presentation - Hitech Projects

Nature-inspired micro-fluidic
manipulation using artificial cilia
Artic
This work is partly funded by the European Commission in the NMP-2004-033274, ARTIC project

Nature-inspired micro-fluidic manipulation using artificial cilia
Why Micro-fluidics?
A European Specific Targeted Research Project
pre-treatment
valves, pumps
sample
DNA amplification
electronics
universal
I/O
detection
Bath, UK
Targeted diagnostics
•Genomics
•Proteomics
•Metabolomics
•Cell Bio
Eindhoven, NL
Groningen, NL
Bucharest, RO
Sample prep is key
Freiburg, DE
Liquids research, UK
•“Sample preparation” and “micro-fluidics” are intimately connected
•For complete solution, sample prep and micro-fluidics are indispensible
•Philips can make a difference in micro-fluidics and sample-prep
•Up to now, this has been an underestimated field within Philips
Philips, NL
Delft, 2 NL
http://www.artic-project.eu/

Fluid propulsion in micro channels using
magnetically-actuated artificial cilia: a biomimetic
approach
Syed Khaderi 1 , Michiel Baltussen 2 , Patrick Anderson 2 , Daniel Ioan 3 ,
Jaap den Toonder 2 and Patrick Onck 1
1
University of Groningen, 2 Eindhoven University of Technology,
3
Universitatea Politehnica din Bucuresti

Fluid propulsion Why in Micro-fluidics? lab-on-a-chip
Lab on a chip manufactured by Siemens
pre-treatment
valves, pumps
DNA amplification
electronics
universal
I/O
sample
detection
•“Sample preparation” and “micro-fluidics” are int
•For complete solution, sample prep and micro-flu
•Philips can make a difference in micro-fluidics an
•Up to now, this has been an underestimated field
http://starcentral.mbl.edu/eutree_workshop/protistiary/rarbur/rarbur_01.htm
Design externally controlled artificial cilia that can create flow in micro-channels.

Approach
Questions:
• Cilia geometry
• Material properties
• Initial configuration
• Magnetic field
• Flow generated
Magnetostatics
Solid mechanics
Fluid mechanics

Super-paramagnetic cilia
Periodic array of cilia
Tapered cross-section
Rotating magnetic field

Metachronal motion of cilia
Image source: http://starcentral.mbl.edu/eutree_workshop/protistiary/rarbur/rarbur_01.htm

Metachronal motion of cilia

Summary
• A tapered super-paramagnetic film mimics the
beat motion of natural cilia.
• Synchronously beating cilia create a
fluctuating fluid flow.
• Metachronal motion of cilia drastically
reduces the negative flow, increasing the net
fluid transport.

Fluid propulsion by cilia in a shear-thinning fluid
Michiel Baltussen, Patrick Anderson,
Jaap den Toonder

Background
Artificial cilia Lab-on-Chip Medical diagnostics Biological fluids Saliva
Saliva is a water based polymer solution -> non-Newtonian
Investigate the differences between
a Newtonian and a non-Newtonian fluid driven by cilia

Background
• Saliva rheological data is scarce
• We measured the shear-viscosity
Human Whole Saliva, test of 6 different individuals:

Model
Constitutive equations:
-Neo-Hookean solid
-Newtonian or shear-thinning fluid

Results: ciliar motion
Newtonian: 0.1 Pas
Shear-Thinning: saliva
Forward stroke
Backward stroke
Motion when the flow is time periodic

Results: flowrate

Conclusions & Future Work
• The motion of cilia in a shear-thinning fluid
differs from the motion in a Newtonian fluid
• The net flow is more sensitive to the actuation
force
• Perform simulations with a viscoelastic model

Fabrication of artificial rubber cilia by
photolithography
Jacob Belardi, Nicolas Schorr, Oswald Prucker,
Stephen Wells, Vijay Patel, Jürgen Rühe

System
Elastic polymer matrix filled
with magnetic nanoparticles
Large cilia arrays
Challenge:
How to generate different polymeric structures
in a standard lithography process
Polymeric anchoring strip

Two color lithography process
Cilia
Anchors
MABP crosslinker
OPA crosslinker
H
C
H
O
O
O
hydrophilic surface
sacrifial layer
H
C
H
O
O
O
H
C
OH
O
O
magnetic rubber/
cilia structures
development
(rinse with toluene)
H
C
OHO
O
UV-A (365 nm)
hydrophilic coating
release
(rinse with water)
UV-C (250 nm)

Artificial cilia arrays
Rubber cilia
- Stable – covalent attachment to surface
- Very flexible
- Magnetic content: 38 % by weight (TGA,XPS)
Cilia arrays
Hundreds of individual cilia
High yield of working cilia (>99%)
Variable geometry
Cilia in different sizes and shapes available
Integration in microfluidic channel
Channel formed by substrate with cilia,
PDMS casket and glass top plate

Conclusions
We use photoreactive copolymers and
ferrofluids to fabricate artificial cilia
UV
Two color lithography uses two different
crosslinkers, sensitive to different types of
UV-radiation
The cilia consist of rubber matrix, filled with
magnetic nanoparticles and are anchored to
the surface with one end
Large arrays of cilia were produced and high
yields of working cilia were achieved
The process is very flexible and allows to
produce cilia with different geometries

Magnetically actuated polymer flap arrays
as an example for artificial cilia
Nicolas Schorr, Jacob Belardi, Oswald Prucker,
Stephen Wells, Vijay Patel, Jürgen Rühe

Magnetic actuation
Setup for magnetic actuation:
• Closed microfluidic chamber /w cilia substrate
• Rotating permanent magnet underneath chamber
• Observation through microscope in top view.
• Rotating magnet generates a field which rotates
in the opposite direction.

Magnetic actuation
• Initial position of cilia is parallel to the substrate.
• Upon field rotation cilia flip into an upright position and back.
Composite flaps can be actuated using rotating magnetic fields

Asymmetric motion
Snapshots of a single flap taken during
a half rotation cycle of the magnet
Asymmetric response of the flaps in
shape and response time.
FLOW

Effective Flow
• Z-profile follows basic parallel plate model
• Velocities of up to hundreds of m/s
• Effective flow rates of ~30l/min

Conclusions
• Magnetically actuated artificial cilia can generate net flow in microchannels.
• Effective flow rates of up to 30 l/min are possible. Such values are
comparable to values found for other microfluidic pumps.
• Artificial cilia do not require external connections, and are compatible with
bio-fluids.

An integrated system with magnetically driven
artificial cilia
Bogdan Craus, Nicolas Schorr, Jacob Belardi, Jeanette
Hussong, Michel Jongerius, Jaap den Toonder

Concept
Epifuorescent
microscope
µPIV
B
Sketch of device for generation fluid flow:
•magnetic actuation system with integrated fluidic cartridge
•fluid characterization can be done by µPIV.

Approach
Microfluidic device requirements
• optical access for cilia and flow characterization
• minimum flow resistance
• reusable optical part
• fluid compatibility (control of cilia hydrophobicity)
• tracer particle compatibility
Magnetic actuator requirements
• available space limited by optical access and
cartridge design 40mm X 20mm X 5mm
• B > 25mT
• field uniformity acceptable variation no
more than 5% per cilia length. Note that
quantitative measurements of local fluid velocity
are possible with a resolution higher than 200μm
(and better).
FEM simulations
100µm 100µm

Results
Cilia side
view
through
prism
a) images of a cilium with increasing magnetic field applied in the vertical plane and zero
background flow; the width of the cilium is 20μm; b) projected length as a function of
applied field in zero and 300μL/min background flow; c) side view image of a cilium
covered with fluorescent particles; d & e & f) the same cilia measured in a background
flow of 300µl/min at magnetic field values of 0A/m, 12kA/m and 24kA/m

Summary
•Integrated system in which magnetically actuated artificial cilia
generate flow through microchannels
•Microfluidic cartridge
•Magnetic actuation system
•Concept allows optical characterization of the flow and the cilia
movement
•Concept is suitable for a real (lab on a chip) device using ciliadriven
flow
•Experiments show characterization of cilia by themagnetic field,
and with or without background flow.

Experimental investigation of the flow
induced by artificial cilia in micron-sized
channels
Jeanette Hussong, Nicolas Schorr, Jacob Belardi,
Bogdan Craus, Jerry Westerweel

Approach
CCDcamera
1
Computer
Trigger &
timing unit
Laser
filter
cube
lens
Microscope
CCDcamera
2
Motion controler &
Signal generator
motor

Results
direction of net flow

Median velocity [mm/s]
Vertical magnetic field [mT]
Results
2
1
200
100
*1
0
0
-1
-2
*1
0 50 100 150 200 250 300
Magnet orientation []
-100
-200

z-position [m]
Results
500
400
,
300
200
100
h=40
0
-50 0 50 100 150
velocity [m/s]

Conclusions
The cilia-induced flow is strongly oscillatory, indicating
that fluid transport can be enhanced if the cilia beat is
improved.
Without backpressure the artificial cilia induce a net
volume flow rate of ~14 l/min at 10 Hz actuation.
100
0
-100