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Published byValentine Boyd Modified over 9 years ago
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Towards a Bioartificial Kidney: Validating Nanoporous Filtration Membranes
Jacob Bumpus, BME/EE 2014 Casey Fitzgerald, BME 2014 Michael Schultis, BME/EE 2014
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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). Improve patient outcomes Reduce economic burden of treatment Concept illustration of an implantable bioartificial kidney. Courtesy of Shuvo Roy 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):
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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 Screenshots courtesy UCSF School of Pharmacy
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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
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Clinical Relevance Our design:
Increase Experimental Relevance Control Efficiency Reduce Man hours Disorder Lost $ Lost time 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 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)
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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
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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.
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Factors Software Platform Software concurrency Hardware connections
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
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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
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System and Environment
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Experimental Setup – Dialysis Mode
Filtration Membrane Peristaltic Pump Peristaltic Pump Pressure Transducer Pressure Transducer Air Air Air Regulator Syringe Pump PSI Dialysate Side Blood Side To House Air To House Air
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Feedback Control Diagram
Voltage Signal 1 Pressure Transducer 1 Pressure (Blood) ADC Arduino/LabVIEW Setpoint Flows or Waveforms Peristaltic Pumps RS-232 Signals Flow Rate Σ Pump VI HP ΔP PID Loop ΔV Σ Σ Error Voltage Pressure Regulator 1 Pressure (Blood) Voltage Setpoint Pressure Voltage Pressure Regulator 2 Pressure (Dialysate) Σ Conversion VI ADC Pressure Transducer 2 Voltage Signal 2 Pressure (Dialysate)
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Control Box Concept Power Supply Control Box: Front View
AC Power Line H Pressure Transducers N Power Supply G 1 2 4 3 6 5 8 7 24 Pressure Regulators 12 1 2 3 4 5 6 7 8 5 -12 General Purpose USB 1 2 3 4 5 6 7 14 13 12 11 10 9 8 Through Hole Board R C Control Box: Front View USB Hubs and Female Connector Ports Control Box: Top View
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Ultrasound Blood Velocity Reading
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Estimated Waveform Velocity (cm/s) Time (s)
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Generated Pressure Waveform
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Comparison
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Software Architecture Diagram
Top Level Menu Quadrant 1 Quadrant 2 Quadrant 3 Quadrant 4 Hydraulic Permeability Filtration Dialysis
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Experimental Runtime GUI
Hardware select (Pump, Transducer/Regulator, Balance) Hardware select (Pump, Transducer/Regulator, Balance) Hardware select (2x Pump, 2x Transducer/Regulator, Balance, Syringe Pump) Experimental Runtime GUI Peristaltic Pump Mass Balance Pressure Transducer Syringe Pump Experiment Overview Air Regulator Calibration
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Top Level Menu
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Hardware Select
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Experimental Runtime GUI
Experiment Overview Pressure Transducer Transducer Calibration
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Experimental Runtime GUI
Mass Balance Peristaltic Pump Syringe Pump In Progress
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Hydraulic Permeability Experiment
Load from File
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Hydraulic Permeability Results
Experiment Results Data Log
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Error Handling Demo gif
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? Error Handling Demo gif
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Recent Progress LabVIEW Control of
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
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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
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Gantt Chart
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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
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Questions?
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Hydraulic Permeability Mode
Fissell, William H., et al. "High-performance silicon nanopore hemofiltration membranes." Journal of membrane science 326.1 (2009):
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Filtration/Dialysis Mode
Ideal Filtration Example 1 psi Pressure Example 2 psi Pressure Filtrate Mass/ Original Mass (θ) Size (arbitrary units)
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Previous System
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Previous Interface
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Appendix: Feedback Control Simplified
Arduino/LabVIEW Σ Pressure Regulator 1 PID Loop Pressure Regulator 2 Pressure Transducer 2 Pressure Transducer 1 Conversion VI Setpoint Pressure Pressure (Dialysate) Voltage Signal 1 ADC Signal 2 ΔV Error (Blood)
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Appendix: Feedback Control Diagram
Voltage Signal 1 Pressure Transducer 1 Pressure (Blood) ADC Arduino/LabVIEW Setpoint Flow or Waveform Peristaltic Pump RS-232 Signal Flow Rate Σ Pump VI PID Loop ΔV Σ Σ Error Voltage Pressure Regulator 1 Pressure (Blood) Voltage Setpoint Pressure Voltage Pressure Regulator 2 Conversion VI ADC Pressure Transducer 2 Voltage Signal 2 Pressure (Dialysate)
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