Artery-on-a-Chip:
A Microfluidic Platform to Investigate Small Artery Function
1C
Lochovksy, 1S Yasotharan, 1A Vagaon, 1D Lidington,
1,2J Voigtlaender-Bolz, 1S-S. Bolz, 1A Günther
1University
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of Toronto, 2St. Michael’s Hospital, Toronto
Motivation, basic biology, current methods
A microfluidic platform for investigating blood vessels
Viability of vessels on chip
New tools for vascular biology and beyond
Why Small Resistance Arteries
Small resistance arteries: vessels prior to
capillary beds
Tissue Components: approx. 10%
endothelium, 60% smooth muscle, 30%
tissue
Highly elastic compared to capillaries, which
are fragile (95% endothelium)
Inner Outer Diameters (for mice)
R, resistance
Resistance Arteries regulate flow and
pressure drop in circulatory system
Control of blood pressure 
key element in hypertension
Conventional Methods: Cannulation & Pressure Myographs
pipettes
3cm
• Expensive, not scalable
• Platform is not versatile
(spatially, temporally)
• Method is time
consuming
• Requires high degree of
skill and training
Duling et al. Am J Physiol. 241(1), 1981
Present Microfluidic Strategies for Cardiovascular Applications
Choi et al. Nat. Mater. 6 (11), 2007
Chiu et al, PNAS, 97(6) 2000
Poster PS-9A-147, Nano to Macro Fluidic Technology
Advances
I, Exhibit Hall C tomorrow, 9-1pm
Vickerman et al.
Lab Chip 8(9) Session
2008
Tanaka et al. Lab Chip
7(2) 2007
We present one of the first organ-based microfluidic approaches
for cardiovascular research
Device Fabricated using Soft-Lithography
Master fabrication
– Spincoat Su8 for ~150µm
depth
– Verify depth using
profilometer
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2.
3.
4.
Glass Slide
Su-8
Transparency
Expose
Replica Molding, Integration
– Mold microchannel network in
elastomer (poly-dimethylsiloxane or
PDMS); the master acts as a stamp
– Degas (~2hr) and cure (~2hr)
– Plasma bond to glass slide with
tubing inserts, pin device
Xia et al, Annu. Rev. Mater. Sci., 37 (5) 1998
Microfluidic Platform
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Superfusion: flow around the vessel
– inflow  mixing outflow (green)
Perfusion: flow through lumen of the vessel
– inflow  outflow (blue)
Suction: vessel fixation (-45mmHg)
– At 8 points (orange)
All lines are liquid filled
Superfusion
Inlets and Mixing
Region of Loading Bath
Interest
(ROI)
Vessel Loading Procedure on Chip
Artery
Loading
Channel
Perfusion
Fixation
Channel
Superfusion
Microfluidic Chip achieves Flow Separation
between Superfusion and Perfusion
Concentration
Velocity
Poster PS-9B-164, Nano to Macro Fluidic Technology
Advances session II, Exhibit Hall C, tomorrow, 1-5pm
Small Artery Function
Dose drug of interest
to test smooth muscle
cells (SMCs, outside
vessel) and endothelial
cells (ECs, lumen)
We see a resulting
change in vessel
diameter
Phenylephrine Dose Response Consistent with
Conventional Data
Phenylephrine (PE) acts SMCs as a constrictor,
delivered in 3-(N-morpholino)propanesulfonic
acid (MOPS) solution
Chip is suitable for Endothelial cells and Longterm Culture
Acetylcholine (AcH) is a vasodilator
acting on ECs
Vessels are kept at physiologically
relevant pressure and temperature
Automated Processes
Diameter
Software system developed in Flow Control
MatLab containing:
– Automated/scheduled pumps
and dosing
– Automated image
processing/dose response
measurement
Measurement
Inverted
Microscope
Dose varies: 0  0.3  0.9  1.5
Automated dose response of vessel with PE on chip, repeated 10 times
Vessel response is diminished as more dose sequences are completed
Artery in Spatially Inhomogeneous
Microenvironment
Embryo
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Lucchetta et al. Nature 434 (7037) 2005
Results show Uni-sided Constriction
Summary
• Scalable microfluidic platform for
loading blood vessels developed
• Consistency of artery functional
responses, and feasibility of longterm culture
• Demonstrated automated approach
to dose response measurements
• Showed dose response in a
inhomogeneous microenvironment
Acknowledgements
• Guenther Lab group (Prof. Axel Guenther)
– Vessel members: Sanjesh, Sascha, Calvin, Alfred, Xiao
• Physiology Lab (Prof. Steffen-Sebastian Bolz, Andrei, Julia, Meghan)
• OGS, U of T Open, Barbara & Frank Milligan Fellowship
• OCE (Champions of Innovation), NSERC (Idea to Innovation)
• Industrial Collaborators: OAI Technologies, Quorum Technologies (Guelph),
Nanopoint Imaging (Honolulu)