Microfluidic Analysis of Vertebrate Red Blood Cell Characteristics


Book Description

Continuous multidisciplinary advancements in medicine, science and engineering have led to the rise of biomedical microfluidic devices for clinical diagnoses, laboratory research for modeling and screening of drugs or disease states, and implantable organs such as artificial kidneys. Blood is often the biological fluid of choice for these purposes. However, unique hemodynamic properties observed only in microscale channels complicate experimental repeatability and reliability. For vessels with 10-300μm diameters, red blood cell properties such as deformability have a significant impact on hemorheology, and the blood can no longer be considered as a homogeneous fluid. The flowing blood segregates into a red blood cell rich core bounded by a cell-free layer composed almost entirely of plasma. Viscous forces dominate flow behavior, and shear rates at the wall are much higher than in arteries and veins. The overall viscosity becomes dependent on vessel diameter. These unique characteristics are interesting from a biophysics perspective, but the value of biomedical microfluidic technologies makes research in this regime even more critical. Accordingly, this work focuses on experimental comparison of the microfluidic flow properties of red blood cells with varying physical characteristics. Blood viscosity in microscale tubes was investigated experimentally for 6 blood types (goat, sheep, pig, llama, chicken and turkey) at a range of hematocrits (0-50%). The selected blood types represented a small sample of the wide-ranging red blood cell characteristics found in mammals, birds, reptiles, amphibians and fish. These red blood cells vary in size over an order of magnitude, represent shapes ranging from biconcave to ellipsoidal, and include both nucleated cell types found in birds, amphibians and reptiles and denucleated mammalian cells. Pressure drop experiments at physiologically relevant flow rates were carried out for rigid tubing diameters ranging from 73μm - 161μm. The resulting viscosities were normalized relative to the measurements made of the homologous plasma for each species. The viscosity of blood in this regime is much different than in larger vessels (>500μm) or in small capillaries (




Analysis of Red Blood Cell Mechanical Properties


Book Description

Decreased deformability of human red blood cells (RBCs) is both a cause of disease and biomarker for disease (1). To traverse blood capillaries, the biconcave disk-shaped RBC must deform dramatically, since the diameter of the unconstrained RBC is larger than that of the capillaries. If the RBC becomes immobilized in a capillary, hypoxia and tissue injury may result, potentially leading to death. Changes in RBC deformability may be attributable to genetics (e.g. sickle cell anemia (2) and spherocytosis (3)), drug exposure (e.g. pentoxifylline (4)), and disease (e.g. diabetes (5) and malaria (6)). Within the past 15 years, microfabrication techniques have enabled the creation of pores comparable in size and shape to the smallest human capillaries (7) and slits in the spleen (8). We use this microfabrication ability to create devices that analyze and separate RBCs of different deformability. The first device we create is an automated 'deformability cytometer' that measures dynamic mechanical responses of 103~104 individual cells in a cell population. Fluorescence measurements of each cell are simultaneously acquired, resulting in a population-based correlation between biochemical properties (e.g. cell surface markers) and dynamic mechanical deformability. This device is especially applicable to heterogeneous cell populations, and we demonstrate its ability to mechanically characterize a small number of ring-stage malaria-infected RBCs in a large population of healthy RBCs. Next we present a device whose design is based on the architecture of the human spleen. This device is able to continuously separate more deformable from less deformable RBCs. We demonstrate the ability of this device to separate schizont-stage malaria-infected RBCs from healthy RBCs. Together, these devices enable the analysis and separation of single-RBCs based on deformability.




Dynamics of Blood Cell Suspensions in Microflows


Book Description

Blood microcirculation is essential to our bodies for the successful supply of nutrients, waste removal, oxygen delivery, homeostasis, controlling temperature, wound healing, and active immune surveillance. This book provides a physical introduction to the subject and explores how researchers can successfully describe, understand, and predict behaviours of blood flow and blood cells that are directly linked to these important physiological functions. Using practical examples, this book explains how the key concepts of physics are related to blood microcirculation and underlie the dynamic behavior of red blood cells, leukocytes, and platelets. This interdisciplinary book will be a valuable reference for researchers and graduate students in biomechanics, fluid mechanics, biomedical engineering, biological physics, and medicine. Features: The first book to provide a physical perspective of blood microcirculation Draws attention to the potential of this physical approach for novel applications in medicine Edited by specialists in this field, with chapter contributions from subject area specialists




The Red Cell Life-Cycle From Erythropoiesis to Clearance


Book Description

The eBook ‘The red cell life-cycle from erythropoiesis to clearance’ continues the discussion of questions like: What are the changes associated with red blood cell maturation, adulthood and senescence? What are the determinants of red blood cell life span and clearance? What are the mechanisms in control of red blood cell mass in healthy humans and patients with various forms of anaemia? Can red blood cells be 'trained' to provide the body with more oxygen during endurance exercises? What are the markers of circulating red blood cell senescence and in cells during storage and transfusion? And what can be learned from various species that developed advanced adaptations to maintain oxygen delivery under stress conditions such as exercising to the limit, diving or living in anaerobic aquatic habitats or at high altitude? Within the approximately 120 days (or 40 in a mouse, or 150-170 in a horse) life span of 'healthy' red blood cells, many cellular properties change leading to aged mixed cell populations in the circulation. Red blood cells seem to be genetically terminated by the time they become red blood cells and the contributions of this eBook increase the understanding of this process. There are surprisingly versatile remodeling processes happening during the red blood cell life span. Numerous disorders are associated with the premature onset of the 'ageing process' of red blood cells. Furthermore, in vitro ageing and/or modifications as well as the slowing down of the modifications is an important issue in transfusion medicine. Many of the molecular mechanisms behind such effects are elucidated in this eBook.




Red Cell Membrane Transport in Health and Disease


Book Description

51 worldwide leading experts in the field of erythrocyte research contributed to this first book on transport processes in red blood cells. It explains the latest findings on the basis of well-established principles, in an accessibly structured and carefully organized compilation.




Angiogenesis Assays


Book Description

Angiogenesis, the development of new blood vessels from the existing vasculature, is essential for physiological growth and over 18,000 research articles have been published describing the role of angiogenesis in over 70 different diseases, including cancer, diabetic retinopathy, rheumatoid arthritis and psoriasis. One of the most important technical challenges in such studies has been finding suitable methods for assessing the effects of regulators of eh angiogenic response. While increasing numbers of angiogenesis assays are being described both in vitro and in vivo, it is often still necessary to use a combination of assays to identify the cellular and molecular events in angiogenesis and the full range of effects of a given test protein. Although the endothelial cell - its migration, proliferation, differentiation and structural rearrangement - is central to the angiogenic process, it is not the only cell type involved. the supporting cells, the extracellular matrix and the circulating blood with its cellular and humoral components also contribute. In this book, experts in the use of a diverse range of assays outline key components of these and give a critical appraisal of their strengths and weaknesses. Examples include assays for the proliferation, migration and differentiation of endothelial cells in vitro, vessel outgrowth from organ cultures, assessment of endothelial and mural cell interactions, and such in vivo assays as the chick chorioallantoic membrane, zebrafish, corneal, chamber and tumour angiogenesis models. These are followed by a critical analysis of the biological end-points currently being used in clinical trials to assess the clinical efficacy of anti-angiogenic drugs, which leads into a discussion of the direction future studies should take. This valuable book is of interest to research scientists currently working on angiogenesis in both the academic community and in the biotechnology and pharmaceutical industries. Relevant disciplines include cell and molecular biology, oncology, cardiovascular research, biotechnology, pharmacology, pathology and physiology.




The Biophysics of Cell Membranes


Book Description

This volume focuses on the modulation of biological membranes by specific biophysical properties. The readers are introduced to emerging biophysical approaches that mimick specific states (like membrane lipid asymmetry, membrane curvature, lipid flip-flop, lipid phase separation) that are relevant to the functioning of biological membranes. The first chapter describes innovative methods to mimic the prevailing asymmetry in biological membranes by forming asymmetrical membranes made of monolayers with different compositions. One of the chapters illustrates how physical parameters, like curvature and elasticity, can affect and modulate the interactions between lipids and proteins. This volume also describes the sensitivity of certain ion channels to mechanical forces and it presents an analysis of how cell shape is determined by both the cytoskeleton and the lipid domains in the membrane. The last chapter provides evidence that liposomes can be used as a minimal cellular model to reconstitute processes related to the origin of life. Each topic covered in this volume is presented by leading experts in the field who are able to present clear, authoritative and up-to-date reviews. The novelty of the methods proposed and their potential for a deeper molecular description of membrane functioning are particularly relevant experts in the areas of biochemistry, biophysics and cell biology, while also presenting clear and thorough introductions, making the material suitable for students in these fields as well.




Platelets in Thrombotic and Non-Thrombotic Disorders


Book Description

This book reviews current science and applications in fields including thrombosis and hemostasis, signal transduction, and non-thrombotic conditions such as inflammation, allergy and tumor metastasis. It is a detailed, up-to-date, highly referenced text for clinical scientists and physicians, including recent developments in this rapidly expanding field. More than a scientific resource, this is also an authoritative reference and guide to the diagnosis.




High Resolution Imaging in Microscopy and Ophthalmology


Book Description

This open access book provides a comprehensive overview of the application of the newest laser and microscope/ophthalmoscope technology in the field of high resolution imaging in microscopy and ophthalmology. Starting by describing High-Resolution 3D Light Microscopy with STED and RESOLFT, the book goes on to cover retinal and anterior segment imaging and image-guided treatment and also discusses the development of adaptive optics in vision science and ophthalmology. Using an interdisciplinary approach, the reader will learn about the latest developments and most up to date technology in the field and how these translate to a medical setting. High Resolution Imaging in Microscopy and Ophthalmology – New Frontiers in Biomedical Optics has been written by leading experts in the field and offers insights on engineering, biology, and medicine, thus being a valuable addition for scientists, engineers, and clinicians with technical and medical interest who would like to understand the equipment, the applications and the medical/biological background. Lastly, this book is dedicated to the memory of Dr. Gerhard Zinser, co-founder of Heidelberg Engineering GmbH, a scientist, a husband, a brother, a colleague, and a friend.




Red Cell Metabolism


Book Description