WO2007130682A2 - Dispositif et procédé de séparation et de concentration de particules microfluidiques - Google Patents

Dispositif et procédé de séparation et de concentration de particules microfluidiques Download PDF

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Publication number
WO2007130682A2
WO2007130682A2 PCT/US2007/011060 US2007011060W WO2007130682A2 WO 2007130682 A2 WO2007130682 A2 WO 2007130682A2 US 2007011060 W US2007011060 W US 2007011060W WO 2007130682 A2 WO2007130682 A2 WO 2007130682A2
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WO
WIPO (PCT)
Prior art keywords
flow
fluid
particle
segment
particles
Prior art date
Application number
PCT/US2007/011060
Other languages
English (en)
Other versions
WO2007130682A3 (fr
Inventor
Gregory W. Auner
Chung Chu Chen
Original Assignee
Wayne State University
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 Wayne State University filed Critical Wayne State University
Publication of WO2007130682A2 publication Critical patent/WO2007130682A2/fr
Publication of WO2007130682A3 publication Critical patent/WO2007130682A3/fr
Priority to US12/265,291 priority Critical patent/US7837944B2/en

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D45/00—Separating dispersed particles from gases or vapours by gravity, inertia, or centrifugal forces
    • B01D45/04—Separating dispersed particles from gases or vapours by gravity, inertia, or centrifugal forces by utilising inertia
    • B01D45/08—Separating dispersed particles from gases or vapours by gravity, inertia, or centrifugal forces by utilising inertia by impingement against baffle separators
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D45/00—Separating dispersed particles from gases or vapours by gravity, inertia, or centrifugal forces
    • B01D45/04—Separating dispersed particles from gases or vapours by gravity, inertia, or centrifugal forces by utilising inertia
    • B01D45/06—Separating dispersed particles from gases or vapours by gravity, inertia, or centrifugal forces by utilising inertia by reversal of direction of flow
    • 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
    • G01N15/0255—Investigating particle size or size distribution with mechanical, e.g. inertial, classification, and investigation of sorted collections
    • 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

Definitions

  • The. present invention relates to flow separating and concentrating devices and, more particularly, flow units and methods of separating and concentrating microfluidic particles.
  • FFF field-flow fractionation
  • capillary hydrodynamic fraction is a technique that was used to analyze the size distribution of particle growth during emulsion polymerization.
  • hydrodynamic chromatography HDC is a technique that has been tested on separation of fluorescent nano-spheres and macromolecules. Although both CHDF and HDC do not require external fields, these separation processes are (as mentioned) not continuous and require a relatively long separation time and complicated injecting devices. These attributes are not suitable for large-scale cell or particle preparation.
  • SPLITT pinched inlet split-flow thin fractionation
  • the present invention generally provides microfluidic devices and methods for particle concentration and separation. Embodiments of the present invention provide continuous processing ability independent of a requirement of external fields. The devices and methods of the present invention are able to separate and concentrate particles by particle size and density.
  • the present invention provides a microfluidic separator that employs a momentum-driven particle separation principle.
  • the separator provides a relatively high throughput with continuous-flow processing without a need of external fields for separation.
  • the separator is configured to be stacked with arrays of other separators for large- volume cell separation.
  • the separator has a relatively small size that is suitable as a portable device and for micro-scale analysis.
  • the separator is relatively cost effective and easy to be fabricated.
  • the present invention provides a flow unit for microfluidic particle separation and concentration.
  • the unit comprises a nozzle segment defined by a first member and a second member.
  • the nozzle segment has an opening through which fluid and microfluidic particles enter the flow unit.
  • the nozzle segment has a narrowing portion at which the first and second members narrow from the opening to increase momentum of the fluid through the nozzle segment.
  • the unit further comprises a turn segment defined by the first member formed to flare outwardly downstream from the narrowing portion to change flow direction of the fluid consistent with the first member.
  • the unit further comprises a diffuser segment defined by the second member extending past the turn segment to facilitate separation of the microfluidic particles from the fluid due to the inability to follow the fluid flow.
  • the present invention provides a flow device for microfluidic particle separation and concentration.
  • the device comprises a plurality of the flow units for microfluidic particle separation and concentration.
  • the flow units are disposed in an array and are arranged in a cascading fashion.
  • the present invention provides a method of separating and concentrating microfluidic particles. The method comprises receiving a fluid and microfluidic particles to be separated and concentrated, and accelerating the speed of the fluid and microfluidic particles to increase the momentum thereof.
  • the method further includes influencing a change in direction of the fluid, and facilitating separation of the microfluidic particles from the fluid due to the inability to follow the fluid flow.
  • Figure 1a is a plan view of a flow unit design for separation and concentration of microfluidic particles in accordance with one embodiment of the present invention
  • Figure 1 b is a plan view of the flow unit design in Figure 1a depicting flow particle separation
  • Figure 2 is a plan view of a particle concentrator having an array of the flow units in accordance with another embodiment of the present invention.
  • Figure 3a is a perspective view of an array of the flow units depicting three-dimensional particle motion therethrough;
  • Figure 3b is a perspective view of another array of the flow units depicting stream function of particle motion therethrough;
  • Figure 3c is a perspective view of yet another array of the flow units depicting pressure and velocity distribution of particle motion therethrough;
  • Figure 4 is a plan view of a particle concentrator having an array of the flow units in accordance with another embodiment of the present invention.
  • Figure 5a is a perspective view of an array of the flow units depicting separation of particles by size
  • Figure 5b is a perspective view of an array of the flow units depicting separation of particles by density
  • Figures 6a-6c are cross-sectional views of layers for fabrication of a particle concentrator in accordance with one example of the present invention.
  • the present invention generally provides microfluidic devices and methods for particle concentration and separation.
  • Embodiments of the present invention provide microfluidic devices having a continuous processing ability independent of a requirement for the use of external fields.
  • the devices and methods of the present invention are able to separate and concentrate particles by particle size and density.
  • the present invention provides a microfluidic separating and concentrating device comprising a nozzle segment through which fluid and microfluidic particles enter and gain momentum, a turn segment that changes flow direction of the fluid, and a diffuser segment that facilitates separation of the microfluidic particles from the fluid.
  • FIGs 1a and 1 b illustrate a flow unit 10 for microfluidic particle separation and concentration in accordance with one embodiment of the present invention.
  • the flow unit 10 comprises a nozzle segment 12 defined by a first member 13 and a second member 14.
  • the nozzle segment 12 has an opening 20 formed by the first and second members 13, 14 through which fluid and microfluidic particles enter the flow unit 10.
  • the nozzle segment 12 Downstream from the opening 20, the nozzle segment 12 has a narrowing portion 22 at which the first and second members 13, 14 narrow relative to the opening 20.
  • the narrowing portion 22 serves to increase momentum of the fluid and particles through the nozzle segment 12.
  • the nozzle segment 12 accelerates the speed of fluid and particles. As result of increased momentum, particles start to resist a directional change, e.g., a change in direction near a sharp turn (discussed below).
  • Fluids and particles mentioned in the present application may include any suitable fluid and particle to be separated and concentrated without falling beyond the scope or spirit of the present invention.
  • Such fluids and particles may include water and particulates thereof for applications such as bacteria detection or quality monitoring; blood components such as white and red blood cells, platelets, and plasma; target cells for applications such as isolation for disease diagnostic and genomic applications; polymer beads, ceramics, and pharmaceutical emulsions for applications such as particle sizing.
  • the flow unit 10 further comprises a turn segment 24 having a sharp turn 30 where, after acceleration in the nozzle segment 12, the fluid and relatively large or denser particles start to separate from each other due to the inability to follow the fluid flow.
  • the turn segment 24 is defined by the first member 13 and is formed to flare outwardly downstream from the narrowing portion 22 to change flow direction of the fluid consistent with the first member 13.
  • the turn segment 30 is a U-shaped turn, but may be formed in any other suitable shape without falling beyond the scope or spirit of the present invention.
  • the increased momentum in the nozzle segment 12 forms an inability of the particles to follow the fluid flow through the directional change of the turn segment 24. Due to this inability, the particles flowing adjacent the first member 13 of the flow unit 10 are not able to follow the fluid, and other smaller or lower density particles, around the turn segment 24. Rather, the relatively larger or denser particles pass the turn segment 24 and cross the dividing streamline toward the second member 14 as shown in Figures 1a and 1 b. Denser and larger particles have higher momentum relative to less dense and smaller particles at a constant speed, and are easier to be separated. Thus, as the average particle size or particle density decreases, the fluid drag force has a greater affect on the particle separation.
  • Figures 1 a and 1b further depict a diffuser segment 32 of the flow unit
  • the diffuser segment 32 is defined by the second member 14 extending past the turn segment 24 to facilitate separation of the microfluidic particles from the fluid.
  • the diffuser segment 32 serves to further aid in the separation at a flowing dividing segment 34 (discussed below) as shown in the particle path in Figure 1 b.
  • the flow unit 10 further comprises a flow dividing segment 34 where fluid flow is evenly distributed into two different openings of the two succeeding flow units. As shown in Figures 1a and 1b, the left side of the flow dividing segment 34 includes relatively smaller particle size and particle density than the particles that flow through the right side.
  • One aspect of the present invention includes a microfluidic particle separator and concentrator device having an array of the flow unit discussed above and illustrated in-part in Figures 1 a and 1b.
  • a microfluidic particle separator and concentrator device having an array of the flow unit discussed above and illustrated in-part in Figures 1 a and 1b.
  • Such a device preferably includes a plurality of the flow unit 10 in staggering and cascading relationship.
  • each stage of each flow unit has an offset, Woffeet, to its preceding one.
  • W Off e ⁇ t By staggering the flow units with the offset W Off e ⁇ t , fluids and particles may be divided into at least two downstream flow units as shown in Figure 1a. This may also be facilitated also by splitting the exit or downstream outlet.
  • the separation of particle sizes may range between about 5 and 20 micron and particles densities ranging between about 600 and 2700 kg/m 3 . •
  • Flow dynamics of the microfluidic concentrator and separator device may be provided by simulation for analysis. This may be accomplished by any suitable system and software such as CFD-ACE+TM software from ESI US R&D, Inc. of Huntsville, AL, USA.
  • the simulation employed transient incompressible flow and spray models.
  • the spray model was configured to track a discrete phase (e.g. solid particles) through a calculation domain by solving the governing mass, momentum, and energy conservation equations in a Lagrangian frame of reference.
  • the flow model solved the time dependent continuity equation, the pressure-based Navier-Stokes equations, and the energy balance equation.
  • the particles can exchange momentum with the surrounding ambient fluid (continuous phase).
  • the governing equation for the particle may be represent as follows:
  • p p , V p , and U p are the density, volume and velocity of the particle, respectively.
  • C D is the drag coefficient of particle.
  • PL and UL are the density and velocity of the surrounding liquid.
  • a p is the particle projected area.
  • G is the gravity and S is the additional source term.
  • FIG. 2 illustrates a microfluidic particle concentrator device 110 in accordance with another embodiment of the present invention.
  • the device 110 includes an array of 25*50 flow units 112.
  • each flow unit 112 has the same components as the flow unit 10 discussed above.
  • the device 110 comprises a sample inlet 114 through which liquids with particles may be introduced.
  • a body 120 of the device 110 containing the array of 25x50 flow units 112 receives the liquids with particles for particle concentration.
  • fluid is split into two outlets 122,124 downstream of the flow unit array.
  • the device comprises a liquid outlet 122 and a particle outlet 124 downstream from the body 120. Most of the liquids without or with fewer particles will exit at the liquid outlet 122. The concentrated liquids with particles may be collected at the particle outlet 124.
  • Figure 3a depicts a 4x4 array of the flow units 10 (mentioned above shown in Figures 1a and 1 b) to illustrate three-dimensional particle motion therethrough.
  • 10 ⁇ m particles were introduced into an opening of a flow unit at the far left side of the array as depicted in Figure 3a.
  • Figure 3b shows (in color) a 4x8 array of the flow units to illustrate the stream function map of particle motion through the array.
  • velocity (vectors) and pressure (color) distribution are shown in Figure 3c.
  • the particles that were introduced into the opening of the flow unit at the far left side (relative to Figure 3c) of the inlet streamlined an exit to the far right side of the outlet of the array in Figure 3c.
  • concentration of particles may be accomplished from any location of the inlet to one side of the outlet in a microfluidic particle concentrator comprising a 4x8 array of flow units mentioned above.
  • Figure 4 shows a design of a microfiuidic particle separator device 210 with a 25*50 flow unit array (incorporating the flow units depicted in Figures 1a and 1 b) in accordance with another embodiment of the present invention.
  • liquid with particles are introduced into an inlet portion 212 (top-left relative to Figure 4) having a relatively small opening. Liquids without particles were fed to the relatively wider buffer inlet 214 with higher flow rate.
  • separated particles may be collected at various ports or branches 220, 222, 224, 226, 228 at the end of the flow unit array.
  • less dense and smaller particles may collected at branch 220 while greater densities and particle sizes particles may be collected in sequence at branches 222, 224, 226, and 228.
  • Figures 5a and 5b further illustrate size and density separation by microfiuidic simulation.
  • Figure 5a shows particle with sizes ranging from 5 to 20 ⁇ m separated.
  • Figure 5b shows 20 ⁇ m particles with densities ranging from 600 to 2700 Kg/m 3 separated.
  • the efficiency of particle separation may be limited when the size becomes very small, e.g., diameters less than about 1 ⁇ m. As briefly mentioned above, the limitation may be experience because the drag force is believed to be more dominant than the momentum force for the size of particles. Meanwhile, the maximum size of particles is limited by the minimum channel width of the designed device. With a relatively large array (about 100 x 200 or higher), a 100 times of concentration increase or more distinct particle separation may be attained with this particle separation technology.
  • Figures 6a-6c depict layers or wafers for fabrication of a microfluidic particle separator and concentrator device in accordance with one example of the present invention.
  • the layers are provided in steps in accordance with the making of an E-coli pre-concentrator.
  • a silicon wafer 310 is patterned using standard photolithography and is dry-etched by deep reactive ion etching to form a connection port (mask 1 ) 320 having oxide layers 323.
  • a negative photoresist SU-8 layer 330 may be used to construct the micro-sharp turn array of the mask 2 identified by reference numeral 340.
  • SU-8 is a commonly used photoresist material, and is known to be relatively stable and inert. It is also known to provide dependable biocompatibility.
  • a glass (e.g., PyrexTM) wafer 350 is then used as a top cover of pre-concentrator 360 to provide optical access of a light source and a photo detector.

Abstract

L'invention concerne une unité d'écoulement destinée à la séparation et à la concentration de particules microfluidiques. L'unité comporte un segment de tuyère, un segment de déviation et un segment de diffuseur. Le segment de tuyère est défini par un premier élément et un deuxième élément, et présente une ouverture à travers laquelle entrent du fluide et des particules microfluidiques. Le segment de tuyère est doté d'une partie en rétrécissement au niveau de laquelle les premier et deuxième éléments rétrécissent à partir de l'ouverture pour augmenter l'énergie cinétique du fluide à travers ceux-ci. Le segment de déviation est défini par l'évasement du premier élément vers l'extérieur en aval de la partie en rétrécissement pour modifier la direction d'écoulement du fluide par rapport au premier élément. Le segment de diffuseur est défini par le prolongement du deuxième élément au-delà du segment de déviation pour faciliter la séparation des particules microfluidiques du fluide du fait de leur incapacité à suivre l'écoulement du fluide.
PCT/US2007/011060 2006-05-05 2007-05-07 Dispositif et procédé de séparation et de concentration de particules microfluidiques WO2007130682A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/265,291 US7837944B2 (en) 2006-05-05 2008-11-05 Device for separating and concentrating microfluidic particles

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US79799806P 2006-05-05 2006-05-05
US60/797,998 2006-05-05

Related Child Applications (1)

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WO2007130682A2 true WO2007130682A2 (fr) 2007-11-15
WO2007130682A3 WO2007130682A3 (fr) 2008-06-19

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010011934A3 (fr) * 2008-07-24 2010-04-29 The Trustees Of Princeton University Dispositif de réseau de bosses présentant des espaces asymétriques pour la ségrégation de particules

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1603878A (en) * 1924-05-19 1926-10-19 Gen Electric Eliminator
US4990740A (en) * 1989-03-06 1991-02-05 The Dow Chemical Company Intra-microspray ICP torch
WO1998058725A1 (fr) * 1997-06-23 1998-12-30 Mesosystems Technology, Inc. Dispositif permettant d'extraire des particules d'une veine fluide et de les concentrer
US20040232052A1 (en) * 1998-11-13 2004-11-25 Call Charles John Methods and devices for continuous sampling of airborne particles using a regenerative surface

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1603878A (en) * 1924-05-19 1926-10-19 Gen Electric Eliminator
US4990740A (en) * 1989-03-06 1991-02-05 The Dow Chemical Company Intra-microspray ICP torch
WO1998058725A1 (fr) * 1997-06-23 1998-12-30 Mesosystems Technology, Inc. Dispositif permettant d'extraire des particules d'une veine fluide et de les concentrer
US20040232052A1 (en) * 1998-11-13 2004-11-25 Call Charles John Methods and devices for continuous sampling of airborne particles using a regenerative surface

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010011934A3 (fr) * 2008-07-24 2010-04-29 The Trustees Of Princeton University Dispositif de réseau de bosses présentant des espaces asymétriques pour la ségrégation de particules
US8579117B2 (en) 2008-07-24 2013-11-12 The Trustees Of Princeton University Bump array device having asymmetric gaps for segregation of particles
US8783467B2 (en) 2008-07-24 2014-07-22 The Trustees Of Princeton University Bump array device having asymmetric gaps for segregation of particles

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