SIMULATING FLUID FLOW THROUGH A CULTURE CHIP FOR CELL ...
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SIMULATING FLUID FLOW THROUGH A CULTURE CHIP FOR CELL MIGRATION
STUDIES IN MICROGRAVITY
ATUL DHALL
CASTRACANE LAB
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THE PROJECT
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GOAL: To study cancer cell migration in microgravityNEED: To uncover potential therapeutic targets for cancer cells
CNSE Role: Design cell migrationexperiments and study howmigration differs in microgravity
SpacePharma Role: Build an end-to-end system to facilitate suchstudies in Low Earth Orbit
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LAB BACKGROUND - NANIVID
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Raja et al. (2012) | Williams et al. (2016)
Scale bar: 100 µm
2 μM EGF Negative Control
• Nano Intravital Device – an implantabledevice to study cancer cell migration
• Releases EGF causing migration ofcancer cells
We are trying to rework such experiments in microgravity
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THE MIGRATION LAB
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Illustration of the migration lab
Source: SpacePharma, Inc.
We build the chips
Develop Research Strategy
Customize Lab
Place Lab inMicrogravity
Control Experimentfrom Earth
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ROLE OF COMSOL MULTIPHYSICS
To simulate fluid flow through the chips we build
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By default gravitational forces are not taken into account
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USE OF COMSOL MULTIPHYSICS
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Computational Fluid Dynamics Module
Single phase flow (spf) study on cell growth media (DMEM)under laminar conditions
• To determine optimum shape of culture chip andoperating flow rate range
Transport of diluted species (tds) study for diffusion ofchemoattractant (EGF) across a migration channel
• To conduct experiments on practical timescales andestimate migration rate
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INITIAL CULTURING SYSTEM
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Media Inlet for flushing
Media Inlet for cell culture
Trypsin Inlet Cell culture chambers
Outlet
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SHAPE OF CULTURE CHAMBER
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Uniform flowRounded rectangle
Uniform flowCircular chamber
Pinched flowCircular chamber
Uniform flowRectangular chamber
m/s
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CURRENT DESIGN OF CULTURE CHIP
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• Current version of the chip has 3 reservoirs• Diameter of inlet and outlet is 1 mm• Migration channel is 5 times narrower than inlet• Height throughout is 1.5 mm
8 mm
12 mm
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FLOW THROUGH CULTURE CHIP
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• VIC = input velocity for the inner chamber
• VOC = input velocity for the outer chambers
• Leakage through all migration channels
VIC = - VOC
Antiparallel case
VIC
VOC
m/s
Leak
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OPTIMAL FLOW RATE FOR CONNECTED CHIP
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Leak
VIC : VOC :: 1 : 6 VIC : VOC :: 1 : 1
VIC : VOC :: 6 : 1 VIC : VOC :: 18 : 1
Beyond a threshold ratio, VIC becomes too large in comparison to VOC and media leaks through the third channel
VIC
VOC
m/s
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WHAT ABOUT DIFFUSION OF EGF ?
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Inward diffusion of chemoattractant (EGF)
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EGF DIFFUSION
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• Diffusion of 0.04 mM EGF across a 0.6 mm long channel
• Diffusion coefficient of EGF taken as 5.18 X 10-11 m2/s
• Timescale of diffusion is practical for conducting cellmigration experiments in culture chips
• Cell migration is normally a few hundred µm/hr in thepresence of a chemoattractant gradient
t = 0 s t = 500 s t = 1000 s
mM
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SUMMARY
• Microgravity leads to changes in proteomic and genomicexpression of cancer cells
• Migration studies in microgravity can help uncover noveltherapeutic targets for metastatic behavior
• Spf studies led to improving the shape of the culture chamberand gauging an optimal operating flow rate range
• Tds studies point to the timescale over which diffusion of EGFcan take place
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FUTURE CHIPS
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• 3D printed mold using FormLabs Form 1+
• 8 inlets, 2 outlets and a membrane
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ACKNOWLEDGMENTS
Dr. James Castracane
Dr. Natalya Tokranova
Dr. Madhu Hemachandra
Tim Masiello
Matt Strohmayer
Logan Butt
Andee Ott
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Office of the Chief Scientist (Israel) and SUNY Polytechnic Institute for funding
Dr. Molly Mulligan
Dr. Yair Glick
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THANK YOU
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SUPPLEMENTAL
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Nickerson et al. (2004)