April 13, 2004 Design of a Prenatal Perfusion System PROJECT PROPOSAL Timothy Bachman Garrett Grindle Leigh McClure Scott Morley Bioengineering 1160/61 April 13, 2004

April 13, 2004 Overview The practice of fetal heart surgery to correct congenital heart defects has been limited by the lack of a fetal CPB system. It is believed that if congenital heart defects are corrected early, that blood flow patterns can be restored and the heart will develop normally Mortality – CHD: 4109 There is an extremely small demand for a fetal CPB system – probably 100’s of cases per year.

April 13, 2004 Overview (cont) This group has designed, constructed, and tested a prototype prenatal perfusion system comprised of: –Pump –Venous and arterial cannulas –Controller Existing pumps were evaluated and deemed inappropriate for the application We have developed a novel, pulsatile pump

April 13, 2004 Project Objectives Design a cardiac perfusion system capable of providing ex utero fetal cardiac support for up to 2 hours –Variable, pulsatile flow 300 – 1000 mL/min 120 – 180 BPM Mean arterial pressure 40 – 50 mmHg –Minimal priming volume Less than 15 mL

April 13, 2004 Market and Competition Research Competitors –Stanford/UCSF group (one case w/ J&J’s pump) Commercial Competitors –Blood pump companies: J&J, Medtronic, Cobe, etc –No competing commercial products at this time Strengths and Weaknesses vs. Stanford/UCSF’s Group –Stanford has not published their work. Our competitive advantage or disadvantage has not yet been determined. Catheter-based solutions (Verimetra)

April 13, 2004 Design Concepts Considered Existing pumps – Nimbus Centrifugal Pump New Pump Design –Rotary or centrifugal (design too difficult, pulsatility likely difficult to achieve) –Positive displacement pumps Imitates ventricle behavior Inherent pulsatility Ease of design/construction Availability of resources (materials and controller) Nimbus Centrifugal Pump

April 13, 2004 Design Solidworks Model (exploded view) Pneumatically driven positive displacement pump One-way valves direct flow 6 mL stroke volume Compatible with IMO controller Modular design for valve and bladder testing

April 13, 2004 Materials Chamber: Acrylic stock Bladder: Medical grade PU Cannulae/Tubing: Off the shelf (Medtronic/Tygon) Valves: Check valves – not medical grade

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Mock Loop

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Project Mgmt: Schedule and Milestones Conceptual Design Complete: Actual: 1/17/04 –Choose pump –Cannula size and insertion sites –Determine console requirements and electrical safe guards Primary Design Complete: 2/21/04 Actual: 2/15/04 –Apply engineering model to determine dimensions –Determine Specific Components –Preliminary drawing and parts list Design Refinement Complete: 3/13/04 –Integrate components –Manufacturing protocol –Final drawings, parts list, and testing protocol Prototype Fabricated: Org: 4/6/04 Rev.: 3/21/04 Actual: 4/2/04 Testing Complete: Org.: 4/12/04 Rev.: 4/2/04 Actual: 4/09/04 Business Plan SBIR Complete: Org.: 4/14/04 Actual: 4/20/04

April 13, 2004 Future Design Work Complete pressure/flow characterization in a physiologic mock loop Valve evaluations or new valve design Evaluate bladder design for flow optimization Redesign pump with integrated valves Design/build drive system for this specific application

April 13, 2004 Considerations for Future Development Economic –Good project for university level development –Projected market size is very small  not commercially attractive Manufacturability –Current product design is relatively simple to manufacture –Future designs should use medical grade products and be evaluated for durability and sterilization compatibility –Final manufacturing (for human use) would require a cleanroom Human Factors –Console design, setting of use (OR) Regulatory Issues –HDE qualification would simplify approval process

April 13, 2004 Regulatory Strategy: Humanitarian Device Exemption (HDE) Similar to a pre-market approval (PMA) Exempt from effectiveness requirements “intended to benefit patients in the treatment or diagnosis of diseases or conditions that affect fewer than 4,000 individuals [per year] in the United States” - CDRH

April 13, 2004 Team Responsibilities Action ItemBachmanGrindleMcClureMorley Pump DesignLead Current pump evaluationsXXXX Solid modelingX CFDif req. Cannula DesignLead Evaluation of available cannulas XXXX Console DevelopmentX Regulatory and QSX Mock Loop and Experimental Protocol Design X HFEXX Fabrication and Procurement PumpXX CannulasX ConsoleX Prototype EvaluationXXXX SBIRX

April 13, 2004 Acknowledgements Frank Pigula, M.D. Pediatric Cardiothoracic Surgeon, Boston Children’s Hospital William Federspiel, Ph.D. Director Artificial Lung Lab, MIRM Brian Frankowski Designer, Artificial Lung Lab, MIRM Heidi Eash Lab Manager, Artificial Lung Lab, MIRM

April 13, 2004