Tentative plans prof LIU - IFM

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Bilaga 4. Tentative plans for the chair.
Tentative plans for the chair in Sensor Science at IFM,
Linköping University
Sensor Science is in my opinion a true multidisciplinary research area, which requires input,
skills and competence from many different disciplines. My intention is to establish a strong
multidisciplinary research group in sensor science and technology by recruiting and
examining graduate students and post docs from different academic areas. I will concentrate
my research efforts in two main areas. I) Transducer physics and biosensor chip technology;
II) Artificial biosensing interfaces and molecular films. Novel transducers based on optical
and electrochemical detection principles will be developed to meet the increasing demands
from the molecular biology and sensing community. I plan to focus on optical “imaging” and
electrochemical microelectrode array sensors for parallel detection of a multitude of
molecular recognition events. This research requires advanced patterning technologies, and a
proper surface chemistry/biology. I’m convinced that my experience in surface chemistry,
self-assembly, and interfacial analysis will provide a good platform for the design of highly
specific sensing interfaces. I would also like to bring modern analytical tools which normally
are found in the surface physicists laboratory into the sensor science community, including,
for example, surface vibrational spectroscopy (infrared and Raman), X-ray photoelectron
spectroscopy (ESCA), and scanning probe microscopy (AFM, STM).
PLANNED RESEARCH
Transducer physics: Optical biosensing is an area, which has attracted my interest over the
years. My main interest concerns surface plasmon resonance (SPR)-based transducers, and I
propose to continue current activities on imaging SPR for multispot and multiparameter
detection. The multispot approach will be used to increase the throughput of modern sensing
systems. Micro- and nanotechnologies as well as so-called soft lithography “micro contact
printing” CP will be important manufacturing tools for the generation of patterned surfaces
and novel sensing chips. The multiparameter approach means that one monitor a single
biomolecular interaction phenomenon with several transducer principles, e.g., by combining
of SPR/amperometry, SPR/Raman spectroscopy, amperometry/surface acuostic wave(SAW)
devices. The idea is to obtain a complete picture of the recognition event. Complementary
competence in the field of micro- and nanofabrication is crucial for both approaches, and I
will establish the necessary collaborations with scientists at other universities and research
institutes.
Surface modification and artificial biosensing interfaces: I plan to concentrate the
fundamental part of my surface chemistry research on the development of accurate strategies
for the preparation and structural/functional characterization of bio-organic interfaces. This
part of the research will involve development of accurate 2-D surface chemistries for
derivatization of solid substrates (metals, semi-conductors, oxides, polymers) using, e.g., selfassembly, Langmuir-Blodgett, vesicle fusion and polymer grafting techniques. The generated
model surfaces will then be used as templates for the development of artificial surfaces for
application in areas like affinity biosensing and transmembrane sensing.
Affinity biosensing: An advantageous presentation (orientation) of the immobilized
recognition molecule is of vital importance in label-free biosensing. Another issue that must
be carefully considered is non-specific binding of unwanted biomolecules onto the transducer
substrate (sensing layer). I intend to dedicate a significant part of my research on the
development of 2D- and 3D-modifications that display low levels of non-specific binding
(NSB). These layers will subsequently be tested and evaluated in our projects on
Bilaga 4. Tentative plans for the chair.
DNA(oligonucleotide) sensing as well as in our bilateral project with the Pisa group on
structure-function and minimun sequence analysis of growth factors.
Biomimetic bilayer and transmembrane sensing: Membrane bound proteins and receptors
play an important role in the complex cascade of interactions occurring at and across
biological cell membranes. Despite this importance, the molecular understanding of
transmembrane processes is still far from complete. On the other hand, operating as molecular
machines, they seem to be an attractive approach for molecular device applications, including
smart biosensors. One of the main challenges in today's biosensor design is to develop
artificial structures that enables us to mimic and monitor these molecular recognition and
signal transduction events. The idea of this research is to combine skills and experience from
different disciplines (materials and transducer physics, organic and surface chemistry,
molecular and cell biology) in the assembly process of a functional phospholipid bilayer
structure, with and incorporated transmembrane protein, on a transducer substrate, Fig 1.
Ca
Ca
2+
2+
Ca
2+
Ca
2+
V
A
Ca
2+
Ca
2+
Hydrogel
Fig. 1. Artificial transmembrane structure immobilized on surface of an amperometric microelectrode
2+
transducer. The bilayer contains a transmembrane protein that, e.g., opens an ion channel Ca because of a
recognition (key-lock) event. Vesicle fusion techniques will be used to prepare the bilayer on top of the hydrogel.
I intend to address this interesting research and engineering problem by using a combination
of molecular templates prepared by solution self-assembly and Langmuir Blodgett techniques.
Grafting techniques using polymer- and/or oligosaccharide building blocks will then be
attached to the template in order to provide a spacious and biocompatible environment, a
hydrogel, for the transmembrane loops, Fig. 1. This part of the research will be undertaken in
collaboration with Dr’s Konradsson and Svensson at the Chemistry Department, LiU. The
bilayer structure, with the incorporated transmembrane protein, will then be deposited using
vesicle fusion techniques at the department of Faculty of Health Sciences, (prof. K.-E.
Magnusson), LiU. Another important issue to address is the choice of transducer principle to
monitor the molecular events. Electrochemical and optical transducers (BIA-technology)
seem to be the most promising ones because they can easily be miniaturized and fabricated in
large series.
Interfacial water and its role in molecular recognition: Although water is a common
molecule on earth - its behaviour at or near surfaces is far from fully understood. Despite the
lack of detailed knowledge, it is becoming generally accepted in the surface science
community that the first layer(s) of water molecules near a solid surface possess different
properties than those further away, and that they thereby may alter the conditions for chemical
interactions occurring at the solid surface. The role of water at complex biological interfaces
and around active sites is even less understood than at inorganic/organic surfaces even though
Bilaga 4. Tentative plans for the chair.
several attempts have been undertaken to include water as an important structural component
to explain the kinetics of receptor-ligand interactions as well as charge(proton) transport in
enzymes. One of the surprizing findings in molecular recognition is that certain key-lock
reactions occur at a very high speed, close to speed determined by the diffusion (Do) constant
of the mobile component. This type of rapid interaction phenomenon is most likely caused by
so-called facilitated diffusion. The hypothesis is that the water molecules form an organized
hydration layer around the active pocket of the receptor, and that the strong and long-ranged
dipole field from this organized water forces the ligand to pre-align in a favourable orientation
before it reaches the receptor. Thus, the kinetics of receptor-ligand interaction may largely be
determined by the ability to form an organized layer of water molecules around the interaction
pocket. I intend to build up artificial surfaces and study the influence of water organization
around active sites using biosensor technologies and traditional surface science techniques.
UNDERGRADUATE TEACHING AND COURSE DEVELOPMENT
The research activities in sensor science must also spill over to undergraduate teaching. I can
immediately foresee three main areas within which I can contribute as a lecturer in the
undergraduate civil engineer programs (Y, TB) at LiU:



Transducer physics and detection principles
Surface modification and immobilization
Surface physics/chemistry and interfacial analysis
I’ll also propose to the program boards of the two profiles (Y, TB) to give a new course on the
general concepts of adsorption. I think that this type of course is missing in both programs.
The course should concentrate on adsorption phenomena occurring at the gas/solid and
liquid/solid interface. It should, for example, contain a discussion on isotherms, kinetics, mass
transport and modelling of adsorption phenomena from complex solutions.
I plan also to keep my teaching duties in Chemical Surface Physics and Surface Science
within the Technical Biology program.
Bo Liedberg
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