Numerical investigation of impeller design variation on mechanical blood pump hemodynamics

Mechanical heart assist device is an emerging treatment for end-stages of heart failure which is an alternative to heart transplant due the shortage of heart donors. Despite the clinical success of “Left Ventricular Assist Devices (LVAD)”, the development still continue as new designs are progressively being tested to address the ever existing complications. Developing these blood pumps requires determining a balance in providing adequate pump performance while giving attention to possible occurrence of blood damage. This study utilized a proposed design concept of a hybrid bearing system and evaluate its’ merits of adapting the concept from a perspective of computational fluid dynamic (CFD) approach. Two design parameters were chosen for this study; the conical shape of the impeller bottom that functions to provide both radial and axial stability and secondly, the inclusion of a groove profile intended to complement the system as a hydrodynamic bearing as well as improving washout flow. Four model variations were constructed from the design parameters for comparison with the number of mesh between 8.9 to 9.8 million nodes. Menter’s Shear Stress Transport (SST) turbulent model was used to simulate 3 different operating speeds (2000 rpm, 3000 rpm, 4000 rpm) at 5 varying flowrate (3, 4, 5, 6, 7 L=min). Evaluation involved assessing the model variants based on several performance criteria. Ranked selection method was used to rate and select the better performing model variation with a good compromise between the level of blood damage potential (hemolysis index) and the pump performance although heavier emphasis on blood damage was chosen as a priority. In the analysis, CFD results showed that the inclusion of conical shape has negligible effect on pump head with a minor 0.8 percent difference, however it does present a potential area of stagnant flow, reducing washout by 28.3 percent. The groove profile along with conical shaped impeller present high shear stress region at the impeller bottom area that caused an increase in hemolysis index by an average of 15.4 percent. Ranking and selection of the model variants resulted in the flat groove configuration scored as the best performing configuration that gives the good compromise of pump performance and hemolysis

Preclinical Biocompatibility Assessment of Pediatric Ventricular Assist Devices

A number of heart assist devices including the PediaFlowTM ventricular assist device (VAD), a magnetically levitated mixed flow rotary blood pump, and the Levitronix® PediVAS™, an extracorporeal magnetically levitated centrifugal blood pump are under development to address the urgent need for mechanical circulatory support suitable for children in heart failure. VADs are associated with a host of biological complications including bleeding, thromboembolism, and infection. The biocompatibility of these new devices must be characterized in a preclinical model (juvenile ovines) to ensure their safety and efficacy in children. However, biocompatibility studies in ovines are limited due to a lack of available assays. Flow cytometric assays were developed to detect ovine platelet activation and function. These assays were applied during in vitro assessment of potential biomimetic coatings for the blood contacting surfaces of pediatric VADs. These assays were then applied in vivo in 5 lambs undergoing a VAD sham surgical procedure for 30 days duration, in 20 lambs implanted with the Levitronix PediVAS for 30 days duration, and in 8 lambs implanted with the three design iterations of the PediaFlow VAD ranging from 6 - 72 days duration. The sham surgical procedure enabled characterization of the effects of the implant surgery on platelet activation. Platelet activation was reduced on surfaces that received a biomimetic coating compared to uncoated surfaces which was in agreement with platelet deposition results. Platelet activation levels rose post-operatively in the sham animals and returned to pre-operative levels at approximately two weeks. In PediaFlow and Levitronix implanted animals platelet activation also rose post-operatively and typically returned to baseline levels. In these implants platelet activation consistently rose following pump or animal complications. In a subset of studies platelet activation was elevated for the duration of the study and this high level of activation generally coincided with increased kidney infarcts or thrombus deposition in the cannulae at necropsy. Overall, the blood biocompatibility of the Levitronix PediVAS and the PediaFlow VAD as represented by a low level of platelet activation observed in the majority of studies is encouraging for the potential clinical use of these devices. The ability of the developed platelet activation assays to differentiate between surface coatings, and to discern trends with respect to pump complications and kidney infarcts following VAD implant demonstrate its utility in assessing the blood biocompatibility of pediatric heart assist devices

Development of Mechanical Cardiovascular Assist Devices for Fontan Patients: Two Novel Approaches

Few therapeutic alternatives exist for patients with a failing single ventricle physiology. To address this need, this thesis project investigated two new therapeutic alternatives, which sought to positively augment the Fontan hemodynamics. The first modality introduced a non-invasive method of external pressure application to the lower extremities. A clinical study (n=2) was conducted, and results indicated an increase in flow as a consequence to an increase in transmural pressure in the lower extremities. The second modality investigated a minimally invasive blood pump. Numerical analyses of the pump were performed to examine hydraulic performance under physiologic conditions. The pump produced pressure rises of 1 to 25 mmHg over flows of 1 to 4 LPM, has a blood damage index less than 1% and was also found to successfully augment the hydraulic energy of the Fontan physiology. This work resulted in substantial progress to develop both modalities and address a significant human health problem

원심력 기반 유체 시스템의 생물의학적 응용에 관한 연구

학위논문 (박사)-- 서울대학교 대학원 : 바이오엔지니어링전공, 2017. 2. 김희찬.This dissertation focuses on the design, fabrication, evaluation, and application of a centrifugal force-based fluidic system based on macro and micro scale engineering disciplines. Unlike other fluid control forces including electrical force, compression force, magnetic force, etc., centrifugal force is capable of manipulating fluids ranging from macro- to micro-scales with high efficiencies regardless of fluid properties. Accordingly, centrifugal force has been extensively used for a great number of biomedical applications. However, the design optimization of such centrifugal force-based fluidic system for practical use is still under investigation due to the inadequate integrating technique, especially for clinical settings, and the strong dependency on geometric designs within spatially varying three different rotational forces (centrifugal, Coriolis, and Euler forces) to precisely regulate the flow of the fluid. Therefore, this dissertation aims to develop a centrifugal force-based fluidic system appropriate for either clinical or biological research environment based on thorough investigations of the fluid flow, the environments created by the rotational forces, and the geometric designs of the system at both the macro- and micro-scale. The macro-scale study involves the evaluation of design strategies for developing a smart all-in-one cardiopulmonary circulatory support device (CCSD) applicable to diverse clinical environments (emergency room (ER), intensive care unit (ICU), operation room (OR), etc.) (Chapter 2, Section 2.1), the evaluation of hemolytic characteristics of centrifugal blood pump (Chapter 2, Section 2.2), and the evaluation of drug sequestration (Chapter 2, Section 2.3) in CCSD component. Smart all-in-one CCSD equipped with a qualified low hemolytic centrifugal blood pump developed in this study resulted in low hemolysis with a free plasma hemoglobin level far less than 50 mg/dL, and an oxygenator membrane made of polyurethane fibers was turned out to be especially susceptible to the analgesic drug loss (41.8%). The micro-scale study involves the numerical evaluation of the Coriolis effects on fluid flow inside a rotating microchannel (Chapter 3, Section 3.1), the feasibility study for the development of a centrifugal microfluidic-based viscometer (Chapter 3, Section 3.2), the evaluation of hypergravity-induced spheroid formation (Chapter 3, Section 3.3), and the cellular adaptation study to hypergravity conditions using human adipose derived stem cell (hASC) and human lung fibroblast (MRC-5) (Chapter 3, 3.4). Application studies performed under fundamental understanding of the microfluidic flows in rotating platform demonstrated new potential uses for centrifugal microfluidic technologies especially for cell research, revealing that hypergravity conditions can be an important environmental cues affecting cellular interactions. Through evaluating various types of centrifugal force-based fluidic system designs for both practical applications and bench-scale experiments, considerable potential of centrifugal force-based fluidic system for introducing new paradigms in the development of medical devices and biomedical research has been demonstrated. The unprecedented integration technique to further miniaturize and improve usability of the centrifugal force-based system might facilitate product innovations, fostering its wide acceptance in the future (Chapter 4).Chapter 1. Introduction 1 1.1 Centrifugal force 1 1.2 Centrifugal force-based biomedical system 2 1.2.1 Cardiopulmonary support system: Macro-scale 3 1.2.2 Centrifugal micro-fluidic biochip: Micro-scale 5 1.3 Research Aims 8 Chapter 2. Macro scale centrifugal-fluidic system for biomedical application 10 2.1 Development of a smart all-in-one cardiopulmonary circulatory support device 10 2.1.1 Introduction 11 2.1.2 Materials and Methods 12 2.1.3 Results and Discussion 14 2.1.4 Conclusion 15 2.2 Evaluation of hemolytic characteristics of centrifugal blood pump 22 2.2.1 Introduction 23 2.2.2 Materials and Methods 26 2.2.3 Results and Discussion 29 2.2.4 Conclusion 33 2.3 Evaluation of drug sequestration in the extracorporeal membrane oxygenation (ECMO) circuit 45 2.3.1 Introduction 45 2.3.2 Materials and Methods 47 2.3.3 Results 50 2.3.4 Discussion 51 2.3.5 Conclusion 54 Chapter 3. Micro scale centrifugal-fluidic system for biomedical application 60 3.1 A numerical study of the Coriolis effect in centrifugal microfluidics with different channel arrangements 60 3.1.1 Introduction 61 3.1.2 Model problem 64 3.1.3 Analytical solution 69 3.1.4 Numerical solution 71 3.1.5 Results 75 3.1.6 Discussion 79 3.1.7 Summary and Conclusion 83 3.2 Centrifugal microfluidic-based viscometer 103 3.2.1 Introduction 103 3.2.2 Materials and Methods 104 3.2.3 Results 105 3.2.4 Discussion 105 3.2.5 Conclusion 106 3.3 Hypergravity-induced multicellular spheroid generation 110 3.3.1 Introduction 111 3.3.2 Materials and Methods 114 3.3.3 Results and Discussion 119 3.2.4 Conclusion 125 3.4 A study on adipose-derived stem cells adaptions to hypergravity environment 144 3.4.1 Introduction 144 3.4.2 Materials and Methods 147 3.4.3 Results 150 3.4.4 Discussion 151 3.4.5 Conclusion 152 Chapter 4. Conclusion and Perspective 161 References 168 Abstract in Korean 193Docto

Microgravity Science and Applications Program Tasks, 1984 Revision

This report is a compilation of the active research tasks as of the end of the fiscal year 1984 of the Microgravity Science and Applications Program, NASA-Office of Space Science and Applications, involving several NASA centers and other organizations. The purpose of the document is to provide an overview of the program scope for managers and scientists in industry, university, and government communities. The report is structured to include an introductory description of the program, strategy and overall goal; identification of the organizational structures and people involved; and a description of each research task, together with a list of recent publications. The tasks are grouped into six categories: (1) electronic materials; (2) solidification of metals, alloys, and composites; (3) fluid dynamics and transports; (4) biotechnology; (5) glasses and ceramics; and (6) combustion

Development of a biohybrid lung

Therapy for patients suffering from acute respiratory distress syndrome (ARDS) is substantially inadequate, resulting in a 40% mortality rate. A biohybrid lung prototype consisting of a rotating endothelialized microporous hollow fiber (MHF) bundle was studied as an alternative solution for improved patient outcome. It is hypothesized that endothelialized MHFs could present a surface mimicking the native vascular lining to reduce thrombotic deposition on underlying MHF. Such an approach might thus allow blood oxygenation and CO2 removal for extended periods with reduced anticoagulation requirements. Development of the biohybrid lung prototype, evaluation of endothelial cell (EC) response to shear stress, influence of endothelialization on gas transfer, and impact of bundle rotational speed on gas transfer and alterations in EC phenotype were studied. MHFs were surface modified to promote EC attachment and proliferation. Endothelialized MHF bundles were rotated in the biohybrid lung prototype up to 1500 RPM (26.4 dynes/cm2). Blood-surface biocompatibility testing was performed on MHFs and MHF bundles in the biohybrid lung prototype, with or without ECs. Partial O2 pressures were recorded for blood samples to measure oxygen buildup within the biohybrid lung. Scanning electron micrographs (SEMs) of thrombotic deposition were taken. Upregulation of e-selectin and p-selectin on ECs were assessed for indication of an inflammatory EC phenotype.ECs maintained near confluent coverage on MHFs under rotation at the tested speeds, and showed minimal p-selectin expression subsequent to rotation. It was observed that even low to moderate levels of EC coverage greatly reduced thrombotic deposition on MHFs. Statistically significant differences in oxygen accumulation between MHF bundles with or without endothelialization in the presence of 95% O2 were not found. Thrombotic deposition on endothelialized MHF bundles was less than or equivalent to thrombotic deposition on non-endothelialized MHF bundles following rotation. Low levels of e-selectin and p-selectin expression were observed following 24 hr hyperoxia. These results suggest that endothelialized MHFs may serve to improve blood-surface biocompatibility in the presence of hyperoxia. Although further development and testing is required, a biohybrid lung employing endothelialized MHFs and a rotating fiber bundle may provide an alternative therapy for patients suffering from ARDS