Towards a Bioartificial Kidney: Validating Nanoporous Filtration Membranes Jacob Bumpus, BME/EE 2014 Casey Fitzgerald, BME 2014 Michael Schultis, BME/EE 2014

Background In 2010, 600,000 patients were treated for end stage renal disease (ESRD) in the US alone Treatment Options: Kidney transplant Donor Shortage Dialysis Costly and time consuming 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):

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

Problem Statement These membranes must be thoroughly tested to verify their filtration characteristics These experiments are manually monitored, and data is collected by hand Current experiments are unable to simulate physiologically relevant fluid flow profiles, and are limited to constant flow rates There are no failsafes to protect these expensive and fragile membranes

Needs Statement To design an integrated hardware/software suite that will streamline verification of nanoporous silicon filtration membranes while maximizing experimental control and minimizing user involvement

Goals Develop an intuitive graphical user interface (GUI) that allows the user to easily control the system Automate the experimental protocol and data collection Allow user-defined hardware setup so that numerous experiments can be run simultaneously Add programatic flow rate control to allow for pulsatility Include failsafes and shutdown procedures to protect these membranes

Clinical Relevance Ease of Use Efficiency Control Relevance Risk Lost Time Lost Money Effort Increase Reduce

Experiments The solution must automate three modes of experimentation Hydraulic Permeability Mode Measures filtration rate as a function of pressure (uL/min/psi) Filtration Mode Collect filtrate samples for further analysis Dialysis Mode Collect samples in a closed blood/dialysate system Filtration and Dialysis Mode should include an option to run with constant flow or a pulsatile waveform

Experimental Setup – Hydraulic Permeability PSI Peristaltic Pump Water Pressure Transducer Air Regulator To House Air Air Filtration Membrane Implantable Device Zero g

Feedback Control Diagram Arduino/LabVIEW Σ Pressure Regulator PID Loop Pressure Transducer Convert VI Setpoint Pressure Pressure Voltage Signal ADC Voltage ErrorV Pump VI Peristaltic Pump Σ Setpoint Flow or Waveform RS-232 Signal Pressure Hagen- Poiseuille Flow Rate ΔPΔP Filtration Membrane Mass Balance Filtration Rate Comparison VI (Actual > Setpoint?) Setpoint Mass Sample Mass Yes/No Shutdown? V

Modified from Zhang, Guanqun, Jin-Oh Hahn, and Ramakrishna Mukkamala. "Tube-load model parameter estimation for monitoring arterial hemodynamics." Engineering Approaches to Study Cardiovascular Physiology: Modeling, Estimation, and Signal Processing (2011): 20. Pulsatility: Replicating Arterial Pressure Waveforms ex vivo

Control Box Concept Pressure Transducers General Purpose USB Pressure Regulators Power Supply AC Power Line USB Hubs and Female Connector Ports H N G Through Hole Board Control Box: Front View Control Box: Top View C R

Hydraulic Permeability Filtration Dialysis Quadrant 1 Quadrant 2 Quadrant 4 Quadrant 3 Top Level Menu Software Architecture Diagram

Hardware select (Pump, Transducer/Regulator, Balance) Hardware select (Pump, Transducer/Regulator, Balance) Hardware select (Pump, Transducer/Regulator, Balance) Hardware select (Pump, Transducer/Regulator, Balance) Hardware select (2x Pump, 2x Transducer/Regulator, Balance, Syringe Pump) Hardware select (2x Pump, 2x Transducer/Regulator, Balance, Syringe Pump) Experimental Runtime GUI Experimental Runtime GUI Pressure Transducer Air Regulator Mass Balance Peristaltic Pump Syringe Pump Experiment Overview Calibration

Experiment Overview Experimental Runtime GUI Pressure Transducer Transducer Calibration

Mass Balance Experimental Runtime GUI Peristaltic Pump Syringe Pump

Hydraulic Permeability Experiment Load from File

Hydraulic Permeability Results Experiment ResultsData 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 Pressure transducer (COMPLETE) Pressure Regulator (COMPLETE) Peristaltic Pump (COMPLETE) Mass balance (COMPLETE) Syringe Pump (TBD) Initial iterations of pulsatile flow Abstract submission to American Society for Artificial Internal Organs (ASAIO) Student Design Competition Fully Automated Hydraulic Permeability and Filtration Experiments Primary Fail-safes and Error handling Parts have arrived

Next Steps Revisit pulsatility using known pressure profiles Evaluate syringe pump functionality/feasibility Compile individual components into a single, unified system Order and assemble box

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. A.B. Bonds Dr. Matthew Walker III JustMyPACE Peer Senior Design Group

Questions?

Feedback Control Diagram Arduino/LabVIEW Σ Pressure Regulator 1 PID Loop Pressure Regulator 2 Pressure Transducer 2 Pressure Transducer 1 Conversion VI Setpoint Pressure Pressure (Blood) Pressure (Dialysate) Voltage Signal 1 ADC Voltage Signal 2 ADC Σ ΔVΔV Voltage Error Voltage Pump VI Peristaltic Pumps Σ Setpoint Flows or Waveforms RS-232 Signals Pressure (Blood) HP Flow Rate Σ Pressure (Dialysate) ΔPΔP

Experimental Setup – Dialysis Mode PSI To House Air Peristaltic Pump Pressure Transducer Dialysate Side Blood Side Pressure Transducer Air Regulator To House Air Air Filtration Membrane Syringe Pump

Hydraulic Permeability Mode Fissell, William H., et al. "High-performance silicon nanopore hemofiltration membranes." Journal of membrane science (2009):

Filtration/Dialysis Mode 0 Ideal Filtration Example 1 psi Pressure Example 2 psi Pressure Filtrate Mass/ Original Mass (θ) Size (arbitrary units)

Previous System

Previous Interface

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 Voltage Signal 2 ADC Σ ΔVΔV Voltage Error Voltage Pressure (Blood)

Appendix: Feedback Control Diagram Arduino/LabVIEW Σ Pressure Regulator 1 PID Loop Pressure Regulator 2 Pressure Transducer 2 Pressure Transducer 1 Conversion VI Setpoint Pressure Pressure (Blood) Pressure (Dialysate) Voltage Signal 1 ADC Voltage Signal 2 ADC Σ ΔVΔV Voltage Error Voltage Pump VI Peristaltic Pump Σ Setpoint Flow or Waveform RS-232 Signal Flow Rate Pressure (Blood)

Top Level Menu

Hardware Select

Design 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