Lab-On-A-Chip Sensor for On-Site Detection and Sizing of Nanoparticles

1. Lab-On-A-Chip Sensor for On-Site Detection and Sizing of Nanoparticles A. A. S. Bhagat and I. Papautsky BioMicroSystems Research Laboratory www.biomicro.uc.edu Department of Electrical and Computer Engineering College of Engineering, University of Cincinnati

2. Why Separate Particles? • Fate and transport of micro- and nano- particles • Water and air quality • Enter human metabolic system – inhaling, drinking • Lung and intestinal tract inflammation • Nanomanufacturing – tighter size control • Biological sample preparation • Cell sorting • Bacteria detection - sample pre-concentration • Virus detection

3. Microfiltration • Typically use membrane-based filtration • Dependent on pore size – cannot be used for wide range of sizes • Need periodical cleaning • High cost for small particle sizes H. Sato et al. (2004)

4. Membrane-less Separation Techniques Field Flow Fractionation (FFF) Pinched Flow Fractionation (PFF) Split-flow thin fractionation (SPLITT) Myers et al. (1997) Hydrodynamic Chromatography (HDC) Yamada et al. (2004) Blom et al. (2004) Electrophoresis/Dielectrophoresis Jiang et al. (1997) Hwang et al. (2003)

5. Inertial Microfluidics: Hydrodynamic Lift Shear induced inertial lift force (FIL) Parabolic velocity profile of Poiseuille flows Particles roll down towards microchannel walls Directed away from microchannel center

6. Shear induced inertial lift force (FIL) Parabolic velocity profile of Poiseuille flows Particles roll down towards the microchannel walls Directed away from the microchannel center Wall induced lift force (FWL) Flow field around particles disturbed due to presence of walls Wall induced asymmetric wake exerts a lift force on particles Directed away from the microchannel wall Inertial Microfluidics: Hydrodynamic Lift

7. Shear induced inertial lift force (FIL) Parabolic velocity profile of Poiseuille flows Particles roll down towards the microchannel walls Directed away from the microchannel center Wall induced lift force (FWL) Flow field around particles disturbed due to presence of walls Wall induced asymmetric wake exerts a lift force on particles Directed away from the microchannel wall Inertial Microfluidics: Hydrodynamic Lift FIL FWL Asmolov, J. Fluid Mech., 1999

8. Hydrodynamic Particle Focusing Input Downstream • Inertial lift forces equilibrate • Particles equilibrate around the channel periphery • “Tubular pinch” effect – Segre and Silberberg (1962) Segre and Silberberg, J. Fluid Mech., 1962 Chun et al., Phys. Fluids, 2006 Bhagat et al., Lab Chip, 2008 Bhagat et al., Phys. Fluids, 2008 Flow rate increased from Rep = 0.007 to Rep = 0.692

9. Dean Flows • Two counter rotating vortices • Results in “Helical Flow” • Particles experience Dean drag: Ookawara et al., Chem. Eng. J., 2004

10. Inertial lift force pushes particles towards equilibrium positions • Dean drag aids/opposes particle migration to equilibrium positions • Particles with ap/Dh > 0.07 equilibrate at the inner wall • Particles with ap/Dh < 0.07 are entrained in the Dean vortices Outlet Inlet Bhagat et al., Lab Chip, 2008 Bhagat et al., Phys. Fluids, 2008

11. Particles equilibrate in a single focused stream • Inertial lift forces dominant - particles equilibrate near inner wall • De = 0.2 - 0.94

12. Separation Principle • Position of the particle stream depends on the ratio of lift and drag forces:

13. Fabrication • A 5 loop Archimedean spiral • Length: 40 cm • Width: 500 µm • Height: 90 µm to 140 µm • Outlets: 100 µm wide

14. 10 µm Particles • For a given channel height, the particle stream moves away from the channel wall at increasing De, indicating a dominance of Dean drag • Particle stream position can be altered either by increasing De or by increasing the channel height

15. 20 µm particles 15 µm particles Dean drag dominates Lift force dominates Lift force dominates

16. Multi-Particle Separation • Mixture of 10 µm (DAPI), 15 µm (FITC), and 20 µm (TRITC) particles was run through a 130 µm high channel at De = 14.4 • Particle streams focused 180 µm (10 µm), 120 µm (15 µm), and 65 µm (20 µm) from inner wall

17. Flow Cytometry Data • Separation efficiencies of 85-90% were obtained • May be improved for monodispersed particle solutions

18. Particle Separation/Filtration • Complete filtration of sub-micrometer particles • Extraction of particles from a mixture 590 nm 1.9 µm & 590 nm 780 nm

19. Conclusions • First demonstration of multiple particle separation using inertial microfluidics in spiral microchannels • Passive separation technique capable of very high throughput particle sorting • 80~90% separation efficiency • Planar and passive nature of this technique enables easy integration with other lab-on-a-chip components

20. Acknowledgements • National Institute of Occupational Safety and Health (NIOSH) Health Pilot Research Program (T42/OH008432-04) • University of Cincinnati Institute for Nanoscale Science and Technology