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.

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1 Lab-On-A-Chip Sensor for On-Site Detection and Sizing of Nanoparticles A. A. S. Bhagat and I. Papautsky BioMicroSystems Research Laboratory 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 Split-flow thin fractionation (SPLITT) Pinched Flow Fractionation (PFF) Yamada et al. (2004) Hydrodynamic Chromatography (HDC) Blom et al. (2004) Jiang et al. (1997) Field Flow Fractionation (FFF) Myers et al. (1997) Electrophoresis/Dielectrophoresis Hwang et al. (2003)

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

6  Shear induced inertial lift force (F IL )  Parabolic velocity profile of Poiseuille flows  Particles roll down towards the microchannel walls  Directed away from the microchannel center  Wall induced lift force (F WL )  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 (F IL )  Parabolic velocity profile of Poiseuille flows  Particles roll down towards the microchannel walls  Directed away from the microchannel center  Wall induced lift force (F WL )  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 F IL F WL Asmolov, J. Fluid Mech., 1999 Inertial Microfluidics: Hydrodynamic Lift

8 Hydrodynamic Particle Focusing  Inertial lift forces equilibrate  Particles equilibrate around the channel periphery  “Tubular pinch” effect – Segre and Silberberg (1962) Chun et al., Phys. Fluids, 2006 Bhagat et al., Lab Chip, 2008 Bhagat et al., Phys. Fluids, 2008 Segre and Silberberg, J. Fluid Mech., 1962 InputDownstream Flow rate increased from Re p = to Re p = 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 a p /D h > 0.07 equilibrate at the inner wall  Particles with a p /D h < 0.07 are entrained in the Dean vortices Bhagat et al., Lab Chip, 2008 Bhagat et al., Phys. Fluids, 2008 Inlet Outlet

11  Inertial lift forces dominant - particles equilibrate near inner wall  De = Particles equilibrate in a single focused stream

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  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 10 µm Particles

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

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

18 Particle Separation/Filtration  Complete filtration of sub-micrometer particles  Extraction of particles from a mixture 780 nm 1.9 µm & 590 nm 590 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/OH )  University of Cincinnati Institute for Nanoscale Science and Technology