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
1
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
2
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)
3
Membrane-less Separation Techniques
Field Flow Fractionation (FFF)
Pinched Flow Fractionation (PFF)
Myers et al. (1997)
Hydrodynamic Chromatography (HDC)
Yamada et al. (2004)
Split-flow thin fractionation (SPLITT)
Blom et al. (2004)
Electrophoresis/Dielectrophoresis
Jiang et al. (1997)
Hwang et al. (2003)
4
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
5
Inertial Microfluidics: Hydrodynamic Lift
 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
6
Inertial Microfluidics: Hydrodynamic Lift
 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
FIL
FWL
FL 
4 U f2C L a 4p
Dh2
Asmolov, J. Fluid Mech., 1999
7
Hydrodynamic Particle Focusing
Input
 Inertial lift forces equilibrate
 Particles equilibrate around the channel
periphery
 “Tubular pinch” effect –
Segre and Silberberg (1962)
Downstream
Segre and Silberberg, J. Fluid Mech., 1962
Chun et al., Phys. Fluids, 2006
Flow rate increased from Rep = 0.007 to Rep = 0.692
Bhagat et al., Lab Chip, 2008
Bhagat et al., Phys. Fluids, 2008
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Dean Flows
De = 0.23
De = 0.47
De = 0.94
Inlet
Outlet
Inlet
 Two counter rotating vortices
 Results in “Helical Flow”
 Particles experience Dean drag:
FD  3U D a p
2nd Loop
Outlet
Dh
De  Re
2R
Ookawara et al., Chem. Eng. J., 2004
9
Inlet
Outlet
 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
Bhagat et al., Lab Chip, 2008
Bhagat et al., Phys. Fluids, 2008
10
Particles equilibrate
in a single focused
stream
 Inertial lift forces dominant - particles equilibrate near inner wall
 De = 0.2 - 0.94
11
Separation Principle
 Position of the particle stream depends on the ratio of
lift and drag forces:
FL
 a 3p
FD
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Fabrication
5
4 3 2
6
7
8
1
Inlets
Outlets
 A 5 loop Archimedean spiral
 Length: 40 cm
 Width: 500 µm
 Height: 90 µm to 140 µm
 Outlets: 100 µm wide
13
10 µm Particles
0.5
90um
110um
130um
0.4
x/W
140um
0.3
0.2
0.1
0
0
4
8
12
16
20
Dean number (De)
 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
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20 µm particles
15 µm particles
0.5
0.5
90um
90um
110um
110um
130um
0.4
130um
0.4
140um
0.3
x/W
x/W
140um
Dean drag
dominates
0.2
0.3
Lift force
dominates
0.2
0.1
0.1
Lift force
dominates
0
0
0
4
8
12
Dean number (De)
16
20
0
4
8
12
16
20
Dean number (De)
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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
16
(× 103)
250
150
SSC - A
1
10 µm
particles
0.9
20 um
100 50
150100
200150
250200
(× 103)
250
(× 103)
Output 3 Output 3
20 µm
particles
100
10 µm
particles
15 um
0.7
10 um
0.6
0.5
0.4
0.3
0.2
15 µm
particles
150
SSC - A
15 µm
particles
20 µm
particles
Normalized particle count
0.8
(× 103)
250
(× 103)
250
10 µm
particles
150
15 µm
particles
15 µm
particles
15 µm
particles
FSC - A FSC - A
200
20 µm
particles
20 µm
particles
(b)
100
100
100
50
SSC - A
(× 103)
250
200
SSC - A
15 µm
particles
20 µm
particles
150
(× 10 )
250
Output 2 Output 2
20 µm
particles
50
250
(× 103)
(b)
200
150
200
(× 103)
250
250200
(× 103)
200
200150
FSC - A FSC - A
10 µm
particles
10 µm
particles
50
150100
(a)
100
150
15 µm
particles
10 µm
particles
10050
50
Output 1 Output 1
200
20 µm
particles
SSC - A
150
SSC - A
100
15 µm
particles
20 µm
particles
50
150
50
100
10 µm
particles
Input
100
(× 103)
250
200
Input
200
(× 10 )
250
Flow Cytometry Data
0.1
10 µm
particles
0
50
100 50
150100
200150
250200
(× 103)
FSC - A FSC - A
(c)
50
250
(× 103)
3
4
5
6
7
8
Outputs
10050
150100
200150
250200
(× 103)
FSC - A FSC - A
(d)
2
50
50
50
50
1
250
(× 103)
(d)
 Separation efficiencies of 85-90% were obtained
 May be improved for monodispersed particle solutions
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Fluorescence intensity
0.8
0.7
0.6
1.9
Particle Separation/Filtration
0.5
Outlet
0.4
Outlet
0.3
0.2
590 nm
0.1
590 nm
0
0
20
40
60
100
80
Microchannel w
1.9 µm & 590 nm
780 nm
 Complete filtration of sub-micrometer particles
 Extraction of particles from a mixture
18
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
19
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
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