Inflow cannula design for biventricular assist devices

Cardiovascular diseases are a leading cause of death throughout the developed world. With the demand for donor hearts far exceeding the supply, a bridge-to-transplant or permanent solution is required. This is currently achieved with ventricular assist devices (VADs), which can be used to assist the left ventricle (LVAD), right ventricle (RVAD), or both ventricles simultaneously (BiVAD). Earlier generation VADs were large, volume-displacement devices designed for temporary support until a donor heart was found. The latest generation of VADs use rotary blood pump technology which improves device lifetime and the quality of life for end stage heart failure patients. VADs are connected to the heart and greater vessels of the patient through specially designed tubes called cannulae. The inflow cannulae, which supply blood to the VAD, are usually attached to the left atrium or ventricle for LVAD support, and the right atrium or ventricle for RVAD support. Few studies have characterized the haemodynamic difference between the two cannulation sites, particularly with respect to rotary RVAD support. Inflow cannulae are usually made of metal or a semi-rigid polymer to prevent collapse with negative pressures. However suction, and subsequent collapse, of the cannulated heart chamber can be a frequent occurrence, particularly with the relatively preload insensitive rotary blood pumps. Suction events may be associated with endocardial damage, pump flow stoppages and ventricular arrhythmias. While several VAD control strategies are under development, these usually rely on potentially inaccurate sensors or somewhat unreliable inferred data to estimate preload. Fixation of the inflow cannula is usually achieved through suturing the cannula, often via a felt sewing ring, to the cannulated chamber. This technique extends the time on cardiopulmonary bypass which is associated with several postoperative complications. The overall objective of this thesis was to improve the placement and design of rotary LVAD and RVAD inflow cannulae to achieve enhanced haemodynamic performance, reduced incidence of suction events, reduced levels of postoperative bleeding and a faster implantation procedure. Specific objectives were: * in-vitro evaluation of LVAD and RVAD inflow cannula placement, * design and in-vitro evaluation of a passive mechanism to reduce the potential for heart chamber suction, * design and in-vitro evaluation of a novel suture-less cannula fixation device. In order to complete in-vitro evaluation of VAD inflow cannulae, a mock circulation loop (MCL) was developed to accurately replicate the haemodynamics in the human systemic and pulmonary circulations. Validation of the MCL’s haemodynamic performance, including the form and magnitude of pressure, flow and volume traces was completed through comparisons of patient data and the literature. The MCL was capable of reproducing almost any healthy or pathological condition, and provided a useful tool to evaluate VAD cannulation and other cardiovascular devices. The MCL was used to evaluate inflow cannula placement for rotary VAD support. Left and right atrial and ventricular cannulation sites were evaluated under conditions of mild and severe heart failure. With a view to long term LVAD support in the severe left heart failure condition, left ventricular inflow cannulation was preferred due to improved LVAD efficiency and reduced potential for thrombus formation. In the mild left heart failure condition, left atrial cannulation was preferred to provide an improved platform for myocardial recovery. Similar trends were observed with RVAD support, however to a lesser degree due to a smaller difference in right atrial and ventricular pressures. A compliant inflow cannula to prevent suction events was then developed and evaluated in the MCL. As rotary LVAD or RVAD preload was reduced, suction events occurred in all instances with a rigid inflow cannula. Addition of the compliant segment eliminated suction events in all instances. This was due to passive restriction of the compliant segment as preload dropped, thus increasing the VAD circuit resistance and decreasing the VAD flow rate. Therefore, the compliant inflow cannula acted as a passive flow control / anti-suction system in LVAD and RVAD support. A novel suture-less inflow cannula fixation device was then developed to reduce implantation time and postoperative bleeding. The fixation device was evaluated for LVAD and RVAD support in cadaveric animal and human hearts attached to a MCL. LVAD inflow cannulation was achieved in under two minutes with the suture-less fixation device. No leakage through the suture-less fixation device – myocardial interface was noted. Continued development and in-vivo evaluation of this device may result in an improved inflow cannulation technique with the potential for off-bypass insertion. Continued development of this research, in particular the compliant inflow cannula and suture-less inflow cannulation device, will result in improved postoperative outcomes, life span and quality of life for end-stage heart failure patients

DESIGN OPTIMIZATION AND PRECLINICAL TESTING OF PEDIATRIC ROTARY BLOOD PUMPS AND COMPONENTS: TOWARDS THE PEDIAFLOW® VAD

Limited options exist for children (BSA<1.5 m2) requiring long-term mechanical circulatory support (MCS). Unlike adults where compact, 3rd generation, continuous-flow, implantable rotary blood pumps (RBPs) are now the standard for ventricular assist device (VAD)-indications, the only pediatric-approved chronic MCS device is the Berlin Heart® EXCOR®: a 1st generation pulsatile, pneumatically-driven, paracorporeal life-saving technology albeit with a substantial risk profile associated with frequent neurological and coagulation-related serious adverse events. In support of the smallest and most vulnerable patients, the goal of this research is to facilitate the development and translation of next-generation pediatric RBPs, including the University of Pittsburgh-led Consortium’s PediaFlow®: a miniature, implantable, rotodynamic, fully magnetically levitated, continuous-flow pediatric VAD intended to support patients between 3 to 15 kg at a flow rates of 0.3-1.5 L/min for up to six months. Presented here is the i) development of a standardized method for in vitro mechanical blood trauma testing of pediatric MCS devices; ii) design and ex vivo evaluation of a novel, pediatric-appropriate, suction resistant, placement insensitive, left ventricular drainage cannula; iii) creation of an MCS-tailored monitoring software for preclinical testing; iv) development of a PediaFlow®-specific flow estimation algorithm; and v) hemocompatibility findings in vitro and in vivo of the 4th generation PediaFlow® (PF4) VAD. The PF4, comparable in size to an AA battery, is the embodiment of more than a decade of extensive computational and experimental efforts over the span of four device iterations to minimize size, optimize performance, and maximize safety. This dissertation represents the work and results to date of PediaFlow® PF4 on the path to preclinical testing to submit an Investigation Device Exception (IDE) application in anticipation of eventual clinical trials

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

Modern Telemetry

Telemetry is based on knowledge of various disciplines like Electronics, Measurement, Control and Communication along with their combination. This fact leads to a need of studying and understanding of these principles before the usage of Telemetry on selected problem solving. Spending time is however many times returned in form of obtained data or knowledge which telemetry system can provide. Usage of telemetry can be found in many areas from military through biomedical to real medical applications. Modern way to create a wireless sensors remotely connected to central system with artificial intelligence provide many new, sometimes unusual ways to get a knowledge about remote objects behaviour. This book is intended to present some new up to date accesses to telemetry problems solving by use of new sensors conceptions, new wireless transfer or communication techniques, data collection or processing techniques as well as several real use case scenarios describing model examples. Most of book chapters deals with many real cases of telemetry issues which can be used as a cookbooks for your own telemetry related problems

Brain-Targeted Drug Delivery

Brain diseases currently affect one in six people worldwide; they include a wide range of neurological diseases, from Alzheimer’s and Parkinson’s diseases to epilepsy, brain injuries, brain cancer, neuroinfections, and strokes. The treatment of these diseases is complex and limited due to the presence of the blood–brain barrier (BBB), which covers the entirety of the brain. The BBB not only has the function of protecting the brain from harmful substances; it is also a metabolic barrier and a transport regulator of nutrients/serum factors/neurotoxins. Knowing these characteristics when it comes to the treatment of brain diseases makes it easier to understand the lack of efficacy of therapeutic drugs, resulting from the innate resistance of the BBB to permeation. To overcome this limitation, drug delivery systems based on nanotechnology/microtechnology have been developed. Brain-targeted drug delivery enables targeted therapy with a higher therapeutic efficacy and fewer side effects because it targets moieties present in the drug delivery systems

Aerospace Medicine and Biology: A cumulative index to a continuing bibliography

This publication is a cumulative index to the abstracts contained in Supplements 138 through 149 of AEROSPACE MEDICINE AND BIOLOGY: A CONTINUING BIBLIOGRAPHY. It includes three indexes -- subject, personal author, and corporate source