BEST e - Technische Universiteit Eindhoven

BEST e
Institute of
Biomedical Engineering Sciences
& Technology / eindhoven
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Table of Contents
2
1. Introduction 4
2. Education 6
Graduate School BEST/e 6
School for Medical Physics and Engineering SMPE/e 6
3. Research 8
Mission Statement 8
Molecular Bioengineering and Molecular Imaging (MBEMI) 8
Biomechanics and Tissue Engineering (BMTE) 10
Biomedical Imaging and Modeling (BIOMIM) 10
4. Collaboration with Maastricht 14
5. Department of Biomedical Engineering 16
5.1 Biomedical Chemistry 16
5.1.1 Dendritic architectures 16
5.1.2 Supramolecular Biomaterials 18
5.1.3 Protein Engineering 19
5.1.4 Clinical Chemistry 19
5.2 Biomedical NMR 20
5.2.1 The cardiovascular system 21
5.2.2 Molecular imaging 21
5.2.3 Skeletal muscle 22
5.3 Soft Tissue Biomechanics and Tissue Engineering 24
5.3.1 Tissue Engineering 24
5.3.2 Soft Tissue Mechanics 26
5.3.3 Multi-Phase Mechanics 27
5.4 Cardiovascular Biomechanics 28
5.4.1 Hemodynamics and Vascular Biomechanics 28
5.4.2 Cardiac Biomechanics 30
5.5 Bone and Orthopaedic Biomechanics 31
5.5.1 Mechanical Properties of Bone & Osteoporosis 31
5.5.2 Mechanobiology of Tissue Differentiation 32
5.5.3 Osteoarthrosis & Artificial joints 34
5.5.4 The healing touch of a plasma needle 35
5.6 Biomedical Image Analysis 36
5.6.1 Multi-scale image structure 36
5.6.2 Visualization and Clinical Applications 38
5.6.3 Molecular Imaging of the Ischemic Heart 39
5.7 Biomodeling and Bioinformatics 40
5.7.1 Protein, Membrane, and Cell Simulations 40
5.7.2 Tissue simulations
5.7.3 Metabolic pathways, genetic algorithms,
41
bioinformatics 42
6. Department of Electrical Engineering 44
6.1 BioSignals and Regulation
6.1.1 Generic methods from system and control
44
theory for biosystems
6.1.2 Applications in computational Systems Biology
44
and physiology 46
6.2 Medical Signal Processing 47
6.2.1 Fetal monitoring. 47
6.2.2 Neuromonitoring 48
6.2.3 Medical image and video processing chains 50
6.2.4 Peri-operative signal processing 51
7. Department of Applied Physics 52
7.1 Molecular Biosensors for Medical Diagnostics
7.1.1 Properties, actuation and detection of magnetic
52
nanoparticles 52
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7.1.2 Biophysics: protein detection, biochemical binding,
and cell diagnostics 54
8. Department of Mechanical Engineering 56
8.1 Micro- and Nanoscale Engineering
8.1.1 Bead based fluid actuation techniques for
56
immunoassay devices 56
8.2 Mechanics of Materials 58
8.2.1 Mechanics of biomedical devices 58
8.2.2 Injury biomechanics 59
8.3 Dynamics and Control Technology 60
8.3.1 Medical Robotics 61
9. Department of Mathematics and Computer Science 62
9.1 Differential Equations in the Life Sciences
9.1.1 Mixed finite elements for the modeling of
62
cartilaginous tissues
9.1.2 Metabolic Control Analysis in spatially
62
heterogeneous systems 64
9.1.3 Is bone remodeling an optimization algorithm? 65
10. Research Input 66

Introduction
4
Technology has become indispensable in current medical research, diagnostics, treatment and care.
Representative examples are found in protein engineering for biomolecular imaging and novel drug
design, various imaging modalities, including vital imaging to study molecular events at the cellular
and tissue level, functional MRI and ultra-sound, image analysis, treatment using artificial implants,
the emerging field of regenerative medicine, including tissue engineering, and the use of
computational tools to enhance diagnostics and surgical intervention.
Research in biomedical engineering sciences aims to further the use of engineering principles
and tools to unravel the pathophysiology of diseases and to enhance diagnostics, intervention and
treatment of diseases. The choice made in Eindhoven, in collaboration with the University of
Maastricht, is to focus our main research efforts on three interrelated themes:
• Molecular bioengineering and molecular imaging,
• Biomechanics and tissue engineering,
• Biomedical imaging and modeling.
Advances in molecular biology enable the detailed investigation of the pathophysiology of many
diseases, as well as their treatment. Critical parameters in this research are the ability to synthesize
new supramolecular systems and to manipulate proteins. These capabilities enable biomolecular
imaging, using for instance confocal microscopy at the cellular and tissue level, and MRI to examine
molecular events in the whole body. Treatment involves the design of new drugs and site specific drug
delivery systems. Furthermore, our synthetic capabilities foster the design of new materials in which
biological systems are mimicked or expanded in order to obtain materials with new functions or
properties. Applications are found in the field of biosensors and regenerative medicine and tissue
engineering.
Introduction
The rapidly emerging field of tissue engineering aims to reconstitute functional tissues and
organs, either in-vitro or in-vivo. We have chosen to focus our research effort on load bearing tissues
with emphasis on cardiovascular tissues. The prime challenge is to create living, autologous tissues
that can sustain physiological loading, adapt to functional demand changes and grow. The key
biomechanical questions are how biological structure relates to biomechanical properties, how
mechanical loading modulates the microstructure (mechanotransduction), and what biochemical and
mechanical environment should be created inside bioreactor for optimal function tissue formation.
These questions are closely related to the in-vivo remodeling response of biological tissues. Various
pathologies in bone and cardiovascular disease are directly related to the mechanical loading of these
tissues. Fundamental understanding of mechanotransduction pathways, the advance of computational
methods in combination with functional imaging and image analysis, will enable patient specific
diagnostics and intervention planning.
A variety of imaging modalities exist today, e.g. MRI, ultra-sound, etc. Rather than the design of
new imaging hardware, our focus is on using this hardware for functional imaging and to enhance
their image analysis capabilities by using techniques from mathematics, computer science, physics,
electrical engineering and medicine. To further functional imaging, using MRI, our capability to
manipulate biomolecules is of critical importance. Computational modeling of, for instance,
cardiovascular flow, the mechanical response, and events at the cellular level, will advance the
functional performance of MRI.
Computational modeling at the molecular and the cellular level will enhance our fundamental
understanding of the cell metabolism and transport mechanisms in and between cells and lead to the
design of new drugs and drug delivery systems.
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Education
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The Institute of Biomedical Engineering Sciences & Technology/eindhoven (BEST/e) is host of two
(post-)graduate schools of the Technische Universiteit Eindhoven (TU/e): the Graduate School BEST/e
and the School for Medical Physics and Engineering SMPE/e.
Graduate School BEST/e
The Graduate School BEST/e is responsible for two master programs, Biomedical Engineering (BME)
and Medical Engineering (ME) as well as the post-graduate PhD program of the department of
Biomedical Engineering. The Education Committee of BEST/e is especially engaged with the following
tasks:
• policy making in master education at BME and ME,
• control of admission to (pre)master programs at BME and ME,
• continuing education in (bio)medical engineering and research.
School for Medical Physics and Engineering SMPE/e
SMPE/e offers post-graduate, professional training programs for students with a background in
engineering physics, (bio)medical engineering, electrical engineering and mechanical engineering
who want to become specialists medical physicists (SMP), qualified medical physicists (QMP) or
qualified medical engineers (QME) eventually with an EFOMP registration (BIG-registration in the
Netherlands).
Education

Research
8
Research within the Institute BEST/e is focused on three major themes:
• Molecular Bioengineering and Molecular Imaging (MBEMI)
• Biomechanics and Tissue Engineering (BMTE)
• Biomedical Imaging and Modeling (BIOMIM)
Each theme covers a coherent and well defined discipline. Research projects frequently, if not
generally, are performed across these disciplinary and departmental borders. It is the explicit objective
of BEST/e to stimulate and nourish this cross disciplinary attitude among scientific staff and young
scientists. This philosophy is reflected in the mission statement.
Mission Statement
The mission of BEST/e is to be an internationally recognized research institute that offers (post)
graduate programs to educate scientists and engineers for advanced biomedical research and
development, who master a cross disciplinary approach.
Molecular Bioengineering and Molecular Imaging (MBEMI)
Research in the theme Molecular Bioengineering and Molecular Imaging is based on a molecular
approach of biomedical engineering problems using knowledge from several fields of study like
organic chemistry, biochemistry, polymer chemistry, physical chemistry and chemical physics.
Research within this theme aims at designing, synthesizing and characterizing new molecules or
materials for various applications, e.g. drug delivery systems, imaging (MRI and optical imaging),
Research

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tissue engineered heart valves, molecular imaging, the molecular basis for disease processes and
repair, and biomaterials for vascular replacement. The second major aim of the research in this theme
is the development of MR imaging, MR spectroscopy and optical imaging techniques for the in vivo
measurement of vital molecular and cellular processes. The research is performed in Eindhoven and
Maastricht in various groups.
Biomechanics and Tissue Engineering (BMTE)
Within the theme Biomechanics and Tissue Engineering we apply principles from fluid and solid
mechanics, and biology, to a variety of biomedical problems and devices. In particular, cause and
aetiology, prevention, diagnosis and treatment of medical conditions and diseases of the cardiovascular
and the musculoskeletal systems are examined. Treatment may involve the engineering of
living tissues and artificial implants, such as heart-valves, small diameter blood vessels, orthopaedic
implants, and extracorporeal systems and devices. These developments critically rely on the
availability of various technologies, such as bioreactors and testing procedures, which are subjects of
research. In all cases, numerical and experimental techniques offer powerful tools for biologically and
clinically relevant research in these areas.
Biomedical Imaging and Modeling (BIOMIM)
Within this theme methods and techniques from mathematics, computer science, physics, electrical
engineering and medicine are used in the imaging and modeling of biomedical systems. In both
research and clinical diagnostics these methods are applied to measure, understand, predict and depict
the structure, function and metabolism of living cells and tissues.
Research
In the modeling groups emphasis is on methods and techniques on the molecular and cellular
levels to enhance the understanding of cell metabolism and transport mechanisms in and between
cells. This understanding is applied to the design of new drugs, drug delivery systems, and medical
treatments of diseases.
In the imaging groups emphasis is on the analysis and exploitation of the multi-scale structure
of images, on advanced visualization methods for multi-spectral data, on diffusion tensor imaging, on
computer-aided diagnosis, image analysis for molecular imaging, and neurosurgical navigation.

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MBEMI BMTE BIOMIM
Department of Biomedical Engineering
• Biomedical Chemistry •
• Biomedical NMR •
• Soft tissue Biomechanics and Tissue Engineering •
• Cardiovascular Biomechanics •
• Bone and Orthopaedic Biomechanics •
• Biomedical Image Analysis •
• Biomodeling and Bioinformatics •
Department of Electrical Engineering
• BioSignals and Regulation •
• Medical Signal Processing •
Department of Applied Physics
• Molecular Biosensors for Medical Diagnostics •
Department of Mechanical Engineering
• Micro- and Nanoscale Engineering •
• Mechanics of Materials •
• Dynamics and Control Technology •
Department of Mathematics and Computer Science
• Differential equations in the Life Sciences •
Research

Collaboration with Maastricht
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The educational program of the department of Biomedical Engineering is executed in collaboration
with the University of Maastricht (UM), in particular the department of Medicine and the department
of Health Sciences. In a number of research areas close ties exists between research groups of the
TU/e, the UM, and the academic hospital of Maastricht (azM). This is expressed by the dual, part-time
appointments of several professors within each others institution. Frequently, the research associated
with the part-time appointment at the TU/e is fully integrated with the existing research program of
the host group, which is explicitly expressed in this brochure. In other cases, the research activity is an
entity of its own, and integrated within research institutes of the UM, e.g. CARIM and NUTRIM, and
for that reason has not been duplicated in this brochure.
Collaboration with Maastricht

Department of Biomedical Engineering
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5.1 Biomedical Chemistry
(Prof. dr. Bert Meijer)
approx. 14 FTE research
By now it is generally recognized that molecular engineering of functional materials is one of the key
aspects in the progress of biomedical engineering. Especially the interactions of novel molecules and
materials with proteins and cells, which rely on the possibility to precisely tune molecular structure
and collective properties, are being regarded as of paramount importance in this young and fast
moving field.
Through mutual collaboration, three major lines of research come together in addressing two
technological targets: molecular imaging and the development of biomaterials. In our approach these
targets are addressed through the design and synthesis of novel, functional and precisely defined
hybrid materials with dimensions between 5 and 20 nm that are constructed through combining
biomolecules (peptides, proteins) and (macro)molecular systems.
5.1.1 Dendritic architectures
(Prof.dr. Bert Meijer, dr.ir. Marcel van Genderen)
The research area of supramolecular architectures is devoted to using the multivalency of the dendritic
framework and other well-defined macromolecules or supramolecular complexes for biomedical
applications. These structures combine the precise chemical nature of an organic compound with the
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cooperativity in interactions of a macromolecule. In particular, we aim to attach multiple peptides or
proteins in a controlled way to multivalent scaffolds, both via covalent and non-covalent synthesis.
These new architectures will then be tested in various applications, e.g. drug delivery, targeted MRI
contrast agents, and polymer diagnostics or therapeutics.
5.1.2 Supramolecular Biomaterials
(Prof.dr. Bert Meijer, dr. Nico Sommerdijk)
The research of the Biomimetic Materials Group is aiming at the realization of biomaterials using the
supramolecular interactions, in particular hydrogen bonding, between macromolecules to achieve
control over their organization, but also as a modular tool to provide them with the bio-functionality
required for optimal performance. With this approach we target implantable biomaterials such as
scaffolds for tissue engineered heart valves, bone replacement materials and coatings for implants.
The use of supramolecular interactions serves not only to generate materials with the required
mechanical properties, but also provides a modular approach to the introduction of functional groups,
such as oligo-peptides that for example stimulate cell adhesion or induce the nucleation of
biominerals. To this end two hydrogen bonding moieties are explored: the ureido-pyrimidinone (UPy)
group and the bis-urea blocks, both capable of forming a fourfold hydrogen bonding interaction with
neighboring (macro)molecules. The fundamental properties of these molecular building blocks are
studied in close collaboration with the members of the Supramolecular Chemistry Group of our
Laboratory and applied to arrive at novel biomaterials with improved mechanical and bioactive
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properties. For the implementation of the resulting materials we collaborate with a number of groups
in the biomedical field both within and outside our university.
5.1.3 Protein Engineering
(Prof.dr. Bert Meijer, dr. Maarten Merkx)
Within the research area of protein engineering we are aiming at the development of novel artificial
proteins for biomedical applications and the fundamental understanding of the interactions of
proteins with small and large molecules. Currently, sensor proteins are being developed for the
intracellular imaging of copper and gaseous messenger molecules such as CO and NO. Techniques
from molecular biology (such as phage display) are used to study the interaction between (synthetic)
materials and biopolymers (peptides, proteins, DNA/RNA).
Finally, new approaches are explored to synthesize multivalent protein and peptide oligomers that can
find applications as antibody mimics and provide insights into the role of protein oligomers in amyloid
diseases such as Alzheimer.
5.1.4 Clinical Chemistry
(Prof.dr.ir. Huib Vader)
According to the formal definition, Clinical Chemistry/Clinical Biochemistry is a scientific discipline
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within medicine. It includes the analysis of body fluids, cells end tissues and the interpretation of the
results in relation to health and disease. The discipline encompasses fundamental and applied
research into the biochemical and physiological processes of human and animal life and application
of the resulting knowledge and understanding to diagnosis, treatment and prevention of disease.
The (applied) research area of the clinical chemistry group presently focuses on endocrinology
(especially the influence of thyroid function of the mother during pregnancy on the development of
the child), biomarkers for oxidative stress and the application of new analytical techniques in clinical
chemistry.
5.2 Biomedical NMR
(Prof.dr. Klaas Nicolay)
approx. 7 FTE research
The Biomedical NMR group (NMR: nuclear magnetic resonance) aims to explore novel biomedical
applications of magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques. MRI and
MRS offer exciting possibilities for the non-invasive investigation of a range of structural, functional
and metabolic parameters in living organisms. The present MR research that is both conducted in
animal models and man can be subdivided in three main topics.
Biomedical Engineering
5.2.1 The cardiovascular system
(Prof.dr. Klaas Nicolay, dr.ir. Gustav Strijkers)
Our MR research on the cardiovascular system is aimed at the development of new diagnostic
techniques for the detection of biological processes that are characteristic of the entire time-course of
cardiovascular disease development, including atherosclerosis and cardiac failure. Most of the
research is done in mice, because of the opportunities offered by transgenic and knock-out mouse
models. The MRI tools developed are used to monitor disease progression and to test novel
therapeutic interventions.
5.2.2 Molecular imaging
(Prof.dr. Klaas Nicolay, dr.ir. Gustav Strijkers)
MRI has a lot to offer to biomedical research and healthcare. The changes in MRI contrast that
accompany disease often only occur in a late stage and can have multiple causes. The emerging
technology of molecular imaging aims to visualize specific molecular markers of disease. Our research
on this topic focuses on the use of targeted MRI contrast agents to quantify the in-vivo distribution of
biological markers that are characteristic to a specific step in a disease process. Another focus is the
optimization of the MRI pulse sequences in terms of contrast-to-noise ratio they achieve and
quantification of the local contrast agent concentration. The tools that are developed are evaluated
in-vitro with the use of cultured cells and in-vivo in mouse cardiovascular disease models.
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5.2.3 Skeletal muscle
(Prof.dr. Klaas Nicolay, dr. Jeanine Prompers, dr.ir. Gustav Strijkers)
The research in this domain focuses on the development of non-invasive, MR-based assays for
measuring the structure, function and metabolism of skeletal muscle in-vivo. Muscle disorders and
other diseases with severe consequences for muscle function have a major impact on the quality of life
of the patient and represent a major socio-economic burden. Examples include pressure sores that
develop during hospitalization and type 2 diabetes that is caused by an impaired insulin sensitivity of
skeletal muscle. It is our aim to develop MR imaging and spectroscopy methods that enable us to
identify the risk factors that lead to muscle injury, to objectively diagnose muscle status and to monitor
the possible beneficial effects of therapeutic and lifestyle interventions. Studies are done in carefully
controlled animal models as well as in human patients.
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5.3 Soft tissue Biomechanics and Tissue Engineering
(Prof.dr.ir. Frank Baaijens)
approx. 19 FTE research
Living tissues show an intriguing, active response to mechanical loading. Not only is the intrinsic
mechanical response complicated, the ability of living tissues to adapt to mechanical loading by
changing their structure and composition is fascinating. For example, tissue proliferation and
differentiation is significantly affected by mechanical loading. A quantitative understanding of these
phenomena, through experimentation and computational modeling, is of crucial importance for many
biomedical applications.
5.3.1 Tissue Engineering
(Prof.dr.ir. Frank Baaijens, prof.dr. Simon Hoerstrup, prof.dr. Mark Post, prof.dr. Josef Bartunek, dr. Carlijn
Bouten, Prof.dr.ir. Han Meijer)
Tissue engineering aims at the in-vitro generation of living tissue substitutes to repair or replace
affected tissues and organs in the human body. It is a fast emerging discipline at the interface of the
engineering and life sciences and generally implies the seeding of cells on pre-shaped temporary
biodegradable carrier materials (scaffolds) to form a construct that is cultured outside the body under
conditions that favor tissue formation. In our group, research concentrates on the creation of tissues
that serve a predominantly biomechanical function, such as cardiovascular tissues and skeletal
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muscle. A combination of experimental and computational research approaches is pursued to
engineer functional, load-bearing tissues with targeted mechanical properties. The main challenges
are to quantify structure-function properties of the developing tissue and to manipulate these with
adequate mechanical conditioning protocols in bioreactors to achieve targeted properties that ensure
in-vivo survival. Thorough investigation of the effects of mechanical stimuli on tissue growth and
adaptation, as well as on damage and de-adaptation are indicative for success in this area. This requires
vital imaging and testing techniques to monitor tissue structure and function in space and time. As
the engineered tissue consists of cells, scaffold material and extra cellular matrix, these components –
as well as their mutual interactions – are included in our studies. Created tissues are applied as in-vitro
model systems or for implantation purposes.
5.3.2 Soft Tissue Mechanics
(Prof.dr.ir. Frank Baaijens, prof.dr. Dan Bader, dr.ir. Cees Oomens)
The objective of this subprogram is to study the mechanical behavior of soft biological tissues. This
implies determination of constitutive equations, but also understanding the influence of mechanical
loading on damage and adaptation of soft tissues. The ultimate goal is to identify early markers for
tissue damage that can be used in biosensors for risk assessment or as leads for bio-molecular imaging
purposes. This includes the study of physiological processes taking place at the tissue and cell level.
The latter is a major development and trend over the last decade were cell biology and biochemistry is
integrated with mechanics. To study these phenomena a hierarchical approach or multi-scale approach
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is adopted, using in-vitro and in-vivo model systems ranging from studies on individual cells, tissue
engineered constructs to animal and human studies, combined with theoretical modeling to bridge
the gap between scales. The most important application area is development of pressure ulcers
(decubitus). Other application areas are interaction of skin with personal care products and comfort
analysis if car seats.
5.3.3 Multi-Phase Mechanics
(Prof.dr.ir. Frank Baaijens, dr.ir. Jacques Huyghe)
This subprogram is focused primarily on intervertebral disc mechanics. Of particular interest is the
integration of 3D deformational behavior of the disc with its swelling propensity. Spin-off areas are the
swelling of shale formation and its implication for bore hole stability in oil industry, the design of a
swelling disc prosthesis and divers applications of the porous media mechanics to biological tissues
such as skin and cartilage. Experimental work on human and animal intervertebral disc samples are
combined with advanced mixture finite element analyses on the disc. The numerical formulations are
developed in cooperation with the Mathematics Department and the Civil Engineering Department of
the University of Stuttgart. MRI-experiments on disc tissue and substitutes are done at the Physics
Department
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5.4 Cardiovascular Biomechanics
(Prof.dr.ir. Frans van de Vosse)
approx. 10 FTE research
In our research we focus on model-based biomechanical analysis of the cardiovascular system,
relevant for pathophysiology, diagnostics and treatment of diseases. Although the research generally
stems from questions arising from clinical practice, it often remains fundamental in nature and is
based on mathematical models that originate from classical disciplines (physics, mathematics and
biology). In order to develop, validate and analyze these mathematical models, we use and expand
advanced experimental techniques like laser-Doppler anemometry (LDA), particle image velocimetry
(PIV), ultrasound Doppler (USD), sensor technology and video imaging, as well as computational
methods, like finite (FEM) and spectral element (SEM) methods.
5.4.1 Hemodynamics and Vascular Biomechanics
(Prof.dr.ir. Frans van de Vosse, prof.dr. Nico Pijls, prof.dr. Bas de Mol, dr.ir. Peter Bovendeerd, dr.ir. Marcel
Rutten)
Hemodynamical factors, like local pressure, velocity, wall shear stress and wall deformation play a key
role in the genesis and development of vascular disease and are crucial for the well functioning of the
heart and its natural valves. In our group, hemodynamical (mathematical) fluid structure interaction
models and corresponding computational methods are developed to help in the interpretation of
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diagnostic measurements and to predict the impact of clinical interventions like balloon angioplasty,
stent or vascular prosthesis implants, bypass surgery and medication. In-vitro and ex-vivo experiments
are designed and carried out to assess the parameters that define the constitutive and adaptive or
remodeling behavior. Basic aspects of non-invasive diagnostics methods like MRI, CT, X-ray and
ultrasound techniques are investigated and evaluated for this purpose. Finally, medical devices like
pressure and flow sensors, particularly those used for advanced diagnostic measurements like
coronary catheterization are still in the development stage. Research also concentrates on
biomechanical aspects of these systems and devices.
5.4.2 Cardiac Biomechanics
(Prof.dr.ir. Frans van de Vosse, prof.dr. Bas de Mol, prof. Michael Jacobs, dr.ir. Peter Bovendeerd, dr.ir. Marcel
Rutten)
Cardiac biomechanics research is dedicated to the understanding how individual heart-muscle cells
contribute to the contractile function of the complete heart, both in healthy and in pathological
conditions. We are particularly interested in the adaptation of the heart muscle to changes in
mechanical load or electrical activation, for instance induced by cardiac arrest or pacemakers. We
develop and validate powerful mathematical models and computational methods for electrical
conductance, excitation and muscle contraction of the complete heart. These models help to enhance
diagnostic measurements and planning of treatment modalities. In-vitro and ex-vivo experiments are
designed to assess the parameters that define the constitutive behavior en to validate the outcome of
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computational simulations. Research also concentrates on biomechanical aspects of therapeutic
devices like pacemakers and mechanical cardiac assist devices. Sophisticated models, both for the
device that is studied and the physiological system it is used for, are developed to improve technology
and diagnostic procedures. Mechanical and biological heart valves are based on high-end technology
with respect to material, function, durability, and safety. We develop and apply in-vitro and ex-vivo
experimental as well as computational methods for development and evaluation purposes.
5.5 Bone and Orthopaedic Biomechanics
(Prof.dr.ir. Rik Huiskes)
approx. 8 FTE research
The field of bone and orthopaedic biomechanics is directed towards mechanics and biology of bone,
in relation to prevention, diagnosis and treatment of medical conditions and diseases of the
musculoskeletal system. Both basic and applied research is conducted. Present research activities can
be categorized into three main subjects.
5.5.1 Mechanical Properties of Bone & Osteoporosis
(Prof.dr.ir. Rik Huiskes, dr.ir. Bert van Rietbergen)
Bone is a porous, composite tissue, consisting of mineralized collagen. Its main function is to provide
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strength and stiffness to the musculoskeletal system. This function can be compromised by
osteoporosis in post-menopausal women, due to the biological consequences of hormone deficiencies,
and also in the elderly in general, due to reduced activities. Osteoporosis is a common condition in
elderly Caucasian and Asian populations, with dramatic effects on risks of fractures in the hip, the
spine and the wrist. It is known that bone mass and strength rely on usage; in other words, they rely
on the dynamic forces of daily living.
In our research program we attempt to quantify the relationship between bone micromorphology
and material characteristics, on the one hand, and bone strength on the other. For that
purpose we apply refined imaging methods to model and quantify morphology (micro-computertomography)
in combination with large-scale micro-FEA (finite element analysis) and experimental
testing devices. Our goal is to be able to estimate bone strength clinically for early detection of
osteoporosis.
Secondly, we attempt to develop effective preventive measures against osteoporosis, by exploiting the
natural effects of mechanical forces on bone mass. For that purpose, we investigate the effects of forces
on the bone-cell metabolic activities of bone maintenance and adaptation.
5.5.2 Mechanobiology of Tissue Differentiation
(Prof.dr.ir. Rik Huiskes, dr. René van Donkelaar, dr.ir. Keita Ito)
Tissue-differentiation processes take place in the embryonic development of bone, where the soft
tissues are eventually mineralized and remodeled into bone. A similar process takes place in
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regeneration of bone, during healing of bone fractures, and during the ingrowth phases of surgical
implants. It is known that these differentiation processes, in which one tissue type is replaced by
another, are modulated by stimuli derived from mechanical tissue variables, such as pressure, strain
or fluid transport. Using computer-simulation methods based on FEA, in combination with animalexperimental
data, we attempt to discover the most effective mechanical conditions for the tissuedifferentiation
processes. One aspect of this, the mineralization of cartilage, is embedded in a trans-
European research program.
The information we seek is important for the prevention and treatment of congenital
musculoskeletal deformities in children, the design and application of fracture-fixation devices to
promote bone healing, for tissue engineering of articular-cartilage and meniscal implants, and for the
design and fixation of artificial joints.
5.5.3 Osteoarthrosis & Artificial joints
(Prof.dr.ir. Rik Huiskes, prof. Ruud Geesink)
Wear of human joints is, next to osteoporosis, the most common musculoskeletal disease in the
elderly. Its development is thought to be an effect of a disturbed balance between strength of articular
cartilage, its lubrication mechanism (both of which have a genetic component) and dynamic joint
loading (which depends on mechanical usage). However, there are also indications that the process of
destruction originates in the underlying bone. The knee and the hip are the most commonly affected
joints. Small defects can be repaired surgically with transplanted or, potentially, tissue engineered
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implants. In severe cases of osteoarthrosis, however, the only cure is an artificial joint.
In this research program we conduct in-vitro and animal experiments with tissue-engineered
cartilage replacements, to enable cartilage repair in this way. Using computer simulations with FEA,
we attempt to delineate the causal aspects of the disease. We also perform mechanical analyses of
artificial joints (i.e. hip and knee prostheses), to study fixation strength and in growth processes for the
purpose of improved designs and surgical equipment. Pre-clinical testing methods for new designs
are also developed.
5.5.4 The healing touch of a plasma needle
(dr. Eva Stoffels-Adamowicz)
Acute cell death (necrosis) is inevitable in conventional surgery; it leads to inflammation, pain,
impaired tissue repair and scar formation. Operation without necrosis is possible by means of the
novel cold-plasma technology. Tissues are exposed to a cold ionized gas (plasma), which supplies
chemically active species to the target area, in a non-contact and painless way. Treated cells respond
with apoptosis (programmed cell death), or detachment and migration. Applications of plasma
treatment include microsurgery, disinfection, wound healing and treatment of caries. Current
research focuses on inducing apoptosis, cleaning dental cavities, and improving the performance of
the plasma instrument.
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5.6 Biomedical Image Analysis
(Prof.dr.ir. Bart ter Haar Romeny)
approx. 9 FTE research
The mission of the Biomedical Image Analysis (BMIA) group is to design highly effective algorithms
for quantitative image analysis and visualization. Images are made in such quantities today, that
advanced 3D visualization techniques and computer-aided diagnosis (CAD) have become a necessity.
Every major vendor has a line of sophisticated diagnostic workstations, on which a wide array of
visualization functions and image analysis techniques are implemented. Modern computer vision
techniques have sparked the advent of effective CAD algorithms, e.g. in mammography and thorax
investigations. The BMIA group focuses on 3 key directions, with a balance between fundamental
research, visualization, and applications (both clinical and in life sciences).
5.6.1 Multi-scale image structure
(dr. Luc Florack, prof.dr.ir. Bart ter Haar Romeny)
The automatic recognition of tumors, vessels and other structures in images for 3D visualization and
computer-aided diagnosis (CAD) is a challenging task. Most algorithms are highly specific, and a
generic theory is still missing. The research is inspired by recent neurophysiological findings in the
human visual system (bio-mimicking), and axiomatic physical and mathematical approaches. They
indicate that a multi-scale approach is essential for developing a robust theory for the hierarchical
Biomedical Engineering
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analysis of images. The BMIA group has a strong mathematical backbone, and is internationally
among the pioneers in this field. Focus is on analyzing the ‘deep’ hierarchical multi-scale structure of
images, and to develop contextual models for the Gestalt laws for perceptual grouping. Applications
are image-based retrieval from a medical image database, segmentation for 3D visualization, catheter
enhancement, quantitative analysis of motion, and vascular analysis.
5.6.2 Visualization and Clinical Applications
(dr. Anna Vilanova, prof.dr.ir. Frans Gerritsen)
Diffusion Tensor Imaging (DTI) is a relatively new MRI technique, which is capable of new forms of
analysis of fibrous tissues (brain white matter, muscle fibres, tumors) by generating tensor-valued
voxels. New interactive visualization methods for this new class of images are developed. The
interactive software package “DTI-Tool” has successfully been used in a clinical study to hypoxia
problems in newborns.
3D visualization is essential for the surgeon to prepare the operation. The BMIA group integrates
the visualization and advanced computer vision research, as they are complementary and mutually
beneficial. We currently study the use of graphics cards for fast and economic 3D visualizations, and
how the optimal transfer function for 3D visualization can be automatically found from the data.
Clinical applications of image analysis focus on computer-aided diagnosis, in particular for
automated breast tumor detection with dynamic contrast-enhanced MRI, pulmonary vessel tree
segmentation and automatic detection of pulmonary emboli in high resolution CT scans of the lungs,
Biomedical Engineering
cardiac motion analysis, automatic colon polyp detection in low-dose CT, cardiovascular flow
calculations to determine risk factors in abdominal aorta aneurysms, and enhanced precision
navigation for neurosurgery with intra-operative MRI.
5.6.3 Molecular Imaging of the Ischemic Heart
(drs. Hans van Assen, prof.dr.ir. Bart ter Haar Romeny)
The BMIA research in Molecular Imaging is aimed at quantitative analysis of molecular images,
notably from multi-spectral MRI, high-field MRI, 2-photon spectroscopy and ultrasound. The focus is
on the development of effective algorithms to detect motion (optic flow), and to exploit multispectral
data for pattern recognition, tissue typing and visualization. A statistical classification tool for multispectral
MRI data of atherosclerotic plaque is developed, and a robust multi-scale application for the
extraction of a dense motion field from MRI tagging time sequences of the moving heart. With the
Vital Images group (microscopy, UM) we study remodeling parameters of blood vessels and collagen.
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5.7 Biomodeling and Bioinformatics
(Prof.dr. Peter Hilbers)
approx. 8 FTE research
In the group BioModeling and bioInformatics we study the modeling of processes in living systems,
ranging from atomic interactions within a single molecule to interacting ensembles of organisms.
Next to the research on biomedical modeling methods and techniques in general, we study specific
biomedical applications both on the cellular and the tissue level. Central themes in these activities are
biomedical models, bioinformatics, the implementation of these models in algorithms and computer
simulations.
Current research on the level of the biological cell is on biomolecular modeling of protein
systems and of diffusion processes in cell membranes, gene expression profiling and clustering
techniques for microarray data analysis, and metabolic pathways, while on the level of tissues and
organs the research topics are bone growth and adaptation models, genetic algorithms, and computer
simulations of the electrical behavior of the heart.
5.7.1 Protein, Membrane, and Cell Simulations
(Prof.dr. Peter Hilbers, dr.ir. Koen Pieterse, ir. Bart Markvoort)
Computer simulations are used to study biomedical systems and processes on the cellular level such
as vesicle formation, transport processes through the cell membrane and structured based modeling
Biomedical Engineering

42
of protein-ligand interactions. Many of these processes occur on time scales still unreachable by
modern computers. In order to allow simulations on relevant biological time scales as well as large
systems, we are developing new computational methods and techniques and use a combination of
large scale parallel computing and simplified models, e.g. a coarse grained approach for modeling the
interactions between water and membrane molecules. Current applications include phospholipid
membranes and vesicles (liposomes), their formation, shaping, budding and fusion. Where atomistic
details are a prerequisite, fully atomistic simulations are performed to investigate e.g. possible drugs
for aldosterone synthase inhibition to treat heart failure.
5.7.2 Tissue simulations
(Prof.dr. Peter Hilbers, dr.ir. Ronald Ruimerman, ir. Nico Kuijpers)
The formation and adaptation of biological structures, such as heart tissue and bone, is strongly
influenced by external factors, such as mechanical loading, and by aging and age-related diseases.
Since these processes are in general difficult to study by experiments, computer modeling and
simulations of these processes is challenging. For both the most common heart arrhythmia disease,
atrial fibrillation, and for the age-related disease in bone, osteoporosis, we are developing theories and
models. In these theories cell-biological, metabolic processes are treated and coupled to mechanical or
electrical stimulations of cells. The theories are now applied to simulations of realistic tissues and the
effects of medical treatment are investigated.
Biomedical Engineering
5.7.3 Metabolic pathways, genetic algorithms, bioinformatics
(Prof.dr. Peter Hilbers, dr.ir. Huub ten Eikelder, dr. Dragan Bosnacki)
The understanding of biological networks, such as metabolic and signal transduction pathways, is
crucial for understanding molecular and cellular processes. Our aim is to study various statical,
dynamical and evolutionary aspects of such networks with applications to realistic case studies (e.g.
signaling pathways involved in Type 2 diabetes, pathways relevant for the cardiovascular and
nutritional research fields). To this end we develop novel methods and tools. The methods are mostly
algorithmic and they span over various sub disciplines of computer science, like graph theory, formal
methods, and genetic algorithms. The results are used to search for unanticipated network
interactions as well as to new patterns of regulation that could eventually pave the way toward humanengineered
biological networks. In parts of this subprogram there is a strong collaboration with the
group of Van den Bosch of the electrical engineering department.
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Department of Electrical Engineering
44
6.1 BioSignals and Regulation
(Prof.dr.ir. Paul van den Bosch)
approx. 5 FTE research
Main aim is the development of powerful quantitative methods for the highly qualitative, experiencebased
sciences of biology, physiology and biomedicine, which lack mostly strong quantitative
statements and clear explanations of phenomena. Based on our knowledge on modeling, system
identification and “optimal” experiment design, and our domain knowledge of basic physiological
phenomena, we develop new quantitative models and generic identification and analysis tools. Similar
mathematics and computational methods can be applied to different physiological systems and
biomedical problems. All research is in cooperation with physiologists of Maastricht, Birmingham and
Utrecht and with industry (Siemens, Unilever, Philips).
6.1.1 Generic methods from system and control theory for biosystems
(Prof.dr.ir. Paul van den Bosch, dr.ir. Natal van Riel 1 )
We adapt existing techniques to suit the specific problems and requirements in biomedical research
(few data, large variances in both data and biological subject), such that optimally informative
experiments can be designed to estimate the most relevant parameters with the highest possible
accuracy. Fundamental cellular processes, such as transcription, protein-protein interactions and cell
signaling, possess switch-like dynamics. Models that combine continuous dynamics and discrete
1 Dept. of Biomedical Engineering
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46
events (so-called hybrid models) provide computationally efficient approximations of these
nonlinearities, as well as the largely different time scales present in biological systems. Methods for
the description, analysis and quantification (parameter estimation) of biological hybrid systems are
being investigated. It is our ambition to use the tremendous amount of qualitative information from
physiologists for our quantitative approach. This qualitative knowledge will be used to constrain the
parameter space of our quantitative models. With few measurements still more accurate and
physiologically more relevant parameter estimates are to be expected.
6.1.2 Applications in computational Systems Biology and physiology
(Prof.dr.ir. Paul van den Bosch, dr.ir. Natal van Riel)
We apply our research on modeling and identification of physiological systems, in the interesting area
ranging from the rather microscopic level of systems biology up to the high aggregation level of
clinical measurements. Computational models are being developed of the protein networks and
feedback control mechanisms involved in DNA damage and repair, for example for optimizing
radiotherapy (UM). Besides the intracellular metabolic networks and calcium cycling also the effects
of the endothelial barrier on the transport and uptake of glucose and fatty acids by the myocytes is
being investigated; for skeletal muscle in collaboration with Birmingham, for the heart with UM.
Together with UM, the effect of diabetic cardiomyopathy on calcium handling and excitationcontraction
coupling in the intact heart is studied.
Electrical Engineering
6.2 Medical Signal Processing
(Prof.dr.ir. Jan Bergmans)
approx. 6 FTE research
This research group develops new signal-processing techniques and systems for patient monitoring,
aimed at improved diagnosis, improved patient comfort, lower costs, and lower risks to the patient. A
close collaboration exists with the Catharina Hospital in Eindhoven (CZH), the Maxima Medical
Center in Veldhoven (MMC), and Kempenhaeghe Epilepsy Hospital in Heeze (KEH). Within BEST/e
there is a close collaboration with the Biosignals and Regulation group. Emphasis is primarily on
clinical applications, with ambulatory spin-offs. The work uses and extends key concepts from signal
theory, information theory, and adaptive system theory, and builds extensively on experience from
mature signal-processing application areas such as audio and speech coding, video processing, and
digital communications.
6.2.1 Fetal monitoring
(Prof.dr.ir. Jan Bergmans, prof.dr. Guid Oei, dr.ir. Massimo Mischi)
This work involves a close collaboration with MMC and Philips Research. In high-risk pregnancies,
the state of the fetus must be carefully and frequently monitored to be able to intervene promptly when
necessary. Existing fetal monitoring techniques such as the cardiotocogram (CTG) have serious
accuracy limitations and are only applicable in the hospital. Our research targets an
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electrophysiological alternative for the CTG that overcomes these drawbacks. The ultimate objective is
a monitoring system with wearable electrode arrays that provides early warnings for preterm delivery
(through extraction of the uterine electromyogram (EMG)) and deterioration of fetal condition
(through extraction of the fetal ECG in relation to the uterine EMG). Key challenges relate to the
separation and interpretation of the small and non-stationary information-bearing signal components,
within a strong and nonstationary mixture of disturbances such as maternal ECG and sensor and fetal
movement artifacts. To address these challenges, we use advanced analysis-by-synthesis techniques,
originally developed for speech coding.
6.2.2 Neuromonitoring
(Prof.dr.ir. Jan Bergmans, dr.ir. Pierre Cluitmans)
The objective is to develop brain monitoring techniques with significantly improved spatio-temporal
resolution and improved resilience to artifacts and nonstationarities. Key applications include
detection and prediction of epileptic seizures in institutionalized patients. This work involves a close
collaboration with KEH. It uses multiple sensor types (e.g. EEG, 3D accelerometry, ECG) to develop
a robust ambulatory solution with performance comparable to the current ‘golden standard’, which is
based on a combination of EEG and video. Assessment of attention deficits in children. These deficits
affect around 3 to 5 per cent of all children, and are currently mainly assessed by means of behavioral
tests. This research seeks to supplement these tests by an EEG-based analysis for specific event-related
potentials. Eventually this should permit an earlier and more objective diagnosis.To support these and
Electrical Engineering

50
other applications, novel artifact-handling approaches are developed, based, for example, on video
registration of eye movements as a basis for almost perfect elimination of eye-movement artifacts.
6.2.3 Medical image and video processing chains
(Prof. Peter de With)
This research involves a close collaboration with Philips Medical Systems (PMS). It explores novel
architectures and algorithms for future image and video processing systems within PMS. The
emphasis is on architectures that are chain-oriented, as opposed to component-oriented. Key
architectural challenges include: flexibility with respect to input sources, data representations (e.g.
2D/3D), and output devices/monitors; support for volumetric imaging and processing; scalability (in
terms of both hardware and image quality); and display efficiency.
Key algorithmic challenges include efficient compression of 3D data sets, efficient video scaling
and formatting, and improved visualization for novel (LCD) monitors. This work builds on extensive
experience in video coding and architectures for consumer electronics.
Electrical Engineering
6.2.4 Peri-operative signal processing
(Prof.dr.ir. Jan Bergmans, prof.dr. Erik Korsten, dr.ir. Hans Blom, dr.ir. Massimo Mischi)
This research involves a close collaboration with CZH. It aims at novel patient monitoring techniques
to assess cardiovascular condition before, during or after surgery. Two key approaches are pursued:
Model-based analysis using ultrasound contrast agents (UCAs). A small UCA bolus is injected into the
blood stream. An ultrasound image of the dispersed bolus is recorded as it passes the chambers of the
heart, and the resulting indicator-dilutor curves are analyzed. In this minimally-invasive manner,
simultaneous assessment of all critical heart parameters is possible. Important advantages ensue over
existing approaches, which tend to be more invasive, more risky, more costly, less accurate, and less
comprehensive. Apart from diagnostic applications of UCAs, therapeutic applications receive
increasing attention. Model-based analysis of respiratory and circulatory signals during weaning, to
estimate e.g. the pulmonary blood volume.
Key technical challenges relate to the very low signal-to-noise ratios, and to a priori unknown and timevarying
system parameters. To resolve these challenges, adaptive parametric signal-processing
approaches based on the maximum-likelihood principle are used, borrowed from digital
communications and speech processing.
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Department of Applied Physics
52
7.1 Molecular Biosensors for Medical Diagnostics
(Prof.dr.ir. Menno Prins, dr. Leo van IJzendoorn, dr.ir. Arthur de Jong)
approx. 2 FTE research
Molecular biology and medical sciences are advancing to a level at which human health and disease
can be traced down to molecular origin. Consequently biosensors for the detection of specific
molecular markers in minute samples of body fluid or tissue have the potential to revolutionize
medical diagnostics. The group studies the detection and manipulation of magnetic nanoparticles and
their use in biochemical studies. The aim is to design and make new types of research devices, which
will be used for biological studies and which have potential to be applied in integrated medical
biosensors. Optical imaging is an important tool in the experiments with particles and biological
materials. The group integrates expertise from a large number of fields including physics, chemistry,
biochemistry, electronics, micro fluidics and device technology. Cross-disciplinary collaborations with
groups inside and outside TU/e are a key element of our research. The group has access to device
technologies from Philips Research.
7.1.1 Properties, actuation and detection of magnetic nanoparticles
(dr. Leo van IJzendoorn, dr.ir. Arthur de Jong, prof.dr.ir. Menno Prins)
Magnetic nanoparticles are the nanoscopic tool for manipulating biochemical molecules. The
properties of different classes of magnetic particles (e.g. superparamagnetic or ferromagnetic
Applied Physics

54
particles) and their behavior in fluids are investigated by optical microscopic methods. Global as well
as local magnetic fields are used for particle transportation and to apply forces to biochemical
molecules. We study on-chip sensors for the detection of magnetic particles as labels of biochemical
molecules. Responses are studied for different magnetic particles, forms of actuation, and positions of
the beads on the sensor. The detection limit is studied for single beads of various types and sizes. The
studies are supported by modeling of on-chip and near-chip magnetic fields. Experiments with
different magnetic field configurations are used for bead studies and for subsequent biochemical
research.
7.1.2 Biophysics: protein detection, biochemical binding, and cell diagnostics
(dr.ir. Arthur de Jong, dr. Leo van IJzendoorn, prof.dr.ir. Menno Prins)
The physics associated with magnetic bead actuation and detection is linked to biochemical assays. For
example, a sandwich immuno-assay involves the use of magnetic particles labeled with antibodies in
combination with a sensor surface also covered with antibodies. We study bio-molecular binding and
unbinding, as influenced by magnetic forces, pH, temperature, buffer composition, specific protein
concentrations etc. We also plan to study biosensor concepts for sensitive and rapid molecular
diagnostics of cellular materials and tissue.
Applied Physics

Department of Mechanical Engineering
56
8.1 Micro- and Nanoscale Engineering
(Prof.dr. Andreas Dietzel)
approx. 3 FTE research
8.1.1 Bead based fluid actuation techniques for immunoassay devices
(Prof.dr. Andreas Dietzel, prof.dr.ir. Menno Prins 2 )
In future molecular diagnostics, very small quantities of material (e.g. 100 molecule copies) need to
be detected reliably in a very complex sample matrix (e.g. full blood). This requires front-edge
innovations in the fields of device design and fabrication, the physical actuation and detection
methods, and in the (bio)chemistries. A very promising approach is to use small particles, also called
beads or nanoparticles, because these can perform efficient biological functions. Examples of such
functions are mixing of small sample volumes, specific binding to biological molecules, concentration
of biological molecules into an even smaller volume, or the labeling of molecules immobilized on a
sensor surface. The detection can for example have an optical basis (e.g. fluorescence) and/or can be
based on magnetic principles (e.g. magneto-resistive sensors in the case of magnetic labels) and/or
electrical principles. Efficient interactions between the beads and the fluid shall be forced by particle
movement, for instance by magnetic or acoustic excitation. The actuation functionalities and the
design of the micro fluidic structures should be robust against natural variations of fluid properties,
such as viscosity, capillary tension, and cell content. Micro fluidic test chips shall be fabricated using
fast prototyping techniques such as soft lithography. In addition, fabrication techniques that have the
potential to be transferred into high volume production of disposable test chips shall be developed.
2 Dept. of Applied Physics
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58
8.2 Mechanics of Materials
(Prof.dr.ir. Marc Geers)
approx. 1 FTE research
Biomechanical engineering related research at the Mechanics of Materials (McMat) section of the
Department of Mechanical Engineering is shortly described. The McMat section is part of the
interdepartmental Materials Technology Institute, where a close co-operation with BMT groups exists.
Within the field of biomechanical engineering, the following research topics are of interest for the
Mechanics of Materials group: (i) mechanics of biomedical devices; (ii) Injury biomechanics.
8.2.1 Mechanics of biomedical devices
(Prof.dr.ir. Marc Geers, dr.ir. Hans van Dommelen, dr.ir. Piet Schreurs)
This topic addresses the mechanics of technical devices that are used as biomedical engineering
solutions, where the mechanical function (deformability, strength, damage, etc.) plays an essential
role. At present, initiatives have been taken to explore and start up research for cardiovascular stents.
Mechanical Engineering
8.2.2 Injury biomechanics
(Prof.dr.ir. Marc Geers, dr.ir. Hans van Dommelen)
Injury of the human body occurs by deformation of anatomical structures beyond their failure limits
resulting in damage of tissues or alterations in the normal function. The research field injury
biomechanics uses the principles of mechanics to study the behavior of biological material under
extreme loading conditions. Knowledge of this behavior is essential in order to be able to develop
adequate measures for protection of the human body under these extreme loading conditions.
Research focuses on a fundamental understanding of the development of local damage phenomena
and relating injury mechanisms to macroscopic loading conditions in automotive crash situations.
This approach involves research at various length scales, from the cellular level up to the whole human
body. The bridging of these length scales can provide the missing link between cellular mechanism of
injury development and the macroscopic mechanism of mechanical loading in real-life accidents.
Engineering solutions for the prevention of injury based on knowledge of the above aspects are also
the subject of research.
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60
8.3 Dynamics and Control Technology
(Prof.dr.ir. Maarten Steinbuch)
approx. 3 FTE research
The general research objective of the Dynamics and Control Technology group is the study of all
aspects related to dynamics and control of high-performance mechanical systems. This covers the full
range of topics such as design, modeling and analysis of mechanical systems, controller synthesis,
signal and performance analysis. Practical and experimental validation is, where possible, part of the
research.
8.3.1 Medical Robotics
(Prof.dr.ir. Maarten Steinbuch, dr.ir. Nick Rosielle, dr. Eva Stoffels 3 )
In this research area, special attention is given to explore the experience and research results for
design principles, systems and control and mechatronics with respect to its applicability in bioapplications,
such as medical devices and instruments. Some examples are control of test instruments
and reactors for tissue engineered bio-material, haptics in medical robotics, and plasma needle
instruments. The application of motion technology in medical environments differs from the high
performance mechatronic motion systems in that the environment is uncertain and changing over
time. Hence, performance and stability robustness issues, as well as the use of adaptive estimators and
feedback control are essential.
3 Dept. of Biomedical Engineering
Mechanical Engineering

Department of Mathematics and Computer Science
62
9.1 Differential equations in the Life Sciences
(Prof.dr.ir. Hans van Duijn and prof. dr. Mark Peletier)
approx. 2 FTE research
Mathematical models are a powerful tool in understanding the complex behavior of biological and biomedical
systems. Within CASA (the Centre for Analysis, Scientific Computing and Applications) we
develop mathematical methods, both analytical and numerical, to extract the maximum of information
from these models, understand their limitations, and provide suggestions for improvement.
Applied mathematics is not uniquely connected to one biological or bio-medical application -
applications of mathematics are everywhere. As a consequence, the areas in which our group is active
are very varied; below is a list of recent projects that may serve to illustrate the breadth and scope of
our interests.
9.1.1 Mixed finite elements for the modeling of cartilaginous tissues
(Prof.dr.ir. Hans van Duijn, dr. Rik Kaasschieter, drs. Kamyar Malakpoor, and prof.dr. Mark Peletier)
The swelling and shrinking behavior of cartilaginous tissues can be modeled by a four-component
mixture theory in which deformable and charged porous medium is saturated with a fluid with
dissolved ions. This theory results in a coupled system of non-linear parabolic differential equations
together with an algebraic constraint for electroneutrality. The goal of this project is the threedimensional
computational solution of the system of equations. A suitably chosen mixed finite
Mathematics and Computer Science

64
element method fulfils the conservation laws exactly and yields non-oscillatory solutions. This choice
should be based on a thorough understanding of the system of equations. Furthermore, a suitable
choice for the time-integration is needed as well as an efficient solution procedure for the resulting
non-linear equations. The numerical results will be compared with measurements that will be
obtained in a related project.
9.1.2 Metabolic Control Analysis in spatially heterogeneous systems
(Prof.dr. Mark Peletier)
Metabolic Control Analysis is a type of sensitivity analysis tailored to (time-dependent) ODEs that
describe biochemical reaction networks. A concept that is central to this theory is that of ‘control’, the
degree of influence that a given parameter may have over the system. So-called summation theorems
combine and limit the control that different parameters may have. Our contribution was to generalize
this framework from ODEs to PDE systems with non-trivial diffusive effects. By exploiting the scaling
invariance in these systems we extended the classical results and identified a new summation
theorem. As a by-product we showed that it is possible to bound the control of the diffusion coefficient
explicitly.
Mathematics and Computer Science
9.1.3 Is bone remodeling an optimization algorithm?
(Prof.dr. Mark Peletier)
BEST e
Bone remodeling is the continuous maintenance and adaptation of the sub-millimeter structures in
trabecular bone (see section 5.5). Recent computational models of this process, such as those
developed in the group of prof. dr. R. Huiskes, aim to represent the biological mechanism in as much
detail as possible, and thus represent a departure from the decade-old optimization paradigm.
Inspired by the former lack of anatomical and biochemical data, this paradigm stated that the actual
biological mechanism seeks the optimum of some function representing ‘strength’, and that it is more
important to know the strength function itself than to know the process that optimizes this function.
In this project we aim to connect these two views, by investigating if and how the Huiskes
computational model can be viewed as an optimization algorithm for some (still unknown) strength
functional. Such a connection, or lack thereof, should give insight into the evolutionary reasons behind
the actual remodeling mechanism.

Research Input
66
FTE (according to research norm)
20
18
16
Biomedical Chemistry - 2002
2003
2004
2005
Biomedical NMR - 2002
2003
2004
2005
Soft tissue Biomech. & Tissue Eng. - 2002
2003
2004
2005
Cardiovascular Biomechanics - 2002
2003
2004
2005
Bone and Orthopaedic Biomechanics - 2002
2003
2004
2005
Biomedical Image Analysis - 2002
2003
2004
14
12
10
8
6
4
2
0
BEST/e research input TU/e dept. BMT
2005: total staff ca. 76 FTE research
Tenured Staff PostDocs PhDs
2005
Biomodeling and Bioinformatics - 2002
2003
2004
2005
FTE (according to research norm)
20
18
16
14
12
10
8
6
4
2
0
BioSignals and Regulation - 2002
2003
2004
2005
Medical Signal Processing - 2002
BEST/e research input TU/e depts. E, TN, W, Wsk/Inf (rough estimation)
2005: total staff ca. 22 FTE research
2003
2004
2005
Mol. Biosensors for Medical Diagnostics - 2002
2003
2004
2005
Micro- and Nanoscale Engineering - 2002
2003
2004
2005
Mechanics of Materials - 2002
2003
2004
Tenured Staff PostDocs PhDs
2005
Dynamics and Control Technology - 2002
2003
2004
2005
Diff. equations in Life Sciences - 2002
2003
2004
2005
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Picture Index
68
P 7 Prof.dr. Klasien Horstman teaches the subject “Medical Ethics”, to prepare
students for the application of technical knowledge in an ethical
responsible way.
P 9 Prof.dr.ir. Frank Baaijens (left) and prof.dr.ir. Frans v/d Vosse (right) in the
Cell & Tissue Engineering Lab.
P 13 Footbridges connect the different buildings on the campus of the
Technische Universiteit Eindhoven.
P 15 Every year the Department of Biomedical Engineering organizes the BME
Research Day in Maastricht or Eindhoven.
P 17 MRI-machines (Magnetic Resonance Imaging) are frequently used by
researchers of the division Molecular Bioengineering & Molecular Imaging.
P 23 A Medical Engineering graduate student using an MRI Machine.
P 25 Bioreactor for tissue engineered heart valves.
P 29 Students during Skills Lab.
P 33 Footbridge connecting the main campus to the University sports facilities.
P 37 Advanced computer programs are used by researchers of the division
Biomedical Imaging & Modeling.
P 41 “The Flying Pins” is an artwork located next to the campus of the
Technische Universiteit Eindhoven.
P 45 Laboratory of the Department of Electrical Engineering .
P 49 Impression of the main building (Hoofdgebouw) of the TU/e.
P 53 The Dommel, a small river, runs through the campus of the TU/e.
P 55 Students relaxing on one of the many grassy areas of the campus.
P 57 Footbridges connect the different buildings on the campus of the
Technische Universiteit Eindhoven.
P 61 Plasma needle.
P 63 Impression of the campus of the Technische Universiteit Eindhoven.
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Colophon
70
12
Final editor:
Prof.dr.ir. Frank Baaijens
Dean of the Department of Biomedical Engineering
Produced by
Dr.ir. Ivonne Lammerts
Co-ordinator BEST/e
Drs. Marije de Jong
Public Relations BME
Designer:
Robert Brannan, Nuenen
Photography by:
Bart van Overbeeke, Eindhoven
Rob Stork, Eindhoven
Norbert van Onna, Eindhoven
Reprographics & Printing:
Lecturis, Eindhoven
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