Towards a Bioartificial Kidney:
Validating Nanoporous Filtration Membranes
Jacob Bumpus, BME/EE 2014
Casey Fitzgerald, BME 2014
Michael Schultis, BME/EE 2014
Background
•
600,000 patients were treated for end stage renal
disease (ESRD) in the US alone in 2010
• Current treatment procedures include kidney
transplant and routine dialysis
• Dialysis: COSTLY
•
•
•
•


$$: ~$65,000/patient/yr.
TIME: often requiring 3 treatments /wk.
Significant shortage of donor organs for transplant
means that many patients are left with no options
other than years of routine dialysis
Development of an implantable bioartificial kidney
(BAK) would revolutionize treatment of end stage
renal disease (ESRD).
Concept illustration of an implantable bioartificial kidney. Courtesy of Shuvo Roy
Improve patient outcomes
Reduce economic burden of treatment
Image Citation:
Fissell, William H., Shuvo Roy, and Andrew Davenport. "Achieving more frequent and
longer dialysis for the majority: wearable dialysis and implantable artificial kidney
devices." Kidney international 84.2 (2013): 256-264.
Background
•
Dr. Fissell is working to develop
an implantable bioartificial
kidney using nanoporous silicon
membranes as biological filters
•
These chips feature nanometerscale pore arrays, invisible to
optical characterization methods
Screenshots courtesy UCSF School of Pharmacy
http://pharmacy.ucsf.edu/kidney-project/
Problem Statement
• In order to verify the silicon chips received from their collaborators, the
Fissell Lab uses a set of experiments to measure the chips’ filtration
performance under a variety of conditions and correlate this to their pore sizes
• The Fissell lab must manually configure these filtration experiments, monitor
them continuously throughout their duration (sometimes days to weeks
long), and collect data by hand
• Current experiments are unable to simulate physiologically relevant fluid
flow profiles, and are limited to constant flow rates
• No failsafes exist in order to protect the silicon membranes from being
damaged in the event of deviations from preset conditions
•
Our design:
•
Increases efficiency of experimentation
by fully automating a variety of test
protocols, allowing the group to
characterize more chips
•
•
Efficiency
Control
Experimental
Relevance
Lost time
Lost $
Disorder
Man hours
Reduce
•
Reduces project risk of lost time and
money by adding failsafes against chip
fracture ($1000’s/chip)
Maximizes experimental control by
tightly coupling pressure monitoring to
hardware output and adjusting for
temporal drift
Adds greater experimental relevance
by allowing an adaptable physiological
input platform, including simulation of
pathophysiologic pressure conditions
(hypertension)
Increase
Clinical Relevance
Needs Statement
To design an integrated hardware/software suite that
will streamline verification of these silicon
membranes while maximizing experimental control
and precision and minimizing user involvement
Goals
•
Experimental setups should be fully automated, permitting the lab technician to
begin the experiments and then cease involvement except for occasional system
monitoring
•
Allow user-defined hardware setup so that numerous different experiments can be
run from the same system that is modular and expandable
•
An intuitive graphical user interface (GUI) should be developed in order to allow the
user to control multiple experiments in an effective and efficient manner so that
setting the experiment parameters is secondary to deciding what the parameters should be.
•
Add flow rate control and dialysate measurement to the current pressure control
feedback system.
Factors
• Software Platform
•
LabVIEW more $ / much less development time
• Software concurrency
•
More fewer programs running but internals are more complex
• Hardware connections
•
Fewer cheaper in size and $ but more technically challenging
Experiments
• The solution must automate three modes of experimentation
• Hydraulic Permeability Mode
•
Measures convective flow across membrane at various pressures (uL/min/psi)
• Filtration Mode
•
Collect filtrate samples at various pressures for further analysis
• Dialysis Mode
•
Sets and Measures diffusive flow across membrane with no pressure differential
• Filtration and Dialysis Mode should include an option to run with constant
flow or a periodic waveform
SYSTEM AND ENVIRONMENT
Experimental Setup – Dialysis Mode
Peristaltic Pump
Filtration
Membrane
Peristaltic Pump
Air Regulator
Dialysate Side
Blood Side
To House Air
Syringe Pump
PSI
PSI
To House Air
Feedback Control Diagram
Pressure
Transducer 1
Voltage
Signal 1
ADC
Setpoint Flows
or Waveforms
Arduino/LabVIEW
Pump VI
Σ
ΔV
Σ
Error
PID Loop
Voltage
Conversion VI
Setpoint
Pressure
Pressure
(Blood)
RS-232
Signals
Peristaltic Flow
Pumps Rate
Pressure
Transducer 2
ΔP
Voltage
Pressure
Pressure
Regulator 1 (Blood)
Voltage
Pressure Pressure
Regulator 2 (Dialysate)
ADC
Voltage
Signal 2
HP
Pressure
(Dialysate)
Σ
Σ
Control Box Concept
AC Power Line
Pressure Transducers
1
2
4
3
6
5
7
8
Pressure Regulators
1
2
4
3
5
6
7
8
General Purpose USB
1
2
3
4
5
6
7
Power
Supply
H
N
G
24
12
5
-12
Through Hole Board
R
8
9
10
11
12
13
Control Box: Front View
14
C
USB Hubs and Female Connector Ports
Control Box: Top View
Ultrasound Blood Velocity Reading
Velocity (cm/s)
Estimated Waveform
Time (s)
Generated Pressure Waveform
Comparison
Software Architecture Diagram
Top Level Menu
Quadrant 1
Hydraulic
Permeability
Quadrant 2
Quadrant 3
Filtration
Quadrant 4
Dialysis
Hardware select
Hardware select
(Pump, Transducer/Regulator, Balance)
(Pump, Transducer/Regulator, Balance)
Hardware select
(2x Pump, 2x Transducer/Regulator, Balance,
Syringe Pump)
Experimental
Runtime GUI
Peristaltic
Pump
Syringe
Pump
Pressure
Transducer
Air
Regulator
Calibration
Mass
Balance
Experiment
Overview
Top Level Menu
Hardware Select
Experimental Runtime GUI
Experiment Overview
Pressure Transducer
Transducer Calibration
Experimental Runtime GUI
Mass Balance
Peristaltic Pump
Syringe Pump
Hydraulic Permeability Experiment
Load from File
Hydraulic Permeability Results
Experiment Results
Data Log
Fail Safes
• Set point = 0
•
Overrides the PID controller
• Record Max/Min Pressure
•
•
Alert user of potential errors
Next: Automatic shut-down
• Error Handling
•
What to do if something
goes wrong?
Recent Progress
•
LabVIEW Control of
•
•
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Pressure transducer (COMPLETE)
Pressure Regulator (COMPLETE)
Peristaltic Pump (COMPLETE)
Mass balance (COMPLETE)
Syringe Pump (IN PROGRESS)
LabVIEW PID feedback loop for pressure setup
Improved/updated circuitry
Initial iterations of pulsatile flow
Abstract submission to American Society for Artificial Internal Organs (ASAIO)
Student Design Competition
Fully Automated Hydraulic Permeability Experiment
Initial Fail-safes and Error handling
Next Steps
• Continue to iterate towards more physiologically
relevant pulsatility
• Develop Dialysate Mode Automation
•
Incorporate syringe pump control into complete system
• Finalize power supply and order all components
• Develop a 1st iteration CAD model of our hardware
container
Gantt Chart
Special Thanks To:
• Vanderbilt University Medical Center
• Vanderbilt School of Engineering
• Vanderbilt Renal Nanotechnology Lab
•
Dr. William Fissell
•
Joey Groszek
• Dr. Amanda Buck
• Dr. Tim Holman
• Dr. Matthew Walker III
• JustMyPACE Peer Senior Design Group
Questions?
Hydraulic Permeability Mode
Fissell, William H., et al. "High-performance silicon
nanopore hemofiltration membranes." Journal of
membrane science 326.1 (2009): 58-63.
Filtration/Dialysis Mode
Filtrate Mass/
Original Mass (θ)
Ideal Filtration
Example 1 psi Pressure
Example 2 psi Pressure
0
Size (arbitrary units)
Previous System
Previous Interface
Appendix: Feedback Control Simplified
Voltage
Signal 1
Pressure
Transducer 1
Pressure
(Blood)
ADC
Arduino/LabVIEW
Σ
ΔV
Σ
Error
PID Loop
Voltage
Conversion VI
Setpoint
Pressure
ADC
Voltage
Signal 2
Pressure
Transducer 2
Voltage
Pressure
Regulator 1
Voltage
Pressure
Regulator 2
Pressure
(Dialysate)
Appendix: Feedback Control Diagram
Pressure
Transducer 1
Voltage
Signal 1
ADC
Setpoint Flow
or Waveform
Σ
Arduino/LabVIEW
ΔV
Σ
Error
Pump VI
RS-232
Signal
Peristaltic
Pump
PID Loop
Voltage
Pressure
Regulator 1
Voltage
Pressure
Regulator 2
Voltage
Conversion VI
Setpoint
Pressure
ADC
Voltage
Signal 2
Pressure
(Blood)
Pressure
Transducer 2
Pressure
(Dialysate)
Flow
Rate
Pressure
(Blood)
Σ