This document describes the design of an open source pressure control system to study the response of endothelial cells to pressure in vitro. The system uses a syringe pump with an Arduino microcontroller and PID control algorithm to maintain a constant pressure. 3D printed components and readily available parts keep the total cost around $350, much lower than commercial alternatives. The goal is to control pressure accurately enough to observe endothelial cell and vascular structure responses. Future work includes improving the portable design and using it to study differences between arterial and venous endothelial cells or blood vessel formation under pressure.

1. b
Design and Engineering of Open Source Hardware for Pressure Regulation in the
Study of Vascular Processes
Alexander Novokhodko1, Christian Mandrycky1, and Ying Zheng1,2,3
1Department of Bioengineering, 2Center for Cardiovascular Biology, 3Institute of Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA ZHENGLAB
Goal: Controlling Pressure to study endothelial cell
response in vitro
Approach:
o Syringe Pump based Control System
o Ensuring Steady Flow
o In vitro microvessels in flow chamber
3
Existing Problems:
Oscillation at set point:
• Current Percent Error: 2.95%, 2.97%, 4.547%.
Imperfect Adaptation: Steady state deviation from set
point
• .0935%, 1%, 2.835%
Target: Maximum Percent Error + Adaptation must not
exceed 2% to match [6]
• Currently, worst case error is 7.382%. Too high!
Solution: PID Control (Proportional, Integral,
Differential)
• Problem: Motor step size is too large to implement a
PID Duty Cycle
• Solution: Gearing down the motor (see Figure 6)
Unsteady flow: Flow is currently pulsatile/disrupted
• Adjust when the valve (figure 5) is open or closed
Figure 1: Forces on Endothelial
Cells. [1]
Results
The Biological Need: Cells Under Pressure
Problem: High cost of
commercially available hardware
• $4,767 for Constant Pressure
Syringe Pump from Harvard
Apparatuses [6]
Solution: Open Source Hardware
Exchange of CAD files
• OpenSCAD
• My work is based on “Open-
Source Syringe Pump Library” [7]
published in PLOS ONE
• Creative Commons Attribution
License
3D Printing
• Low cost (see Table 1)
Rapid Prototyping
• See Figures 5 and 6
Customizability
Arduino Microcontroller
• Arduino code and explanation of
algorithm available upon request
Why Open Source Hardware?
Endothelial cell response to blood
pressure:
• Vasoconstriction, vasodilation
• Veins vs. Arteries
• Venous endothelial cells differ
from arterial ones. [2]
• Why? Pressure? Or different
signals during development?
• Can we use this to prevent
saphenous vein graft failure
during coronary bypass
surgery?
Vasculogenesis/Angiogenesis during
development
• Once the embryonic heart starts
beating the vasculature remodels. [3]
How?
Steady flow:
• Outside the largest arteries, flow is
steady, not pulsatile
• Except in the aorta, flow is laminar [4]
• Pressure is approximately constant
In vitro studies:
• Study effect of pressure in isolation
• Control pressure to study other
variables
Need: Pressure Control System that
maintains steady laminar flow
References
1. Davies, P. & Tripathi, S. Mechanical stress mechanisms and the cell. An endothelial paradigm.
Circulation Research 72, 239-245 (1993).
2. dela Paz, N. & D’Amore, P. Arterial versus venous endothelial cells. Cell Tissue Res 335, 5-16 (2008).
3. Mechanisms of angiogenesis. Nature 386, 671-674 (1997).
4. Stein, P. & Sabbah, H. Turbulent blood flow in the ascending aorta of humans with normal and
diseased aortic valves. Circulation Research 39, 58-65 (1976).
5. Klabunde, R. CV Physiology: Systemic Circulation. Cvphysiology.com (2016). at
<http://www.cvphysiology.com/Blood%20Pressure/BP019.htm>
6. Standard PHD ULTRA™ CP Syringe Pump. Harvard Apparatuses (2016). at
<http://www.harvardapparatus.com/pumps-liquid-handling/syringe-pumps/constant-
pressure/standard-phd-ultra-trade-cp-syringe-pump.html>
7. Wijnen, B., Hunt, E. J., Anzalone, G. C., & Pearce, J. M. (2014, September 17). Open-Source Syringe
Pump Library. PlosONE, 9(9), 1-8. doi:10.1371/journal.pone.0107216
8. Tiny Planetary Gears Set by aubenc. Thingiverse.com (2012). at
<http://www.thingiverse.com/thing:23030>
9. Zheng, Y. et al. In vitro microvessels for the study of angiogenesis and thrombosis. Proceedings of the
National Academy of Sciences 109, 9342-9347 (2012).
Figure 2: Pressure in different parts
of the circulation [5]
Control Systems
Figure 3: Basic Schematic of Syringe Pump-
Based Constant Pressure System
Figure 4: Maintaining a constant water pressure across a flow chamber
Future Applications:
Casing: To improve portability and usability
Vasculogenesis/Angiogenesis: Prepare flow chambers
with collagen seeded with endothelial cells
• Apply constant pressure at inlet
• Observe vasculogenesis in pressurized vs. control gel
Veins vs. Arteries
• Make flow chambers with channels, seeded with
endothelial cells.
• The vessels in “In vitro microvessels for the study of
angiogenesis and thrombosis” [9] are a starting point
• Apply pressures characteristic of veins and arteries
(Figure 2) and observe differences in cell phenotype
Component Cost
Arduino Uno R3 (Atmega328 -
assembled)
$24.95
3D-Printed Components (PLA
filament)
<$4.00
NEMA-17 Stepper Motor $14.00
Omega Low Pressure Transducer $205.00
Polulu Adjustable Boost
Regulator
$11.95
Readily Available Mechanical
Components (bolts, z-couplings,
nuts, resistors, wires, etc.)
<$10.00
Two-way normally closed
solenoid pinch valve; 12 VDC,
1/32" ID x 3/32" OD tubing
$62.00
Adafruit Motor/Stepper/Servo
Shield for Arduino v2 Kit - v2.3
$19.95
Total 351.85
Table 1: Cost of pump
components
Figure 6: Geared down motor 3D
printed prototype. Derived from [8]
Figure 5: Clockwise from top left:
1: Circuit Diagram of Control
System, 2: Valve on Outlet, 3: Flow
validation via fluorescence
microscopy 4: Pump during flow
validation.
Figure 7: In vitro microvascular
networks are the specialty of the
Zheng Lab [9]
Acknowledgements: We acknowledge the support from the Zheng lab and NIH awards (1DP2DK102258 and UH2/UH3 TR000504)