1. Using Microfluidics to Study Tumor Hypoxia
Yunli E. Chu, Alan Soetikno, Sandra Lam, Steven C. George
Department of Biomedical Engineering, Washington University in St. Louis
INTRODUCTION MODELS AND RESULTS
METHODS
CONCLUSIONS
ACKNOWLEDGEMENTS
We have created a novel, physiologically-relevant
microfluidic device capable of replicating the tumor
microenvironment. By using an oxygen scavenger
channel adjacent to the tumor chamber, we are
able to precisely control the spatial and temporal
distribution of oxygen surrounding the tumors.
Therefore, we work to replicate tumor hypoxia,
an important physiological event responsible
for tumor metastasis.
• The device consists of two tissue chambers, a
tumor chamber and a vessel chamber, that are
approximately 0.1 mm3 in size and are connected
by three 30 μm wide pores.
• The vessel chamber was loaded with endothelial
cells and fibroblasts on day 0, while the tumor
chamber was loaded with MDA-MB-231 breast
cancer cells on day 4.
• Sodium sulfite was pumped through the adjacent
scavenger channels to create an oxygen sink.
COMSOL Model
Figure 2. COMSOL
model of oxygen
tension. The
computational model
shows the creation of
an oxygen gradient as
indicated by the
increasing oxygen
tension as distance
from the scavenger
channels increases.
PhLIM
Figure 1. Schematic of the microfluidic device
Tumor Response to Hypoxia
• We are able to create a mature vascular network and
culture MDA-MB-231 breast cancer cells in the device.
• Our device provides fine control over oxygen tension in
the tumor microenvironment.
• Our device is capable of replicating key characteristics of
tumor progression, making it a more physiologically-
relevant model of cancer metastasis than traditional
methods.
Special thanks to Dr. George, Sandra Lam, and members of the George
Lab. This research was supported by the NIH UH2-TR000481 (SCG).
George LabTransport and Tissue Engineering
Figure 3. Angiogenesis
and tumor cell migration.
A) The low oxygen
environment in the tumor
chamber induced the
sprouting of vessels from
the vessel chamber,
indicated by the arrow.
B) Low oxygen tension also
induced the migration of
MDA-MB-231 cancer cells
toward the vessel network,
a key sign of tumor
progression
Figure 4. Oxygen gradient. Phosphorescence lifetime
microscopy confirmed the existence of an oxygen gradient in
the device.
Vessel Chamber
Tumor Chamber
Scavenger Channels
Tumor Media Line
Vessel Media Line
0
1
2
3
4
5
6
7
0 500 1000 1500 2000 2500
OxygenConcentration(%)
Position from Scavenger Channel (μm)
Oxygen Measurements
No Cells
No Scavenger
Scavenger
Scavenger added
A)
B)