410

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2024/010576 WO2024148321A1 (fr) 2023-01-06 2024-01-05 Dispositif microfluidique 3d et procédé de séparation de particules par taille à partir d'une suspension

Country Status (1)

Country Link
WO (1) WO2024148321A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5842787A (en) * 1997-10-09 1998-12-01 Caliper Technologies Corporation Microfluidic systems incorporating varied channel dimensions
US20060087918A1 (en) * 2003-06-11 2006-04-27 Agency For Science, Technology And Research Micromixer apparatus and methods of using same
US20130130226A1 (en) * 2010-03-04 2013-05-23 Chwee Teck Lim Microfluidics Sorter For Cell Detection And Isolation
US20180185846A1 (en) * 2015-07-02 2018-07-05 Nanyang Technological University Leukocyte and microparticles fractionation using microfluidics

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5842787A (en) * 1997-10-09 1998-12-01 Caliper Technologies Corporation Microfluidic systems incorporating varied channel dimensions
US20060087918A1 (en) * 2003-06-11 2006-04-27 Agency For Science, Technology And Research Micromixer apparatus and methods of using same
US20130130226A1 (en) * 2010-03-04 2013-05-23 Chwee Teck Lim Microfluidics Sorter For Cell Detection And Isolation
US20180185846A1 (en) * 2015-07-02 2018-07-05 Nanyang Technological University Leukocyte and microparticles fractionation using microfluidics

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