Modular Hardware Interface for Nanoporous Membrane Filtration Experiments

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

Background600,000 patients were treated for end stage renal disease (ESRD) in the US alone in 2010Current treatment procedures include kidney transplant and routine dialysisDialysis: 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 outcomesReduce economic burden of treatmentConcept illustration of an implantable bioartificial kidney. Courtesy of Shuvo RoyImage 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 international84.2 (2013): 256-264.BackgroundDr. 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 Pharmacyhttp://pharmacy.ucsf.edu/kidney-project/

Problem StatementIn 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 sizesThe Fissell lab must manually configure these filtration experiments, monitor them continuously throughout their duration (sometimes days to weeks long), and collect data by handCurrent experiments are unable to simulate physiologically relevant fluid flow profiles, and are limited to constant flow ratesNo failsafes exist in order to protect the silicon membranes from being damaged in the event of deviations from preset conditions

Clinical RelevanceOur design:Increases efficiency of experimentation by fully automating a variety of test protocols, allowing the group to characterize more chipsReduces project risk of lost time and money by adding failsafes against chip fracture ($1000s/chip)Maximizes experimental control by tightly coupling pressure monitoring to hardware output and adjusting for temporal driftAdds greater experimental relevance by allowing an adaptable physiological input platform, including simulation of pathophysiologic pressure conditions (hypertension)

Needs StatementTo design an integrated hardware/software suite that will streamline verification of these silicon membranes while maximizing experimental control and precision and minimizing user involvementGoalsExperimental 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. FactorsSoftware PlatformLabVIEW more $ / much less development time

Software concurrencyMore fewer programs running but internals are more complex

Hardware connectionsFewer cheaper in size and $ but more technically challenging

ExperimentsThe solution must automate three modes of experimentationHydraulic Permeability ModeMeasures convective flow across membrane at various pressures (uL/min/psi)

Filtration ModeCollect filtrate samples at various pressures for further analysis

Dialysis ModeSets 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 waveformSystem and Environment Experimental Setup Dialysis ModePSIPSITo House AirPeristaltic PumpPeristaltic PumpPressure TransducerDialysate SideBlood SidePressure TransducerAir RegulatorTo House AirAirAirFiltration MembraneSyringe PumpFeedback Control DiagramArduino/LabVIEWPressure Regulator 1PID Loop

Pressure Regulator 2Pressure Transducer 2Pressure Transducer 1Conversion VISetpoint PressurePressure(Blood)Pressure(Dialysate)VoltageSignal 1ADCVoltageSignal 2ADCVVoltageErrorVoltageVoltagePump VIPeristaltic PumpsSetpoint Flows or WaveformsRS-232SignalsPressure(Blood)HPFlow RatePressure(Dialysate)PControl Box ConceptPressure Transducers12436587General Purpose USB1234567141312111098Pressure Regulators12345678Power SupplyAC Power LineUSB Hubs and Female Connector Ports

HNG24125-12Through Hole BoardControl Box: Front ViewControl Box: Top ViewCR

Ultrasound Blood Velocity Reading

Estimated Waveform

Time (s)Velocity (cm/s)Generated Pressure Waveform

Comparison

Hydraulic PermeabilityFiltrationDialysisQuadrant 1Quadrant 2Quadrant 4Quadrant 3Top Level MenuSoftware Architecture DiagramExperiment OverviewExperimental Runtime GUIPressure TransducerTransducer Calibration

Mass BalanceExperimental Runtime GUIPeristaltic PumpSyringe Pump

InProgress

Hydraulic Permeability Experiment

Load from File

Hydraulic Permeability Results

Experiment ResultsData Log

Fail SafesSet point = 0 Overrides the PID controllerRecord Max/Min PressureAlert user of potential errorsNext: Automatic shut-downError HandlingWhat to do if something goes wrong?

Error Handling Demo gif

Recent ProgressLabVIEW Control ofPressure transducer (COMPLETE)Pressure Regulator (COMPLETE)Peristaltic Pump (COMPLETE)Mass balance (COMPLETE)Syringe Pump (IN PROGRESS) LabVIEW PID feedback loop for pressure setupImproved/updated circuitryInitial iterations of pulsatile flowAbstract submission to American Society for Artificial Internal Organs (ASAIO) Student Design CompetitionFully Automated Hydraulic Permeability ExperimentInitial Fail-safes and Error handlingNext StepsContinue to iterate towards more physiologically relevant pulsatilityDevelop Dialysate Mode AutomationIncorporate syringe pump control into complete systemFinalize power supply and order all componentsDevelop a 1st iteration CAD model of our hardware containerGantt Chart

Special Thanks To:Vanderbilt University Medical CenterVanderbilt School of EngineeringVanderbilt Renal Nanotechnology LabDr. William FissellJoey GroszekDr. Amanda BuckDr. Tim HolmanDr. Matthew Walker IIIJustMyPACE Peer Senior Design Group

Questions?Hydraulic Permeability Mode

Fissell, William H., et al. "High-performance silicon nanopore hemofiltration membranes."Journal of membrane science326.1 (2009): 58-63.Filtration/Dialysis Mode0Ideal FiltrationExample 1 psi PressureExample 2 psi PressureFiltrate Mass/ Original Mass ()Size (arbitrary units)Previous System

Previous Interface

Appendix: Feedback Control SimplifiedArduino/LabVIEWPressure Regulator 1PID Loop

Pressure Regulator 2Pressure Transducer 2Pressure Transducer 1Conversion VISetpoint PressurePressure(Dialysate)VoltageSignal 1ADCVoltageSignal 2ADCVVoltageErrorVoltageVoltagePressure(Blood)Appendix: Feedback Control DiagramArduino/LabVIEWPressure Regulator 1PID Loop

Pressure Regulator 2Pressure Transducer 2Pressure Transducer 1Conversion VISetpoint PressurePressure(Blood)Pressure(Dialysate)VoltageSignal 1ADCVoltageSignal 2ADCVVoltageErrorVoltageVoltagePump VIPeristaltic PumpSetpoint Flow or WaveformRS-232SignalFlow RatePressure(Blood)