Feasibility testing of the Inspired Therapeutics NeoMate mechanical circulatory support system for neonates and infants.

Inspired Therapeutics (Merritt Island, FL) is developing a mechanical circulatory support (MCS) system designed as a single driver with interchangeable, extracorporeal, magnetically levitated pumps. The NeoMate system design features an integrated centrifugal rotary pump, motor, and controller that will be housed in a single compact unit. Conceptually, the primary innovation of this technology will be the combination of disposable, low-cost pumps for use with a single, multi-functional, universal controller to support multiple pediatric cardiopulmonary indications. In response to the paucity of clinically available pediatric devices, Inspired Therapeutics is specifically targeting the underserved neonate and infant heart failure (HF) patient population first. In this article, we present the development of the prototype Inspired Therapeutics NeoMate System for pediatric left ventricular assist device (LVAD) support, and feasibility testing in static mock flow loops (H-Q curves), dynamic mock flow loops (hemodynamics), and in an acute healthy ovine model (hemodynamics and clinical applicability). The resultant hydrodynamic and hemodynamic data demonstrated the ability of this prototype pediatric LVAD and universal controller to function over a range of rotary pump speeds (500-6000 RPM), to provide pump flow rates of up to 2.6 L/min, and to volume unload the left ventricle in acute animals. Key engineering challenges observed and proposed solutions for the next design iteration are also presented.

Development of Inspired Therapeutics Pediatric VAD: Computational Analysis and Characterization of VAD V3.

PURPOSE: Pediatric heart failure patients remain in critical need of a dedicated mechanical circulatory support (MCS) solution as development efforts for specific pediatric devices continue to fall behind those for the adult population. The Inspired Pediatric VAD is being developed as a pediatric specific MCS solution to provide up to 30-days of circulatory or respiratory support in a compact modular package that could allow for patient ambulation during treatment. METHODS: Hydrodynamic performance (flows, pressures), impeller/rotor mechanical properties (torques, forces), and flow shear stress and residence time distributions of the latest design version, Inspired Pediatric VAD V3, were numerically predicted and investigated using computational fluid dynamics (CFD) software (SolidWorks Flow Simulator). RESULTS: Hydrodynamic performance was numerically predicted, indicating no change in flow and pressure head compared to the previous device design (V2), while displaying increased impeller/rotor torques and translation forces enabled by improved geometry. Shear stress and flow residence time volumetric distributions are presented over a range of pump rotational speeds and flow rates. At the lowest pump operating point (3000 RPM, 0.50 L/min, 75 mmHg), 79% of the pump volume was in the shear stress range of 0-10 Pa with < 1% of the volume in the critical range of 150-1000 Pa for blood damage. At higher speed and flow (5000 RPM, 3.50 L/min, 176 mmHg), 65% of the volume resided in the 0-10 Pa range compared to 2.3% at 150-1000 Pa. CONCLUSIONS: The initial computational characterization of the Inspired Pediatric VAD V3 is encouraging and future work will include device prototype testing in a mock circulatory loop and acute large animal model.

Development of Inspired Therapeutics Pediatric VAD: Benchtop Evaluation of Impeller Performance and Torques for MagLev Motor Design.

PURPOSE: Despite the availability of first-generation extracorporeal mechanical circulatory support (MCS) systems that are widely used throughout the world, there is a need for the next generation of smaller, more portable devices (designed without cables and a minimal number of connectors) that can be used in all in-hospital and transport settings to support patients in heart failure. Moreover, a system that can be universally used for all indications for use including cardiopulmonary bypass (CPB), uni- or biventricular support (VAD), extracorporeal membrane oxygenation (ECMO) and respiratory assist that is suitable for use for adult, neonate, and pediatric patients is desirable. Providing a single, well designed, universal technology could reduce the incidence of human errors by limiting the need for training of hospital staff on a single system for a variety of indications throughout the hospital rather than having to train on multiple complex systems. The objective of this manuscript is to describe preliminary research to develop the first prototype pump for use as a ventricular assist device for pediatric patients with the Inspired Universal MCS technology. The Inspired VAD Universal System is an innovative extracorporeal blood pumping system utilizing novel MagLev technology in a single portable integrated motor/controller unit which can power a variety of different disposable pump modules intended for neonate, pediatric, and adult ventricular and respiratory assistance. METHODS: A prototype of the Inspired Pediatric VAD was constructed to determine the hemodynamic requirements for pediatric applications. The magnitude/range of hydraulic torque of the internal impeller was quantified. The hydrodynamic performance of the prototype pump was benchmarked using a static mock flow loop model containing a heated blood analogue solution to test the pump over a range of rotational speeds (500-6000 RPM), flow rates (0-3.5 L/min), and pressures (0 to ~ 420 mmHg). The device was initially powered by a shaft-driven DC motor in lieu of a full MagLev design, which was also used to calculate the fluid torque acting on the impeller. RESULTS: The pediatric VAD produced flows as high as 4.27 L/min against a pressure of 127 mmHg at 6000 RPM and the generated pressure and flow values fell within the desired design specifications. CONCLUSIONS: The empirically determined performance and torque values establish the requirements for the magnetically levitated motor design to be used in the Inspired Universal MagLev System. This next step in our research and development is to fabricate a fully integrated and functional magnetically levitated pump, motor and controller system that meets the product requirement specifications and achieves a state of readiness for acute ovine animal studies to verify safety and performance of the system.

Design and Computational Evaluation of a Pediatric MagLev Rotary Blood Pump.

Pediatric heart failure (HF) patients have been a historically underserved population for mechanical circulatory support (MCS) therapy. To address this clinical need, we are developing a low cost, universal magnetically levitated extracorporeal system with interchangeable pump heads for pediatric support. Two impeller and pump designs (pump V1 and V2) for the pediatric pump were developed using dimensional analysis techniques and classic pump theory based on defined performance criteria (generated flow, pressure, and impeller diameter). The designs were virtually constructed using computer-aided design (CAD) software and 3D flow and pressure features were analyzed using computational fluid dynamics (CFD) analysis. Simulated pump designs (V1, V2) were operated at higher rotational speeds (~5,000 revolutions per minute [RPM]) than initially estimated (4,255 RPM) to achieve the desired operational point (3.5 L/min flow at 150 mm Hg). Pump V2 outperformed V1 by generating approximately 30% higher pressures at all simulated rotational speeds and at 5% lower priming volume. Simulated hydrodynamic performance (achieved flow and pressure, hydraulic efficiency) of our pediatric pump design, featuring reduced impeller size and priming volume, compares favorably to current commercially available MCS devices.

Platelet activation after implantation of the Levitronix PediVAS in the ovine model.

The Levitronix PediVAS is an extracorporeal magnetically levitated pediatric ventricular assist system with an optimal flow rate range of 0.3-1.5 L/min. The system is being tested in preclinical studies to assess hemodynamic performance and biocompatibility. The PediVAS was implanted in nine ovines for 30 days using either commercially available cannulae (n = 3) or customized Levitronix cannulae (n = 6). Blood biocompatibility in terms of circulating activated platelets was measured by flow cytometric assays to detect P-selectin. Platelet activation was further examined after exogenous agonist stimulation. Platelet activation increased after surgery and eventually returned to baseline in animal studies where minimal kidney infarcts were observed. Platelet activation remained elevated for the duration of the study in animals where a moderate number of kidney infarcts with or without thrombotic deposition in the cannulae were observed. When platelet activation did return to baseline, platelets appropriately responded to agonist stimulation, signifying conserved platelet function after PediVAS implant. Platelet activation returned to baseline in the majority of studies, representing a promising biocompatibility result for the Levitronix PediVAS.

Computational Fluid Dynamics and Experimental Characterization of the Pediatric Pump-Lung.

The pediatric pump-lung (PediPL) is a miniaturized integrated pediatric pump-oxygenator specifically designed for cardiac or cardiopulmonary support for patients weighing 5-20 kg to allow mobility and extended use for 30 days. The PediPL incorporates a magnetically levitated impeller with uniquely configured hollow fiber membranes into a single unit capable of performing both pumping and gas exchange. A combined computational and experimental study was conducted to characterize the functional and hemocompatibility performances of this newly developed device. The three-dimensional flow features of the PediPL and its hemolytic characteristics were analyzed using computational fluid dynamics based modeling. The oxygen exchange was modeled based on a convection-diffusion-reaction process. The hollow fiber membranes were modeled as a porous medium which incorporates the flow resistance in the bundle by an added momentum sink term. The pumping function was evaluated for the required range of operating conditions (0.5-2.5 L/min and 1000-3000 rpm). The blood damage potentials were further analyzed in terms of flow and shear stress fields, and the calculations of hemolysis index. In parallel, the hydraulic pump performance, oxygen transfer and hemolysis level were quantified experimentally. Based on the computational and experimental results, the PediPL device is found to be functional to provide necessary oxygen transfer and blood pumping requirements for the pediatric patients. Smooth blood flow characteristics and low blood damage potential were observed in the entire device. The in-vitro tests further confirmed that the PediPL can provide adequate blood pumping and oxygen transfer over the range of intended operating conditions with acceptable hemolytic performance. The rated flow rate for oxygenation is 2.5 L/min. The normalized index of hemolysis is 0.065 g/100L at 1.0 L/min and 3000 rpm.

Computational characterization of flow and hemolytic performance of the UltraMag blood pump for circulatory support.

The Levitronix UltraMag blood pump is a next generation, magnetically suspended centrifugal pump and is designed to provide circulatory support for pediatric and adult patients. The aim of this study is to investigate the hemodynamic and hemolytic characteristics of this pump using the computational fluid dynamics (CFD) approach. The computational domain for CFD analysis was constructed from the three-dimensional geometry (3D) of the UltraMag blood pump and meshed into 3D tetrahedral/hybrid elements. The governing equations of fluid flow were computationally solved to obtain a blood flow through the blood pump. Further, hemolytic blood damage was calculated by solving a scalar transport equation where the scalar variable and the source term were obtained utilizing an empirical power-law correlation between the fluid dynamic variables and hemolysis. To obtain mesh independent flow solution, a comparative examination of vector fields, hydrodynamic performance, and hemolysis predictions were carried out. Different sizes of tetrahedral and tetrahedral/hexahedral mixed hybrid models were considered. The mesh independent solutions were obtained by a hybrid model. Laminar and SST κ-ω turbulence flow models were used for different operating conditions. In order to pinpoint the most significant hemolytic region, the flow field analysis was coupled to the hemolysis predictions. In summary, computational characterization of the device was satisfactorily carried out within the targeted operating conditions of the device, and it was observed that the UltraMag blood pump can be safely operated for its intended use to create a circulatory support for both pediatric and adult-sized patients.

Computational design and in vitro characterization of an integrated maglev pump-oxygenator.

For the need for respiratory support for patients with acute or chronic lung diseases to be addressed, a novel integrated maglev pump-oxygenator (IMPO) is being developed as a respiratory assist device. IMPO was conceptualized to combine a magnetically levitated pump/rotor with uniquely configured hollow fiber membranes to create an assembly-free, ultracompact system. IMPO is a self-contained blood pump and oxygenator assembly to enable rapid deployment for patients requiring respiratory support or circulatory support. In this study, computational fluid dynamics (CFD) and computer-aided design were conducted to design and optimize the hemodynamics, gas transfer, and hemocompatibility performances of this novel device. In parallel, in vitro experiments including hydrodynamic, gas transfer, and hemolysis measurements were conducted to evaluate the performance of IMPO. Computational results from CFD analysis were compared with experimental data collected from in vitro evaluation of the IMPO. The CFD simulation demonstrated a well-behaved and streamlined flow field in the main components of this device. The results of hydrodynamic performance, oxygen transfer, and hemolysis predicted by computational simulation, along with the in vitro experimental data, indicate that this pump-lung device can provide the total respiratory need of an adult with lung failure, with a low hemolysis rate at the targeted operating condition. These detailed CFD designs and analyses can provide valuable guidance for further optimization of this IMPO for long-term use.

Functional and biocompatibility performances of an integrated Maglev pump-oxygenator.

To provide respiratory support for patients with lung failure, a novel compact integrated pump-oxygenator is being developed. The functional and biocompatibility performances of this device are presented. The pump-oxygenator is designed by combining a magnetically levitated pump/rotor with a uniquely configured hollow fiber membrane bundle to create an assembly free, ultracompact, all-in-one system. The hemodynamics, gas transfer and biocompatibility performances of this novel device were investigated both in vitro in a circulatory flow loop and in vivo in an ovine animal model. The in vitro results showed that the device was able to pump blood flow from 2 to 8 L/min against a wide range of pressures and to deliver an oxygen transfer rate more than 300 mL/min at a blood flow of 6 L/min. Blood damage tests demonstrated low hemolysis (normalized index of hemolysis [NIH] approximately 0.04) at a flow rate of 5 L/min against a 100-mm Hg afterload. The data from five animal experiments (4 h to 7 days) demonstrated that the device could bring the venous blood to near fully oxygen-saturated condition (98.6% +/- 1.3%). The highest oxygen transfer rate reached 386 mL/min. The gas transfer performance was stable over the study duration for three 7-day animals. There was no indication of blood damage. The plasma free hemoglobin and platelet count were within the normal ranges. No gross thrombus is found on the explanted pump components and fiber surfaces. Both in vitro and in vivo results demonstrated that the newly developed pump-oxygenator can achieve sufficient blood flow and oxygen transfer with excellent biocompatibility.

Assessment of hydraulic performance and biocompatibility of a MagLev centrifugal pump system designed for pediatric cardiac or cardiopulmonary support.

The treatment of children with life-threatening cardiac and cardiopulmonary failure is a large and underappreciated public health concern. We have previously shown that the CentriMag is a magnetically levitated centrifugal pump system, having the utility for treating adults and large children (1,500 utilized worldwide). We present here the PediVAS, a pump system whose design was modified from the CentriMag to meet the physiological requirements of young pediatric and neonatal patients. The PediVAS is comprised of a single-use centrifugal blood pump, reusable motor, and console, and is suitable for right ventricular assist device (RVAD), left ventricular assist device (LVAD), biventricular assist device (BVAD), or extracorporeal membrane oxygenator (ECMO) applications. It is designed to operate without bearings, seals and valves, and without regions of blood stasis, friction, or wear. The PediVAS pump is compatible with the CentriMag hardware, although the priming volume was reduced from 31 to 14 ml, and the port size reduced from 3/8 to (1/4) in. For the expected range of pediatric flow (0.3-3.0 L/min), the PediVAS exhibited superior hydraulic efficiency compared with the CentriMag. The PediVAS was evaluated in 14 pediatric animals for up to 30 days, demonstrating acceptable hydraulic function and hemocompatibility. The current results substantiate the performance and biocompatibility of the PediVAS cardiac assist system and are likely to support initiation of a US clinical trial in the future.

Computational and functional evaluation of a microfluidic blood flow device.

The development of microfluidic devices supporting physiological blood flow has the potential to yield biomedical technologies emulating human organ function. However, advances in this area have been constrained by the fact that artificial microchannels constructed for such devices need to achieve maximum chemical diffusion as well as hemocompatibility. To address this issue, we designed an elastomeric microfluidic flow device composed of poly (dimethylsiloxane) to emulate the geometry and flow properties of the pulmonary microcirculation. Our chip design is characterized by high aspect ratio (width > height) channels in an orthogonally interconnected configuration. Finite element simulations of blood flow through the network design chip demonstrated that the apparent pressure drop varied in a linear manner with flow rate. For simulated flow rates <250 mul min, the simulated pressure drop was <2000 Pa, the flow was laminar, and hemolysis was minimal. Hemolysis rate, assayed in terms of [total plasma hemoglobin (TPH) (sample - control)/(TPH control)] during 6 and 12 hour perfusions at 250 mul/min, was <5.0% through the entire period of device perfusion. There was no evidence of microscopic thrombus at any channel segment or junction under these perfusion conditions. We conclude that a microfluidic blood flow device possessing asymmetric and interconnected microchannels exhibits uniform flow properties and preliminary hemocompatibility. Such technology should foster the development of miniature oxygenators and similar biomedical devices requiring both a microscale reaction volume and physiological blood flow.

Optimization of a miniature Maglev ventricular assist device for pediatric circulatory support.

A miniature Maglev blood pump based on magnetically levitated bearingless technology is being developed and optimized for pediatric patients. We performed impeller optimization by characterizing the hemodynamic and hemocompatibility performances using a combined computational and experimental approach. Both three-dimensional flow features and hemolytic characteristics were analyzed using computational fluid dynamics (CFD) modeling. Hydraulic pump performances and hemolysis levels of three different impeller designs were quantified and compared numerically. Two pump prototypes were constructed from the two impeller designs and experimentally tested. Comparison of CFD predictions with experimental results showed good agreement. The optimized impeller remarkably increased overall pump hydraulic output by more than 50% over the initial design. The CFD simulation demonstrated a clean and streamlined flow field in the main flow path. The numerical results by hemolysis model indicated no significant high shear stress regions. Through the use of CFD analysis and bench-top testing, the small pediatric pump was optimized to achieve a low level of blood damage and improved hydraulic performance and efficiency. The Maglev pediatric blood pump is innovative due to its small size, very low priming volume, excellent hemodynamic and hematologic performance, and elimination of seal-related and bearing-related failures due to adoption of magnetically levitated bearingless motor technology, making it ideal for pediatric applications.

Computational and experimental evaluation of the fluid dynamics and hemocompatibility of the CentriMag blood pump.

The CentriMag centrifugal blood pump is a newly developed ventricular assist device based on magnetically levitated bearingless rotor technology. A combined computational and experimental study was conducted to characterize the hemodynamic and hemocompatibility performances of this novel blood pump. Both the three-dimensional flow features of the CentriMag blood pump and its hemolytic characteristics were analyzed using computational fluid dynamics (CFD)-based modeling. The hydraulic pump performance and hemolysis level were quantified experimentally. The CFD simulation demonstrated a clean and streamlined flow field in the main components of the CentriMag blood pump. The predicted results by hemolysis model indicated no significant high shear stress regions in the pump. A comparison of CFD predictions and experimental results showed good agreements. The relatively large gap passages (1.5 mm) between the outer rotor walls and the lower housing cavity walls provide a very good surface washing through a secondary flow path while the shear stresses in the secondary flow paths are reduced, resulting in a low rate of hemolysis ([Normalized Index of Hemolysis] NIH = 0.0029 +/- 0.006) without a decrease of the pump's hydrodynamic performance (pressure head: 352 mm Hg at a flow rate of 5.0 L/min and a rotational speed of 4,000 rpm).