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