Biomedical Engineering Challenges

A Chemical Engineering Insight

Vincenzo Piemonte, Angelo Basile, Taichi Ito, Luigi Marrelli, Vincenzo Piemonte, Angelo Basile, Taichi Ito, Luigi Marrelli

• Publisher: Wiley
• Year: 2018
• Print ISBN: 9781119296041
• eBook ISBN: 9781119296010
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Biotechnology
• Index: Biological Sciences

An important resource that puts the focus on the chemical engineering aspects of biomedical engineering

In the past 50 years remarkable achievements have been advanced in the fields of biomedical and chemical engineering. With contributions from leading chemical engineers, Biomedical Engineering Challenges reviews the recent research and discovery that sits at the interface of engineering and biology. The authors explore the principles and practices that are applied to the ever-expanding array of such new areas as gene-therapy delivery, biosensor design, and the development of improved therapeutic compounds, imaging agents, and drug delivery vehicles.

Filled with illustrative case studies, this important resource examines such important work as methods of growing human cells and tissues outside the body in order to repair or replace damaged tissues. In addition, the text covers a range of topics including the challenges faced with developing artificial lungs, kidneys, and livers; advances in 3D cell culture systems; and chemical reaction methodologies for biomedical imagining analysis. This vital resource:

• Covers interdisciplinary research at the interface between chemical engineering, biology, and chemistry
• Provides a series of valuable case studies describing current themes in biomedical engineering
• Explores chemical engineering principles such as mass transfer, bioreactor technologies as applied to problems such as cell culture, tissue engineering, and biomedical imaging

Written from the point of view of chemical engineers, this authoritative guide offers a broad-ranging but concise overview of research at the interface of chemical engineering and biology.

1
Introduction

Luigi Marrelli

Department of Engineering, University Campus Biomedico of Rome, Italy

Biomedical Engineering (BE) is a complex applied science that has applications in the fields of medicine concerning diagnosis, therapy and rehabilitation. As in all sectors of technology characterized by complexity, the capability of solving problems and developing new devices for therapy and rehabilitation or to devise innovative techniques for diagnosis and treatment of pathologies requires synergy of various forms of expertise. This need is especially felt in BE where the subject of research is the human body with its complex operations: molecular mechanisms, chemical and biochemical intracellular reactions, control systems, functions of human organs and so on.

Despite the complexity of the biological system that doctors and biomedical engineers must relate to, the elements of which the human body is composed and the functions they perform have a close affinity with the operations carried out in a chemical plant [1] where some raw materials undergo a series of transformations (reactions, separation operations, mass and heat exchanges, etc.) in order to obtain useful products and energy. In the last century, this analogy has led to striking graphic representations of the human body and of its functions as an industrial plant. It is worth mentioning the picture [2] named “Der Mensch als Industriepalast,” a creation by Fritz Kahn, a German doctor, science writer and pioneer of information graphics.

Indeed, the human body is composed of a solid structure of support and a casing that encloses a series of organs with functions of mass exchange, synthesis and transformation, and are connected to each other by a network of ducts passed through by fluids. A pumping system equipped with valves has the task of ensuring blood circulation in the vascular circuit. The digestive system, through complex chemical reactions, transforms ingested raw materials into useful substances and energy needed for the operation of the whole system. The muscular system can be regarded as a set of actuators responsible for moving several parts of the body whereas the peripheral nervous system supplies sensory stimuli coming from the environment to the central nervous system that supervises the control and processing of various functions in a similar way to what happens in the system of sensors, monitoring and automatic control in an industrial plant.

Beyond this evocative picture, however, the analogy suggests the idea that many sophisticated techniques of chemical engineering (CE) could be usefully applied to face the technical challenges of BE. Since the beginnings of its history, CE has dealt with unit operations for the separation of mixtures, humidification of gases, chemical reactors, mass, heat and momentum transport, properties of materials and so on, on the basis of scientific fundamentals that are phase equilibria thermodynamics, chemical and biochemical kinetics, transport phenomena, automatic control and mathematical tools needed to better understand many complex phenomena and to represent the behavior of equipment through theoretical or semi‐empirical models useful for the simulation and the optimization of the process. Therefore, CE can provide skills to the solution of problems that BE has to face and, vice versa by a cross‐fertilization process, can receive from BE valuable input for the development of innovative methods and processes deduced from the behavior of biological systems.

The fields where CE can provide fundamental contributions are numerous and range from the macroscale of artificial and bio‐artificial organs to the nanoscale of chemical‐physical properties of materials of cell micro‐reactors. Furthermore, also in the industrial biotechnology and pharmaceutical fields, CE points out its potentiality in the large‐scale production of drugs and in sophisticated methods of targeted drug delivery.

Organs like the kidney, liver or heart‐lung system have, among their functions, those of cleaning the blood from toxins or excesses of substances and of exchanging oxygen and carbon dioxide. When native organs are not able to correctly perform these functions for pathological reasons, an artificial kidney, artificial liver or lung oxygenation unit can substitute or at least support the damaged vital functions and allow the patient to stay alive indefinitely or, at least, long enough for the possibility of carrying out transplantation or revival of the native organ. Nowadays, ultrafiltration technology by selective membranes is an acquired asset in CE that can provide a key contribution to the development of increasingly effective and low‐cost artificial organs. Some chapters of the present book are devoted to artificial organs and their behavior.

However, just separation operations and selective transport are not enough in many cases to mimic the functions of the native organ: complex organs such as the liver or pancreas carry out synthesis functions and biochemical reactions not currently reproducible by artificial systems. This need has led to the development of bio‐artificial or hybrid organs in which the artificial component is coupled with a biological element; that is, a cell tissue able to perform functions not reproducible by a totally artificial system.

Therefore, hybrid organs are characterized by the presence of a kind of bioreactor where cells are kept in the optimal conditions for their survival and, in particular, to perform the functions of which they are responsible. The use of living cells as engineering materials is the basis of the so‐called tissue engineering [3] where chemical engineering, material science and life sciences skills are involved. In the field of tissue engineering, the scaffold or support technology provides an important step in the growth and differentiation of the desired tissue. Even in this case, chemical reaction engineering and theory of reactors, the typical hallmarks of chemical engineers’ activity, play a fundamental role in modeling, designing and properly running the bioreactor used for growing the new tissue.

A technology still under study is the development of an artificial pancreas. The purpose of this device is monitoring and properly releasing insulin, a hormone produced by β cells of the pancreatic islets of Langerhans, that regulates the absorption of glucose from blood and its conversion into glycogen or triglycerides. If β cells do not work, insulin can no longer be synthesized or secreted into the blood resulting in a high blood glucose concentration (type 1 diabetes). In order to solve this problem, chemical engineers are working on a computerized device able to monitor continuously blood glucose levels and to actuate micro‐pumps for delivering insulin contained in a small reservoir. Chapter 5 of the present book is devoted to the artificial pancreas.

A well‐known field of CE deals with scale‐up techniques; that is, similar criteria needed to develop an industrial plant from information on the behavior of a pilot or bench scale plant. In the past, these techniques have already provided fundamental results for designing and running plants devoted to manufacturing products essential to human health. A typical early example is the process of producing penicillin on an industrial scale, suggested at the end of the World War II by Margaret Hutchinson Rousseau [4], a young chemical engineer. The industrial production process is based on an aerobic submerged fermentation. When penicillin was first made, the fungus Penicillum notatum was used and the yield of the process was about 1 mg/dm³. Nowadays, using a different mold species (Penicillum chrysogenum) and by improving fermentation operating conditions and downstream processing, such as extraction techniques, a yield of 50 g/dm³ is reached.

The opposite side of the coin is represented by scale‐down techniques; that is, by the techniques to implement micro‐devices [5, 6]. These devices are composed of a network of microchannels connecting micro‐reactors, mixers, pumps and valves contained in vessels whose dimensions are in the order of micrometers with controlled volumes down to picolitres. At this scale, fluid transport in capillaries is laminar and the resulting very high surface area to volume ratio affects mass and heat transfer rates and catalytic reaction rates that depend on the interface area. Microfluidic devices (lab‐on‐chip assemblies) are increasingly used to carry out chemical and biochemical reactions for applications in the genomic field, immunoassays, sensors, drug discovery, new catalyst development and many other forthcoming uses.

Properties of materials is another field where CE together with material science can provide an important contribution to BE. Scaffolds used in tissue engineering have to be biocompatible and biodegradable [1] to allow their use in contact with biological material and their absorption by the surrounding tissues when scaffolds are used in implantable devices. In any case, the degradation rate of the support must be compatible with the rate of making new tissue and with the integration of this one with the surrounding tissues. A very important property of the scaffold is its porosity and the distribution of pore sizes to allow three‐dimensional tissue growth. A fractal geometry approach has proven to be useful for the characterization of these properties.

The knowledge of rheological properties of biological fluids [7] is another essential requirement for a proper design of extracorporeal devices. Blood is a suspension made of an aqueous solution (plasma) of electrolytes, sugars and proteins and of a corpuscular part composed of erithrocytes, leucocytes and platelets. Plasma is a Newtonian fluid with a viscosity of

at 37 °C. Whole blood, on the other hand, shows non‐Newtonian behavior ranging from Bingham to pseudoplastic fluid behavior depending on the value of the shear stress. Non‐Newtonian characteristics are clearer in the thinnest ducts as capillaries.

These rheological properties make the modeling of blood flow particularly complex [8, 9] in the various blood ducts, especially if one wishes to account for the transient behavior of the flow due to heartbeat and for non‐stiffness of blood vessels. Moreover, in the case of blood circulation in extracorporeal devices, a non‐neglig...

Table of contents

• Cover
• Title Page
• Table of Contents
• List of Contributors
• Preface
• 1 Introduction
• 2 Artificial Kidney: The New Challenge
• 3 Current Status and New Challenges of the Artificial Liver
• 4 A Chemical Engineering Perspective on Blood Oxygenators
• 5 Model Predictive Control for the Artificial Pancreas
• 6 Multiscale Synthetic Biology
• 7 Chemical Reaction Engineering Methodologies for Biomedical Imaging Analysis
• 8 Noninvasive and Label‐Free Characterization of Cells for Tissue Engineering Purposes
• 9 TMS‐EEG
• 10 Thermal Treatments of Tumors
• Index
• End User License Agreement