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Biomolecular integration with composite electroactive polymer structures

Ziel



This research proposal addresses a fundamental issue that exists in current techniques for interfacing biomolecules with (opto)electronic devices, namely the design of tailored artificial interfaces that are inherently capable of molecular recognition. Our primary aim is to develop novel strategies that will provide methods for precise control of the spatial distribution and the orientation of complex biological macromolecules immobilised on surfaces, thus creating a fundamental basic skill set for future applications in bioelectronics.
In order to address these issues of molecular engineering at interfaces, we have assemblled a consortium of scientists with expertise in nano-fabrication, protein engineering, surface analysis, physical chemistry, and polymer science. Our approach to the subject is therefore multi-disciplinary and "convergent", in which we will seek to precisely control the nature of the biological material (through molecular engineering), whilst at the same time, structuring the underlying materials using nano-technology. Necessarily we will also have to bridge the interface between the biological and electronic environments, using tailored thin biocompatible conducting matrices. In this latter respect, we will use functionalised polymers derived from pyrrole, which will be electrochemically deposited on metal surfaces. It is important to note that these polymeric materials have three distinct advantages over other strategies for modifying interfaces (e.g. self-assemblled monolayers).
- They are physically robust, giving structural rigour and flexibility tote interface.
- The films can be used to modify a wide range of electrode materials,including C, Pd, Au and Pt.
- Finally, since the polymer's gross structure is controlled both by the applied electrochemical potential and the counter-ion used during polymer growth, there is the possibility of changing the physical character of the film (e.g. the conductivity, thickness porosity) by changing the polymerization conditions. This latter point is important, as polymers can be used to make a three dimensional interface, with higher surface areas for interaction.
In this application, we envisage that by judicious derivatization of the monomer, we will have the capacity to produce devices that interact specifically with proteins, carrying complementary functionalities. Indeed, three of the applicants in this programme (Professor Garnier, Dr Cass and Dr Cooper) have independently demonstrated the potential application of conducting plastics in disparate aspects of signal transduction, brought about by biomolecular recognition, i.e. either for electrochemical measurement of ligand-binding, or as artificial electron donor-acceptors.
Over the next three years, we propose to build upon this initial work by introducing novel binding functional groups into biomolecules via protein engineering methods, at all times making full use of our knowledge of the 3-D structure and its relationship with biological functionality. At each stage in the process of assembling these artificial engineered interfaces, detailed structural and functional characterization will be carried out, such that we will be able to understand the rationale of design. We will refer to this approach as the BICEPS (Biomolecular Integration with Composite Electroactive Polymer Structures) strategy.
Four types of biomolecular interaction will be exploited in order to assemble the interfaces, namely: Biotin/Avidin, ss DNA/ ss DNA, Chelators/Metal ions, Prosthetic Groups/Apo Proteins. These different types of biological interaction will offer us variations in affinity, specificity and geometry of binding and so will provide a "library" of surface chemistries for elaboration of the interface. In all cases the preferred site of functionalization of the pyrrole monomer will be the synthetically challenging 3-position, which is important as it will enable us to maintain high electrically conductivities in the resulting polymers.
An essential feature of this programme will be rigorous characterization at each stage of the molecular design process. For functionalised monomers, standard analytical methods such as spectroscopy and elemental analysis will be employed. Following electro-deposition, the polymers will be further analysed by a range of surface techniques, particularly scanned probe microscopy, molecular and atomic spectroscopy, enabling us to probe the bio-electronic environment at a nano-scale. These surface techniques will subsequently be extended to include a wider range of methods, including micro-gravimetry, electrochemistry combined with SPR and near and far-field optical methods based on fluorescence microscopy.
Although the programme is primarily concerned with a fundamental investigation of the fusion of nano-technology with the fields of protein engineering and polymer synthesis, throughout the three years there will be a close contact with a major French pharmaceutical company, who are interested in aspects of micro-fabrication of arrays of biopolymers and micro-machining devices for high through-put detection of nucleotide sequences.

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Koordinator

IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE
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SW7 2AY London
Vereinigtes Königreich

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