microfluidic approaches to characterize the mechanical...
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Microfluidic approaches to characterize the mechanical properties of capsules and cells
Anne Le GoffAnne-Virginie Salsac
Dominique Barthès-Biesel
Université de Technologie de CompiègneBiomechanics & Bioengineering
Biological Fluid-Structure Interactions
Capsules and cells
Capsule : Liquid droplet enclosed within a thin deformable membrane.
•Artificialcapsule
ICMR,Reims
ThinmembraneInternal substance
Microcapsule: 1 µm -1 mm
•Cellsarenaturalcapsules
Redbloodcells
White bloodcells
http://www.eurostemcell.org
www.swri.org/
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www.cnrs.fr
mon-herboris terie.com
Cosmetics
Foodindustry
Textileindustry
Pharmaceutics
Applications of encapsulation
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ΔP
D
aspiration
Micropipette aspiration experiments
Formicrometriccapsules
Thesetechniquesdonotallowtocharacterizeanentirecapsulepopulation
Indentation experiments with AFM (atomic force microscope)
d
P R.RicciMaccarinietal.2002
⇒
Membrane characterization techniques
Measurement of microcapsule membrane elasticity using a microfluidic technique:
Discrimination between populations
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Thi Xuan Chu, Anne-Virginie Salsac, Eric Leclerc & Dominique Barthès-Biesel
* BMBI (UMR CNRS 7338), Université de Technologie de Compiègne, France
Hélène Wurtz, Florence Edwards-Lévy
ICMR (UMR CNRS 7312), Faculté de Pharmacie, Université de Reims, France
(Edwards-Lévy et al., Int. J. Pharm. 1993)
pH = 5 - 8 1: Emulsification
tr = 5 – 30 min2: Membrane formation
Ovalbumin Buffer Cyclohexane
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2.5% (w/v) Terephtaloyl Chloride solution
1550 rpm
Team of F. Edwards-Lévy, Université de Reims Champagne Ardenne
Method: interfacial cross-linking
Microcapsule fabrication
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Lefebvre etal.PhysFluids2008Huetal.PRE2013
1cm
Capillarytube
Siliconpipe
FLOW75 µm
Flow rate: 0.13 – 0 .54 ml/h
Pressure drop along the microchannel: 2.2 – 9.13 bar
Microfluidic characterization technique
Shape of capsules flowing under confinement
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μμ Gsa R
Cylindricaltube
Fluidvelocity U
Fluid structure interaction code• Capsule wall: Lagrangian tracking• Fluids: boundary integral method
Model input• Size ratio a/R• Constitutive law: Neo-Hookean (NH)• Capillary number : Ca = μ U/Gs
Model output• Deformed profile• Vcaps/U• Pressure loss• Membrane elastic tension• Energy of deformationLefebvre & Barthès-Biesel JFM 2007
Hu et al. JFM 2012
Numerical simulation
Choice of constitutive law : Neo-Hookean (NH)
Velocity Vcaps
Contour extraction
Numerical Simulation
a/R
a/R
constitutive law
Ca
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Lefebvre & al Phys. Fluids 2008Hu et al. JFM 2012
Inverse analysis
tr = 5 min, pH 5
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Gs constant with a/R
Shear modulus identification
• Gs increaseswithtr
17• Discriminationbetweenmicrocapsulepopulations
Shear modulus identification
Chu et al. JCIS 2010
• Microfluidic technique is able to distinguish between capsules prepared under different physico-chemical conditions
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Mechanical characterization by inverse analysis of deformed capsule profiles
• Measurement of viscous properties
• Downscaling
• Cell / Capsule - wall interaction
US UR = US /2
Elastic properties Viscous properties
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Transient behaviorPY Gires & Van Tuan Dang
Cell deformation in confined flow
10µm
Challenges
• Qualityoflithography&pollution• Inhomogeneityofcellcontent
N. Munier
Mechanical characterization of cell elastic moduli
Healthy RBC
Infected RBC
Antia & al Cellular Microbiology (2008)
Some pathologies, for instance malaria, alter cell mechanical properties
Measuringcellelasticpropertiescouldprovideabiomechanicaldiagnostictool
Interaction with walls
•Biologicalexamples •Medicalapplications
Targeted drug delivery
Leukocytes at inflammation sites
Platelets at endothelial lesion sites
Questions
• Howisacellcapturedbyatargetsite?• Whatistheshapeofacapturedcellunderflow?
Malaria-infected RBC
Platelet-wall interaction
20 µmX 30 acceleration
plain glass ligand-coated surface
Platelet-wall interactionCollaboration with D. Baruch (INSERM), J. Pujos & M. Reyssat (ESPCI)
0 mm 2 mm 4 mm 6 mm 8 mm
Conclusion
• Inverse analysis technique is validated to measure the elastic modulus of the membrane of capsules flowing through a narrow capillary
• Analysis of the transient shape of relaxing capsules allows an estimation of membrane viscosity
• The collective behavior of cells flowing through a ligand-coated channel can provide information about cell-scale adsorption / desorption constants
Thank you for your attention
Membrane rupture Diffusion through themembrane
- Protects theinternalsubstance- Controls exchanges withtheexternalmedium
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Role of the capsule membrane
Compressionexperiments
D0D
F[Carin etal.2002]
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Limitedtomillimetriccapsules
Ωà Force
Shearingexperiments
Membrane characterization techniques
a/R = 1
uc = 1.4 mm/s
a/R = 0.95
uc = 4.8 mm/s
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Microcapsules, tr = 5 min, pH 5
Shear modulus identification
•Gs constantpH5– 7.4(tr =5min)•SimilartrendofGswithpHwhentr increases
•Gs increasesatpH8 16
Chu et al. JCIS 2010
Shear modulus identification
Relaxation time
PY Gires & Van Tuan Dang
phase 1 phase 2
OngoingworkAddingviscosityinthenumericalsimulations