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

2. 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

3. 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

4. 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

5. 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)

6. 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

7. 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.

8. 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

9. 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

10. 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

11. SYSTEM AND ENVIRONMENT

12. Experimental Setup – Dialysis Mode

13. Feedback Control Diagram

14. Unified Box Concept

15. 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

16. LTspice Modeling of Power Electronics

17. Ultrasound Blood Velocity Reading

18. Estimated Waveform Time (s) Velocity (cm/s)

19. Generated Pressure Waveform

20. Comparison

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

22. 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

23. Top Level Menu

24. Quadrant

25. Hardware Select

26. Experiment Overview Experimental Runtime GUI Pressure Transducer Transducer Calibration

27. Mass Balance Peristaltic Pump Syringe Pump

28. 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

29. 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 1 st iteration CAD model of our hardware container

30. Gantt Chart