Microfluidic approaches to characterize the mechanical...

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/

4

www.cnrs.fr

mon-herboris terie.com

Cosmetics

Foodindustry

Textileindustry

Pharmaceutics

Applications of encapsulation

6

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

1

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