2. - CytoFluidix
Transcription
2. - CytoFluidix
Inertial Microfluidics Workshop Manipulating Fluids and Particles Dino Di Carlo, Ph.D. Department of Bioengineering University of California, Los Angeles MicroTAS 2014, San Antonio TX USA Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Acknowledgements • Jerry Wu (Inertial microfluidic demo) uFlow and flow programming • Keegan Owsley • Baskar Ganapathysubramanian (Iowa State) • Dan Stoecklein (Iowa State) Inertial microfluidic physics review (Lab on a Chip) • Hamed Amini (Illumina) • Wonhee Lee (KAIST) Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Outline • • • • • • • • Why study inertial microfluidics? Inertia in microscale flows (Reynolds Number) Inertial focusing of particles Inertial ordering of particles Particle-induced flows Channel geometry-induced flows Inertial separation demonstration uFlow demonstration Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Why Study Inertial Microfluidics? Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Focusing of cells and particles • Flow cytometry – No sheath fluid – High rates of operation • Concentrating cell and particle solutions – Continuous – High rates of operation – Size-based effects Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Focusing of cells and particles • Solution exchange – Automated sample preparation operations – High rates of operation • Uniform response to stimuli – Magnetic deflection – Deformability cytometry Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Ordering of cells and particles • Cytometry – Non-overlapping cell signals – Operation at higher rates • Uniformizing concentration – Dispensing of cells – Cell printing Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Particle-induced flows • Solution exchange – Automated sample preparation operations – High rates of operation • Mixing of flows – Improve transport and reaction in fluid – Increase transport to particle surface and surface reactions Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Channel geometry-induced flows • Solution exchange – Automated sample preparation operations – High rates of operation • Fabricating materials – Complex fiber shapes – Complex particle shapes • Routing reactions Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Inertia in microscale flows?? typical dimensions: w = h = 50 m typical particle/obstacle size and velocity: a = ~10 m Um = 0.1-1 m/s typical pressure drops: 10-100 PSI (70-700 kPa) Channel Reynolds Number Rc Dino Di Carlo, Ph.D. U mh = ~ 5 - 50 Particle Reynolds Number www.biomicrofluidics.com U ma2 Rp h = ~ 0.2 - 2 Microfluidic Biotechnology No lateral migration of spherical particles in Stokes flow 0 Navier-Stokes Equations: u u u p 2 u t Stokes flow – linear differential equation 0 p 2 u If for u positive, Fz is positive, linearity gives for –u, -Fz Symmetry indicates Fz = 0 Mirror-symmetry time reversal theorem, Bretherton, JFM 1965 Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Two important effects 1. Confinement – Particle or obstacle dimensions are of similar order as the channel dimensions → interactions with walls 2. High Shear Rates – Allow for significant velocity differences over small length scales and therefore inertial asymmetries → i.e. leads to Dean flow, obstacle-induced secondary flows Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Small channels achieve high shear rates while avoiding turbulence Rc Rp 2 h a2 2 h a2 Rc 2000 R p 0.1 Constraints: Avoid turbulence while achieving significant shear-rate induced inertial effects For 10 m particles implies: h < ~1.4 mm Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Inertial focusing Segre and Silberberg. Nature. 1962 Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Particle Focusing and Ordering in Microchannels Flow velocity: ~ 0.1-1 m/s Channel size: ~ 50 m wide Particle size: ~ 10 m wide Polystyrene Flow Dino Di Carlo, Ph.D. www.biomicrofluidics.com Hur et al. Lab Chip 2010 Microfluidic Biotechnology Origins of inertial migration An interlude of mathematics… Close your eyes Cox and Brenner. Chem. Eng. Sci. 1968, Ho and Leal. J. Fluid Mech. 1974, Schonberg and Hinch. J. Fluid Mech. 1989, Asmolov. J. Fluid Mech. 1999, Matas et al. J. Fluid Mech. 2004 Dino Di Carlo, Ph.D. www.biomicrofluidics.com Di Carlo Lab Chip 2009 Microfluidic Biotechnology Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Implications of the dependence on curvature in velocity Dino Di Carlo, Ph.D. www.biomicrofluidics.com Amini et al. Lab Chip 2014 Microfluidic Biotechnology Effect of channel shape on equilibrium position Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Finite size effects on inertial lift Dino Di Carlo, Ph.D. www.biomicrofluidics.com Di Carlo PRL 2009 Microfluidic Biotechnology Particle size and viscosity affects focusing position Dino Di Carlo, Ph.D. www.biomicrofluidics.com Hur et al. Lab Chip 2011 Microfluidic Biotechnology Deformability-induced lift • Generally towards regions of lowest shear rate (i.e. channel centerline) Chan and Leal. J. Fluid Mech. 1979 Tam and Hyman. J. Fluid Mech. 1973 Dino Di Carlo, Ph.D. Doddi and Bagchi. Int. J. Multi. Flow. 2008 Pozrikidis. Ann. Biomed. Eng. 2005 www.biomicrofluidics.com 26 Microfluidic Biotechnology Particle equilibrium position depends on rotational diameter Dino Di Carlo, Ph.D. www.biomicrofluidics.com Hur et al. Appl. Phys. Lett. 2011 Microfluidic Biotechnology Separating particles by shape Dino Di Carlo, Ph.D. www.biomicrofluidics.com Masaeli et al. Phys Microfluidic Rev X. 2012 Biotechnology Inertial ordering Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Mechanism of dynamic self-assembly? Channel cross section Equilibrium positions What repulsive and attractive interactions are there? Dino Di Carlo, Ph.D. Lee, Amini, www.biomicrofluidics.com Stone, Microfluidic Di Carlo. Biotechnology PNAS 2010 Stokes flow with confinement Shear flow Unconfined Confined Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Wall reflection of the stresslet Flow field due to scattering of external flow (perturbation velocity field) Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Viscous reversing streamlines Stokes Flow, Re = 0 Reversing stream lines Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Experimental observation of reversing streamlines Dino Di Carlo, Ph.D. Lee, Amini, www.biomicrofluidics.com Stone, Microfluidic Di Carlo. Biotechnology PNAS 2010 Confinement and inertia = ordering Dino Di Carlo, Ph.D. Lee, Amini, www.biomicrofluidics.com Stone, Microfluidic Di Carlo. Biotechnology PNAS 2010 Channel Wall 1. 2. 3. 4. 5. Viscous disturbance from neighboring particle (repulsive) Flow profile amplifies interparticle distance (repulsive) Inertial lift leads to return to focusing position or Overshooting leads to reduction in distance again (transient attractive) Settling towards the inertial focusing equilibrium Key Point: No attractive interaction once focused! Dino Di Carlo, Ph.D. Lee, Amini, www.biomicrofluidics.com Stone, Microfluidic Di Carlo. Biotechnology PNAS 2010 Implications of this mechanism: Controlling Particle Spacing 1. Expansion reinitiates repulsive interaction 2. Distances stretched by contraction 3. No attractive interaction to pull particles back to pre-expansion distances Dino Di Carlo, Ph.D. Lee, Amini, www.biomicrofluidics.com Stone, Microfluidic Di Carlo. Biotechnology PNAS 2010 Particle-induced flows Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Net disturbance around a particle net recirculation Dino Di Carlo, Ph.D. Amini et al. www.biomicrofluidics.com PNAS 2012 Microfluidic Biotechnology Particle position in the channel affects disturbance flow Dino Di Carlo, Ph.D. Amini et al. www.biomicrofluidics.com PNAS 2012 Microfluidic Biotechnology Particle rotation increases trasnsport and translation decreases transport Dino Di Carlo, Ph.D. Amini et al. www.biomicrofluidics.com PNAS 2012 Microfluidic Biotechnology Implications of this Mechanism: Channel geometry-induced flows Controlling Particle Spacing 1. Expansion reinitiates repulsive interaction 2. Distances stretched by contraction 3. No attractive interaction to pull particles back to pre-expansion distances Dino Di Carlo, Ph.D. Amini www.biomicrofluidics.com et al.Microfluidic Nature Comm 2013 Biotechnology Dean flow Secondary rotational flows – two counter-rotating vortices for most conditions Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Superposition of inertial lift and dean flow r 1 2 Dean number H De Re 2r Dean flow velocity U D ~ De 2 / H Dean drag force if particle is held stationary in an inertial lift equilibrium position FD ~ U m2 aH 2 r 1 Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Balance of forces in curved channels Inertial lift FL U m2 a 2 a H Dean drag f c1 xc , Rc ( Ha )4 f c 2 xc , Rc Compare to weaker portion of lift 2 FL r a f Rc Rf ~ FD H H FD ~ U m2 aH 2 r 1 1. Differential focusing of different sized particles 2. Variation of focusing with flow rate If Rf < 1 over entire domain then solution will be mixed Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Improved focusing in curved channels Mixing action of Dean flow is important Dino Di Carlo, Ph.D. Gossett www.biomicrofluidics.com and Di Microfluidic Carlo. Anal. Chem. 2009 Biotechnology Focusing phase diagram in curving channels Dino Di Carlo, Ph.D. Gossett www.biomicrofluidics.com and Di Microfluidic Carlo. Anal. Chem. 2009 Biotechnology Inertial flow deformation around a pillar Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Operating range for pillars with relatively uniform transport normalized transport V y mean z 0 Vx avg λ Reynolds number Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Pillar diameter can tune the strength of the secondary flow V y mean z 0 Vx avg D w 2.2 normalized transport λ normalized pillar diameter Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology channel aspect ratio Mode of operation is governed by flow parameters normalized pillar diameter Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Position-dependent fluid manipulation Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Net secondary flows can be sequentially superimposed, enabling fluid shape engineering OPERATOR LIBRARY s operations on cross section of flow f1 x f1 ( x ) f2 x f2 f2 ( s ) f2 ( x ) f1 ( f 2 ( s )) f3 x f3 ( x ) f 3 ( f1 ( f 2 ( s ))) f 2 ( f 3 ( f1 ( f 2 ( s )))) Dino Di Carlo, Ph.D. www.biomicrofluidics.com f1 f3 s undergoes a sequence of local transformations: f2, f1, f3, f2 associated with a sequence of specific channel structures to achieve a complex final shape F(s) f2 F( s ) Microfluidic Biotechnology Sculpting flow with sequences of pillars Discretization, similar to musical notes: Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Designing a CAD program to control flow shape Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Hierarchical assembly of complex operations on the flow Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Steps to a higher level function Creation of add vertex function via recursion (i), mirroring (ii), and shaping (iii). Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology Demonstrations • Inertial focusing / separation • uFlow – flow programming. Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology End Thank you ! Dino Di Carlo, Ph.D. www.biomicrofluidics.com Microfluidic Biotechnology