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Author: Gene Yu
Co-Authors: Dr. AlexBlake
Dr. David Eddington
July 29, 2010
NSF Research Experiences for Undergraduates (REU) in
Novel Advanced Materials and Processing with Applications in Biomedical, Electrical and Chemical
Engineering
Objective
 Design localized and
automated delivery system for
microfluidic brain slice
devices (μBSDs)


Delivers chemicals/drugs and
gases
Automatically mixes oxygen
 Characterize delivery of
chemicals through tissue
Image taken from
Mohammed, J, Caicedo, H, Fall, C, & Eddington, D. (2008). Microfluidic
add-on for standard electrophysiology chambers. Lab Chip, 8, 1048-1055.
Motivation
 μBSDs allow in vitro study of:
 Neurogenesis
 Synaptogenesis
 Regeneration
 Protein expression
 Responses to physical trauma
Image taken from
http://www.koki.hu/cdnb/research/research.html
Rambani, K, Vukasinovic, J, Glezer, A, & Potter, S. (2009).
Culturing thick brain slices: an interstitial 3d microperfusion
system for enhanced viability. Journal of Neuroscience
Methods, 180, 243-254.
Relevance
 Chemical Delivery
 Spatial resolution


Current systems affect entire slice
with drug
Desire stimulation of specific areas
 Oxygen Delivery
 Automatic Mixing


Saves money
Pre-mixing is not required
 Automation
 Multi-tasking
Image modified from
http://www.imagingeconomics.com/issues/articles/MI_2006-08_01.asp
Oxygen Mixing and Delivery
Experimental Set-Up
Valves
Y Connector
Output Tube
Gas Feed Lines:
0% and 21%
 Oxygen
concentration
measured by a
NeoFox Fiber
Optic Oxygen
(FOXY) sensor
Oxygen Mixing and Delivery
Output
Average Experimental
Oxygen Levels (%)
Oxygen Output
22
20
18
16
14
12
10
8
6
4
2
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21
Desired Oxygen Levels (%)
Oxygen Mixing and Delivery
Graphical User Interface (GUI)
Delivery Characterization
μBSD Design
Reservoir
T Channel
Delivery Channel
Delivery Characterization
Experimental Set-up
DI Water Lines
T Channel
Valve
μBSD
Vacuum Line
Delivery Characterization
No Tissue Delivery
10ms
15ms
20ms
25ms
2x5ms
3x5ms
4x5ms
5x5ms
Delivery Characterization
Linear Relationships: No Tissue
860
Width (µm)
1320
Width (µm)
Delivery Characterization
Linear Relationships: With Tissue
Intensity
Intensity
Full Dose Chemical Delivery
2
160
140
120
100
80
60
40
20
0
Time (min)
Maximum Intensities
y = 4.9048x + 12.668
R² = 0.898
0
0
20
10
10
20
Valve Open Time (ms)
30
30
Intensity
Intensity
Pulsing Dose Chemical Delivery
2
Time (min)
160
140
120
100
80
60
40
20
0
Maximum Intensities
y = 19.75x + 1.389
R² = 0.972
0
0
4
2
2
4
Number of 5ms Pulses
6
6
Delivery Characterization
GUI
Conclusions
 Oxygen Delivery


Precise and accurate
results
Reliable oxygen switching
 Chemical Delivery



Demonstrated linear
relationship
Area of effect: ~2mm x
2mm
Selective and
independent valve control
Acknowledgements
 Funding



NSF-REU
DoD-ASSURE
EEC-NSF Grant # 0755115
 REU Directors


Christos G. Takoudis, Ph.D.
Greg Jursich, Ph.D.
 Research Advisor

David Thomas Eddington, Ph.D.
 Mentors


Alexander Blake, Ph.D.
Gerardo Mauleon