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 is costly, averaging approximately $65,000/patient annually and time consuming, in
many cases requiring thrice weekly treatment
•
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 artificial, implantable kidney would revolutionize treatment of end stage
renal disease (ESRD).
•
Improve patient outcomes
•
Reduce economic burden of treatment
Background
•
Dr. Fissell is working to develop an implantable bioartificial kidney using
nanoporous silicon membranes as biological filters
•
These chips feature nanometer-scale pore arrays, invisible to optical
characterization methods
•
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
Problem Statement
• The Fissell lab must manually configure 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
Clinical Relevance
•
Our design:
• Increases efficiency of experimentation by fully automating a variety of test
protocols, allowing the group to characterize more chips
•
Reduces project risk of lost time and money by adding failsafes against chip
fracture ($1000’s/chip)
•
Maximizes experimental control by tightly coupling temperature and
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)
Primary Objective
•
A robust testing and characterization platform is needed to
streamline verification of these nanoporous filtration
membranes.
•
Our primary objective is to develop an elegant, dynamic
hardware control system that maximizes experiment control
and precision while minimizing user involvement during
filtration experiments for the verification of nanoporous silicon
membranes
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 and 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
Performance Criteria
• The final design iteration should be implemented by April 21st
• The system should require minimal user involvement (<5min setup, <10min/day
monitoring)
• Pressure and Flow throughout the close system must be regulated (+/-20%) to
include:
•
Fail-safes that protect nanoporous silicon chips from breaking (due to pressure
spikes)
•
Flow profiles that mimic physiological waveforms (pulsatile flow).
• Data must be automatically acquired and saved periodically.
• The completed system will be designed so that an individual with limited experience
can easily and quickly learn to run these complex experimental protocols
Solution Description
• 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
• Each mode should include an option to run with constant flow or a periodic
waveform
SYSTEM AND ENVIRONMENT
Experimental Setup – Dialysis Mode
Feedback Control Diagram
Unified Box Concept
Circuit Analysis
• Power Requirements
• Pressure Regulator
• +18 to +28V
• DC Fan
• +24 V
• Arduino Mega
• +7 to +12V
• 8 INA122P Instrumentation Amps
• -4 to +10V
• 8 LM 741 Operational Amplifiers
• -4 to +10V
LTspice Modeling of Power Electronics
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
Quadrant
Hardware Select
Experimental Runtime GUI
Experiment Overview
Pressure Transducer
Transducer Calibration
Mass Balance
Peristaltic Pump
Syringe Pump
Recent Progress
• The following components and software utilities are shown to be interoperable,
indicating strong technical feasibility of the project goals:
•
Pressure transducer control & communication
•
Pressure regulator control & communication
•
LabVIEW PID feedback loop for pressure setup
•
Improved/updated circuitry
•
LabVIEW control of peristaltic pumps
•
Initial tests of pulsatile flow
•
Serial communication to mass balance
•
Abstract submission to American Society for Artificial Internal Organs (ASAIO)
Student Design Competition
•
Software program for Hydraulic Permeability experiment
•
Successful initial test of fully automated operation
Next Steps
• Continue to iterate towards more physiologically
relevant pulsatility
• Remotely control the syringe pump and add to the
software program for the Filtration Mode protocol
• Compile a list of all our electronic components
inventory
• Develop a 1st iteration CAD model of our hardware
container
Gantt Chart